Table of Contents
Home¶
Welcome to the online home of the Vanderbilt Internal Medicine Residency Handbook (VIMBook.org). The Handbook is a peer-reviewed, yearly-updated, publicly-available resource, currently in its 6th Edition (2024-25).
Chief Editors for the 6th Edition:
Spencer Lessans, MD, Julie Giannini, MD, and Kristijan Bogdanovski, MD
A QR code to the online version can be found on the back cover of the handbook. An LLM-enhanced Chatbot version of the handbook is currently under development.
Introduction ↵
Acknowledgements¶
The Vanderbilt University Medical Center (VUMC) Internal Medicine Housestaff Handbook began with an Internal Medicine Resident Quality Improvement Project which was led by Michael J. Neuss, MD, PhD, under the guidance of Jennifer K. Green, MD, MPH in 2019.
We would like to thank the following individuals for their contributions to the 6th edition of the Housestaff Handbook:
- The many VUMC residents (past and present) who have meticulously authored each section of this handbook.
- The VUMC faculty who carefully reviewed each topic for its accuracy.
- Lauren Chan MD, and Jacqueline Visina MD, the 5th edition's co-editors-in-chief, whose guidance was instrumental in the transition between editions.
- Chase Webber, DO, who was a sounding board for our new ideas throughout the year as the Handbook’s faculty advisor.
- C. Beau Hilton, MD for his work in updating and improving the online version of this handbook.
- ViTAL Center and William Anderson Spickard Scholars fund, for supporting the publication of the physical copy of the book.
- John McPherson, MD, Jane Freeman MD, Hilary Tindle MD PhD, Kristy Braden and Maria Kasel, for their unwavering support.
Editors, Authors, and Reviewers¶
Editors-in-Chief¶
Kristijan Bogdanovski, MD, Julie Giannini, MD, and Spencer Lessans, MD
Resident Editors¶
Anesthesia: Alex Brown, MD and Camile Adajar, MD
Cardiology: John Mitchell, MD, Emily Walsh, MD, and Nicholas Weinand, MD
Critical Care: Alexandra Flemington, MD
Endocrinology: Kinsley Ojukwu, MD (2023)
Gastroenterology: Katy Welp, MD
Geriatrics: Mallory Bryant, MD
Hematology/Oncology: Thomas Gracie, MD, Matthew Lu, MD, and Alexis Froehlich, MD
Hepatology: Ahmad Yanis, MD
Hospital Medicine: Christine Hamilton, MD
Infectious Diseases: Alexis Froehlich, MD
Nephrology: Emily Walsh, MD
Neurology: Meghan Nicholas, MD, Lauren Osborne, MD, and Eesha Oza, MD
Ophthalmology: Jonathan Barnett, MD (2023)
Outpatient Medicine: Lauren Waskowitz, MD
Palliative Care: Liana Mosley, MD
Physical Medicine & Rehabilitation: Jakob Dovgan, MD, Douglas Bryant, MD, William Galbraith, DO, and Nicholas Abramson, MD (2023)
Procedures: Rochelle Prokupets, MD
Psychiatry: Benjamin Johnson, MD
Pulmonary: Bailey DeCoursey, MD and Justin Smith, MD
Radiology: Austin Glenn, MD, Lane Polk, MD, Kyle Maughan, MD & Nicholas Schreiter, MD
Rheumatology: Tina Arkee, MD and Lale Ertuglu, MD
Toxicology: John Mitchell (2023)
Faculty Reviewers¶
Anesthesia: Brandon Pruett, MD
Cardiology: Lisa Mendes, MD and Jared O'Leary, MD
Critical Care: Todd Rice, MD
Endocrinology: Laura Heller, MD
Gastroenterology: Patrick Yachimski, MD
Geriatrics: Mariu Duggan, MD, MPH
Hematology/Oncology: Rajiv Agarwal, MD and Vivek Patel, MD
Hepatology: Manhal J. Izzy, MD
Hospital Medicine: Chase J. Webber, DO
Infectious Diseases: Milner Staub, MD, MPH and Sean Kelly, MD
Nephrology: JP Arroyo, MD, PhD, Edward Gould, MD, and Beatrice Concepcion, MD
Neurology: Matthew Meriweather, MD
Ophthalmology: John Bond, MD
Outpatient: Jennifer K. Green, MD, MPH
Palliative Care: Mohana Karlekar, MD
Physical Medicine & Rehabilitation: C. J. Plummer, MD
Procedures: Garren Montgomery, MD
Psychiatry: Kristopher Kast, MD and David Marcovitz, MD
Pulmonary: Meredith Pugh, MD
Radiology: Reza Imani, MD
Rheumatology: Kevin Byram, MD
Toxicology: Rebecca E. Bruccoleri, MD and Saralyn R. Williams, MD
Disclaimers¶
The handbook is not a substitute for clinical judgment and is intended as an educational guide. Content reflects current national guidelines, as well as practice at VUMC and the Nashville VA. The handbook is not intended to replace more comprehensive references or guides.
Images are used sparingly, but when used are created by the authors themselves, available by public domain, or reproduced under fair use.
Rationale¶
The aim of this handbook is to provide specific, systems-based guidance on practice at VUMC and the VA. We hope to provide readers with direct and actionable guidance, consolidating the combined wisdom of generations of residents and faculty experts.
The Handbook represents a coordinated effort to disseminate details of our practice in a standardized, peer-reviewed format. The guidance provided by the handbook makes legible evidence-based practice as well as the oral tradition of a resident guiding an intern, or an attending a resident. We hope that this handbook will inspire confidence and learning, whether the reader is an intern on July 1 or a senior resident who wishes to refresh their memory of a topic.
Web App Setup¶
This site is optimized for use on mobile devices. It is possible to set up a link from your device's home screen that gives it the look and feel of a web app.
- iOS users: Go to VIMBook.org . At the bottom of the screen, hit the "Share" icon (box with upward facing arrow). Hit "Add to Home Screen." Rename it to your liking. The gold Vanderbilt icon will appear on your home screen, and you can click this icon to be taken directly to the website.
- Android users: Go to VIMBook.org . Press Menu, then select "Bookmarks." Hold it down until "Add Shortcut to Home Screen" appears, and click it. This will place an icon on your home screen, and you can click this icon to be taken directly to the website.
Ended: Introduction
Anesthesia & pain management ↵
Acute Pain¶
Camille Adajar and Frances Alexandra Brown
Multimodal pain regimen suggestions¶
- Tylenol
- Dose: 1,000mg PO Q8H (can reduce to 650 based on age or comorbidities)
- Indications: Analgesic and antipyretic
- Contraindications: Cirrhosis -- limit to 2000mg daily
- Gabapentin
- Dose: 300mg PO Q8H (reduce to 100mg, Q12H dosing, or hold based on renal function, age, or sedation level)
- Indications: Neuropathic pain
- Contraindications: decreased CrCl
- Side effects: sedation, respiratory depression
- Robaxin
- Dose: 500mg PO Q8H
- Indication: muscle relaxant
- Contraindication: IV formulation has preservative that is nephrotoxic
- NSAIDs (check for adequate renal function and GI contraindications)
- Toradol 15-30mg IV Q6H x 5 days
- Ibuprofen 600mg Q6H
- Indications: analgesic, anti-inflammatory, antipyretic
- Contraindications: CKD/AKI, ulcers, GI bleed
Other methods¶
- Thoracic epidural catheter (TEC) - These are done and managed by the
Acute Pain Service. With any issues or concerns, APS needs to be
contacted.
- Indications: pain relief in thoracic dermatome distributions (rib fractures, BOLTs, etc.)
- Contraindications
- Low platelets/INR > 1.5/coagulopathy
- Hypotension
- Positive blood cultures, fever, white count, etc.
- TECs stay in 5-7 days, risk of infection increases beyond that point.
- TECs run an infusion of Ropivacaine and Hydromorphone in the epidural space
- Do NOT need to d/c anticoagulation to pull TEC
- Pt can only be on 5000 units of Subq heparin
- Pain service can pull TEC 4hrs after last SQH dose
- They cannot be on the weight adjusted 7500 units
- No Lovenox/Enoxaparin while TEC in place
Chronic Pain¶
Suboxone/Buprenorphine management¶
- Can restart home regimen if they have taken their suboxone in the last 48 hours
- Look at CSMD on EPIC to verify their home regimen
- If re-initiation is needed, consult addiction psych
- Important for patients taking suboxone to remain on the medication
- If pain is an issue, continue their medication and consult either chronic pain or acute pain service and addiction psych
Methadone management¶
- Patients need to be evaluated by addiction psychology service for methadone recommendations while inpatient (often requires QTc monitoring)
- Patients should be continued on home regimen
Anesthesia consulting pain services
Consulting Acute Pain Service (APS)¶
- If refractory to multimodal pain regimen above, consider consulting
APS for:
- Acute pain due to surgery in the last 7-10 days
- Acute pain due to new trauma
- APS also provides services for patients who are receiving regional anesthetic (nerve blocks, nerve catheters) techniques
Consulting Perioperative Consult Service¶
- Periop provides pain management and implements enhanced recovery after surgery (ERAS) for specific surgical patients on the ERAS pathway
Consulting Chronic Pain Service (CPS)¶
- Service for patients with chronic pain and cancer-related pain
- If a patient is having an acute flare of a chronic problem that is
not related to surgery or trauma, consult CPS
- Examples: IBD flare, chronic pancreatitis, sickle cell pain crisis
- Consultation available Monday through Friday 7am-3pm
- The Transitional Pain Service (TPS) is a division of CPS: evaluate chronic pain patients preoperatively in clinic or before hospital discharge for outpatient pain management recommendations after surgery
Ended: Anesthesia & pain management
Cardiology ↵
Acute Coronary Syndromes¶
Kelly Vogel
Background¶
- Completely or partially occluding thrombus on a disrupted atherothrombotic coronary plaque leading to myocardial ischemia/infarction
- STEMI: Elevated troponin & elevation in ST segment or new LBBB with
symptoms
- > 0.1 mV in at least 2 contiguous leads
- Exception, in V2-V3:
- > 0.2 mV in men older than 40 y/o
- > 0.25 in men younger than 40 y/o
- > 0.15 mV in women
- NSTEMI: Evidence of myocardial necrosis (elevated troponin) w/o ST segment elevation
- Unstable Angina: Angina without evidence of myocardial necrosis (normal troponin)
- Newer nomenclature: occlusion and non-occlusion MI (OMI and NOMI)
- Occlusion MI: near or total occlusion with insufficient collateral circulation causing active infarction, further broken into STEMI (+) OMI or STEMI (-) OMI; both considered a type I MI
- Non-occlusion MI: no occlusion or sufficient collateral circulation to avoid active infarction, further broken into STEMI (+) NOMI or STEMI(-) NOMI; can be either type I or II MI
- Other causes of myocardial injury: coronary spasm, embolism, imbalance of oxygen demand and supply 2/2 fever, tachycardia, hypo-/hypertension
Presentation¶
- Symptoms
- Classic Angina: dyspnea on exertion, substernal, pressure or vice-like quality, improved with rest. Note that response nitroglycerin is no longer in the guidelines.
- Anginal Equivalents: nausea, weakness, epigastric pain (esp. in age
> 65 y/o, women, diabetics)
- Change in pt's baseline angina, especially onset at rest
- Physical Exam: sinus tachycardia, diaphoresis
- If large infarct, can present with symptoms of acute heart failure
Evaluation¶
- EKG: Compare to prior EKG and assess for
- New ST elevations or ST depressions
- T wave inversions: not specific but more concerning if deep (> 0.3mV)
- Biphasic T waves and deep T wave inversions in leads V2 & V3 (Wellens sign [LAD])
- Cardiac biomarkers: troponin I is most sensitive for myocardial injury
- ACC/AHA guidelines recommend both EKG and trop q2-6 hours
- Consider this if high suspicion for ACS despite normal initial markers
- If negative x2, OK to stop trending
- Other labs: lipid panel, TSH, A1C
Management¶
STEMI¶
- STAT page Cardiology on call via Synergy (whether in VA or Vanderbilt)
- ASAP: aspirin 325mg, heparin drip (high intensity nomogram, with bolus)
- Hold P2Y12 until discussed with cards fellow
NSTEMI¶
- Medical management followed by left-heart catheterization within 48
hours
- General: bedrest, telemetry, repeat EKG with recurrent chest pain, NPO at midnight
- Place cath case request (see “pre-catheterization” management below)
Anti-thrombotic therapy¶
Antiplatelet agents - ASA 325 mg loading dose then 81 mg daily after - Do not give P2Y12 receptor blocker until discussed with cardiology fellow - Clopidogrel: prodrug that is metabolized to active form (can have undermetabolizers), irreversible inhibition - Ticagrelor: reversible inhibitor - Prasugrel: prodrug but more rapidly metabolized than clopidogrel with less variation, irreversible inhibition, do not use w/ age > 75 or weight \< 60 kg - Prasugrel and ticagrelor are superior to clopidogrel but have higher bleeding risk - Cangrelor: IV, rarely used
Anti-coagulants: Unfractionated heparin drip - Type this in Epic and select “nursing managed” protocol for “ACS” - VA: it can be found under the “Orders” tab along the left-hand column. - Enoxaparin (LMWH) can be used but requires preserved renal function (CrCl > 30) and most interventionalists prefer heparin prior to LHC
Pre-Catheterization Care¶
- Ensure pt. is NPO at MN for planned cath
- Continue anticoagulation with heparin gtt
- Place cardiac catheterization request (must be in cardiology context). Can also call cath lab to ensure pt. is scheduled appropriately
Post-Catheterization Care Catheterization Documentation¶
- The most appropriate guidance for post-cath care is in the cardiac catheterization report
- VUMC: Epic Cardiac tab Cardiac Catheterization/Intervention Report
- VA: Note tab Post-Procedure note and Cardiac Catheterization note
- If there is a delay in filing the final report at VUMC: Review the Cardiac Catheterization Nursing Documentation which shows if stents were deployed
Post-Catheterization Heparin¶
- Medical management w/o intervention: stop heparin unless directed in report
- If indication for CABG (ex: Left main, proximal LAD), continue heparin gtt until surgery
- PCI placed: stop heparin and continue/start DAPT as directed by cardiology
- Other medical indication for anticoagulation (DVT/PE, atrial fibrillation): restart ~ six hours after catheterization
Cath Site Checks¶
- 6 - 8 hours post catheterization (typically can be signed out as 0000 cath check), only needed for femoral arterial access
- Look, listen, feel: evaluate for hematoma & pseudoaneurysm; call
fellow if concerned
- Small amount of bruising and mild tenderness at the site is normal
- Listen above and below the site for a bruit; the area should be soft
- Hypotension after femoral access is concerning for RP bleed
- Apply pressure, STAT page interventional fellow, do NOT take pt to scanner prior to hearing back, order blood if needed
- Femoral oozing: Cardiology fellow, will need to hold pressure
- Radial oozing: instruct nurse to re-inflate the TR band and restart the clock on deflation
Post ACS Care¶
- Echo prior to discharge
- DAPT: Aspirin 81 mg daily and P2Y12 agent
- Beta blocker in all patients within 24 hours
- Metoprolol, carvedilol & bisoprolol have proven mortality benefit with reduced EF
- High intensity statin (ex: rosuvastatin 40 or atorvastatin 80). See outpatient lipids section
- ACEi/ARB if anterior STEMI
- Lifestyle Modification: weight loss, smoking cessation, diabetes control
- See heart failure section for management of HFrEF
ACS Complications¶
- VT/VF, sinus bradycardia, third-degree heart block, new VSD, LV perforation, acute mitral regurgitation, pericarditis and cardiogenic shock; More common with STEMI->CCU post-cath
Arrhythmias¶
Acute management¶
- 12-lead EKG if possible and have defib pads on patient
- Is the pt unstable (hypotensive, signs/symptoms of hypoperfusion)?
- Is the information real?
- Review tele strips if stable: VUMC Web Resources -> VUH PIICiX Philips Web -> patient selection -> alarm review (vuhphilipsweb.app.vumc.org)
- Review past EKGs to determine if patient has had this rhythm before
- Ensure pt has good IV access
- Labs: BMP, Mg, TSH, and ± troponin, tox screen
Bradyarrhythmias - Lin Cao¶
Background¶
- Broadly classified as sinus node dysfunction (pacing defect) or atrioventricular block (conduction defect)
- Clinical presentation varies widely based on underlying cause,
timing, degree of block/dysfunction
- Unlikely to cause symptoms if HR >50
- Symptoms include syncope/presyncope, dyspnea, angina
Potential Etiologies¶
- Infection (including perivalvular abscess from endocarditis)/sepsis
- Ischemia
- Rheumatologic/Inflammatory
- Post-cardiac surgery
- Hypothyroidism
- Sleep apnea
- Infiltration (amyloid, hemochromatosis)
- High vagal tone (pain, nausea)
- Medications: Antihypertensives, antiarrhythmics, psychoactive meds, anesthetics, cannabis, muscle relaxants, etc.
AV Block
Evaluation¶
- TTE if structural disease suspected
- Ambulatory cardiac monitoring if frequently symptomatic
Management¶
- Avoid nodal blocking agents – Adenosine, Beta-blockers, CCBs, Digoxin
- Observation if asymptomatic
- Treat identified underlying causes
- If symptomatic or high-grade block (Mobitz II or complete heart block), EP consult for pacemaker evaluation
- If unstable:
- Atropine (0.5 mg every 3 to 5 minutes; maximum total dose: 3 mg)
- Do NOT use in heart transplant
- Call CCU Fellow
- Dopamine (5 to 20 mcg/kg/minute) OR Epi (2 to 10 mcg/min)
- Transvenous pacing (Pacer pads on the defib device are capable of pacing, but don’t forget to sedate!)
Tachyarrhythmias - Narrow complex - Manasa Atyam¶
Background¶
- Three causes of tachyarrhythmias
- Re-entry: patient with structural heart disease (ex post-infarction scar)
- Abnormal Automaticity: electrolyte abnormalities or acute ischemia (Purkinje fibers)
- Triggered Activity: early and late after depolarizations. Ex: Hypokalemia, ischemia, infracts, excess calcium and drug toxicity
Evaluation¶
- Unstable tachyarrhythmia
- Start with treatment, determine type later
- Synchronized cardioversion: place defibrillator pads, consider 0.5-2mg IV midazolam for sedation, prepare for synchronized cardioversion at 200J (can ↑ to 300-360 J)
Tachyarrhythmia differential
Management¶
- Sinus tachycardia- Almost always secondary
- Address underlying causes: fever/sepsis, hypo/hypervolemia, anxiety, anemia, PE, ACS, hypoxia, pain, urinary retention, withdrawal
- Atrial Fibrillation/Flutter – See Atrial fibrillation section
- AVNRT/Orthodromic AVRT
- Look for p buried in QRS, rate 150-250, AVRT will have delta waves when NSR
- Vagal maneuvers (1st line): Sit patient upright have them blow into tip of 10cc syringe for 10-15 seconds rapidly lay supine and raise legs
- Adenosine (2nd line): therapeutic (break AVRT/AVNRT) and diagnostic
(allows visualization of underlying rhythm)
- Do NOT give in heart transplant, severe COPD, pre-excitation causing wide complex tachycardia (WPW antidromic AVRT)
- Peripheral line at AC or above w/ arm elevated: 6mg x1, 6mg x1 (if not effective after 1-2 min), 12mg x1 (if refractory to 6mg)
- Central line: cut dose in half to 3mg x1, 3mg x1, 6mg x1
- Multifocal atrial tachycardia
- 3 or more p wave morphologies. Seen in cardiac and pulmonary disease
- Usually does not cause hemodynamic instability
- BBs and non-DHP CCBs can be effective, need to address underlying issue
Drug | Dosing | Benefits | Side Effects |
---|---|---|---|
Metoprolol | 5mg IV q5m x3 PO metoprolol tartrate 12.5mg q6 hours ↑ every 6 hr to target |
Good 1st line agent Less BP effect than dilt |
Hypotension, Negative inotropy |
Diltiazem | 10-20 mg IV over 2m q15m x2 drip = 5-15 mg/hr |
Good 1st line w/ normal EF with drip needed | Hypotension Avoid in HFrEF |
Esmolol | 500 mcg/kg bolus drip = 50-200 mcg/kg/min |
Rapid onset/offset RBC metabolism |
Hypotension |
Amiodarone | 150 IV over 10-30m, then 1 mg/m for 6h, then 0.5mg/m for 18h | Minimal BP effects Long lasting; Relatively fast onset (acute effect is mostly beta blockade) |
Pulmonary and thyroid toxicity Cardioversion |
Digoxin | 500mcg IV x1, then 250mcg IV q6h x2-3 | Great for reduced EF, positive inotropy | Slow onset Depends on vagal tone – poor in hyper- adrenergic states |
Procainamide | 20-50 mg/min loading, 1-4 mg/min maintenance | Use in pre-excitation syndromes (i.e. WPW), does not inhibit AV nodal conduction | Lupus-like syndrome Hypotension |
Tachyarrhythmias - Wide Complex and PVCs¶
Manasa Atyam
Definitions¶
Ventricular tachycardia (VT): a run of 3+ PVCs
- Sustained VT: VT for 30 seconds or shorter if it requires intervention
- Nonsustained VT (NSVT): VT for \< 30 seconds
- VT storm: 3+ separate episodes of sustained VT within 24 hrs.
VT Morphologies
- Monomorphic VT: similar QRS configuration from beat to beat
- Usually 2/2 scar-mediated VT from prior infarction
- Polymorphic VT: a continuously changing QRS configuration from beat
to beat
- Ischemia until proven otherwise
- Torsades de Pointes (TdP): a form of polymorphic VT with a continually varying QRS that appears to spiral around the baseline of the ECG in a sinusoidal pattern
- Ventricular fibrillation (VF): chaotic rhythm characterized by undulations that are irregular in timing and morphology, without discrete QRS complexes
Ventricular Tachycardia vs. SVT with aberrancy
- VT: The action potential originated in the ventricles (ex: VT)
- Supraventricular tachycardia with aberrancy: the action potential originates from a focus above the ventricles & conducts through the AV node with a delay or block resulting in a wide QRS (mimics VT)
- Ex: sinus tachycardia w/ bundle branch block (block may be rate dependent), AF w/ LBBB
Many ways to differentiate VT vs. SVT w/ aberrancy
- Consult cardiology for assistance
- Look for ECG features suggestive of VT
- Very broad complexes >160 ms
- RsR’ complex with a taller left rabbit ear In V½
- AV dissociation (P/QRS dissociation)
- Capture Beats: native QRS complexes making a cameo during the VT
- Fusion Beats: QRS which appears like a signal average of VT and native complex
- There are more advanced criteria to help distinguish. The aVR (Vereckie) criteria is one example that is fast and accurate
Management¶
Unstable
- Sedate with midazolam 1-2mg
- Cardioversion for monomorphic VT. Synchronized shock at 100-200J
- Defibrillation if VF/polyVT
Stable
- Medications (as below)
Drug Name | Dosing | Mechanism | Side Effects |
---|---|---|---|
Amiodarone | 150mg IV over 10 min, then 1mg/min for 6 hours; repeat bolus if VT recurs | Class III -K+ channel blocker; has class Ia, II, & IV effects |
Bradycardia, hypotension (acutely) |
Lidocaine | 1-1.5 mg/kg (usually 75-100 mg) at a rate of 25-50mg/min; lower doses of .5-.75mg/kg can be repeated every 5-10 min as needed | Class IB -fast Na+ channel blocker-> slows conduction |
Slurred speech, AMS, seizures, bradycardia |
Procainamide | 20-50mg/min until arrhythmia terminates or max dose 17mg/kg is reached | Class IA -fast Na+ channel blocker -> slows conduction -K+ channel blocker-> prolongs repolarization |
Bradycardia, hypotension, torsades, drug-induced lupus Avoid in HF pts, prolonged QT |
-
Cardioversion If refractory to medical management
-
Treatment of underlying cause if identifiable
- Ischemia, electrolyte disturbances, heart failure, drugs
Premature Ventricular Complexes (PVCs)¶
Background¶
- Premature Ventricular Complex (PVC): early ventricular depolarization ± mechanical contraction
- PVC burden: % of beats of ventricular origin / total beats over a 24h period
- PVCs are common: Up to 80% of apparently healthy people have PVCs
- Normal number of PVCs in an adult is \<500 in 24h
Etiologies¶
- HTN with LVH, prior MI/scar, HF, myocarditis, ARVC, HCM, idiopathic VT, OSA, pHTN, COPD, thyroid disease, substance use (EtOH, nicotine, stimulants, caffeine)
Inpatient Evaluation & Management¶
- 12 lead EKG: conduction disease, long QT syndrome, Brugada syndrome, ARVC
- Labs: K, Mg, TSH, drug screen
- Evaluate for QT prolonging agents (risk of Torsades)
- Evaluate tele for PVC burden
- Inpt consult to EP for PVCs rarely warranted unless significant PVC burden (>5 PVC/min, consistently) in setting of reduced LVEF.
- For pts with >5 PVC/min or pts with symptoms, discharge with Ziopatch (VA) or mobile cardiac telemetry (VU) and obtain TTE if none recent.
Atrial Fibrillation & Flutter¶
Matt Gayoso
Background¶
- AF: 12-lead EKG with absence of p-waves and irregularly irregular QRS complexes
- Flutter: sawtooth atrial F waves (300 BPM) with regular or regularly irregular QRS complexes
- Ventricular rate ratio of F waves: V waves ~150 (2:1), ~100 (3:1), or ~75 (4:1)
- 3 classifications
- Paroxysmal (terminates within 7 days)
- Persistent (persisting beyond 7 days)
- Permanent (normal rhythm cannot be restored)
- Rapid ventricular response (RVR) is HR > 100 (ie AF/Flutter w/ tachycardia)
- AF/RVR is far more often a consequence of hypotension than the cause of it
Evaluation¶
- Causes: Mnemonic “H PIRATES”
- Hypertension
- Pneumonia, Pericarditis, Post-op
- Ischemia (rare)
- Rheumatic Valve
- Atrial Myxoma or Accessory Pathway
- Thyrotoxicosis
- Ethanol or Excess Volume
- Sick sinus, Sepsis
Management¶
- Treatment goals
- Rate control, Goal HR \< 110 (RACE II)
- Rhythm control (if indicated)
- Stroke prevention (CHADS2VASc)
Rate control:¶
- RVR ~ sinus tach of AF; Always work to address the underlying cause (infection, volume overload, etc). Rate control is rarely an emergency unless the patient is unstable
- If stable with RVR (SBP >90)
- IV if HR > 130 or symptomatic (metop 5 mg IV or dilt 15-20 mg IV), otherwise do PO
- AV nodal blocking agents
- B-blockers: Start with metop tartrate (titratable) consolidate to succinate. Avoid in decompensated or borderline HF
- Calcium channel blockers (diltiazem): avoid in HFrEF
- Peri stable (SBPs 80s-90 with preserved perfusion)
- Amiodarone: Consider if decompensated HF, accessory pathway, anti-coagulated. Caution that you may cardiovert pt (stroke risk)
- Unstable (SBPs \<80)
- Cardioversion
Rhythm control¶
- New onset a-fib (first time diagnosis): most pts will be a candidate for trial of cardioversion
- If onset clearly within 48 hours, can proceed without TEE. Often TEE is done anyway (pt may have had intermittent asymp AF)
- If onset >48 hours or unclear, will need TEE to rule out LAA thrombus
- Pharmacologic options include class 1C: flecainide, propafenone
(avoid in structural heart disease) and class 3: Amiodarone,
dronedarone, sotalol, ibutilide, dofetilide (some require loading
inpt)
- Caution using antiarrhythmics in any pt you wouldn't electrically cardiovert without TEE
- Consider EP consult for ablation in symptomatic paroxysmal or persistent AF refractory to anti-arrhythmic drugs, AF in HFrEF, or flutter
Stroke Prevention (for AF and flutter)¶
- CHA2DS2-VASc risk score >2 in M or >3 in F should prompt long term AC in AF persisting >48 hours
- DOACs (apixaban, dabigatran, edoxaban, rivaroxaban) are preferred to warfarin except in moderate to severe MS or mechanical valve
- If cardioversion planned for new onset AF, start AC as soon as possible
- Post-cardioversion, anticoagulate for at least 4 weeks due to atrial stunning and stroke risk
- If no contraindications or procedures, continue anticoagulation while inpatient
- Typically do not need to bridge AC for AF in the setting of procedures unless mechanical valve is present. Decide on a case by-case basis
- Left atrial appendage closure can be considered in those with increased risk of bleeding (WATCHMAN, Amulet devices)
Autonomics and Orthostatic Hypotension¶
Emily Walsh
Background¶
- Orthostatic Hypotension (OH): SBP ↓ > 20 mmHg, DBP ↓ > 10 mmHg), or HR Increase > 30 within 3 min of standing up or head-up tilt to 60% on a tilt table
- Etiologies: Neurogenic OH (nOH) vs non-neurogenic OH
- nOH associated with autonomic failure
- Blunted tachycardia during hypotension characteristic of autonomic failure
- nOH: If HR rise is \<15
- nOH also associated with periods of high BP (supine hypertension)
- Ex: Neurodegenerative disease, neuropathy (diabetes, amyloid, paraneoplastic, etc)
- Other causes: volume depletion (most common), medications (diuretics, alpha-1 blockers, BB, etc), pump failure (severe AS, arrhythmia)
- nOH associated with autonomic failure
Evaluation¶
- Orthostatic vitals signs (checking supine, sitting, and standing with 5-minute wait in each position)
- Volume status exam
- Labs: CBC, CMP, EKG, TSH, B12, , LFTs
- Consider SPEP/UPEP, paraneoplastic panel, autonomic function testing depending on clinical context
Management¶
-
Conservative:
- TED hose and abdominal binder for ambulation
- Drink 16oz of fluid 15 min prior to standing
- If they have supine HTN, keep HOB 30-45 degrees at all times
- Add 2.3-4.6g of salt per day to diet (if no contraindications)
- Avoid high temperatures (which cause peripheral vasodilation)
-
Pharmacologic therapies (see table):
Drug | Dose | Mechanism | Side effects |
---|---|---|---|
Fludocortisone (Florinef) | 0.1mg QD ↑ by 0.1 mg Max: 0.3 mg QD |
Mineralocorticoid increase blood volume. Enhances sensitivity to circulating catecholamines | Edema HTN HypoK Do not use in CHF |
Midodrine | 2.5mg TID ↑ by 2.5mg Up to 10mg TID |
Peripheral-selective α1 agonist → constricts both aa & vv | Supine HTN Pilomotor reactions Pruritus GI upset Avoid in uncontrolled HTN, urinary retention, heart disease |
Droxidopa | 100mg ↑ by 100mg Up to 600mg TID |
NE precursor → carboxylated to NE. Can cross BBB. | Supine HTN, less than midodrine |
Atomoxetine | 10mg or 18mg | SNRI | Do not use w/ glaucoma or MAOI |
- Supine HTN therapies: transdermal nitroglycerin (preferred); minoxidil, hydralazine, or clonidine in select patients
Bedside Echocardiography¶
Jamie Pfaff
Finding an Ultrasound¶
- MICU: radiology room behind charge nurse's desk in middle hallway
- VA ICU: In front of resident workspace
- 8N: Behind nursing station before entering cleaning supply room
- 8S: In supply closet to left as you walk toward nursing station - (door code is 1-3-5)
- 6MCE: COVID restricted (ask nurses)
- CCU/5N only: supply room on left as entering CCU
- Round wing: 5th floor, ask nurses
TTE Standard Views¶
Parasternal long¶
- Probe position: Rotate probe 180 degrees with right edge of probe/probe marker pointing toward pt’s left shoulder
- Make sure probe is centered over mitral valve (In right spot if you can see MV and AV)
- E Point Septal Separation (EPSS)
- Distance separating the anterior MV leaflet from the septal wall as measure of LV systolic function (easy evaluation of systolic function)
- Place M mode spike at tip of mitral leaflet and hit M mode (perpendicular to septum)
- Identify E point (passive filling of LV) and determine distance
from interventricular septum (IVS)
- <7mm = Normal
- >10mm = HF
- Confounders that elevate EPSS: AR, MS
Parasternal short¶
- Probe position: Rotate probe 180 degrees with right edge of probe/probe marker pointing toward patient’s left shoulder
- Good position to assess EF by visualizing wall thickening
Apical four chamber¶
- Probe position: Slide down and look near patient’s left nipple (or in the intermammary fold after lifting up breast tissue if needed - at PMI if able to palpate)
- Good to assess EF by visualizing cardiac shortening
Subxiphoid¶
- Probe position: Push probe head into pt’s abdomen just below xiphoid and flatten probe to make nearly parallel to pt’s position, marker to pt’s left
- Troubleshooting: shift probe slightly left of midline (toward pt’s right) and angle toward heart/right to use liver as acoustic window or ask pt to take big breath (moves heart closer to probe)
- Best window to visualize pericardial effusion
IVC¶
- Probe position: subxiphoid area with probe marker facing toward pt’s head tilted slightly left of midline, trace IVC into RA to verify correct vessel (vs aorta)
- IVC size and collapsibility used as a surrogate for CVP and RAP
- <2.1 cm and >50% collapse: RAP ~3mmHg
- <2.1 cm and < 50% collapse or >2.1cm and >50% collapse: RAP ~8mmHg
- >2.1cm, <50% collapse: RAP ~ >15mmHg
Resources¶
- https://www.coreultrasound.com/basic-cardiac-function/
- http://pie.med.utoronto.ca/tte
- https://www.echocardiographer.org/TTE.html
- App: FATE CARD (Focus Assessed Transthoracic Echocardiography) https://test.usabcd.org/fate-card/ https://apps.apple.com/us/app/fate-card/id413628612
Cardiac Devices¶
Matt Gayoso
Pacemakers:¶
- Provide anti-bradycardia pacing by stimulating myocardium
-
Peripheral permanent pacemakers (PPMs)
- SubQ generator, transvenous leads
- Single chamber RV or RA lead
- Dual chamber RV and RA leads (most common)
- BiV (CRT- cardiac resynchronization therapy): RV, RA, and LV (coronary sinus) leads
- SubQ generator, transvenous leads
-
Leadless pacemaker (Micra)
- Implanted generator in RV
-
Indications
- Symptomatic sinus node dysfunction: sinoatrial exit block, sinus pause, sinus bradycardia, tachy-brady syndrome
- Degenerative AV block: 2nd degree type II (Mobitz II) or 3rd degree
- Neurocardiogenic syncope
Implantable Cardioverter/Defibrillators (ICDs)¶
- Types:
-
Transvenous: defibrillation coil ± pacing lead
- Detect and treat VT/VF
- Anti-tachycardic pacing (ATP)- attempts to pace out of VT to prevent a shock
- Defibrillation if ATP unsuccessful
-
Subcutaneous: defibrillation only, all extravascular
- Indications:
- Primary prevention
- HFrEF
- EF \<35% and NYHA II-III or EF \<30% and NYHA I
- Must be >90d from revasc, >40d from MI, and on GDMT >90d if non-ischemic
- Arrhythmogenic syndromes
- Arrhythmogenic RV cardiomyopathy, Brugada syndrome, HCM and cardiac sarcoid with specific risk factors
- HFrEF
- Secondary prevention
- Sudden cardiac death
- Sustained VT/VF
- Inducible VT on EP study with history of syncope
- Primary prevention
Cardiac Resynchronization Therapy (CRT)¶
- BiV pacer that coordinates LV/RV contraction through synchronized activation of each ventricle following atrial contraction.
- -P: CRT pacing only
- -D: ICD function
- Class I indications: LBBB and QRS≥150 with EF90d, NSR
Loop Recorders¶
- implantable devices for monitoring arrhythmias (most often Afib)
LVADs¶
- augment cardiac output for end-stage heart failure
Interpreting Pacemaker Codes¶
1st Letter | 2nd Letter | 3rd Letter | 4th Letter | |
---|---|---|---|---|
A: atrial, V: ventricular, D: dual, O: none, I: inhibition, R: rate-adaptive | Chamber Paced | Chamber Sensed | Response to Sensed Beat | Program Features |
Examples of Common Pacing Modes¶
- VVI: Single RV lead that delivers a beat if no beat sensed. Often used with chronic AF with bradycardia
- DDDR: Senses and paces both the atria and ventricle. If beat not sensed within a predefined interval, beat delivered. R indicates rate responsivity (changes rate based on changes in patient activity)
- Magnet: Paces at a fixed rate without respect to native electrical activity (AOO,VOO,DOO). Deactivates ICD shock. Often used in surgery or at end of life to avoid ICD shocks
Peri-Procedural Anticoagulation:¶
- NOAC: hold 24-72h before procedure and 24-72h following procedure
- Warfarin: continue through procedure
- Antiplatelet: continue through procedure
- Heparin and heparin related products to be avoided peri-implantation due to higher rates of pocket hematoma
Placement Complications¶
- Pocket hematoma - Cardiac Tamponade
- Pneumothorax - Infection
- Myocardial Perforation - Lead Displacement or Disconnection
Long term Complications¶
- Secondary device Infection
- Lead fracture (lead lifetime 10-15 years)
-
Insulation failure
The Pacemaker ID app is free and is useful for identifying device brand for interrogation
When differentiating PPM vs. ICD, look for a coil and charge generator to identify the ICD.
Chest Pain¶
Claire Lo
Chest Pain / Angina:¶
- Symptoms determine likelihood that chest pain has a cardiac etiology
- Cardiac > possible cardiac > noncardiac is more useful than typical vs atypical angina
Diagnoses Not to Miss: “The Serious Six” (3 Heart, 2 Lung, 1 Esophagus)¶
- Acute Coronary Syndrome
- Aortic Dissection/Aneurysm
- Cardiac Tamponade
- Pneumothorax
- Pulmonary Embolus
- Mediastinitis (e.g, esophageal perforation)
Other Differential Diagnoses¶
- Skin/subcutaneous: Laceration, herpes zoster, cellulitis, abscess
- Musculoskeletal: Costochondritis, rib fracture, myositis, sprain/strain
- Pleural space (no pain receptors in the lung): PNA, tumor, pleuritis
- Heart: Myocarditis, pericarditis, spontaneous coronary artery dissection (SCAD), coronary vasospasm, aortic stenosis, stress-induced cardiomyopathy (Takotsubo), decompensated heart failure
- GI: GERD, esophagitis, rupture, impaction, diaphragmatic hernia
- Trachea: Tracheitis, tracheal tear
- Nervous system: thoracic radiculopathy
Physical Exam¶
- Vitals: BP in both arms (do while interviewing - quick, easy, inexpensive)
- Hemodynamic profile (warm/dry, warm/wet, cold/dry, cold/wet)
- Palpate chest: evaluate costochondral junction, subcutaneous emphysema, examine skin
- Cardiac: murmurs, rub for pericarditis, JVD for heart failure or PE with RV strain
- Pulm: absent breath sounds for PTX, crackles for left heart failure, PNA
- Abdomen: abdominal pain mistaken or referred as chest pain
- Extremities: asymmetric leg swelling (>2 cm difference) for DVT/PE
Diagnostic Studies¶
- EKG: ACS (STEMI, new LBBB, ST depressions, TWI, Wellens sign), pericarditis, pericardial effusion
- Labs: Troponin (ACS, PE, myocarditis), CBC, BNP, lactate
- CXR: PTX, PNA, dissection, esophageal rupture
- Bedside ultrasound: pericardial effusion, R heart strain for PE, wall motion abnormality for infarct/ischemia or stress-induced CM, valvular disease, lung sliding/PTX
- CTA: gold standard for PE. Dissection can be diagnosed w/ CTA, MRA, or TEE
Evaluation for Coronary Disease |
||||
---|---|---|---|---|
Test | Indications | Benefits | Risks | Considerations |
EKG Stress | Low to Intermediate risk patients Do not stress active or suspected ACS Serves as screening with high NPV |
Functional status w/ Bruce treadmill protocol | Exercise tolerance limits use |
Cannot have LBBB, nondiagnostic if 85% target HR not achieved |
Dobutamine Echo Stress | More sensitive than EKG | Contraindicated: arrhythmias, LVOT obstruction, HTN, AS | Can be useful to eval low grade low flow AS Hold BB |
|
SPECT stress | More sensitive than echo, Assess viability |
Adenosine or Regadenason contraindicated in reactive airway disease | No caffeine or theophylline prior | |
PET stress | Better PPV than Echo Assess viability |
Better for pts with larger abdominal girth (less diaphragmatic attenuation) | ||
Cardiac MRI | Assesses viability | Can assess nonischemic vs ischemic cardiomyopathy; HR must be < 70, gold standard for structure and function | ||
Coronary CT | Very high NPV for stenosis | Contrast media reactions CIN lower risk than cath |
Might have poor lumen visualization if heavy calcium burden HR < 70 |
|
Coronary Angiogram | STEMI High risk NSTEMI: Refractory angina, new arrhythmia, cardiogenic shock (HF) Suspected true ACS Diagnostic and Therapeutic |
Direct visualization of lumen Therapeutic PCI |
CIN with contrast Cath site complications Rare: SCAD, cholesterol emboli |
Positive Screen (above) necessitates LHC Case request cath lab NPO MN prior Groin check if femoral access |
Heart Failure¶
Leonie Dupuis
Background¶
ACC/AHA Stages of HF
- Stage A: At risk but without structural heart disease, symptoms, or cardiac biomarkers
- Stage B: no symptoms/signs of HF; presence of structural heart disease, incr filling pressures, or incr cardiac biomarkers
- Stage C: + structural HD, + prior or current symptoms
- Stage D: marked HF, symptoms interfere with daily life and recurrent hospitalizations
NY Heart Association (NYHA) Functional Classes of HF
- Class I: Normal physical activity is not limited
- Class II: Comfortable at rest; normal physical activity results in HF symptoms
- Class III: Comfortable at rest; less than normal activity leads to HF symptoms
- Class IV: Inability to perform any physical activity without symptoms
Etiologies¶
- HFrEF (Clinical diagnosis + LVEF \< 40%)
- Ischemic (approx. ⅔): Obstructive CAD, previous/current myocardial infarction
- Non-ischemic:
- Load: HTN, valvulopathy
- Arrhythmia: tachyarrhythmia, pacemaker induced
- Myocardium
- Toxins (EtOH, drugs, chemo, radiation),
- Inflammatory (infections, autoimmune),
- Metabolic (thyroid, thiamine deficiency),
- Infiltrative (amyloid, sarcoid, hemochromatosis)
- Stress induced/takotsubo CM
- Genetic
- Idiopathic
- HFpEF: HTN, CAD, obesity, DM, infiltrative, hypertrophic cardiomyopathy
Causes of Heart Failure Exacerbations (FAILURES)¶
- Forgetting medications or taking drugs that can worsen HF (e.g. BB, CCB, NSAIDs, TZDs), chemo (anthracyclines, trastuzumab)
- Arrhythmia/Anemia: AF, VT, PVCs; Increased arrhythmia burden on device check?
- Ischemia/Infarction/Infection: myocarditis; Acute vascular dysfunction (e.g. endocarditis), especially mitral or aortic regurgitation.
- Lifestyle choices: Dietary indiscretions - high salt, EtOH, excessive fluid intake. Obesity.
- Upregulation (of CO): pregnancy and hyperthyroidism
- Renal failure: acute, progression of CKD, or insufficient dialysis (Increased preload)
- Embolus (pulmonary) or COPD (leads to increase right-sided afterload)
- Stenosis (worsening AS, RAS) leading to hypertensive crisis high left-sided afterload
Presentation¶
- Volume overload: shortness of breath, dyspnea on exertion, Orthopnea, PND
- Nausea/poor po intake (hepatic and gut congestion)
- Confusion (decreased CO)
- Exam: Edema (legs, sacrum), rales, S3, S4, murmur (AS, MR), elevated JVD, + hepatojugular reflex, ascites
Evaluation¶
- CBC, CMP, Magnesium, Lactate, TSH, iron studies
- Troponin, ECG
- BNP (Pro-BNP if on Entresto) – high negative predictive value for HF (false negative can occur in obese patients)
- CXR – differentiate other causes of dyspnea
- TTE
- Determine hemodynamic and volume profile
- Cold vs warm
- Dry vs wet
Cardiac Index | Euvolemia | Hypervolemia | |
---|---|---|---|
Low | Warm Extremities Adequate UOP Normal PPP |
Warm and Dry Forrester Class I Tx: GDMT as tolerated |
Warm and Wet Forrester Class II Tx: Diuresis, Vasodilators |
Normal | Cardiogenic Shock Cool Extremities Renal Failure Narrow PP |
Cold and Dry Forrester Class III Tx: Inotropes |
Cold and Wet Forrester Class IV Tx: Diuresis +Tailored therapy (+/- vasodilators, inotropes) |
Management of exacerbations¶
- Tele, Daily STANDING weights, 2L fluid restriction, 2g sodium diet, strict I/Os
- Diuresis: Place on 2.5 x home dose of IV diuretic, dose BID-TID (DOSE Trial)
- Goal is to be net negative (generally 1-2 L per day but patient dependent)
- Check BMP BID and Mg QD, keep K>4 and Mg>2
- Low threshold for substantial increase (double) in loop vs transition to drip if not diuresing adequately
- Can also augment with sequential nephron blockade (thiazides, acetazolamide)
- Lasix 40mg PO = Lasix 20mg IV = Torsemeide 20mg PO/IV = Bumex 1mg PO/IV
- Continuation/optimization of GDMT (below)
Guideline-Directed Medical Therapy for HFrEF¶
General Principles¶
- Starting patients on low dose of multiple agents preferred to max dose of single agent
- D/C summary should have discharge weight, GDMT and diuretic regimen, and renal function
- Daily home weights with rescue diuretic plan (pm dose for 3 lbs in 1 day, 5 lbs in 3 days
Drug | Indication | Mechanism/ Benefits | Precautions |
---|---|---|---|
Beta Blockers | |||
Carvedilol Metoprolol succinate Bisoprolol |
HFrEF <40 % Stage C HF (NYHA class I – IV) |
Reduces catecholamine stimulation. Decreased HR, myocardial energy demand, less adverse remodeling. | Avoid if pt is decompensated (cold); “start low and go slow” Can continue during exacerbation if patient compensated |
ARNIs | |||
Sacubitril/ valsartan | HFrEF < 40% NYHA class II – IV Used in place of ACE/ARB |
Prevents vasoactive natriuretic peptide degradation involved in pathogenesis of HF (+ action of ARB) | Need a 36 hr wash-out period if transitioning from ACEi to ARNI Hypotension Risk of angioedema |
ACEIs | |||
Lisinopril Enalapril Captopril Ramipril |
HFrEF <40 % Stage C HF (NYHA class I – IV) |
Blocks harmful effects of RAAS activation and attenuates adverse cardiac and vascular remodeling | Risk of angioedema Monitor renal function and K |
ARBs | |||
Losartan Valsartan Candesartan |
HFrEF <40 % Stage C HF (NYHA class I – IV) |
See ACEIs | See ACEIs Preference for ARB > ACEi if plans to start ARNI |
MRAs | |||
Eplerenone Spironolactone |
NYHA class II-IV and GFR >30 |
Diuretic and blood pressure lowering effects and blocks deleterious effects of aldosterone on the heart (including hypertrophy and fibrosis) | Hyperkalemia – avoid if CrCl <30 or K >5 |
SGLT2i | |||
Dapagliflozin Empagliflozin |
HFrEF <40% with and without DM NYHA class II-IV In conjunction with background GDMT |
Osmotic diuresis and natriuresis, improve myocardial metabolism, inhibit sodium-hydrogen exchange in myocardium, reduce cardiac fibrosis | UTI/ GU infections Risk of ketoacidosis (both DKA and euglycemic) |
Vasodilators | |||
Hydralazine Isosorbide Dinitrate |
Persistently symptomatic black patients despite ARNI/ BB/ MRA/ SGLT2i NYHA class III-IV |
Reduces cardiac afterload and preload and may also enhance nitric oxide bioavailability Reduction in mortality for African American patients |
Hypotension |
Ivabradine | |||
Ivabradine | HFrEF <35%, on maximally tolerated BB, sinus rhythm with HR > 70 NYHA class II or III |
If current inhibitor involved in SA node activity Decr HR associated with improved outcomes |
Need sinus rhythm Caution in sinus node disease and conduction defects |
Iron Repletion (IV) | |||
Iron sucrose Ferric carboxymaltose Iron dextran |
Ferritin <100 µg/L or ferritin 100-299 µg/L AND transferrin saturation <20% | Decreases HF hospitalizations Improves exercise function and QOL |
Risk of anaphylaxis higher in iron dextran |
Device therapies (after optimization of medical GDMT for 3 months)¶
- Cardiac resynchronization therapy (CRT)
- Class I indication: NYHA class II to IV, LVEF ≤35% with QRS ≥150 ms and left bundle branch block (LBBB)
- ICD
- Class I indication: NYHA class II – VI with LVEF \<35% (must have >1yr expected survival and 40+ days from MI)
- Mitra Clip
- Criteria: moderate to severe mitral regurgitation (3-4+), on maximally tolerated GDMT, an ejection fraction >20%, and a left ventricle end-systolic dimension of less than 7 cm
Guideline-Directed Medical Therapy for HFpEF¶
- Medications overlap with HFrEF treatment (above) but outcomes are less
significant
- SGLT2 inhibitors can decrease HF hospitalizations and CV mortality
- MRAs can decrease HF hospitalizations
- ARBs and ARNis can be used to decrease hospitalizations
- Diuretics as needed for congestion (no morbidity or mortality benefit)
Approach to the ECG¶
Melis Sahinoz
Method = mastery, approach each EKG the same.
Rate¶
- Regular rhythms = “Rule of 300” = 300 ÷ (large boxes between QRS complexes)
- 1 box = 300 bpm, 2 boxes = 150 bpm, 3 boxes = 100 bpm, 4 boxes = 75 bpm, 5 boxes = 60 bpm, 6 boxes = 50 bpm
- Irregular rhythms or severe bradycardia = (total number of QRS complexes on ECG) x 6
Rhythm¶
- Determine regular vs irregular: calipers or march out QRS complexes on paper
- Criteria for Sinus rhythm: P before every QRS; Upright P in Lead I, II; Negative in aVr
Axis¶
- Normal: - 30o to + 90o
- Quick method: Leads I and II
- Normal Axis: Upright in I and II
- Left Axis Deviation: Upright in I, down in II
- Causes: LVH, LBBB, Left anterior fascicular block, prior inferior MI
- Right Axis Deviation: Down in I, up in II
- Causes: RVH, RBBB, Left posterior fascicular block, prior lateral MI, PE
Intervals¶
- PR Interval: normal 120 – 200 ms
- If < 120 ms, consider pre-excitation with accessory pathway (i.e. WPW)
- If > 200 ms, first degree AV block
- QRS Complex: 60 – 100 ms (normal)
- If 100-120 ms: Incomplete BBB or non-specific intraventricular conduction delay (IVCD)
- If > 120ms: complete BBB, ventricular tachycardia, hyperkalemia
- QT interval: Normal duration < 450ms in men and < 460ms in women
- QT is inversely proportional to HR (QT interval shortens at faster HRs)
- Quick estimate: normal QT is less than half the preceding RR interval
- QTc estimates the QT interval at a HR of 60 bpm (to allow for comparison across HRs)
- A couple of formulas exist to calculate QTc:
- QTcB= most commonly used due to simplicity, most accurate HR of 60
- QTcF= more accurate when HR is outside the range of 60-100
- Clinically significant when generally QTc > 500 ms
- Causes of Prolonged QTc: hereditary, medication-induced (anti-emetics, ABX, psychiatric meds), hypokalemia, hypomagnesemia, hypocalcemia, ischemia
Morphology¶
- P wave: P waves in limb leads should be ≤2.5 small box high and ≤2.5
small box wide
- Right Atrial Enlargement: Peaked P Wave in Lead II that measures >2.5 mm
- Left Atrial Enlargement
- Lead II: Bifid P Wave (two humps) with total duration > 110 ms
- Lead V1: Biphasic P wave, terminal deflection > 1mm wide and deep
- If ≥ 3 different P wave morphologies in same lead: wandering atrial pacemaker (HR < 100) or multifocal atrial tachycardia (HR > 100)
- QRS complex
- Voltage
- Low voltage: QRS amplitude < 5mm in limb leads or < 10mm in
precordial
- Causes: pericardial effusion, infiltrative cardiomyopathy, obesity
- Right Ventricular Hypertrophy: Tall R Waves in V1 (> 7mm) and right axis deviation
- Left Ventricular Hypertrophy: multiple criteria exist
- Sokolow-Lyon criteria is a common example: S in V1 + R in V5 or V6 >35mm, R in aVL ≥ 1.1 mV
- Low voltage: QRS amplitude < 5mm in limb leads or < 10mm in
precordial
- Voltage
- Conduction delays
- RBBB: Wide QRS and RSR’ in V1 or V2; deep broad S In lateral leads
- LBBB: Wide QRS, large S in V1, broad monophasic R wave in lateral leads (I, aVL, V6)
- R wave progression
- R wave normally gets progressively larger from V1 to V6
- If the transition does not occur by V4, this is called "poor R wave progression". This is seen in chronic lung disease, LVH, left anterior fascicular block, and anterior MI.
- Q-wave: Small Q waves are normal in most leads
- Never normal in V1-V3
- Pathologic Q waves: > 1 box wide and 2 boxes deep or > 25% height of R wave
- ST Segment
- ST Elevation: STEMI, LBBB (ST elevation in leads with deep S waves), LVH, ventricular paced rhythm, pericarditis (associated with PR depression), coronary vasospasm, Brugada syndrome
- ST Depression: ischemia, reciprocal change in STEMI, posterior myocardial infarction (V1-V3), digoxin, hypokalemia
- See ACS section for STEMI criteria, Wellens Syndrome
- T wave
- Normal T waves are upright in all leads except aVR and V1
- Inverted T Waves
- Acute ischemia (if present in contiguous leads), LBBB (in lateral leads), RBBB (V1-V3), LVH (‘strain’ pattern similar to LBBB), RVH (RV ‘strain’ in V1-V3 or inferior leads), PE (right heart strain or part of S1,Q3,T3), intracranial pathology
- Peaked T Waves
- Hyperkalemia vs ‘hyperacute’ T waves that precede ST elevation and Q waves in STEMI
Inpatient Hypertension¶
Nicholas Weinand
Background¶
- Hypertensive urgency: SBP > 180mmHg/DBP > 120mmHg
- Hypertensive emergency: SBP > 180mmHg/DBP > 120mmHg + end organ damage
Evaluation¶
- Are there signs/symptoms of end organ damage?
- Neurologic symptoms: agitation, delirium, stupor, seizures, visual disturbances
- Focal neurologic deficits
- Chest pain
- Back pain (consider aortic dissection)
- Dyspnea (consider pulmonary edema)
- BMP, LFTs, Troponin, BNP: Lab findings suggestive of end-organ damage
Management¶
- Goal is to lower BP back to normal over 24-48 hours
- Initial lowering should be 10-20% in minutes if HTN emergency; goal should be 10-20% in 2-4 hours if HTN urgency
- Typically aim for initial goal BP near 160/110
- Exceptions to gradual lowering include:
- Acute stroke: call code stroke, lower ONLY if BP > 185/110 in pts under consideration for reperfusion therapy; or BP > 220/120 in pts not candidates for reperfusion therapy
- Aortic dissection: Goal = rapidly lower BP in minutes to target of 100-120 systolic to avoid aortic shearing forces
-
Pharmacologic therapy
- Ensure their home medicines have been restarted at appropriate doses, formulation (long acting vs. short), and dosing intervals
- If pt has a rapid acting anti-HTN med, can consider giving a dose early or an "extra dose" and then up titrating their overall daily dose
-
Rescue therapies
- Captopril PO (12.5mg or 25mg dosed Q8H; conversion ratio of captopril:lisinopril = 5:1)
- Hydralazine PO (10-20mg initial dosing Q6H)
- Isosorbide dinitrate PO (5-20mg TID)
- Nifedipine XL PO (dose at 30mg initially, max 90 mg BID; NOT sublingual)
- Labetalol IV (10-40mg initially; dosed up to every 20-30mins)
- Hydralazine IV (10-20mg initially; dosed up to every 30 mins).
- Nitropaste 1” (can add/wipe away for titration; dose Q6H until oral meds can be started for better long-acting control)
- Dialysis if missed session
Additional Information¶
-
Refractory HTN: try additional agents listed above vs. escalation of care for drip (nicardipine, nitroglycerin, nitroprusside, esmolol).
-
Most drips that can be done for this indication are done in stepdown and usually require no-titration of the infusion and occasionally the MD to be bedside to initiate the infusion.
-
This includes diltiazem, labetalol, nitroglycerin, and verapamil drips. Nicardipine, esmolol, and nitroprusside drips are not allowed on step down.
Pulmonary Embolism¶
Anna Berry
Background¶
A thrombus originating in a deep vein (LE > UE) embolizing to the pulmonary arterial circulation.
- Risk Factors = Virchow’s Triad
- Stasis: immobilization, hospitalization, spinal cord injury, or long travel
- Hypercoagulable state: cancer, prothrombotic genetic conditions such as Factor V Leiden, OCPs, antiphospholipid syndrome, nephrotic syndrome, pregnancy, infection, etc.
- Endothelial Injury: surgery, trauma
Most originate from a DVT in the iliac, femoral, and popliteal veins
Presentation¶
- Dyspnea and tachypnea
- Respiratory alkalosis on blood gas from hyperventilation
- Hypoxemia
- Sinus Tachycardia or atrial arrhythmias
- Hemoptysis
- Lower extremity pain, swelling, and redness – occurs in 50% of pts with DVT
- RV Failure (large PE) – elevated JVP, hypotension, syncope, R parasternal heave, accentuated P2, hepatomegaly
Evaluation¶
- If hemodynamically unstable and PE suspected, provide hemodynamic support (ie. O2, pressors, etc.) and perform emergent bedside TTE
-
If no RV strain evident on TTE, low likelihood of hemodynamically significant PE. Consider other causes of shock.
-
Hemodynamically stable
- EKG
- Most commonly sinus tachycardia
- Less commonly and indicative of large PE: RAD, RVH, RBBB, RA enlargement, S1Q3T3 (deep S in lead I, deep Q and inverted T in lead III), TWI in V1-V3
- CXR: Typically normal. May see linear atelectasis, pleural effusion, PA cutoff sign
- Labs: ABG, troponin, BNP
- May consider lower extremity dopplers
- Imaging vs d-dimer based on pre-test probability:
- Low pre-test probability (use Wells Criteria) d-dimer
- For moderate to high pre-test probability CTA Chest PE protocol
- If high pre-test probability or moderate pre-test probability with >4 hour delay in work-up, start empiric anticoagulation if bleeding risk is acceptable while work-up is ongoing
- TTE
- EKG
Management¶
PE Class: | Low risk | Submassive | Massive |
---|---|---|---|
Definition | Hemodynamically stable No evidence of right heart strain or myocardial necrosis on labs or TTE |
Hemodynamically stable Evidence of right heart strain or myocardial necrosis: RV strain on TTE (ex: D-sign), BNP >150, trop >0.05 |
Hemodynamically unstable (ex: SBP<90) Evidence of RV strain |
Management | Start anticoagulation LWH or heparin gtt (if renal impairment) Can also use NOAC. Rivaroxaban & apixaban can be used as initial management. Edoxaban & dabigatran can be used after 5-10 days of parenteral therapy |
Provide hemodynamic support, monitor for decompensation Start anticoagulation with unfractionated heparin gtt STAT consult cardiology for consideration of catheter directed thrombolysis (EKOS) or embolectomy |
Provide hemodynamic support. Start anticoagulation with unfractionated heparin gtt Page CCU fellow STAT. Consider systemic tPA (this is a fellow/attending level decision). Discuss with cardiology catheter directed thrombolysis (EKOS) or embolectomy |
tPA Considerations¶
- Dose is 100mg tPA over 2hrs
- Most effective within 24 hours but effective up to 14d
- Contraindications:
- Absolute:
- CNS Pathology: hemorrhagic or ischemic CVA within 3 mo, AVM, CNS neoplasm, recent surgery
- Trauma: Recent head trauma w/ fx or injury
- Relative
- Surgery: surgery w/in 3 wks
- Heme: active bleeding, bleeding diathesis, plt \< 100, oral AC
- Age: >75 yo, dementia
- Absolute:
Long-term management¶
-
Anticoagulation
- NOAC - Remember to give initial loading dose (duration of load varies with each agent)
- Warfarin (Coumadin): Goal INR 2-3, requires frequent monitoring
- Need to bridge with heparin or lovenox
- Pharmacy consult, and will need to be set up with coumadin clinic at the time of dc
-
IVC filter: only if AC is contraindicated, bleeding risk unacceptably high, recurrent PE despite optimal AC (placed by IR or Interventional cards)
## Duration of Anticoagulation:
- Major reversible/transient risk factors (surgery, trauma): 3-6 months
- Idiopathic, unprovoked, or with less compelling risk factors: 12 months
- Major permanent risk factors (cancer, homozygote F5L or prothrombin gene mutation, APLS, protein C/S deficiencies, AT III deficiency): At least 1 year, preferably lifelong.
- Recurrent DVT/PE: lifelong
- Consider etiology of recurrent VTE: cancer screenings, family hx of hypercoagulable disorders, features of autoimmune disease
Pericarditis¶
John Mitchell
Background¶
- Inflammation of the pericardial sac
- Etiologies:
- Infectious: Viral (Coxsackievirus, adenovirus, COVID-19), bacterial (TB, staph, strep), fungal
- Inflammatory: Rheumatologic (most commonly SLE and RA), post-radiation, vaccine reaction, post pericardiotomy syndrome
- Cardiac: Infarction (Dressler syndrome) and myocarditis
- Miscellaneous: Trauma (including procedures e.g. cath, cardiac surgery), metabolic (uremia, hypothyroid), drug-induced, malignancy
- Idiopathic (most common cause, assumed to be viral/post-viral)
Presentation¶
- At least two criteria of four should be present:
- Sharp substernal pleuritic chest pain that is better with leaning forward
- Pericardial friction rub
- New widespread ST elevation and PR depression
- New or worsening pericardial effusion
- Chest pain almost always present. Pericardial rub highly specific
- Even small effusion can help confirm diagnosis, but lack thereof does not rule it out
Evaluation and Management¶
- Always: EKG, chest x-ray, BMP, CBC, troponin, ESR, CRP and TTE
- TTE should be performed ASAP if tamponade suspected
- In select populations if warranted: Blood cultures, ANA, RF, anti-CCP, PPD, chest CT
- Treatment:
- NSAIDs (or glucocorticoids if contraindications to NSAIDs) AND
colchicine
- Ibuprofen 600-800mg TID (duration based on symptom resolution and normalization of CRP)
- Prednisone 0.2-0.5mg/kg daily for 2 weeks followed by tape
- Colchicine 0.6mg orally BID for 3 months
Right Heart Catheterization¶
Ahmad Yanis
Pulmonary artery catheter (PAC): Multilumen catheter that sits in the right heart to provide invasive measurement of hemodynamic parameters
Indications for PAC placement¶
-
Diagnose undifferentiated shock
-
Severe cardiogenic shock
-
Diagnose pulmonary hypertension
-
Diagnose left -> right shunting
-
Diagnose valvular and pericardial disease
-
Titrating medications, specifically inotropes, pulmonary vasodilators, diuresis
Contraindications to PAC placement¶
-
Infection at the insertion site
-
RA/RV mass or thrombi
-
Tricuspid or pulmonic valve endocarditis
-
Mechanical tricuspid or pulmonic valves
-
Presence of RV assist device
Complications of PAC placement¶
-
Arrythmias: VT, RBBB, 3rd degree AV block if preexisting LBBB
-
Infection (endocarditis of the pulmonary valve)
-
Bleeding
-
Pulmonary embolism and pulmonary Infarct
-
Pneumothorax
-
Air embolism
-
Pulmonary artery perforation / rupture
-
Endocardial/valvular damage
PAC Pressure Tracings¶
Definition | Normal "Rule of 5s" |
|
|
---|---|---|---|
Central Venous Pressure (CVP) |
Pressure in superior vena cava, often an indicator of volume status | 0 - 5 mmHg | Elevated CVP is indicative of cardiac dysfunction and/or fluid
retention Low CVP is indicative of volume depletion or decreased venous tone |
Right Atrial Pressure (RAP) | Surrogate for preload, should be same as CVP | 0 - 5 mmHg | Elevated with disruption in forward cardiac flow or increase in intravascular volume |
Right Ventricle Pressure ( | Right ventricular systolic and diastolic pressures; RVSP can be surrogate for PASP | 25/5 mmHg | Elevated with diseases that elevate PA pressure and pulmonic valve disorders. Severe RVP elevations are generally chronic while acute conditions typically have RVSP <40-50. |
Pulmonary Artery Pressure (PAP) | Measured as systolic, diastolic, and mean pressures. Diagnoses pHTN. | 25/10 mmHg Mean: 10 - 19 mmHg |
Elevated In acute conditions (PE, hypoxemia induced pulmonary vasoconstriction) or pHTN (mean PAP > 20 mm Hg) |
Pulmonary Artery Wedge Pressure (PAWP or wedge) | Pressure measured by wedging the PAC into a small pulmonary arterial branch; surrogate for left atrial pressures and LVEDP | 10 mm Hg | Increased with elevated LVEDP: systolic or diastolic heart failure, mitral and aortic valve disorders, hypervolemia, R to L shunts, tamponade, constrictive/restrictive cardiomyopathy |
Thermodilution Cardiac Output & Index | Amount of blood pumped in one min. CI is the cardiac output divided by body surface area (to standardize for body size) | CO: 3.4-15 L/min CI: 2.8-4.2 L/min/m^2 |
Low CI: systolic/diastolic heart failure, severe valvular disorder (MR, AS), RV failure, pHTN, cardiogenic shock. Elevated CI (high-output state): sepsis, anemia, thyrotoxicosis, A-V shunt |
Mixed central venous oxyhemoglobin saturation (SvO2) |
% of oxygen bound to Hgb in blood returning to the right side of the heart, reflects total body O2 extraction | 65-70% | High SvO2 (> 65%) = decreased O2 demand or “high flow” states seen in distributive shock (sepsis) Low SvO2 (< 50%) = decreased O2 delivery seen in cardiogenic or hypovolemic shock. In low SvO2 states, there is less O2 supply to same demand) |
Calculating Hemodynamic Parameters from PAC Pressures¶
Definition | Normal Values | Interpretation | |
---|---|---|---|
Fick CO and CI | Calculated CO based on Oxygen consumption (VO2), Hbg, and O2 sats of arterial and venous blood | 4-7 L/min 2.5-4 L/min/m2 |
See "Cardiac Index" above. |
Systemic Vascular Resistance (SVR) | Measurement of afterload; helpful in delineating the etiology of shock as well as guiding afterload-reduction therapy in HFrEF | 700-1200 dynes*s*cm-5 | Elevated SVR is seen in hypovolemic, cardiogenic, and obstructive shock Decreased SVR is seen in distributive shock (sepsis, anaphylaxis, neurogenic) |
Transpulmonary gradient (TPG) | Differentiates between pre- and post-capillary pulmonary hypertension. | < 12 mmHg | A TPG value greater than 12 mmHg indicates that a component of the pHTN is secondary to pulmonary vascular disease |
Pulmonary Vascular Resistance (PVR) | Gold standard in the estimation of the severity of pre-capillary
pHTN Reflects the pressure drop across the pulmonary system only and is independent of the LA, mitral valve and the LV |
< 3 Wood Units 30-90 dynes*sec*cm5 |
Elevated PVR (>3 Wood units) suggests pre-capillary pHTN Normal PVR seen in pulmonary venous hypertension (diastolic dysfunction) |
Pulmonary artery pulsatility index (PAPi) | Pulmonary pulse pressure relative to preload (RAP), Indicator of RV function | > 0.9 | PAPi < 0.9 predicts in-hospital mortality and/or need for RVAD in acute MI. Can be decreased in pure RV failure or biventricular failure |
Cardiac Power | Cardiac output relative to afterload, a measure of LV contractile reserve | Normal > 1 | CP< 0.6 strongly suggestive of LV failure Found to be a strong independent hemodynamic correlate in pts with cardiogenic shock. Predictor of mortality in CCU |
Cardiogenic Shock¶
Sims Hershey
Definition¶
- Impairment of CO due to primary cardiac disorder that results in end-organ hypoperfusion and hypoxia
- Mortality of up to 40-50%
Etiology¶
- Cardiomyopathic: myocardial infarction with LV dysfunction (most common cause), exacerbation of heart failure, PHTN exacerbation, myocarditis, myocardial contusion, drug-induced
- Arrhythmic: atrial tachycardias (atrial fibrillation/flutter, AVRT, AVNRT), VT/VF, complete heart block, 2nd degree heart block
- Mechanical: valvular insufficiency, valvular rupture, papillary muscle rupture, critical valvular stenosis, ventricular septal wall defect, ruptured ventricular wall aneurysm, atrial myxoma, HOCM
Presentation and diagnostic criteria¶
- "Cold and wet" - decreased perfusion due to reduced cardiac output with pulmonary congestion and/or increased left sided filling pressures. May also be "cold and dry" in the setting of normal PCWP with low cardiac output.
- Signs of end-organ hypoperfusion - AMS, cold and clammy skin, decreased UOP (\<30cc/hr), and elevated lactate (>2).
- SBP \< 90 mmHg for >30min or needing vasopressors to achieve this goal, usually with narrow pulse pressure
- Initially, SVR is elevated in the s/o hypoperfusion. SVR then declines in progressive shock due to vasodilation in the s/o systemic inflammation causing elevated NO in the shock state.
Evaluation¶
- EKG
- Labs: CBC, CMP, BNP, troponin, lactate
- Evidence of end organ damage: lactic acidosis, acute kidney injury, acute liver injury
- Echocardiogram: assess EF and valves
- LHC If ischemia (see ACS)
- Hemodynamic monitoring via Swan-Ganz or PA catheter:
- No benefit for general shock but does improve in-hospital mortality for those with cardiogenic shock
- PA catheter hemodynamic profile:
- Cardiac index \< 2.2, cardiac power \<0.6, SVR 800-1600, SVO2 \<60%
- LV-dominant: RA (CVP) \<15, PCWP >18, PAPi >1.5 (pulmonary artery pulsatility index)
- RV-dominant: RA >15, PCWP \<18, PAPi >1.5
- Bi-V-dominant: RA >15, PCWP >18, PAPi >1.5
- PAPi \< 1 indicates that patient will likely need RV support
- CP \< 0.5 strongest independent hemodynamic correlate of mortality in CS
- See right heart cath section for interpreting PA catheter profiles
Management (medical & mechanical circulatory support)¶
Medical management¶
- Medical management: focus on optimizing preload, afterload, and
contractility
- Preload: IV diuresis -- hypotension IMPROVES with diuresis in cardiogenic shock
- Afterload: IV -- nitroglycerine, nitroprusside; PO -- hydralazine, isosorbide dinitrate; vasoconstricting pressors (phenylephrine, vasopressin) if needing BP support
- Contractility - Inodilators (increase contractility, decrease afterload -- milrinone, dobutamine) or inoconstrictors (increase contractility and afterload -- epinephrine, norepinephrine)
Mechanical circulatory support indications¶
- Shock refractory to >1 pressor
- Shock 2/2 MI (physiology: unloads LV, increases systemic perfusion, increases myocardial perfusion, and provides hemodynamic support during PCI)
Types of mechanical circulatory support (MCS)
Intra-aortic Balloon Pump | V-A ECMO | Tandem Heart | Impella | |
---|---|---|---|---|
Dynamics | Inflates during diastole, deflates during systole | Blood from femoral vein is oxygenated and pumped to femoral artery | LV: blood aspirated from LA to femoral artery RV: blood aspirate from RA to PA |
Impella 2.5, 5.0 & CP: Blood aspirated from LV to aortic root Impella RP: Blood aspirated from IVC and delivered to PA |
Flow | 1 LMP | 4.5 LPM | 4-5 LPM | 2.5: 2.5 L/min CP: 3.33 L/min 5.0: 5 L/min RP: 4 L/min |
Support | LV | BiV | LV, RV, or BiV | LV or RV (RP) |
Effects | Reduces afterload Increases stroke volume (SV) Increases coronary perfusion Reduces LV preload and PCWP |
Increases afterload Reduces SV Reduces LV preload and PCWP Improves tissue perfusion |
Increases afterload Reduces SV Reduces LV preload and PCWP Improves tissue perfusion |
Reduces SV Reduces preload and PCWP Improves tissue perfusion |
Complications | Thrombocytopenia Thrombosis Arterial obstruction Aortic rupture or dissection Air embolism |
Circuit thrombosis LV dilation Hypothermia Gas embolism |
Tamponade d/t perforation Thrombosis Embolism (gas or thrombus) Arterial Shunt |
Pump migration Hemolysis Aortic regurg LV perf VT/VF |
Possible contraindications to mechanical circulatory support:¶
- Aortic regurgitation, intracardiac shunt via ASD, VSD, or PFO, severe RV dysfunction, LA or ventricular thrombus, aortic dissection, uncontrolled sepsis, severe coagulopathy or bleeding diathesis
Daily management of MCS devices:¶
-
Ensure optimal placement of device with daily CXR/Echo
-
Anticoagulation (based on device)
-
Hematoma monitoring at device site
-
Check distal pulses to monitor for limb ischemia
Syncope¶
Sarah Myers
Background¶
- Definition: abrupt, transient loss of consciousness with rapid & spontaneous recovery
- Presyncope – symptoms occurring before syncope including lightheadedness, tunnel vision/other visual disturbances
Classification¶
- Cardiac syncope
- Tachyarrhythmias: VT, SVT
- Bradyarrhythmias: sinus node dysfunction, AV blocks (high grade)
- Structural: Aortic Stenosis, HCM, cardiac tamponade, congenital anomalies, masses/tumors
- Vascular: Pulmonary embolism, aortic dissection, severe pHTN
- Noncardiac syncope
- Reflex mediated
- Vasovagal; most common form of reflex mediated syncope
- Can occur sitting/standing or with trigger (stress, pain, medical settings)
- Classically has prodrome of nausea, diaphoresis, tunnel vision followed by hypotension and/or bradycardia
- Situational (micturition/defecation/coughing)
- Carotid sinus sensitivity syndrome
- Vasovagal; most common form of reflex mediated syncope
- Orthostatic
- Medications (diuretics, nitrates/CCB/alpha blockers, TCAs)
- Volume depletion (hemorrhage, dehydration)
- Autonomic dysfunction
Differential diagnosis¶
- Seizure, stroke, metabolic derangements, Intoxication/withdrawal,
hypoglycemia, head trauma
- With rare exceptions, these do not result In complete LOC with spontaneous recovery
Evaluation¶
- History and physical are essential for evaluation of a syncopal event
- Characteristics associated with cardiac syncope
- Male, >60, known structural/ischemic heart disease, brief/no prodrome, syncope while supine/at rest or during exercise, family hx of SCD/premature death, abnormal exam
- Characteristics associated with noncardiac syncope
- Younger age, syncope while standing or with positional changes, prodrome (nausea, vomiting, warmth), specific triggers, previous episodes that have been similar
Workup¶
- EKG on all patients with syncope, monitor those who are admitted on telemetry
- CBC, CMP, troponin, BNP (If cardiac cause suspected), POC glucose, UDS, orthostatic VS
- EEG and neuroimaging if concern for seizure activity or focal neuro deficit
- TTE and consider stress testing particularly in exertional syncope
Management¶
- Cardiac: managed as indicated based on pathology
-
If arrhythmia is suspected but not captured on admission, consider discharge with event monitor
-
Noncardiac
-
Reflex
- Vasovagal- consider tilt table testing If recurrent or diagnosis not clear
- Situational- mainly avoiding triggers
- Carotid sinus syndrome- may require PPM
-
Orthostatic
- Medication related
- Appropriate to hold potentially offending medications (diuretics, vasodilators) during evaluation
- Monitor for worsening supine hypertension, arrhythmias, or heart failure when holding
- Volume depletion; resuscitate as appropriate
- Autonomic dysfunction: see autonomics section
- Medication related
-
Driving: TN law does not require any MD to inform the state of TLOC
- Should still recommend patients not drive while work-up ongoing. Document all conversations about driving with patients
Valvular Heart Disease¶
Audrey White
Aortic stenosis¶
Chloe Carr
Etiology¶
- Degenerative calcification of the aortic cusps
- Congenital bicuspid aortic valve
- Chronic deterioration (calcific)
- Prior rheumatic fever/inflammation
Presentation¶
- Usually asymptomatic
- Angina, syncope, exertional dyspnea, heart failure (HF carries worse prognosis) when severe
- Typically aged 70 – 80 y/o; if bicuspid aortic valve expect 10-20 yrs earlier
- Physical exam: Systolic crescendo-decrescendo murmur that radiates
towards the carotids
- Late peaking murmur, faint or absent S2, or delayed carotid upstroke suggest severe AS
Evaluation¶
- TTE with doppler is test of choice
Severity | Valve Area (cm2) | Mean Gradient (mmHg) | Velocity (m/s) |
Indexed Valve Area (cm2/m2) |
---|---|---|---|---|
Mild | >1.5 | <20 | 2.0-2.9 | >0.85 |
Moderate | 1.0-1.5 | 20-39 | 3.0-3.9 | 0.60-0.85 |
Severe | <1.0 | >40 | >4.0 | <0.6 |
Critical | <0.5 | -- | -- | -- |
AS stages¶
- A: at risk of AS (those with bicuspid anatomy or calcification
- B: Asymptomatic non-severe AS
- C: asymptomatic AS
- C1: normal EF
- C2: abnormal EF
- This stage might benefit from exercise or stress testing to elicit symptoms
-
D: Symptomatic AS
-
Some with symptomatic AS might not have enough LV reserve to produce high velocities and gradients (ex EF of 10% w/ critical valve area) = low flow/low gradient AS; consider dobutamine to unmask AS
Management¶
- No proven effective medical therapy
- Definitive treatment is valve replacement for:
- Stage D
- Stage C with inducible symptoms on stress testing, low EF, or undergoing other cardiac procedure
- Rapid progression (increase in velocity >0.3m/sec per year)
- Consult cardiac surgery for determination of SAVR vs TAVR
- In general, high risk surgical patients benefit most from TAVR
- At VUMC: If determined to be intermediate to high operative risk by Cardiac Surgery, they will often recommend contacting the TAVR team for evaluation
- Avoid rapid hemodynamic shifts and aggressive changes in preload or afterload
- Aim for normotension
- Avoid preferential vasodilators such as hydralazine or nitroglycerin
- Significant vasodilation may ↓ coronary filling pressures -> myocardial ischemia
Monitoring¶
- Severe AS: TTE q 6-12 months
- Moderate AS: TTE q 1-2 years
- Mild AS: TTE q 3-5 years
Post AVR anticoagulation¶
- All patients will get 3-6 months of AC s/p AVR
- Continued duration based on type of AVR
- Bioprosthetic (TAVR and some SAVRs): antiplatelets alone after Initial AC
- Mechanical: lifelong AC with warfarin only
Aortic Regurgitation¶
Hannah Granger
Etiology¶
- Primary valve disease (rheumatic disease, bicuspid aortic valve, infective endocarditis, syphilis)
- Primary aortic root disease (medial degeneration, aortic dissection, Marfan’s syndrome, bicuspid aortic valve, syphilis, non-syndromic familial)
Presentation¶
- Acute AR: LV cannot respond to increased volume to maintain stroke volume pulmonary edema and cardiogenic shock
- Chronic AR: indolent presentation, often patient will develop symptoms of heart failure including DoE, orthopnea, PND
- Physical exam: “Water-hammer” pulses, wide pulse pressure, laterally displaced PMI, high pitched “blowing” decrescendo murmur best heard at third intercostal space at left sternal border, S3
Management¶
- Acute severe AR
- Page cardiac surgery for urgent surgical repair
- Vasodilators such as nitroprusside and diuretics can be used to stabilize patient
- Though pts with aortic dissection are often treated with beta blockers, these should be used with caution if there is concomitant severe AR as it may block compensatory tachycardia and lead to marked hypotension
-
Chronic severe AR
- Medical management
- Early symptoms of exercise intolerance can be treated with diuretics
- Systolic BP should also be controlled with goal SBP \< 140 in chronic AR
- Medical management
-
Repeat imaging should be performed 3-6 month to assess for depressed LVEF or LV dilation
-
Stages of Chronic AR: Ranging from Stage (A): Asymptomatic but “At Risk” AR to Stage (D) Symptomatic Severe AR
- If symptoms are present, automatically Stage D, otherwise Progression through stages is determined by AR Jet Width
- Class I indications for Valve Repair:
- Stage D (Symptomatic)
- Stage C (Asymptomatic Severe AR) with LVEF \< 55%
- Severe AR and undergoing cardiac surgery for other indication
Mitral Regurgitation¶
Krissie Lobon
Etiology¶
-
Primary MR – caused by direct involvement of the valve apparatus (leaflets or chordae tendineae)
- Most common cause: Degenerative/myxomatous mitral valve disease (mitral valve prolapse with flail leaflet, mitral annular calcification, chordal rupture)
- Rheumatic fever
- Infective endocarditis
- Papillary muscle rupture following acute (inferior) MI
-
Secondary MR (also called functional MR)- caused by changes of the LV that lead to valvular incompetence
- Dilated Cardiomyopathy
- HOCM with systolic anterior motion
- Coronary Artery Disease or prior MI leading to papillary muscle tethering
Presentation¶
- Acute MR- sudden onset reduction in forward cardiac flow and left
atrial/pulmonary vein volume overload
- Dyspnea with flash pulmonary edema
- Left-sided heart failure
- Chronic MR- progressive symptoms d/t cardiac remodeling to
compensate for mitral flow reversal
- Progressively worsening heart failure: dyspnea, orthopnea, PND
- LV dilation from volume overload
- LA remodeling/dilation leading to afib
Auscultation¶
- Holosystolic murmur, best heard at Apex, Radiation to the Axilla
- Frequently associated with S3
- Murmur may be absent in acute MR due to large regurgitant orifice/low velocity regurgitant jet
- Increases w/ increased preload or afterload
Evaluation¶
- CXR: assess for pulmonary edema, typically normal cardiac silhouette in acute MR. Cardiomegaly and LA enlargement in chronic MR.
- ECG: often non-specific if chronic LA enlargement notable on p wave morphology (p-mitrale). Chronic MR often c/b development of atrial fibrillation.
- Echocardiography needed for confirming diagnosis
- TEE, CMR, or cardiac catheterization performed when insufficient or discordant information from TTE. TEE used to guide MV interventions
Chronic MR stages¶
- A: No symptoms
- B: >mild MR w/o hemodynamic changes or symptoms
- C: Severe MR w/o symptoms
- C1: preserved EF and normal LV size
- C2: reduced EF (\<60%), dilated LV (LVESD > 40mm)
- D: Severe/symptomatic
Management¶
Acute hemodynamically significant MR¶
- Urgent surgical repair or replacement
- Medical stabilization as a bridge to surgery
- Afterload reduction is key to promote forward flow
- Vasodilators (nitroprusside, nitroglycerin) reduce afterload
- Diuresis to reduce preload and improve pulmonary edema
- IABP placement can be used as mechanical afterload reduction
Chronic severe primary MR¶
- Surgical repair favored over valve replacement
- Class I:
- Asymptomatic patients w/ LVEF 30-59% or LVESD > or equal 40mm
- Symptomatic patients w/ EF > 30%
- Class II:
- A: asymptomatic patients with progressive EF decline or LV dilation on serial monitoring; or very severe MR
- B: new onset AF
- Secondary MR can consider MV repair with persistent class III-IV symptoms while on guideline directed medical therapy
- In HFrEF, consider MitraClip after volume optimization (see Heart Failure section)
Mitral Stenosis¶
Krissie Lobon
Etiology¶
- Characterized by thickened mitral valve leaflets and fused leaflet tips.
- Rheumatic Fever (leading cause worldwide)
- Calcification of the mitral valve annulus (common in high income countries)
- Autoimmune Diseases: SLE, Rheumatoid arthritis
Presentation¶
- Progressive symptoms: Asymptomatic Heart Failure
- Orthopnea
- PND
- Hoarseness/Dysphagia (compression of recurrent laryngeal nerve/esophagus by enlarged left atrium from pressure overload)
- Symptoms of Right Heart Failure
- Acute Symptoms may present in settings of increased cardiac output
(pregnancy, sepsis, or exercise) or tachyarrhythmias
- Dyspnea
- Fatigue
- Palpitations
Physical exam¶
- Low-pitched rumbling, diastolic Murmur, best heard at apex,
low-pitched, rum
- Loud S1, opening snap after S2
- Prominent P2 if pulmonary HTN develops
- Pulmonary Rales
Stages of MS¶
-
A: At risk of MS, characterized by mild valve doming during diastole, asymptomatic
-
B: Progressive MS, characterized by commissural fusion, increased transmitral flow velocities, asymptomatic
-
C: Asymptomatic Severe MS, characterized by above + mitral valve area \<1.5cm2
-
D: Symptomatic Severe MS, characterized by above criteria + decreased exercise tolerance
Evaluation¶
- CXR: LA enlargement, increased pulmonary vasculature
- Echocardiography: thickening of mitral valve leaflets, decreased area of valve leaflets, left atrial enlargement
Management¶
- Varies between rheumatic MS and calcific MS (in general, intervention of calcific MS is very challenging and high risk)
- Severe, symptomatic rheumatic MS:
- Percutaneous mitral balloon commissurotomy (PMBC)
- Surgical repair/replacement if patient failed PMBC or undergoing other cardiac surgery
-
Calcific MS has a poor prognosis with 5-year survival \<50%, Intervention is higher risk and should be reserved for severely symptomatic patients
-
No role for commissurotomy with calcific MS
- Surgical valve replacement may be considered for severely symptomatic patients (technically challenging)
Anticoagulation¶
- Anticoagulation is indicated if:
- Mechanical prosthetic mitral valve
- Warfarin, goal INR 3-4 lifelong
- Bioprosthetic mitral valve replacement
- Warfarin, goal INR 2-3 for first 3-6 months
- Atrial Fibrillation regardless of CHADS2VASC score
- Mechanical prosthetic mitral valve
2020 ACC/AHA Heart Valve Disease Guidelines: Mitral Stenosis Management Algorithm
Ended: Cardiology
Critical care ↵
ABCDEF (A2F) Bundle¶
Kaele Leonard
Background¶
- Post-Intensive Care Syndrome (PICS): complex constellation of cognitive, physical, and psychological impairments that impact most survivors of critical illness, leading to disability, frailty, and poor quality of life
- Predicted by (1) duration of immobility and (2) delirium
- Both are reduced by >80% compliance with ABCDEF (A2F) Bundle concepts
- ABCDEF (A2F) Bundle: Interprofessional, evidence-based safety bundle of care principles to help reduce LOS, mortality, bounce-backs, and the duration of ICU delirium and coma
- Goal: allow pt to “prove us wrong” about readiness for liberation from devices, sedatives, etc.
Assess, prevent, and manage pain¶
- Tools to assess pain using facial expressions, body movements, muscle tension, compliance with ventilator, or vocalization for extubated pts
- Ex: Critical Care Pain Observation Tool (CPOT): scale 0-8, uncontrolled pain >=3
- Uncontrolled pain increases risk for delirium, limits inspiratory effort & weaning from ventilator, and limits ability to mobilize
- Treatment: multi-modal: parenteral opioids, neuropathic meds (e.g., gabapentin, ketamine), adjunctive non-opioids analgesics (e.g., acetaminophen, NSAIDs), nonpharmacologic interventions (repositioning, heat/cold)
Both spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs)¶
- SATs = daily sedative interruptions
- RN-driven protocol involving safety checklist: no active seizures, alcohol withdrawal, agitation, paralytics, myocardial infarction, or increased ICP
- If pass SAT, proceed to SBT
- If fail SAT (anxiety, agitation, pain, resp distress) restart sedation at ½ doses
- SBTs = PS ventilation (Fi02 ≤ 50%, PEEP ≤ 7.5; typically 40% and 5/5) for ≥ 30 minutes
- RT or physician/APP-driven protocol with safety screen: passed SAT, O2 sat ≥ 88%, inspiratory efforts, no myocardial ischemia, no/low vasopressor support
- If pass SBT, physician/APP judgment on extubation
- If fail SBT (RR > 35 or < 8, O2 sat < 88%, resp distress, mental status change) restart full ventilatory support
- Evidence:
- Liberated pts from mechanical ventilation 3 days sooner, decreased ICU and hospital length of stay by 4 days, and 14% absolute reduction in mortality at 1 year
Choice of analgesia and sedation¶
- Richmond Agitation-Sedation Scale (RASS): sedation & level of arousal assessment tool (Figure 1)
- Target light sedation of RASS -1 to 0 with goal of (1) pt following commands without agitation and (2) limiting immobilization
- Over-sedation: hold sedatives till target, then restart at ½ prior dose
- Analgosedation with focus on treating pain first and then adding sedation meds PRN
- Sedatives: dexmedetomidine (dex) or propofol >>> benzodiazepines (increased delirium risk)
Delirium- assess, prevent, and manage¶
- Screening for delirium: q4h using CAM-ICU (Figure 2)
- Affects 60-80% of ventilated pts and associated with increased morbidity and mortality, longer ICU and hospital length of stay, long-term cognitive dysfunction
- Risk factors and treatment: see Delirium section in Psychiatry
Early mobility and exercise¶
- Prolonged immobilization during critical illness leads to ICU-acquired weakness, associated with worse outcomes: ↑ mechanical ventilation, increased hosp length of stay, greater mortality, and greater disability
- Consult PT/OT to initiate rehab at the beginning of critical illness
- Can be done safely in pts receiving advanced support
Family engagement and empowerment¶
- Especially important when pts are unable to communicate themselves
- Incorporate family at the bedside and on rounds to learn pt preferences and values, engage in shared-decision making, and address questions and concerns
Acute Respiratory Distress Syndrome (ARDS)¶
JC Armstrong
Background¶
- A syndrome of diffuse systemic inflammation which damages the alveoli/capillary endothelium interface causing fluid and protein accumulation within the interstitium and alveoli leading to impaired gas exchange, decreased lung compliance, and pulmonary hypertension.
- ARDS new definition: Onset within 1 week of known insult with new/worsening respiratory status with bilateral opacities seen on CXR/CT or bedside US not fully explained by cardiac failure/volume overload with PaO2:FiO2 ≤ 300 or SpO2:FiO2 ≤ 315 with respiratory support of PEEP ≥ 5 or HFNC ≥ 30L.
Triggers:¶
- Direct
- Pneumonia (viral and bacterial)
- Aspiration
- Lung contusion d/t trauma
- Direct inhalation injury
- Primary Graft dysfunction of pulmonary transplant
- Indirect
- Non-pulmonary Sepsis (most common cause)
- Massive Blood Transfusion/TRALI
- Hematopoietic stem cell transplantation
- Drugs (Opioids, TCAs, ASA, cocaine, amiodarone, chemotherapy, salicylates)
- Pancreatitis
- Burns
- Radiation
Evaluation¶
- Severity: Based on PaO2/FiO2 ratio with PEEP 5 cm H20
- PaO2- arterial pressure of O2 (Obtained by ABG)
- FiO2- Fraction of inspired oxygen (expressed as a decimal between 0.21 and 1.0)
PaO2/FiO2 ratio | SpO2/FiO2 (if SpO2 ≤ 97%) if intubated | PEEP or HFNC (Optiflow) | |
---|---|---|---|
Mild | 300-201 | 246-315 | ≥5 or ≥30L |
Moderate | 200-101 | 149-245 | ≥5 or ≥30L |
Severe | <100 | <148 | ≥5 or ≥30L |
Management¶
- Frequently requires intubation as non-invasive ventilation is not often effective.
- Interventions with mortality benefit
- Low tidal volume(Vt) ventilation (LTVV)
- Goal Vt is 4-8 mL/kg of ideal body weight
- Target plateau pressure of 30 cm H2O
- Oxygenation goal: PaO2 55-80 mmHg or SpO2 88-95%
- Slowly titrate PEEP and FiO2 concurrently to achieve oxygenation goals
- pH goal: \(\ge\) 7.20; “permissive hypercapnia”
- Treat ventilator dyssynchrony
- Proning
- Can be considered if moderate to severe ARDS and oxygenation does not improve with LTVV
- Most recent study (PROSEVA) suggested mortality benefit to proning patients with moderate to severe ARDS
- Not routinely done at VUMC
- Low tidal volume(Vt) ventilation (LTVV)
- Interventions that probably won’t hurt the patient but with less data to support them
- Conservative fluid management with IV diuresis as needed (at risk for pulmonary edema d/t vascular leak); goal of net even or negative. FACTT study demonstrated 2 more ventilator-free days with aggressive diuresis, but no mortality difference
- Glucocorticoids in ARDS d/t septic shock, COVID, CAP, steroid-responsive conditions; may shorten time on ventilator but may also result in some neuromuscular weakness
- American Thoracic Society Guidelines of 2024 placed emphasis on early ECMO involvement and neuromuscular blockade in severe ARDS patients. Two trials on neuromuscular blockade (ACURASYS and ROSE) with conflicting results. EOLIA suggest benefit to ECMO in patients with P/F<80 or hypercapnic respiratory acidosis.
Brain Death¶
Anna Berry
Background¶
- Brain death= complete and permanent loss of brain function. Defined by coma with loss of capacity for consciousness, brainstem reflexes, and the ability to breathe independently
Checklist for Determination of Brain Death (American Academy of Neurology)¶
1. Prerequisites (all must be checked)¶
- Coma, irreversible and cause known
- Neuroimaging explains coma – usually CT or MRI
- Absence of CNS depressing drugs
- No evidence of residual paralytics (electrical stimulation if paralytics used)
- Absence of severe acid-base, electrolyte, endocrine abnormality
- Normothermia or mild hypothermia (core temp >36°C)
- SBP ≥100 mmHg
- No spontaneous respirations
2. Examination (all must be checked) – Attending MUST be present for brain death exam¶
Test | Regions Tested | Indications of Brain Death | Cautions |
---|---|---|---|
Consciousness | Rostral brainstem, thalamus, bilateral cerebral hemispheres | No response to noxious auditory, visual, or tactile stimulation | Use of adequate stimulation is important, including noxious tactile stimulus of the cranium (supra-orbital notch and temporomandibular joint, intra-nasal stimulation) as well as the torso and limbs |
Pupillary reflex | Upper brainstem | No response to bright light | Use of medications may affect pupillary reactivity History of corneal trauma or ophthalmic surgery may affect reactivity Quantitative pupillometry may be a useful adjunct for detection of subtle reactivity |
Corneal reflex | Middle-to-upper brainstem | No eyelid response when pressure is applied at the border of iris with a cotton swab on a stick | Use of adequate pressure should be ensured; the lateral conjunctiva, which is less sensitive than the proximal conjunctiva, should be avoided |
Oculocephalic reflex ("doll's eye" maneuver) | Middle brainstem | No eye movement with head turning | Use of this approach should be avoided when the integrity of the cervical spine is questionable |
Oculovestibular reflex ("cold caloric" reflex test) | Middle brainstem | No eye movement within 60 seconds of instillation of ice water | Clear pathway to intact tympanic membrane should be ensured; head should be elevated to an angle of 30 degrees; wait 5 minutes between testing of each ear |
Gag reflex | Lower brainstem | No gag reflex in response to bilateral stimulation of the posterior pharynx with a tongue depressor or suction catheter | Avoid manipulation of endotracheal tube, if present |
Cough reflex | Lower brainstem | No cough in response to deep bronchial suctioning | May be absent in patients with phrenic nerve palsy resulting from injury to the cervical cord |
Motor response | Brainstem, cerebral hemispheres | No cerebrally mediated response to deep nail-bed pressure or proximal stimulation of trunk or arms and legs | May be difficult to distinguish spinally mediated responses from cerebrally mediated responses; expertise and, in some instances, ancillary testing may be required |
Greer DM, Determination of Brain Death. NEJM. 2021;385;2554-61. doi: 10.1056/NEJMcp2025326
3. Apnea testing (all must be checked) – Attending MUST be present¶
- Pt is hemodynamically stable
- Ventilator adjusted to provide normocarbia (PaCO2 35–45 mmHg)
- Preoxygenate with 100% FiO2 and PEEP of 5 cmH2O for >10 min to PaO2 >200 mmHg
- Provide oxygen via a suction catheter to the level of the carina at 6 L/min or attach T-piece with continuous positive airway pressure (CPAP) at 10 cmH2O
- Disconnect ventilator
- Spontaneous respirations absent
- Arterial blood gas drawn at 8–10 minutes, pt reconnected to ventilator
- PCO2 ≥60 mmHg, or 20 mmHg rise from normal baseline value; OR:
- Apnea test aborted due to spontaneous respirations present, hemodynamic instability, or hypoxia
4. Ancillary testing (Order one test if clinical examination cannot be fully performed due to pt factors or if apnea testing inconclusive/aborted)¶
- Cerebral angiogram
- HMPAO SPECT (Single photon emission computed tomography)
- EEG & TCD (transcranial Doppler)
Organ donation caveats¶
- Discussions about organ donation should take place between Tennessee Donor Services (TDS) and the surrogate. You SHOULD NOT be having conversations with the surrogate about donation. Direct questions to TDS
Running Codes¶
Jacqueline Visina
Arrival to a Code¶
- Questions to ask when you arrive: Is someone running the code? What is the pt’s code status? Who is doing compressions? Pads on the pt? IV access?
- Take charge: establish if anyone is actively running the code. If someone is running the code, introduce yourself and ask how you may be helpful. If someone is NOT, have someone begin chest compressions IMMEDIATELY and assume responsibility for the running the code
- IV access: IV access preferred, if no immediate IV access, place IO
- Obtain a brief medical history and events surrounding the code and the pt’s code status
- Have someone find the nearest crash cart and get pads on the pt as soon as possible
Running the Code¶
- Assess the rhythm
- If Vfib/VT, immediately shock
- For polymorphic VT, this is ischemia until proven otherwise unless the pt is on a large amount of QTc prolonging medications.
- If PEA/Asystole- resume compressions, give Epi 1mg ASAP
- Strong ACLS
- Q2min- pulse check, rhythm check, shock?
- Remember the two interventions with proven mortality benefit are high quality chest compressions and early defibrillation. Do not interrupt these actions for other things
- Monitor the quality of chest compressions
- Warn resuscitators when shock is being delivered
- Consider Advanced Airway
- Remember chest compressions save lives. Not intubation. Do not stop compressions for intubation
- Stay Calm
- Closed Loop communication- continue giving instructions, use names, minimize interruptions
- Do not move from foot of bed if you are running the code
- Ensure delivery of adequate compressions. Avoid excessive ventilation
- If you are running the code, it is helpful to maintain a constant verbal running summary of interventions that have been tried and the course of the code
- Have a member of the team locate an ultrasound for line placement and diagnostics
- **Allow family to be present - If family present, ensure that some healthcare provider (nurse, APP, resident, attending) is with the family (to answer questions, explain what is going on)
- H’s and T’s: Treat Reversible Factors
- Some of the fellows here will empirically give 2 grams of magnesium, 1 amp of D50, 1 amp of bicarb, and 1g calcium chloride at the onset of the code irrespective of presenting rhythm
- Can send Labs – ask for a “loaded gas.” This will usually be a VBG/ABG with lactate, K, Ca, and Hgb. Often information does not result quick enough to change immediate management. Have someone look up most recent labs in Epic (looking for recent hyperK, acidosis)
Terminating a Code¶
- Consider initial rhythm, pt comorbidities, cardiac vs non-cardiac arrest, bedside echo findings. ROSC or rhythm changes during code?
- Persistent ETCO2 < 10 mmHg after 20min CPR has minimal survival
- Ask your team if they have any other therapies that they feel would be indicated
- Ask if anyone remains in favor of continuing CPR
- When unanimous, terminate the code and announce time of death. Thank your team. Take a moment of silence for the deceased pt
Post-Arrest Care¶
- Immediately following ROSC is the most dangerous point of ACLS
- Airway: Secure airway if not done during code, ensure RT avoids hypoxia or hyperoxia
- BP: MAPs>65, IVF and/or pressors if needed
- If on floor, prioritize moving pt to a unit for ongoing care once hemodynamically stable enough for transfer. Would not delay for other diagnostics/interventions (lines, CXR, etc)
- Cardiac: obtain EKG. Assess if urgent cardiac intervention is required for STEMI vs unstable cardiogenic shock vs VT storm or Vfib
- Neuro: if not following commands, consider TTM. TTM is still performed at VUMC with a strict protocol and inclusion criteria. If there is any question about TTM eligibility, page the CCU fellow
- Send rainbow labs (CBC, CMP, Mg, coags, trop, lactate, VBG/ABG). Treat rapidly reversible causes
- CXR
- Propofol/fentanyl infusion if the pt is intubated. Pressor of choice post ROSC is usually levophed
- If not done during the code, usually central access will be obtained and an arterial line will be placed
*Intern role during codes: maintain hand on femoral pulse, place IO if needed, or have access to the pt’s chart to answer questions that arise during the code. If family is not available, looking up primary contact information is invaluable. In the MICU, your role is to grab the yellow IO kit prior to leaving for the code
**Family presence during CPR: studies show that it reduces the frequency of PTSD-related symptoms and does not interfere with medical efforts
Treatable Causes of Cardiac Arrest: The H’s and T’s | |
---|---|
H's | T’s |
Hypoxia | Toxins |
Hypovolemia | Tamponade |
H+ | Tension Pneumothorax |
Hypo/Hyper K | Thrombosis: Pulmonary |
Hypothermia | Thrombosis: Coronary |
MICU/CCU Drips¶
Patrick Barney
Most have order sets in Epic. Typically choose Titration Allowed” in ICU
Vasopressors¶
Drug | Dose | Receptors | Indications | Considerations |
---|---|---|---|---|
Norepinephrine (Levophed) | 1 – 100 mcg/min | α1 > β1 | 1st line septic shock | Peripheral ischemia, skin necrosis |
Phenylephrine (Neosynephrine) | Bolus: 0.05 – 0.5 mg q 10-15 min Infusion: 40-360 mcg/min |
α1 | Periprocedural hypotension (Neostick), pts w/ tachyarrhythmias, Critical AS or HOCM with severe LVOT obstruction and shock | Reflex bradycardia, Peripheral ischemia, skin necrosis |
Epinephrine | 1 – 40 mcg/min | α1=β1=β2 | Post PEA arrest, Anaphylaxis, Septic shock (severe), Cardiogenic shock | Tachy-arrhythmias, Peripheral ischemia, skin necrosis |
Vasopressin | 0.04 U/min (no titration); | V1, V2, V3 | 2nd line septic shock, Right heart failure | Hyponatremia, Bradycardia |
ANG II | 20 – 40 ng/kg/min | ANG II | Refractory vasodilatory shock | Thrombosis - pt MUST have chemical DVT ppx. Contraindicated in heart failure |
Dopamine | 2 – 20 mcg/kg/min | Dopamine (1-5 mcg) > β1 (5-10 mcg) >α1 (>10mcg) | Hypotension, Cardiogenic shock | Tachy-arrhythmias, Peripheral ischemia, skin necrosis |
Dobutamine | 2.5 – 20 mcg/kg/min | β1 >>> β2 | Cardiogenic shock | Vasodilation Hypotension, Tachycardia, Tachyphylaxis |
Milrinone | 0.375 – 0.75 mcg/kg/min | PDE-3 | Cardiogenic shock | Hypotension, Renally cleared |
Sedatives/Anxiolytics¶
Drug | Dose | Class | Metabolism | Side Effects |
---|---|---|---|---|
Propofol | Infusion: 5 – 150 mcg/kg/min | General anesthetic (GABA R agonist) | Hepatic, Renal (minor) | Severe hypotension, bradycardia, hypertriglyceridemia, propofol infusion syndrome (rare) Monitor for toxicity with q4 day TGs and CK |
Dexmedetomidine (Precedex) | Infusion: 0.1 – 1.5 mcg/kg/h | Central α2 agonist | Hepatic | Hypotension, bradycardia |
Midazolam (Versed) | Push: 0.5 – 5 mg Infusion: 0.25 – 5 mg/h (no max dose) |
Benzodiazepine | Hepatic & Renal | Hypotension, risk of benzodiazepine withdrawal if used for long periods with sudden discontinuation |
Lorazepam (Ativan) | Push: 0.5 – 10 mg Infusion: 0.5 – 5 mg/h (no max dose) |
Benzodiazepine | Hepatic | Hypotension. Propylene glycol carrier – AGMA |
Ketamine | Push: 1-2 mg/kg Infusion: 0.2 mg/kg/h, titrate by 0.1 q15min |
NDMA antagonist | Hepatic | Delirium/hallucination – use caution in patients with psychiatric history, hypertension, tachycardia Pretreat with 0.4 mg IV glycopyrrolate to avoid hyper-salivation |
Analgesics¶
Drug | Dose | Metabolism | Side effects |
---|---|---|---|
Fentanyl | Push: 25 – 100 mcg Infusion: 25 – 400 mcg/h |
Hepatic | Hypotension, Serotonin syndrome, chest wall rigidity at high doses |
Morphine | Push: 1 – 5 mg q1-2h prn Infusion: 1 – 5 mg/h |
Hepatic/Renal | Hypotension (profound), itching, constipation, HA; avoid in renal failure |
Hydromorphone (Dilaudid) | Push: 0.25–1mg q1-2h prn Infusion: 0.5–3 mg/h |
Hepatic | Hypotension, respiratory depression, itching |
Anti-Arrhythmics¶
Drug | Dose | Indications | Side effects | Comments |
---|---|---|---|---|
Adenosine | 6 – 12 mg IV rapid push and flush; may repeat x2 | PSVT conversion | Complete AV nodal blockade | 10 second half-life Must have continuous EKG/tele monitor |
Amiodarone | ACLS: 300 mg IV push Non-emergent: 150 mg over 10 min then 0.5 mg/min |
Vtach/Vfib, Afib | Pulm, ophthalmic and thyroid toxicity w/ chronic use | Less hypotension than other agents, safe in heart failure. May chemically cardiovert pts, caution if off therapeutic AC |
Diltiazem | Push: 10 – 20 mg q15 min x 2 if no response Infusion: 5 – 15 mg/h |
Afib, Aflutter, PSVT | Bradycardia, hypotension | Avoid use in pts with HfrEF |
Lidocaine | ACLS: 1 mg/kg x 1 Infusion: 1 – 4 mg/min |
Vtach | Bradycardia, Heart block | Avoid use in liver failure/ Okay for HfrEF. Often 1st line CCU med for VT/ May need to check levels if using for longer than 24 hours |
Procainamide | 15 mg/kg over 30 min then 1 – 6 mg/min | Vtach, refractory afib | Bradycardia, hypotension | Drug-induced lupus, cytopenias |
Anti-Hypertensives¶
Drug | Class/MOA | Dose | Indications | Side effects | Comments |
---|---|---|---|---|---|
Esmolol | Beta blocker | Bolus: 1mg/kg over 30s Infusion: 50-300mcg/kg/min (max 300) |
Aortic dissection, HTN emergency | Bradycardia, hypotension | Titrate to desired BP or HR. Caution in HfrEF |
Nicardipine | CCB | Infusion: 5-15mg/h (max 15) | HTN emergency | Bradycardia, hypotension | Titrate to desired BP, avoid in HfrEF |
Nitroprusside | Metabolized to NO → vasodilatory effect (arterial roughly = venous) | Infusion: 0.3mcg/kg/min; titrate q2min to max 10mcg/kg/min | HTN emergency, flash pulmonary edema, HfrEF for afterload reduction | Hypotension, cyanide toxicity | Contraindicated in hepatic and renal failure |
Nitroglycerin | NO mediated venous > arterial vasodilation | Infusion: start 0.25mcg/kg/min, titrate by 1mcg/kg/min q15min (max 10mcg/kg/min) | Refractory angina, flash pulmonary edema, HTN emergency | Hypotension, headache, palpitations | Contraindicated in severe RHF and concurrent use of PDE-5 inhibitor |
ICU Delirium¶
Phil Schmitt
Background¶
- Delirium is a DSM-V diagnosis based on acute-onset fluctuating attention and awareness, unlike the chronic changes seen in dementia. It is largely interchangeable with Encephalopathy.
- This becomes more difficult to assess when patients are sedated, intubated, etc. in the ICU
- Very well-studied at VUMC, more resources found at: https://www.icudelirium.org.
- Associated with higher morbidity and mortality compared to those who do not experience delirium and duration of delirium also associated with higher morbidity and mortality.
Evaluation¶
- Can present as either hyperactive (agitated, trying to leave bed, etc.) or hypoactive (somnolent, minimally interactive, etc.).
- Do neuro exam to rule out focal deficits. Basic ICU/coma neuro exam detailed below:
- For ICU Patients, consider sedation when doing neuro exam - propofol and other anesthesia dampens brainstem + peripheral reflexes
- Always remember patients can be encephalopathic and evolve another acute neurological syndrome. Follow up any odd/changing exam findings.
- Perform the CAM-ICU for scoring – ICU nurses perform this q4h as part of routine ICU care
- See RASS scoring table in ABCDEF Bundle Critical Care chapter.
Differential Diagnosis¶
- Most typically due to changes in environment, alterations in sleep cycle, reduced cognitive reserve from critical illness, dementia, neurodegeneration, etc.
- other differentials fit in a modified VITAMINS PO mnemonic
Category | Causes |
---|---|
Vascular | Ischemic stroke, CNS hemorrhage, arrhythmia, carotid stenosis |
Infectious |
|
Trauma | Falls, TBI, etc. |
Autoimmune | Autoimmune encephalitis, SLE, CNS vasculitis among others |
Metabolic |
|
Ingestion |
|
Neoplasm | Brain mets, primary CNS tumors, CA associated with paraneoplastic syndromes (SCLC, Multiple myeloma, ovarian teratoma, etc.) |
Seizure | |
Pain | Always important to consider, especially in geriatric pts |
Oxygenation | Hypoxia |
Management¶
- Initial toxic/metabolic/infectious workup can include: CBC, CMP, TSH, Folate, Vitamin B12, UA, blood cultures, CT Head w/o. Look through med list to see if there are any sedating medications that could be contributing and try to minimize as much as possible.
- Definitive treatment is addressing underlying etiology.
- First-line symptomatic treatment includes delirium precautions, such as keeping blinds open during daytime, limiting daytime naps, redirection when agitated, lights on during day, TV on during day, family at bedside (opposite of these at night). There is an order in Epic called Nursing: Delirium Care, which can be found as part of the Geriatric Delirium Care order set, that has all these precautions listed out.
- Although they do not provide mortality benefit in ICU delirium patients (and debatably worsen mortality), antipsychotics can be used if needed for more severe agitation IE pulling at lines, physical aggression. Start with one-time dose of zyprexa 2.5 mg or 5 mg, can escalate to 1 mg haldol if refractory. Check an EKG for QTc prolongation (>440ms) prior to giving.
Intubation and Extubation¶
Daniel Motta-Calderon
Intubation¶
Background¶
- Intubation is the definitive therapy for pts with worsening respiratory failure
- Indications for intubation- hypoxic or hypercarbic respiratory failure, airway protection
Intubation checklist¶
- Prepare the pt
- IV access: at least two large bore IV access sites.
- Optimize position: Supine sniffing position
- Assess the airway: Assess for difficult intubation predictors (opening mouth <3cm, Mallampati ≥ III, neck circumference >40cm, thyromental distance <6cm, head-neck extension <30 degrees)
- Optimal pre-oxygenation: using FiO2 100% (facemask, high flow nasal cannula)
- Optimize medical status: resuscitation, temporize hyperkalemia, Hb >7
- Prepare the equipment
- Monitoring: SpO2, capnography, telemetry, BP
- Equipment: bag valve mask, 2 endotracheal tubes (ETT) with cuffs checked, direct laryngoscope, videolaryngoscope, bougie/stylet, working suction, supraglottic airway, oropharyngeal airway
- Medications: paralytic (ex: rocuronium, succinylcholine), induction sedative (ex: etomidate, ketamine, propofol), analgesics (ex: fentanyl), maintenance sedative, IVF hanging in room, pressors (ex: Neostick)
- Prepare the team
- First and second intubators, RT, RN, someone to monitor hemodynamics
Rapid-sequence intubation (RSI)¶
- Preferred method of induction, associated with increased first-attempt success and fewer intubation-related complications
- -Simultaneous IV administration of rapidly acting paralytic and induction agents to achieve sedation and paralysis
Post-intubation:¶
- Ensure correct placement of ETT with capnography and confirming bilateral breath sounds
- Secure ETT with taping, tying or tube holder
- Obtain post-placement CXR
Immediate complications of intubation:¶
- Aspiration: Suction airway, ideally prior to initiation of positive pressure ventilation to prevent distal movement of aspirated contents. Cricoid pressure maneuver historically used to reduce risk but unclear if it works so often not performed
- Cardiovascular collapse: May be hypotension or sympathetic surge (hypertension, tachycardia, arrhythmias). Manage with fluids/pressors if need, rule out other causes (ex: hypoxia, PTX)
- Hypoxemia: Preoxygenate with 100% FiO2 to minimize risk. Rescue maneuvers with bag mask ventilation if needed
- Mechanical injury: Dental, soft tissue, tracheal, laryngeal. Retrieve any dislodged teeth, suction blood
Extubation¶
Are they a good candidate for extubation?¶
- Are they oxygenating well? SpO2 ≥90% with FiO2 ≤50% and PEEP ≤8cm H20
- Has the underlying cause of their respiratory failure improved?
- Did pt pass their SBT?
- See ABCDEF Bundle section for details on SBT
- Is pt able to protect their airway?
- Is the pt on a stable pressor requirement or no pressors?
- Is pt coughing and clearing secretions?
- Is pt off sedation, alert and following commands?
- Positive cuff leak? (See below for steps)
- Consider calculating the rapid shallow breathing index (RSBI): RR/tidal volume (L)
- Set PS at 0cm H2O, and PEEP at 5cm H2O and, measure VT & RR for one minute.
- RSBI ≥ 105 predicts likely failure to wean. The use of a RSBI is attending dependent.
Post-extubation complications¶
- Post-extubation stridor: 2/2 laryngeal edema
- Positive cuff leak test= high risk methylprednisolone 20mg IV Q4H for 4 doses prior to extubation to prevent
- If after extubation: methylprednisolone 40mg IV + inhaled racemic epinephrine. If stridor >60minutes, consider reintubation
- Cuff leak test:
- Suction secretions and set the ventilator into the AC mode
- Inflate the cuff and record inspiratory and expiratory VT to evaluate for differences between the two volumes
- Deflate the cuff record the expiratory VT over the next six breathing cycles. Average the three lowest expiratory VT values
- The cuff leak volume is the difference between the inspiratory VT (measured before the cuff was deflated) and the averaged expiratory VT. If the difference is <100cc, this is considered failure but is not an absolute contradiction to extubation
- Post-extubation respiratory failure
- Recurrent hypoxic or hypercarbic respiratory failure
- Assess for aggravating factors (volume overload, shock, AMS, etc.)
- For hypercarbic respiratory failure, may trial BiPAP. If unsuccessful -> reintubate
- Preventative post-extubation BiPAP not routinely used in all pts but consider in select populations at high risk for failure: severe COPD with preexisting chronic hypercarbia, cardiogenic pulmonary edema
Modes of Oxygen Delivery¶
Blake Funke
System | L/min | % O2 | Comments |
---|---|---|---|
Blow by (ex: Trach collar) | 21-100% | ||
Nasal cannula | 1-8 | 25 – 45% | |
Large bore nasal cannula | Up to 15 | Up to 65% | Can be identified by larger bore tubing (often green) and nose piece. Colloquially referred to as HFNC at VUMC, but true HFNC = optiflow |
Venturi mask | 4 to 15 | 24 – 50% | Actual FiO2 is dependent on pt effort |
Non-rebreather | 10 to 15 | 65-95% | Often used as a bridge to higher level of O2 therapy |
HFNC: Optiflow, AirVo, Vapotherm | Up to 60 | 30-100% | Delivers 0.5-1 cm/H2O of PEEP per 10L of flow |
** Use of all of the above modes of O2 requires a spontaneously breathing pt
Non-invasive positive pressure ventilation:¶
- CPAP
- Indications: obstructive sleep apnea, tracheomalacia
- Settings: CPAP, FiO2
- BiPAP
- Indications: hypercapnic respiratory failure (RF), hypoxic RF, pulmonary edema, obstructive sleep apnea, obesity hypoventilation syndrome, RF 2/2 neuromuscular disease
- Settings: IPAP, EPAP, FiO2, RR (sometimes)
Mode | You set | Not set | Comments |
---|---|---|---|
Pressure support (PS) | PEEP PS above PEEP FiO2 |
TV RR Inspiratory flow |
Similar to Bipap. Frequently used for vent weaning / SBT. Requires spontaneously breathing pt |
Volume Control (AC/VC) | PEEP RR TV Inspiratory flow FiO2 |
Inspiratory pressure | Mandates a minute ventilation; limits volutrauma (i.e. can guarantee low tidal volume ventilation) **Primary mode used in MICU (mode used in major ARDS trials) |
SIMV (Synchronized Intermittent Mandatory Ventilation) | PEEP RR TV PS above PEEP FiO2 |
Pt gets VC breath for set rate, but if tries to breath over this will get PS breath; VC and PS breaths are synchronized when able | |
Pressure Control (AC/PC) | RR Inspiratory Pressure PEEP Inspiratory Time (or I:E ratio) FiO2 |
TV | Minimizes barotrauma (i.e. sets a max inspiratory pressure) → does not guarantee a specific minute ventilation (must monitor PCO2 with blood gases) Does not have natural ventilator alarms for protection – need to increase low minute ventilation alarm threshold |
PRVC (Pressure Regulated Volume Control) | PEEP RR TV Inspiratory flow Pressure max FiO2 |
Adaptive pressure control (NOT actually a volume control mode); tries to limit both barotrauma and volutrauma but if in conflict, minute ventilation will drop (i.e. need to monitor PCO2 with blood gases like any other PC mode) Con: More the pt works, the less the ventilator does |
|
APRV / Bilevel | PEEP (PLow) Pressure High Time Low Time High FiO2 |
TV | Long periods of inspiratory holds and very brief expirations (i.e. releases), for refractory hypoxemia. Often difficult to ventilate pts on this mode |
Obstructive Shock¶
Seth Alexander
Background¶
- Obstructive shock occurs when there is increased resistance to forward blood flow which can occur due to:
- Resistance in the cardiovascular circuit (i.e., pulmonary embolism, HOCM, critical aortic stenosis)
- Extrinsic compression on the heart (i.e., pericardial tamponade, tension pneumothorax, dynamic hyperinflation (auto-PEEP), restrictive cardiomyopathy)
- Risk factors vary based on the underlying pathology but include:
- PE: Known DVT, prothrombotic conditions, malignancy, recent orthopedic surgery
- Pneumothorax: Recent chest trauma/thoracic procedures, mechanical ventilation, COPD/emphysema, endobronchial valve placement
- Tamponade: Recent cardiac procedure, ESRD, cancer, trauma
Clinical Signs/Symptoms¶
- General: Hypotension, tachycardia, hypoxemia, elevated JVP
- Tension pneumothorax: Unilateral breath sounds, tracheal deviation away from the pneumothorax, CXR with one lung collapsed, and mediastinal shift away from the PTX
- Pulmonary embolism: Right heart strain on EKG (right axis deviation, S1Q3T3, ST depressions in inferior leads/precordial leads, new RBBB), chest pain, hypoxia, sense of impending doom
- Cardiac tamponade: distant heart sounds (Beck’s Triad with JVD and hypotension), electrical alternans, and/or low amplitude on EKG
- POCUS findings:
- PE/causes of increased heart pressures: distended IVC, RV dilation, McConnell’s sign, Septal D sign
- Pneumothorax: Lack of lung sliding
- Cardiac tamponade: Diastolic collapse of the RV, large pericardial effusion
Approach in the Hemodynamically Unstable Patient¶
- Initial workup: order: STAT CBC, EKG, troponin, VBG, CXR. Evaluate the patient at bedside and bring an ultrasound if available to perform POCUS.
- Pulmonary Embolism – STAT CTA chest, supportive measures (pressors, supplemental O2), and activate PERC team for discussion regarding mechanical thrombectomy or chemical thrombolysis. Start high-dose therapeutic heparin gtt once clot has been identified – bolus unless contraindicated (i.e., recent GI bleed).
- NOTE: First line is LMWH due to faster onset of action and longer time in therapeutic range. At VUMC, we often start heparin gtt first because if pt is going for EKOS, they need to be able to turn off AC quickly. We recommend starting heparin gtt until decision for EKOS has been made. If no EKOS, switch to LMWH.
- Cardiac tamponade – emergency procedural management with cardiothoracic surgery (pericardiocentesis vs drain). 500cc-1L IVF bolus can improve preload and temporarily improve cardiac output.
- Tension pneumothorax – if there is no lung sliding on POCUS or the STAT CXR shows evidence of tension PTX, emergent needle decompression (14-gauge needle in either the 2nd intercostal space mid-clavicular line or the 4th/5th intercostal space anterior axillary line) vs urgent chest tube placement with pulmonology (if at the VA overnight, ED attending can place one).
Further Evaluation and Management¶
- Pulmonary Embolism
- Evaluate the source for the embolism (four extremity dopplers)
- If no risk factors for VTE are identified, you could consider a benign hematology outpatient referral for a hypercoagulable work-up.
- See “Pulmonary Embolism” in cardiology for more information
- Cardiac Tamponade, HOCM, and Critical Aortic Stenosis
- Formal echo should be obtained at some point during the admission.
- These are all worsened by a drop in the patient’s preload; AVOID diuretics or other medications which may worsen obstructive pathophysiology if possible.
- Preload support (IVF, dobutamine in AS) can help temporize patients pending medical or procedural interventions.
- Consultation to cardiology and/or cardiothoracic surgery is warrant to discuss management.
- For more on management of aortic stenosis, see “Valvular Heart Disease” in Cardiology”
- Tension Pneumothorax
- Once hemodynamically stabilized, consult to pulmonology for chest tube placement is indicated in large, hemodynamically significant pneumothoraces to ensure resolaution.
- For more on chest tubes, see “Chest Tubes” in Pulmonary.
Refractory Hypercapnia¶
Amelia Muhs
Background¶
- Inadequate clearance of CO2 leading to respiratory acidosis (pH ≤ 7.20) despite maximum RR&TV (i.e. minute ventilation) tolerated without causing barotrauma or autoPEEP
- Common causes:
- Obstructive lung disease (COPD, emphysema, asthma)
- Hypoventilation (sleep apnea, obesity, sedative medications (i.e. opiates), neuromuscular weakness, chest wall trauma, ascites/pleural effusion)
- Increased CO2 load (shock, sepsis, malignant hyperthermia)
- Presentation:
- Shortness of breath, AMS, somnolence, hypoxemia, tachycardia, HTN (in some cases)
Evaluation¶
- Physical exam, mental status, recent medications
- ABG or VBG – if increased PCO2 and normal pH, always treat the pH and not the PCO2 (i.e., may be compensated chronic hypercarbia and blowing off more CO2 may be harmful)
Management Algorithm¶
- Special considerations
- If history of OSA, make sure they are on home CPAP/BiPAP
- If opiate related, trial Narcan
- Bronchodilators for reactive airway diseases
- BiPAP
- Contraindicated if pt unable to remove BiPAP mask on their own
- Increase MV by increasing Δ between IPAP/EPAP or increasing RR
- Mechanical ventilation
- Allows you to control rate and TV (in VC modes)
- To increase MV and CO2 clearance:
- Increase RR
- 30-35 breaths/min is about as high as you can go
- Need to keep in mind I/E time to avoid breath stacking/autoPEEP
- Some signs of autoPEEP include worsening hypotension and the expiratory limb on the flow waveform on the vent not returning to zero
- Increase TV -> we usually start at 4-6mL/kg PBW. You can consider increasing to 8mL/kg PBW as long as plateau pressures remain < 30 cm H2O
- Goal peak pressures ≤ 35 cmH2O / plateau pressures ≤ 30 cmH2O
- Increase RR
- ARDS -> permissive hypercapnia (goal pH ≥ 7.2)
- V-V ECMO / Extracorporeal carbon dioxide removal (ECCO2R)
- Indications for ECMO for hypercapnia:
- Severe dynamic hyperinflation and/or severe respiratory acidosis
- pH ≤ 7.25 with PaCO2 ≥ 60 for 6h with RR at 35/min and TV increased to target maximum MV while keeping plateau pressure ≤ 32 cmH2O
- Similar considerations and contraindications as refractory hypoxemia (see section)
- Benefits: Reduces work of breathing, promotes early ventilator weaning/extubating allows early mobilization and recovery
- Indications for ECMO for hypercapnia:
Refractory Hypoxemia¶
Amelia Muhs
Background¶
- Inadequate arterial oxygenation despite high levels of inspired O2 or the development of barotrauma in mechanically ventilated pts
- Generally start to consider the interventions below if needing FiO2 >80%
- Differential:
- Worsening underlying primary process (e.g. progressive ARDS)
- PE
- Pneumothorax
- Fluid overload
- Ventilator-associated Pneumonia
- New ARDS
Evaluation:¶
- Always get CXR STAT if pt has new or worsening O2 requirement
- ABG
- Can use POCUS to check for lung sliding (pneumothorax) or RV enlargement/septal bowing/McConnell’s sign (RV strain in PE)
Initial management¶
- Remember – if at any point the pt is rapidly decompensating, you can always disconnect them from the vent and bag them until they recover/while calling for help
- Early consideration of ECMO consult in appropriate pts (discuss with MICU fellow)
- Optimize fluid status -> consider diuresis/dialysis if not making urine
- Consider higher PEEP strategy
- Increased PEEP -> higher mean airway pressure, generally improves oxygenation especially with diffuse pulmonary pathologies
- Exceptions may include certain focal/shunt pathologies (e.g. dense lobar PNA)
- Worsening oxygenation may occur with overdistension of alveoli -> increase dead space ventilation; generally determined empirically at the bedside
- Titrate up slowly; generally do not exceed PEEP 18
- Limited by high plateau pressures/barotrauma, overdistension/dead space ventilation, decreased preload/venous return
- ARDSnet FiO2/PEEP Tables: At VUMC we typically use the Lower PEEP table
- Increased PEEP -> higher mean airway pressure, generally improves oxygenation especially with diffuse pulmonary pathologies
Lower PEEP/higher FiO₂¶
FiO₂ | 0.3 | 0.4 | 0.4 | 0.5 | 0.5 | 0.6 |
---|---|---|---|---|---|---|
PEEP | 5 | 5 | 8 | 8 | 10 | 10 |
FiO₂ | 0.7 | 0.7 | 0.7 | 0.8 | 0.9 | 0.9 |
---|---|---|---|---|---|---|
PEEP | 10 | 12 | 14 | 14 | 14 | 16 |
FiO₂ | 0.9 | 1.0 |
---|---|---|
PEEP | 18 | 18-24 |
Higher PEEP/lower FiO₂¶
FiO₂ | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 |
---|---|---|---|---|---|
PEEP | 5 | 8 | 10 | 12 | 14 |
FiO₂ | 0.4 | 0.4 | 0.5 | 0.5 | 0.5-0.8 | 0.8 | 0.9 |
---|---|---|---|---|---|---|---|
PEEP | 14 | 16 | 16 | 18 | 20 | 22 | 22 |
FiO₂ | 1.0 | 1.0 |
---|---|---|
PEEP | 22 | 24 |
- Other recruitment maneuvers
- Reposition pt – can try elevating HOB or positioning so “good lung” is down
- If concern for mucus plug, consider need for bronch
- If concern for significant atelectasis can try recruitment maneuvers with the vent including sustained inflation (setting expiratory pressure to ~30 for ~30 seconds) and PEEP titration (setting PEEP to 20-25 and decreasing by 2cm at a time) – call the fellow before attempting
Management Algorithm for refractory hypoxemia:¶
- Inhaled vasodilators: Distribute preferentially to well-ventilated alveoli -> local vasodilation -> improved V/Q matching
- VUMC formulary preference: inhaled epoprostenol (aka Flolan)
- Alternatives: inhaled milrinone, inhaled nitric oxide
- Data suggest improved PaO2/FiO2; large RCT without evidence for mortality benefit
- Deep sedation (RASS -4 or -5)
- Promotes ventilator synchrony
- Neuromuscular blockade (paralysis) – call your fellow before doing this
- Rationale: maximal vent synchrony (eliminates residual chest wall/diaphragm tone)
- Pt MUST be RASS -5 (need analgesia + sedation)
- Trial one time IV push of vecuronium 0.1 mg/kg
- If improved vent synchrony/oxygenation, consider cisatracurium (Nimbex) drip
- Data are mixed ACURASYS 2010 (improved 90-day mortality but underpowered likely overestimating benefit); ROSE 2019 (no difference in 90-day mortality)
- Prone positioning (Need attending approval)
- Pts with moderate to severe ARDS (PaO2/FiO2 ratio < 150)
- At VUMC, we use regular ICU beds and manually flip pts; cycle prone 16h/supine 8h
- When proning or supining a pt, always have a provider who can intubate in the room in case unplanned extubation occurs
- Considerations: need a team of people to reposition, high risk of ET tube malposition, difficult to access lines/perform procedures, high risk of pressure injuries
- Data: PROSEVA 2013 -> proning improved 28-day mortality; study c/b imbalances between groups
- Alternative ventilator modes (usually PC or APRV/BiLevel/BiVent)
- APRV/BiVent should be avoided in people with bad obstructive lung dx, hemodynamic instability, refractory hypercarbia
- Venovenous (V-V) ECMO
- Indications for hypoxemia:
- PaO2/FiO2 < 50 with FiO2 >80% for >3h OR
- PaO2/FiO2 < 80 with FiO2 >80% for >6h AND
- Mechanical ventilation ≤ 1 week
- Absolute Contraindications:
- Poor short-term prognosis (e.g. metastatic cancer)
- Irreversible, devastating neurologic pathology
- Chronic respiratory insufficiency without the possibility for transplant
- Can calculate RESP score -> predicts in-hospital survival with ECMO
- CONSULT EARLY if a pt may be a candidate; allows ECMO team to assist with evaluation
- Data:
- CESAR 2009: improved 6-month survival without severe disability
- EOLIA 2018: no mortality benefit but 28% crossover from control to ECMO arm dilutes potential effects
- Indications for hypoxemia:
Sepsis¶
Jacob Lee
Definitions (Sepsis 3):¶
- Sepsis: organ dysfunction (change in total SOFA score ≥ 2 points) from dysregulated host response to infection
- Septic shock: sepsis + vasopressor requirement to maintain MAP ≥ 65 mmHg + serum lactate > 2 mEq/dL despite adequate volume resuscitation
Evaluation: Early screening for/identification of infection¶
- Screening: preferably incorporate multiple
- SIRS, NEWS, MEWS superior to qSOFA as single-agent-screening tools (more sensitive)
- SIRS:
- SIRS, NEWS, MEWS superior to qSOFA as single-agent-screening tools (more sensitive)
Criteria | Values |
---|---|
Respiratory Rate (RR) | Greater than 20/min |
Temperature (T) | Less than 36°C or Greater than 38°C |
Heart Rate (HR) | Greater than 90/min |
White Blood Cell Count (WBC) | Less than 4x10^9/L or Greater than 12x10^9/L or Greater than 10% bands |
- SOFA (more specific): PaO2/FiO2, Thrombocytopenia, Hyperbilirubinemia, Hypotension, AMS, Kidney Injury, UOP. https://www.mdcalc.com/calc/691/sequential-organ-failure-assessment-sofa-score
- Source Evaluation: Cultures before starting antibiotics is preferred. However, do not delay antibiotics for cultures if unable to obtain them promptly. Blood cx x2 (preferably from peripheral veins via venipuncture), Urine cx
- Consider sputum cx, wound cx, other body fluid cx (thoracentesis, paracentesis, LP, joint aspiration) based on clinical picture
- Make sure to do a full body physical exam to assess for SSTI/obvious wounds.
- Limitations to source control: lines, drains, catheters, ports, etc
- Labs: Lactate, CBC w/ diff, BMP, HFP
- Consider DIC labs for septic shock (LDH, Haptoglobin, Fibrinogen, PT, PTT, INR)
- Imaging: X-ray, CT, or US depending on suspected source
Management:¶
- After screening, early antibiotic administration and fluid resuscitation
- Antibiotics: earlier the better (septic shock – within 1 hour; sepsis alone – within 3 hours)
- Empiric treatments: should target organisms based on suspected source
- Include MRSA coverage (vancomycin/daptomycin (unless PNA suspected)/linezolid/ceftaroline) - if risk factors for MRSA (previous MRSA infection, known MRSA colonization, close contact with MRSA, cavitation on CXR, dialysis, immunosuppressed, recent antibiotics, recent hospitalization)
- Pseudomonas coverage not always needed, but generally preferred for sicker patients (zosyn/cefepime/gentamicin) with MDR risk factors (recent antibiotics, recent hospitalization, immunosuppression, hemodialysis).
- Fungal coverage: fluconazole/micafungin if high risk for candida (neutropenic, receiving TPN, abdominal surgery, recent antibiotic usage, >1 site of colonization), voriconazole/itraconazole if high risk for aspergillus (asthma with hemoptysis, nodules/cavitations on lung imaging), liposomal amphotericin if high risk for mucor/Rhizopus or disseminated crypto (uncontrolled DM with sinus pain/proptosis, uncontrolled HIV, immunosuppression with nodules on lung imaging)
- MDR coverage: if prior MDR infection (-penem) or high risk (dual Gram-Negative coverage)
- If in the ICU ID approval is not needed for meropenem. If on the floor, there is an antibiotic approval pharmacist that can be paged for meropenem.
- Anaerobic coverage: recommended for lung abscess or empyema (IDSA Guidelines), intra-abdominal infection, not recommended (new IDSA guidelines), but in some instances may consider for aspiration PNA (low quality evidence, guidelines mixed) (flagyl/zosyn/Unasyn/clindamycin)
- Atypical coverage: consider if concern for community respiratory source (azithromycin/Levaquin/doxy); should be given to any patient admitted to ICU for community-acquired pneumonia
- Source Control: If unable to find source despite routine imaging, could consider PET vs tagged WBC scan.
- De-escalation: When source control obtained, use susceptibilities, and clinical evaluation to decide how and when to de-escalate and discontinue antimicrobials; procalcitonin trend may also be helpful in certain clinical situations
- Empiric treatments: should target organisms based on suspected source
- Fluids: initial resuscitation at least 30 mL/kg (ideal body weight) of balanced IV crystalloid fluid (prefer LR > NS) should be given within the first 3 hours. General rule of thumb is to give at least 1-3L.
- Assess fluid responsiveness with an intravascular volume assessment (leg raise, US IVC, pulse pressure); important for addressing need for vasopressors but limited in overall predictive ability
- Blood: when Hb < 7, unless otherwise indicated (Hb <8 for CAD, brisk bleed suspected)
Post-Resuscitation Management¶
- Access – if in shock, hemodynamic monitoring with arterial line is preferred; will need central access to run pressors (can run them peripherally if line is above the AC, levo is less than 15 mcg/min, and if needing for <48 hours).
- Vasopressors: start if MAPs persistently < 65 mmHg after fluid resuscitation
- Via CVC, PICC, or Port, or peripherally briefly
- Target MAP ≥ 65 mmHg using lactic acid as guide to adequate perfusion
- 1st Line NE, 2nd Line Vasopressin, 3rd Line Epi, 4th Line Dopamine
- SOAP II Trial: NE > Dopamine (less arrhythmias)
- Other options:
- Phenylephrine-may be useful in tachyarrhythmias to slow HR. Also comes in the code cart which makes this a good option if other pressors aren’t immediately available
- Ang II -contraindicated in patients with CHF, VTE/hypercoagulable, thrombocytopenia <50k, severe bronchospasm
- Ang II needs approval from MICU director for order
- Low CO: dobutamine + NE OR Epi single agent
- Need ulcer prophylaxis w/ PPI (preferably PO if possible)
- Steroids: persistent septic shock w/ ongoing pressor requirements, add IV corticosteroids (particularly beneficial in ARDS, severe CAP)
- Hydrocortisone 100 mg q8 or 50 mg q6 IV ± fludrocortisone 50 µg (if concerned for adrenal insufficiency) enteral daily for 7 d or until ICU discharge
- Additional management:
- NaHCO3 – may be useful if pH ≤ 7.1
- Early enteral nutrition (within 72 hours) if possible, would start at a trickle / trophic rate
- AVOID beta-blockers unless you think HR compromising cardiac output by limiting diastolic filling/lack of atrial kick in afib; this is a physiologic compensatory response
Definition of Shock¶
Jonathan Napper
"Shock is the clinical expression of circulatory failure that results in inadequate cellular oxygen utilization." - Jean-Louis Vincent, M.D., Ph.D., and Daniel De Backer, M.D., Ph.D.
Subtypes (further outlined below):¶
- Distributive (septic, anaphylactic, neurogenic, and rarely adrenal)
- Cardiogenic (cardiomyopathies, arrhythmias, severe valvular diseases)
- Hypovolemic (bleeding, volume deplete states)
- Obstructive (PE, tension PTX, cardiac tamponade, restrictive cardiomyopathies, constrictive pericarditis)
Signs:¶
- Systolic BP < 90 mmHg or MAP < 70 mmHg, with associated tachycardia AND
- Clinical signs of tissue hypoperfusion.
- Cutaneous (cold, clammy skin w/ vasoconstriction and cyanosis, evident in low-flow states)
- Renal (UOP of <0.5ml/kg of body weight/hr)
- Neurologic (AMS typically with obtundation, disorientation confusion).
- Hyperlactatemia (indicates abnormal cellular oxygen metabolism)
Management of Shock¶
Alex Toporex, Soibhan Kelley
Cardiogenic Shock¶
Background¶
- Pathophysiology: CO/CI decreased, SVR increased, PCWP and RAP elevated (left heart failure) or PCWP low/normal and RAP elevated (right heart failure)
- Etiologies: Cardiomyopathy (LHF, RHF or biventricular), arrhythmia, mechanical such as acute AR (ex: dissection) or MR (ex: ruptured papillary muscle)
Presentation¶
- Edematous, elevated JVP, “cold and wet”; hypoxia w/crackles and pulm edema on CXR; mixed venous sat < 50-60%; POCUS with plump, non-compressible IVC, reduced EF, and B-lines
Management¶
- See cardiogenic shock in cardiology section
Distributive Shock¶
Background¶
- Pathophysiology: severe, peripheral vasodilation
- CO/CI increased, SVR decreased, PCWP and RAP normal to low
- Etiologies: sepsis (most common), anaphylaxis, neurogenic, adrenal insufficiency, pancreatitis
- Signs/symptoms:
- Sepsis: localizing signs of infection; tachycardia, tachypnea, may be hypo/hyperthermic; POCUS with hyperdynamic cardiac function
- Anaphylaxis: history of anaphylaxis; urticaria, edema, diarrhea, wheezing on exam
- Neurogenic: history of CNS trauma; focal neurologic deficits on exam
- Adrenal insufficiency: hx chronic steroid use, may have GI symptoms, hyponatremia (common), hyperkalemia (rare), hypoglycemia, hypo/hyperthermia, NAGMA
- Pancreatitis: abdominal pain, elevated lipase, evidence on CT scan
Management¶
- Sepsis: see sepsis section
- Anaphylaxis: 0.3mg IM epinephrine ASAP to be repeated q5-15min x 3; after third IM epi, consider IVF and epi gtt if persistent hypotension. Adjuncts: albuterol nebs for bronchospasm, H1 and H2 blockers, ± glucocorticoids (methylprednisolone 1mg/kg). EPINEPHRINE SAVES LIVES.
- Neurogenic: caution with IVF resuscitation, can worsen cerebral and spinal cord edema; preferred pressors are norepinephrine and phenylephrine; for neurogenic shock 2/2 spinal cord pathology, consider higher MAP goal 85-90 mmHg
- Adrenal insufficiency: stress dose steroids with hydrocortisone 100mg IV q8h or 50mg q6h
- Pancreatitis: IVF + pressors; trend H/H and Ca; treat complications (necrotizing pancreatitis, abdominal compartment syndrome); address underlying etiology (see GI section)
Hypovolemic Shock¶
Background¶
- Etiologies: Hemorrhagic and non-hemorrhagic
- Signs/symptoms:
- Hemorrhagic: Common sources include GI, retroperitoneal (*needs high index of suspicion), traumatic, intraabdominal, thighs, thorax.
- Non-hemorrhagic: 2/2 GI losses or decreased PO intake
- POCUS with thin, collapsible IVC
Management (Hemorrhagic)¶
- Ensure good access with two large-bore (at least 18G) IVs ideally in AC or above; Cordis or MAC CVC (can also use dialysis catheter, if necessary)
- Hyperacute bleed:
- 1:1:1 ratio FFP:Plt:RBC (balanced resuscitation), trauma blood (fastest way to get RBCs); massive transfusion protocol (MTP)
- Monitor iCa and replete (citrated blood products will deplete Ca)
- Minimize crystalloid if possible, w/primary use to prevent immediate hemodynamic collapse (contributes to coagulopathy, hypothermia, acidemia, trauma/surgery)
- Permissive hypotension until source control/transfusions with arterial bleeds (high MAP/SBP -> clot destabilization); trend POC lactate/exam to guide
- Acute traumatic arterial bleed or post-partum hemorrhage consider TXA (1-2g bolus)
- Reverse anticoagulation, if applicable
- Vasopressors -> generally poorly effective, would start with norepinephrine
- Source control -> GI, IR, or EGS
- Variceal bleed: See GI Bleeding section for specific management
Management (Non-Hemorrhagic)¶
- Aggressive IVF resuscitation (balanced crystalloid); target MAP ≥65
- Can support BP during resuscitation with pressors (usually norepinephrine)
Obstructive Shock¶
- See Obstructive Shock section
Temperature Abnormalities¶
Soibhan Kelley
Hypothermia¶
Background¶
- Core temperature <35°C (95°F). Mild 32-35C (90-95F), moderate 28-32C (82-90F), or severe <28C (82F) ± pulseless
- Ensure thermometer is “low-reading,” standard thermometers not accurate
- Core temperature can be measured w/ bladder catheter probe or esophageal probe (may be falsely ↑ if heated oxygen being delivered). Rectal temp can be used but is less accurate
- Etiologies
- Heat loss: environmental, burns, iatrogenic (CRRT, cold IVF, massive transfusion protocol), vasodilatory drugs/toxins
- Decreased heat production: endocrinopathies (hypothyroidism, adrenal insufficiency, hypopituitarism, hypoglycemia), thiamine deficiency
- Impaired regulation: Spinal cord injury, hypothalamic lesions, drugs (classes including antihyperglycemics, beta blockers, sedatives, ETOH, alpha agonists, general anesthetics)
- Multiple mechanisms: sepsis, pancreatitis, DKA
Evaluation¶
- Infectious work-up
- POC blood glucose, TSH/FT4, cortisol, lipase, UA, UDS, EtOH level, additional tox as appropriate, DKA work-up if relevant
- Physical exam + history for exposures and trauma
- CBC, CMP, Lactate, ABG, CK, PT/PTT, Fibrinogen
- EKG
Management¶
- Treat underlying cause [see appropriate sections]
- Mild hypothermia
- Passive external rewarming (PER): blankets, increase ambient temperature
- Note that PER requires sufficient underlying physiologic reserve to generate heat. This is often impaired in elderly pts, malnutrition, sepsis
- Moderate hypothermia, refractory mild hypothermia, or cardiovascular instability:
- Active external rewarming (AER): forced warm air (ie Bair Hugger), heated blankets, heat lamps, hot packs (consider burn risk)
- Severe hypothermia or refractory moderate hypothermia:
- Active core rewarming: Warmed IV crystalloid (limited rewarming potential unless large volume but will decrease ongoing losses), warmed humidified inspired air, warmed bladder lavage
- More extreme methods such as peritoneal/thoracic lavage more likely to be used in severe environmental cases in ED
- Pulseless severe hypothermia (“You aren’t dead unless you are warm and dead”)
- Continue CPR until re-warmed as severe hypothermia is neuroprotective and pts can have good neurologic outcomes despite hours of CPR
- ACLS medications and shocks will have poor effectiveness; prioritize circulation (i.e. chest compressions) and rewarming
- Consider ECMO (likely venoarterial if pulseless); would need transfer to CVICU
- Identify and manage complications: bradycardia/heart block, arrhythmias, shock, coagulopathy/DIC, rhabdomyolysis; rebound hyperkalemia/hypoglycemia with rewarming
Fever and Hyperthermia¶
Background¶
- Fever: T >38.0°C (100.4°F) driven by hypothalamus activity in response to systemic triggers (i.e. cytokines); may use lower threshold for immunocompromised pts
- Hyperthermia: T >41.0 C (105.8°F) uncontrolled heat production with failure of thermoregulation
- Infectious etiologies:
- Considerations in the ICU include central-line associated blood stream infection, catheter-associated UTI, pneumonia (including ventilator-associated), sinusitis (esp. in pts with NGT or ETT), clostridium difficile, acalculous cholecystitis
- Non-infectious etiologies:
- Drug fever
- Difficult to distinguish from other causes; Can begin hrs-wks after starting a drug
- Sources: antibiotics (penicillins, cephalosporins, sulfonamides), anticonvulsants (phenytoin, carbamazepine, phenobarbital), allopurinol, heparin, dexmedetomidine
- Drugs of abuse with sympathomimetic activity (cocaine, meth, ecstasy)
- Anticholinergic or salicylate intoxication
- Idiosyncratic drug reactions
- Serotonin syndrome
- Neuroleptic malignant syndrome
- Malignant hyperthermia
- Transfusion reactions
- PE/DVT
- Endocrine: hyperthyroidism/thyroid storm, adrenal insufficiency
- CNS pathology (intracranial bleed/stroke, particularly hypothalamic region)
- Malignancy
- Heat stroke (exertional or non-exertional)
- Other inflammatory states: Pancreatitis, gout, pericarditis, pneumonitis
- Drug fever
Evaluation¶
- Infectious work-up ± LP; may consider pan-scan if unable to identify source
- POC glucose, BMP, LFT, Mg/Phos, CBC w/diff
- Consider coags + fibrinogen (DIC), CK/UA (rhabdo), UDS, acetaminophen and salicylate levels, TSH/FT4, cortisol, lipase, ABG
- Review medication list: antibiotics, serotonergic drugs, anti-psychotics, recent sedation for OR, or recently intubated with succinylcholine, dexmedetomidine
- Consider CT/MRI head
Management¶
- Treat underlying etiology [see appropriate sections]
- Serotonin syndrome -> stop serotonergic drugs; add cyproheptadine
- Malignant hyperthermia ->activate malignant hyperthermia team; add dantrolene
- Cooling
- Target <38.0°C (100.4°F)
- Surface cooling: Ice (bath, or ice packs more likely in our MICU), evaporative cooling with misted lukewarm water and fan
- Internal cooling: Cold IV fluids, dry ventilation (evaporative) with non-humidified nasal cannula or vent circuit
- Avoid shivering -> give opiates (except in serotonin syndrome), precedex, propofol, benzos, ketamine
- Antipyretics
- Acetaminophen, NSAIDs
- Block prostaglandin-mediated temperature elevations
- Effective for most causes of fever- infection, pancreatitis, DVT/PE, pneumonitis
- AVOID for true hyperthermia (ineffective and potentially harmful) -> neuroleptic malignant syndrome, malignant hyperthermia, serotonin syndrome, heat stroke
- Monitor for complications
- Rhabdomyolysis, DIC, arrhythmias
- If high suspicion for infection and not improving on antibiotics, consider other infectious etiologies including fungal (ex: candida)
Tracheostomy¶
Jared Freitas
Indications for Tracheostomy¶
- Prolonged mechanical intubation and weaning
- Tracheal stenosis
- Acute airway obstructions (head and neck cancers)
- Trauma
- Neuromuscular disease
Benefits of Tracheostomy vs ET tube¶
- Improved pt comfort and decreased need for sedation
- Easier access to trachea for suctioning / airway hygiene
- Reduced laryngeal damage
- Increased ability to communicate (i.e. speaking valve)
- May decrease risk of developing ventilator associated pneumonia (mixed data)
- May reduce time to wean from the vent and decrease time in the hospital (mixed data)
Timing of Tracheostomy:¶
- No mortality difference or ↓ in hospital length of stay for early (day 4) vs late (day 10)
- Generally performed after 2 weeks of intubation, but not backed by data
- Pts that might get tracheostomy earlier: anticipated prolonged mechanical ventilation (i.e. those with acute neurologic injury affecting spinal cord)
Types of Tracheostomy Tubes:¶
- Different brands: most common in hospital = Shiley
- Components:
- Faceplate: keeps tube in place, has the model and size on it
- Inner cannula: can be removed, cleaned and replaced in case of obstruction
- Cuff (may or may not have): allows for pt to be ventilated; may prevent some aspiration
- Fenestration (may or may not have): allow speaking without valve
- Common sizes:
- Initial: 8-0; Standard downsizing: 6-0
- Lengths: standard vs. larger XLT (P = longer proximal end, D = longer distal end)
- Presenting on ICU rounds = size/cuff status/brand (e.g. 8-0 cuffed Shiley)
Speaking Valves:¶
- Passy Muir Valve (PMV): one-way valve placed on the outer portion of the trach; air moves in with inspiration but is blocked and thus funneled up through the vocal cords during exhalation allowing for phonation
- Contraindication: severe upper airway obstruction or aspiration risk, copious secretions, decreased cognitive status, severe medical instability, or inability to tolerate cuff deflation
- IMPORTANT SAFETY PRINCIPLE: cuff must be deflated, since air needs to be able to travel back up the airway, if the cuff is not deflated and you put the PMV on, then pt cannot exhale
Maintenance of Tracheostomy Tubes:¶
- Inner cannula should be cleaned 2-3 times per day
- Daily stoma care should be initiated to prevent pressure ulcers and stoma infections
- As needed suctioning for secretions
Complications and airway emergencies in a tracheostomy pt:¶
- Hemorrhage (mild bleeding from surface vessels and granulation tissue is common, major bleeding is rare -> think erosion into brachiocephalic [innominate] artery)
- Airway damage -> subglottic or tracheal stenosis; tracheobronchitis
- Fistulas (tracheoarterial, tracheoesophageal)
- Unintended tracheostomy tube dislodgement:
- Bag mask (use hand/gauze to occlude stoma) or intubate from above (i.e. through the mouth); if complete laryngectomy then must use stoma
- Fresh trach (≤ 14 days): do NOT replace due to risk of misplacement into the mediastinum and loss of airway; airway management from above
- Older trach: can be replaced at bedside with obturator by trained staff
- All pts with trachs have a yellow sign above bed with date, type, size of trach as well as a replacement trach with obturator in the room
Secretion Management¶
- Respiratory hygiene (“pulmonary toilet”): heated vent, guaifenesin, hypertonic saline, DuoNebs, cough assist device, appropriate suctioning (too much = worsen secretions), acapella, IS
Introduction to Vent Management¶
Jared Freitas
Ventilator Settings:¶
- See above table in Modes of Oxygen Delivery for variables adjusted in each ventilator mode
- Trigger: what initiates a breath; time, flow, or pressure (pt triggers are flow and pressure; ventilator breaths are trigged by time)
Static Ventilator Readouts:¶
- Plateau pressure (Pplat): measure with inspiratory hold, assesses static lung compliance
- Auto-PEEP: measure with expiratory hold; occurs when volume of previous breath is not entirely expelled before the next breath is initiated
Dynamic Ventilator Readouts:¶
- Measured RR: in most modes, pt may trigger breaths above set RR; if set and measured RR match consider ↓ respiratory drive (sedation, neurologic injury) or iatrogenic over-ventilation
- VTi / VTe: tidal volume of inspiration (VTi) and expiration (VTe)
- VTi should approximately equal VTe, if not then concern for air leak (e.g. cuff leak or pneumothorax) or auto-PEEP
- Minute ventilation: calculated from VTe x RR; higher MV = more CO2 clearance
- Peak pressure: highest pressure reached in the entire ventilator cycle
Critical Non-ventilator hemodynamic readouts:¶
- SpO2: if poor waveform or discordant with PaO2, may need serial ABG
- HR: quickest indicator of emergencies such as pneumothorax, PE, ventilator disconnection
- Blood pressure: positive pressure ventilation decreases preload and afterload; depending on the underlying pt physiology, increases in positive pressure may be detrimental or beneficial for BP
Alarm Type | What is causing the alarm? | Troubleshooting |
---|---|---|
High Peak Pressure | Static compliance issue (stretch of the lung - doesn’t change with airflow) vs dynamic compliance issue (resistance of the circuit when there is air flowing) |
Step 1: Check plateau pressure by performing inspiratory hold. Must be in VC mode. High Peak and Low Plateau = Dynamic compliance issue -> High Resistance
High Peak and High Plateau = Static compliance issue -> Worsening alveolar process
|
Low Tidal Volume/Low Minute Ventilation (VE) | Pt is not getting the desired tidal volume/VE that was set in the vent parameters. The alarm reports exhaled VE. May cause inadequate ventilation, CO2 retention, potentially hypoxia |
Compare inspiratory tidal volumes (Vti) with expiratory tidal volumes (Vte) on the ventilator. If Vti>Vte, check for a leak in the system
If low tidal volumes and no leak (ie. Vti = Vte) and RR WNL
If low RR and no leak and Vt at goal
|
Apnea | No breaths are being triggered by the vent - your pt is NOT breathing - this is an emergency |
***Check that pt hasn’t self-extubated, trach hasn’t fallen out, or been unhooked from vent*** If self-extubated or tracheostomy decannulated, then immediately start bagging the pt (may need to bag from trach stoma if s/p laryngectomy). Have nurse call staff assist for re-intubation if necessary or have trach team called to replace a fresh (<7 days old) trach |
Ended: Critical care
Demo ↵
Pleural Effusions¶
Eddie Qian
Background¶
There is a normal influx of fluid into the pleural space due to leaky capillary membranes and the pleural space’s negative pressure. This fluid is constantly reabsorbed by lymphatics. An imbalance in the system will result in accumulation.
-
Some examples:
-
Increased influx: increased filtration from the capillaries from high intravascular hydrostatic pressure (i.e., heart failure, renal failure) or low intravascular oncotic pressure
-
Other liquid entry into the pleural space through anatomic deficits: CSF, chyle, urine, blood, ascites (the diaphragm is naturally porous)
-
Decreased efflux: obstruction of the parietal pleural stoma (from protein or cellular debris in exudative pleural effusions)
-
Increased systemic venous pressure (lymphatic system drains into the systemic venous circulation so high venous pressure prevents lymphatics from draining appropriately)
-
Evaluation¶
Imaging¶
- CXR: lateral decubitus position (if effusion moves with gravity, suggests free flowing)
- Ultrasound: assess size, location, loculations (fibrinous septations which may prevent simple drainage)
- CT Chest with contrast (not always indicated; helpful to eval septations)
Thoracentesis (see Procedures section)¶
Will it change management?
If septated or empyema, consider pulm consult for chest tube.
Orders:
- Always: Pleural LDH, protein, cell count/diff, culture
- Don’t forget serum LDH & protein!
- Consider: pleural cytology, hematocrit, triglycerides, glucose, amylase
Interpretation:
Lights Criteria | >=1 of the following = exudative |
---|---|
pleural protein : serum protein | > 0.50 |
pleural LDH : serum LDH | > 0.60 |
pleural LDH : upper limit of normal of serum LDH | > 0.66 |
- Transudative: CHF exacerbation, hepatic hydrothorax, atelectasis (caused by increased intrapleural negative pressure), hypoalbuminemia, renal failure
- Exudative: infections (bacterial, TB, fungal), malignant, rheumatologic, PE
Pearls about initial tests:
- Protein: >5 think TB or malignancy, =< 0.5 think urine, CSF, peritoneal dialysate
- Glucose: =< 60 think about malignancy, TB, rheumatologic, and less specific hemothorax or parapneumonic
- Cell count/differential: polys represent an acute process, monocytes represent a chronic process, lymphocytes think about TB or malignancy, eosinophils think about air/blood, TB, malignancy, asbestos, drugs
- Two separate processes may co-occur and a transudate may mask an exudative effusion; if concerned for this and you have clinical stability, trial diuresis prior to thoracentesis.
References
Ended: Demo
Endocrinology ↵
Adrenal Incidentalomas¶
Matthew Gonzalez
Background¶
- Adrenal mass >1cm, discovered by chance on radiographic imaging
- Less than 1% are malignant
- Supportive of benign: <4cm in size, smooth borders, homogenous appearance, <10 HU (Hounsfield units), rapid (>50% washout) contrast washout (on "adrenal phase" imaging)
- Supportive of malignancy: >4cm in size, irregular borders, > 20 HU on unenhanced CT, delayed contrast washout (<50% washout), tumor calcifications, increase in size over time, presence in young pts and hx cancer
Evaluation¶
- All incidentalomas should be screened for pheochromocytoma (~3% incidence) before operative intervention (24h urine fractionated metanephrines, catecholamines, plasma fractionated metanephrines)
- Cortisol secreting adenoma (~6% incidence) causing Cushing's syndrome: baseline serum DHEAS, low dose (1mg) overnight dexamethasone suppression test
- Aldosterone secreting adenoma (<1% incidence) causing hyperaldosteronism: if hypertensive (HTN) or hypokalemic order plasma aldosterone and renin, confirmatory testing with sodium loading (oral vs IV) and 24h urine aldosterone, sodium, and creatinine
Management¶
- If benign appearing and not hormone producing: interval imaging in ~1 year, and repeat hormone work up
- Unilateral adrenal incidentaloma
- If progression free (stable size, and not hormone producing) can consider monitoring cessation after 4 years
- Pheochromocytomas should undergo surgical evaluation for removal
- Alpha blockade (phenoxybenzamine) + propranolol prior to resection to avoid HTN crisis
- Aldosteronoma: should undergo surgical evaluation for definitive treatment; if unable to undergo surgery can use mineralocorticoid antagonist (e.g. spironolactone)
- Cortisoloma: if clinical significant should undergo surgical removal, will need perioperative glucocorticoid administration to avoid iatrogenic adrenal insufficiency
- Macroadenomas (masses >4cm) are usually malignant and should be considered for surgical resection due to higher risk of carcinoma
- Bilateral adrenal incidentalomas
- Surgical evaluation + will need adrenal venous sampling to confirm laterality in hormone producing tumors.
Additional information¶
- There can be coexisting adrenal incidentaloma and bilateral secretion of aldosterone – may require adrenal venous sampling to confirm
- Not all hyperaldosterone states will have both HTN and hypokalemia
- Subclinical Cushing's syndrome may be present based on initial dexamethasone suppression test, perform additional testing to determine if clinically significant
Adrenal Insufficiency¶
Griffin Bullock
Background¶
- Differential: Primary (Adrenals) vs Secondary (Pituitary):
- Exogenous steroid use (>10mg for >3wks) undergoing severe physiologic stress or sudden discontinuation of steroid
- Autoimmune adrenal insufficiency (Addison’s)
- Infection/Infiltration: tuberculosis, sarcoidosis, malignancy
- Hemorrhage (Waterhouse-Friderichsen syndrome)
- Pituitary mass/tumor, infarct, infiltration, surgery
- Trauma
Presentation¶
- Generalized weakness, lightheaded, abdominal pain, nausea, weight loss, fatigue
- Lab Abnormalities: hyponatremia, hyperkalemia, hypoglycemia
Evaluation¶
- Inpt Setting
- Draw AM cortisol and ACTH (ideally 8am) 0.25mg cosyntropin cortisol 1h after
- Cortisol level ≥18-20 rules out primary adrenal insufficiency (and most secondary)
- Draw AM cortisol and ACTH (ideally 8am) 0.25mg cosyntropin cortisol 1h after
- Outpt Setting
- Draw AM cortisol level for screening (>15 rules typically rules out adrenal insufficiency)
- ACTH stimulation for confirmation
Management¶
- Consult endocrine if ACTH stimulation test is abnormal
- Outpt: physiologic replacement doses usually with hydrocortisone (dosed 8am and ~2-4pm to mimic physiology). Can be dosed based on BSA or estimation based on weight. Ranges from ~20-40mg total daily (ex. 15mg AM, 10mg PM). Pt to increase if acute illness.
- Adrenal crisis (if concerned, treat first, test later)
- BMP, glucose monitoring, ACTH level, serum cortisol
- Fluid resuscitation: NS or D5NS. Do not use hypotonic saline.
- Hydrocortisone 100mg x1 followed by 50mg q8h
Central Diabetes Insipidus¶
Chloe de Crecy
Definition¶
- Lack of antidiuretic hormone results in free water excreted at kidneys
Etiology¶
- Idiopathic, autoimmune, tumors (primary or secondary), infiltrative (Langerhans cell histiocytosis), congenital, trauma, surgery, severe shock/ischemia
Presentation¶
- Polyuria, nocturia, polydipsia
- Elevated Na and osmolality, only if impaired thirst. Can be normal due to compensatory thirst
- Decreased bone mineral density (unclear pathophysiology)
Evaluation¶
-
- Confirm polyuria w/ low Uosm (DDx: psychogenic polydipsia, central DI, nephrogenic DI)
-
- Water restriction. If urine concentrates (Uosm>700), it is primary polydipsia not DI.
-
- Desmopressin trial (after Na >145) to differentiate between nephrogenic vs central. Central DI responds to desmopressin.
-
- MRI to investigate cause
Management¶
- Desmopressin (ADH analog) - PO, IV forms. Given at bedtime.
- Goal: reduce nocturia to improve sleep
- Risk: hyponatremia
Inpatient Diabetes Mellitus (DM)¶
Will Bassett, Sebastian Hinojosa
Background¶
- Blood glucose (BG) goal
- Wards: <140mg/dL fasting; <180mg/dL random;
- ICU: 140-180mg/dL (NICE-SUGAR Trial)
- Avoiding hypoglycemia (≤70mg/dL) is more important than targeting ideal BG
- For pts with terminal illness, limited life expectancy, or high risk for hypoglycemia (E.g. pts with liver disease, impaired kidney function, elderly, poor caloric intake, low BMI), a less aggressive insulin regimen and higher BG target ranges may be reasonable
- Qs to ask diabetic pt inpt: Type, age of onset, outpt provider, home regimen, method of checking sugars, last HgbA1c, steroids, complications, hypoglycemia (episodes and awareness)
Management¶
- Insulin therapy should be initiated for the treatment of persistent hyperglycemia starting at ≥180 mg/dL (checked on at least two occasions)
- Basal (long acting), prandial (premeal, short acting), and correction (sliding scale) insulin is the preferred regimen for most pts
- Initial orders on admission
- Typically HOLD all home oral diabetes medications
- Order set “SUBCUTANEOUS INSULIN ORDER(S)”
- Hemoglobin A1c: Obtain on all pts with diabetes or hyperglycemia (BG >140mg/dL) if not performed in the prior 3 months
- Fingerstick blood glucose: Typically AC/HS (before meals and nightly)
- Hypoglycemia management: Select all of these
- Basal insulin: Select insulin glargine
- Type 2 DM, consider ↓ home dose (50-60% to home dose) as often inpts have reduced PO intake and ↓ renal function
- Type 1 DM, DO NOT hold basal insulin, and avoid ↓ < 80% of home dose
- Insulin lispro meal: ↓ home dose by 50%, do not give while NPO
- Insulin lispro correction: Start with low or medium sliding scale and ↑ prn
- Carb-controlled or carb-restricted diet (‘no concentrated sweets’ at VA)
- Insulin adjustments
- If BGs persistently ≥180
- Calculate all insulin needs over 24h (basal + mealtime + sliding scale)
- Give 50% as basal and other 50% as 3 divided mealtime doses
- E.g. 10 basal + 0 mealtime + 14 sliding scale total = 24 units total daily = 12u basal + 4u TID with meals
- In insulin naïve pts, consider weight-based dosing as outlined under additional information
- In insulin naïve pts at high risk for hypoglycemia, may be reasonable to start with basal plus correctional insulin alone and readjust after 24-48 hours
- Calculate all insulin needs over 24h (basal + mealtime + sliding scale)
- If BGs < 70
- If overnight/AM, reduce basal insulin dose
- If daytime/post-prandial hypoglycemia, reduce mealtime and sliding scale
- If endocrine consulted for inpt glucose management, notify >24h prior to discharge for recommended discharge regimen
- If BGs persistently ≥180
Steroid-induced hyperglycemia¶
- Steroids increase insulin resistance causing elevated postprandial BG
- Insulin adjustments
- Double mealtime + correction dose while leaving basal dose the same
- Modified basal-bolus regimen (30% basal, 70% bolus
- Add NPH once daily (weight + dose based, per below*) if on daily prednisone
- Prednisone 10 mg = 0.1 u/kg NPH
- Prednisone 20 mg = 0.2 u/kg NPH up to 0.4 u/kg daily
- *lower dose if AKI, administer at the same time as prednisone dosing
- On discharge, if steroids will be longstanding, increase home insulin regimen per inpt requirements. If steroids will be tapered or discontinued soon after, either continue hospital regimen for remainder of steroid course or return to home regimen (hyper >hypoglycemia).
Additional Information¶
- Weight-based insulin dosing
- Used when starting insulin on pts with type 2 DM who are insulin naïve and hyperglycemic in the hospital
- Calculate total daily dosing (TDD) between 0.3 to 0.5 units/kg/day. Then split into 50% bolus and 50% as 3 divided prandial doses
- E.g. 80kg pt using low start of 0.3 u/kg/day would have TDD of 24 units. This equals 12u basal and 4u prandial insulin
- Consider lower starting insulin TDD of 0.2 units/kg in pts at high risk for hypoglycemia
- Tube feeds
- For continuous tube feeds, dose regular insulin q6h (not TID AC as they don’t have distinct “meals”)
- Consolidate for bolus feedings based on 24-hour insulin needs prior to discharge
- Insulin pumps
- Individuals who are comfortable using their diabetes devices, such as insulin pumps and CGM, should be allowed to use them in an inpt setting if they are well enough to care of the devices and have brought the necessary supplies. This requires a Diabetes Consult.
- Order POC BG checks AC/HS for nurse to chart and fill out MedEx pump contract
Diabetic Ketoacidosis (DKA)¶
Will Bassett, Matthew Gonzalez
Background¶
- Classically in type 1 diabetes but can also occur in insulin-dependent type 2 diabetes
- Definition: ↑ blood glucose (typically >350) w/ high anion gap and ketones in blood/urine
- If glucose is significantly elevated but little to no ketones/anion gap present, you likely have HHS, which is typically associated with ↑ serum osm and BG > 600
Evaluation¶
- Labs: BMP with anion gap (AG), CBC, phos, blood gas, serum osms, UA, consider beta-hydroxybutyrate
- Workup aimed at discovering the underlying cause (The "I’s"):
- Infection/ Inflammation: CBC, CXR, UA/UCx, LFTs; consider BCx, lipase (pancreatitis). Note: Leukocytosis will be present in DKA, even if infection isn’t the precipitating factor
- Ischemia (MI, CVA, mesenteric ischemia): EKG, Troponin, CT(A) if clinical suspicion
- Intoxication - Ethanol (can cause ketosis with or without acidosis), cocaine, MDMA
- Impregnation - Beta HCG if appropriate
- Insulin-openia/Iatrogenic: steroids, SGLT2 inhibitors, other meds, insulin delivery failure (pump failure, insulin degraded by heat, etc.)
- Remember to correct sodium for hyperglycemia (Na + 2.4mEq * (BG-100))
Management¶
- Initial monitoring: q2-4h BMPs (monitor K closely), q1h BG finger sticks
- Can space less frequently once gap is closed x 2 and pt off insulin infusion
- Ensure IV access
- Start IV fluids, insulin, and potassium as below
- Start insulin gtt
- Start subcutaneous long-acting insulin as soon as insulin drip/IV insulin is started
- Either start home long-acting (dose reduce as needed) or if insulin naïve, Lantus 0.2-0.3u/kg/day
- Lactated ringers’ preferred fluid if no contraindication
- Dextrose should be added when BG <200 (or clear liquid diet)
- Turn off insulin drip when anion gap is closed/bicarb has normalized on two consecutive BMPs
- Consult endocrinology early
- Management algorithm on next page (Diabetes Care. 2009 Jul; 32(7): 1335–1343)
- Note: pts are usually deficient in total body potassium even if serum potassium is high
Additional Information¶
- Pts on insulin drip can be admitted to stepdown (8MCE) with order set
- Pts can be admitted to stepdown on a subcutaneous insulin protocol with mild DKA with endocrinology guiding insulin management
- Avoid ordering C-peptide if concern for new type 1 diabetes, beta islet cells can be "stunned" with recent hyperglycemic states and may be falsely low
- SGLT2 inhibitors, are being prescribed much more often and can cause a euglycemic DKA, where acidosis and ketosis present but no elevated BG
Hyperthyroidism¶
Griffin Bullock, Lauren Waskowicz
Background¶
- Excess thyroid hormone caused by increased synthesis, excessive release of preformed thyroid hormone or endogenous/exogenous release of hormone from extrathyroid source
- Low TSH and High T4 and/or T3 (primary): Graves’, Toxic goiter, TSH-producing adenoma, hyperemesis gravidarum, subacute granulomatous thyroiditis, amiodarone, radiation, excessive replacement, struma ovarii
- Low TSH/Normal T4 and T3: Subclinical hyperthyroidism, central hypothyroidism, non-thyroidal illness, recovery from hyperthyroidism, pregnancy (physiologic)
- Subclinical Hyperthyroidism: repeat testing to verify abnormality is not transient
Presentation¶
- Sx: Heat intolerance, tremor, palpitations, anxiety, weight loss (w/ normal/increased appetite), increased BM frequency, SOB
- Physical Exam: Goiter, tachycardia/Afib, stare/lid lag, marked muscle weakness (rare presentation of thyrotoxic periodic paralysis), hyperreflexia
- Graves Specific Findings: proptosis/exophthalmos, infiltrative dermopathy (localized or pretibial myxedema)
Evaluation¶
- TSH, free T4, free T3 (only T3 or T4 may be elevated, though both often are)
- Biotin affects assay, causes falsely ↓ TSH and falsely ↑ FT4/FT3
- CBC: may have a normocytic anemia due to increased plasma volume
Management¶
- Methimazole, PTU, beta blockers, radioiodine ablation, surgery
- Endocrine referral
Hypoglycemia¶
Will Bassett
Background¶
- Definition: BG <70mg/dL
- Generally worse outcomes than hyperglycemia
- Causes: infection, liver failure, iatrogenic (e.g. insulin not adjusted for AKI or being NPO)
- Symptoms vary from tremor, palpitations, delirium, dizziness, AMS, coma (can mimic stroke)
Management¶
- Give PO carbohydrate load (15-20g oral glucose) if pt is alert and tolerates PO
- Give IV D50 if severe (<50), or cannot take PO
- Repeat measurements every 15 minutes in the first hour and treat again as needed
- Give glucagon 0.5-1mg SQ/IM if no IV access and impaired consciousness
- Effect is transient and IV access should be obtained ASAP for glucose infusion
- Do NOT hold basal insulin for T1DM: treat the low, then reduce dose if needed
Hypothyroidism¶
Griffin Bullock
Background¶
- Elevated TSH and low FT4 (primary hypothyroidism)
- Hashimoto’s (autoimmune) thyroiditis, iodine deficiency, drugs (amiodarone, dopamine antagonists), adrenal insufficiency, thyroid hormone resistance (genetic), non-thyroidal illness (recovery phase), post-surgery or ablation for hyperthyroidism
- Elevated TSH and normal FT4: subclinical hypothyroidism
- Low-Normal TSH, low FT4: central hypothyroidism, sick euthyroid
Presentation¶
- Often non-specific and vague: fatigue, cold intolerance, weight gain, constipation, dry skin, myalgia, edema, menstrual irregularities, depression, mental dysfunction
- Goiter, bradycardia, diastolic hypertension, delayed relaxation following reflex testing
- Lab abnormalities: microcytic anemia, hypercholesterolemia, hyponatremia, elevated CK
Evaluation¶
- TSH: If elevated repeat TSH and obtain T4
- Lipid panel, CBC, BMP
Management¶
- Treatment required if ↓ T4, significantly ↑ TSH (>10), or symptoms with any lab abnormality
- Titrate therapy to a normal TSH (unless central hypothyroidism, then target free T4 levels)
- Observation of asymptomatic pts with subclinical hypothyroidism (normal T4, mild ↑ TSH)
- Treatment is with formulation of T4 (full replacement is approximately 1.6 mcg/kg/day)
- Initial Dose:
- Young/healthy pts: full anticipated dose
- Older pts or pts with CAD, atrial fibrillation: 25-50 mcg daily
- Increased doses required for: pregnancy, estrogen therapy, weight gain, PPI therapy, GI disorders (↓ absorption), ferrous sulfate therapy
- Risks of overtreatment: cardiac effects, increase risk of osteoporosis
Additional information¶
- Pts should take Levothyroxine alone, 1h prior to eating to ensure appropriate absorption. Calcium, iron, PPIs interfere the most with absorption.
- Of note, missed doses can be taken along with the next dose.
- Symptoms improve in 2-3 weeks. TSH steady state requires 6 weeks.
- Dose can be titrated every 6 weeks based on TSH.
- Pregnancy: Pregnancy causes lab changes due to differing levels thyroid binding globulin. Use tables based on trimester to interpret values.
- TPO antibody testing should be conducted, as if abnormal this affects risk of complications
- Hypothyroid pts are at increased risk for preeclampsia, placental abruption, preterm labor/delivery
- Refer to endocrine for close monitoring and adjustment to avoid fetal complications
Osteoporosis¶
Claire Lo
Background¶
- Definition: decreased bone mass leading to increased risk of fracture
- Differential: malignancy (e.g., multiple myeloma), elder abuse (e.g., spiral fractures of long bones), hyperparathyroidism, Paget’s disease
Post-Menopausal Women | Pre-Menopausal Women | |
---|---|---|
Risk Factors | current smoker, >3 alcoholic drinks/day, chronic glucocorticoids (>4 weeks), previous fracture, parental history of fracture, RA, low-weight bearing status | Female Athlete Triad (disordered eating, amenorrhea, bone loss) |
Presentation | height loss, fragility fracture (GLF, minor trauma) | repetitive long bone stress fractures, atypical fractures (pubic ramus, femoral neck, non-metatarsal foot bones) |
Screening | all women 65yo+ (Grade B USPSTF) | women <65yo w/ clinical risk factors via FRAX score (Grade B USPSTF) |
Tests | Gold Standard: DEXA hip and lumbar spine Labs: 25[OH]D, calcium, phosphorus, albumin, total protein, LFTs (ALP), PTH |
|
Diagnosis | T score ≦ -2.5 at femoral neck or spine OR fragility fracture of vertebra, pelvis, wrist, humerus, rib | |
Management | vitamin D supplementation, calcium if necessary, smoking cessation, weight bearing activity, Rx | |
Monitoring | DEXA q 2 years (for osteoporosis), q 4 years (for osteopenia), q15 years (for normal BMD). |
Evaluation¶
- Interpretation of DEXA Score
- Osteoporosis: T score ≦ -2.5
- Osteopenia: -1.0 > T score > -2.5
- Normal bone mineral density: T score -1.0
- Interpretation of FRAX (Fracture Risk Assessment Tool):
- 10-year risk of major osteoporotic fracture (Google “FRAX tool.”)
Pharmacologic Management¶
- Indications: T score ≦ -2.5 (osteoporosis) OR -1.0 > T score > -2.5 with FRAX>3% for hip fracture
- First line: oral bisphosphonates (alendronate 10mg qd, at least 30min before food)
- If eGFR<30: refer to endocrinology for IV zoledronic acid or IV denosumab
- If severe (T score< -3.0): consider anabolic (e.g., teriparatide) as first line agent
Additional Information¶
- There is currently no recommendation to screen men for osteoporosis.
Outpatient Diabetes Management¶
Matthew Lu
Background¶
- Type I Diabetes - insulin deficiency (GAD65, IA2, ZnT8 antibodies positive, Insulin and C-peptide inappropriately low)
- Type II Diabetes - insulin resistance (generally associated with obesity)
- Classification by HgA1c: Pre-diabetes: 5.7 to 6.4%; Diabetes: >= 6.5
Management:¶
- Lifestyle changes:
- Exercise 175 minutes weekly
- Caloric restriction for weight loss of 10%
- Low carb or Mediterranean diet, reduce normal portions by 10-20%, limit sugary drinks, drink large glass of water before meals
- BP Goal generally < 130/80
- ACE-inhibitor is first-line anti-hypertensive
- Manage complications of diabetes
- Increased cardiovascular risk (2-4x risk of MI, CVA or death)
- High intensity statin if clinical ASCVD present
- Moderate intensity statin if age > 40 or with ASCVD risk factors (LDL >100, HTN, smoking, FHx of CVD, CKD)
- Consider aspirin if ASCVD > 10% (balanced against bleeding risk)
- Smoking cessation
- Baseline ECG at diagnosis
- Retinopathy – annual retinal exams
- Peripheral Neuropathy – annual foot exams, can use gabapentin if present
- Autonomic Neuropathy – ED, orthostatic hypotension, gastroparesis
- Nephropathy – annual creatinine and urine microalbumin (albumin/creatinine ratio) - need repeat measurements 3mo apart to confirm albuminuria
- Normal: < 30mg/g
- Moderate albuminuria: 30-300 mg/g (consider starting ACE-I)
- Severe albuminuria: > 300 mg/g i(should be on ACE-I)
- If persistent despite ACE-I, start SGLT2 inhibitor (if GFR allows)
- If persistent despite SLGT2 inhibitor, start finerenone
- Consider involving nephrology
- Increased cardiovascular risk (2-4x risk of MI, CVA or death)
- Glycemic goals:
- Fasting glucose 80-130 mg/dL, postprandial (90-120 min after meal) < 180mg/dL
- A1c goal: generally < 7%, < 7.5% for 65 yrs, < 8% for poor health or life expectancy < 10 yrs
- Medications for glycemic control
- For pre-diabetes, encourage lifestyle management and consider starting metformin
- If initial HgA1c < 9%
- 1st agent: metformin (usually decreases HgA1c by 1-2%) – start at 500mg daily and increase by 500mg every 1-2 weeks if no GI side effects up to goal 2000mg daily
- If eGFR < 45, then half dose
- If eGFR < 30, then discontinue
- 2nd agent (if HgA1c still not at goal within 3 months):
- GLP-1 agonist generally preferred (best weight loss benefit, usually decreases HgA1c by 1%)
- SGLT2 inhibitor preferred if pt has HF or DM nephropathy (usually decreases HgA1c by 1%)
- Consider sulfonylurea if pt on HD
- 3rd agent (if HgA1c still not at goal after additional 3 months)
- GLP-1 agonist or SGLT2 inhibitor (whichever was not started as second agent)
- 1st agent: metformin (usually decreases HgA1c by 1-2%) – start at 500mg daily and increase by 500mg every 1-2 weeks if no GI side effects up to goal 2000mg daily
- If initial HgA1c > 9%
- Start metformin AND GLP-1/DDP4-I OR insulin
- How to initiate insulin
- Start with long-acting insulin nightly (10 units or 0.1 units/kg/d)
- Check fasting glucose daily and increase insulin by 2 units q 2-3 days until fasting glucose within goal (80-130mg/dL)
- If hypoglycemia occurs, decrease insulin by 4 units or 10% (whichever is greater)
- If A1c > 7% after 3mo, add mealtime insulin
- Check post-prandial glucose and start with 4 units short acting insulin at meals where post-prandial glucose > 180. Adjust by 2 units q 3 days until post-prandial glucose < 180.
- Start with long-acting insulin nightly (10 units or 0.1 units/kg/d)
- When HgA1c < 6.5% consider de-escalating medications
- Other medication class options: sulfonylureas, DDP4-I, thiazolidinediones
Outpatient Medical Weight Loss¶
Liana Mosley
Background¶
- 74% of US adults are overweight/obese
- Target weight loss of 5-7% body weight for prevention of co-morbidities
- In general, encourage lifestyle modifications (dietary interventions, exercise) first
- See Obesity/Nutrition under Outpt Medicine
Management¶
- Consider referral to medical weight loss: BMI ≥ 30 or ≥ 27 with with ≥ 1 co-morbidity
- Referral to surgical weight loss: BMI ≥ 35 or ≥ 30 with with ≥ 1 co-morbidity
Medication | Mechanism | Side Effects | Other considerations |
---|---|---|---|
Metformin | Unclear MOA, potentially appetite suppression | N/V/D, lactic acidosis in renal failure | 1st line, low cost, T2DM prevention/treatment |
Orlistat (Xenical) | Reduces fat absorption | Fatty diarrhea, gas, abdominal pain | Significant side effect profile |
Phentermine-topiramate (Qsymia) | Appetite suppression, early satiety | Constipation, dizziness, dry mouth, taste changes, anxiety, insomnia, HTN, tachycardia, cognitive slowing | Risk of rebound weight gain. Discontinuing can lead to withdrawal |
Phentermine (Ionamin) | Reduces appetite, FDA-approved for short-term use (up to 12 wks) | Constipation, dizziness, dry mouth, taste changes, anxiety, insomnia, HTN, tachycardia | Risk of rebound weight gain. Discontinuing can lead to withdrawal |
Naltrexone-bupropion (Contrave) | Appetite suppression, early satiety | Constipation, diarrhea, dizziness, dry mouth, HA, increased BP, tachycardia, insomnia, liver damage, N/V, SI | Risk of rebound weight gain. Discontinuing can lead to withdrawal |
Liraglutide (Saxenda) | GLP-1 agonist Appetite suppression | Victoza: low dose formulation, FDA approved for T2D but not weight loss N/V/D, constipation, abdominal pain, HA, tachycardia, dizziness, injection site reaction, pancreatitis | Contraindicated: pancreatitis, medullary thyroid ca, MEN2A/MEN2B |
Semaglutide (Wegovy/ Ozempic/ Rybelsus) | GLP-1 agonist Appetite suppression Rybelsus = PO option, FDA approved for T2D but not weight loss | N/V/D, abdominal pain, constipation, injection site reaction, pancreatitis STEP8 RCT: Semaglutide >Liraglutide | Contraindicated: pancreatitis, medullary thyroid ca, MEN2A/MEN2B |
Tirzepatide (Mounjaro) | GLP-1 agonist + GIP receptor agonist (first in class) | N/V/D, abdominal pain, constipation, injection site reaction, pancreatitis T2DM: superior to GLP1 agonist (lowered A1c 2.0-2.5%) Obesity: weight loss of 15-20% from bl | Contraindicated: pancreatitis, medullary thyroid ca, MEN2A/MEN2B |
Panhypopituitarism¶
Chloe de Crecy
Etiology¶
- Originates from hypothalamus vs anterior pituitary. Time course: acute vs insidious.
- Hypothalamic: mass (benign vs malignant), radiation, infiltrative dz (sarcoid), infections (TB), TBI, stroke
- Pituitary: mass (adenoma, cysts), surgery, radiation, infiltrative dz (hypophysitis, hemochromatosis), infection, infarction, apoplexy, genetic mutations, empty sella
Evaluation¶
- Not all hormones are always affected. Secretion of GH and gonadotropins more likely affected than ACTH and TSH.
- Consult Endocrine
HPA Axis | Symptoms | Testing | Replacement |
---|---|---|---|
CRH – ACTH – Cortisol (Adrenals) | Fatigue, weight loss, hypoglycemia | AM cortisol (decreased) ACTH (decreased) Cosyntropin Stim test |
Hydrocortisone (~15-25mg total daily) Prednisone |
TRH – TSH – T4/T3 (Thyroid) | Fatigue, cold intolerance, constipation, bradycardia, skin changes, anemia, delayed reflexes | TSH, T4, T3 (all decreased) | Levothyroxine |
GnRH – LH/FSH - Estrogen, androgens (Gonads) | Hypogonadism F: anovulation, hot flashes, vaginal atrophy, decreased bone density M: decreased energy/libido, low energy, decreased muscle mass, decreased spermatogenesis |
F w/ amenorrhea: LH, FSH, estradiol, medroxyprogesterone challenge (withdrawal bleeding) M: LH |
F: estradiol (+ progestin if uterus) M: Testosterone (injection, gel, patch) or hCG if trying to conceive |
GHRH – Growth hormone – liver, fat | Children: short stature Adults: decrease in lean body mass, decrease in bone density, dyslipidemia |
IGF-1 (decreased) | Recombinant growth hormone |
Dopamine (inhibitor) – Prolactin – mammary glands | Inhibited lactation | Not done | Not done |
Severe Hypertriglyceridemia¶
Chloe de Crecy
Background¶
- Elevated triglycerides (TG) on a fasting lipid panel
- Normal: <150 mg/dL
- Moderate HTG: 150-499 mg/dL
- Moderate to severe HTG: 500-999 mg/dL
- Severe HTG: >1000 mg/dL
- Nearly all pts with severe HTG have a genetic predisposition + additional risk factor (e.g. DM, alcohol abuse, oral estrogen, hypothyroidism, nephrotic syndrome, propofol, ART)
- Risks of hypertriglyceridemia: pancreatitis (requires serum TG >500 mg/dL), ASCVD
- Signs: xanthomas, hepatosplenomegaly, lipemia retinalis, milky appearance of plasma
- Sxs: short-term memory loss, abdominal pain, flushing with ETOH
Evaluation¶
- Lipid panel: usual outpt screening, acute pancreatitis, cutaneous xanthomas, familial HTG, monitoring HTG treatment
- Note: Na, glucose, amylase, LDL readings can be affected by HTG
- Consider sending A1c, Cr, TSH
- Assess medication list for secondary causes
Management¶
- HTG induced pancreatitis
- If pt has hypocalcemia, lactic acidosis, or multi-organ dysfunction
- Initiate plasmapheresis and monitor serum TG after each cycle until <500
- Severe dietary fat restriction (<5%) until TG <1000
- If none of the above and pt is hyperglycemic
- Start insulin gtt, IVF, monitor q1h BG and q12h TG
- Discontinue insulin when serum TG <500
- Severe dietary fat restriction (<5%) until TG <1000
- If none of the above and pt is euglycemic
- Start insulin gtt + dextrose, Monitor q12h TG until <500
- Severe dietary fat restriction (<5%) until TG <1000
- If pt has hypocalcemia, lactic acidosis, or multi-organ dysfunction
- Long-term Management (once TG <1000, otherwise decreased efficacy)
- Pharmacologic: fibrates (most commonly fenofibrate), statins, niacin, omega-3 fatty acids
- Nonpharmacologic: discontinue ETOH use, dietary fat and sugar restriction (target fat intake at <10% of calorie intake), exercise
Steroid Conversion Chart¶
Neil Phillips
Drug Name | Equivalent doses (mg) | Anti-inflammatory activity relative to hydrocortisone | Duration of action (hrs) |
---|---|---|---|
Hydrocortisone (cortisol) | 20 | 1 | 8 to 12 |
Cortisone acetate | 25 | 0.8 | 8 to 12 |
Prednisone | 5 | 4 | 12 to 36 |
Prednisolone | 5 | 4 | 12 to 36 |
Methylprednisolone | 4 | 5 | 12 to 36 |
Triamcinolone | 4 | 5 | 12 to 36 |
Dexamethasone | 0.75 | 30 | 36 to 72 |
Betamethasone | 0.6 | 30 | 36 to 72 |
Stress Dose Steroids¶
Griffin Bullock
Primary Options¶
- Dexamethasone 4mg IV: does not affect cortisol assays, ideal if diagnosis uncertain
- Hydrocortisone 100mg IV bolus then 50mg q8h until stable: greater mineralocorticoid activity. Ideal if adrenal insufficiency known/confirmed or if hyperkalemic (K>6.0)
When to Use¶
- Concern for adrenal crisis
- Pts with known adrenal insufficiency:
- Minor Illness: ↑ dose x3 for 3 d or until clinically improved & acute stress resolved
- Surgery: dependent on severity of operation
- Minor (e.g. hernia repair): hydrocortisone 25mg for 1 day
- Moderate (e.g. cholecystectomy): 50-75mg day of surgery and post-op day 1
- Major (e.g. CABG): 100-150mg daily 2-3 days (would consult endocrine)
- Trauma, critical illness, or unclear give stress dose
Thyroid Nodules¶
Terra Swanson
Background¶
- ~50% of adults will have a thyroid nodule on ultrasound
- Benign: goiter, cyst, inflammatory, Hashimoto’s, follicular adenoma (microadenoma)
- Malignant: follicular, papillary, medullary, anaplastic, metastatic, thyroid lymphoma
- Risk factors for malignancy: age <30, head or neck radiation, family history of thyroid cancer
Evaluation¶
- Initial work-up after a nodule is found (either clinically or incidentally on imaging)
- TSH, Free T4, Thyroid U/S
Management¶
- If Low TSH: Likely a hyperfunctioning nodule (benign in 95% of cases)
- Order Iodine-123 or technetium-99m thyroid scan
- If hyperfunctioning → measure T3/free T4 if ↑, treat for hyperthyroidism
- If non-functioning → proceed as if TSH were normal
- Order Iodine-123 or technetium-99m thyroid scan
- Normal or elevated TSH:
- FNA indicated based on U/S findings listed below (determined by TI-RADS system)
- Nodules >1cm that have high- or intermediate-suspicion pattern
- Nodules >1.5cm that have low-suspicion pattern
- Nodules >2cm that have very-low-suspicion pattern
- FNA cytology determines the plan of action:
- Benign → periodic US monitoring at 12-24mo, then at increasing intervals
- Indeterminate → repeat FNA in 3-12 months
- Malignant → surgical referral
- FNA indicated based on U/S findings listed below (determined by TI-RADS system)
- Nodules that do not meet FNA criteria, US findings determine the timing for follow-up imaging:
- High suspicion: 6-12mo
- Low to intermediate suspicion: 12-24mo
- Nodules >1cm with very ↓ suspicion OR pure cyst: >24mo if at all
- Nodules <1cm with very ↓ suspicion OR pure cyst: no further imaging necessary
Thyroid Storm¶
Gaby Schroeder
Background¶
- Diagnosis is based on recognition of exaggerated signs/symptoms of thyrotoxicosis leading to multi-organ dysfunction in the setting of precipitating event
- Common Precipitants: Grave’s Disease, surgery, trauma, pregnancy, stress, infection, MI/PE, medication non-compliance, iodine loads
- Use Burch-Wartofsky Point Scale (BWPS); available on MD Calc
- >highly suggestive
- >25-44 impending storm
- <25 unlikely to represent storm
Management¶
- ENDOCRINE EMERGENCY - if suspected consult Endocrine ASAP
- Therapies directed towards thyroid gland
- PTU: Preferred, 500-1000mg loading dose, followed by 250mg q4 -6 hours (PO, rectal)
- Methimazole: q4-6 hours, dose varies (PO, rectal, IV)
- Therapies directed toward decreasing T4 to T3 conversion
- Propranolol (60-80mg PO q4)
- Hydrocortisone (300mg x1, 100mg q8) - treats high incidence of co-existing adrenal insufficiency
- Cholestyramine 4g QID can be considered to reduce enteric recirculation
- Refractory Storm: plasmapheresis and plasma exchange
- Close hemodynamic monitoring, may need vasopressors (consider transfer to ICU)
Ended: Endocrinology
Gastroenterology ↵
Acute Abdominal Pain¶
Alex Mamunes
General Approach¶
-
Rule out life threatening causes: Obstruction, Perforation, Dissection, AAA rupture, Inferior MI, Ectopic Pregnancy
-
History: pain quality/timing/location/severity, aggravating and alleviating factors (eating, bowel movements, position), nausea/emesis, bowel changes, flatus & prior episodes
-
Initial labs: CBC, BMP, LFTs, INR, lactate, lipase, U/A, urine hCG
System | Causes | Common features | Workup |
---|---|---|---|
Esophagus | Esophagitis – GERD, EOE, candida, HSV, CMV, pill, functional | Epigastric pain, nocturnal reflux, odynophagia, dysphagia, thrush, immunocompromised | Trial PPI, nystatin swish and swallow, consider EGD |
Stomach | Dyspepsia | Epigastric pain, indigestion, bloating | H. pylori testing, Trial PPI, ± EGD |
Peptic ulcer disease | NSAID use, better or worse w/ food, ± melena | CBC, H. pylori testing, EGD | |
Gastritis | NSAID use, ETOH abuse, burning epigastric pain | ||
Liver | Hepatitis: Ischemic, Viral, ETOH, trauma, toxins, autoimmune, congestive | RUQ pain ± jaundice EtOH, Tylenol or IVDU |
LFTs, INR, ETOH, Tylenol lvl, viral panel, RUQ U/S + dopplers; CT |
Spleen | Splenomegaly: increased size, infarct, abscess | LUQ pain | Physical exam, CT |
Biliary | Biliary colic | Overweight, ♀, 40’s, lasts hrs, worse with food, RUQ pain scapula |
LFTs, RUQ U/S |
Cholecystitis | RUQ pain (Murphy’s sign), nausea, emesis with fever | ||
Choledocholithiasis | RUQ pain, N/V with jaundice | CBC, LFTs, RUQ U/S, blood cx | |
Ascending cholangitis | RUQ pain, N/V, jaundice, fever; hypotension, AMS | ||
Pancreas | Acute or chronic Pancreatitis; Complications (fluid, collection, necrosis, pseudocyst) | ETOH use, gallstones, epigastric pain back, N/V Chronic pancreatitis: calcifications on CT |
Lipase, CT A/P (rarely necessary within 24-48 hrs), RUQ U/S for gallstones |
Intestines | Gastroenteritis | N/V, sick contact, undercooked food, travel | Supportive care |
Diverticulitis | Older, h/o diverticulosis, LLQ pain with fever | CBC (leukocytosis) CT A/P w contrast |
|
Constipation | h/o IBS, narcotic use, unable to pass stool, straining | KUB | |
Bowel Obstruction/Ileus | Prior hernia, abd surgery or malignancy, pain, nausea, emesis, distention inability to pass stool or flatus | KUB (air fluid levels) CT is more sensitive If concerned, page EGS and consider NGT to suction |
|
Acute Small Bowel Mesenteric Ischemia | Vascular disease, A-Fib, dissection, thrombosis, rapid onset, severe, periumbilical with N/V, recent hypotensive episode, post-prandial | CBC (leukocytosis) BMP (metabolic acidosis), Lactate CT A/P w contrast (CTA if suspicion) |
|
Colonic non-occlusive Mesenteric Ischemia: ischemic colitis | Cramping pain, laterally (most often left), urge to defecate + hematochezia | CBC, BMP, Lactate CT A/P w contrast +/- colonoscopy |
|
Appendicitis | Periumbilical to RLQ with N/V, later fever | CBC, Lactate, CT A/P w/contrast | |
IBD Flare | H/o Crohn’s or UC, Abd pain, fever, diarrhea, hematochezia | CBC, Lactate, CTE, ESR, CRP, C-diff, GIPP | |
C. diff colitis | Antibiotic exposure, diarrhea, abdominal cramping | C-diff PCR, CBC (leukocytosis) KUB (megacolon) |
|
Ogilvie’s syndrome | Pseudo-obstruction in elderly pt, signs of obstruction w/o mechanical cause | CBC, lactate, CT A/P w contrast | |
Volvulus | Progressive abdominal pain, nausea, distention, constipation, vomiting | CBC, lactate CT A/P w contrast |
|
Typhlitis | Neutropenia, abdominal pain (often RLQ), fever | CBC with diff, CT A/P w/ contrast, blood cx, C-diff; empiric abx |
|
OBGYN | Ectopic pregnancy | Sexually active, 6-7 wks after LMP, RLQ or LLQ pain + vaginal bleeding | Urine hCG, pelvic US, CBC, T&S |
Pelvic inflammatory disease, endometritis, Tubo-ovarian abscess |
Sexually active, h/o STI, purulent discharge, cervical motion tenderness, ± fever | Pelvic exam w/ culture, GC probe, pelvic US | |
Ovarian torsion | Young, sudden onset & severe, often with N/V | Pelvic US w/ doppler | |
Kidney | Nephrolithiasis | h/o kidney stones, Crohn’s disease, sharp flank pain, paroxysms, ± hematuria | U/A, CT A/P without contrast |
UTI | Suprapubic pain, dysuria, cloudy urine, new odor | U/A with culture | |
Pyelonephritis | Flank pain, fever/chills, CVA tenderness, usually UTI symptoms | U/A with culture, BMP CT A/P w/contrast |
|
Urinary Retention | Older pt, male with BPH, anticholinergics | Post-void residual | |
Renal infarct | h/o vascular disease or A-fib, acute flank pain with N/V, +/- fever, HTN | CBC, BMP, UA, ECG (r/o a-fib) CT A/P w contrast |
|
Vascular | Myocardial infarction | CAD risk factors, DoE, epigastric, diaphoresis | ECG, troponin |
Aortic Dissection | Vascular Risk factors, sudden onset, tearing pain back | CT dissection rule out | |
AAA rupture | Vascular risk factors, sudden onset back, hypotensive, pulsatile abdominal mass | CT A/P w contrast, consult vascular surgery | |
MSK/skin | Herpes zoster | Immunocompromised, dermatomal rash, burning pain | Physical exam Vesicle PCR for zoster |
Muscle strain | h/o trauma, overuse, heavy exercise, worse with twisting or bending | Physical exam; rest, NSAIDs | |
Hernia | Bulge, worse w/valsalva | CT A/P non con | |
Pulmonary | Pneumonia | Productive cough, fever | CXR, CBC, sputum cx |
Pulmonary embolus | Tachycardia, tachypnea, hypoxemia | ECG, trop, BNP CTA chest |
|
Functional | IBS, depression, dyspepsia, anxiety abdominal migraine, functional | Imaging negative Otherwise negative workup |
Above workup |
Other | Adrenal crisis | Hypotension, fatigue, lethargy, N/V, weight loss, hyperpigmentation | BMP (↓Na, ↑K, ↓ Glu) Cort. stim |
Intra-abdominal abscess | Prior intra-abdominal disease or surgery, fever | CBC, blood cx CT A/P w/ contrast |
|
DKA | Nausea, emesis, general abdominal pain | CBC, BMP, U/A β–hydroxy butyrate |
|
Hypercalcemia | N/V, constipation, ↑ thirst, ↑ urination, bone pain, muscle weakness, confusion, fatigue |
BMP, ionized calcium, PTH, Vit D, PTHrp | |
Acute intermittent porphyria | Severe, poorly localized with motor/sensory neuropathy, red urine, tachycardia | Urinary PBG |
Acute Diverticulitis¶
Michael Koenig
Background¶
- Inflammation and/or infection of a diverticulum, a small out-pouching along wall of colon
- Presence of colonic flora on urine culture or pneumaturia suggests colovesical fistula
- Most pts with uncomplicated diverticulitis have significant improvement 2-3 days after antibiotics
Presentation¶
- Lower abdominal pain (85% LLQ), tenderness to palpation on exam, N/V, low-grade fever, change in bowel habits (constipation or diarrhea)
Evaluation¶
- CBC w/diff, CMP, Lipase, U/A, β - hCG
- Imaging: CT abdomen/pelvis with oral and IV contrast
- CT findings: localized bowel wall thickening (>4mm), paracolic fat stranding, presence of colonic diverticula
Management¶
- Bowel rest vs. clear liquids (advance diet as tolerated)
- PO or IV antibiotics: should cover GNRs and anaerobic organisms
- Zosyn, cefepime + metronidazole, or meropenem (if high risk for organisms w/ESBL)
- Cipro/flagyl if PO
- If low risk and mild disease, may not need antibiotics
- Continue IV abx until abdominal pain/tenderness is resolved (usually 3-5 days), then transition to oral: cipro + metronidazole or Augmentin to complete 10-14 d course
- Colonoscopy after complete resolution of symptoms (6 – 8 weeks) to definitively rule out presence of underlying colorectal cancer (unless performed in last year)
Complications¶
- Pts who fail to improve or deteriorate require repeat imaging
- Abscess continue antibiotics & percutaneous drainage (if possible) for abscesses > 4 cm
- Surgery if no improvement 2-3 days after drainage
- Obstruction: radiographic differentiation between acute diverticulitis and colon cancer is difficult; thus surgical resection of bowel is needed to relieve obstruction and rule out cancer
- Fistula: Rarely heal spontaneously, require surgical correction
- Perforation:
- Microperforation (contained perforation):
- Presence of small amount of air bubbles, but no oral contrast outside of colon on CT
- Most treated with IV abx and bowel rest like uncomplicated diverticulitis
- Frank perforation:
- Intraabdominal free air, diffuse peritonitis requires emergency surgery
Acute Pancreatitis¶
Alex Wiles
Background¶
- Common causes: Gallstones (40%), EtOH (30%)
- Other causes: post-ERCP, pancreatic cancer/obstruction, blunt abdominal trauma, hypertriglyceridemia (TG >1000), hypercalcemia, drugs (thiazides, protease inhibitors, azathioprine, 6MP), mumps, Coxsackie, vasculitis, pregnancy, genetic (PRSS1, SPINK1, CFTR), autoimmune (IgG4), scorpion venom
- Several scoring systems:
- BISAP (BUN >25, Impaired mental status, SIRS, Age >60, Pleural
effusion)
- 0–2 Mortality <2%; 3-5 Mortality >15%
- APACHE II (MD Calc, several factors)
- 0–8 Mortality <4%; > 8 Mortality 11–18%
- BISAP (BUN >25, Impaired mental status, SIRS, Age >60, Pleural
effusion)
Presentation¶
- Must have 2 out of the three:
- Pain characteristic of pancreatitis (sharp, epigastric, radiating to back)
- Imaging characteristic of pancreatitis (US, CT, MRI)
- Enzymes (lipase or amylase) >3x ULN (use lipase, much more specific)
- *If pain is characteristic and lipase > 3x ULN, no need for CT A/P
- Grading Severity:
- Mild: no organ failure or systemic complications
- Moderate: transient organ failure (<48 hours)
- Severe: persistent organ failure (>48 hours)
Evaluation¶
- Lipase, CBC, CMP, lipid panel, lactate, direct bilirubin
- Obtain RUQ U/S for all pts, evaluates for gallstones
- CT A/P w/ IV contrast if indicated
- Reserved for patients not improving at 48-72 hour to assess for complications
- If performed at onset, underestimates severity (necrosis takes 72 hours from onset)
Management¶
- Fluids, Fluids, Fluids:
- First 12-24 hrs: IVF at 200 to 500 cc/hr, or 5-10 cc/kg / hr (2.5 –
4 L within first 24 hrs)
- Follow HCT and BUN as markers for successful fluid resuscitation
- Aggressive IVF in first 24 hours reduces both morbidity and mortality
- Persistent hemoconcentration at 24 hr is associated with necrotizing pancreatitis
- First 12-24 hrs: IVF at 200 to 500 cc/hr, or 5-10 cc/kg / hr (2.5 –
- Pain Control:
- Common starting narcotic regimen is oxycodone 10 mg q6h PRN and hydromorphone 0.5 mg q4h for breakthrough
- Nutrition:
- NPO but start PO diet as soon as patient can tolerate (even within 24 hours)
- Clear liquid diet or mechanical soft and advance as tolerated
- Low fat diet (Fatty acids → CCK → trypsinogen to trypsin)
- If NPO > 72 hours, attempt PO and if fail, place Dobhoff for enteral nutrition at latest by day five… outcomes with NG/NJ >>> TPN
- Antibiotics:
- Fever, leukocytosis common, not an indication for ABX as the necrosis is sterile
- Infection of the necrosis should be suspected with failure to improve 7 days after onset
- Cefepime + Flagyl or carbapenem
- EUS or IR guided drain for aspirate: can be done on immature collections for diagnostic purposes but typically only done if collection is walled-off—at least 4 weeks
- Endoscopic Intervention (cystogastrostomy) has emerged as first-line therapy for symptomatic pseudocysts or walled-off pancreatic necrosis , with step-up therapy to video assisted retroperitoneal debridement (VARD) or surgery when needed
Additional Information¶
- If choledocholithiasis on Imaging urgent ERCP for patients with cholangitis or obstructive jaundice, otherwise elective ERCP
- If Intermediate probability for choledocholithiasis MRCP or EUS or (for patients requiring cholecystectomy Intraoperative cholangiogram
- If biliary sludge but no stones on U/S, still consider cholecystectomy (likely microlithiasis)
- Complications:
- ARDS, abdominal compartment syndrome, AKI, DIC
- < 4 weeks after pancreatitis: Peripancreatic fluid collection, acute necrotic collection
-
6 weeks after pancreatitis: Pancreatic pseudocyst, walled-off necrosis (WON)
- Most fluid collections should be followed over time as acute collections can resolve and are unable to be sampled safely with EUS
- Gallstone pancreatitis:
- All pts should have cholecystectomy once recovered (recurrence is 25-30%) with EGS
- Performed during initial admission in cases of mild acute pancreatitis
Biliary Disease¶
Alex Wiles, Anton de Witte
Pearls¶
- ERCP is not available at VA: requires fee-basis consult to VUMC, contact GI to arrange
- Prior cholecystectomy CBD normally dilates to 10 mm, not pathologic
- Pneumobilia generally indicates performance of prior biliary sphincterotomy and/or biliary stent
- CBD dilation classically > 6mm, but CBD dilates with age: 70 yo 7mm, 80 yo 8mm; opiates can also cause biliary dilatation
Biliary Colic¶
- Transient biliary obstruction typically at the GB neck without GB inflammation (no fever)
- Presentation: Constant (not colicky) intense, dull RUQ pain and N/V for 30 minutes to 6 hours, then resolves, provoked by fatty foods (CCK), absent Murphy’s sign
- Biliary colic generally consists of discrete episodes separated by weeks to months, and not daily pain
- Evaluation: Normal (CBC, LFTs, Lipase, Lactate)
- Imaging: RUQ U/S: cholelithiasis (stones in GB)
- Management: Elective cholecystectomy as outpatient
Acute Calculous Cholecystitis¶
- Inflammation of the GB from an obstructing stone in the GB neck or cystic duct
- Ddx: PUD, pancreatitis, choledocholithiasis, ascending cholangitis, IBD, Fitz-Hugh Curtis
- Presentation: Severe constant RUQ pain, fever/chills, N/V, + Murphy sign
- Evaluation: CBC (leukocytosis), CMP (mild AST/ALT ↑), Lipase, Lactate, BCx x2
- Imaging: RUQ U/S: gallstones + GB wall thickening or pericholecystic
edema
- If U/S non-diagnostic (no stones or GB inflammation) HIDA Scan (lack of GB filling)
- Management
- NPO, IVF, IV Abx until resolved or surgical removal
- Urgent Cholecystectomy (<72H) with EGS;
- If poor surgical candidate: Cholecystostomy with IR; endoscopic drainage options for selected patients (i.e. poor surgical candidates also with ascites)
- Complications: gangrenous cholecystitis, perforation, emphysematous cholecystitis, chole-cysto-enteric fistula, gallstone ileus
Acute Acalculous Cholecystitis¶
- Inflammation of the GB without obstructing stone (due to stasis and ischemia)
- Presentation: Seen in critically ill/ICU pts; similar history as above; may present as unexplained fever or RUQ mass (rarely jaundice)
- Ddx: calculous cholecystitis, pancreatitis, hepatic abscess
- Evaluation: Same as acute calculous cholecystitis
- Imaging: GB wall thickening, pericholecystic edema, intramural gas, GB distention
- Management
- Supportive care, antibiotics, GB drainage
- IVF, correct electrolyte abnormalities, NPO
- Broad spectrum antibiotic coverage
- Place CT-guided procedure consult for cholecystostomy placement vs Endoscopic drainage (transpapillary cystic duct stent via ERCP or cholecystoduodenostomy by EUS)
- Consult EGS if necrosis, perforation, or emphysematous changes present
Choledocholithiasis¶
- Obstruction of biliary outflow by CBD stone without inflammation (no fever)
- Impacted cystic duct stone (cholecystitis) with compression of the CBD (Mirizzi syndrome)
- Presentation: RUQ pain (can be painless), N/V and jaundice
- Evaluation:
- CMP and D-bili (Bili/ALP/ GGT ↑↑↑, AST/ALT mild ↑), CBC (Leukocytosis suggests cholangitis), Lipase
- Imaging: RUQ U/S: dilated CBD (ULN is 6mm) MRCP/EUS vs ERCP (see
below)
- MRCP preferred given non-invasive but has lower sensitivity for smaller stones (consider EUS if still have suspicion despite negative MRCP or if patient contraindication to/intolerance of MRI)
- Management:
- NPO & IVF, pain control PRN
- Stratify risk to determine whether to pursue MRCP (noninvasive, diagnostic) vs ERCP
- If any one of the following, patient is HIGH risk consult GI for ERCP + EGS to consider cholecystectomy
- CBD stone on imaging
- Acute cholangitis
- Tbili > 4 AND dilated CBD (>6mm with GB, > 8mm without GB)
- If any one of the following, patient is INTERMEDIATE risk consider MRCP (or EUS or cholecystectomy with intraoperative cholangiogram)
- Abnormal liver enzymes
- Age > 55
- Dilated CBD on U/S with Tbili < 4
- If CBD stone seen on MRCP or EUS ERCP,
- If no CBD stone but patient has GB sludge or cholelithiasis EGS consult for cholecystectomy + intraoperative cholangiogram
Acute Cholangitis¶
- Bacterial infection of biliary tract 2/2 obstruction (typically stones) or prior instrumentation (ERCP)
- Pts with malignant obstruction typically do not develop cholangitis
- Presentation: Charcot triad (RUQ pain, fever, jaundice); Reynolds’ Pentad (AMS, Hypotension)
- Evaluation
- CBC, CMP (D bili, ALP ↑↑↑) Blood Cultures, Lipase, Lactate
- CRP, AST/ALT can be ↑↑ as well
- Imaging: RUQ U/S: dilated CBD (ULN is 6mm), no need for MRCP/EUS
- Consider MRCP overnight if ERCP is not being done emergently
- Management
- NPO, IVF
- Consult GI for urgent/emergent ERCP (generally within 24 hr)
- If ERCP not feasible or fails to establish biliary drainage, can consider EUS-guided biliary drainage, percutaneous transhepatic cholangiography, or surgical decompression
- Antibiotics for Biliary Disease (IDSA Guidelines):
- Mild to moderate acute cholecystitis (stable):
- Ceftriaxone 2g daily, Cefazolin 1-2g q8H
- Cholangitis or Severe acute cholecystitis (unstable or
immunocompromised):
- Zosyn 3.375g q8H, Meropenem 1g q8H or Cipro 500 q12H and Flagyl 500 q8H
- Healthcare-associated Biliary infections: consider Vancomycin (order w/ PK consult)
Clostridioides Difficile Infections¶
Anton de Witte
Background¶
- Clostridioides difficile is the causative bacteria for antibiotic-associated colitis
- Always consider C. diff in a hospitalized patient with unexplained leukocytosis
- Microbiology: Anaerobic gram-positive, spore-forming, toxin-producing bacillus
- Outside colon, exists in spore form – resistant to heat, acid, and antibiotics (why we must wash our hands)
- Spores are transferred from environment to person, once in intestine convert to functional vegetative, toxin-producing forms susceptible to antibiotics
- To be pathogenic, must release toxin (A+B) to cause colitis and diarrhea
- Risk Factors: Antibiotic use (during use or typically up to 1 month after use), age >65, hospitalization, enteral feeding, obesity, stem cell transplant, chemo, IBD, cirrhosis, ± PPI use (no clear causal relationship)
Presentation¶
- Spectrum from asymptomatic carrier to fulminant colitis with toxic megacolon
- Asymptomatic carrier: 20% of hospitalized patients (50% of adults in long term care facilities)
- Non-severe disease: watery diarrhea (>3 unformed stools in 24 hours), lower abdominal pain, nausea, ± fever, leukocytosis (WBC >15,000)
- Severe disease: diarrhea, diffuse abdominal pain, abdominal distention, fever, lactic acidosis, AKI (Cr > 1.5), marked leukocytosis (sometimes >40,000)
- Fulminant disease: Severe criteria + hypotension/shock, ileus (rare), or megacolon (>7cm colon diameter and/or >12cm cecum diameter)
- Recurrent disease (relapse > reinfection): resolution of symptoms on therapy followed by reappearance of symptoms within 2-8 weeks after stopping therapy; (Up to 25% of patients have recurrence)
- If symptoms never resolve, consider refractory C. diff or alternative diagnosis
Evaluation¶
- Stool PCR for toxigenic strains (very sensitive, can detect
asymptomatic carriers w/o toxin production); with reflex EIA (enzyme
immunoassay) for toxins A and B (specificity of 99%)
- PCR (+)/Toxin (-) = carrier
- PCR (+)/Toxin (+) = treat
- PCR (-) = no treatment
- Imaging
- Nonsevere disease: no imaging necessary
- Severe or fulminant disease: CT a/p with oral and IV contrast
- Endoscopy: Typically used when alternative diagnosis is suspected; not warranted for classical symptoms, positive laboratory tests, or clinical response to treatment
Management¶
- Contact precautions until at least 48 hours after diarrhea resolves
- Classify patient disease severity to guide treatment algorithm
- Do not repeat stool testing – 50% remain positive after treatment up to 6 weeks later
Clinical Condition | Treatment |
---|---|
Non-fulminant disease | |
Initial episode (non-severe or severe) | -First line: PO Vancomycin 125mg QID x 10 days OR PO Fidaxomicin 200mg BID x 10 days -Second line: (only for non-severe disease in low-risk patients): PO Metronidazole 500mg TID x 10-14 days |
Recurrent episode | Consult GI First Recurrence: -First line: PO Fidaxomicin 200mg BID x 10 days -Second line: Vancomycin Taper (PO 125mg QID x 14 days PO 125mg BID x 7 days PO 125mg QD x 7 days PO 125mg q72h x 2-8 weeks) -Adjunctive therapy: IV Bezlotoxumab 10mg/kg x1 Second or Further Recurrence: -Same as above -Consider Fecal Microbiota Transplantation (FMT) |
Fulminant disease | |
Fulminant disease | Consult GI and EGS Ileus Absent: -PO Vancomycin 500mg QID + IV Metronidazole 500mg TID Ileus Present -Same as above + consider Vancomycin enemas 500mg q6h Consider colectomy or FMT |
Chronic Pancreatitis¶
AJ De Witte
Definition¶
A syndrome characterized by irreversible chronic progressive pancreatic inflammation, fibrosis, and scarring, resulting in damage to and loss of exocrine (acinar), endocrine (islet cells), and ductal cells
Etiology¶
TIGAR-O mnemonic
- Toxic Metabolic: EtOH, tobacco use, hyperCa (Ca > 12), HLD (fasting TG > 300, nonfasting > 500), CKD 5, medications, toxins
- Idiopathic: early onset (age \< 35), late onset (age > 35)
- Genetic: Autosomal dominant (PRSS1 gene), recessive (CFTR, SPINK1, etc.)
- Autoimmune: IgG4-related (AIP type 1), AIP type 2
- Recurrent, severe acute pancreatitis
- Obstructive: pancreas divisum, ampullary stenosis, main duct pancreatic stones or strictures, widespread calcifications, mass causing duct obstruction
Presentation¶
- Abdominal pain (most common)
- Exocrine insufficiency: diarrhea, steatorrhea, weight loss
- Typically occurs later in disease process
- Endocrine insufficiency: diabetes
- Occasionally asymptomatic
Evaluation¶
- Imaging: CT or MRI (may be negative early in course of disease)
- If CT or MRI negative but suspicion for CP remains high, consider EUS ± biopsy or secretin-enhanced MRCP
- Labs:
- BMP, LFTs, lipid panel, PeTH
- Consider genetic testing, especially in younger patients and/or patients without clear etiology
- Pancreatic function testing diagnoses exocrine insufficiency but
is not necessary for diagnosis of CP
- Gold standard = 72-hour fecal fat (> 7g of fat per 100g stool per day) - rarely done
- More practical = fecal elastase (<100 = diagnostic, 100-200
= indeterminate)
- Must be performed on formed stool, can be false positive If watery specimen
- Do not have to stop pancreatic enzymes to measure
- Lipase and amylase levels can be elevated, but are usually normal due to pancreatic scarring and fibrosis
Management¶
- Tobacco and EtOH cessation
- Pancreatic enzyme replacement therapy if evidence/diagnosis of
exocrine insufficiency
- Usual dose: 50,000 units/meal + 25,000 units with snacks
- Should take with first bite of a meal and consider adding extra enzymes or splitting up dose throughout meal if lasting longer than 15 mins
- If lack of response: try increasing dose, confirm compliance, add PPI, split up dose throughout meal, look for concurrent GI disorders
- Pain: Tylenol + NSAIDs > Opioids (Tramadol), consider SSRI/SNRI/TCA
or gabapentin
- For refractory pain, other options include celiac plexus blockade or total pancreatectomy with islet auto transplant
- Vitamin supplementation + Vit D + Ca
- Consider antioxidants (selenium, ascorbic acid, β-carotene, and methionine, vitamin E) – mixed evidence but some studies have shown improved pain control
- Routine testing for osteoporosis and fat-soluble vitamin deficiencies
Constipation¶
Chelsie Sievers
Background¶
- Definition: presence of lumpy/hard stools, straining, use of digital maneuvers, sensation of incomplete evacuation, frequency \<3 BM per week.
- Common etiologies: opioid-induced, medications (anti-depressants, iron, anticholinergics) hypothyroidism, hypokalemia, pregnancy, IBS, neurogenic (trauma, MS, Parkinson disease, diabetes, autonomic dysregulation).
- Always think about risk of obstruction (prior abdominal surgeries, oncology history or risk for GI/GU malignancies, history of IBD/Crohn’s).
Evaluation¶
- Evaluate etiologies plus lifestyle factors (low fiber intake, low fluid intake, reduced mobility, acute illness)
- Clinical diagnosis, no need for imaging unless concerned for obstruction → KUB/ CT
- BMP + Mg to evaluate electrolytes, consider TSH if chronic
- Rectal exam to exclude rectal mass or fecal impaction (constipation + diarrhea doesn’t exclude impaction/obstruction. Overflow around mass = encoparesis)
Management¶
- Stop or minimize offending medications if possible
- Optimize lifestyle factors: out of bed, walking hallways, increase fluid intake, + cup of coffee if appropriate.
- Escalating pathway: ensure meds are scheduled not PRN
- MiraLAX (PEG) 17g BID (can give TID) + Senna nightly (can > increase to BID and/or 2 tabs) → Bisacodyl suppository → enema > (tap water or SMOG) → stronger osmotic laxative (lactulose > 20mg once, Mag-citrate, Golytely) → escalate lactulose dosing > 20 – 30 mg q2hrs
- Other considerations:
- Avoid Fleet enemas (sodium-phosphate) in CKD and geriatric > populations
- “The hand that writes for opioids also writes a bowel regimen”
- Generally, start with scheduled MiraLAX (PEG) 17g daily + senna nightly
- If severe and unrelieved by escalating therapies, can try methylnaltrexone
- Lactulose can cause severe bloating and cramping
- In patients unable to take PO: place DHT to deliver meds or rectal lactulose (important for patients with cirrhosis with AMS/HE).
- In patients with CF (at risk for distal intestinal obstruction syndrome): ensure have pancreatic enzymes ordered, managed more like constipation than true obstruction: PO/ NGT MiraLAX QID or Golytely.
- Acute colonic pseudo-obstruction (Ogilvie's syndrome): >12cm cecal diameter = severe dilation, risk of perforation. Treated with neostigmine, 2mg IV over 3 to 5 minutes. Monitor for bradycardia, hypotension, and dysrhythmias (relative contraindications: recent MI, asthma, PUD, epilepsy). Decompression with colonoscopy used in some cases.
- Consider pelvic floor dysfunction, pelvic floor PT may be helpful
Laxatives | ||
---|---|---|
Mechanism | Examples | Effects |
Bulking-agent | Psyllium seed (Metamucil), methylcellulose (Citrucel) | Absorb water and increase fecal bulk |
Osmotic Laxatives | Polyethylene glycol (PEG = MiraLAX and Golytely), lactulose, mag-citrate | Hyperosmotic substances, pull fluid into GI tract |
Stimulant Laxative | Senna, Bisacodyl (Dulcolax) | Stimulates peristalsis |
Stool Softener | Docusate (Colace) | Generally ineffective |
Opioid antagonist | Methylnaltrexone (Reslistor) | Peripheral acting opioid antagonist, inhibits opioid-induced decreased gastrointestinal motility |
cGMP Agonist | Linaclotide (Linzess), Plecanatide (Trulance) | Stimulates intestinal secretion of Cl-/HCO3- |
Prostaglandin derivative | Lubiprostone (Amitiza) | Increases intestinal chloride-rich fluid secretion |
Diarrhea¶
Charles Oertli
Background¶
-
3 BM/day OR abnormally loose stool
- Acute (<2 weeks), persistent (2-4 weeks), or chronic (>4 weeks)
- 95% of acute diarrhea is self-limited & no additional treatment needed
- Most cases of acute diarrhea are due to infections
- Non-infectious etiologies become more common with increasing duration
- Voluminous watery diarrhea more likely disorder of small bowel
- Small volume frequent diarrhea more likely disorder of colon
- Nocturnal diarrhea suggests an inflammatory or secretory etiology
Acute Diarrhea¶
Etiology¶
- Watery diarrhea: viral gastroenteritis (norovirus, rotavirus, enteric adenovirus), C. diff, C. perfringens, S. Aureus, Bacillus cereus, enterotoxigenic E. coli, Cryptosporidium, Listeria, Cyclospora, vibrio cholerae, (Giardia is typically more chronic), Tropheryma whipplei, COVID
- Inflammatory diarrhea: Salmonella, Campylobacter, Shigella, EHEC, Yersinia, E histolytica, invasive viruses (CMV, HSV), Non-cholera vibrio. Look for red flag symptoms (see below).
- Medications, specifically antibiotics
Presentation¶
- Evaluate for red flags (BATS are Vulnerable vampires)
- Bloody stools,
- Antibiotics/Recent hospitalization
- Any antibiotic can cause C. diff; the longer the treatment, the more likely
- Most common to cause C. diff: Clindamycin >> Penicillins/Cephalosporins/Fluoroquinolones
- Too many stools: >6 unformed stools/day
- Sepsis (Fever) or Severe abdominal pain
- Vulnerable (Age >70 yr, immunocompromised, IVDU, IBD, pregnant, travel)
Evaluation¶
- All patients: CBC w/ diff and BMP to eval for leukocytosis (C.diff), AKI, electrolyte abnormalities, thrombocytopenia/anemia (HUS), eosinophilia (parasites)
- If red flag symptoms or diarrhea > 7d: ESR/CRP, C.diff, GIPP
- If immunocompromised: consider CMV, MAC, microsporidia
- If abdominal pain: consider CT A/P with IV contrast
- If concern for IBD or hx of IBD: CT Enterography with PO and IV contrast
- Blood Cultures if febrile/septic
Management¶
- All patients: supportive care with PO or IVF, electrolyte repletion
- If C.diff negative or treatment for C.diff started, ok for
symptomatic treatment with Loperamide
- Start with Loperamide 4mg x1 then transition to 2mg QID (AC+HS) (maximum 16mg/day)
- If fever or inflammatory symptoms and C.diff not back, ok for Bismuth subsalicylate (Pepto-Bismol) 30mL or 2 tablets q30min x8
- Indications for antibiotics:
- GIPP negative for Shigella, 0157:H7 (can precipitate HUS) and salmonella (can prolong carrier state)
- Empiric antibiotic therapy ONLY if toxic appearance or high concern for progressive illness/decompensation
- Ciprofloxacin 500 mg BID or levofloxacin 500 mg daily x 3-5 days
- Azithromycin 500 mg daily x 3 days
- Ampicillin + gentamicin used for pregnant women to cover for Listeria
- C. diff positive (see section below)
Approach to Chronic Diarrhea¶
Causes of Watery Diarrhea | ||
---|---|---|
Secretory | Motility | Osmotic |
Microscopic colitis Bile acid malabsorption Carcinoid Crohn’s disease Gastrinoma VIPoma Mastocytosis Addison’s disease |
Hyperthyroidism Diabetes Amyloidosis Systemic scleroderma |
Lactose intolerance Bile salt diarrhea Sugar alcohols: sorbitol, mannitol, xylitol |
Meds: antibiotics, caffeine, colchicine, NSAIDs, antineoplastics, antiarrhythmics (digoxin), metformin, carbamazepine | Meds: macrolides, metoclopramide, bisacodyl, senna, pyridostigmine | Meds: citrates, lactulose, magnesium-containing antacids, mycophenolate, antibiotics, propranolol, hydralazine, procainamide |
Functional: IBS |
Causes of Fatty Diarrhea (Steatorrhea) | |
---|---|
Malabsorption | Inflammatory |
Celiac disease Gastric bypass Short bowel syndrome Tropical Sprue Whipple disease Small intestinal bacterial overgrowth (SIBO) Post-infectious malabsorptive diarrhea Maldigestion Pancreatic insufficiency Hepatobiliary disorders |
Diverticulitis Ischemic colitis Neoplasia Radiation colitis Arsenic poisoning Microscopic colitis Invasive infections: bacterial (tuberculosis, yersinosis), viral (CMV, HSV), Parasites (amebiasis, strongyloidiasis) Inflammatory bowel disease |
Evaluation¶
- Labs: CBC w/ diff, CMP, ESR/CRP, TSH, celiac serologies if high suspicion (anti-TTG)
- Spot fecal elastase Steatorrhea (greasy, malodorous stools that float)
- Colonoscopy indicated if alarm symptoms are present ( >45 yrs and hasn’t had one, or \<45 yrs and concern for IBD, CMV, ischemic colitis or microscopic colitis)
- If concern for IBS: Rome IV criteria (see section on “IBS” below)
Management¶
- IBS: trial elimination diet/low FODMAP, antidiarrheals
- Pancreatic insufficiency: enzyme replacement (Creon), consult nutrition for assistance
- Celiac: eliminate gluten, will need outpatient nutrition follow-up
- Bile acid malabsorption: can try cholestyramine (can affect absorption of other meds)
Esophageal Disorders¶
Caroline Barrett
Dysphagias¶
- Oropharyngeal dysphagia = difficulty initiating a swallow
- Associated with coughing, choking, nasopharyngeal regurgitation, and aspiration
- Causes: Structural (Zenker’s diverticula, malignancy, goiter, stricture, radiation injury, infection), Neuromuscular (stroke, Parkinson disease, dementia, ALS, MS)
- Esophageal dysphagia: Difficulty swallowing several seconds after initiation; associated w/sensation of food getting stuck in esophagus
- Dysphagia to solids = mechanical obstruction
- Foreign body: Inability to swallow solids and/or liquids,
including oral secretions
- Most common foreign body = food in esophagus
- Progressive: esophageal stricture, peptic stricture, esophageal, cancer
- Intermittent: esophageal ring/web, eosinophilic esophagitis (particularly in young pts)
- Foreign body: Inability to swallow solids and/or liquids,
including oral secretions
- Dysphagia to solids and liquids = motility disorder
- Causes: achalasia, scleroderma, distal esophageal spasm (DES), hypercontractile (nutcracker) esophagus
Evaluation¶
- If oropharyngeal dysphagia: videofluoroscopic modified barium swallow and fiberoptic endoscopic evaluation of swallowing (FEES)
- When to order barium esophogram:
- Pre-endoscopy if clinical history suspicious for proximal esophageal
lesion (i.e. Zenker’s) or known complex stricture (post-caustic
injury or radiation)
- Don’t order if a food impaction is suspected or if imminent endoscopy
- Post-endoscopy if mechanical obstruction is still suspected (EGD can miss lower esophageal rings or extrinsic esophageal compression)
- Pre-endoscopy if clinical history suspicious for proximal esophageal
lesion (i.e. Zenker’s) or known complex stricture (post-caustic
injury or radiation)
- EGD if concerns for mechanical obstruction
- Manometry for motility disorders
Management¶
- Food impaction: IV glucagon to relax lower esophageal sphincter to allow food passage
- Otherwise, requires urgent upper endoscopy for removal
- Additional management is specific to the final diagnosis
Odynophagia¶
- Pain with swallowing
- Associated with esophagitis
PIECE mnemonic for esophagitis:
- Pill-induced: NSAIDs, ART, KCl, doxycycline, bisphosphonates
- Discontinue culprit med or substitute with liquid formulation; prevent by taking culprit meds w/ 8oz water and sit upright for 30 mins after
- Infectious: usually in immunosuppressed pts
- Candida Esophagitis: most common in HIV or heme malignancies, pts on
antibiotics and steroid use
- Can exist without OP thrush
- Diagnosis: white mucosal plaque-like lesions on EGD biopsy and culture
- HSV Esophagitis. Occurs most commonly in solid organ, BMT transplant
recipients, and immunosuppressed patients
- Diagnosis: well-circumscribed ulcers on EGD, biopsy or brushings of ulcer edge
- Rx: acyclovir 400mg PO five times daily for 14-21 days (immunocompromised) or acyclovir 5mg/kg IV q8h for 7-14 days if unable to tolerate PO; 200mg PO five times daily or 400mg PO three times daily for 7-10 days (immunocompetent)
- CMV Esophagitis: suspect in HIV pts w/ CD4\<50
- Diagnosis: linear/longitudinal ulcers on EGD, biopsy
- Rx: ganciclovir 5mg/kg IV q12h for 21-42 days; change to PO once pt able to tolerate; If contraindication to ganciclovir (leukopenia, thrombocytopenia) can use Foscarnet. PO valganciclovir can be used in patients who can tolerate and absorb oral medications. Treatment duration is 3-6 weeks based on expert opinion and response to disease
- Eosinophilic Esophagitis (see below)
- Caustic: alkali-induced injury, acid-induced injury, acute period (several days) following esophageal radiofrequency ablation for Barrett’s.
- GERD (see below)
GERD¶
Background
- Condition that develops when reflux of stomach contents causes symptoms and/or complications
- Classified base on appearance of esophageal mucosa on EGD
- Erosive esophagitis: endoscopically visible breaks in distal esophageal mucosa + GERD
- Nonerosive reflux disease: presence of symptoms of GERD without esophageal mucosal injury
Presentation
- Esophageal symptoms: heartburn, regurgitation, chest pain, dysphagia, globus sensation, odynophagia
- Extra-esophageal symptoms: chronic cough, hoarseness
- Complications: Esophageal stricture, Barrett’s esophagus, esophageal adenocarcinoma
Evaluation
- Dx can often be made clinically in pts with classic heartburn and/or regurgitation
- If dx uncertain, can perform ambulatory pH monitoring + impedance
- EGD indicated for the following:
- Presence of alarm features (dysphagia, persistent vomiting, GI cancer in 1º relative, odynophagia, GI bleeding, weight loss, iron deficiency anemia, ≥age > 60 y/o with new-onset GERD symptoms)
- Risk factors for Barrett’s esophagus (duration of GERD at least 5-10 years [must be present], >50 yo, male, white, hiatal hernia, obesity, nocturnal reflux, tobacco use, first-degree relative w/ Barrett’s and/or adenocarcinoma)
- Abnormal UGI tract imaging (i.e. luminal abnormalities).
- Continued symptoms despite adequate PPI therapy
Management
- Lifestyle and dietary modifications in all pts (weight loss; elevate HOB; avoid precipitants such as fatty foods, caffeine, alcohol, spicy foods, large meals, late night meals)
- Mild/intermittent symptoms (\<2 episodes/wk) and no erosive esophagitis step-up therapy q4-8 wks until symptoms are controlled, then continue for at least 8 wks:
- Low-dose H2RA prn standard dose H2RA BID (min 2 wks) discontinue H2RA and start daily low dose PPI standard dose PPI
- Frequent symptoms (>2 episodes/wk, and/or severe symptoms that impair QOL) step-down therapy in order to optimize symptom relief
- Standard-dose PPI daily (8 wks) low-dose PPI daily H2RA (if
mild/intermittent symptoms) stop if asymptomatic
- PPIs should be prescribed at lowest dose and for shortest duration appropriate
- Instruct patients on optimal PPI use: most effective at gastric acid suppression when taken 30-60 minutes before a meal
- Taper if taking for >6 months and plan to discontinue
- Medications:
- Low dose H2RA: famotidine 10mg BID
- Standard dose H2RA: famotidine 20mg BID
- Low dose PPI: omeprazole 10 mg daily
- Standard dose PPI: omeprazole 20 mg daily
Additional Information
- Erosive esophagitis and Barrett’s esophagus:
- Require maintenance acid suppression with a standard dose PPI daily given likelihood of recurrent symptoms and complications if stopped
- Recurrent Symptoms (⅔ of pts with nonerosive reflux disease
relapse when acid suppression is discontinued):
- If ≥3 months after discontinuing repeat 8-week course
- If <3 months of discontinuing, EGD (if not already performed) to rule out other etiologies or complications
Eosinophilic Esophagitis¶
Background
- Pt usually with a history of asthma/allergies/eczema
- Dysphagia (most commonly to solid foods), food impaction, central chest pain, GERD/refractory heartburn, upper abdominal pain
Evaluation
- Diagnostic criteria
- Symptoms related to esophageal dysfunction
- EGD with >15 eos/hpf on biopsy and exclusion of other causes
- 50-60% pts will have elevated serum IgE lvl; peripheral eosinophilia can be seen but is generally mild.
Management
- Standard dose PPI for 8 weeks ± elimination diet if still symptomatic after 4 weeks, increase PPI to BID if responsive, continue PPI at lowest dose possible for symptom control
- Alternative treatment is swallowed budesonide or fluticasone
- Intermittent dilation of strictures to relieve dysphagia, but no effect on underlying inflammation
- Should undergo evaluation by allergist, given strong association with allergies
Gastroparesis¶
Hashim Hayat
Background¶
- Syndrome of objectively delayed gastric emptying in absence of mechanical obstruction
- Etiology: Diabetes (most common), post-surgical (gastric or bariatric surgery), thyroid dysfunction, autoimmune or neurologic disorders, medication-induced (GLP-1 agonists, narcotics, anticholinergic agents
Presentation¶
- Nausea, vomiting (may contain food eaten several hours prior), abdominal pain (dull, crampy; rarely a predominant symptom), early satiety, postprandial fullness, bloating, weight loss in severe cases
Evaluation¶
- Exclude mechanical obstruction and mucosal disease with CTE and EGD
- Scintigraphic gastric emptying study = gold standard for diagnosis (measures gastric retention of solids at 4h)
- Stop medications that may affect gastric emptying 48 hrs prior to testing
- Must have blood sugar \< 275 (Hyperglycemia delays gastric emptying)
Management¶
- Support with IVF and electrolytes – PO intake preferred
- Glycemic control in diabetics
- Stop offending medications
- Nutrition consult for teaching on frequent small volume meals that are low in fat and soluble fiber
- If continued symptoms after above, try prokinetics and antiemetics
- Prokinetics
- Liquid formulations preferred for better absorption
- Give 15min before meals and at bedtime.
- First line is Reglan. If no response, try Domperidone and subsequently erythromycin (not good for long term, pts develop tachyphylaxis)
- Antiemetics: helps symptoms but do not improve gastric emptying
- In severe cases patients may require enteral feeding (post pyloric preferred) or venting g-tube
- Emerging endoscopic treatment options: G-POEM (gastric peroral endoscopic myotomy)
GI Bleeding¶
Matthew Meyers
Background¶
- Intraluminal blood loss anywhere from the nasopharynx/oral cavity to the anus
- Don’t forget epistaxis or oropharyngeal bleeding as possible source of melena
- IV PPI prior to endoscopy may ↓ need for endoscopic therapy but does not impact transfusion requirement, rebleeding risk, need for surgical intervention, or mortality
- Classification: relative location to the Ligament of Treitz (LoT)
- Upper = proximal to LoT
- PUD, gastritis (alcohol, stress, NSAIDs, ASA), esophagitis, variceal bleed, Mallory-Weiss tear, AVM, Dieulafoy’s lesion, aorto-enteric fistula, gastric antral vascular ectasias, malignancy
- Lower = distal to LoT
- Diverticular bleed, ischemic/infectious/IBD/radiation colitis, malignancy, angiodysplasia, anorectal (hemorrhoids, anal fissure), Meckel’s diverticulum, post-polypectomy bleed
Presentation¶
- Hematemesis (very specific for upper GI bleed), hematochezia (usually lower although brisk upper possible), melena (usually upper), coffee-ground emesis, epigastric/abdominal pain, acute or chronic, hx of GI bleed and prior endoscopies, NSAID use, alcohol use, anticoagulant use, hx of cirrhosis
- Exam: VITALS – assess stability to determine resuscitation needs, MICU vs. floor; orthostatic vs, rectal exam every time (smear stool on white tissue paper to look for melena), look for signs of cirrhosis (jaundice, palmar erythema, ascites, spider angiomata)
Evaluation¶
- CBC, PT/INR, CMP, Lactic Acid, Blood Gas
- EGD: usually best
- Difficulty localizing GIB: pill-capsule, balloon enteroscopy Meckel’s scan, tagged RBC scan
- Massive lower GI bleeds will require arteriography
Management¶
- Secure airway (intubation) if comatose, extremely combative, or massive hematemesis
- At least 2 large bore IV’s (> 18 gauge) – ask nurses directly to ensure these are placed
- Maintain active type and screen
- Bolus IVF to maintain MAP >65H/H monitoring q6-q12 hours; transfusions as indicated
- IV PPI (pantoprazole) 40 mg BID if thought to be upper/possible ulcer
- If cirrhotic, Ceftriaxone 1g daily for empiric SBP prophylaxis
- If possibility of variceal bleed: Octreotide IV 50 mcg x1 then 50 mcg/hr drip x 3-5 days
- NPO if unstable vs. clear liquids (no reds or purples) until morning for EGD
- Never give prep to a patient for colonoscopy (GoLytely) without discussing with GI fellow
- Consult gastroenterology to facilitate endoscopy
- If endoscopy is unable to stop bleeding IR is next who can embolize
- If embolization fails EGS for source removal
GI Manifestations of COVID¶
Taylor Riggs
Background¶
- GI manifestations are reported up to 60% of patients with COVID
- GI symptoms may be the only symptom or precede other symptoms
- GI manifestations are felt to be due to expression of ACE2 receptor throughout the GI tract
Presentation¶
- Diarrhea – more common in severe disease
- ~20% have diarrhea as first symptom of COVID; on average, lasts about 5 days
- Nausea and vomiting – associated with more severe disease
- Mesenteric ischemia – likely due to intestinal microvascular injury
- Elevated liver enzymes – likely due to inflammatory response and direct virus-related toxicity
- Hepatocellular pattern of injury most common; elevated bilirubin seen in severe disease
- Usually self-limited
- Pancreatitis has been reported in several cases, but no causal link has been established
Management¶
- Largely supportive care
- Monitor LFTs, coags, consider checking lipase if abdominal pain
- If LFTs not improving after several days or underlying chronic liver disease, obtain RUQ U/S, consider hepatitis serologies
- Consider medications/antiviral medications as culprit and discontinue as indicated
Irritable Bowel Syndrome¶
Hashim Hayat
Background¶
- Diagnose by the Rome IV criteria, no longer a diagnosis of exclusion
- Recurrent abdominal pain on average at least 1 day/week in the last
3 months with an onset at least 6 months prior, associated
with two or more of the following criteria
- Pain related to defecation
- Change in frequency of stool
- Change in form (appearance) of stool
- Patient has none of the following warning signs: >50yrs, evidence of GIB, nocturnal pain or BMs, unintentional weight loss, family hx of colorectal cancer or IBD, palpable abdominal mass or LAD, IDA, +FOBT
- Classified based on predominant bowel habits
- Diarrhea: >25% BMs with Bristol stool types 6 or 7
- Constipation: >25% BMs with Bristol stool types 1 or 2
- Mixed: both of above
Evaluation¶
- Thorough H&P for alarm symptoms as above
- Consider limited testing with CBC, CMP, CRP, celiac serology, fecal calprotectin
Management¶
- Treatment involves lifestyle and dietary modifications, psychosocial treatment, and pharmacologic treatment
- Pain:
- Peppermint oil (smooth muscle relaxant) – IBGuard, Iberogast
- Antispasmodics: Hyosciamine acts faster than Dicyclomine
- TCAs: Amitriptyline or nortriptyline (causes less constipation so better in IBS-C)
- Bloating:
- Low FODMAP diet
- Rifaximin as empiric treatment for SIBO
- No evidence for probiotics (can potentially worsen bloating 2/2 SIBO)
- Bowel regulation:
- IBS-D: Start with Loperamide (up to 16g daily), consider Lomotil if refractory
- IBS-C: Miralax, fiber supplement (Ispaghula husk orange), Linzess (first line but can be expensive), Trulance, or Amitiza
- Other
- Psychotherapy, CBT
- SSRIs, SNRIs for concomitant mood disorders
- Gabapentin, lyrica
Inflammatory Bowel Disease¶
Francesca Raffa
Background¶
- Ulcerative colitis (UC): colon only (can have backwash ileitis); contiguous lesions; mucosal inflammation
- Crohn’s disease (CD): any part of the GI tract; “skip lesions”; transmural inflammation
- Important historical considerations to include in your documentation
and presentation:
- Location of disease (CD: LB/SB, LB only, SB only; UC: proctitis, left-sided or pancolitis)
- Complications: Fistulizing, strictures, perianal, prior surgeries, current IBD treatment
- Include last endoscopies and imaging findings; current and prior IBD treatment and reason for transition (SEs, failure), primary IBD provider
Presentation¶
- UC: frequent diarrhea (often bloody), tenesmus, urgency, abdominal
pain; may have fever, malaise, and weight loss
- Complications: severe bleeding/anemia, fulminant colitis, toxic megacolon
- CD: abdominal pain, nausea/vomiting, fever, malaise, weight loss;
May also have diarrhea (± bloody depending on CD location)
- Complications: fistulas (entero-enteric, entero-vesicular, entero-cutaneous, rectovaginal, perianal, retroperitoneal), abscesses, strictures, obstruction
- Extra-intestinal (EI): arthritis, sacro-iliitis, uveitis, episcleritis, aphthous ulcers, erythema nodosum, pyoderma gangrenosum, PSC (esp. UC), nephrolithiasis, thromboembolism
Evaluation¶
- CBC w/diff, CMP, CRP, ESR, ± blood cultures
- If diarrhea: GI Pathogen panel and C. diff
- If anemic: obtain iron studies and type & screen
- If weight loss or concern for malnutrition: albumin, pre-albumin, Vitamin D, B12, folate
- Imaging:
- CT Enterography (oral contrast) preferred in CD, for luminal/extra-luminal complications
- How to order CTE: “CT abdomen pelvis enterography”, order barium (Volumen) 0.1% oral suspension x2, 1st dose to be given by nurse 60 min before study, 2nd study to be given 30 min before (nurse should be in contact with CT tech)
Management¶
- Acute Flare
- Pain control: usually a major component of hospital course
- Avoid NSAIDs, oral pain medications are preferred
- If pain is difficult to control, consider Acute Pain Service consult
- Narcotics and Imodium are contraindicated in toxic megacolon
- Antibiotics: appropriately treat infections (intra-abdominal or perianal abscess) with antibiotics (consider prior culture data, often use cipro/flagyl)
- VTE Prophylaxis: All IBD patients, even if having blood in stool (unless requiring transfusion) as they are at much higher risk of VTE
- Nutrition: Nutrition consult for all IBD patients; For severe malnutrition or if prolonged bowel rest is needed, TPN is sometimes initiated
- Anemia: Ferritin \<100 or iron sat \<20 with ferritin \<300, consider iron infusions (if no bacteremia) or transfuse for severe anemia
- Smoking Cessation (esp. with CD): discuss smoking cessation & consult tobacco cessation
- Consult Colorectal Surgery (not EGS): SBO, toxic megacolon, bowel perforation, peritonitis
- Immunosuppression: (Infections must be ruled out and/or treated before starting)
- Steroids:
- Methylprednisolone (Solumedrol); often 20 mg BID for three days
- Transition to oral (40 mg prednisone daily) once clinically improved/tolerating PO; typically prescribe a prolonged taper on discharge (often down by 5 mg every week)
- If severe proctitis: consider rectal steroids (hydrocortisone enema/foam)
- If lack of response to steroids: additional medical therapy
(biologics), bowel rest with TPN, or surgical intervention
- Infliximab (Inflectra) is available at VUMC
- If patient fails to respond to steroids, should consider possibility of CMV colitis (usually evaluated by biopsy on flex sig or colonoscopy)
- Prior to initiating a biologic, all patients must have the following negative studies within the last year: Quantiferon Gold and CXR, Hepatitis B serologies, HIV, urine histoplasma Ag (some providers)
Intestinal Ischemia¶
Michael Koenig
Acute Mesenteric Ischemia¶
- Sudden onset ↓ or absence of blood flow to the small intestines
- Mesenteric Arterial Occlusion:
- Arterial Embolism: Associated with cardiac arrhythmias (atrial fibrillation), valvular disease, endocarditis, ventricular aneurysm, aortic atherosclerosis, and aortic aneurysm
- Arterial thrombosis: Most commonly from atherosclerotic disease; can also be 2/2 abdominal trauma, infection, or dissection
- Venous thrombosis:
- Associated w/ hypercoagulable states, malignancy, prior abdominal surgery, abdominal mass venous compression, intra-abdominal inflammatory processes
- Non occlusive mesenteric ischemia:
- Intestinal hypoperfusion and vasoconstriction; associated with decreased cardiac output, sepsis, vasopressor use
Presentation¶
- Early: Abdominal pain is most common symptom, abdominal distension
- Abdominal tenderness is not prominent early (“pain out of proportion to the exam”)
- Arterial occlusion: Sudden onset, severe periumbilical pain, nausea, and emesis
- Venous thrombosis: More insidious onset abdominal pain, waxing and waning
- Nonocclusive mesenteric ischemia: variable location and severity of abdominal pain; often overshadowed by a precipitating disorder
- Late: As transmural bowel infarction develops, abdomen becomes distended, bowel sounds become absent, and peritoneal signs develop
Evaluation¶
- Type and Screen, Lactic acid, BMP, CBC
- Imaging: KUB: Normal in > 25% of cases
- Ileus w/ distended bowel loops, bowel wall thickening, ± pneumatosis intestinalis
- Free intraperitoneal air immediate abdominal exploration
- CT Angiography: no oral contrast, obscures mesenteric vessels, ↓ bowel wall enhancement
- Focal or segmental bowel wall thickening, intestinal pneumatosis, portal vein gas, porto-mesenteric thrombosis, mesenteric arterial calcification, mesenteric artery occlusion
Management¶
- General: IVFs, NPO, hemodynamic monitoring and support (try to avoid vasoconstricting agents), anticoagulation, broad-spectrum antibiotics, pain control
- If develops peritonitis or evidence of perforation on CT EGS consult for surgery
- Mesenteric arterial embolism: Embolectomy vs. local infusion of thrombolytic agent
- Mesenteric arterial thrombosis: Surgical revascularization vs. thrombolysis with endovascular angioplasty and stenting
- Venous thrombosis: Anticoagulation; possible thrombolysis if persistent symptoms
- Nonocclusive occlusion: Treat underlying cause, stop vasoconstriction meds, consider intra-arterial vasodilator infusion
Chronic Mesenteric Ischemia¶
Background¶
- ↓ blood flow to intestines, typically caused by atherosclerosis of mesenteric vessel
- High-grade mesenteric vascular stenoses in at least two major vessels (celiac, SMA, or IMA) must be established
Presentation¶
- Recurrent dull, crampy, postprandial abdominal pain
- Pts develop food aversion and often have associated weight loss
Evaluation¶
- CTA abdomen/pelvis is preferred (>90% sensitivity and specificity)
- Can also consider duplex U/S and gastric tonometry
Management¶
- Conservative management if asymptomatic: smoking cessation and secondary prevention to limit progression of atherosclerotic disease
- Nutritional evaluation
- Revascularization (open vs. endovascular) is indicated if symptoms are present
- Mesenteric angioplasty and stenting is first-line therapy
- Goal is to prevent future bowel infarction
Ischemic Colitis¶
Background¶
- Sudden, transient reduction in blood flow to colon
- Typically at “watershed” areas, such as the splenic flexure and rectosigmoid junction
- Most often nonocclusive (95% of cases) and affects older adults
- Risk factors: ACS, hemodialysis, shock, aortoiliac instrumentation, cardiopulmonary bypass, extreme exercise (marathon running)
Presentation¶
- Rapid onset, mild cramping abdominal pain, associated with urge to defecate, hematochezia
- Tenderness present (typically over left side)
Evaluation¶
- Lactic acid (nonspecific but elevated), LDH, CPK, CBC (leukocytosis), BMP (metabolic acidosis)
- KUB; if peritonitis or signs of severe ischemia → surgery
- CT A/P with IV contrast (and oral contrast if patient can tolerate)
- Consider CTA A/P if suspicion for vascular occlusion
- Colonoscopy confirms diagnosis.
- Edematous, friable mucosa; erythema; and interspersed pale areas; bluish hemorrhagic nodules representing submucosal bleeding
- Segmental distribution, abrupt transition between injured and non-injured mucosa
Management¶
General: IVFs, bowel rest, antibiotics (Zosyn vs CTX/flagyl)
Ischemic Colitis Management | ||
---|---|---|
Classification | Management | |
Mild | No risk factors (see below) | Supportive care and observation Antibiotics can be stopped if no ulceration |
Moderate | 1-3 risk factors | Same as mild ischemia if no vascular occlusion Systemic anticoagulation +/- vascular intervention if mesenteric occlusion |
Severe | > 3 risk factors, peritoneal signs, pneumatosis, pneumoperitoneum, gangrene or pancolonic ischemia on colonoscopy | Consult EGS for abdominal exploration and segmental resection |
Risk factors: male, SBP <90, HR >100, WBC>15k, Hgb <12, Na <136, BUN >20, LDH >350, isolated right-sided colonic involvement, abdominal pain with rectal bleeding |
Nausea & Vomiting¶
Taylor Riggs
Etiology¶
VOMMIIT mnemonic
-
Vestibular: Labyrinthitis, vestibular neuritis, meniere’s disease, cerebellar stroke
-
Obstruction: adhesions, hernia, volvulus, constipation, gastric outlet obstruction
-
Motility: gastroparesis, GERD, autonomic dysfunction
-
Medications: antibiotics, SSRI, opioids, cannabinoid hyperemesis
-
Infection: gastroenteritis, hepatitis, pyelonephritis, cholecystitis
-
Inflammation: PUD, pancreatitis
-
Toxins: uremia, ketoacidosis, hypercalcemia, chemotherapy
Evaluation¶
-
All patients: CBC (leukocytosis, Hgb), BMP (AG, Ca, lytes, AKI), LFTs, lipase, lactate, UA
-
If risk factors: consider TSH, AM cortisol, troponin, β hCG, UDS
-
EKG to eval for ischemia and baseline QTc
-
Imaging:
- If concern for obstruction (abd distention, decreased BMs) KUB, consider CT A/P
- If concern for biliary pathology (RUQ pain, abnl LFTs) RUQ U/S
- If vestibular/concern for CNS pathology CTH vs MRI brain
Management¶
Address underlying cause and stop medications as appropriate
- Many antiemetics prolong QTc, however in patients without underlying cardiac conduction abnormality, electrolyte abnormality, or organ failure the risk of QTc prolongation leading to significant arrhythmia is low.
- Obtain screening EKG in patients with underlying heart disease, electrolyte abnormalities, organ failure or on other QTc prolonging meds (antiarrhythmics, antipsychotics, antibiotics)
- 4-8 mg of IV Zofran is estimated to prolong QTc by ~6ms
- Try to pick a medication that will address the underlying etiology of nausea
- If patient does not respond to a medication in a certain class, try a medication from a different class (see below)
Anti-Emetics | |||
---|---|---|---|
Med (by class) | Typical Dose | Side Effects | Prolongs QT? |
Serotonin antagonists | |||
Ondansetron (Zofran) | 4-8mg PO/IV q6h | Constipation, headache, arrhythmia, serotonin syndrome | Yes |
Granisetron (Kytril)1 |
1 mg PO BID, 2mg pre-chemo, OR 10mcg/kg IV pre-chemo | ‘’ | Yes |
Dopamine Antagonists | |||
Prochlorperazine (Compazine) | 5-10 mg PO/IV q6h, 25 mg PR q6h | EPS, less sedation than H-blockers (e.g. Phenergan) | Yes |
Haloperidol (Haldol) |
0.5-1 mg PO/IV q6h | EPS, arrhythmia | Yes |
Zyprexa (Olanzapine) | 5 -10mg PO qdaily | EPS, constipation, anticholinergic | Mild ^ |
Dopamine and Serotonin Antagonists | |||
Metoclopramide (Reglan) | 10 mg PO/IV q6h | EPS/dystonia, arrhythmias, drowsiness/dizziness, diarrhea | Yes |
GABA-A Agonist | |||
Lorazepam (Ativan) |
0.5-1mg PO/IV q6h PRN | Sedation, delirium, amnesia, respiratory depression | No |
H1 Antagonists | |||
Promethazine (Phenergan) | 12.5 - 25mg PO /PR /IV q6h (avoid IV use if possible) | Sedation, EPS (D2 antagonist also), arrhythmias, blurry vision | Yes |
Diphenhydramine (Benadryl) | 25-50mg PO/IV q6h | Sedation, delirium, urinary retention, ileus | Yes |
Meclizine (Antivert) |
12.5-25mg PO q6h | Sedation, dizziness, falls, blurry vision | Yes |
Anticholinergics | |||
Scopolamine | 1 mg patch q3day | Dry mouth, blurry vision, drowsiness | No |
Glucocorticoids | |||
Dexamethasone | 4-8mg PO/IV prior to chemo or XRT, typically use with other agents | Hyperglycemia, fluid retention, delirium | No |
NK1 Antagonists | |||
Aprepitant | Given prior to/with chemo | Fatigue, neutropenia | No |
CBD Agonists | |||
Dronabinol | 2.5-5mg BID | Dizziness, increased appetite, Tachycardia, hypotension | No |
Peptic Ulcer Disease¶
Michelle Izmaylov
Background¶
- Ulceration in the GI tract wall extending through the muscularis mucosa into deeper layers
- Most common in the stomach and proximal duodenum
- Less common in the lower esophagus, the distal duodenum, or the
jejunum
- ↑ suspicion for unopposed hypersecretory states, like Zollinger-Ellison syndrome
- Causes: NSAID use and Helicobacter pylori >> steroids, malignancy, and acute stress
Presentation¶
- Episodic gnawing or burning epigastric pain, 2 - 5 hr after meals, nausea, vomiting, heartburn, bloating, postprandial belching, and loss of appetite
- Nocturnal pain: acid is secreted in absence of a food buffer
- Classic teaching for ulcers: Gastric (pain worse w/eating); Duodenal (pain better w/eating)
- May be asymptomatic until complications such as hemorrhage or perforation
- Alarm features: unintentional weight loss, persistent vomiting, melena, progressive dysphagia, early satiety, recurrent vomiting, palpable abdominal mass, lymphadenopathy, family history of upper gastrointestinal cancer, and iron deficiency anemia
Evaluation¶
- CBC and H Pylori testing if no strong NSAID use history
- Urea breath or stool antigen (pt needs to stop PPI for 1-2 weeks, to avoid false - for both)
- EGD: if alarm features or patient is older than 55
Management¶
- General: treat underlying cause (i.e. H. pylori, stop NSAIDs, etc), encourage smoking cessation, and limit alcohol intake to 1 drink/day.
- If complicated peptic ulcer (i.e. bleeding, perforation, or gastric
outlet obstruction):
- EGD to determine etiology and for possible treatment
- IV PPI (if bleeding IV PPI for 72 hrs after endoscopic treatment oral PPI)
- If uncomplicated peptic ulcer (not caused by H. pylori):
- Antisecretory therapy with oral PPI (i.e. omeprazole 20 to 40 mg
daily):
- If caused by NSAIDs: Duration: \<1 cm ulcer 4-6 wks; ≥1 cm ulcer 6-8 wks
- If not caused by NSAIDs, Duration:
- Duodenal ulcer: 4 weeks
- Gastric ulcer: 8 weeks
- Antisecretory therapy with oral PPI (i.e. omeprazole 20 to 40 mg
daily):
- If ulcer caused by H. pylori:
- Treat with PPI BID for 14 days with an appropriate combination antibiotic regimen.
- Confirm H. pylori eradication (via stool antigen test, urease breath test, or EGD >4 weeks after completion of therapy). If not eradicated, retreat
Additional Information¶
- Continue maintenance PPI therapy (omeprazole 20 mg daily) for the
following:
- Peptic ulcer >2 cm and age >50 or multiple co-morbidities
- Frequently recurrent peptic ulcers (>2 in one year)
- H. pylori-negative, NSAID-negative ulcer disease
- Failure to eradicate H. pylori (including salvage therapy)
- Condition requiring long term aspirin/NSAID use
- Persistent ulcer on repeat EGD (if performed)
- Indications for repeat EGD (8-12 weeks):
- Persistent/recurrent symptoms despite medical therapy
- Complicated ulcer (bleeding), with evidence of ongoing bleeding
- Giant gastric ulcer (>2 cm) or features of malignancy at index endoscopy
- Gastric ulcer that was not biopsied or inadequately sampled on initial EGD
- Gastric ulcer in pt w/risk factors for gastric cancer (>50 yo, H. pylori, immigrant from high prevalence area [Japan, Korea, Taiwan, Costa Rica], FHx, presence of gastric atrophy, adenoma, dysplasia, intestinal metaplasia)
Small Bowel Obstruction (SBO)¶
Alex Wiles
Background¶
- Risk Factors: prior abdominal surgeries (adhesions), malignancy, hernia, intestinal inflammation (IBD)/stricture, radiation, abscess, foreign bodies
- Indicators for bowel ischemia: fever, leukocytosis, tachycardia, peritonitis
- Ddx: early appendicitis, large bowel obstruction, Ogilvie’s, DKA, Pancreatitis, IBD, Gastric outlet obstruction
Presentation¶
- Nausea, emesis, intermittent colic, bloating, constipation
- Obstipation if completely obstructed, loss of flatulence
- Exam: classically with “tinkling” bowel sounds, tympanic abdomen, distended abdomen
Evaluation¶
- CBC, BMP, lipase, hepatic function panel, lactate (sensitive, not specific for ischemia)
- Start with KUB to rule out perforation but typically will require CT (x-ray only ~80% sensitive)
- CT abdomen/pelvis with IV contrast is optimal study if adequate
renal function
- No oral contrast (American College of Radiology (ACR) Appropriateness Criteria) as it will not aid diagnosis and can lead to aspiration; IV helps evaluate ischemia
- Key word: transition point
- Non-specific signs of bowel inflammation: bowel wall thickening, submucosal edema
Management¶
- Consult EGS: if any concern for SBO, evaluate need for urgent surgery
- Surgical indications complete obstruction, CT with ischemia, perforation
- Gastric decompression: place NGT (prevent aspiration)
- NPO until obstruction relieved and NGT removed
- Fluids: two large bore IVs (nursing communication); LR bolus + maintenance while NPO
- If no resolution of partial obstruction at 48 hours:
- Fluoroscopy Upper GI small bowel ft (follow through)
- In comments, write “Gastrografin contrast” (water-soluble contrast) which osmotically reduces bowel wall edema and aids peristalsis
- If gastrografin reaches the colon within 24 hours, it predicts clinical resolution of SBO without surgery
- Note: this can also be therapeutic for pSBO and get bowels moving
Ended: Gastroenterology
Geriatrics ↵
Dementia¶
Thomas Horton
Background¶
- Alzheimer’s Disease (AD): short-term memory deficits prominent
- Vascular Dementia: “Stepwise decline” in memory and functional status
- Lewy Body Dementia: hallucinations, memory difficulties with atypical Parkinsonism early
- Frontotemporal Dementia: behavioral (aggressive or disinhibited), language (primary progressive aphasias) or memory (Alzheimer’s/FTD overlap) variants
- Posterior Cortical Atrophy: visual difficulties and ocular apraxia preceding memory problems
- Creutzfeldt-Jakob Disease (CJD): manifests with subacute cognitive decline, seizures, vision loss, personality changes. Can develop startle myoclonus
- Corticobasal degeneration: focal neurologic changes with parkinsonism
- Neurosyphilis: rare, but treatable, present with a range of cognitive changes. Develop meningovascular encephalitis. Pts can develop an arteritis, headache, and hydrocephalus.
- Normal Pressure Hydrocephalus (NPH): “wet, wacky and wobbly” meaning incontinence, gait apraxia and cognitive changes (usually frontal symptoms)
- Autoimmune Dementias: includes limbic encephalitis (like NMDA) where there are memory and personality changes, autonomic changes, hallucinations, and seizures
Normal Aging | Mild Cognitive Impairment | Alzheimer’s Dementia (DSM V Diagnostic Crit.) |
---|---|---|
Mild decline in working memory More effort/time needed to recall new info New learning slowed but well compensated by lists, calendars, etc. + No impairment in social & occupation functioning |
Subjective complaint of cognitive decline in at least one domain + Cognitive decline is noticeable and measurable + No impairment in social & occupation functioning |
Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains + Causes significant impairment in social & occupation functioning + Other medical & psychiatric conditions, including delirium, have been excluded + Insidious onset and gradual progression of impairment in at least two cognitive domains |
Cognitive domains: learning/memory, language, executive function, complex attention, perceptual motor, social cognition |
Alzheimer’s Disease | Vascular Dementia | Lewy Body Dementia | Frontotemporal Dementia | |
---|---|---|---|---|
Onset | Gradual | Sudden or stepwise | Gradual | Gradual (age < 60) |
Cognitive Domains & Symptoms | Memory, language, visuospatial | Depends on location of ischemia | Memory, visuospatial | Executive dysfunction, personality changes, disinhibition, language, +/- memory |
Motor Symptoms | Rare early Apraxia later |
Correlates with ischemia | Parkinsonism | None |
Progression | Gradual (over 8-10 years) | Gradual or stepwise with further ischemia | Gradual, but faster than Alzheimer’s disease | Gradual, but faster than Alzheimer’s disease |
Imaging | Possible global atrophy | Cortical or subcortical on MRI | Possible global atrophy | Atrophy in frontal & temporal lobes |
Evaluation¶
- MINI-COG: Screening test for cognitive impairment (highly sensitive)
- Ask pt to remember three words (banana, sunrise, chair). Ask pt to repeat immediately
- Ask pt to draw clock. After numbers are on the face, ask pt to “set
hands to 10 past 11”
- Correct is all numbers in right position AND hands pointing to the 11 and the 2
- Ask pt to recall the three words
-
MOCA: Montreal Cognitive Assessment
- Lengthier test of cognition (but highly specific for cognitive impairment)
- Useful for detecting subtle deficits as in Mild Cognitive Impairment (MCI)
- Scores:
- 18-25: Mild cognitive impairment
- 10-17: Moderate cognitive impairment
- <10: Severe cognitive impairment
-
Rule out reversible causes of dementia-like symptoms: DEMENTIA
- Drugs
- Emotional (depression)
- Metabolic (CHF, COPD, CKD, OSA)
- Endocrine (hypothyroidism, hyperparathyroidism, hyponatremia)
- Nutrition (B12 deficiency)
- Trauma (chronic SDH)
- Infection
- Arterial (vascular)
- B12, thyroid studies
- RPR, HIV testing in at-risk patient groups
- Neuropsych testing can be done for more clear patterns of dysfunction
- MRI brain with contrast if concerned for inflammatory or infectious
causes
- CJD: cortical ribboning on DWI with T2 hyperintensity in the thalamus and basal ganglia
- Sulcal crowding and bowing of the corpus callosum can be seen in NPH on imaging
Management¶
- Targeting Cognitive Impairment
- Cholinesterase Inhibitors: Donepezil, rivastigmine
- Indicated for any stage (except FTD)
- SE: GI (nausea, diarrhea), bradycardia, orthostasis
- NMDA antagonists: Memantine
- Indicated in moderate to severe AD in combination with cholinesterase inhibitors
- Fewer SE than cholinergic medications
- Cholinesterase Inhibitors: Donepezil, rivastigmine
- Vitamin supplementation (i.e. Vitamin E)
- Unclear benefit in delaying progression of dementia
- Targeting Behaviors
- Non-pharmacologic management has the best evidence of effectiveness
- Depression: Treat with antidepressants (SSRI’s)
- Sleep Disturbance: Mirtazapine (7.5 mg nightly) or Trazodone (25 mg nightly)
- Agitation: Try SSRI (citalopram, sertraline)
- Consider antipsychotics (black box warning increased risk of death in elderly)
Falls¶
Thomas Horton
Background¶
- Screen annually for falls in the past year
- History of fall is a strong risk factor for future falls
- Recommended History Screening Tool: CDC STEADI Algorithm
- Physical Exam Screening Tools:
- If potentially unstable injuries (new spine fracture or lower extremity fracture): Ask ortho to clear the patient for mobility
- If no potentially unstable injuries, attempt to get the patient out
of bed
- If lying down, have them lift each leg off the bed
- If they can do this, ask them to sit up on side of bed
- If they can do this, ask them to stand
- If they can do this without assistance, then observe them walk
- The Timed “up and Go” Test (TUG) tool for fall risk
- Have the patient rise from sitting in a chair, walk 10 feet forward, turn around, walk back to chair, and sit down
- Patients who require > 10 seconds are at increased risk for falls
- Med Rec:
- Antipsychotics, antidepressants, anticholinergics, anxiolytics, sedatives/hypnotics, anti-hypertensives, antiarrhythmics, steroids, statins all can increase risk of falls
Management¶
- Rule out other causes: Cardiac, Neurologic, Infectious
- Check Vitamin D levels (goal > 30) and supplement (800-1000 IU daily) if at increased fall risk
- Assess visual acuity (e.g. expedite cataract surgery)
- Hearing assessment (audiology screen)
- Consult Inpatient PT/OT and refer for HH PT/OT for home safety evaluation at discharge
- Recommend non-skid shoes with a backing (sneaker)
- Modify extrinsic risk factors for falls: removal of fall hazards, placement of handrails
- Referral to Exercise programs: At VUMC = Dayani Center “Ambulatory Referral to Medical Fitness” outpatient order
Frailty¶
Thomas Horton
Background¶
- Syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes
Evaluation¶
- FRAIL Scale Identifies frailty in community dwelling elders (1 -2 =
prefrail; > 3 = frail)
- Fatigue: are you Fatigued more often than not?
- Resistance: are you able to climb a flight of stairs?
- Aerobic: are you bale to walk a block?
- Illness: Do you have more than five illnesses?
- Loss: Have you lost more than 5% of weight in 6 months?
- Order Vitamin D and B-12 Levels.
Management¶
- Adapt interventions to the individual, incorporating patient preferences and stage on the spectrum of frailty
- Exercise programs with additional physical and occupational therapy input if indicated.
- Optimize nutrition via supplementation (Vit D, B12)
- Comprehensive Geriatric Assessment; Outpatient PACE
Functional Status¶
Thomas Horton
Background¶
- Functional status: Ability to perform activities necessary in daily life (ADL)
Basic ADL’s | Instrumental ADL’s | Advanced ADL’s |
---|---|---|
Dressing Eating Ambulating/transfer Toileting/continence Hygiene (bathing) |
Shopping Housekeeping & laundry Handling medications Accounting (finances) Food preparation Telephone Transportation (driving) |
Fulfill societal, community and family roles Participate in recreational tasks |
Evaluation¶
- Katz ADL scale, Lawton-Brody IADL scale, Get up and Go test, MMSE, Geriatric depression scale.
- Vulnerable Elders Scale-13: Identifies community dwelling pts at risk for decline over 5 yrs
- Functional decline is not normal with aging and warrants detailed physical, cognitive, and psychosocial evaluations
Malnutrition¶
Thomas Horton
Background¶
- Needs to meet two or more of following criteria:
- Insufficient calorie intake
- Weight loss
- Loss of muscle mass
- Loss of subcutaneous fat
- Localized fluid accumulation that may mask weight loss
- Diminished functional status as measured in handgrip strength
- Reversible causes of malnutrition:
- Food security (poverty), dental status (dentition, gum health), dietary restrictions, food-related functional status (shop, prepare meals, feed self), depression, dementia, alcoholism, swallowing ability
Evaluation¶
- Assess for depression
- Screening with Mini Nutritional Assessment (good sensitivity and specificity)
- Order: CBC, CMP, TSH
- Nutritional deficiencies: B12, folate, vitamin D
- Consider CT C/A/P depending on history
- Refeeding: K, Phos, Mg BID until stable and no longer having to replete
Management¶
- Manage reversible causes of malnutrition as above
- Medications: consider Remeron (7.5 mg nightly). Avoid Megace (NNH = 23 for death)
- Liberalize dietary restrictions
- Nutritional Supplementation: Oral enteral supplements (i.e. nutritional shakes)
Medication Management¶
Thomas Horton
- Medication Reconciliation Upon Admission
- Evaluating for Polypharmacy – Beer’s Criteria
- Pharmacologic changes in the elderly
- Pharmacokinetic (PK): Decreased hepatic and renal clearance. Reduction in first pass metabolism. Drug distribution changes due to decreased TBW and lean body mass resulting in relative increase in fat.
- Pharmacodynamic (PD): Exaggerated responses to pharmacologic therapy (therapeutic and adverse effects).
- Avoid Prescribing Defaults:
- NSAIDs can lead to gastritis, which can lead to prescription of PPI
- Diuretics can lead to urinary incontinence, which can lead to prescription of oxybutynin
- HCTZ can lead to hyperuricemia which can lead to prescription of allopurinol
- Discharge Tips for med adherence: provide pillboxes & arrange blister packs for meds
- Recommended Tools: deprescribing.org (App available); medstopper.com
Geriatrics Overview¶
Thomas Horton
4 M’s of Age-Friendly Care¶
Endorsed by the IHI to provide best evidence-based care to older patients across all settings of care:
- What **M**atters Most: Understand each patients specific healthcare goals in the short and long term. Ask “what matters most” and align the care plan with what matters.
- **M**edication: Aim to reduce adverse drug events in the elderly by thorough med rec and avoiding potentially inappropriate medications (e.g. Beers Criteria) when possible
- **M**entation: Identify, treat, and manage dementia, depression, and delirium across various settings of care.
- **M**obility: Assess and optimize mobility
Vanderbilt’s FACETS Inpatient Geriatrics Curriculum: https://sites.google.com/view/facetscourse
Physiological Changes with Aging¶
- Cardiovascular: Decreased vascular compliance and increased stiffness (intimal thickening). Decreased cardiac output. Maximum achievable HR decreases. Increase in systolic BP with decrease in diastolic BP (wider PP).
- Endocrine/Immune: Impairment of glucose tolerance (insulin resistance). Decreased sympathetic response to stress. Impairment of T-cell immunity and increased susceptibility to infection.
- Gastrointestinal: Decreased GI absorption, gastric emptying, motility, acid secretion, and hepatic blood flow. Reduced appetite and alterations of taste and smell.
- Musculoskeletal: Decreased bone density, muscle mass and strength. Increased fracture risk.
- Neurologic: Reduced cortical volume. Blunted vision, auditory function, and vibrotactile sensation. Decreased autonomic neural response. Slowed cognition and reflexes.
- Pulmonary: Increased chest wall rigidity. Decreased respiratory muscle strength. Decreased FEV1; FVC. Diminished ventilatory response to hypercapnia and hypoxia.
- Renal: Increased glomerulosclerosis. Decreased GFR and renal clearance of drugs/metabolites (↓ 1mL/min per year after age 40; Cr may stay the same due to reduced muscle mass). Reduced tubular function.
Urinary Incontinence and Foley Catheters¶
Thomas Horton
Background¶
Types of UI | Mechanism | Associated Symptoms |
---|---|---|
Stress | Incompetent urethral sphincter (post-prostatectomy) |
UI with physical exertion (cough, laughter, sneeze) |
Urge | ↑ bladder contraction from detrusor instability (infection, stone, T2DM, caffeine, meds, BPH |
Frequency, nocturia, sudden urge |
Overflow | ↓ contractility/outlet obstruction (BPH, anticholinergic medications, T2DM, pelvic trauma, spinal cord disease, MS, polio) | Hesitancy, weak stream, sense of incomplete emptying |
Functional | Physical, emotional, or cognitive disability | Depression, pain, evidence of physical, sensory, or cognitive impairment |
Evaluation¶
- Medication Reconciliation:
- Alcohol, α-Adrenergic agonists, α-Adrenergic blockers, ACE inhibitors, Anticholinergics, Antipsychotics, Calcium channel blockers, oral estrogen, GABAergic agents, NSAID’s, narcotics
- Order Hemoglobin A1C, Electrolytes (particularly calcium), UA
- Rule out retention using PVR
- Rectal exam to rule out fecal impaction
Management¶
- Skin care for urinary incontinence:
- Barrier creams: Venelex, petroleum, zinc oxide
- Diapers only when up out of bed
- Chucks while in bed (don’t hold moisture up close to the skin like diapers do)
- Offer toileting Q1-2hours
- Indications for a foley:
- Inability to void
- Need for accurate UOP monitoring when patient unable to comply
- Urinary Incontinence AND open sacral or perineal wound
- Perioperative Use
- Comfort care at end of life
Ended: Geriatrics
Hematology oncology ↵
Anemia¶
Margaret Wheless
First establish acuity: bleed or consumptive process vs slow onset anemia - Check vitals for hypotension, tachycardia. - Check Hgb trend from prior if available. - Examine patient for pallor, rapid onset fatigue, AMS, feeble pulses and any signs of bleeding. - Consider risk factors such as recent procedure, blood thinner use, falls, new medications. - STAT repeat CBC along with haptoglobin, LDH, HFP(bilirubin) to rule out hemolysis - If no sx/signs of acute bleeding, move onto general anemia eval below. - Note: CBC does not accurately reflect blood loss in acute rapid bleeding scenarios so do not be falsely reassured by normal hematocrit in GI bleeds/trauma patients.
Presentation¶
- Symptoms: fatigue/malaise, dyspnea on exertion, angina (if history of CAD)
- Signs
- Pallor, tachycardia, orthostatic hypotension, purpura, glossitis, koilonychia (in IDA)
- Jaundice (if hemolysis)
- Splenomegaly: suggests extramedullary hematopoiesis or sequestration
- Neurologic symptoms: suggests B12 deficiency
Evaluation¶
- CBC w/diff, reticulocyte count, peripheral blood smear, iron studies (TIBC, ferritin)
- Reticulocyte index (RI) > 2%: blood loss vs hemolysis; see below
- Hemolysis labs: Bilirubin, LDH, haptoglobin
- RI < 2%: hypoproliferative à stratify based on RBC size
- Microcytic (<80) vs. Normocytic (80-100) vs. Macrocytic (>100)
Reticulocyte Index >2%¶
Background¶
- Etiology: consumption vs. blood loss
- Loss: acute bleed vs iatrogenic from labs
- Hemolysis: microangiopathic hemolytic anemia (MAHA), autoimmune hemolytic anemia (AIHA), intrinsic RBC defects
Evaluation¶
- LDH, ↑ indirect bilirubin, ↓ haptoglobin, PT/PTT
- Note: haptoglobin can be low in cirrhosis (made by liver), recently transfused blood, large hematoma
- Peripheral blood smear: evaluated for schistocytes, bite cells, spur cells, spherocytes, etc.
- Direct antiglobulin test (DAT) to evaluate for autoimmune hemolytic anemia
Extrinsic RBC causes¶
- If schistocytes ± thrombocytopenia = MAHA: TTP, other TMA syndromes (HUS, drug-induced, complement-mediated), DIC, HELLP, mechanical valves, malignant HTN, cocaine, scleroderma renal crisis
- If DAT positive = AIHA
- Consider cold agglutinin titer
Intrinsic RBC causes¶
- Sickle cell disease: chronic hemolysis + splenic sequestration crisis where RI is↑ vs aplastic crisis where RI is↓ (see sickle cell section)
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Severe B12 deficiency
- Spur cell anemia (found in advanced cirrhosis)
- PNH
- G6PD: bite cells, Heinz bodies
- Usually precipitated by drugs: nitrofurantoin, dapsone, sulfonamides, rasburicase, primaquine
Management¶
- MAHA
- DIC: sepsis, malignancy, pregnancy (See “Disseminated Intravascular Coagulation” section)
- Treat underlying cause
- If active bleeding: FFP, cryoprecipitate (to keep fibrinogen>100), and platelets
- TTP: Order ADAMTS13 (prior to plasma transfusion or exchange).
- If concern for TTP you should immediately consult Heme and Nephrology
- HUS: + shiga toxin, AKI, diarrhea
- IVF, antibiotics only to treat extra-renal disease, transfusion as necessary
- DIC: sepsis, malignancy, pregnancy (See “Disseminated Intravascular Coagulation” section)
- AIHA:
- Cold (rare): IgM binds at temp <37
- Caused by lymphoproliferative disorder (Waldenstrom’s), mycoplasma, EBV, HIV
- Consult Heme. Treat underlying condition. Consider rituximab (steroids ineffective)
- Warm: IgG
- Idiopathic or associated with lymphoma, SLE, drugs, babesiosis, HIV
- Can use steroids, IVIG, rituximab
- Cold (rare): IgM binds at temp <37
RBC Size Framework¶
Normocytic anemia: MCV 80-100¶
- Etiologies:
- Anemia of inflammation (formerly chronic disease): (may also be microcytic)
- Anemia of CKD: low Erythropoietin (EPO) levels
- Endocrine disease (hypothyroidism, adrenal insufficiency): ↓metabolic demand/O2 requirement
- Mixed macrocytic/microcytic disease may have a normal MCV: look for ↑RDW
- Pure red cell aplasia: associated with destructive Ab (CLL, thymoma, parvovirus, autoimmune)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Splenic sequestration
- Bone marrow failure or infiltration (typically will see pancytopenia)
- Vitamin C deficiency, copper deficiency
- Bone marrow biopsy may be indicated if no identifiable cause or anemia is associated with other cytopenia’s
Microcytic anemia: MCV <80¶
- mnemonic: SALTI
- *S*ideroblastic, *A*nemia of chronic disease, *L*ead poisoning, *T*halassemia and *I*ron-deficiency
Disease | Etiology | Evaluation | Considerations |
---|---|---|---|
Sideroblastic | MDS Idiopathic EtOH, Lead, Isoniazid Cu deficiency |
Fe: ↑↑ Ferritin: ↑ to normal TIBC: normal Smear: basophilic stippling BMBx: ringed sideroblasts |
In clinical practice this is usually acquired; either due to alcohol (can resolved with cessation) or primary bone marrow disorder (e.g. MDS-RARS) |
Anemia of Inflammation (formerly chronic disease) | Chronic inflammation, malignancy, HIV, autoimmune dz, heart failure, etc. | Fe/TIBC >18% Fe: ↓↓ Ferritin: ↑↑ TIBC: ↓↓ |
Treat underlying disease Replete Fe if ferritin <100 or TIBC <20% EPO if Hgb <10 and serum EPO <10 |
Thalassemia | ↓ synthesis of α or β chains leads to ↓ erythropoiesis and ↑ hemolysis Family Hx of anemia Mentzer’s index: MCV/RBC <13 = thalassemia Normal Fe studies; can mimic microcytic anemia and Fe overload from transfusions |
Diagnosis: Hb electrophoresis (α will be normal) α thal more common in Asian/African descent β thal common in Mediterranean descent |
Tx: transfusions, folate, Fe chelator depending on severity |
Iron (Fe) deficiency | Chronic bleeding: colon cancer, heavy menstrual periods, cirrhosis (portal gastropathy) Supply: malnutrition, Crohn’s dz, Celiac dz, subtotal gastrectomy, atrophic gastritis Demand: pregnancy |
Fe/TIBC <18% Fe:↓↓ TIBC:↑ nl to ↑ Ferritin: < 100 Mentzer’s index: >13 |
Consider celiac testing based on clinical suspicion Investigate for GIB or source of blood loss Oral Fe: 6wks to correct anemia, 6mo to replete stores; dose every other day (↑ absorption w/ ↓ GI side effects); add Vit C for ↑ absorption If can’t tolerate PO consider IV Fe (Avoid when bacteremic) HFrEF: IV Fe if ferritin <100 OR 100-300 w/ Fe sat <20% |
Macrocytic Anemia: MCV >100¶
- Non-megaloblastic
- ETOH, liver disease, hypothyroidism, MDS
- Medications that impair DNA synthesis: zidovudine, 5-FU, hydroxyurea, ara-C, AZT, MTX
- Megaloblastic
- B12 deficiency
- Presentation: neurologic changes (subacute combined degeneration), paresthesias, ataxia, dementia (reversible with early treatment)
- Etiology: malnutrition (alcoholics, vegan), pernicious anemia, gastrectomy, Crohn’s disease, chronic pancreatitis, celiac disease
- Diagnosis: ↓B12, ↑MMA, ↑homocysteine
- Treatment: either monthly IM or PO B12 (1% paracellular absorption demonstrated to be sufficient for repletion)
- Folate deficiency
- Etiology: malnutrition, decreased absorption (e.g. celiac disease), impaired metabolism (MTX, TMP), ↑requirement (hemolysis, malignancy, dialysis)
- Diagnosis: ↓folate, ↑homocysteine, MMA will be normal
- Treatment: PO folate 1-4mg daily
- B12 deficiency
Anticoagulation¶
Madeleine Turcotte
Agent | Treatment Dose | Renal Dose | Prophylaxis | Monitoring | Hold prior to procedure |
---|---|---|---|---|---|
Unfractionated heparin | 80 U/kg bolus, then 18 U/kg/hr | No change necessary | 5000 U q8h | PTT (automatic in order set) | 6 hours |
Enoxaparin (Lovenox) | 1 mg/kg q12h or 30 mg BID |
1 mg/kg daily | 40 mg daily | LMWH level (anti-Xa level) Best checked 4 h after 4th dose |
12 hours |
Warfarin (Coumadin) | Start 2-5mg daily and monitor INR Can consult Pharmacy |
No change necessary | N/A | PT/INR Use Chromogenic Factor X assay if pt has APLS |
Several days (Goal INR <1.5) |
Dabigatran (Pradaxa) | After 5 days of a parenteral AC, 150 mg BID | Avoid use | N/A | Can test drug level if concerned | At least 48hrs |
Rivaroxaban (Xarelto) | 15 mg BID x21 d then 20 mg daily | Avoid use in CrCl<30 | 10mg QD | At least 48hrs | |
Apixaban (Eliquis) | 10mg BID x7d, then 5mg BID | VTE: No adjustment | 2.5 mg BID | >A Fib: 2.5mg BID, if 2 of the following: Cr 1.5, Age > 80, Weight < 60kg | At least 48hrs |
Edoxaban (Savaysa) | After 5 days of a parenteral AC, 60 mg daily | 30 mg for CrCl 15-50 Avoid if CrCl > 95 |
N/A | Best studied option in renal dysfunction | At least 48hrs |
Additional Information¶
- VA is starting to move towards rivaroxaban and apixaban for extended secondary thromboprophylaxis
- Write in your PADR for apixaban citing “pt uses a pillbox and cannot use dabigatran”
- Renal dysfunction: favor warfarin, apixaban or edoxaban
- Hx of GI bleed: avoid dabigatran, rivaroxaban, edoxaban (may have higher risk of GI bleed)
- Pregnancy: UFH/LMWH (other agents may cross the placenta)
- BMI >40: Apixaban or rivaroxaban can be used per 2016 ISTH guidelines (but avoid dabigatran)
- GI malabsorption (e.g. Crohn's): Caution with DOACs, consider enoxaparin
Transitioning between Anticoagulants with DOACs¶
From | To | Timing |
---|---|---|
DOAC | Warfarin |
Low-moderate risk DVT/PE: start warfarin while pt is on DOAC, stop DOAC on day 3 of warfarin therapy, and check INR on day 4 High risk DVT/PE: start LMWH or UFH, then start warfarin |
DOAC | LMWH | Stop DOAC and start LMWH when due for next DOAC dose |
DOAC | UFH | Start IV heparin with bolus when next DOAC dose is due |
LMWH | Warfarin | LMWH and warfarin given simultaneously until INR is therapeutic for 24h |
LMWH | DOAC | Stop LMWH and start DOAC when due for next dose of LMWH (within 2h) |
UFH | DOAC | Start DOAC when IV stopped (30min prior to cessation if high risk for thrombosis) |
Warfarin | DOAC | Start DOAC when INR < 2.0 |
Peri-procedural Management of Anticoagulation¶
- Temporary IVC filter indicated in pts with very recent acute VTE (within 3-4 weeks) if the procedure requires AC delay >12 hours
- For those at high risk of thromboembolism
- Consider continuing AC for low-bleeding-risk procedures like dental procedures, cutaneous biopsy/excision, ICD placement, and endovascular procedures.
- Can bridge with LMWH or heparin drip
Stop before procedure | Restart after procedure | |
---|---|---|
Warfarin | 5 days prior, check INR day of | 12 to 24 hours after |
Dabigatran | 48 hours prior (longer if CrCl 30-50 or procedure is high bleeding risk) | 1 day after (2 days if high bleeding risk) |
Rivaroxaban | ||
Apixaban | ||
Edoxaban | ||
Heparin | Stop infusion 4-5 hours prior | 24 hours after |
Enoxaparin | 12 - 24 hours prior | 24 hours after (48-72 hours if high bleeding risk) |
Strategies for Reversal of Anticoagulation¶
Warfarin¶
- Vitamin K: onset within a few hours but takes 24-48 hrs for full effect
- Life threatening bleeding: Give IV Vitamin K 10 mg over 30 minutes.
- Intracranial bleed, bleed with hemodynamic instability, emergent procedure non-life threatening
- INR <5: Vitamin K not recommended
- INR 5-10: Vitamin K 1-5 mg IV or PO
- INR >10: Vitamin K 5mg PO or 5 mg IV
- Prior to surgery
- Rapid reversal INR > 5: 5mg Vit K IV (24 hours prior to procedure)
- FFP: 15 ml/kg (e.g. 4 units/70 kg person) if need reversal <24 hrs, plus give Vitamin K
- KCentra ($$$): Contains Factors II, VII, IX, and X with Protein C, Protein S, and heparin
- Given instead of plasma when insufficient time for plasma/Vit K to work (i.e. for life threatening hemorrhage)
- Avoid giving in HIT
- Administer with Vitamin K
Dabigatran¶
- Idarucizumab ($$$) will reverse if prolonged thrombin time (remember to check): Consult Hematology
Factor Xa inhibitors: rivaroxaban, apixaban, edoxaban¶
- FEIBA (Factor VIII inhibitor bypassing activity): can promote coagulation but is NOT a reversal agent; limited data to support use
- Consult Hematology before using; andexanet alfa (FDA approved) is not on VUMC formulary but is on the VA formulary
Bleeding Coagulopathies¶
Hayley Hawkins
- Bleeding tendency or dysfunction in clot formation can occur from either a quantitative or qualitative platelet defect, deficiency or inhibitor of coagulation factors, or compromise of vascular integrity
- Platelet disorders will present with mucocutaneous bleeding, petechiae, mild bleeding immediately following surgery, impaired wound healing
- Coagulation defects will present with deep tissue bleeding in joints/muscles resulting in hemarthroses, hematomas, sometimes delayed but severe bleeding after surgery, and intracranial hemorrhage
Qualitative or Quantitative Platelet Defects¶
- Thrombocytopenia: see "thrombocytopenia" section
von Willebrand Disease (vWD)¶
- Most common inherited bleeding disorder, but can be secondary or acquired by other disease states
- Three types
- Type 1 (most common): quantitative defect with normal vWF function
- Type 2: qualitative defect with abnormal vWF function despite normal quantity
- Type 3 (rare): complete absence of vWF, phenotypically similar to hemophilia A (vWF forms complex with factor VIII)
- Causes of acquired vWD
- Lymphoproliferative disorders: CLL, NHL, plasma cell dyscrasias
- Myeloproliferative disorders: PV, ET, or myelofibrosis
- Autoimmune diseases: SLE
- Sheer stress: aortic stenosis – Heidi syndrome, LVAD, ECMO
- Hypothyroidism
- Diagnosis:
- “vW Profile” = vWF Ag, Factor VIII Activity, Ristocetin Cofactor Activity
- Management:
- Major bleeding or major surgery: give VFW concentrate (some formulations have FVIII)
- Minor bleeding or surgery or prophylaxis: DDAVP, TXA or aminocaproic acid in some circumstances
Other causes of qualitative platelet defects¶
- Uremic platelet dysfunction
- Medications: NSAIDs, anti-platelets (ASA, Plavix), SSRIs (serotonin required for platelet activation), and melatonin (suggested by pre-clinical studies)
Deficiency or Inhibitor of Coagulation Factors¶
Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency)¶
- X-linked recessive inheritance
- Frequently presents with hemarthroses and hematomas
- Diagnosis: Isolated prolonged PTT with normalization upon mixing study
- Management: Purified/recombinant Factor VIII or IX, mild disease can be managed with desmopressin, consult Benign Hematology on admission
Acquired FVIII Inhibitor¶
- Onset in older age (60s) and frequently presents with significant intramuscular hematomas
- Disease associations in 50% of cases (other 50% idiopathic): autoimmune (e.g. SLE), malignancy (paraneoplastic), Pemphigus, drug-induced (e.g. interferon, penicillins), or chronic GvHD
- Diagnosis: Elevated PTT that does not normalize with mixing study
- Management:
- Always consult Hematology (rare disorder with major bleeding complications)
- Bleeding: Typically need a factor VIII bypassing agent (FEIBA)
- Immunosuppression: prednisone 1mg/kg, rituximab often also used front line
Other Causes¶
- Factor VIII deficiency: see vWD above
- Vitamin K deficiency
- Caused by malnutrition, liver disease (biliary obstruction), or iatrogenic with warfarin
- Diagnosis: elevated PT, prolonged PTT if severe, hepatic function panel
- Management: IV vitamin K 10mg x 3 days
- DIC and liver dysfunction/cirrhosis
- A FVIII level can help distinguish between the two (elevated or normal in liver dysfunction and decreased in DIC since it is not hepatically derived)
- Amyloidosis: can cause factor X deficiency
- Medications: warfarin, DOACs
Compromise of Vascular Integrity¶
- Amyloidosis: can present as GI bleeding, purpura or ecchymoses (e.g. Raccoon eyes)
- Vasculitis: purpura, alveolar hemorrhage (DAH), intracranial hemorrhage, GI bleeding
- Vitamin C deficiency: can present with bleeding gums, GI bleeding, ecchymoses, hematomas, anemia
- AVMs (fragile vessels that easily bleed)
- Hereditary hemorrhagic Telangiectasia
- 2nd most common inherited bleeding disorder
- Often presents with epistaxis, GI bleeding
- AVMs found in GI tract, lung (may cause shunting), liver (can contribute to cirrhosis), brain
- vWD
- von Willebrand multimers play direct role in modulating angiogenesis
- Heidi Syndrome: acquired vWD due to aortic stenosis, presents with GI bleeding from AVMs
Bone Marrow Transplant¶
Chelsie Sievers
Background¶
- Donor selection
- Autologous: self, no matching required (no GVHD risk, but also no graft-vs-tumor effect)
- Allogeneic: non-self, matching based on HLA (more matched = less GVHD risk)
- Matched-related donor (MRD): fully matched sibling
- Matched-unrelated donor (MUD): from NMDP database
- Haploidentical: half matched sibling or parent
- Source of stem cells:
- Peripheral blood stem cells (PBSCs) vs. bone marrow-derived cells vs umbilical cord
- Conditioning regimens:
- Myeloablative vs. reduced-intensity conditioning (RIC)
- GVHD prophylaxis (for allo-SCT)
- Regimen varies: can include tacrolimus, MMF, MTX, or thymo and alemtuzumab during conditioning
Complications/Adverse Effects:¶
- Infectious
- Neutropenic fever, neutropenic enterocolitis (typhlitis)
- Bacterial infections
- Viral infections
- CMV: check weekly PCR levels post-allo-SCT
- All CMV+ recipients are treated with letermovir prophylactically regardless of donor status
- EBV: check weekly PCR levels post allo-SCT. If EBV VL >1000 on two occasions, can treat with pre-emptive rituximab to reduce the risk of PTLD
- CMV: check weekly PCR levels post-allo-SCT
- Invasive fungal infections (e.g. aspergillus, candida)
- Non-infectious
- Nausea, vomiting, diarrhea, mucositis, cytopenias
- Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS)
- Pathophysiology: sinusoidal endothelial cell damage from conditioning chemo -> post-sinusoidal portal HTN -> cytokine release -> multiorgan failure and death
- Diagnosis: total bili >2, hepatomegaly/RUQ pain, weight gain > 2-5%
- Evaluation: RUQ U/S with doppler
- Treatment: Per heme attending; generally supportive, consider defibrotide
- Graft failure:
- Primary: persistent neutropenia without engraftment
- Secondary: delayed pancytopenia 2/2 immune phenomena or infection after engraftment
- Engraftment syndrome:
- Pathophysiology: PMN recovery -> cytokine storm -> vascular leak
- Symptoms: fever, tachycardia, hypotension, SOB, pulmonary edema, rash, weight gain, bone pain, confusion
- Diagnosis: clinical
- Treatment: high-dose IV steroids
- Idiopathic pneumonia syndrome (IPS)
- Umbrella term that also includes peri-engraftment respiratory distress syndrome (PERDS) and diffuse alveolar hemorrhage (DAH)
- Pathophysiology: Lung injury from conditioning -> cytokines -> recruitment of alloreactive T cells -> progressive lung injury resembling ARDS
- Diagnosis: multi-lobar airspace opacities and hypoxia in absence of infection
- Evaluation: imaging, bronchoscopy with BAL
- Management: Prednisone 1-2 mg/kg or pulse 1g/d x3 days; etanercept 2nd line
- Acute GVHD
- Only in allogenic; increased risk with more HLA mismatch
- Pathophysiology: donor T cells attack recipient (Th1-mediated)
- Symptoms: skin rash, cholestatic liver injury, diarrhea
- Treatment: IV steroids (methylprednisolone 1-2mg/kg x 5d)
- If refractory: mycophenolate, etanercept, ruxolitinib, antithymocyte globulin
- Chronic GVHD (typically after T+100)
- Can involve all organs but typically see a scleroderma-like picture (xerophthalmia, xerostomia dysphagia, arthritis, skin changes, malar rash, obliterative bronchiolitis, cholestatic liver injury, cytopenias)
- Treatment: Steroids (also photophoresis for skin), Consider trials of ruxolitinib, ibrutinib, rituximab if refractor,
- Post-transplant lymphoproliferative disorders (PTLD) - Pathophysiology: B-cell proliferative disease typically from latent EBV - Symptoms: fever, weight loss, fatigue, lymphadenopathy, extra-nodal masses, ↑ EBV PCR
CAR T-cell Therapy¶
Chelsie Sievers
Background¶
- Chimeric antigen receptor T cells (CAR-T) are a type of autologous T-cell therapy collected from the pt and genetically modified to contain an extracellular tumor-specific antigen target linked to the internal component of the T-cell receptor.
- Goal: Pt's own T-cells can specifically target the tumor cell population.
- FDA approved therapies: Kymriah (CD19), Abecema (BCMA), Breyanzi (CD19), Tecartus (CD19), Yescarta (CD19)
Complications:¶
- Cytokine release syndrome
- Pathophysiology: Supraphysiologic immune cell response with release of inflammatory cytokines.
- Grading
- Grade 1: fever ≥ 100.4, no hypotension, no hypoxia
- Grade 2: fever ≥ 100.4, hypotension not requiring vasopressors and/or hypoxia requiring < 6L
- Grade 3: fever ≥ 100.4, hypotension requiring a vasopressor, hypoxia requiring > 6L or non-rebreather
- Grade 4: fever ≥ 100.4, hypotension requiring multiple vasopressors, hypoxia requiring positive pressure
- Work-up: blood and urine cultures (IV abx if needed)
- Treatment:
- ICU transfer (grade 1 okay for floor)
- Acetaminophen for fever
- Tocilizumab 8 mg/kg IV (max 800mg; up to 3 doses in 24 hours, 8 hours apart)
- Dexamethasone 10 mg IV q 6 hours (grade 3-4)
- Immune effector cell-associated neurotoxicity syndrome: ICANS
- Pathophysiology: high systemic inflammation -> leaky blood brain barrier -> encephalopathy ± cerebral edema
- Grading
- Based on ICE score: Orientation: orientation to year, month, city, hospital (4 points); Naming: ability to name 3 objects (e.g. point to clock, pen, button) (3 points); following commands: ability to follow simple commands (e.g. “Show me 2 fingers” or “Close your eyes and stick out your tongue”) (1 point); writing: ability to write a standard sentence (e.g. “Our national bird is the bald eagle”) (1 point); attention: ability to count backwards from 100 by 10 (1 point)
- Grade 1: ICE score: 7-9
- Grade 2: ICE score: 3-6
- Grade 3: ICE score 0-2
- Grade 4: ICE score 0
- Work-up: Neuro consult, fundoscopic exam for papilledema, consider MRI brain w/and w/o contrast, consider EEG, consider non-con CT head if headache/lethargy.
- Treatment
- q4hr neuro checks (q1hr if grade > 2 → ICU transfer)
- Keep Na 135-145 with hypertonic saline if necessary (Na 145-150 if grade 4)
- Consider thiamine supplementation 500mg q8hr
- Steroids
- Grade 2-3: dexamethasone 10 mg q 6 hours (if seizure give 20mg x 1, then 10mg q6hrs)
- Grade 4: methylprednisolone 1000 mg IV q 24 x 3 days
Disseminated Intravascular Coagulation (DIC)¶
Hannah Angle, Eric Singhi
Background¶
- Abnormal activation of coagulation and fibrinolysis, leading to simultaneous clotting and bleeding
- Widespread thrombi formation results in consumption of coagulation factors and platelets (consumption coagulopathy)
Etiologies¶
- Sepsis (especially gram-negative rods), liver disease, pancreatitis, trauma (especially CNS), severe burns, insect/snake venom
- Malignancies: acute leukemia (especially APL), mucin-secreting pancreatic/gastric adenocarcinoma, brain tumors, prostate cancer
- Obstetric complications: preeclampsia/eclampsia, placental abruption, acute fatty liver of pregnancy
- Acute hemolytic transfusion reaction (ABO incompatible transfusion)
Evaluation¶
- Exam findings: petechiae, ecchymoses, bleeding (mucosal, IV sites, surgical wound sites, hematuria), thrombosis (cold, pulseless extremities)
- Laboratory evaluation
- Initial workup: CBC, PT/INR, aPTT, fibrinogen, d-dimer, peripheral blood smear
- Serial DIC labs: q6-8h fibrinogen, PT/INR, aPTT (space out when lower risk)
- Lab abnormalities suggestive of DIC: prolonged aPTT and PT/INR, thrombocytopenia, low fibrinogen, elevated D-dimer, schistocytes
- Since Factor VIII is not produced in the liver, it can help distinguish between DIC and liver dysfunction: Factor VIII should be elevated/normal in liver disease and decreased in DIC
Management¶
- TREAT THE UNDERLYING CAUSE
- Supportive measures:
- Vitamin K for INR > 1.7 or bleeding
- Cryoprecipitate (10 units) if fibrinogen < 100
- Platelet transfusion as normally indicated
- DVT ppx if not bleeding and platelet > 50
- VTE: therapeutic anticoagulation if platelet > 50 and no massive bleeding
Hypercoagulable States¶
Chris Cann
Background¶
- Virchow’s triad:
- Hypercoagulability
- Stasis
- Endothelial injury
- Diagnostic thrombophilia testing indications
- Idiopathic or recurrent VTE
- First VTE at <40 years old
- VTE in the setting of strong family history
- VTE in unusual vascular site (cerebral, renal, mesenteric)
- Recurrent pregnancy loss
- Must consider if thrombophilia testing will change clinical management
- If the unprovoked VTE warrants indefinite anticoagulation then testing may not be helpful
- However, if VTE provoked by minor risk factor (OCPs) with an underlying thrombophilia might change the decision, then testing may be informative
- Separated into acquired and hereditary conditions
- Hereditary:
- Factor V Leiden mutation
- Prothrombin mutation
- Protein C or S deficiency
- Antithrombin deficiency
- Acquired
- Antiphospholipid syndrome (APLS)
- Myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria
- Heparin induced thrombocytopenia (HIT)
- Major surgery/trauma
- Nephrotic syndrome
- Smoking
- Pregnancy
- Oral contraceptives
- Immobilization (bedridden, hip/knee replacement)
- Active malignancy
- Estrogen replacement therapy
- Note: Travel (plane, train, automobile) is NOT on this list and this is NOT considered a provoking risk factor
- Hereditary:
- Testing: All specific testing for hereditary disorders and APS should be performed at least 4-6 weeks after an acute thrombotic event or discontinuation of anticoagulant/thrombolytic therapies to avoid interference.
Antiphospholipid Antibody Syndrome (APLS)¶
Background¶
- Most common acquired disorder (anti-phospholipid antibodies present in 3-5% population)
- Recurrent pregnancy loss, provoked DVT in young, unprovoked VTE and arterial thrombosis in young, thrombosis unusual sites, thrombosis in autoimmune disease
- This is a clinicopathologic diagnosis (need both clinical and laboratory criteria)
Evaluation¶
- Positive for at least 1 lab criterion on at least 2 occasions, at least 12 weeks apart:
- Lupus anticoagulant: can occur in relation to drugs or infection; transient are associated with thrombotic risk
- Anticardiolipin antibodies
- β 2GP1 (anti- β2-glycoprotein) antibodies
- Must also meet at least 1 of the following clinical criteria:
- Vascular thrombosis: DVT, arterial thrombosis, or small vessel thrombosis of any organ
- Pregnancy loss: there are specific criteria for this–consult UpToDate or other resource
Management¶
- Aspirin for primary prevention; warfarin for treatment (INR 2-3)
- Do NOT use DOACs for triple positive APLS (see TRAPS trial: rivaroxaban inferior to warfarin)
- Rituximab for recurrent thrombosis despite anticoagulation (controversial): call Hematology
Catastrophic APLS¶
Presentation¶
- Widespread thrombosis with multi-organ failure
- Intra-abdominal: Renal failure, pancreatitis, adrenal and splenic infarcts, mesenteric ischemia
- Pulmonary: respiratory failure
- CNS involvement including stroke
- Systemic inflammatory response syndrome (due to tissue necrosis)
- TMA/DIC syndrome
Diagnostic criteria¶
- Evidence of multi-organ involvement (3 or more)
- Confirmed by imaging techniques
- Renal involvement can be defined as rise in serum creatinine by 50%, severe systemic hypertension, or proteinuria (>500mg/d)
- Development of manifestations simultaneously or within 1 week
- Confirmation by histopathology of small vessel occlusion
- Laboratory confirmation of aPL antibodies (detected on 2 occasions 12 weeks apart)
Management¶
- Parenteral anticoagulation and high dose steroids
- For refractory cases: PLEX, rituximab
Heparin-induced Thrombocytopenia (HIT)¶
- Separated into Type 1 and Type 2
- Type 1: Mild and self-limited (not immune-mediated)
- Occurs within the first 2 days of first-time exposure
- Platelet count normalizes with continued heparin therapy
- Type 2 (what we typically refer to as HIT): Immune mediated
- Fall in platelet 30% to over 50% (even if platelet count >150) and/or thrombotic event has occurred
- 4-10 days after new exposure to heparin derivative OR ≤
- 1 day after restarting heparin derivative that had been used 30-100 days prior
- If exposed to heparin within 100 days, will have platelet drop within 24 hr
- Fall in platelet 30% to over 50% (even if platelet count >150) and/or thrombotic event has occurred
- Type 1: Mild and self-limited (not immune-mediated)
- Frequency: unfractionated heparin > LMWH; surgical wards > medical wards
- 50% will have thrombotic event in 30 days if HIT is untreated with 20% mortality
- Arterial thrombi are common in HIT
- HIT results from antibodies to complexes of platelet factor 4 (PF4) and heparin, further activating platelets (the activated platelets aggregate causing thrombocytopenia)
Evaluation¶
- 4T score (0-8 points):
- Thrombocytopenia (0-2 pts): degree and nadir of platelet count drop
- Timing (0-2 pts): timing of fall after initial or recurrent heparin exposure
- Thrombosis (0-2 pts): thrombosis, skin necrosis, non-necrotizing lesions, acute systemic reaction to heparin
- Other causes of thrombocytopenia (0-2 pts): more points if no alternate cause
- Solid-phase ELISA for heparin-PF4 antibodies
- 0.2-0.4 is indeterminate
- >0.4 is positive
- >1.4 HIT is likely
- >2 confirms HIT
- The lab at VUMC will perform functional SRA reflexively for all values >0.2
Management¶
- 0-3 points: Low concern for HIT; can restart heparin
- 4-5 points: Intermediate probability (~10%); hold heparin, start non-heparin anticoagulant
- 6 points: High probability (~50%); hold heparin, start non-heparin anticoagulant
- Argatroban (direct thrombin inhibitor) for prophylaxis and treatment of thrombosis
- Avoid platelet transfusions as can increase thrombogenic effect
- Avoid warfarin until complete platelet recovery as may cause microthrombosis
- Hematology consult for all confirmed HIT
Factor V Leiden Mutation¶
Evaluation¶
- Activated protein C resistance assay
- APC ratio in pt vs. normal
- Normal >2.0, heterozygotes 1.5-2.0, homozygotes <1.5
- FVL mutation is then determined via PCR
- Screen with APC assay rather than PCR initially; cost effective
Management¶
- VTE treatment same as general population
- VTE 4-8x risk in heterozygotes; 80x risk in homozygotes
- Avoid OCPs: increased risk for VTE
Prothrombin Gene Mutation¶
Evaluation:¶
- PCR of G20210A mutation (2-4% prevalence)
Management:¶
- VTE treatment same as general population and avoid OCPs
Protein C and S Deficiency¶
Background¶
- Autosomal dominant; first event occurs between 10-50 years of age
- Synthesized in liver and Vit K dependent; therefore low levels in hepatic dysfunction and warfarin use/vitamin K deficiency
- Protein C: low in settings of thrombosis, DIC, nephrotic syndrome, intra/post-op
- Protein S: low in infectious (HIV) and autoimmune processes (IBD)
- Protein S decreases during pregnancy (decreased free protein S, normal total protein S)
- Do not misdiagnose a pregnant pt with PS deficiency
Evaluation¶
- Functional Protein C and S assays
Management¶
- VTE treatment same as general population
- Avoid OCPs
- High risk pts may require protein C concentrate prior to surgery
- Increased risk of warfarin-induced skin necrosis
Antithrombin Deficiency¶
Background¶
- Autosomal dominant, does not skip generations
- VTE in unusual sites (cerebral sinuses, renal veins)
- Present < 50, but rarely in first two decades
- Decreased in liver disease, nephrotic syndrome, protein losing enteropathy, burn, trauma, bypass surgery, metastatic tumors, premenopausal, OCP use, pregnancy
Evaluation¶
- Functional antithrombin activity (AT-heparin cofactor assay)
- Then perform antigen quantity testing
Management¶
- Can use argatroban as does not require antithrombin function
- Warfarin preferred in VTE (titrate up based on expression of antithrombin deficiency)
Acute Leukemia¶
Kenna Koehler
Background¶
- AML: proliferation of myeloid blasts
- Most common acute leukemia in adults
- Median age of diagnosis is 65 years old
- AML has been associated with environmental factors (e.g. exposure to chemicals, radiation, tobacco, chemotherapy) and genetic abnormalities (e.g. trisomy 21; Fanconi anemia; Bloom's syndrome; various familial mutations)
- Pts with clonal hematopoiesis (MDS, myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, aplastic anemia) are at risk of transforming into AML
- APML
- ALL: proliferation of lymphoid blasts
- ⅔ of cases are B-cell ALL
- Blasts accumulate in the bone marrow, blood, and other tissues
Presentation¶
- Various cytopenias: anemia, thrombocytopenia, leukopenia, neutropenia
- Can have elevated, normal, or low WBC
- Weakness, fatigue, infections, gingival bleeding, weight loss, ecchymosis, epistaxis, bone pain, fever, leukemia cutis
- Electrolyte abnormalities (tumor lysis syndrome)
- Extramedullary hematopoiesis: splenomegaly, hepatomegaly, lymphadenopathy
Evaluation¶
- Diagnosis of acute leukemia requires one of the following
- 20% blasts in the bone marrow
- 20% blasts in the peripheral blood
- Presence of specific cytogenetic abnormality: t(8;21), inv(16), or t(15;17)
- Diagnosis of APML
- Should suspect APML based on presence of atypical promyelocytes in bone marrow or peripheral blood (these cells typically have finely dispersed chromatin, prominent nucleoli, high nuclear to cytoplasmic ratio, and creased, folded, bilobed, kidney-shaped, or dumb-bell shaped nuclei) or the presence of Auer rods
- Diagnosis is confirmed with presence of PML::RARA fusion gene and/or the associated chromosomal translocation t(15;17)(q24.1;q21.2)
- DIC: PT/INR, PTT, fibrinogen
- TLS: potassium, uric acid, phosphorous
- Neutropenic fever
- Leukostasis
Management¶
- Consult Hematology early
- Obtain blood consent and double lumen PICC for access
- Telemetry,TTE
- Daily labs: CBC w/ diff, CMP, coags
- Monitor for TLS, DIC, neutropenic fever
- TLS prophylaxis with allopurinol
- If concerned for APML, start ATRA right away (can start this before definitive diagnosis)
- Can use hematology order set for nurse-driven PRBC, platelet, and electrolyte repletion
- Will need specialized testing: bone marrow biopsy, molecular testing
Additional information¶
- APML is a medical emergency due to high rate of mortality, especially from massive hemorrhage due to coagulopathy. This is why it’s extremely important to start ATRA as soon as possible, even before definitive diagnosis is made
- Differentiation syndrome: promyelocytes differentiate
- Signs and symptoms: fever, SOB, hypotension, peripheral edema, pleural effusion, AKI
- Diagnosis: No defined criteria. If suspicious, discuss with hematology fellow
- Management: Steroids. If critically ill, hold ATRA and ATO and consider hydroxyurea
- AML is broken down into 3 risk categories based on molecular studies:
- Good risk: t(8;21), inv(18), t(16;16), NPM1+
- Intermediate risk: normal karyotype, FLT3+
- FLT3 inhibitors are midostaurin and gilteritinib
- Poor risk: TP53, everything else
Leukemia treatment overview¶
- General strategy is to use “induction” chemotherapy to try to induce clinicopathologic (as opposed to molecular) “remission”
- Defined as count recovery and <5% blasts in bone marrow (on day 28)
- Pts stay in hospital until neutrophil count >500 (typically ~4 weeks)
- From there, bone marrow transplant (for high-risk disease) or “consolidation” chemo for normal-risk or low-risk disease
AML treatment¶
- Induction
- Typical is “7+3” i.e. cytarabine on days 1-7 and idarubicin on days 1-3
- If therapy-related AML, MDS-related AML, or AML with cytogenetics similar to MDS, use “Vyxeos” which is liposomal daunorubicin and cytarabine on days 1, 3, and 5
- There are other induction regimens that can be used depending on specific cytogenetics and pt frailty, which is beyond the scope of the handbook
- Consolidation
- Typically “HiDAC”(high-dose Ara-C i.e. cytarabine)
- Generally too toxic for pts with age > 60, so a dose reduction is used
- In the case of relapse, typical treatment is a different high-dose chemo and BMT if possible
- Typically “HiDAC”(high-dose Ara-C i.e. cytarabine)
ALL treatment¶
- Typical induction is “HyperCVAD” (hyper-fractionated cyclophosphamide, vincristine, doxorubicin (“A” due to trade name Adriamycin), and dexamethasone
- If t(9;22) (Philadelphia chromosome), use tyrosine kinase inhibitor (TKI)
- If CD20+, use rituximab
Overview of Common Chemotherapy Regimens:¶
Regimen | Components | Use |
---|---|---|
7+3 | Cytarabine (Ara-C) x 7 d and anthracycline (e.g. idarubicin x3 d) | AML Induction |
Vyxeos | Cytarabine + liposomal daunorubicin | AML-MRC or t-AML |
CLAG-M | Cladribine, cytarabine (Ara-C), Filgrastim (G-CSF), mitoxantrone | AML induction (relapsed/refractory) |
HIDAC | high-dose cytarabine | AML consolidation |
ATRA | All-trans retinoic acid given with arsenic trioxide (ATO) | APML |
HyperCVAD/MA | CVAD = Cyclophosphamide, vincristine, doxorubicin, dexamethasone MA = methotrexate/cytarabine (Given as alternating cycles) |
ALL |
Leukocytosis¶
Kenna Koehler
Background¶
- Common progenitor cells (stem cells) are located in the bone marrow and give rise to erythrocytes, myeloblasts, megakaryoblasts
- Normal WBC can vary by age and pregnancy, for the purpose of this section will assume this is for an average, non-pregnant adult
- Chronic mild neutrophilic leukocytosis (10-20k) is common with tobacco use and obesity, both due to mechanisms related to chronic inflammation
- Reactive (typically 11k-30k): surgery, exercise, trauma, burns, emotional stress
- Leukemoid reaction (typically 50k-100k): severe infections (fulminant C difficile), organ rejection
- If greater than 100k, think leukemia or myeloproliferative disorder
Evaluation¶
- Neutrophilia: neutrophil count >7k
- Bacterial infection, pregnancy, rheumatologic disease, steroids, beta agonists, lithium, colony-stimulating factors, splenectomy or functional asplenia, congenital (hereditary/chronic idiopathic neutrophilia), Down syndrome, leukocyte adhesion deficiency, malignancy, smoking, obesity
- Lymphocytosis: >40% of WBC count or >4,500k/mm3
- Infections (pertussis, syphilis, CMV, EBV, hepatitis A/B/C, toxo), hypersensitivity reactions, thyrotoxicosis, Addison's disease, hematologic malignancies, “reactive”
- Monocytosis: >8% of WBC count or >880/mm3
- Infections (TB, fungal disease, protozoa, tick-borne), autoimmune disease, malignancy (CMML)
- Eosinophilia: >500/mm3
- Hypersensitivity (asthma, urticaria, atopic dermatitis, eosinophilic esophagitis), drug reactions, malignancies, connective tissue disease, idiopathic hypereosinophilic syndrome, infections (helminths, Scarlet fever, Hansen's disease), sarcoidosis, SLE
- Hypereosinophilia if AEC>1500, typically merits heme evaluation
- Hypereosinophilic syndrome: AEC>1500 and organ dysfunction from eosinophils
- Basophilia (>100/mm3)
- CML, thyroid disease, IBC, chronic dermatitis, infections (varicella)
Lymphoma¶
Danielle Fishman
Background¶
- Classically characterized by lymphadenopathy and constitutional “B” symptoms: fevers, drenching night sweats and weight loss
- Hodgkin (10%): superficial, nodal disease with orderly spread
- Bimodal distribution: 15-35 years and >50 years; M>F
- CD15+, CD30+ (Reed Sternberg cells “owl eyes”)
- Associated with EBV in immunocompromised pt
- Non-Hodgkin (90%): diffuse, nodal and extranodal disease with noncontiguous spread
- Average 65 years, M>F, 85-90% B-cell
- Associated with immunodeficiency (HIV, post-transplant), autoimmune disease, infection (EBV, HTLV-1, H pylori, HCV, Borrelia, C psittacosis, Coxiella)
General Evaluation¶
- History: B symptoms, pruritus (10-15% of pt with HL), history of radiation
- Physical Exam
- Evaluate head and neck, tonsils, axilla, testes, liver, spleen
- Lymphadenopathy: painless, firm, fixed, >1cm
- Lab tests:
- CBC, CMP, LDH, uric acid, phosphorus
- Consider HBV, HCV, HIV, EBV, Quant gold, treponemal Ab, ANA
- Imaging:
- CT chest, abdomen, pelvis
- Most will eventually need PET-CT. MRI brain if neuro symptoms
- Consider LP for NHL with high risk of CNS involvement or presence of neurological symptoms
- Risk factors: Burkitt, lymphoblastic, testicular involvement, double/triple hit
- Multiple LPs may be required to diagnose CNS lymphoma
- Diagnosis requires tissue
- Excisional lymph node biopsy: Surgical Oncology consult
- Core biopsy: CT guided procedure consult
- Of note, steroids may impact value of biopsy results
- Lugano Classification: staging of lymphoma
- One - 1 LN region or single extra lymphatic organ/site without nodal involvement
- Two - >2 LN regions, same side of diaphragm
- Three - LN regions on both sides of diaphragm
- Four - Disseminated disease w/ 1+ extralymphatic organ
- Hodgkin:
- IPS negative prognostic calculator: albumin <4, hemoglobin <10.5, male, stage IV disease, age>45, WBC count> 15K, lymphocyte <8% of WBC count
- Non-Hodgkin:
- Good prognosis: Follicular, marginal zone, mycosis fungoides/Sezary syndrome
- Poor prognosis: DLBCL – can arise from low grade lymphoma (Richter transformation); Double/Triple hit: bcl-2, bcl-6, or myc aberrations; mantle cell, Burkitt, lymphoblastic lymphoma, and anaplastic large cell lymphoma
General Management:¶
- ECG and TTE to establish pre-chemotherapy cardiac function—many chemo regimens with anthracyclines
- Daily labs: CBC, TLS, LDH
- TLS prophylaxis: mIVF, allopurinol
Common Chemotherapy Regimens for Lymphoma:¶
Regimen | Components | Use |
---|---|---|
R-CHOP | rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone | NHL |
R-EPOCH | etoposide plus the drugs above (dosing is different) | NHL (Double/Triple hit) |
Hyper-CVAD | cyclophosphamide, vincristine, doxorubicin, and dexamethasone | NHL |
HD-MTX + R | high dose methotrexate + rituximab | Primary CNS Lymphoma |
ABVD | doxorubicin, bleomycin, vinblastine, dacarbazine | HL |
Myelodysplastic Syndromes¶
Peter Hanna
Background¶
- MDS is a malignant clonal myeloid disorder resulting in ineffective (dysplastic) hematopoiesis leading to peripheral cytopenias and a risk of transformation to acute myeloid leukemia (AML)
- Usually idiopathic, a disease of the elderly (median onset at age 70)
- The WHO has several classification schemes for MDS
- Most important for classification is the percent of blasts in the bone marrow
- Note >20% blasts in marrow = AML. Thus MDS and AML are on a continuum
Presentation¶
- 50% asymptomatic; symptoms can include nonspecific but gradual fatigue, weakness
- Dysplastic cells do not work properly à infections and bleeding are more likely
- Macrocytic anemia is most common finding; followed by bicytopenia or pancytopenia
- Isolated neutropenia or thrombocytopenia are unusual but possible
- Ask about secondary causes
- Exposure to chemicals (benzene, crude oil/gasoline industry, cigarette smoke), chemotherapy, radiation
- Medications, alcohol use, chronic infections (HIV)
Evaluation¶
- Goal is to rule out reversible causes of dysplasia and cytopenias
- CBC w/differential, peripheral smear, B12, folate, HIV
- Consider copper and zinc
- Dysplastic changes on peripheral smear: hypogranulated/hyposegmented neutrophils, hypogranulated platelets and macrocytosis of RBCs
- Circulating myeloblasts can be seen
- Final diagnosis made by bone marrow biopsy
Management¶
- Molecular characteristics define the “risk” of the disease and dictates treatments
- Prognostic scoring tools: revised international prognostic staging system (R-IPSS)
- Management general paradigm
- Asymptomatic: with low-risk disease: monitoring
- Low-risk disease + symptoms due to anemia only: transfusions, erythrocyte stimulating agents, and treatment with Luspatercept
- MDS with isolated del(5q): treated with lenalidomide
- High-risk pts: treated with hypomethylating agents
- Only curative intervention: hematopoietic stem cell transplant (HSCT)
Myeloproliferative Neoplasms (MPNs)¶
Christina Snider
Background¶
- MPNs: chronic myeloid disorders caused by abnormal proliferation of mature bone marrow cell lineages (granulocytes, erythrocytes, or megakaryocytes)
- MPNs differ from myelodysplastic syndrome (MDS); cells in MPNs are normally developed (i.e. not dysplastic)
- Four “classic” MPNs: polycythemia vera, essential thrombocythemia, primary myelofibrosis and chronic myeloid leukemia (CML)
Polycythemia Vera¶
Background¶
- Polycythemia is a general term: Men = Hb/Hct > 16.5/49%; Women = Hb/Hct > 16/48%
- Relative polycythemia: concentrated H/H due to decreased plasma volume
- Diuretic use, vomiting, diarrhea; H/H should normalize with fluid resuscitation
- Absolute polycythemia: increased RBC mass
- Primary polycythemia: inherited/acquired mutation in RBC progenitor
- Secondary polycythemia: increase in RBC mass due to elevated serum EPO
- Hypoxia/cardiopulmonary associated (chronic pulmonary disease, R-to-L cardiac shunts, sleep apnea, obesity hypoventilation syndrome, chronic carbon monoxide poisoning, including heavy smoking)
- Kidney associated causes (following renal transplant, renal artery stenosis, hydronephrosis)
- Autonomous EPO production from an EPO-producing tumors (rare)
- Steroid Use
- Epidemiology: Median age of diagnosis is 60 years; 25% cases present at age <50 years.
- >95% PV pts have JAK2 V617F mutation, but JAK2 V617F mutation is not specific to PV and can be seen in other MPNs
Presentation¶
- Incidentally elevated H/H
- Splenomegaly, generalized pruritus (post-warm bath/shower), unusual thrombosis
- Erythromelalgia: intermittent occurrence of red, hot, painful extremities
Evaluation¶
- CBC w/ diff and peripheral smear
- EPO level
- Rule out secondary causes: sleep study, carboxyhemoglobin, steroids
- Peripheral blood screen for JAK2 V617F mutation
Management¶
- PV treatment aims to prevent thrombosis and bleeding events.
- Phlebotomy: maintain Hct <45% (one unit 500 mL decreases Hct by 3%)
- ASA 81 mg for thrombosis prevention and symptom control
- Hydroxyurea: indicated for high-risk pts (>60 years old or with history of thrombosis)
- Interferon-alfa, busulfan, or ruxolitinib: indicated in select high-risk pts
Essential Thrombocythemia (ET)¶
Background¶
- Clonal stem cell disorder with increased platelet counts (>450k/uL)
- Risks of thrombosis and hemorrhage
- Median age of diagnosis: 60 years. Twice as common in females.
Presentation¶
- Incidental thrombocytosis on CBC
- Splenomegaly, unusual thrombosis, and erythromelalgia
Evaluation¶
- Screen for conditions that cause reactive thrombocytosis: chronic inflammatory diseases, infections, bleeding/hemolysis, iron deficiency, post splenectomy
- CBC with smear (platelet anisocytosis) ranging from very small to giant platelets
- CMP, LDH, uric acid, iron studies
- BCR ABL1 testing should be sent to exclude CML
- Bone marrow bx with staining, cytogenetics, and molecular testing for JAK2, CALR, MPL mutations
Management¶
- Avoid ASA 81 in pts with platelet counts >1 million complicated by acquired von Willebrand syndrome due to increased risk of bleeding
Treatment of ET | ||
---|---|---|
Risk Score (IPSET-thrombosis) | Features | Treatment |
High | Hx of thrombosis and/or >age 60 with JAK2 V617F mutation | cytoreduction (target plt 100-400k) with hydroxyurea, systemic anticoagulation ±antiplatelet agent |
Intermediate | Age >60, no JAK2 V617F mutation, no history of thrombosis | |
Low | Age =<60 w/ JAK2 V617F mutation and no history of thrombosis | observation vs. daily ASA 81 |
Very low | Age=<60, no JAK2 V617F mutation, no history of thrombosis |
Primary Myelofibrosis (PMF)¶
Background¶
- Clonal proliferation of myeloid cells with variable morphologic maturity resulting in reactive marrow fibrosis and extramedullary hematopoiesis
- Least favorable prognosis out of MPN
Presentation¶
- Fatigue, weight loss, low grade fever, bone pain, and night sweats
- Marked splenomegaly ±hepatomegaly (due to extramedullary hematopoiesis)
Evaluation¶
- Smear: teardrop shaped RBCs (dacrocytes)
- Bone marrow biopsy: “dry tap” due to extensive reticulin and/or collagen fibrosis mutually exclusive mutations in JAK2, MPL, or CALR
Management¶
- Low risk pts: observe if asymptomatic
- Cure by allogenic HCT transplantation in young, high-risk pts
- Treatment of anemias include transfusion support
- Surgical splenectomy if abdominal pain or transfusion dependent anemia (used very infrequently)
Chronic Myeloid Leukemia (CML)¶
Background¶
- Definition: MPN characterized by the overproduction of myeloid stem cells that can differentiate
- Chronic phase:
- Fatigue, weight loss, bleeding
- Abdominal fullness and early satiety due to splenomegaly
- WBC typically >100k. Smear shows neutrophilic cells in all stages of maturation with <2% blasts
- Accelerated phase: Refractory leukocytosis, 10-19% blasts in peripheral blood or bone marrow, worsening peripheral basophilia, thrombocytopenia
- Blast phase = acute leukemia: >20% blasts in peripheral blood or bone marrow, extramedullary proliferation of blasts
Evaluation¶
- Typical findings in blood and bone marrow and confirmation of Philadelphia chromosome (BCR-ABL1 fusion gene) via conventional cytogenetics, FISH, or rt-PCR
Management¶
- Hydroxyurea can be used to reduce WBC while awaiting confirmation
- Oral tyrosine kinase inhibitors (TKI): Imatinib, dasatinib, nilotinib, and ponatinib
- Allogenic hematopoietic cell transplantation: curative option for pts in accelerated and blast phase, as well as young pts with chronic phase CML who do not respond to TKI therapy
Neutropenia & Neutropenic Fever¶
Jennifer Marvin-Peek
Background¶
- Neutropenia: absolute neutrophil count (ANC) < 1500
- Severe neutropenia: absolute neutrophil count (ANC) <500 (Use manual count if available)
Mechanism | Causes | Example(s) |
---|---|---|
Neutrophil production | Drug associated | - Cytotoxic or immunosuppressive agents - Methimazole, PTU, colchicine - Macrolides, bactrim, dapsone, vancomycin - Amphotericin, acyclovir, ganciclovir - TCAs, clozapine, carbamazepine, valproate - ACEI, digoxin, propranolol, procainamide |
Radiation exposure | ||
Malignancies | ||
Infection | - Hepatitis, HIV, EBV, CMV - Rickettsia, tularemia, typhoid, TB |
|
Nutritional deficiency | Vitamin B12, folate, copper | |
Other | Aplastic anemia, benign ethnic neutropenia | |
Redistribution | Splenomegaly | Margination and sequestration |
Congenital | Genetics | Benign ethnic neutropenia, familial neutropenia |
Immune destruction | Autoimmune | RA, SLE |
Other | Autoimmune neutropenia |
Management¶
- If ANC <500
- Check all lines/IVs for erythema and induration daily
- Check mouth for mucositis, mouth care after meals and before bed
- Assess for Neutropenic Fever and Complications – see below
- Evaluate for indications for prophylaxis – see below
- No evidence to support use of neutropenic diet
- No digital rectal exams or enemas/suppositories (risk of bacterial translocation)
Neutropenic Fever¶
Definition¶
- ANC <500 and T> 100.4 °F or 38.0 °C
- Neutropenic pts are unable to mount an adequate immune response and can become critically ill very quickly
- Do not wait for a temp re-check, you need to start antibiotics immediately
Evaluation¶
- Chest X-ray
- Two sets of blood cultures (one from PICC/port if present)
- Urinalysis AND urine culture (not the reflex order set)
- If diarrhea, get C. diff PCR
- If abdominal pain, get CT A/P with IV contrast
Management¶
- Empirically treat with cefepime
- Indications for vancomycin
- Hemodynamically unstable
- Severe mucositis
- Focal consolidation on CXR
- Erythema/induration around line
- Concern for skin/soft tissue infection
- GPCs in blood
- Fever continues >24h on cefepime
- Additional Coverage:
- If abdominal pain/diarrhea: Flagyl 500mg q8h
- Concern for C-diff: PO vancomycin 125mg q6h
- Still fevering on cefepime at 72 hrs (differs by attending): meropenem
- Fungal coverage: consider if risk factors (TPN) or persistent fevers (>72hrs)
- Micafungin 100 mg IV daily or voriconazole 200mg PO BID
Neutropenic Complications¶
Mucositis¶
- Can range from mouth soreness to severe erosions preventing eating/drinking
- Can become secondarily infected with Candida, HSV
- Management:
- Routine oral care with a soft toothbrush to remove plaque
- Oral rinses with saline and/or sodium bicarbonate
- Magic mouthwash for symptomatic relief (or viscous lidocaine at the VA)
- Typically recovers quickly when ANC > 500
- Management:
Neutropenic enterocolitis (typhlitis)¶
- Life-threatening bacterial translocation due to breakdown of gut-mucosal barrier
- Presentation: Abdominal pain + fever
- ± abdominal distension, nausea, vomiting, watery and/or bloody diarrhea
- Diagnosis: CT A/P with contrast, consider C. diff PCR if diarrhea
- Treatment
- Cefepime/Flagyl OR Zosyn
- If no perforation/abscess on CT scan, typically continue until 14 days after ANC recovers >500 and abdominal pain resolves
- Can change to cipro/flagyl once ANC >500
- If perforation/abscess: will need imaging to confirm resolution, and longer duration of abx
Neutropenic Prophylaxis¶
- Used if ANC is expected to be < 500 for > 7 days
Most Common Regimens | Alternatives | |
---|---|---|
Bacterial | levofloxacin 500mg daily (renally dosed) | cefdinir 300mg BID |
Viral | valacyclovir 500mg BID | acyclovir 400mg BID (renally dosed) |
Fungal | fluconazole 400mg daily | Posaconazole 300mg BID x2 days -> 300mg daily (AML induction for aspergillus) micafungin 50mg IV daily |
PJP (if steroids) | inhaled pentamidine 300mg qmonthly | dapsone (check G6PD) Avoid Bactrim (risk of myelosuppression) |
Filgrastim (G-CSF – Neupogen/Zarxio /Granix)¶
- Induces bone marrow production of neutrophils
- Dose: either 300mcg or 480mcg (rounded from 5 mcg/kg/day)
- Common side effects: fatigue, nausea
- PEG-filgrastim (Neulasta): long-acting version that is only given as an outpt
Oncologic Emergencies¶
Alex DeWeerd
Leukostasis¶
Definition:¶
- Hyperleukocytosis is a WBC count >100,000/microL most commonly in a patient with leukemia. Leukostasis is hyperleukocytosis + clinical symptoms of decreased tissue perfusion in end organs (CNS, lungs, heart, kidneys, etc)
Pathophysiology:¶
- Leukostasis is thought to be due to increased blood viscosity caused by a large population of leukemic blasts that are less deformable than mature leukocytes. As blasts increase in the blood, plugs of these more rigid cells form in the microcirculation and impede flow. The blast-endothelial cell interactions lead to endothelial cell damage, cytokine release, and subsequent hemorrhage and local hypoxemia within tissues most notably the CNS and lungs.
Presentation¶
- Primarily occurs with AML and ALL. This is not common with CLL or CML, which present with high leukocyte counts in the absence of a significant increased portion of peripheral blasts
- Respiratory: dyspnea, hypoxia (note CXR can show diffuse interstitial or alveolar infiltrates or may be normal)
- PaO2 by ABG often falsely low from WBC consuming O2 in vitro. Trust SpO2.
- CNS: headache, AMS, vision changes, dizziness, tinnitus, gait instability, neuro deficit
Evaluation¶
- CBC w/ diff and peripheral blood smear
- Imaging: CT head to evaluate neuro deficit and to check for ICH
- Chest X-Ray vs. CT chest to evaluate dyspnea and air space abnormalities
Management¶
- Call Hematology
- Emergent cytoreduction
- Leukapheresis: page Nephrology and place dialysis catheter.
- Hydroxyurea and chemotherapy per hematology fellow
- Transfer/admit to ICU
Tumor Lysis Syndrome (TLS)¶
Background¶
- Lysis of malignant cells either spontaneously or in response to chemotherapy causing release of K, Phos, nucleic acids, and cytokines
- Consequences:
- Hyperkalemia: most urgent and immediately life threatening
- Hyperphosphatemia: binds Ca and leads to CaPhos crystal deposition à AKI, HypoCa
- Hyperuricemia (from breakdown of DNA) à precipitation in renal tubules à AKI
- Hypocalcemia: can cause mental status changes, neuromuscular irritability/spasms
- Hypotension, AKI from cytokine release
- TLS labs
- Uric acid ≥ 8, Ca2+ ≤ 7, K+ ≥ 6, or PO43- ≥ 4.5 OR
- >25% change from baseline in these values
Evaluation¶
- Risk Stratification:
- Highest risk after starting chemotherapy, but can occur spontaneously
- Highest risk if rapidly progressive, chemo-sensitive, myelo or lymphoproliferative disease; bulky disease, extensive organ/marrow infiltration
- Tumor characteristics which confer a higher risk of developing TLS
- High (>5% risk): ALL (WBC> 100K or LDH 2x ULN), AML (WBC> 100K), Burkitt’s (III/IV or LDH≥2xULN, DLBCL with bulky disease, intermediate risk + AKI/CKD
- Intermediate: ALL (WBC<100K, LDH <2x ULN), AML (WBC 25-100K), Burkitt’s LDH<2x ULN), DLBCL (non-bulky, LDH>ULN), CLL (if tx with fludarabine, rituximab, lenalidomide, or venetoclax +LN 5-10 cm or ALC≥25K), plasma cell leukemia, rare chemo-sensitive solid tumors (small cell)
- Low: all others
Management¶
- Prevention:
- High risk: q6-8h TLS labs, IVF (±loop diuretic if volume overload), allopurinol, ± rasburicase
- Intermediate – q8h TLS labs, IVF, allopurinol
- Low – daily TLS labs, IVF
- IVF: goal to maintain UOP 80-100 mL/hr
- Allopurinol: 300 mg PO BID for CrCl > 20 mL/min, UpToDate renal dosing if lower
- Rasburicase ($$$): contraindicated in G6PD (send G6PD if not urgent and AA, Asian or Jewish descent)
- Given if uric acid > 8 mg/dL. Get fellow approval before ordering
- Treatment: (Can use as night/cross cover handoff)
- K+ > 5.5: STAT EKG, lokelma 10g TID, 10 U insulin+ 1 amp D50
- If EKG changes, then calcium gluconate and D5W at 100 mL/hr with repeat BG in 1 hr
- Uric acid > 8 with 25% change from baseline: page hematology fellow to discuss rasburicase
- PO4 > 4.5 with 25% change from baseline: start/↑ phos binder (sevelamer)
- IV calcium: do not administer unless symptomatic AND hyperphosphatemia is corrected
- With high phos, IV calcium can lead to calcium deposition and renal failure
- Hemodialysis: may be necessary if poor renal function and/or anuria. Consider Nephrology consultation early if worsening Cr, refractory symptoms, or refractory electrolyte abnormalities.
- K+ > 5.5: STAT EKG, lokelma 10g TID, 10 U insulin+ 1 amp D50
Superior Vena Cava (SVC) Syndrome¶
Background¶
- Commonly associated malignancies: lung cancer (NSCLC or SCLC), Non-Hodgkin or Hodgkin lymphoma, mediastinal germ cell tumors, thymic malignancies
- Partial or complete obstruction of the SVC impedes blood return from the upper extremities, head, neck, and brain resulting in upstream congestion
- Can be secondary to a mass in the mediastinum or thrombosis (e.g. foreign body, central venous catheter)
Presentation¶
- Facial or neck swelling without generalized edema
- Sense of head fullness, exacerbated by leaning forward or lying down
- Pulmonary: dyspnea, stridor, hoarseness, cough (due to edema narrowing the nasal passages and larynx or mechanical airway obstruction)
- Physical exam
- Facial/neck edema particularly of the eye lids in the morning, distended neck and chest veins
- Can also sometimes see upper extremity swelling, papilledema, plethora
- Look for associated lymph node enlargement anywhere particularly including supraclavicular, cervical, and axillary region
Evaluation¶
- CXR: may show mass, perihilar or mediastinal disease, mediastinal widening, or pleural effusion
- Contrasted CT scan ± CT Venography: phased to get a view of clot contribution to obstruction to guide decision regarding anticoagulation or stenting
- Radiology attending can coordinate with techs (requires verbal direct request)
- MRI/MRV may provide additional information (often not possible due to pt too sick)
- Non-malignant causes on the differential: post-radiation fibrosis, fibrosing mediastinitis (can be seen from prior infections such as histoplasma, TB, nocardiosis, aspergillus, blastomycosis), central AV fistula
Management¶
- Assess airway and prepare for intubation if needed
- Keep head of bed elevated
- Thrombosis:
- Removal of lines/catheters associated with thrombus
- Consideration of anticoagulation
- Tumor compression: the type of tumor guides treatment (tissue biopsy is key)
- Stat/urgent consultations:
- Interventional radiology: possible stenting/dilatation (Fastest modality, if available)
- Radiation oncology: radiation therapy (Takes days to weeks to work)
- Medical oncology: help with diagnosis and chemotherapy (Fast if highly chemo-responsive cancer
- Interventional pulmonology: help with tissue dx
Spinal Cord Compression¶
Background¶
- Malignancies where cord compression is most commonn
- Multiple myeloma, lymphoma (both Hodgkin and NHL); lung, breast, and prostate cancer
- Tumor mass, compression, and often displaced bone -> occupies the epidural space and impinges the thecal sac or nerve roots of the spinal cord or any spinal nerves including the cauda equina. This can lead to edema of the spinal cord white and gray matter, which eventually leads to infarction of the cord. This vasogenic edema is where glucocorticoids can play a role.
Presentation¶
- Back pain (most often initial symptom, typically worse at night), motor, or sensory deficits
- Cauda equina syndrome: bowel or bladder incontinence, ataxia
Evaluation¶
- Neurologic exam with sensation testing seeking level below an identified dermatome
- Back pain that exacerbated by movement -> mechanically unstable spine until proven otherwise (requires surgical evaluation and potential stabilization)
- Lab testing: If no known malignancy check CBC, CMP, SPEP, and (in males) PSA
- Bladder U/S if suspicion or retention with or without overflow incontinence
- If suspected, order whole spine MRI w and w/o contrast. If pt unable to have MRI, CT myelography may be considered.
Management¶
- Immediate high dose steroids: give dexamethasone to minimize mineralocorticoid effects. Most common dosing is 10mg IV x1 followed by 4mg PO or IV q6h
- Consider stat/urgent consultation with:
- Spine Team (Neurosurgery or Orthopedic surgery holds pager): consult early, ask for an operative plan from them ASAP. Affects other possible interventions.
- Radiation oncology: one of the rare cases where overnight radiation would be considered. Requires that patient is able to lie flat for a CT simulation (rad onc orders this), and rad onc cannot proceed until Spine surgery makes a definitive call about whether or not to operate first
- Medical oncology: help with diagnosis and chemotherapy
- Ensure regular neuro-vascular checks and close monitoring
Brain Metastases¶
Background¶
- Common malignancies: Lung (NSCLC), breast, kidney, colorectal carcinomas, and melanomas
- Significantly more common than primary brain tumors
- 80% of brain metastasis occur in the cerebrum at grey/white matter junction via hematogenous spread (smaller blood vessel diameter at the junction essentially traps tumor cells)
Presentation¶
- Highly variable: so consider brain mets any cancer pt with neurologic or behavioral changes
- Headache: worse in the mornings, with bending over or with Valsalva
- Nausea/vomiting
- Cognitive dysfunction: changes in memory, mood or personality
- Neuro: focal neurologic deficits, seizures, stroke (particularly melanoma, choriocarcinoma, thyroid, and renal carcinomas)
- Signs of elevated ICP: papilledema, vision changes, drowsiness, presyncope Evaluation
- STAT CT if concerned for stroke or elevated ICP
- MRI with contrast: most sensitive, can differentiate between metastases vs. other lesions
- Suggestive features: multiple lesions, location, circumscribed margins, vasogenic edema, contrast enhancement
- If pt has no known primary tumor: consider CT C/A/P ± PET to identify primary
- Biopsy with histopathology and IHC: if diagnosis in doubt or if only a single lesion is present
Management¶
- If severe HA, N/V, focal neuro deficits: systemic glucocorticoids
- Dexamethasone 10mg IV x1 followed by 4mg IV q6h (or PO if tolerated)
- Stat/urgent consults:
- Neurosurgery: diagnostic/therapeutic intervention. Note they will need a tissue diagnosis ASAP if not known; except in cases of emergency; affects operative plan.
- Radiation oncology: will also need tissue diagnosis, and will have to coordinate with neurosurgery about timing of surgery versus radiation. Patient must be able to lie flat; they will need a CT simulation if radiation is to be offered.
- Medical oncology: help with diagnosis and chemotherapy. Evolving systemic therapies can be effective for controlling metastatic disease to the brain, particularly with melanoma and NSCLC subtypes (ALK, EGFR)
- Ensure regular neuro-vascular checks and close monitoring
- Do not perform LP without input from neurology
Pancytopenia¶
Matthew Lu
Background¶
- Pancytopenia is a decrease in all peripheral blood lineages (RBC, WBC, PLT). Many causes of pancytopenia can also cause bicytopenia, so bicytopenia is often worked up in a similar manner
Framework for differential¶
- Impaired production
- Bone marrow infiltration/replacement
- Hematologic malignancies (Acute leukemias, lymphoma, etc.), metastatic solid tumors, myelofibrosis, MDS
- Infections: TB, NTM, Fungal
- Bone marrow suppression/aplasia
- Vitamin/nutritional deficiencies: B12, folate, copper (can be caused by zinc toxicity)
- Aplastic anemia (AA)
- Infection: HIV, hepatitis, parvovirus B19, EBV, CMV, tick-borne
- Medications (see below)
- Toxins: ethanol
- Sepsis
- Peripheral destruction
- TMA syndromes: TTP, HUS,
- Autoimmune hemolytic
- Evan’s syndrome (idiopathic or secondary)
- Autoimmune disorders: SLE
- Myelo- or lymphoproliferative disorders: CLL, CML, multicentric Castleman’s
- Infection: EBV, CMV, HIV, hep B, hep C
- Sequestration (splenomegaly)
- Combined process: PNH (associated with AA), SLE, malignancies, HLH, Crohn’s, infections
Evaluation¶
- HPI: B-symptoms, fatigue, dyspnea, infections, bleeding/bruising
- Medications
- NSAIDs, anti-epileptics, chemotherapy, antimicrobials/antivirals (Bactrim, valganciclovir, linezolid, RIPE therapy), immunosuppression (MMF, azathioprine, tacrolimus), anti-gout (allopurinol, colchicine), anti-thyroid (methimazole)
- PMHx: autoimmune disease (SLE, RA, Scleroderma), radiation, gastric surgery, malabsorption (e.g. celiac, Crohn’s), liver disease, malignancy, transplant
- Social Hx: EtOH use, malnutrition, occupational exposures, exposures to TB, leishmaniasis, or ticks
- Exam: lymphadenopathy, hepatosplenomegaly, neuropathy, rashes, petechiae, stigmata of liver disease, cachexia, oral lesions
- Diagnostic studies
- CBC w/ diff, peripheral smear, IPF, reticulocyte count
- TMA/DIC labs: PT/PTT/Fibrinogen, CMP, LDH, haptoglobin, smear
- Viral studies: hepatitis B/C, EBV, CMV, HIV, parvovirus B19
- Infectious work up (as clinically indicated): non-invasive fungal, Quant-gold/AFB, Anaplasma/Erhlichia PCR, RMSF
- Nutritional studies: B12, folate, copper, zinc, iron
- Abdominal ultrasound (for splenomegaly)
- HLH (as clinically indicated): ESR/CRP, ferritin, triglycerides, soluble IL-2R, biopsy (liver or bone marrow)
- Autoimmune (as clinically indicated): ANA w/ reflex, C3/C4, ESR/CRP
- Can consider: flow cytometry, bone marrow biopsy, cytogenetics and FISH (typically driven by hematology recs)
Management¶
- Emergencies that may require urgent evaluation, management, or hospitalization
- Febrile neutropenia (ANC < 500), symptomatic anemia (cardiac symptoms), platelets < 10k or < 50k with bleeding, abnormal blood smear (schistocytes or blasts)
- When pancytopenia is slow, progressive over time, or acute without any other precipitating factors and a specific etiology is in mind (e.g. HLH or marrow infiltrating infection), consult hematology for consideration of bone marrow syndromes and/or bone marrow biopsy
- Note: Bone marrow biopsy for acquired pancytopenia in the hospital setting often will not yield results that will change clinical management (I.e. most likely will just show an aplastic marrow)
Paraneoplastic Syndromes¶
Bailey DeCoursey, Justin Lo
Hypercalcemia of Malignancy¶
Background¶
- Caused by PTHrP production, osteolytic lesions, and/or rarely exogenous Vit D
- PTHrP: breast cancer, NSCLC (squamous)
- Osteolysis: multiple myeloma, Breast Cancer;
- Exogenous vit D: lymphoma
Evaluation¶
- Correct [Ca2+] for hypoalbuminemia: [Ca2+] + 0.8 x (4.0 – albumin)
- Send basic hyperCa+2 work-up: PTH, vit D, etc (see “Hypercalcemia” section)
- PTHrP is called “Parathyroid Hormone-related Peptide-ARUP” in Epic
Management¶
- First line: IVF without calcium such as Normosol; goal urinary output of 150-200 mL/hr
- Strict I/Os: cautious IV fluids in pts with cardiac or renal dysfunction
- Add Furosemide if hypervolemic (do not empirically start)
- Second line: zoledronic acid 4mg IV (takes 24-48 hours to see effect)
- AMS or severe hypercalcemia (>14mg/dL): calcitonin 4 IU/kg (requires attending approval)
SIADH¶
Background¶
- Euvolemic hypotonic hyponatremia with urine sodium >20 and typically urine Osm >100
- Associated with: SCLC (most common), head/neck cancers, breast cancer
- See "Hyponatremia” section for additional information
Management¶
- Free water restriction to 800mL/day
- Refractory: salt supplementation (e.g. salt tabs) ± loop diuretic
Carcinoid Syndrome¶
Background¶
- Episodic flushing, diarrhea, wheezing/SOB due to secretion of histamine & serotonin
- Most common: Neuroendocrine tumors, GI (often with mets to liver and lung)
Evaluation¶
- Urine: UR 5-HIAA (ARUP)
- Imaging to identify tumor(s): CT C/A/P
Management¶
- Short-term treatment: subQ or IV octreotide (see UpToDate for dosing)
- Antidiarrheals (Imodium, Lomotil) to slow transit
- Long-term treatment: depot (IM) forms of octreotide and lanreotide
Autoimmune Encephalitis, Encephalomyelitis, and Myelitis¶
Background¶
- Encephalopathy (limbic or brainstem) ± myelitis (limb ataxia, sensory deficits)
- Associated with small cell lung cancer and checkpoint inhibitor therapy
Evaluation¶
- LP: make sure to order CSF oligoclonal bands and CSF IgG index
- “Paraneoplastic AutoAb Eval-MAYO” (add "CSF" to the front of the order name if for LP)
- NMDA-R can be ordered as a standalone test
- CT head
- EEG if concern for subclinical seizures
Management¶
- Consult Neurology for possible immunosuppressive therapy (steroids, IVIG)
Lambert-Eaton Myasthenic Syndrome (LEMS)¶
Background¶
- Muscle weakness due to autoantibody against calcium channels resulting in ↓ ACh release
- Associated with SCLC (most common) & lymphoma
- See “Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS)” section in Neurology
Plasma Cell Dyscrasias¶
Rahul Shah, Jennifer Marvin-Peek
Background¶
- A heterogenous group of benign, premalignant, and malignant conditions characterized by clonal proliferation of plasma cells
- Results in over-production of monoclonal immunoglobulins or polypeptides (e.g. M-protein) that can be detected in serum and/or urine
- Includes monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), multiple myeloma (MM), Waldenstrom’s macroglobulinemia (WM), extra-medullary plasmacytoma, AL amyloidosis, POEMS syndrome
- Spectrum of MGUS, SMM, and MM represents natural progression of same disease process
- Complications: increased infectious risk, cytopenias, renal failure, hyperviscosity syndrome, malignant hypercalcemia, pain crisis from bony disease
- Elevated gamma/protein gap (serum total protein minus albumin >4) often prompts work-up for an underlying plasma cell dyscrasia (high specificity but low sensitivity)
Symptoms | Signs |
---|---|
Fatigue, weakness, weight loss Bone pain Paresthesias, neuropathy, radiculopathy Visual disturbances(if hyperviscosity present) Lymphadenopathy (uncommon) Fever (uncommon) |
Anemia (Hgb <10) 10>Renal insufficiency (Cr > 2) Hypercalcemia (Ca > 11.5) Elevated protein gap (Total protein - Alb > 4) Osteolytic bone lesions (typically central) Unexplained heavy proteinuria Rouleux formation on blood smear |
Evaluation¶
- CBC w/ diff, peripheral blood smear, CMP (for Ca, Cr, albumin), LDH, CRP, urinalysis
- SPEP with immunofixation, UPEP (24-hour urine) with immunofixation, serum free light chains (FLC)
- Quantitative immunoglobulins (IgA, IgM, IgG, IgD, IgE)
- If Hgb <10, Cr >2, Ca >11.5, M-protein >1.5, non-IgG M-spike, abnormal FLC ratio:
- Bone marrow biopsy + cytogenetics
- β2-microglobulin, serum viscosity (in WM)
- Skeletal imaging to identify bone lesions: skeletal survey (x-ray) often done initially, then more sensitive CT/PET-CT/MRI if biopsy shows SMM/MM
- If considering amyloidosis: abdominal wall fat pad biopsy with Congo red staining typically sufficient vs. direct biopsy of amyloid-involved tissue
Additional Tips for Lab Interpretation | ||
---|---|---|
SPEP/UPEP | Free light chains (FLC) | Urinalysis |
Initial screening test to look and quantify M-protein Serum immunofixation determines clonality (e.g. mono or polyclonal) Monoclonal spike >1.5 is indicative of underlying dyscrasia Polyclonal spike suggests infectious, inflammatory, or reactive etiology |
Ratio of kappa/lambda >3 highly suggestive of plasma cell dyscrasia or amyloidosis Ratio 1.65 to 3 can be due to infectious process or renal insufficiency Helpful in pts that only produce Bence-Jones protein (FLC w/o heavy chain) which isn’t seen on SPEP |
Detects albumin, not light chains In myeloma cast nephropathy, dipstick will be negative since proteinuria is from FLC (i.e. Bence-Jones proteinuria) In AL amyloid, dipstick will be positive 2/2 albumin loss from nephrotic syndrome |
MGUS | SMM | MM | |
---|---|---|---|
% Plasma Cells in BM | <10% | 10-60% | ≥ 10% (typically >30%) |
Monoclonal Protein | IgG, IgA, IgM: 1.5 -3 | IgG or IgA >3 | IgG or IgA >3 |
Laboratory studies | Normal Hgb, Ca, Cr | Normal Hgb, Ca, Cr | ↓Hgb, ↑Ca, ↑Cr |
Symptoms | None | None | Lytic bone lesions, fatigue |
Prognosis | 1% / year progression to MM | 10% / year progression to MM | R-ISS staging (see below) |
Monitoring and/or Treatment | Monitoring only
Yearly: Symptom check SPEP, FLC, CBC, BMP |
Monitoring only
In 2-3 months, repeat SPEP, FLC, CBC, BMP Yearly skeletal survey |
Chemotherapy, plus SCT for eligible pts |
Multiple Myeloma¶
Evaluation¶
- Diagnosis requires clonal bone marrow plasma cells ≥10% or bony/extramedullary plasmacytoma AND one or more end-organ event (CRAB criteria) or biomarker of myeloma
- CRAB criteria
- Hypercalcemia, renal impairment, anemia, bone osteolytic lesions
- Biomarkers of multiple myeloma
- Clonal bone marrow plasma cells ≥ 60%
- Serum FLC ratio ≥ 100 or ≤ 0.01
- >1 focal lesion ≥ 5mm on MRI
- >Skeletal imaging: whole-body PET-CT or CT preferred, MRI, bone survey (x-ray)
Management¶
- First-line induction therapy typically is RVd: immunomodulatory agent (lenalidomide [Revlimid]), proteasome inhibitor (bortezomib [Velcade]) and dexamethasone
- Consolidation therapy includes autologous SCT for transplant eligible pts
- Maintenance therapy is often given indefinitely, typically lenalidomide or bortezomib
- Relapsed disease is often treated with anti-CD38 monoclonal Ab (daratumumab) with a steroid and either immunomodulatory drug or proteosome inhibitor; CAR-T also recently approved for relapsed MM
- Supportive Care
- VTE prophylaxis with DOAC or LMWH if on an immunomodulatory agent with 2 VTE risk factors; if only 0-1 VTE risk factors à aspirin
- EPO and G-CSF for treatment-related anemia and neutropenia
- Bisphosphonate (ideally zoledronic acid) to reduce risk of fractures; analgesia ± radiotherapy for bone pain and palliation
- (Val)acyclovir if on bortezomib for VZV prophylaxis
Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia (IgM)¶
Presentation¶
- Hyperviscosity syndrome: blurred vision, dizziness, diplopia, hypoxia, ataxia, vertigo, stroke, coma
- Peripheral neuropathy
- Retinal changes: dilated veins, hemorrhages, papilledema
- Cryoglobulinemia: large IgM complexes precipitate out in the cold, causing Raynaud's, urticaria, purpura, acral cyanosis, tissue necrosis
Evaluation¶
- Requires: IgM monoclonal gammopathy on SPEP, BM biopsy with ≥10% lymphocytes with plasmacytoid differentiation (late stage B-cell differentiation), and MYD88 mutation
- CBC, coagulation studies, cryoglobulins, IgM, β2-microglobulin
- Serum viscosity: If <4 symptoms are rare, If >6 typically symptomatic.
Management¶
- Asymptomatic pts managed with close observation
- Symptomatic hyperviscosity is treated with plasmapheresis
- Induction: may include bendamustine ± rituximab if IgM level is <4000 (rituximab can temporarily ↑ IgM and ↑ risk of hyperviscosity syndrome)
- Monitor response with: IgM levels, monoclonal IgM on SPEP
Other Plasma Cell Dyscrasias¶
Light Chain (AL) Amyloidosis¶
- Extracellular deposition of misfolded light chains (most commonly kidney and heart)
- Features: nephrotic syndrome, restrictive cardiomyopathy, peripheral neuropathy, HSM, macroglossia, easy bruising/bleeding, dysautonomia/orthostasis
- Diagnosis
- Need ALL 4: amyloid related systemic syndrome, positive congo red staining on any tissue, evidence that amyloid is light chain related, evidence of monoclonal plasma cell disorder
POEMS Syndrome¶
- Cause unknown, possibly chronic overproduction of pro-inflammatory cytokines such as VEGF
- Features: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (usually λ light chain), Skin changes
- Diagnosis:
- Mandatory criteria: peripheral neuropathy, monoclonal plasma cell disorder
- Major criteria (need ⅓): osteosclerotic lesions, VEGF, Castleman disease
- Minor criteria (need ⅙): organomegaly, volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis or polycythemia
Castleman Disease¶
- Angiofollicular lymph node hyperplasia
- Antibodies to HHV-8 implicated in >50% of cases
- Features: lymphadenopathy, fever, night sweats, fatigue, fluid accumulation, violaceous lymph node biopsy w/characteristic hematopathology papules
Indications for Inpt Radiation Oncology Consultation¶
Jayden Gracie
Initial Considerations:¶
- Is this really cancer? Must have a tissue diagnosis prior to consultation
- Is problem urgent? Clinic opens at 7:30am, so do not consult until after 7:30am unless emergent
- Urgent conditions (Inpt consultation indicated, weekend treatment unlikely)
- Rule of thumb: true emergencies (label consult, 'Urgent,' may treat even on a weekend)
- Spinal cord compression
- Airway collapse from mass effect
- Life-threating hemorrhage from mass
- Symptomatic brain mets (seizures, FND, etc.)
- Anaplastic thyroid cancer
- Pain crisis from bone metastases
- Requiring rapid turnaround: keloids (post-surgical for keloid prevention), heterotopic ossification)
- Everything else is generally treated outpt. Order an ambulatory referral for those pts.
- For pts whose outpt radiation gets interrupted by admission, no need for consult. Page Rad-Onc to close the loop.
- If in doubt, page Rad-Onc to discuss prior to placing consult.
- Have non-radiation interventions been discussed with the team/consultants first?
- Airway compromise: first consult IP/ENT for stent placement/trach
- Cord compression or symptomatic brain mets: consult Neurosurgery for possible intervention
- Spinal instability/pathologic fracture: calculate a Spinal Instability Neoplastic Score (SINS). If >6, consult Spine to assess for instability and surgical candidacy. They must have an attested note prior to radiation planning. Not that radiation helps with tumor pain but does not help with instability or pain from the fractures themselves.
- SVC syndrome: Consult IR for emergent percutaneous stent placement if 4_ points on Kishi scoring system. Engage Med Onc since chemo has a faster effect (especially in SLCL) than radiation (days). Consider surgical consult if concerned for thymoma
- Is the pt fit enough for radiation? Common precluding factors:
- Pt is too unstable
- Cannot lie flat or stay still for 10 min of treatment, 30min-45min for planning (delirium, dyspnea, uncontrolled pain, seizing)
- Head/neck radiation requires a facemask; claustrophobia should be addressed prior (benzos)
Pre-consultation workup:¶
- Brain mets
- If symptomatic, dexamethasone 10mg IV load followed by 4mg q6 thereafter (with PPI). Rad onc can help with taper plan. Do not stop during active treatments.
- MRI with and without, labelled 'Cmelak Sequence' in comments section. May also be a 'For Radiation Planning' box.
- CSF sampling if suspicious of leptomeningeal spread
- DO NOT stop keppra If already onboard for seizures.
- Spine mets
- Damage becomes irreversible around 48 hours from symptom onset. Do not delay treatment and consultation (spine, rad onc, etc.).
- STAT MRI with and without contrast.
- Dexamethasone 10mg IV load followed by 4mg q6 thereafter (with PPI). Rad onc can help with taper plan. Do not stop during active treatments.
Logistical Considerations¶
- Treatment planning takes several days to plan except in urgent/emergent circumstances.
- Rad-Onc arranges ALL TRANSPORT for their pts. No need for primary team to do anything.
- Pts must get a “CT sim” image in Rad-Onc department before starting any treatment.
- Let Rad-Onc know if pts are going for other procedures/imaging on a treatment day, or if pt is refusing treatment.
- Radiation plans cannot be transferred into or out of the Vanderbilt system. Let Rad-Onc know a few days in advance if transfers between Vanderbilt centers will be needed.
- Pts cannot get radiation at 90% SNFs. Radiation must be completed prior to dispo.
- Most CLCs do not transfer pts back and forth to radiation treatments, so if planning to discharge to CLC, radiation needs to be finished inpt or start after the CLC.
- In general, most curative RT treatments take several weeks. Most palliative regimens take 1-10d.
Radiation at the VA¶
- Pts need prior authorization before Rad-Onc is allowed to see VA pts at VUMC. To obtain PA, consult Med Onc and email Dr. York (medical oncologist at the VA). This may take a couple days. For Emergent cases, you do NOT have to wait on the PA. Rad-Onc can arrange for transport.
- Rad-Onc attendings do not have access to the VA system. Notes will be in VUMC system.
Radiation Toxicity¶
Jayden Gracie
Radiation pneumonitis¶
- 6 weeks to 6 months after RT to chest
- Presents like pneumonia with cough and SOB, so need to rule out PNA
- Imaging: chest X-ray or CT
- Treatment: steroids
Radiation dermatitis¶
- Onset during or shortly after treatment
- Variable: redness, dry desquamation (peeling, dry skin), or wet desquamation (blistering and oozing)
- Treatment
- Aquaphor or Aquaphor + lidocaine
- Lidocaine can sometimes burn over wet desquamation. For wet desquamation (especially if looks potentially infected), start on Silvadene until it dries up. Then add non-adhesive barrier dressings.
- Topical corticosteroids are helpful for itching (e.g. OTC hydrocortisone)
- Sitz baths and peri bottles useful for perineal skin reaction after RT to chest.
Mucositis¶
- Treatment
- Salt water and baking soda rinses to help clear debris out of mouth.
- Magic mouthwash, swish and spit if mouth only (as many times a day as they want) or swish and swallow up to every 4h. Can give viscous lidocaine if pt prefers.
- For weight loss >15lbs during treatments: consider G-tube but want to avoid if possible since slows swallowing function recovery
- Can try soft or liquid diet, protein drinks
- For esophagitis, can order carafate liquid formulation (to coat esophagus). May require prior auth, indication is radiation esophagitis. Consider PPI
Secretions and mouth dryness¶
- Glycopyrrolate or Mucinex can help with thick secretions but can be drying.
- Baking soda and salt, sugarless gum
- Can try Levsin, scopolamine patches.
Nausea¶
- Evaluate for and treat constipation, secretions, and acid reflux
- Zofran is 1st line followed by compazine
Pain Flares¶
- Present with treatment of bony mets in up to 40% of pts. Spikes in pain usually occur either toward the end of treatment or a few days after due to inflammation.
- Treat with steroid taper per Rad-Onc
Radiation-associated dysuria¶
- Presents with UTI-like symptoms during treatment.
- Rule out UTI
- Treatment: Hydration. Can try NSAIDs and phenazopyridine (note urine color change). Consider short steroid course next.
Bowel toxicity¶
- Upper: nausea/vomiting, loose/watery stools.
- Lower: loose/watery stools, cramping, tenesmus, urgency
- Treatment: Try low residue diet, anti-diarrheal agents (Imodium, Lomotil), sucralfate, protozoa/5-ASA enemas
- Consider cessation or break of RT
Sickle Cell Crisis¶
Michael J. Neuss
Background¶
- Present with severe pain in bone, joints, chest, abdomen
- Causes: (HIDISC) Hypoxia, Ischemia, Dehydration, Infection, Stress, Cold
- Can’t miss:
- Acute chest: new infiltrate on CXR + another clinical symptom (fever, chest pain, hypoxia). Consult Benign Hematology immediately. Do not wait until the next day.
- PE (ACS less likely in these pts), avascular necrosis of hip, priapism, stroke
Evaluation¶
- Labs: ↑ LDH, Hgb/Hct (low; check versus baseline), retic, smear, WBC
- If febrile: UA + blood cultures
- Hgb S level only in certain circumstances (e.g. guides treatment in acute chest)
- Imaging: CXR, MRI for hip pain, abdominal U/S or CT abdomen
- Maintain active type and cross given probability of alloimmunization
Management¶
- General
- Look for a care coordination yellow note in the Summary Tab
- Heme clinic will have specific management preferences for individual pts
- Maintain hydration, IVF at 150-200 cc/hr (if no contraindication)
- Oxygen: goal sat ~95% (higher O2 goal will help to prevent further sickling)
- Continue folic acid 1 mg QD
- Continue hydroxyurea if uncomplicated pain crisis
- Hold if counts suppressed or concern for infection
- If in the MICU: consider discussion for plasma exchange (if Hgb SS or SC or S-Thal)
- Transfuse: Simple transfusion if Hgb lower than baseline and/or complications
- Avoid transfusions when able, given risk of antibody formation
- Look for a care coordination yellow note in the Summary Tab
- Pain
- Will generally require opiates, often initiation of PCA
- All SS pts should have pain plans. Inpt pain plans are in the problem list under sickle cell disease or in the care coordination section of Epic
- Outpt plans (to which you will transition pts back prior to discharge) are not standardized in location, but can be under Media (with a pain contract) or found in notes
- Acute chest:
- Consult Hematology at time of admission
- Obtain HbS level
- Avoid dehydration. Consider LR @ 125-200 cc/hr but caution with overhydration (may worsen pulmonary edema)
- Incentive spirometry: atelectasis and hypoxia drive V/Q mismatching and further sickling
- Transfuse hgb to goal of 10 (do not exceed to avoid hyperviscosity)
- Pain control per pain plan
- Consider Abx for CAP (vs HAP if risk factors)
- Plasma exchange for moderate-severe cases (driven by hematology)
Therapy Toxicities¶
Rahul Shah
Immune Checkpoint Inhibitor Toxicities¶
- Immune checkpoint inhibitors augment the endogenous immune response against tumors, which may lead to autoimmune-like toxicities, known as immune-related adverse events (irAEs)
- Treatment: low-dose glucocorticoids (prednisone, 0.5 mg/kg) for mild adverse events, high dose glucocorticoids (prednisone, 1-2 mg/kg) for severe adverse events
Adverse Event Type | Incidence with anti-CTLA-4 (e.g. ipilimumab) |
Incidence with anti-PD1/PD-L1 (e.g. nivolumab, pembrolizumab) |
---|---|---|
Skin (rash, pruritus, TEN) | 30% | 30% |
Colitis | 25% | 5% |
Hypothyroidism | 20% | 20% |
Hepatitis | 10% | 1% |
Hypophysitis | 10% | rare |
Pneumonitis | 2-5% | 2-5% |
Myocarditis | <1% | <1% |
Neurotoxicity (GBS, myasthenia gravis, encephalitis) | <1% | <1% |
Cytotoxic Agent Toxicities¶
Class | Agent | Side Effect |
---|---|---|
Alkylating agents | busulfan | pulmonary fibrosis or diffuse alveolar hemorrhage |
cyclophosphamide | myopericarditis, hemorrhagic cystitis (prevention: hydration; monitoring: daily UA, tx: mesna) | |
ifosfamide | encephalopathy (tx: methylene blue), nephrotoxicity, hemorrhagic cystitis | |
Antimetabolites | 5-Fluorouracil (5-FU)/ Capecitabine (metabolized to FU) | myelosuppression, coronary vasospasm, palmar-plantar erythrodysesthesia, mucositis |
cladribine, pentostatin | dose reduced for CrCl | |
cytarabine (Ara-C) | irreversible cerebellar ataxia (if high dose, neuro checks required), conjunctivitis (prevent with prophylactic steroid eye drops) | |
gemcitabine | transient transaminitis, peripheral edema, rash, rarely: pulmonary toxicity, hemolytic uremic syndrome, capillary leak syndrome | |
methotrexate | stomatitis, hepatotoxicity, renal failure, high dose requires leucovorin | |
Antitumor antibiotics | anthracyclines (doxorubicin, daunorubicin, idarubicin) | HFrEF (need TTE prior). Most notable with doxorubicin. |
bleomycin | Pulmonary fibrosis. Potentiated with G-CSF | |
Monoclonal antibodies | alemtuzumab | severe and prolonged cytopenias |
bevacizumab | HFrEF, HTN, hyperglycemia, hypomag, DVT, pulm hemorrhage, GI bleeding/fistulas/perforation, wound healing complications | |
rituximab | hypophos, hepatotoxicity, HBV reactivation (screen all pts), peripheral neuropathy; transfusion reaction during 1st time infusion | |
Platinum agents | cisplatin, oxaliplatin, carboplatin | Nephrotoxicity, worst with cisplatin. Rental tubular acidosis. Neurotoxicity (parasthesias, cold sensitivity, cramps, peripheral neuropathy), ototoxicity (high frequency hearing loss), constipation, hypomag |
Taxanes | docetaxel, paclitaxel | hypersensitivity reaction (often require premedication with steroids and H1/H2 blockers); peripheral neuropathy |
Topoisomerase inhibitors | irinotecan, topotecan, etoposide | irinotecan- acute diarrhea can be treated with atropine; delayed with atropine |
Tyrosine kinase inhibitors | imatinib, dasatinib, nilotinib, bosutinib | QTc prolongation, pulmonary effusion, hepatotoxicity |
Vinca alkaloid | vincristine | peripheral neuropathy and ototoxicity (vestibular system lost first) |
Thrombocytopenia¶
Spencer Lessans
Background¶
- Classified as either mild (100K-150K), moderate (50K-99K), or severe (<50K)
- Can be divided into different causes
- Decreased platelet production
- Decreased TPO: Cirrhosis
- Bone marrow suppression: sepsis, EtOH, infections (HIV, tick-borne [RMSF, anaplasma, erhlichia], leptospirosis, parvovirus aplastic crisis), certain drugs (vancomycin, linezolid, bactrim, valganciclovir, immunosuppressive therapies, chemotherapies, allopurinol, colchicine)
- Bone marrow failure
- Infiltrative: malignancies (leukemia, lymphoma, myeloma, metastatic solid tumors), infections (TB, NTM, fungal infections), fibrosis (myelofibrosis)
- Aplastic anemia
- Nutrient deficiencies: Copper (primary or caused by elevated zinc levels), B12, folate
- Platelet destruction/consumption:
- Immune thrombocytopenia (ITP):
- Drug-induced (quinines, sulfonamides, beta-lactams, vancomycin, meropenem, valacyclovir, PPIs, H2 blockers, anti MTB therapy)
- Heparin-induced thrombocytopenia
- Infections (HIV, HBV, HCV, CMV, EBV, malaria, H. pylori)
- Autoimmune disorders (SLE, scleroderma)
- Thyroid disease
- Bleeding
- Idiopathic
- Thrombotic microangiopathies (TMAs)
- TTP (acquired, hereditary)
- HUS
- DIC (sepsis, APML, pancreatitis, transfusion reaction, HELLP)
- Drug-induced (Calcineurin inhibitors, gemcitabine, cocaine)
- Autoimmune (scleroderma renal crisis)
- Complement-mediated (atypical HUS)
- Catastrophic antiphospholipid syndrome (APLS)
- Hypertensive emergency
- Sequestration: Hypersplenism or splenic sequestration (e.g. cirrhosis)
- Pseudothrombocytopenia: platelet clumping
- Dilutional: gestational thrombocytopenia
- Decreased platelet production
Presentation¶
- Usually asymptomatic
- Bleeding due to low platelet counts presents as petechiae
- Some causes of thrombocytopenia have a paradoxical increased risk of thrombosis (HIT, DIC, TMA, VITT from the AstraZeneca or Johnson & Johnson COVID vaccines)
Evaluation¶
- Repeat CBC w/ diff PLUS a peripheral smear
- Citrated platelet count (to rule out pseudothrombocytopenia though a smear without clumping is sufficient to exclude this) and immature platelet fraction (IPF)
- IPF can help differentiate between decreased platelet production vs. increased platelet production (in setting of destruction/consumption)
- Medication reconciliation to look for any offending drugs
- TMA/DIC labs: Haptoglobin, LDH, LFTs, PT/PTT, fibrinogen, peripheral smear
- Viral serologies: HIV, HBV, HCV, EBV, CMV, parvovirus (if clinically indicated)
- Infectious work-up
- Sepsis: blood cultures
- Fungal work-up (if clinically indicated): 1,3-Beta-D-Glucan, aspergillus galactomannan, urine blasto Ag, urine and serum histo Ag, crypto Ag
- Tick-borne (if clinically indicated): RMSF, Ehrlichia, Anaplasma
- Leptospirosis (if clinically indicated)
- TB and/or NTM (if clinically indicated): AFB, interferon-Gamma release assay
- Autoimmune work-up (if clinically indicated): ESR, CRP, ANA w/ reflex, RF
- Nutritional studies: B12, folate, copper, zinc
- TSH to screen for thyroid disease
- Abdominal U/S to look for splenomegaly (or review recent imaging)
- Bone marrow biopsy (if clinically indicated): co-existing cytopenias raise suspicion for bone marrow involvement (particularly if present prior to admission)
- HIT work-up: Calculate 4T score: if 4+, order HIT Ab ELISA. If (+), serotonin-release assay (SRA) will reflex for confirmation
Management:¶
- Platelet transfusion indications
- CNS or ocular bleeding: <100K
- Pt actively bleeding or plan for OR: <50K
- Plan for central line, bronch, LP, diagnostic endoscopy, or bone marrow biopsy: <20K
- Afebrile, hospitalized pts: <10K
- HIT management: Stop any heparin product and start argatroban.
- Schistocytes on smear:
- Think TTP or DIC when there are schistocytes on smear and thrombocytopenia
- If DIC is excluded, consult Hematology to discuss sending ADAMTS13 and starting PLEX. A Vascath is needed for PLEX
Transfusion Medicine¶
R. Dixon Dorand
- For emergent transfusions, call the blood bank (see directory)
- RNs on 10T and 11N can follow transfusion protocols for pRBCs and plts – enter as a “Nursing Communication” or as part of the Hematology/Oncology Admission Order set.
- At VUMC, all special processing of blood products (such as irradiation) will be decided by blood bank based on special considerations listed in order set. Examples include: stem cell transplant, hematologic malignancy, or thalassemia
- Pts with frequent transfusions (e.g. sickle cell hemoglobinopathy) should have an “RBC Extended Phenotype” ordered (once) for minor RBC antigens to avoid immunization and antibody development to these proteins
- You may ask the VUMC hematology lab to email you pictures of the peripheral smear
- VA: Orders Tab – Blood Bank Orders – follow prompts to select appropriate product. Must order both the blood product AND the transfusion order (“Transfuse blood”)
- You need to specify all special processing such as irradiation
- To order “Type & Screen” as a lab, you must go to Blood Bank Orders
- Type & Screen and Transfusion results are under the Blood tab in Results
Red Blood Cell Transfusion¶
- Volume 200-300 mL per unit prbc
- In general, 1 unit of packed RBCs increases Hgb by 1g/dL and HCT by ~3%
- Assessment of the post-transfusion Hgb can be performed 15 min following transfusion, but ideally 1 hour after completion
Indications:¶
- Hgb <9-10 g/dL: Acute coronary syndrome
- Hgb <8 g/dL or Hct <25: Bone marrow failure or receiving antineoplastic therapy
- Also sometimes used in pts with pre-existing CAD
- Hgb <7 g/dL or Hct <21: ICU, GI Bleeding, oncology pt on treatment
Platelets Transfusion¶
- Indications for transfusion
- <11 k/µL: all pts, reduce risk of spontaneous hemorrhage (use on BMT, Brittingham)
- <50 k/µL: active bleeding, scheduled to undergo select invasive procedure
- <100 k/µL: CNS hemorrhage, intrathecal catheter
- This is also the threshold used for most neurosurgical procedures
Fresh Frozen Plasma (FFP) and Cryoprecipitate (Cryo)¶
Cryoprecipitate: FFP enriched for von Willebrand factor, factor VIII, factor XIII, and fibrinogen
FFP - Once thawed, must be used in 24 hrs (due to decline in labile coagulation factors) - Must be ABO compatible but not crossmatched or Rh typing - Only administer FFP if INR ≥1.7 (FFP will not fix an INR < 1.7)
Indications for transfusion - Bleeding: - FFP If INR >1.7 - Cryoprecipitate if fibrinogen <100. - DIC: - Fibrinogen <100: Transfuse 5 – 10 units cryoprecipitate and repeat fibrinogen. If bleeding, consider raising transfusion threshold of cryoprecipitate to fibrinogen <150 - For elevated INR, consider FFP transfusion. Thresholds for doing this vary by attending - Cirrhosis: - General concept: PT/INR, aPTT are unreliable markers for bleeding. Fibrinogen ≤100 – 120 or thromboelastography are better surrogates for bleeding risk - Transfuse fibrinogen ≤100 – 120 if the pt is actively bleeding or about to undergo a procedure or surgery other than paracentesis - Transfuse FFP based on hepatology team preference (generally few indications for FFP)
Transfusion Premedication and Reactions¶
- If you are concerned about a serious transfusion reaction, pause the transfusion and contact the blood bank ASAP
- Order the transfusion reaction blood testing in Epic. You will send a CBC, the bag of blood products, and the completed form to the blood bank for analysis
Premedication: - Only if history of severe reaction - Diphenhydramine 25-50mg IV - Acetaminophen 650 mg PO - Meperidine 25-50 mg IV (optional for chills) - Hydrocortisone 50 mg IV (optional, for severe reactions or reactions despite acetaminophen and diphenhydramine)
Reaction | Signs & Symptoms | Etiology | Clinical Action |
---|---|---|---|
Allergic (mild) | Pruritus, hives limited to small area | Antibodies to transfused plasma proteins | Pause transfusion. Administer antihistamines. Resume transfusion if improved; NO samples necessary. If no improvement in 30 min treat as moderate to severe. |
Allergic (moderate to severe) | Generalized hives (>2/3 body surface), bronchospasm & dyspnea, abdominal pain, hypotension, nausea, anaphylaxis | Antibodies to transfused plasma proteins usually IgE but can also be IgA. Possible allergen in blood product | Administer antihistamines, epinephrine, vasopressors and corticosteroids as needed. Send product to blood bank. |
Febrile Non-Hemolytic | Rise of temp >1°C, chills, rigors, anxiety. | Cytokines released from residual white blood cells in the blood product | Mild: administer antipyretics as needed |
Acute Hemolytic | Hemoglobinemia /uria, fever, chills, anxiety, shock, flank pain, chest pain, unexplained bleeding, cardiac arrest | Intravascular hemolysis usually due to ABO incompatibility. Recheck for pt ID or clinical error. This is an emergency. | Treat shock w/vasopressors; maintain airway; administer fluids and maintain brisk diuresis; monitor for AKI. Administer blood products as needed after etiology is clear. |
Septic | Rise of temp > 2°C, sudden hypotension or hypertension, shock | Micro-organism (i.e. bacteria) in donor bag (Greater risk in apheresis vs. RBC) | Send bag/tubing to transfusion medicine. Order BCx. Broad spectrum abx Pressor support if necessary. |
TRALI – Transfusion Related Acute Lung Injury | Acute respiratory distress occurring within 6 hours of transfusion. Non-cardiogenic pulmonary edema unresponsive to diuretics; Dx of exclusion. | Usually donor HLA antibodies from transfused plasma. Recipient has corresponding antigens; causes neutrophil activation that results in extravasation of fluid into air spaces | Respiratory support! Most will resolve within 24-96 hours. Steroids, diuretics: no known benefit. |
TACO - Transfusion Associated Circulatory Overload | Cardiogenic pulmonary edema occurring within 6 hours from the end of transfusion. Elevated BNP is often observed. Can be seen with as little as one unit of blood. | Increased oncotic and pulmonary capillary pressures (to a greater extent than crystalloid) resulting in pulmonary edema | Diuretic therapy and supportive care |
Cancer of Unknown Primary¶
Bailey DeCoursey
Background¶
- Cancer of unknown primary (CUP) accounts for 2% of all cancer diagnoses
- Often, CUP is discovered incidentally on imaging tests or due to symptomatic metastasis
Presentation¶
- Asymptomatic and found on imaging
- Often generalized fatigue and weight loss
- May have irregular, persistent lymphadenopathy at a particular site
Initial Evaluation¶
- Physical exam: including pelvic / breast exam for females and prostate/testicular exam for males
- CMP, CBC w/ diff, UA, PSA in males, fecal occult blood screening
- CT C/A/P with contrast (reveals the origin in up to 35% of pts)
- Once lesions are identified pt’s should undergo biopsy of the most accessible lesion
- If imaging is suggestive of GI origin, or pt has liver metastasis without other obvious dominant lesion, colonoscopy should be performed
- If physical exam with breast abnormalities, or pt has axillary lymphadenopathy, bilateral mammography should be performed
- Breast MRI may be considered even in the setting of negative mammography if clinical suspicion is high
Evaluation following biopsy¶
- Adenocarcinoma (70% of CUP)
- Most common primary: pancreas, lung, liver, HPB tree, and kidney
- Interestingly, prostate and breast cancer account for a small percentage of CUP despite being the most common malignancies
- Most common metastasis: liver, lungs, lymph nodes and bones
- Evaluation:
- Primary is most likely to be identified by biopsy
- If clinical suspicion is high for certain primary site, this should be relayed to pathology so they may perform appropriate staining
- Tissue PSA can be positive even in the setting of normal serum PSA
- Serum studies such as CEA, CA19-9, CA 125, CA15-3 are often not sensitive or specific and will often be elevated in the setting of many types of adenocarcinoma
- Neuroendocrine tumors (1% of CUP)
- High grade
- Most common primary: lung (bronchogenic)
- Most common metastasis: mediastinal and retroperitoneal LN
- Evaluation: CT of chest ± bronchoscopy will likely identify site
- If unrevealing, IHC staining and molecular cancer classifying assays will likely be helpful
- Squamous cell carcinoma (5% of CUP)
- Work up depends on the location of adenopathy as follows:
- Upper and mid-cervical lymphadenopathy
- Most common primary: head and neck cancer
- Evaluation: CT head and neck, direct laryngoscopy, nasopharyngoscopy
- Lower cervical/supraclavicular lymphadenopathy
- Most common primary: lung or head and neck
- Evaluation: CT chest, CT head and neck, direct laryngoscopy as indicated
- Inguinal lymphadenopathy
- Most common primary: genital or anorectal origin
- Evaluation
- Females: careful external and internal genital examination
- Males: close external genital examination
- Anoscopy and DRE in all pt
- Upper and mid-cervical lymphadenopathy
- Work up depends on the location of adenopathy as follows:
- In up to 60% of cases, a primary site may never be identified
- Empiric chemotherapy may be initiated in consultation with medical oncology
Venous Thromboembolism¶
Lamiya Rodriguez
Background¶
- Includes both deep vein thrombosis (DVTs) and pulmonary embolism (PE). See “Pulmonary Embolism” section in cardiology for more information on PEs
- Risk factors for provoked DVT/PE
- Major risk factors: major surgery >30 minutes, hospitalization > 3 days, C-section
- Minor Risk Factors: surgery <30 minutes, hospitalization <3 days, pregnancy, estrogen therapy, reduced mobility >3 days
- Non-transient risk factors: malignancy (active), myeloproliferative disorders, IBD, liver disease, hereditary thrombophilia (factor V Leiden and prothrombin gene mutations most common), antiphospholipid syndrome.
Evaluation¶
- Asymmetric calf swelling of >2cm sensitivity and specificity for DVT of 60-70%
- Wells’ Criteria for DVT can help guide diagnostic testing
- If a pt has a low pre-test probability, a negative D-dimer can rule out DVT
- In a high pre-test probability pt a negative D-dimer is less helpful
- Whole-leg ultrasounds with doppler
Management¶
- Prophylaxis: Padua score
- Score > 4 high risk, recommend pharmacologic prophylaxis
- Subcutaneous Low Molecular Weight Heparin (LMWH) or Subcutaneous Heparin
- Score <4 is low risk; recommend ambulation and SCDs
- Score > 4 high risk, recommend pharmacologic prophylaxis
- Treatment (see anticoagulation section)
- Subcutaneous low molecular weight heparin (LMWH, twice a day dosing)
- Oral factor Xa inhibitors: rivaroxaban, apixaban
- Intravenous unfractionated heparin
- Warfarin (with bridge therapy)
- Duration of treatment
- Provoked: 3-6 months or until provoking factor (trauma, surgery, malignancy) is removed
- Unprovoked: typically requires life-long anticoagulation along with assistance from hematology
- Anticoagulation in malignancy
- LMWH or DOAC (most evidence for apixaban and rivaroxaban) while malignancy still active
- Avoid Rivaroxaban and Edoxaban in GI malignancies (increased rates of bleeding)
- Note – in Anti-phospholipid syndrome, can only use warfarin
Additional Information¶
- Should we get a follow up ultrasound?
- A follow up ultrasound at the CONCLUSION of anticoagulation can help establish a post-treatment baseline and provide a baseline study for future comparison that can be critical for the diagnosis of recurrent/new DVT (which is very difficult to determine radiographically without a comparison imaging study)
- What about IVC filters?
- Select circumstances for these: In pts with acute DVT or PE and in whom anti-coagulation is absolutely contraindicated (thrombocytopenia, recent intra-cranial bleed, recent GI bleed) placement of a retrievable IVC filter should be discussed with Hematology and IR
Ended: Hematology oncology
Hepatology ↵
Non Invasive Liver Testing
Shabnam Eghbali
Evaluation¶
-
Who should be evaluated: patients with steatosis noted on imaging or for whom there is a clinical suspicion of MASLD, such as those with metabolic risk factors (e.g., HTN, HLD, T2DM, obesity) or unexplained elevations in liver chemistries
-
Primary risk assessment for MASLD -> FIB-4 – estimates degree of scarring and is based on age, AST, ALT, platelet count; high negative predictive value to exclude advanced fibrosis (F3- 4); less reliable in patients under the age of 35 or over the age of 65
- If FIB-4 <1.3 -> reassess periodically
- Every 1-2 years if T2DM/pre-T2DM or ≥2 metabolic risk factors
- Every 2-3 years if no T2DM and <2 metabolic risk factors
- If FIB-4 ≥ 1.3 -> secondary risk assessment with elastography Vibration-controlled
transient elastography (VCTE) also known as FibroScan if BMI < 35 or MR elastography if BMI > 35)
- Low risk = VCTE <8 kilopascal, MRE without significant fibrosis (F2-4), reassess periodically
- Intermediate/high risk = VCTE >8, MRE F2-4 -> referral to Hepatology
-
If FIB-4 > 2.67 -> immediate referral to Hepatology
-
Secondary risk assessment for MASLD -> (VCTE), also known as FibroScan, which provides following measurements:
- CAP score (dB/m) -> rough estimate of steatosis with relatively limited reliability
- 238 – 260 -> S1 (less ⅓ of liver affected by fatty change)
- 260 – 290 -> S2 (between ⅓ and ⅔ of liver affected by fatty change)
- 290 – 400 -> S3 (mor than ⅔ of liver affected by fatty change)
- Liver stiffness (LSM) (kPa) -> fibrosis score ... ranges differ based on underlying liver disease but approximately,
- 2 – 7 -> F0 to F1
- 8 – 11 -> F2
- 11 – 14 -> F3
- 14 or higher -> F4
-
Limitations to VCTE: not available at all centers, significant central adiposity that interferes with measurements, cardiac device not amenable to use of VCTE
-
AGILE 3+ – a recently developed score based on combination of AST/ALT ratio, platelet count, diabetes, sex, age, LSM
- Shear wave elastography interpretation:
- ≤ 5 kPa -> high probability of being normal
- < 9 kPa -> In the abscence of other known clinical signs, rule out compensated advanced liver disease (cACLD). If there are known clinical signs, may need further test for confirmation
- 9-13 kPa suggestive of cACLD but need further test for confirmation o > 13 kPa Rules in cACLD
-
17 kPa suggestive of clinically significant portal hypertension
Acute Liver Injury and Failure¶
Wrinn Alexander
Background¶
- Acute liver injury (ALI): elevated liver enzymes + INR ≥1.5 without encephalopathy
- Acute liver failure (ALF): elevated liver enzymes + encephalopathy (any degree of AMS or asterixis) in the absence of pre-existing liver disease*
- *Autoimmune hepatitis, HBV, Wilson disease, and Budd-Chiari syndrome can have ALF if they develop new AMS, despite the presence of a pre-existing liver disease
- Hyperacute (< 7 d): most often seen with acetaminophen toxicity, Hepatitis A & E, Ischemic; high risk for cerebral edema
- Acute (7-21 d): Hepatitis B
- Subacute (> 21 d and < 26 wk): most often non-acetaminophen DILI
- Alcohol-associated hepatitis (AH) is not ALF (see above)
- Duration of <26 weeks is a commonly used cut-off
Etiology¶
-
R-factor (if history, exam, and diagnostic data are inconclusive i.e. R-factor is not a replacement to clinical judgement) = (ALT/uln ALT) / (ALP/uln ALP); See chart below
- R > 5 = hepatocellular injury; R<2 = cholestatic injury; R 2-5 = mixed injury
-
Isolated hyperbilirubinemia: Differentiate direct versus indirect
- Direct: Refer to cholestatic pattern
- Indirect: Gilbert vs hemolysis
-
Drugs Associated with liver injury
-
Hepatocellular pattern: acarbose, Acetaminophen, Allopurinol, Amiodarone, Baclofen, Bupropion, Fluoxetine, HAART (Nevirapine), Kava kava, Isoniazid, Ketoconazole, Lisinopril, Losartan, Methotrexate, NSAIDs, Omeprazole, Oxacillin/Nafcillin, Paroxetine, Pyrazinamide, Propylthiouracil, Rifampin, Risperidone, Sertraline, Statins, Tetracycline, Trazodone, Valproic Acid
-
Mixed pattern: Amitriptyline, Azathioprine, Captopril, Carbamazepine, Clindamycin, Cyproheptadine, Enalapril, Flutemide, Nitrofurantoin, Phenobarbital, Phenytoin, Sulfonamides, Trazodone, Verapamil
-
Cholestatic pattern: Amoxicillin-clavulanic acid, Anabolic steroids, Chlorpromazine, Clopidogrel, Oral contraceptives, Erythromycins, Estrogens, Irbesartan, Mirtazapine, Phenothiazines, Terbinafine, Tricyclics
-
Hepatocellular Injury: R factor > 5 (Primary elevation of AST/ALT) | ||
---|---|---|
Acetaminophen intoxication$ | Acetaminophen lvl Aspirin lvl |
|
Acute Viral Hepatitis | Hep A$, B*$, C*, D, E EBV, CMV, HSV, VZV |
Viral serologies (see below), hx of tattoos, IVDU, piercings, blood transfusion prior to 1990s, intranasal cocaine use and mass vaccinations (in 3rd world countries) |
Autoimmune hepatitis\* | Autoantibodies and high serum globulins | Anti-smooth muscle (f-actin), ANA, ANCA, anti-liver kidney microsome (anti-LKM-1), anti-soluble liver antigen/liver-pancreas IgG |
Budd-Chiari Syndrome\* | Hepatic vein obstruction | Ultrasound of abdomen w/ doppler, CT w/ contrast |
DILI – Drug Induced Liver Injury\*$ | Many drugs | See above \*Query NIH Liver Tox database: https://www.livertox.nih.gov |
HELLP Syndrome, Acute Fatty Liver of Pregnancy | Pregnancy | Requires urgent delivery regardless of gestational age |
Ischemic Liver Injury (Shock Liver)$ | Shock (can be of any variety) | AST and ALT can be in the thousands, high LDH, history of hypotension |
Toxins | Ethanol, cocaine, mushroom (Amanita phalloides) | UDS, ethanol level, PEth lvl |
Wilson’s Disease\* | Copper overload | Ceruloplasmin level (screening), 24h urine copper (confirmation), quantitative copper on liver biopsy |
\*May present with chronic liver injury as well; $May present with AST/ALT >100 |
Cholestatic Injury: R Factor \< 2 (Primarily elevated Alkaline phosphatase) | ||
---|---|---|
Acute biliary obstruction | Gallstones | Abdominal ultrasound, MRCP, ERCP |
DILI – Drug-induced liver injury*$ | Many drugs, consult livertox website | Common: Augmentin, Bactrim, amiodarone, Imuran |
Malignancy* | Pancreas, cholangiocarcinoma | CT abdomen, ERCP |
Primary Biliary Cirrhosis* | Autoimmune | Anti-mitochondrial antibody |
Primary Sclerosing Cholangitis* | Autoimmune, associated with IBD | MRCP, ERCP |
Critical illness or COVID cholangiopathy | Hypotension, COVID | MRCP with biliary stenosis, appropriate history |
*May present with chronic liver injury as well; $May present with AST/ALT >100 |
Evaluation¶
- Neurologic Exam:
- See Hepatic Encephalopathy section for grading of HE based on PE/Hx
- Grade I and II HE: cerebral edema uncommon
- Grade III HE: Cerebral Edema in 25-35% of patients
- Grade IV HE: Cerebral Edema in 75% of patients
- Signs of increased intracranial pressure:
- Pupillary changes, Cushing’s triad (HTN, bradycardia, respiratory depression, seizures, increased muscle tone and hyperreflexia, abnormal brainstem reflexes
- See Hepatic Encephalopathy section for grading of HE based on PE/Hx
- Consult hepatology once you suspect ALF! (to assist with workup AND for transplant evaluation)
-
Labs:
- CBC w/diff, CMP, Dbili, Mg, Phos, T&S, BCx, UCx, PT/INR, aPTT, fibrinogen
- Ferritin, Iron, transferrin (HFE gene mutation testing if Tsat ≥45% and/or elevated ferritin) o Amylase, lipase
- Beta-hCG for females of childbearing age; UA to assess for proteinuria if pregnant
- ABG with arterial lactate, ammonia (arterial >124 predicts mortality and CNS complications e.g., need for intubation, seizures, cerebral edema, <75 very unlikely to develop ICH)
- Viral etiologies: Viral hepatitis serologies (HAV panel, HBV panel, HCV IgG ± PCR quant, HDV if known HBV (with low or undetectable HBV load) as Misc Reference Test, Hepatitis E PCR sent as miscellaneous if pregnant or travel to southeast Asia), HIV p24 Ag and HIV Ab, EBV Qt, CMV Qt, HSV ½, Qt, VZV IgM/IgG
- Toxins: UDS, ethanol level ± Peth, acetaminophen level (drawn ≥4 hours after last known ingestion), salicylate level
- Autoimmune/genetic: ANA, ASMA, IgG, AMA (if predominantly elevated ALP), ceruloplasmin, anti-liver/kidney microsomal antibody type 1, anti-liver soluble antigen, alpha-1 antitrypsin
- *You may not order all the workup included above; hepatology will guide you on what exactly will need to be ordered.
-
Imaging:
- RUQ abdominal ultrasound with doppler (important to assess vasculature!)
- Consider CT with contrast in patients with normal renal function and high suspicion of Budd-Chiari syndrome or malignancy with negative ultrasound (better for assessing the hepatic veins) and helps with transplant evaluation
- Consider TTE to rule out cardiac dysfunction; helpful for transplant consideration
- Consider CTH or MRI to assess for cerebral edema (findings include decrease in ventricular size, flattening of cerebral convolutions, reduction in signal intensity of brain parenchyma)
- Consider ERCP/MRCP for cholestatic etiologies
-
Discuss possible liver biopsy if etiology unclear
- Transjugular approach preferred with clinically demonstrable ascites; a known or suspected hemostatic defect; a small, hard, cirrhotic liver; morbid obesity with a difficult- to-identify flank site; or those in whom free and wedged hepatic vein pressure measurements are additionally being sought.
Management¶
- Any pt with concern for ALF should be cared for in MICU (even if mild change in mental status)
- Pts with ALF die acutely from hypoglycemia, cerebral edema, and infection
- ABC’s:
- Intubate for GCS \<8, Grade 3 or 4 HE
- IVF resuscitation with isotonic crystalloid (most pts are volume deplete; avoid hypotonic fluids due to risk of cerebral edema)
- Vasopressive agents for persistent hypotension (norepinephrine preferred)
- Monitoring:
- Q1-2h neuro checks, Q1-2h glucose checks
- Closely monitor CMP, INR q6-8 hrs
- Treatment of Primary Injury
- Early hepatology consult for liver transplant evaluation and assistance in management
- IV N-acetylcysteine - improves transplant-free survival even in
patients WITHOUT acetaminophen induced acute liver failure
- Initial loading dose = 150mg/kg over 1 hour, then 50mg/kg/hr for 4 hours, then 100mg/kg/hr for 16 hours
- Patients with early stage hepatic encephalopathy (grade I/II) have increased transplant free survival, while those with grade III/IV do not
- See below for etiology-specific treatment; hepatology consult for LT eval
- Early toxicology consultation if suspected ingestion/overdose
- For acute management contact Poison Control 800-222-1222
- Treatment of Secondary Complications
- Infection: Rule out infection with CXR, Blood cultures, UA/UCx for every ALF. Antibiotics only if progressing HE, signs of infection, or development of SIRS
- Cerebral edema/increased ICP:
- No role for lactulose in the setting of acute liver failure
- Grade III-IV hepatic encephalopathy: elevated HOB to 30 degrees, quiet and dimly lit room, should be intubated, avoid sedating medications as feasible, and ICP monitor are recommended (if not feasible, hourly neuro checks can be an alternative). If ICP becomes elevated start targeted therapies to reduce intracranial pressure.
- Mannitol or hypertonic saline should be administered for surges of ICP with consideration for short-term hyperventilation
- If high ICP is refractory to osmotic agents, consider phenobarbital, indomethacin, and/or cooling to 33-34 degrees Celsius if awaiting LT
- Seizures: phenytoin (no evidence to support seizure ppx), short acting benzodiazepines if refractory
- Renal Failure: early CRRT if persistent Metabolic Acidosis, Volume Overload, Hyperammonemia, falling UOP
- Coagulopathy: IV Vit K (at least one dose) routinely to rule out Vit K deficiency, products for invasive procedures or active bleeding only
- If trying to differentiate from DIC, can order Factor VIII level (should be normal/high in ALF; low in DIC)
- Metabolic: Correction of hypoglycemia (continuous D20) and electrolyte abnormalities
- Circulatory dysfunction/shock: Goal MAP >75 mmHg. Ensure intravascularly replete, add norepinephrine first line, vasopressin can be used second line but may increase ICP. Consider stress dose steroids for refractory shock
- Additional Supportive Care
- PPI for bleeding ppx
- Enteral nutrition EARLY; avoid TPN if possible
- Prefer propofol for sedation for better neuro exams and may reduce cerebral blood flow
Specific Management by Etiology:¶
- Acetaminophen
- Early toxicology consultation if suspected ingestion/overdose
- For acute management contact Poison Control 800-222-1222
- Activated charcoal within 4 hours of ingestion, most effective within 1 hour
- IV N-acetylcysteine per protocol, look up Rumack-Matthew Nomogram and consult with toxicology
- In Epic: search “N-acetylcysteine” and select order set “Acetaminophen overdose”
-
AFLP/HELLP – delivery
-
Amanita phalloides – IV fluid resuscitation, PO charcoal, IV penicillin, IV acetylcysteine
-
Autoimmune – IV steroids following approval by hepatology (and typically post biopsy). Azathioprine generally deferred until cholestasis resolved (Mycophenolate can be used instead)
-
Budd-Chiari – anticoagulation, IR-guided endovascular therapy, transplant (must rule out underlying malignancy and evaluate for thrombotic disorders)
-
HAV/HEV – supportive care, consider ribavirin for ALF due to HEV
-
HBV – nucleos(t)ide analogue; orthotopic liver transplant
-
HSV – acyclovir
Criteria for Transplantation:¶
- King’s College criteria: helps identify patients needing transplant referral/consideration
- A) ALF due to acetaminophen:
- Arterial pH <7.3 after resuscitation and >24 hr since ingestion, OR
- Arterial lactate >3 after adequate fluid resuscitation, OR
- Grade III- IV HE, and SCr >3.4, and INR >6.5 all within 24h period
- B) ALF not due to acetaminophen: INR > 6.5 OR 3 of the 5 following criteria:
- Etiology: Indeterminate etiology, idiosyncratic drug- induced hepatitis
- Age <10 or >40
- Interval of jaundice to onset of encephalopathy >7 days
- Bilirubin > 17.5mg/dl (300mmol/L)
- INR >3.5
- Other predictors of poor prognosis in absence of transplant:
- Hyperlactatemia: lactate >3.5 after 4 hours of IVF or >3 after 12 hours IVF
- Hyperphosphatemia: Phosphate >3.75 at 48-96 hours
Alcoholic Hepatitis¶
Ahmad Yanis
Background¶
- Acute onset of rapidly progressive jaundice (within prior 8 weeks) in pt with heavy EtOH
intake (>40g in females or >60g in males EtOH/day for >6 mos, or within <60 days of abstinence)
- May present after they have quit drinking due to immunosuppressive effects of alcohol
- Risk Factors: Female, Hispanic ethnicity, binge drinking, poor nutrition, and obesity
Evaluation¶
- AST >60, AST/ALT >1.5, both values <400 IU/L; TBili >3.0 mg/dL, documentation of heavy EtOH use until 8 weeks prior to presentation (some guidelines state 12 weeks)
- Prognostication with Maddrey’s Discriminant Function: 4.6 * (PTpt – PTctrl) + Tbili
- Maddrey > 32 or MELD > 20 = poor 30d prognosis & may benefit from steroids (see below)
- RUQ U/S to rule out obstructive cause of jaundice
- Biopsy is not typically required but will show neutrophilic lobular inflammation, hepatocyte ballooning, steatosis, and pericellular fibrosis.
- Phosphatidylethanol (PEth) level is a biomarker of ethanol consumption over ~ 4wks; >20
ng/mL can indicate chronic moderate/heavy alcohol intake
- A single episode consumption can result in detectable Peth for up to 12 days. Can be elevated for months with regular heavy alcohol intake
- EtOH levels may be negative unless acutely intoxicated
Management¶
- Supportive Care is essential! Consult nutrition, start high protein, high calorie diet, high dose Thiamine x 3d, Folate, MVI
- Full infection workup (CXR, UA, BCx, paracentesis) regardless of symptoms
- Steroids:
- Discuss with hepatology team, >20 clinical trials conducted with inconsistent results
- Largest trial was the STOP-AH Trial (NEJM 2015) which showed improved mortality at 28 days in post hoc analysis, but not at 90 days in patients with Maddrey > 32.
- VA trial (patients with MDF >54) showed increased mortality, indicating a possible ceiling at which point steroids may be harmful.
- Individuals with a neutrophil: lymphocyte ratio of 5-8 are most likely to benefit from steroid use.
- Treatment dose is prednisolone 40mg daily (preferred over prednisone as it requires hepatic metabolism)
- Contraindications to steroids include: presence of infection (must rule out first including TB, active Hep B, sepsis, uncontrolled GI bleeding, AKI w/ Cr >2.5 mg/dL) - The Lille score can be used to assess response to steroids after 7 d of therapy and prognosticate mortality at 6 months
- Lille > 0.45 indicates no response to steroids and predicts 75% mortality at 6 months
- NAC should be considered as adjunctive therapy to steroids
- Discuss with hepatology team, >20 clinical trials conducted with inconsistent results
- Monitor on CIWA
- Psychiatry consultation as appropriate, consideration of medical therapy (see “Substance Use Disorders” section in psychiatry)
Ascites and Hepatic Hydrothorax¶
Thomas Strobel
Ascites¶
Background¶
-
Associated with a reduction in 5 year survival from 80% to 30%.
-
Most often due to portal hypertension. Less common causes include peritoneal or metastatic cancer, heart failure, tuberculosis, nephrotic syndrome, Budd-Chiari, sinusoidal obstructive syndrome (S.O.S), or complications from procedures and pancreatitis
Grade | Definition | Treatment |
Grade 1 Ascites | Only seen on imaging | 2g Na restriction |
Grade 2 Ascites | Moderate, symmetric abdominal distension | 2g Na restriction, diuretics |
Grade 3 Ascites | Marked, tense abdominal distension | LVP + Na restriction, diuretics (unless refractory) |
Evaluation¶
-
Bedside ultrasound on admission to confirm presence of ascites
-
Diagnostic paracentesis in all pts with ascites on admission mainly to rule out occult SBP
- Initial paracentesis or when cause of ascites is uncertain: Total Protein, serum and BF Albumin, cell count w/diff, culture
- Subsequent/Serial paracenteses: cell count w/diff, culture, protein
- Always inoculate culture bottles at bedside (VA does not allow bedside innoculation)
-
See Procedure section for guidance on paracentesis.
-
Serum-ascites albumin gradient (SAAG) = serum albumin - ascites albumin.
0 | 1 | 2 |
---|---|---|
Total Protein Ascites (not serum) | SAAG > 1.1 g/dL (Portal HTN ) | SAAG \< 1.1 g/dL (Non-portal HTN ) |
\< 2.5 g/dL | Cirrhosis | Nephrotic Syndrome Myxedema |
> 2.5 g/dL | Post-hepatic portal HTN: Cardiac Ascites Budd-Chiari | Malignant Ascites Pancreatic Ascites TB |
-
Calculate PMNs from fluid (see SBP below)
-
Other tests:
- Triglycerides: if fluid is milky
- Cytology: if very concerned for peritoneal carcinomatosis. May need up to 3 separate samples (50ml or more) to be able to detect malignant cells
- ADA: if concern for peritoneal TB
- Hematocrit: For bloody appearing fluid (not just serosanguinous) to rule out hemoperitoneum. There needs to be a recent serum HCT for comparison.
- Amylase: If concerned for pancreatic ascites
- Glucose, LDH if concern about secondary peritonitis (see below)
Management¶
-
2000mg sodium restriction per day for all ascites (Grade 1-3)
-
Diuretics (spironolactone and typically furosemide)
- Start at 100mg of spironolactone with up titration to 400mg
- Furosemide is added if insufficient diuresis or if limited by hyperkalemia. Use more loop diuretics in patients with CKD
- If Urine Na:K ratio <1, indicates insufficient natriuresis. Can ↑ doses to a max of 400:160
- If poor response can change to torsemide 10mg and ↑ to 40mg max (per single dose)
- Fluid restriction usually not necessary unless serum sodium <125 mmol/L
-
Large volume paracentesis should be performed for tense ascites or refractory ascites (grade 3), regardless of serum Cr. Pts should be tapped dry with each paracentesis
-
Give 6-8g of albumin per liter of ascites removed, even if < 5L
-
Target weight loss of 0.5 kg/day when diuresing to avoid renal injury
-
Discontinue NSAIDs and ACEI/ARB
Refractory Ascites:¶
-
Two distinctions:
- Diuretic-resistant: lack of response to diuretics (max spironolactone 400mg/lasix 160mg), Na restriction and rapid recurrence following paracentesis
- Diuretic-intractable: unable to tolerate diuretic therapy 2/2 adverse drug effects (unexplained HE, AKI, K abnormalities, hypoNa, intractable muscle cramps)
-
Management aside from liver transplant:
- Discontinue diuretics once refractory ascites has been established
- Consider oral midodrine; can be especially helpful if pt is also hypotensive
- Serial paracenteses, generally arranged OP with IR
- Consider TIPS (trans jugular intrahepatic portosystemic shunt; has survival benefit). Following TIPS, cessation or decrease in ascites should occur in 4-6 weeks
- Consider discontinuing beta blockers in patients with refractory ascites if sBP <90, SCr >1.5, or Na <130
Hepatic Hydrothorax¶
Background¶
-
Transudative effusion, typically unilateral (75% right sided); reflects ascitic fluid that passes through defects in the diaphragm. 10% can develop without clinical ascites.
-
Present in 4-12% of cirrhotics and portends a poor prognosis (75% mortality within 90 days)
Evaluation¶
-
Often suspected clinically, though must exclude pleural/cardiopulmonary process
-
Thoracentesis will demonstrate a transudative effusion and should be evaluated with standard pleural fluid lab tests: cell count, protein, albumin, LDH, culture
- Other considerations: triglycerides, amylase, hematocrit, cytology
-
Rule out SBE which is diagnosed the same as SBP (PMN>250)
Management¶
-
Similar management of ascites as noted above
-
AVOID chest-tube placement. associated with increased morbidity and mortality due to extensive loss of fluid, electrolytes and protein as well as increased infection risk
- PleurX catheters can be considered for palliation (e.g., hospice patients)
-
Refractory Hydrothorax is defined similarly and managed similarly with serial thoracentesis or TIPS.
-
Management of spontaneous bacterial empyema is the same as in SBP (see below)
Cirrhosis Overview¶
Ahmad Yanis
Background¶
- Standard 1-liner for any patient with cirrhosis:
-
Example 1-liner: 65yo M with cirrhosis due to HCV decompensated by ascites and HE (MELD 25) who is listed for transplant and followed by Dr. Izzy
-
Etiology of cirrhosis: HCV>HBV, EtOH, NASH, Wilson’s, hemochromatosis, A1AT deficiency, autoimmune hepatitis, PSC, PBC, congestive hepatopathy (right heart failure), medication- induced
-
Complications that cause decompensation: overt ascites (or hepatic hydrothorax), overt hepatic encephalopathy (HE), esophageal variceal hemorrhage (EVH)
-
Always calculate daily MELD-Na scores (predicts 3 mo survival based on Tbili, Cr, INR, Na)
Evaluation¶
-
Goals: establish etiology, evaluate/treat complications, determine prognosis, and consider transplant evaluation
-
History:
- Symptoms suggesting decompensation: confusion, sleep disturbances, abdominal swelling, lower extremity edema, scleral icterus/jaundice, pruritus, easy bruising/bleeding (skin, mouth, GI tract), dyspnea
- Social history: EtOH and drug use hx, date of last drink, average # of drinks/day, duration of EtOH use, prior rehab, hx of DUI, if there has been continued EtOH use despite knowledge of liver disease; these factors all impact transplant candidacy
- Ascites: compliance with diuretics, compliance with salt restriction, frequency of paracentesis (volume removed, date of last para), h/o SBP, hx of TIPs
- HE: compliance with lactulose, # of BMs per day, any potential triggers (see HE section)
- GIB/EVH: hematemesis, coffee ground emesis, melena, hematochezia (duration, volume, # of bleeding episodes), last EGD (varices, banding) and colonoscopy, compliance with non-selective BBs
-
Physical exam: asterixis, ascites, edema/anasarca, splenomegaly, muscle wasting, gynecomastia, testicular atrophy, palmar erythema, spider angiomata, scleral icterus/jaundice, petechiae/ecchymoses, caput medusa, Terry’s nails
-
Labs
- Initial Workup: CMP, CBC, Coags, UA, HCV/HBV, Fe studies, PEth
- Unless requested by hepatology, defer to outpatient: AFP, ANA, IgG, A1AT, ceruloplasmin, AMA (PBC), ASMA (AIH), anti-SLA (AIH), anti-LKM (AIH)
-
Imaging:
- Abdominal US with duplex unless done in past 6 months or indication for repeating sooner (concern for new portal vein thrombosis)
- For transplant eval, needs triple phase CT A/P (contrasted study, arterial and venous phases) or MRI abdomen with contrast
-
Liver biopsy: gold standard for cirrhosis diagnosis but is not always needed if clinical presentation, labs, and imaging consistent with cirrhosis
Lab abnormalities¶
-
Hyponatremia (see hyponatremia section below)
-
Cirrhotic coagulopathy (increased INR): due to ↓ coagulation factor production
-
Thrombocytopenia: due to splenic sequestration, ↓ TPO production
-
Hypoalbuminemia: indications for 25% albumin transfusion – SBP (1.5g/kg on day 1, 1g/kg on day 3), LVP (6-8g/L of ascites), HRS (albumin challenge: 1g/kg/day with max 100 g/day x 2 days), hypoNa <125 and refractory to fluid restriction
Management¶
-
Nutrition: high protein diet, 2g Na restriction (if ascites present)
- Consider MVI, folate, thiamine (particularly in pts with EtOH use disorder)
- Mediterranean diet for NASH
- Fluid restriction if hyponatremic
-
Immunizations: ensure UTD with HBV/HAV, PPSV23, Prevnar, Flu, COVID-19 vaccines
-
Consider consulting Addiction Psych and Social Work for pts with EtOH use disorder - can assist with arranging Intensive Outpatient Program (IOP), Alcoholics Anonymous (AA)
-
General screenings include HCC screening (q6 months), EVH screening (see section below), monitor for other decompensations and treat accordingly, monitor MELD and consider transplant evaluation when >15
-
Refer to hepatology outpatient
Medication Tips:¶
-
Pain: 2g limit Tylenol, No NSAIDs, limit sedating medications especially with HE.
- Tramadol 25-50mg generally safe to use
-
Pruritus: Sarna lotion, can spot dose antihistamines. Can discuss with pharmacist/attending about starting sertraline, cholestyramine (interacts with many medications), or rifampin.
-
Anxiety/insomnia: hydroxyzine, avoid benzodiazepines
-
If needed for EtOH withdrawal, use lorazepam (Ativan) instead of chlordiazepoxide (Librium) or diazepam (Valium) due to its shorter half life
Coagulopathy in Cirrhosis¶
John Laurenzano
Background¶
- The liver is responsible for production of both pro- (factor II, V, VII, IV, X, and XI) and anti-coagulants (protein C, S) in hemostasis. Factor VIII is the only one not made by the liver.
- Thrombocytopenia is caused by splenic sequestration from portal HTN, failure to produce thrombopoietin (TPO), and bone marrow failure
- Hemostatic changes in cirrhotics are incredibly complex, as they involve both procoagulant and anticoagulants. The current thought is that cirrhosis is NO LONGER considered a condition associated with an overall increased bleeding tendency, as the pro-hemostatic and anti-hemostatic pathways are deranged in a way that counterbalance each other.
Evaluation¶
- INR/PT, and PTT are poorly reflective of bleeding risk
Management¶
-
Pre-procedural FFP is not recommended, as it has potential harm w/o proven benefit
-
Low risk procedures (i.e., paracentesis) do not require pre-procedural blood products and per guidelines there is no established INR or platelet cut off
-
In bleeding pts, the following are recommended per AASLD and AGA guidelines
- IV Vitamin K 10mg x 3 days
- FFP: Not recommended, unless as part of a balanced transfusion effort to avoid transfusion related coagulopathy, or if a TEG screen suggests potential benefit
- Cryoprecipitate: if fibrinogen < 120
- Platelets: No specific targets regardless of bleeding. Pre-procedurally, recommend >50
- Appropriate DVT ppx should be given with few exceptions (plts <50k, active hemorrhage)
- For TEG transfusion recommendations are as follows:
- 10 mg/kg FFP if R-time >10 minutes
- 1u Plts if maximum amplitude <55 mm
- 5u cryo if alpha angle <45
Hepatic Encephalopathy (HE)¶
- Ahmad Yanis
Classifications of HE:¶
- Type A: in patients with acute liver failure
- Type B: in patients with portosystemic shunt without significant liver disease
- Type C: in patients with cirrhosis
- Covert HE: minor or no signs/symptoms but abnormalities on neuropsychological and/or neurophysiological tests
- Overt HE: Clinically appreciable change In mental status (e.g., AxOx2 or asterixis) recurrent (≥ 2 bouts) within 6 months
- persistent if the patient does not return to their baseline performance between bouts.
Evaluation¶
- Asterixis: inability to maintain stable posture; many ways to assess
- Check for clonus
- Have pt “hold out hands like you are stopping traffic” (if following commands)
- Shine light in pupil (look up video of hippus)
0 | 1 | 2 | 3 |
---|---|---|---|
Grade | Behavior change | Asterixis | Cerebral Edema in Acute Liver Failure: |
I | Mild confusion, changes in behavior, increased sleep | No Asterixis | No cerebral edema |
II | Moderate confusion, lethargic | Asterixis | Rare cerebral edema |
III | Marked confusion, arousable but falls asleep, incoherent speech | Asterixis | ~30% cerebral edema |
IV | Coma | No Asterixis | ~75% cerebral edema |
-
Identify precipitants
- Infection (rule out SBP in addition to CXR, BCx, UA/Cx),
- Medication non-adherence (lactulose)
- GI bleed (perform rectal exam and observe Hgb trend)
- Over-diuresis resulting in dehydration, electrolyte abnormalities (especially hypoK)
- Sedatives/benzo/opiate administration (UDS)
- Brain imaging does not provide any diagnostic value for HE but may be utilized if diagnostic uncertainty exists
-
Increase ammonia (NH3) levels do not add any diagnostic, staging, or prognostic value in patients with CLD. A normal ammonia level, however, calls for diagnostic re-evaluation
-
Arterial NH3 is used in acute liver failure for prognostication (not for management)
Management¶
-
Always determine precipitant and treat underlying condition
-
Lactulose 30mL TID initially titrated to 2-3 BMs/D as secondary prophylaxis after the management of first episode of overt HE.
- Titrate dose to at least 4 BMs daily, avoid excessive stool output which may exacerbate HE due to dehydration and electrolyte abnormalities
- Consider lactulose enemas vs DHT placement if pt unable to tolerate PO
- DHT are not contraindicated in patients with esophageal varices, but should be avoided in patients with recent hemorrhage or banding
- Add Rifaximin after the second episode of HE, or if failure to
respond to lactulose
- Frequently requires prior auth for OP approval and is expensive
-
Lactulose is generally continued indefinitely after first episode of HE, though discontinuation can be considered on an individual basis if predisposing factors (recurrent infection, EVH, EtOH use) have resolved, improvement in liver function, and improvement in nutritional status
-
For patients with chronic diarrhea off lactulose, consider adding BCAA (0.25 gm/kg/d)
Hepatocellular Carcinoma (HCC)¶
Julie Cui
Background¶
-
Fifth most common tumor and the second most common cause of cancer related death worldwide
-
The incidence in patients with cirrhosis is 2-4% per year
-
In chronic HBV and NASH, pts can develop HCC without having cirrhosis
Evaluation¶
-
Regular screening in pts with cirrhosis (or chronic HBV without cirrhosis) for HCC
- RUQ U/S q6mo (with or without AFP)
- Routine screening with CT or MRI is not recommended
-
Options If U/S not satisfactory:
- CT A/P w/contrast, in comments specify triple phase for HCC screening
- MRI, specify Gadovist (preferred contrast agent)
- Contrast-enhanced ultrasound
-
AFP trend is more useful than one value in time, though AFP >20 should prompt multiphase CT or MRI for further evaluation
-
Diagnosis can be made either by imaging (most common) or biopsy (rare)
- Triple phase CT demonstrates strong early uptake in arterial phase, with subsequent wash-out in portal-venous phase
- If diagnosis remains unclear: can surveillance imaging or biopsy
- LI-RADS system notes risk of malignancy based on imaging characteristics
0 | 1 | 2 |
---|---|---|
LI-RADS | What does it mean? | What do we do? |
LR-1 to LR-2 | Definitely/Probably benign | Routine surveillance, consider diagnostic imaging within 6 mos |
LR-3 to LR-4 | Indeterminate/Probably HCC | Repeat or alternative diagnostic imaging in 3-6 mos. Consider Bx for LI-RADS 4 |
LR-5 | Definitely HCC | Plan treatment as noted below |
LR-M | Cancer but may not be HCC | NaN |
Management¶
-
Lesions that meet Milan criteria can qualify for MELD exception points and are considered transplant candidates
- This accounts for pts with minimal synthetic dysfunction (and therefore low MELD)
-
Milan criteria:
- Single tumor with diameter >2cm but <5 cm, no more than 3 tumors, each <3 cm
- No signs of extra-hepatic involvement or vascular invasion
-
Liver transplant is definitive treatment, although resection can also be curative (favored in pts with early cirrhosis i.e. Child Pugh A)
- Locoregional therapies: Pts with unresectable disease, or who are not surgical candidates
0 | 1 |
---|---|
Therapy | Details |
Radiofrequency ablation | If in a favorable location and size, IR can percutaneously ablate with a large needle that emits microwave frequencies |
Trans-arterial chemoembolization (TACE) | Chemotherapeutic agents injected into the tumor to occlude the feeding blood supply to the area. |
Trans-arterial radioembolization (TARE) | Like TACE, though radioactive compound (i.e. Y-90) used to occlude the feeding blood supply. |
Stereotactic body Radiation Therapy (SBRT) | Radiation therapy: can be used as an alternative to ablation and is generally performed in those meeting Milan criteria |
Systemic Chemotherapy | For metastatic disease |
Hepatorenal Syndrome¶
Garren Montgomery
Background¶
-
Portal HTN causes shear stress on portal vessels -> endothelium release of vasodilators -> splanchnic vasodilation and reduced effective blood volume (decreased MAP) -> RAAS activation -> sodium and water retention and severe renal vasoconstriction
-
Bacterial translocation (as seen in SBP) -> increased circulating pro-inflammatory cytokines -> splanchnic vasodilation
-
Definitions:
- HRS-AKI (formerly type I HRS): Rise in Cr ≥0.3 within 48h, rise in Cr ≥50% within 7 days, OR UOP <0.5 mL/kg/hr for 6 hours
- HRS-NAKI (“non-AKI”) (formerly type II HRS):
- HRS-AKD: eGFR<60 for <3 months in absence of other structural causes OR % rise in Cr ≤50% using last available Cr over last 3 months as baseline
- HRS-CKD: eGFR<60 for ≥3 months in absence of other structural causes
-
Diagnostic Criteria
- Diagnosis of AKI (see above) without other cause (see below
- No response or inadequate response at 48 hrs after volume expansion with albumin and withdrawal of diuretics
- Absence of proteinuria (<500 mg/d), absence of hematuria (<50 RBCs per HPF), normal renal ultrasound (exclude if patient has known CKD
- Suggestion of renal vasoconstriction with FeNa <0.2, FeUrea <20 (most sensitive diagnostic measure). UNa <20 is suggestive but not diagnostic given baseline sodium avidity in cirrhosis and inability to calculate FeNa
- Cut off for ATN in cirrhosis is a FeNa >0.5, rather than 1 in the general population
Evaluation¶
-
Step 1: Exclude other obvious causes of renal injury such as hypovolemia or ATN
- Common precipitants of AKI: infection, overdiuresis, GI bleeding, recent LVP without subsequent volume expansion, nephrotoxic drugs/NSAIDs
- Workup: BMP, UA with microscopy, urine electrolytes (FeNa, FeUrea), urine protein/Cr ratio, renal ultrasound (to assess for chronicity), diagnostic para to rule out SBP
-
Step 2: Diuretic cessation/albumin challenge
- STOP all diuretics, beta blockers, NSAIDs, ACE/ARBs, anti-hypertensives, vasodilators, nephrotoxins
- START volume expansion with albumin 1g/kg/day (up to a max of 100 g/day) x2 days
-
Step 3: Diagnosis of HRS
- If no other clear cause of AKI is identified and SCr has not improved after 48 hours of diuretic cessation and volume expansion, proceed promptly to vasopressor treatment
Management¶
-
Pharmacologic therapies (in order of preference):
- Terlipressin (± albumin 50g/day, unless there is evidence of volume overload). Most effective medication based on randomized clinical trials, NOW FDA APPROVED and approved for use at VUMC in Transplant Candidates only. Titration is done based on creatinine response.
- Alternatively, consider Norepinephrine (± albumin 50 g/day)
- Requires central access (PICC vs triple lumen) but can be administered on stepdown unit
- Guidelines recommend NE to be dosed at 0.5-3 mg/hr. Would ask fellow, attending or pharmacist for baseline. VUMC protocol for ICU and stepdown:
- Start NE gtt at 3mcg/min. If UOP is <200 or MAP <10mm Hg from baseline, increase by 3 mcg/min every 4 hours
-
Continue to hold diuretics. LVP is still generally considered safe even in HRS if indicated by tense ascites (account for albumin repletion from LVP and HRS protocol). This can be attending specific and would confirm prior to performing
-
Therapy is generally continued until HRS is reversed or the hepatology attending deems it refractory to medical treatment. (Per guidelines, protocol normally discontinued if Cr remains at pretreatment level or above >4 days)
-
Patients with HRS-NAKI (formerly type II HRS) may respond to the above therapies, but recurrence of renal dysfunction after withdrawal of vasoconstrictors is the norm and thus current guidelines do not recommend them for this scenario
-
RRT: Dialysis can be considered for those who fail to respond to pharmacologic therapy, particularly ONLY as a bridge to liver transplant. Decision to initiate should be individualized
-
Liver transplant: The best and most definitive treatment regardless of response to pharmacologic therapy
Simultaneous liver-kidney transplant:¶
-
HRS often resolves with LT alone. Indications for kidney transplant are usually for patients with severe chronic renal dysfunction or on RRT. Must consult transplant nephrology.
-
Criteria for SLKT:
- eGFR <60 for >30 days AND latest eGFR <30
- eGFR <25 for >6 consecutive weeks with a documented eGFR q7 days
- Metabolic syndromes and polycystic disease
-
Can qualify for safety net kidney transplant after liver transplant if eGFR <20 2-12 months post-operatively (would be at higher priority than the rest of the kidney transplant list)
Hyponatremia in Cirrhosis¶
Kinsley Ojukwu
Background¶
-
Hyponatremia in cirrhosis is often defined as serum Na < 135 mmol/L
-
Very common problem; prevalence: ~50% of individuals have serum < 135 mmol/L, ~22% < 130 mmol/L
-
Degree of hyponatremia is associated with progression of cirrhosis; patients with hypona have greater incidence of HE, SBP, and HRS, increased complications & mortality pre/post-tx.
-
Patients most commonly have hypervolemic (dilutional) hypona.
-
Pathophysiology
- Hypovolemic hyponatremia: 2/2 excessive diuretic use
- Hypervolemic hyponatremia: Advanced cirrhosis -> chronic inflammation and fibrosis in liver -> increased resistance to portal flow -> portal hypertension -> release of vasoactive compounds (primarily nitric oxide) -> splanchnic arterial vasodilation -> reduced effective
Evaluation¶
- Uosm, Sosm, UNa to rule out competing processes (e.g. beer potomania)
Management¶
-
Do not correct Na faster than 6-8mEq/L in 24 hours
-
Discontinue anti-hypertensives (including beta blockers) in patients with ascites and hypona.
-
Hold diuretics when Na <125
-
Fluid restriction is recommended only in patients with Na <125. Restriction is generally effective at 1-1.5L and must be less than daily UOP to increase free water excretion
-
Replete K to 4.0
-
25% albumin infusion (1g/kg split into BID dosing), has been shown to increase serum Na and have higher rates of hypona resolution at 30 days
-
Treatment considerations include vasopressors, urea tabs
-
Vaptans are generally not used in clinical practice given recent RCTs showing harm with use
-
Salt tabs should not be used to raise serum Na due to worsening hypervolemia
-
Nephrology should be consulted if not improved after 48 hours
Liver Transplant (LT) Workup¶
Katelyn Backhaus
Background¶
- Model for End-stage Liver Disease (MELD-Na) score: initially developed to predict survivalfollowing TIPS placement, though is now used to objectively rank patients in terms of priority for liver transplant (LT)
- Factors in total bilirubin, creatinine, INR, and Na.
- Exception points given for complications like HCC and hepatopulmonary syndrome (HPS), leading to score in mid to high 20’s even if biologic MELD is low
- Highest score lasts for 7 days
- Listing a patient for LT is determined by a multidisciplinary transplant
committee
- Acute liver failure pts take precedence over decompensated cirrhosis pts for LT
Indications | Contraindications* |
Cirrhosis with MELD ≥ 15 or evidence of decompensation (ascites, variceal bleed, HE, HPS, portopulmonary HTN) | Ongoing substance abuse (must have documented abstinence ≥ 3 mos); some special considerations for pts who did not know of EtOH hepatitis or EtOH use d/o but highly variable |
Acute Liver Failure | Untreated or recurrent malignancy |
HCC that meets Milan criteria | Active Infection, AIDS |
Pts with early hilar cholangio-carcinoma that meets specific criteria | Documented history of medical noncompliance |
Other rare dz (e.g., familial amyloid polyneuropathy or hyperoxaluria) | Lack of Adequate social support |
Anatomic Contraindications; Chronic cardiac/pulmonary conditions that significantly increase perioperative risk (e.g., severe pulm HTN) | |
* Advanced age (>70) is not in itself a contraindication but candidates > 70 should be almost free of comorbidities to be considered for LT* |
Evaluation¶
- Abdominal CT (triple phase) or MRI (multiphase with contrast) to evaluate for hepatic malignancy and vascular anatomy
- Infectious workup: TB testing, HIV, RPR, VZV, CMV, EBV, and Hepatitis A, B, and C¶
-
Cardiac evaluation:
- If RVSP > 40mmHg on TTE, then R Heart Catheterization is indicated
-
PFT’s, carotid US
-
Panorex to identify dental disease; consult OMFS pending results
-
Appropriate cancer screenings (CXR in all patients, CT Chest in prior/current smokers, colonoscopy, pap smear, mammogram, and PSA if applicable)
-
DEXA scan (osteoporosis in up to 55% of individuals with cirrhosis)
-
Certification of completion of intensive outpatient program (IOP) for substance abuse
-
Evaluation by hepatobiliary surgical team after obtaining cross sectional imaging
-
Psychosocial evaluation (consult Psychiatry, social work)
-
Current VUMC policy: pts should be abstinent from alcohol for no less than 3-6 months, although exceptions may be made for early liver transplant based on a very strict protocol. Discuss exception criteria with attending if suspect patient unlikely to survive hospitalization without transplant
-
Both living and deceased donor transplants are offered at VUMC. Donor evaluation, however, cannot be started before the potential recipient is deemed a candidate. Of note, should consider possible simultaneous liver-kidney transplantation for 1) CKD <30mL/min after > 90 days of eGFR<60 or 2) AKI dependent on dialysis >8 weeks or if extensive glomerulosclerosis present.
MASH and MASLD¶
Shabnam Eghbali
Background¶
- Metabolic dysfunction-associated steatotic liver disease (MASLD) presence of hepatic steatosis (>5% of hepatocytes with macro-vesicular steatosis) in the absence of secondary causes (e.g, EtOH or HCV GT3) and at least one of five of the below criteria:
- BMI ≥ 25 OR waist circumference > 94 cm (M) / 80 cm (F)
- Fasting serum glucose ≥ 100 OR 2-hr post-load glucose levels ≥ 140 OR HgbA1c ≥ 5.7% OR T2DM
- Blood pressure ≥ 130/85 OR on anti-hypertensive medication
- Plasma triglycerides ≥ 150 OR on lipid lowering treatment
- Plasma HDL ≤ 40 (M) / 50 (F) OR on lipid lowering treatment
- Metabolic dysfunction-associated steatohepatitis (MASH) evidence of active inflammation and cellular injury ± fibrosis
- Strong association with metabolic syndrome, T2DM, HTN, obesity
- Prevalence of MASLD is 25-30% in general population and is now the leading cause of transplantation in American women
- MASLD is asymptomatic and frequently found incidentally via imaging
- MASH manifests with elevated liver enzymes, typically 2-5x the ULN, in a roughly 1:1 ratio (as opposed to alcoholic steatohepatitis), though ALT may be higher than AST. MASLD or MASH does NOT cause RUQ pain. Patients can still have normal liver enzymes with MASLD or MASH.
Evaluation¶
- Exclusion of alternative causes and comorbid liver conditions: HCV, HBV, EtOH, etc.
- Screen for comorbid metabolic disorders: Lipid panel, hemoglobin a1c
- Primary risk assessment with FIB-4 (see NITs section)
- Diagnosis commonly made via imaging
- US is used most frequently, although conventional B mode US lacks sensitivity for lower degrees of steatosis. As a result, controlled attenuation parameter (CAP) on VCTE (Ie FibroScan) is commonly used.
- MRI is also acceptable. MRI-proton density fat fraction is a precise method for liver fat quantification (available for clinical care at VUMC)
- Liver biopsy should be considered when non-invasive testing suggests significant fibrosis (≥F2)
Management¶
- Aggressive risk factor modification and management of comorbidities (HLD, HTN, T2DM)
- Weight loss: Mediterranean diet>low fat diet (dose dependent improvement), increased coffee consumption is associated with less progression of liver disease
- MASLD (fat only) Weight Loss Goal: > 5% of body weight
- MASH (fat and inflammation) Weight Loss Goal: >10% of body weight
- Consider referral to weight loss clinic (BMI >40, or >35 with metabolic comorbidities)
- Once the patient is diagnosed with MASLD, evaluation for fibrosis is indicated
- Fibrosis-4 (FIB 4) score: First line assessment. Assesses probability of fibrosis.
- Elastography: More accurate can be vibration based (fibroscan), US based (sheer-wave), or MR-based. Available at VUMC and can be ordered by anyone. Insurance will not cover MRE if BMI <35
- Fibroscan: <10kPa r/o advanced chronic liver disease (fibrosis); 10-15kPa are suggestive of advanced chronic liver disease; >15kPa are highly suggestive.
- Encourage etoh cessation; contributes to fatty liver disease progression
- FDA recently approved Rezdiffra (resmetirom) for the treatment of adults with noncirrhotic MASLD with moderate to advanced liver scarring (fibrosis), to be used along with diet and exercise
- SGLT2 Inhibitors: May reduce steatosis in patients with MASLD+ DM
- Vitamin E: Can improve steatosis and inflammation in the setting of biopsy-proven MASH with evidence of hepatic fibrosis (fibrosis score 2+) in patients w/o DM
- GLP-1 agonists: Consider for patients with MASH+DM/obesity as it confers cardiovascular benefit and improves steatosis but probably not fibrosis
- GLP-1/GIP agonist (e.g, semaglutide) Tirzepatide): Can reduce steatosis. Can be use in patients with DM or obesity + NAFLD
- Metformin, DPP4, statins, and silymarin are well studied in MASH and do not offer meaningful histologic benefit
- In the pipeline: FGF21 agonists, THR beta agonists, PPAR agonists
Additional Information¶
-
Statins: should be used for HLD in pts with MASH, MASLD, and MASH cirrhosis
-
Statin use in decompensated MASH cirrhosis is controversial, and they are less likely to derive benefit given overall poor prognosis, discontinue w/acute on chronic liver failure.
Portal Vein Thrombosis (PVT)¶
Pakinam Mekki
Background¶
- Portal Vein Thrombosis (PVT) can worsen decompensation (i.e. variceal hemorrhage), however, worsening portal HTN -> more sluggish flow -> increased risk PVT
Presentation¶
- Often identified asymptomatically on U/S, but can be identified by new or worsening decompensation of portal HTN
- Variceal hemorrhage is the most common decompensating event associated with PVT
- Intestinal ischemia (abdominal pain, hematochezia) from PVT is exceedingly rare but associated with significant morbidity and mortality
Evaluation¶
- RUQ U/S with doppler
- Once identified, should be further assessed with triple phase CT or MRI with Gadovist contrast to exclude HCC with tumor thrombus
-
Pts with newly identified PVT should undergo EGD to evaluate for high-risk varices, both for diagnostic and therapeutic considerations
-
PVT in pts without cirrhosis should prompt evaluation for hypercoagulable disorders
Management¶
-
Start AC if acute thrombus occludes >50% of main portal vein, <50% but extends into SMV, thrombus is symptomatic, or patient is a transplant candidate (irrespective of size). Requires discussion with attending/transplant team.
- Anticoagulation options: warfarin, LMWH, or DOAC
- DOAC’s are safe in Childs Class A, can be used with caution in Childs B, and are contraindicated in Childs C
-
Pts with chronic occlusive PVT (>6 mos) or with cavernous transformation with collaterals do not generally benefit from anticoagulation
-
Pts with high-risk varices should undergo endoscopic management or be on NSBB for prophylaxis for variceal hemorrhage, as noted above
-
TIPS with portal vein recanalization has recently emerged as a therapeutic modality for PVT in LT candidates to allow for anastomosis, in patient’s with chronic PVT and recurrent bleeding/refractory ascites, or in patients whom intestinal ischemia persists despite AC.
-
Pts should undergo follow up intermittently with ultrasound to assess for recanalization. AC may be stopped if there is failure to recanalize.
-
If pts are not candidates for AC, they'll simply be treated for complications of portal HTN
Spontaneous Bacterial Peritonitis (SBP)¶
Bailey DeCoursey
Background¶
-
Infection of ascitic fluid without evidence of a surgical intra-abdominal source
-
Present in approximately ⅓ of patients with cirrhosis who are hospitalized
-
Presentation: fever, abdominal pain, encephalopathy, renal failure, acidosis, and/or leukocytosis
-
Pathophysiology: Combination of GI bacterial flora overgrowth, reduced liver protein production (low complement levels), impaired phagocytic cell function leading to inability to clear pathogens
Evaluation¶
-
Any pt with cirrhosis and ascites who is admitted should have diagnostic para to r/o SBP. Delaying paracentesis > 12 hours is associated with a 2.7-fold increase in mortality.
- Obtain cell count with diff
- Calculate the PMNs: total nucleated cells x % neutrophils.
- PMN > 250 cells is diagnostic of SBP. If there are greater than 100k RBCs, you should correct for them: for every 250 RBCs, subtract 1 PMN
-
A positive ascitic bacterial culture with PMN <250 is called bacterascites and asymptomatic patients with bacterascites should NOT receive antibiotics as it is likely a contaminant (however, repeat paracentesis should be performed to exclude progression to SBP). You will also frequently see culture-negative SBP (neutrocytic ascites) which SHOULD be treated (see below).
Management¶
-
Immediately start empiric antibiotics
- Guidelines recommend cefotaxime IV 2gm q8 hours x 5 days, but we commonly use ceftriaxone IV 2g q24h for 5-7 days at VUMC and Nashville VA
- Most common culprits (E. coli, Klebsiella, streptococcal species, staphylococcal species)
- If SBP developed with recent hospital admission (90 days), recent exposure to BSA, diagnosed >48 hours of admission, or with sepsis, should give zosyn ± vanc if prior infection or positive swab for MRSA. Daptomycin should be added with hx of VRE infection instead of vanc.
- Finally, in patients with current or recent exposure to zosyn consider meropenem for MDR coverage.
- Guidelines recommend cefotaxime IV 2gm q8 hours x 5 days, but we commonly use ceftriaxone IV 2g q24h for 5-7 days at VUMC and Nashville VA
-
IV albumin 1.5 g/kg on day 1 and 1g/kg on day 3
-
NSBB do not need to be discontinued in patients with SBP unless hypotensive (mean arterial pressure <65mmHg). If stopped, the timing of re-initiation is based on recovery of blood pressure
-
PPI’s ↑ risk for SBP in pts with cirrhosis, and should be reviewed for appropriateness
-
Repeat diagnostic paracentesis two days after antibiotics initiated
- If <25% decrease in PMNs, antibiotics should be broadened. Consider secondary bacterial peritonitis.
-
Prophylaxis:
- GI bleed: ceftriaxone 1g dailyàciprofloxacin 500mg BID (preferred) or Bactrim one DS tablet BID x 5-7 days
-
Outpatient lifelong ppx, indications:
- Prior SBP
- Ascitic protein <1.5 AND
- Child Pugh >9 and bilirubin >3 OR
- Renal dysfunction (Cr >1.2, Na <130, or BUN >25)
- Preferred: Bactrim DS tab daily or ciprofloxacin 500mg daily
- Alternatives: cefdinir 300mg daily, Augmentin 875/125 daily
-
If suspicion is high for secondary bacterial peritonitis:
- Examine serum-ascites albumin gradient (SAAG). SBP develops in pts with portal hypertension, defined by SAAG > 1.1 g/dL. SBP is unlikely if SAAG is < 1.1 g/dL.
- While not particularly sensitive, an ascitic leukocyte count of 5-10k should prompt consideration of secondary peritonitis
- Amylase from fluid can also be helpful to point towards pancreatic ascites, while bilirubin can indicate gallbladder perforation.
- Peritoneal fluid CEA and alkaline phosphatase can additionally help identify hollow viscus injury.
- Evaluate with cross-sectional imaging and surgical consultation as appropriate
- Runyon’s Criteria to distinguish, requires ⅔ criteria below (protein, glucose, LDH)
Spontaneous | Secondary | |
---|---|---|
Protein (g/dL) | <1 | >1 |
Glucose (mg/dL) | ≥50 | <50 |
LDH (U) | Elevated, but < 225 | >225 |
Organisms | 0-1 | Polymicrobial |
Transjugular Intrahepatic Portosystemic Shunt (TIPS)¶
Ahmad Yanis
Background¶
-
A TIPS procedure is done by IR to manage sequalae of portal HTN (specifically variceal bleeding and ascites)
-
A low-resistance shunt is created between an intrahepatic branch of the portal vein and the hepatic vein, allowing blood to bypass the high-resistance vessels within the fibrotic liver.
-
Ideally, creating the smallest-necessary caliber shunt is desirable. Recent studies suggest that an 8-mm-diameter PTFE-lined TIPS may be sufficient to prevent variceal rebleeding and potentially decrease the incidence of hepatic encephalopathy
Evaluation¶
-
Indications for TIPS
- Variceal hemorrhage (esophageal, gastric, etc.)
- Early “preemptive” TIPS is an urgent TIPS placement within 72 hrs (preferably within 24 hours) of initial endoscopic hemostasis in pts at high risk for rebleeding (Child-Pugh Class B with active bleeding upon insertion of endoscope or Child-Pugh Class C with recent bleeding
- “Rescue” TIPS is placed in pts with active, uncontrolled variceal bleeding or if bleeding recurs despite maximal endoscopic and pharmacologic therapy
- Refractory ascites (prolongs survival)
- Other: bleeding portal hypertensive gastropathy, bleeding gastric varices, PVT recanalization, Budd-Chiari syndrome, hepatic hydrothorax
- Variceal hemorrhage (esophageal, gastric, etc.)
-
Contraindications to TIPS
- Absolute contraindications
- Primary prevention of variceal bleeding, congestive heart failure, severe tricuspid regurgitation, severe pulmonary hypertension, multiple hepatic cysts or masses, Sepsis, unrelieved biliary obstruction
- Relative contraindications
- Hepatic encephalopathy, hepatic tumors (especially if centrally located), thrombocytopenia, moderate pulmonary hypertension
- Absolute contraindications
-
Pre-procedure preparation
- Labs: CBC, CMP, INR
- Liver imaging to assess portal system patency and exclude liver masses
- Ideally triple phase CT with contrast
- In pts with renal impairment or active variceal bleeding, RUQ U/S with doppler is acceptable
- TTE to evaluate for evidence of congestive heart failure, pulmonary hypertension, or valvular disease.
- Antibiotic ppx with ceftriaxone 1g IV once at the time of TIPS insertion as enteric bacteria within the static portal system can enter systemic circulation
- Patients with HE should receive rifaximin prophylaxis starting 2 weeks before procedure
Management Post-TIPS¶
-
Immediately following TIPS, pts are observed in the hospital overnight for complications
- Monitor CBC and vitals closely. If hemodynamically unstable, STAT CBC and low threshold to obtain CTA A/P to evaluate for a bleeding source
-
TIPS causes a substantial increase in venous return to the heart, which can unmask cardiac dysfunction that was previously compensated for
-
Obtain RUQ U/S with Doppler to assess shunt patency 1 month of TIPS placement, or if ascites and/or variceal hemorrhage reoccur
-
If patient with a TIPS develops refractory HE, can consider TIPS revision to lessen HE symptoms
-
Clearance of ascites is not immediate post-TIPS (may take 6-12 weeks), and patients should be maintained on a sodium-restricted diet and diuretics until ascites is adequately controlled.
-
Hemodynamic Pressure Measurements and Goals
- The HVPG refers to the difference in intravascular pressure between the portal vein and the hepatic vein. During TIPS placement, direct portal pressures are measured and used tocalculate the portosystemic pressure gradient (PSPG)
- In patients with acute, uncontrolled esophageal variceal bleeding, the desired post-TIPS PSPG is <12 mm Hg or, If the former is not feasible, a reduction ≥50% from baseline PSPG
- The desired PSPG for secondary prevention of gastroesophageal variceal bleeding is <12 mm Hg
- In patients not achieving a PSPG <12 mm Hg despite dilation of the stent to a maximum 10 mm of diameter, the addition of nonselective beta-blockers (NSBBs) should be considered
Gastroesophageal Varices and Hemorrhage¶
H. Anh Nguyen
Background¶
- Varices form due to portosystemic collaterals in the setting of portal HTN
- Gastroesophageal varices are present in approximately 50% of patients with cirrhosis and their presence correlates with severity of liver disease
- The risk of mortality with esophageal variceal hemorrhage (EVH) can be up to 15-20%
- Recurrence occurs in over 60% of patients within 1-2 years of the index event
- The most important predictor of hemorrhage is the size of the varices. Other predictors include decompensated cirrhosis (Child B/C) and endoscopic presence of red wale marks or red spots
Variceal Screening¶
-
Not all pts with cirrhosis require screening. Can be omitted without clinically significant portal hypertension (e.g. low liver stiffness (on elastography) and platelets >150) or if pt already on non-selective beta blocker (NSBB) with HR 55-60
-
Compensated cirrhosis without varices: EGD q3yr, unless active liver injury (obesity, EtOH use, ongoing viral infxn), then q2yr
-
Compensated cirrhosis with small varices: EGD q2yr unless active liver injury, then q1yr
-
Decompensated cirrhosis with no or small nonbleeding varices: EGD q1yr, and at initial time of decompensation
Management (Non-Bleeding Varices)¶
-
Primary ppx with either NSBB (preferred) or endoscopic band ligation (EBL)
- Nadolol (given nightly as portal pressures are highest at night) or propranolol (BID)
- Carvedilol has greater portal pressures and may be preferred if tolerated (goal 6.25mg BID)
- For 2 º ppx, initiate ~72hr after acute bleed has resolved and octreotide discontinued
- Discontinue if: hypotension (sBP <90), AKI, SBP or hyponatremia with refractory ascites
-
Secondary ppx with both NSBB and EBL.
- NSBB are associated with reduced mortality, while EBL is not
Management (Bleeding Varices)¶
-
Place two large-bore IVs (18G or larger), resuscitate with blood products and albumin. Activate massive transfusion protocol if needed.
-
Consider intubation if need for emergent EGD, change in mental status, ongoing hematemesis, concern of ability to protect airway
-
Start octreotide 50 mcg IV bolus followed by continuous infusion of 50 mcg/h, to be continued for at least 2 days should EVH be confirmed on endoscopy
-
Ceftriaxone 1g IV q24h for SBP prophylaxis (reduced mortality), then transition to PO ciprofloxacin for total 7-day course
-
Consult GI for upper endoscopy. Endoscopic therapies performed include variceal band ligation and sclerotherapy.
-
Consider balloon tamponade with Blakemore as temporizing measure before definitive management. Patient must be intubated before placement, and preferably GI should be made aware prior to placement.
-
No role for the correction of INR, even in the presence of bleeding as excessive blood products and FFP can increase portal pressures and cause worsening bleeding
- Vitamin K can be given w/ ↑ INR, though is unlikely to help in the acute setting
- Check TEG and fibrinogen and transfuse based on results
- AASLD does not recommend specific platelet targets during variceal hemorrhage
- Administer blood products in balanced ratio to avoid transfusion related coagulopathy (VUMC MTP is 6:4:1 of RBC:FFP:PLT)
Ended: Hepatology
Hospital medicine ↵
AMA Discharges¶
Christine Hamilton
-
Patients who leave AMA are significantly more likely to have hospital readmissions and have higher mortality rates. If paged from the bedside about a patient requesting to leave AMA, call nurse back and then go speak with the patient.
-
Address patient concerns (i.e. pain control, substance withdrawal, fear/anxiety, financial strain, diet) to address reversible causes for contention.
-
Determine capacity to leave: review risks of leaving and medical reasoning to stay (see Medical Decision-Making Capacity under "Psychiatry"). This discussion should be witnessed by nurse or charge nurse if possible. Provider and patient will need to sign AMA discharge form, which nurse can obtain.
-
Send new medications to pharmacy and request hospital follow-up visits if patient leaves
-
Sign discharge order. In the "discharge to" section select "left against medical advice" (for more detailed discharge instructions, see appendices)
-
Clearly document in discharge summary that patient was informed about the risks of leaving, had the capacity to make the decision to leave, and left AMA.
- *Caveat: if patient at any point becomes threatening or you feel unsafe, allow them to leave or contact security
Enteral Nutrition¶
Soibhan Kelley
Indications for enteral feeding¶
- Patients with high nutritional risk who are unable to maintain their own intake
- Guidelines recommend calculating nutritional risk based on validated scoring tool (ex: Malnutrition Screening Tool). This is usually completed by the nutrition team
- Recognize who would benefit from nutrition consult to assist with risk determination
- Patients with >5% weight loss in past 1-3 months or decreased oral intake coupled with increased metabolic demands due to medical illness or surgery
- Patients with low nutritional risk may not need enteral feeding if it is anticipated they will resume intake in 5-7 days
- Critically ill patients: goal is early initiation of tube feeding (within 48 hours)
Contraindications to enteral nutrition¶
- Bowel obstruction or severe ileus
- Ischemic bowel
- Acute peritonitis
- Major gastrointestinal bleeding
- Intractable vomiting
- Significant hemodynamic instability
- Patients who are not adequately volume resuscitated and have significant hemodynamic instability (i.e., have high pressor requirements) are thought to be at increased risk for bowel ischemia
- Pressors in general are not a contraindication to tube feeds. Ok to start once pressors are down-trending or at a stable level
- Patients who are not adequately volume resuscitated and have significant hemodynamic instability (i.e., have high pressor requirements) are thought to be at increased risk for bowel ischemia
Initiating tube feeds¶
-
Enteral access
- Nasogastric or orogastric feeding tube in acute setting. See procedures section for tips on placement
- For most patients, enteral feeding is safe with gastric tube placement
- Consider post-pyloric placement for patients with high aspiration risk, impaired gastric motility, or patients who have demonstrated intolerance with gastric feeding
- Consider percutaneous endoscopic gastrostomy (PEG) tube placement if anticipate enteral nutrition >4 weeks
-
Choice of formula and rate
- Place nutrition consult. RD will calculation caloric and protein needs to determine goal rate and formulation
-
OK to start tube feeds prior to recommendations and adjust later, especially if recommendations will be delayed. It only takes a simple calculation to make a reasonable tube feeding plan
- Use weight-based dosing for calorie requirements
- Use 25-30 cal/kg (use ideal body weight for most patients, use actual weight for underweight patient) to estimate daily needs
- Most common formula used at VUMC is Nutren 1.5 (1.5 cal/ml) or Novasource renal if significant renal impairment (2 cal/ml)
- Patients may need additional free water (most tube feed formulas are comprised of 80-85% water but varies with type). Typically dose as bolus of free water every 4-6 hours.
- May empirically try 250cc free water every 4 hours and monitor Na trends. May need more if already with a large fluid deficit (ex: hypernatremia) or if high volume losses
- May use clinical calculators as below
- Use weight-based dosing for calorie requirements
-
Calculate hourly rate based on daily calorie need and formula calorie density
- Ex: Patient with IBW of 70Kg will need estimated 1,750 calories per day (70 x 25 cal/kg)
- If using Nutren 1.5, this will equal 1,167 ml per day (1,750 divided by 1.5 calories per ml). This would equal a goal rate of about 50ml per hour (rounded up) of Nutren 1.5
- Resources for quick calculations:
- Search for “tube feed cheat sheet” on google and will find reference tables on EMCrit.org that gives you rate per hour for different weights and formula types
- Clincalc.com also has a useful enteral nutrition calculator
-
Start initially at a low rate (such as 10 mL/hr) to assess tolerability and advance to goal
- Advance quickly if no concern for refeeding syndrome (ex: increase by 10cc/hr q6h)
- If risk for refeeding syndrome or other issues with tolerability, typically advance more slowly over several days
Potential Complications¶
-
Aspiration
- Recommendation to keep head of bed elevated at 30 to 45 degrees (low quality, mixed evidence). Consider risks of this positioning (ex: formation of pressure ulcers)
- Consider post-pyloric placement if issues with aspiration (low quality, mixed evidence)
-
Diarrhea or constipation
- Consider wheat dextrin fiber supplement (low quality evidence) but discontinue if not associated with clinical improvement. Avoid less soluble fibers such as psyllium due to risk of clogging tube. Avoid in patients with reduced GI motility due to rare risk of bezoar formation
-
Hyperglycemia
- See endocrine section for management
-
Refeeding syndrome
- Monitor q8 hour Mg, phos, K in high-risk patients (underweight, recent weight loss, prolonged poor intake) and advance to goal slowly
Guidelines for Pregnant Patients¶
Ahmad Dbouk and Samuel Lazaroff
Acute Cystitis:¶
-
Significantly increased prevalence in pregnancy
-
Symptoms: dysuria (urgency/frequency common in pregnancy)
-
Diagnosis: evidence of pyuria and >103 cfu/ml (note, if neg would test for g/c)
-
Treatment: Empiric with cephalexin, cefpodoxime, amoxicillin-clavulanate, fosfomycin. Nitrofurantoin ok in second or third trimester. Avoid Bactrim in first trimester and near term. Tailor based on culture results.
-
Note that asymptomatic bacteriuria is treated in pregnancy (in contrast with general public). Same antibiotic choices as above
Pyelonephritis:¶
- Symptoms: fever, flank pain, and nausea/vomiting, dysuria
- Diagnosis: clinical suspicion + pyuria and bacteriuria
- Treatment: IV antibiotics for 1 st 24-48hrs; beta-lactams preferred
- Mild to moderate: ceftriaxone or cefepime
- Moderate to severe: piperacillin-tazobactam or meropenem
Hyperemesis Gravidarum:¶
- Presentation: Hormone mediated nausea/vomiting typically starting before 9wks GA
- Differential: gastroenteritis, hepatitis, biliary tract disease, obstruction, pancreatitis, pyelonephritis, nephrolithiasis, ovarian torsion, DKA, hyperparathyroidism, migraines, preeclampsia
- Workup: BMP, mg, phos, LFTs, lipase (may be mildly elevated in HG), UA,
- Treatment:
-
- First Line: Ginger, doxylamine (25mg PO q6), pyridoxine (20mg PO q6)
- Second Line: metoclopramide (10mg q6), Promethazine (12.5mg q6)
- Third Line: ondansetron (8mg q12hrs, after 1st trimester)
- Hydration: 1L LR on admission + banana bag q24hrs
-
Hypertension:¶
- Both gestational HTN and preeclampsia/HELLP are typically diagnosed >20w GA
- Tx options: nifedipine, labetalol, methyldopa, hydral (2 nd line), clonidine (2 nd line)
- Avoid: ACEs, ARBs, MRAs, Nitroprusside
Diabetes:¶
- Due to hormonal changes associated with pregnancy, pregnant patients are at higher risk for poor control and DKA
- Oral regimens are generally transitioned to insulin-based regimens.
GERD:¶
- 1st Line: Can use antacids; avoid sodium bicarbonate and magnesium trisilicate
- 2nd Line: Sucralfate 1g PO TID
- 3rd Line: Cimetidine 200mg (30min prior to eating)
Asthma:¶
- Similar rescue and controller medications as in non-pregnant patient
- Would favor using LABA over leukotriene receptor antagonists or theophylline for additional therapy
High Quality Handovers¶
Christine Hamilton
Synopsis¶
-
Include patient's name, age, pertinent medical history, and key hospital diagnoses/events. For example: "John Doe is a 57-year-old man with a past medical history of HTN and HLD who presented with NSTEMI, now s/p LHC on 3/7, on DAPT.
-
Include code status and, if applicable, capacity to leave AMA
To-dos¶
- Should be very specific, and instructions should contain the time a task should be performed, the task itself, and actionable recommendations. For example: "21:00 -- Follow-up intake/output. If urine output is less than 2L, order 160mg IV Lasix."
Contingencies¶
- Should include instructions for common overnight pages as well as patient-specific recommendations. At a minimum, contingencies should address: pain, fever, nausea, hypoxia, hemodynamic instability, tachycardia, and AMS.
I-PASS¶
-
When giving verbal handoff for complicated patients, use the I-PASS technique:
-
I: Illness severity (stable, watcher, unstable)
-
P: Patient summary (one-liner with working/confirmed diagnosis, key elements of hospital course including major medication changes/procedures/interventions, and any pertinent physical exam findings or lab result (important particularly if a patient has known neuro exam findings, baseline severe hyponatremia, etc in the event they are called about this)
-
A: Action list: formatted as to-do's, above
-
S: Situation awareness: i.e., contingency planning
-
S: Synthesis by receiver: summarize the pertinent diagnoses, action list, and clarify any questions
-
Lines and Catheters¶
Seth Alexander
General guidance¶
- Primary goals of line/catheter management:
- Know why it was placed
- Know where it is going (venous, arterial, potential space)
- Know what needs to happn before it can be removed
- Risk of infection: all foreign objects run the risk of introducing microbes during placement or becoming a nidus for microbial growth.
- Lines should only be placed when medically necessary and removed as medically appropriate.
- This chapter does not include additional forms of invasive monitoring devices (i.e., Swan Ganz catheters), surgical/procedural drains, or support devices (i.e., endotracheal tubes, ventricular assist devices, etc.) as these typically require subspecialty consultation/management for consideration and are discussed elsewhere.
Urinary Catheter¶
- Indications: surgery, immobilization, urinary retention, need for strict urine output monitoring (critical illness, diuresis), and open sacral/perineal wounds with incontinence
- Chronic foleys should typically be exchanged on admission
- Duration of use is biggest risk factor for CAUTI
- Best way to prevent CAUTI is to avoid inappropriate placement
- Assess daily whether foley can be removed
- Chronic Foleys generally should be exchanged at time of admission
- Potential complications: Traumatic placement, difficult placement, and CAUTI
- Any concern for catheter obstruction should prompt urgent urology consult
- Determine if coudé catheter placement attempted; can be useful in patients with BPH
- Duration of use is the biggest risk factor for CAUTI; assess daily for need
- Criteria for removal: ability to void independently (with PVR follow-up) and resolution of placement indication
- Alternate devices: Purewick catheter and condom catheter
Central venous catheter¶
- Central venous access can be obtained through large central venous catheters (internal jugular, subclavian, or femoral CVC) or peripherally inserted central catheters (PICC).
- Indications: Vasoactive infusions (pressors, inotropes), long-term antibiotics, inability to obtain peripheral access, caustic agent administration (chemotherapy, antibiotics, etc), and total parenteral nutrition
- Note, single lumen PICC appropriate for most patients; double lumen typically reserved for special populations such as those in the ICU, on chemo, or on TPN
- Potential complications:
- Arterial cannulation, air embolization, thrombus, or mispositioning during placement
- Highest risk of insertion: femoral CVC
- Pneumothorax: Subclavian CVC
- Criteria for removal: discontinuation of agents for which placement was indicated, transition to comfort care, or concern for central line associated bloodstream infection (CLABSI)
- Alternative devices: peripheral venous access (consider US-guided)
- There are indwelling catheters (tunneled ports, Hickman lines) which are more permanent central venous access devices used in patients with need for intermittent ventral venous access, typically placed by IR or surgery
Arterial Lines¶
- Indications: accurate blood pressure measurement, frequent arterial blood draws (ABG)
- Potential complications: arterial occlusion (spasm, thrombus), with resultant ischemia, hematoma formation
- Criteria for removal: resolution of placement criteria
Feeding Tubes¶
- Described in further detail below.
- Placement: We can place dobhoff tubes or replace mature G-tubes
- Troubleshooting: EGS consult for malposition/not functioning, wound consult for skin breakdown
- G-tube study: 30mL Gastrograffin via tube [resident often must push] and KUB
Telemetry¶
Ashley Ciosek
Background¶
- Many monitored pts do not have a true indication
- Leads to alarm fatigue, unnecessary workups, and is expensive
- Cost: about $110 per patient per day
- Telemetry is not a substitute for more frequent vital signs
- Discuss frequently on rounds: reassess need and indication
- Select “MAY” for transfers off telemetry and showering off telemetry among stable patients without troponin elevation or new arrythmia
0 | 1 |
---|---|
Clinical Scenario | Duration |
Cardiac | Cardiac |
ACS Post-MI | 24-48h 48h after revascularization |
Vasospastic angina | Until symptoms resolve |
Any event requiring ICD shocks | Remainder of hospitalization |
New/unstable atrial tachyarrhythmias | Until stable on medical therapies |
Chronic AF w/ recurrence of RVR | Clinical judgement |
Ventricular tachyarrhythmias | Until definitive therapy |
Symptomatic bradycardia | Until definitive therapy |
Decompensated CHF | Until underlying cause treated |
Procedural | Procedural |
Ablation (regardless of co-morbidities) | 12-24h after procedure |
Cardiac surgery | 48-72h, or until discharge if high risk for decompensation |
Non-cardiac major surgery in patient with AF risk factors | Until discharge from step-down or ICU |
Conscious sedation | Until patient awake, alert, HDS |
Miscellaneous | Miscellaneous |
Endocarditis | Until clinically stable |
CVA | 24-48h |
Electrolyte derangement (K, Mg) | Until normalization |
Hemodialysis | Clinical judgement |
Drug overdose | Until free of influence of substance |
Notable non-indications¶
- Rate-controlled afib + clinically stable
- Chronic PVCs
- ESRD on HD
- PCI for non-ACS indication (e.g. pre-transplant)
- Non-cardiac chest pain
- Patient with AICD admitted for non-cardiac condition, non-cardiac surgery, chronic rate-controlled AFib
- Nearly all non-cardiac conditions (e.g. undifferentiated sepsis, stable GI bleed, alcohol withdrawal) upon transfer out of ICU
- Patient in hospice/comfort care
Transitions of Care: Tips for Safe Discharges¶
Christine Hamilton
- Discharge from hospital represents a period of vulnerability for patients. Medical errors (especially medication errors) following discharge are exceedingly common and can lead to adverse events
On Admission:¶
- Admission checklist: verify PCP, primary specialty providers, social support, current living situation, and functional status at the time of admission
- Track any new meds, held/stopped meds, and med dose changes from the beginning
- Consult PT/OT early for anyone who you anticipate may need home health services or need to be discharged to any location besides home
During hospitalization:¶
- Consider barriers to discharge daily and discuss on rounds
- Discuss barriers to discharge, anticipated discharge destination, and any other needs in huddle
- Track any incidental findings or things for PCP to follow-up (e.g., incidental nodules on scans: use .vnincidental)
- Discuss expected discharge timing daily with patient and family if possible, to set expectations
On discharge day:¶
- Communicate with patient's outpatient team (e.g. PCP)
- Typically achieved through the discharge summary
- Include a list of specific, actionable follow-up tasks and
assign a responsible party. Place in easy-to-view spot at the
top of the summary
- E.g., Instead of writing "follow-up BMP after initiation of furosemide," write "PCP to check BMP in 2 weeks after initiation of furosemide"
- Include any pending studies and appointments from hospital admission
- All relevant parties should receive a copy of the discharge
summary (see appendices section for mechanics of discharge process)
- It is useful to send patient with a printed copy of the discharge summary if they will follow-up outside VUMC
- Include a list of specific, actionable follow-up tasks and
assign a responsible party. Place in easy-to-view spot at the
top of the summary
- For high-risk discharges (poor health literacy, hx of being lost to follow-up, follow up outside VUMC), consider calling PCP's office to set follow-up
- Typically achieved through the discharge summary
- Complete an accurate and thorough medication reconciliation
- An accurate discharge medication list depends on having a complete admission medication reconciliation (utilize pharmacy consult!)
- Three steps to medication reconciliation:
- Verification: Performing a Best Possible Medication History
- Clarification: Checking that medications and doses are appropriate
- Reconciliation: Record all medication changes
- Seek to use at least two sources of information
- Keep a list of any held or changed medications in your hospital course. Medication changes can be lost when not communicated during team transitions
- Review medication changes on rounds and with pharmacist on day of discharge (bonus points for day prior to discharge)
- Three steps to medication reconciliation:
- Highlight any significant medication changes on discharge summary
- Can include as follow-up tasks if pertinent (ex: PCP to follow-up BP in 2 weeks. Losartan held on d/c due to AKI but anticipate need to reinitiate once Cr normalizes)
- Be sure to communicate any changes with the patient and/or caregiver
- An accurate discharge medication list depends on having a complete admission medication reconciliation (utilize pharmacy consult!)
- Ensure that appropriate resources and follow-up appointments have been requested* (PT/OT, skilled or non-skilled nursing HH, PCP follow-up, etc.)
- Effectively communicate discharge plan to patient
- Discuss medication changes, tasks for patient to complete, follow-up appointments
- Key points should also be written in the patient instructions box
- Useful to include educational sheets in the AVS (searchable in discharge navigator)
- Utilize the teach-back method to ensure your instructions were effectively communicated
- Discuss medication changes, tasks for patient to complete, follow-up appointments
- At VUMC we are fortunate to have the Discharge Care Center
- Multidisciplinary team including nurses, social workers, care coordinators, and pharmacists
- Phone number is included on discharge paperwork, and patients can contact them 24/7. The DCC also reaches out to patients through an automated system
Wounds − Adapted from Dr. Duggan’s Geriatrics Guide¶
-
To do when admitting a patient with wounds:
- Document ALL wounds that are present on admission. This affects reimbursement
-
Use the Haiku app on your cell phone to document images of wounds in chart
-
Wound Service hours are Monday through Friday, 6 AM - 2 PM
-
If there is an urgent/emergent wound need (i.e. needs surgical eval or management), consult the appropriate surgical service
-
While awaiting consultation, initiate topical wound care orders (detailed below)
-
-
Consider contributing factors: nutritional, pressure-offloading equipment, wound supplies, PT/OT, home health nursing
Types of wounds¶
-
Arterial wound - Calciphylaxis
-
Venous leg wound - Fistula
-
Diabetic foot wound - Abscess
-
Vasculitis - Skin tear
-
Pyoderma gangrenosum - Pressure injury
-
Fungating lesion - Ischemic ulcers / gangrene
Vascular Wound Etiologies¶
-
Arterial: located on distal ends of digits, shallow, well-defined borders, pale/necrotic wound bed, minimal exudate due to poor blood flow, cramping pain or a constant deep ache
-
Diabetic: plantar surface of foot, callused wound margins; usually painless due to neuropathy
-
Venous: located on medial malleolus or gravity dependent areas, irregular edges, ruddy red with yellow slough and copious exudate
Pressure Injury Staging¶
Feature | Deep Tissue Injury | Stage 1 | Stage 2 | Stage 3 | Stage 4 |
---|---|---|---|---|---|
Skin Consistency | Boggy | Boggy | Variable | N/A | N/A |
Skin color/nature of lesion | Non-blanching purple or maroon, may appear as blood-filled blister | Non-blanching erythema | Abrasion, blister, or shallow crater | Variable | Variable. If eschar, must be removed in order to stage, or is unstageable |
Depth | Epidermis intact | Epidermis intact | Through surface of epidermis and outer dermis | SQ tissue to, but not through, fascia | Full-thickness loss w/ destruction, necrosis, or damage to muscle, bone, supporting structures |
Non-Acute Wound Consult Guidelines¶
-
Order “Inpatient Consult to Adult Wound" for these wound types: diabetic foot wounds*, venous, arterial, pressure injuries (consult required for DTI, stage 3, 4, and unstageable), IV infiltrate, skin tears, moisture-associated dermatitis, calciphylaxis, vasculitis, pyoderma gangrenosum, fungating lesion, abscess