What are the initial treatment guidelines for a patient diagnosed with sepsis?

Initial Treatment Guidelines for Sepsis

Administer IV broad-spectrum antibiotics within one hour of sepsis recognition, obtain blood cultures before antibiotics (but never delay beyond 45 minutes), give 30 mL/kg crystalloid bolus for hypotension or lactate ≥4 mmol/L, and start vasopressors if hypotension persists despite fluids—targeting MAP ≥65 mmHg. 1, 2

The Hour-1 Bundle: Five Critical Actions

The Surviving Sepsis Campaign emphasizes immediate implementation of these five interventions within the first hour of sepsis recognition, as each hour of antibiotic delay decreases survival by approximately 7.6% 1:

1. Measure Lactate Immediately

• Draw lactate level at time of sepsis recognition 1, 2
• Remeasure within 2-4 hours if initially elevated (≥2 mmol/L) 3, 1
• Target lactate normalization (<2 mmol/L) as a marker of adequate tissue perfusion 3, 1
• Caveat: Do not use lactate to diagnose sepsis during active labor, as it physiologically elevates in laboring patients 1

2. Obtain Blood Cultures Before Antibiotics

• Draw at least two sets of blood cultures (aerobic and anaerobic bottles) before starting antimicrobials 3, 1, 2
• One set should be drawn percutaneously and one through each vascular access device (unless recently inserted <48 hours) 3
• Critical pitfall: Never delay antibiotics beyond 45 minutes waiting for cultures 1, 2
• If obtaining cultures causes any substantial delay, start antibiotics immediately 3, 1

3. Administer Broad-Spectrum Antibiotics Within 60 Minutes

• Give IV antibiotics within the first hour of sepsis recognition for both septic shock (grade 1B) and severe sepsis without shock (grade 1C) 3, 1, 2
• Select empiric therapy covering all likely pathogens (bacterial, fungal, or viral) with adequate tissue penetration to the presumed infection source 3, 1
• If IV access is delayed in children, give first doses intramuscularly, orally, or rectally 1
• Evidence strength: Multiple retrospective studies demonstrate increased mortality with delayed antibiotics, though some data suggest watchful waiting may be appropriate in non-shocked patients with low infection likelihood 4

4. Rapid 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, 2
• 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
• Consider albumin when patients require substantial amounts of crystalloids 1
• Never use hydroxyethyl starches—they are contraindicated in sepsis 1
• Pitfall: Monitor for fluid overload and pulmonary edema while avoiding inadequate initial resuscitation 1

5. Start Vasopressors for Persistent Hypotension

• Initiate vasopressors if hypotension persists despite adequate fluid resuscitation 3, 1, 2
• Target mean arterial pressure (MAP) ≥65 mmHg 3, 1, 2
• Use norepinephrine as the first-line vasopressor agent 1, 2
• Administer positive inotropes when cardiac failure persists (low cardiac index and mixed venous oxygen saturation) despite adequate volume expansion—this occurs in 10-20% of adult sepsis cases 1

Source Control

• Identify and control the infection source within 12 hours when feasible 1, 2
• Do not delay surgical intervention or drainage procedures 1
• Use the least physiologically invasive effective intervention (e.g., percutaneous drainage rather than surgical drainage of an abscess) 1, 2
• Remove intravascular access devices promptly after establishing alternative vascular access if they are a possible infection source 1

Ongoing Hemodynamic Assessment

After initial resuscitation, frequent reassessment is essential 3, 1:

• Evaluate capillary refill time, skin temperature and mottling, mental status changes 1, 2
• Monitor urine output (target >0.5 mL/kg/hour) 3, 1
• Assess lactate clearance 1, 2
• Use dynamic variables (pulse pressure variation, stroke volume variation) over static variables to predict fluid responsiveness 3, 1
• Perform additional hemodynamic assessment (such as cardiac function evaluation) if clinical examination does not lead to clear diagnosis 3

Antimicrobial De-escalation

• Reassess antimicrobial regimen daily for potential de-escalation once culture results and clinical response are available 3, 1, 2
• Narrow therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted 2
• Use procalcitonin levels to support discontinuing empiric antibiotics in patients with no subsequent evidence of infection 3, 1, 2
• Discontinue combination therapy within 3-5 days in response to clinical improvement and/or evidence of infection resolution 2

Corticosteroid Therapy

• Consider hydrocortisone 200 mg/day for patients with refractory septic shock not responding to vasopressor therapy after at least 4 hours of norepinephrine or epinephrine at 0.25 µg/kg/min 1
• Particularly indicated for patients requiring catecholamines despite adequate fluid resuscitation 1

Respiratory Support

• Administer oxygen to achieve saturation ≥90% and position patients semi-recumbent or laterally 1
• Use non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy 1
• 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

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 1, 2
• Resume oral food intake after resuscitation and regaining of consciousness 1
• Initiate early mobilization and active weaning of invasive support 1

Screening and Performance Improvement

• Hospitals should have a performance improvement program for sepsis, including routine screening of acutely ill, high-risk patients 3, 2
• Screen using clinical criteria: altered mental status, systolic blood pressure ≤100 mmHg, respiratory rate ≥22/min, and signs of tissue hypoperfusion 2
• Important: qSOFA has poor sensitivity (31-50%) and should not delay treatment initiation 1, 2