What is the management of sepsis?

Management of Sepsis

Sepsis management requires immediate initiation of the Hour-1 Bundle: obtain blood cultures, measure lactate, administer broad-spectrum antibiotics within 60 minutes, give 30 mL/kg crystalloid bolus for hypotension or lactate ≥4 mmol/L, and start vasopressors if hypotension persists despite fluids—targeting mean arterial pressure ≥65 mmHg. 1, 2

Immediate Recognition and Assessment

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, identified by an increase in Sequential Organ Failure Assessment (SOFA) score of 2 points or more. 3

• Screen all acutely ill patients using bedside criteria: altered mental status, systolic blood pressure ≤100 mmHg, respiratory rate ≥22/min, and signs of tissue hypoperfusion 2
• Do not wait for qSOFA scores to initiate treatment—qSOFA has poor sensitivity (31-50%) and should never delay therapy 1, 2
• Recognize that each hour of delay in treatment decreases survival by approximately 7.6% 1

Common pitfall: Waiting for laboratory confirmation or complete diagnostic workup before starting treatment. Sepsis is a time-dependent emergency requiring immediate action based on clinical suspicion. 4, 5

The Hour-1 Bundle: Five Critical Actions

1. Obtain Blood Cultures Immediately

• Draw at least two sets of blood cultures (aerobic and anaerobic bottles) before starting antibiotics 1, 6, 2
• Never delay antibiotics beyond 45 minutes if cultures cannot be obtained quickly 6, 2
• Perform Gram stain and microscopic examination when applicable 3

2. Measure Lactate Level

• Measure lactate immediately upon sepsis recognition 1, 2
• Remeasure within 2-4 hours if elevated (≥2 mmol/L) to guide resuscitation 1, 2
• Target lactate normalization as a marker of adequate tissue perfusion 1, 2

Important note: Elevated lactate levels are no longer part of organ dysfunction criteria to define sepsis—high lactate should only be used as one criterion to define septic shock (lactate >2 mmol/L with vasopressor requirement). 3

3. Administer Broad-Spectrum Antibiotics Within 60 Minutes

• Give IV broad-spectrum antimicrobials within one hour of sepsis recognition 1, 6, 2
• Cover all likely pathogens (bacterial, and potentially fungal or viral) with empiric therapy 6, 2
• Use combination therapy with at least two antibiotics of different classes for septic shock 6
• If IV access is delayed in children, give first doses intramuscularly, orally, or rectally 1

Critical point: Each hour of antibiotic delay decreases survival by 7.6%—this is non-negotiable. 1

4. Aggressive Fluid Resuscitation

• Administer 30 mL/kg IV crystalloid bolus rapidly (over 5-10 minutes) for hypotension or lactate ≥4 mmol/L 1, 2
• Use either balanced crystalloids or normal saline as initial fluid of choice 1, 6
• Continue fluid administration as long as hemodynamic factors improve based on dynamic variables (pulse pressure variation, stroke volume variation) or static variables (arterial pressure, heart rate, capillary refill, skin mottling) 1
• More than 4 liters during the first 24 hours may be required in adults 3
• Consider albumin when patients require substantial amounts of crystalloids 1

Never use hydroxyethyl starches—they are contraindicated in sepsis. 1

5. Initiate Vasopressors for Persistent Hypotension

• Start vasopressors if hypotension persists despite adequate fluid resuscitation 1, 2
• Target mean arterial pressure (MAP) ≥65 mmHg 1, 6, 2
• Use norepinephrine as the first-line vasopressor agent 1, 2
• Alternatively, use dopamine or epinephrine in resource-limited settings 3
• Measure arterial blood pressure and heart rate frequently in patients requiring vasopressors 3

Source Control

Identify and control the infection source within 12 hours when feasible—do not delay surgical intervention or drainage procedures. 1, 6

• Use the least physiologically invasive effective intervention (percutaneous drainage rather than surgical drainage when possible) 1, 6
• Typical sources requiring emergent control: abscesses, necrotizing soft tissue infections, gastrointestinal perforation, cholangitis, obstructive urinary tract infection, pleural empyema, septic arthritis 3
• Remove intravascular access devices promptly after establishing alternative access if they are a possible infection source 1
• Check all artificial devices for signs of infection and consider removal if device-related infection is suspected 3

Respiratory Support

• Administer oxygen to achieve saturation ≥90% 1, 6
• Position patients semi-recumbent (head of bed raised 30-45 degrees) 3, 6
• Place unconscious patients in lateral position and keep airway clear 3
• Use non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy 1, 6
• For mechanically ventilated patients with sepsis-induced ARDS, use lower tidal volumes (6 mL/kg ideal body weight) and limit plateau pressures to ≤30 cmH₂O 1, 2

Corticosteroid Therapy

• Administer IV hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) to adult patients requiring escalating dosages of vasopressors 3, 1
• Consider equivalent doses in children with severe shock 3
• Use corticosteroids particularly for refractory septic shock not responding to vasopressor therapy 1

Antimicrobial De-escalation and Duration

• Reassess antimicrobial therapy daily for potential de-escalation once culture results and clinical response are available 1, 2
• Narrow therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted 2
• Discontinue combination therapy within 3-5 days in response to clinical improvement and/or evidence of infection resolution 2
• Use procalcitonin levels to support discontinuing empiric antibiotics in patients with limited clinical evidence of infection 1, 2

Common pitfall: Continuing broad-spectrum antibiotics unnecessarily. De-escalation reduces bacterial resistance and improves outcomes. 3

Ongoing Monitoring and Reassessment

• Never leave septic patients alone—ensure continuous observation 3
• Perform clinical examinations several times per day 3, 6
• Reassess hemodynamic status frequently after initial interventions: capillary refill time, skin temperature, mental status, urine output (target >0.5 mL/kg/hour), and lactate clearance 1, 2
• Worsening or ongoing organ dysfunction and persistence of fever for more than 48-72 hours following treatment initiation should question adequacy of therapy 3

Additional Supportive Care

• Target hemoglobin between 8-9 g/dL for acute anemia, adjusting based on clinical tolerance and central venous oxygen saturation 1, 2
• Provide pharmacological or mechanical deep vein thrombosis prophylaxis in post-pubertal children and adults 3, 1, 2
• Target blood glucose levels ≤180 mg/dL using a protocolized approach 6
• Resume oral food intake after resuscitation and regaining consciousness 3
• Minimize continuous or intermittent sedation in mechanically ventilated patients 6
• Initiate early mobilization and active weaning of invasive support 1

Septic Shock Definition

Septic shock is defined as a subset of sepsis requiring vasopressor therapy to maintain MAP ≥65 mmHg and serum lactate >2 mmol/L (>18 mg/dL) in the absence of hypovolemia. 3