Severe Sepsis Management

Note on terminology: Sepsis-3 (2016) removed "severe sepsis" as a standalone term. What was previously called "severe sepsis" is now simply called sepsis (infection + acute organ dysfunction). Septic shock is the subset with vasopressor requirement + lactate >2 mmol/L despite fluids. This guide covers both.

1. Definitions (Sepsis-3)

SOFA Score Components

• Goldman-Cecil Medicine, screening table; Harrison's Principles 22E, Ch. 315

2. Initial Resuscitation - The "1-Hour Bundle"

A. Within the First Hour (Septic Shock or Lactate ≥4 mmol/L)

1. Measure lactate - repeat if initial >2 mmol/L to assess resuscitation
2. Blood cultures x2 before antibiotics (do not delay antibiotics >45 min to obtain cultures)
3. Broad-spectrum antibiotics - within 1 hour of recognition
4. IV crystalloid - 30 mL/kg within 3 hours (balanced crystalloids preferred)
5. Vasopressors if MAP <65 mmHg despite initial fluids

B. Fluid Resuscitation (SSC 2026 Updated Guidance)

• Preferred fluid: Balanced crystalloids (Lactated Ringer's, Plasma-Lyte) over normal saline - reduces risk of hyperchloremic metabolic acidosis and AKI
• Initial bolus: 30 mL/kg crystalloid in first 3 hours
• Beyond 30 mL/kg: use dynamic hemodynamic parameters (pulse pressure variation, stroke volume variation, passive leg raise response) to guide further fluid
• Albumin: consider when large volumes of crystalloid have been given and patient has persistent hypoperfusion
• Avoid: hetastarch/HES formulations (increased AKI and mortality risk)
• Post-resuscitation: SSC 2026 recommends active fluid removal (diuretics or ultrafiltration) once the acute resuscitation phase has passed - cumulative fluid overload worsens outcomes

SSC 2026 notes that either a liberal or restrictive fluid strategy post-30 mL/kg bolus may be used based on individual patient and health system factors.

3. Antibiotics

Timing

• Septic shock or lactate ≥4 mmol/L: within 1 hour - each hour of delay adds ~7-8% mortality
• Sepsis without shock: within 1-3 hours; if diagnosis uncertain and shock absent, time-limited clinical evaluation is reasonable before committing to empiric therapy
• De-escalate based on culture/sensitivities as soon as possible (stewardship)
• Procalcitonin: do NOT use to decide when to start antibiotics; may help guide when to stop

Empiric Selection by Suspected Source

• Harrison's Principles 22E, Ch. 315; Barash Clinical Anesthesia 9e, Table 57-4

Antibiotic Optimization

• Administer beta-lactams before vancomycin when both are indicated
• Consider prolonged/extended infusion of beta-lactams to optimize time-above-MIC
• Consult pharmacy/infectious disease for PK/PD optimization

4. Source Control

• Mandatory and urgent - identify and eliminate the anatomic infection source as quickly as possible
• Examples: drainage of abscesses (intraabdominal, soft tissue), debridement of necrotizing fasciitis, cholecystectomy/biliary drainage for cholangitis, nephrectomy/stenting for obstructive uropathy
• Remove any infected indwelling catheters
• If source control requires invasive procedure, it should not delay initiation of antibiotics

5. Vasopressors

Key Updates (SSC 2026)

• Peripheral vasopressors are acceptable while obtaining central access - do not delay NE initiation
• MAP target 65 mmHg (not higher targets - moderate evidence)
• Levosimendan and terlipressin are not recommended

6. Corticosteroids

• Indication: Septic shock that remains on vasopressors
• Dose: Hydrocortisone 50 mg IV q6h (200 mg/day) - either bolus or continuous infusion
• Evidence: Two meta-analyses show shorter duration of shock with corticosteroids, though mortality benefit is modest
• SSC 2026: conditional recommendation, low certainty of evidence
• Not recommended in sepsis without shock

7. Respiratory Support

Oxygen

• Target SpO2 92-96% with supplemental O2
• Low-flow O2 → high-flow nasal cannula → non-invasive ventilation before intubation (if appropriate)

Mechanical Ventilation (if ARDS develops)

• Tidal volume: 6 mL/kg predicted body weight (lung-protective)
• Plateau pressure: ≤30 cmH2O
• PEEP: Higher PEEP strategies for moderate-severe ARDS
• Do NOT use incremental PEEP titration strategy
• Prone positioning: ≥12 hours/day for moderate-severe ARDS (PaO2/FiO2 <150)
• Neuromuscular blockade: for prone positioning - intermittent boluses preferred over continuous infusion
• VV-ECMO: consider for severe ARDS failing mechanical ventilation at experienced centers
• Elevate head of bed 30-45° (semi-recumbent) unless contraindicated
• Avoid routine pulmonary artery catheters
• Use weaning protocols + daily sedation interruption (if continuous infusion sedation)

8. Glycemic Control

• Target blood glucose 140-180 mg/dL (7.8-10 mmol/L)
• Avoid tight control <110 mg/dL (hypoglycemia risk)
• Use validated insulin infusion protocols
• Monitor glucose q1-2h when on insulin infusion

9. Adjunctive and Supportive Care

10. Monitoring Adequacy of Resuscitation

• Lactate clearance: target ≥10-20% reduction every 2 hours; normalization (<2 mmol/L) is the goal
• MAP ≥65 mmHg
• Urine output ≥0.5 mL/kg/hr
• Mental status normalization
• Dynamic parameters (PPV, SVV, passive leg raise) to guide ongoing fluid decisions

11. Common Organisms by Source (Quick Reference)

• Harrison's Principles 22E, Ch. 315

12. What's New - SSC 2026 Key Updates

• Fluid resuscitation: more individualized approach - no mandated volume after initial 30 mL/kg; dynamic assessment guides further fluid
• Earlier vasopressors: can be started peripherally; concurrent with fluids in unstable shock
• Active fluid removal recommended post-resuscitation phase (diuretics/ultrafiltration)
• Intermittent NMBA boluses preferred over continuous infusion for ARDS
• VV-ECMO for refractory severe ARDS (conditional)
• Children managed under separate 2026 pediatric SSC guidelines (PMID: 41869844)

• Harrison's Principles of Internal Medicine 22E (2025), Ch. 315 - Sepsis and Septic Shock
• Barash Clinical Anesthesia 9e, Table 57-4 - Management of Sepsis and Septic Shock
• Goldman-Cecil Medicine, Table 94-1 - Screening for Sepsis and Septic Shock
• Surviving Sepsis Campaign International Guidelines 2026 - SCCM/ESICM
• S3 Guideline Update 2025 (PMID: 40824313) - German adaptation of SSC 2021
• Sepsis Alert Systems meta-analysis, JAMA Network Open 2024 (PMID: 39037814)