Management and Treatment of Sepsis

Definition (Sepsis-3, 2016)

The Surviving Sepsis Campaign (SSC), a joint SCCM/ESICM initiative, provides the primary international management framework — last formally revised in 2021, with a 2025 German S3 guideline update.

Immediate Priorities ("The Hour-1 Bundle")

1. Obtain blood cultures before giving antibiotics
2. Administer broad-spectrum antibiotics
3. Measure serum lactate; re-measure if >2 mmol/L
4. Administer 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
5. Apply vasopressors if hemodynamically unstable during/after fluid resuscitation to maintain MAP ≥65 mmHg

1. Resuscitation

Fluid Therapy

• Initial bolus: 30 mL/kg isotonic crystalloid IV for septic shock
• Titrate further fluids to clinical parameters: heart rate, blood pressure, mental status, capillary refill, urine output (target 0.5–1 mL/kg/hr)
• Balanced crystalloids (e.g., lactated Ringer's) are preferred over normal saline — normal saline is associated with hyperchloremic acidosis and adverse renal effects
• Colloids are as effective as crystalloids but more expensive; albumin may be used in patients requiring substantial crystalloid volumes
• Avoid fluid overload, especially in elderly patients, CHF, or renal impairment — these patients still need resuscitation, but require vigilant monitoring

Evidence from the ProCESS, ProMISE, and ARISE trials showed no mortality benefit from rigid EGDT (early goal-directed therapy) protocols versus usual care, provided patients were still identified early, given antibiotics promptly, and resuscitated with ~40–60 mL/kg in the first 6 hours.

Lactate Monitoring

• Elevated lactate (>2 mmol/L) signals tissue ischemia and predicts poor outcomes
• Serial lactate measurement guides resuscitation adequacy; lactate clearance is a useful endpoint
• Caveats: lactate may also rise from β-adrenergic activation, acute lung injury, medications, or hepatic dysfunction — interpret in clinical context

2. Antimicrobial Therapy

• Obtain ≥2 sets of blood cultures (aerobic + anaerobic) before antibiotics, but do not delay antibiotics >45 min to obtain cultures
• Use empirical broad-spectrum coverage guided by suspected source, local resistance patterns, and host immune status
• De-escalate once culture/sensitivity data available (typically 48–72 hrs) — duration: 7–10 days in most cases; longer for immunocompromised, slow clinical response, or S. aureus bacteremia

Antibiotic Selection by Source (Table 127.3, Rosen's EM)

3. Vasoactive Therapy

Vasopressors

• Target MAP: ≥65 mmHg (may need ≥75 mmHg in patients with prior hypertension)
• Add dobutamine (2–15 μg/kg/min) if myocardial dysfunction (low output state) is evident despite adequate preload

4. Source Control

• Drain abscesses, debride infected tissue, remove infected foreign bodies (e.g., IV catheters, prostheses)
• Surgical intervention (e.g., perforated viscus, necrotizing fasciitis, cholecystitis) within 6–12 hours where feasible
• Percutaneous drainage preferred over open surgery when equally effective

5. Respiratory Support

• Septic shock + altered mental status → consider early intubation for airway protection
• Indications: persistent hypoxemia, hypercapnia, profound acidosis, airway compromise
• Mechanical ventilation strategy for ARDS: low tidal volume 6 mL/kg ideal body weight, plateau pressure ≤30 cm H₂O (ARDSNet protocol), higher PEEP to improve oxygenation

6. Corticosteroids

• Hydrocortisone 200–300 mg/day IV (typically 200 mg/day continuous infusion or 50 mg q6h) for refractory septic shock — defined as requiring escalating vasopressors despite adequate resuscitation
• Mechanism: relative adrenal insufficiency is common in septic shock; steroids improve vasopressor sensitivity
• Do not use ACTH stimulation testing to guide steroid use (no longer recommended)
• Taper once vasopressors are discontinued
• Evidence: Cochrane meta-analyses show modest reduction in vasopressor duration and ICU stay; survival benefit is modest and context-dependent

7. Blood Glucose Management

• Target glucose: 140–180 mg/dL (7.8–10 mmol/L) using insulin infusion protocols
• Avoid intensive insulin therapy (target <110 mg/dL) — associated with increased hypoglycemia and harm (NICE-SUGAR trial)

8. Additional ICU Measures

9. Monitoring Endpoints

• Lactate clearance (target ≥10% reduction per 2-hour interval, or normalization)
• MAP ≥65 mmHg
• Urine output ≥0.5 mL/kg/hr
• Mental status improvement
• Central venous O₂ saturation (ScvO₂) — target ≥70%
• SOFA score trend

10. Special Populations

Key Evidence Landmarks