What are the current guideline‑recommended steps for the initial management of an adult patient with suspected sepsis?

Initial Management of Adult Sepsis: Guideline-Recommended Steps

Begin immediate resuscitation within the first hour of recognizing sepsis, focusing on four simultaneous priorities: aggressive fluid bolus, early antibiotics, blood cultures, and lactate measurement. 1

Hour-One Bundle: Critical Actions

Fluid Resuscitation (Start Immediately)

• Administer at least 30 mL/kg of intravenous crystalloid within the first 3 hours of sepsis recognition—this is the cornerstone intervention and must begin before any diagnostic workup delays treatment. 2, 1
• Use isotonic crystalloid solutions (normal saline or balanced solutions such as lactated Ringer's) as first-line therapy; avoid hydroxyethyl starches entirely because they increase acute kidney injury and mortality. 1
• Deliver the initial 500 mL bolus rapidly over 5–10 minutes in shocked patients, monitoring for fluid overload by assessing jugular venous pressure, respiratory rate, and oxygen saturation. 2
• Continue fluid administration in 500 mL increments while hemodynamic improvement persists, using dynamic indices (pulse-pressure variation, stroke-volume variation) or static variables (arterial pressure, heart rate, urine output) to guide ongoing therapy. 1

Antimicrobial Therapy (Within 60 Minutes)

• Give broad-spectrum intravenous antibiotics within 1 hour of sepsis recognition—each hour of delay reduces survival by approximately 7.6%. 1, 3
• Choose empiric regimens that cover all likely pathogens: gram-positive, gram-negative, and anaerobic organisms; add antifungal agents when risk factors such as immunosuppression, prolonged ICU stay, or total parenteral nutrition are present. 1
• Ensure adequate tissue penetration by using appropriate dosing strategies for the chosen agents (e.g., extended infusions of beta-lactams for critically ill patients). 1

Microbiological Diagnosis (Before Antibiotics, But Do Not Delay)

• Obtain at least two sets of blood cultures (aerobic and anaerobic bottles) before starting antibiotics, but do not delay antibiotics more than 45 minutes to obtain cultures. 1
• Sample fluid or tissue from the suspected infection site whenever possible (e.g., urine, sputum, wound drainage, cerebrospinal fluid) and send for Gram stain, culture, and susceptibility testing. 1

Lactate Measurement and Monitoring

• Measure serum lactate immediately at sepsis recognition to identify tissue hypoperfusion. 1
• Repeat lactate within 6 hours after initial fluid resuscitation if the first value is elevated; use lactate normalization as a resuscitation endpoint. 1

Hemodynamic Targets (First 6 Hours)

Mean Arterial Pressure

• Target MAP ≥ 65 mmHg for most patients; this threshold prevents pressure-dependent organ hypoperfusion. 2, 1, 4
• Consider a higher MAP target (70–85 mmHg) in patients with chronic hypertension, as their autoregulatory curve is shifted rightward. 1

Additional Perfusion Endpoints

• Maintain urine output ≥ 0.5 mL/kg/hour (requires urinary catheter placement). 2, 1
• Achieve central venous pressure (CVP) 8–12 mmHg (or 12–15 mmHg if mechanically ventilated). 2, 1
• Target central venous oxygen saturation (ScvO₂) ≥ 70% or mixed venous O₂ saturation ≥ 65% to ensure adequate tissue oxygen delivery. 2, 1
• Monitor capillary refill time (target < 2 seconds), skin temperature, peripheral pulses, and mental status as bedside markers of perfusion. 2, 1

Vasopressor Support (When Fluid Alone Fails)

Initiation Criteria

• Start vasopressors when MAP remains < 65 mmHg despite adequate fluid resuscitation, or emergently in severe shock (e.g., critically low diastolic pressure) even before fluids are complete. 1
• Peripheral administration of norepinephrine is acceptable initially to avoid delays while central venous access is obtained. 1

Agent Selection

• Norepinephrine is the first-choice vasopressor, started at 0.05–0.1 µg/kg/min and titrated to maintain MAP ≥ 65 mmHg; it provides reliable MAP elevation with fewer arrhythmias than dopamine. 2, 1
• Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is needed or to permit a lower norepinephrine dose; never use vasopressin as the sole initial agent. 2, 1
• Epinephrine may be added as a second-line agent when norepinephrine alone is insufficient. 2, 1
• Avoid dopamine except in highly selected patients (e.g., low risk of tachyarrhythmias, bradycardia) because it is linked to more arrhythmias and worse outcomes. 1

Source Control (Within 12 Hours)

• Identify or exclude a specific anatomic infection source requiring emergent control within 12 hours of sepsis onset. 1
• Perform required interventions (drainage, debridement, device removal) as soon as medically and logistically feasible—this is as critical as antibiotics. 2, 1
• Choose the least physiologically invasive effective method (e.g., percutaneous drainage rather than open surgery when appropriate). 1
• Remove intravascular access devices that may be the infection source promptly after alternative access is secured. 1

Antimicrobial Stewardship (Daily Reassessment)

• Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, with the goal of de-escalation. 1
• Narrow to the most appropriate single agent within 3–5 days based on culture data and clinical response. 1
• Plan a total antibiotic course of 7–10 days for most serious infections; extend duration for slow clinical response, undrained foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency. 1

Adjunctive Therapies

Corticosteroids

• Do not use routine IV hydrocortisone in septic shock patients who achieve hemodynamic stability with fluids and vasopressors. 1, 5
• Consider hydrocortisone 200 mg/day (continuous infusion) only if hemodynamic stability cannot be attained despite adequate resuscitation; taper gradually once vasopressors are discontinued. 1, 5

Blood Product Management

• Target hemoglobin 7–9 g/dL unless there is tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage. 1, 5
• Platelet transfusion thresholds: < 10,000/mm³ (no bleeding), < 20,000/mm³ (significant bleeding risk), ≥ 50,000/mm³ (active bleeding or invasive procedures). 1, 5

Prophylaxis

• Provide pharmacologic deep-vein thrombosis prophylaxis (low-molecular-weight heparin or unfractionated heparin) unless contraindicated. 1, 5
• Use stress-ulcer prophylaxis (H₂-blocker or proton-pump inhibitor) in patients with bleeding risk factors. 1, 5

Mechanical Ventilation (When Required)

• For sepsis-induced ARDS, set a tidal volume of 6 mL/kg predicted body weight and keep plateau pressures ≤ 30 cm H₂O. 2, 5
• Apply positive end-expiratory pressure (PEEP) to prevent alveolar collapse; use higher PEEP strategies in moderate-to-severe ARDS. 2, 5
• Maintain head-of-bed elevation of 30–45° to reduce ventilator-associated pneumonia risk. 2, 5
• Consider prone positioning in ARDS patients with PaO₂/FiO₂ ratio < 150 mmHg. 2, 5

Common Pitfalls to Avoid

• Do not rely solely on MAP—normal MAP can coexist with severe tissue hypoperfusion ("cold shock"); always assess lactate, urine output, mental status, and capillary refill. 1
• Do not delay antibiotics to obtain cultures—if cultures cannot be drawn within 45 minutes, start antibiotics immediately and obtain cultures afterward. 1
• Do not assume a universal MAP = 65 mmHg target—adjust upward for chronic hypertension or intra-abdominal hypertension, and consider lower targets in the very elderly. 1
• Avoid fluid overload, especially in patients with peritonitis or at risk for abdominal compartment syndrome; fluid overload can worsen gut edema, raise intra-abdominal pressure, and precipitate respiratory compromise. 1
• Never extubate patients still requiring vasopressors—this is explicitly contraindicated in the guidelines. 5

Ongoing Monitoring and Goals of Care

• Reassess the patient frequently (every 15–30 minutes initially) to evaluate response to treatment and need for escalation of care. 1
• Address goals of care early, ideally within the first 72 hours of ICU admission, incorporating palliative care principles where appropriate. 1