Approach to Sepsis and Septic Shock

Approach to Sepsis and Septic Shock

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, operationally defined as suspected or confirmed infection with SOFA ≥2.

Septic shock is a subset of sepsis characterized by persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg and serum lactate >2 mmol/L despite adequate fluid resuscitation, reflecting severe circulatory and metabolic dysfunction.

Pathophysiology

Infection → immune activation → cytokine release → endothelial dysfunction and increased capillary permeability → vasodilation with relative intravascular hypovolemia → microcirculatory dysfunction (heterogeneous flow, impaired oxygen extraction) → mitochondrial dysfunction → lactate elevation (reflecting hypoperfusion and metabolic stress) → organ dysfunction

Additional mechanisms include myocardial depression, dysregulated coagulation, and microthrombosis.

1. Etiology and Sources

1. Respiratory infections (most common; pneumonia)
2. Intra-abdominal infections
3. Genitourinary infections
4. Skin and soft tissue infections
5. Healthcare-associated infections (devices, procedures)
6. Fungal or viral infections in high-risk patients

2. Risk Factors

1. Advanced age or infancy
2. Immunocompromised states
3. Chronic comorbidities (e.g., diabetes, CKD, malignancy)
4. Indwelling devices
5. Recent hospitalization or surgery

3. Clinical Features

3.1 Early (Sepsis)

1. Fever or hypothermia
2. Tachycardia
3. Tachypnea
4. Altered mental status
5. Leukocytosis or leukopenia

3.2 Septic Shock / Advanced Disease

1. Hypotension or vasopressor requirement
2. Lactate >2 mmol/L
3. Oliguria (<0.5 mL/kg/h)
4. Altered mentation
5. Progressive multi-organ dysfunction
6. Peripheral perfusion may be warm early and cool later

4. Diagnosis and Assessment

1. Suspected infection + SOFA ≥2
2. Measure lactate as a marker of illness severity and hypoperfusion (interpret in context)
3. Obtain blood cultures before antibiotics (do not delay treatment)
4. Continuous reassessment of hemodynamics and organ function

Screening (SSC 2026)

1. Use early warning scores (e.g., NEWS, NEWS2, MEWS, SIRS)
2. Do not use qSOFA alone as a screening tool

5. Management

5.1 Core Principle

Sepsis and septic shock are medical emergencies; initiate treatment immediately

5.2 Antimicrobial Therapy

1. Septic shock → administer antimicrobials immediately (within 1 hour)
2. Probable or definite sepsis → administer immediately (within 1 hour)
3. Possible sepsis (uncertain diagnosis):
• Perform rapid evaluation (within 3 hours)
• Initiate antimicrobials if infection remains likely

Additional principles:

• Start broad-spectrum empiric therapy
• Do not delay antibiotics for biomarkers or imaging
• Reassess daily and de-escalate based on cultures and clinical response

5.3 Fluid Resuscitation

1. Administer at least 30 mL/kg IV crystalloid within the first 3 hours
2. Use actual body weight (consider adjustment in obesity)
3. Prefer balanced crystalloids
4. Reassess frequently and individualize further fluid therapy

Dynamic Assessment Tools

• Passive leg raise
• Stroke volume or cardiac output response
• Capillary refill time
• Bedside ultrasound

Avoid both inadequate resuscitation and fluid overload

5.4 Hemodynamic Management

1. Target MAP ≥65 mmHg
2. First-line vasopressor: Norepinephrine
3. Add vasopressin if needed
4. Add epinephrine if refractory
5. Add dobutamine if myocardial dysfunction with hypoperfusion
6. Hydrocortisone 200 mg/day IV in persistent vasopressor-dependent shock
7. Vasopressors may be initiated early in unstable patients

5.5 Infection Management and Source Control

1. Initiate empiric broad-spectrum antibiotics promptly
2. Reassess daily and de-escalate therapy
3. Perform early source control when indicated
4. Do not delay antibiotics for procalcitonin

5.6 Respiratory Support

1. Avoid hyperoxia
2. Oxygen targets should be individualized based on patient condition
3. HFNC preferred over conventional oxygen
4. NIV may be used in selected patients

Mechanical Ventilation (if required)

1. Tidal volume: 6 mL/kg predicted body weight
2. Plateau pressure ≤30 cmH₂O
3. Apply appropriate PEEP strategies

ARDS Adjuncts

1. Prone positioning ≥12 to 16 hours per day in moderate to severe ARDS
2. Neuromuscular blockade in selected patients

ARDS Diagnosis

1. Berlin criteria
2. Kigali modification (resource-limited settings)

5.7 Adjunctive Care

1. Transfusion: Hb <7 g/dL (restrictive strategy)
2. VTE prophylaxis: LMWH preferred
3. Glucose control:
• Initiate insulin ≥180 mg/dL
• Target 144 to 180 mg/dL
4. Bicarbonate therapy:
• Only if pH ≤7.2 with concomitant AKI (stage 2 to 3)
5. Renal replacement therapy:
• Initiate based on standard clinical indications
6. Nutrition:
• Early enteral feeding within 24 to 72 hours

6. Septic Shock (Quick Summary)

1. Requires vasopressors to maintain MAP ≥65 mmHg despite adequate fluid resuscitation
2. Serum lactate >2 mmol/L
3. Reflects severe circulatory and metabolic dysfunction

7. Monitoring and Targets

1. MAP ≥65 mmHg
2. Urine output ≥0.5 mL/kg/h
3. Lactate trend (clearance over time)
4. Mental status and peripheral perfusion

8. Clinical Pearls

1. Sepsis is a time-critical medical emergency
2. Early antimicrobials and fluid resuscitation are essential
3. Norepinephrine is the first-line vasopressor
4. Lactate reflects illness severity and metabolic stress
5. Use dynamic reassessment rather than fixed protocols
6. Source control is essential for definitive management
7. Avoid fluid overload and unnecessary hyperoxia
8. Reassess frequently and de-escalate therapy

References

1. Harrison's Principles of Internal Medicine, 22^nd Edition
2. Surviving Sepsis Campaign (SSC), 2026