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:

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
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
- 1^st Line NE, 2^nd Line Vasopressin, 3^rd Line Epi, 4^th 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