What is the first-line management of sepsis in an adult patient?

First-Line Management of Adult Sepsis

Administer intravenous broad-spectrum antibiotics within 1 hour of recognizing sepsis, give at least 30 mL/kg of crystalloid fluid within the first 3 hours, and start norepinephrine if mean arterial pressure remains below 65 mmHg despite adequate fluid resuscitation. 1, 2

Immediate Actions (First Hour)

Antimicrobial Therapy

• Give IV broad-spectrum antibiotics within 60 minutes of sepsis recognition; each hour of delay reduces survival by approximately 7.6%. This is the single most time-critical intervention. 1, 3
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but never delay antimicrobial administration beyond 45 minutes to obtain cultures. 1
• Choose empiric therapy that covers gram-positive organisms (including MRSA when risk factors exist), gram-negative bacteria (including Pseudomonas aeruginosa in healthcare-associated infections), and anaerobes for intra-abdominal or aspiration sources. 1
• Add empiric antifungal coverage (e.g., an echinocandin) in patients with immunosuppression, prolonged ICU stay, total parenteral nutrition, or recent broad-spectrum antibiotic exposure. 1

Fluid Resuscitation

• Administer a minimum of 30 mL/kg of IV crystalloid (normal saline or balanced solution) within the first 3 hours. For a 70-kg adult, this equals approximately 2 liters given as rapid 500–1000 mL boluses over 5–10 minutes. 4, 1, 2
• Use isotonic crystalloids as first-line therapy; they are well-tolerated, inexpensive, and have comparable efficacy to colloids. 4, 2
• Continue additional fluids while hemodynamic improvement is observed, guided by dynamic indices (pulse-pressure variation, stroke-volume variation) or static variables (arterial pressure, heart rate, urine output). 4, 1

Hemodynamic Targets (First 6 Hours)

• Target mean arterial pressure (MAP) ≥ 65 mmHg in most adults; for patients with chronic hypertension, aim for 70–85 mmHg because their autoregulatory curve is shifted rightward. 4, 1
• Maintain urine output ≥ 0.5 mL/kg/hour as a bedside marker of adequate renal perfusion. 4, 1, 2
• Target central venous pressure (CVP) 8–12 mmHg (or 12–15 mmHg if mechanically ventilated) to assess fluid responsiveness. 4, 1
• Achieve central venous oxygen saturation (ScvO₂) ≥ 70% (or mixed venous O₂ saturation ≥ 65%) to confirm adequate tissue oxygen delivery. 4, 1
• Monitor clinical perfusion markers: capillary refill < 2 seconds, warm extremities, normal mental status, and palpable peripheral pulses. 4, 1

Vasopressor Therapy

• Start norepinephrine as the first-line vasopressor at 0.05–0.1 µg/kg/min when MAP remains < 65 mmHg after the initial 30 mL/kg fluid bolus. Norepinephrine is more effective than dopamine and causes fewer arrhythmias. 4, 1
• Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is required or to reduce norepinephrine dose; vasopressin should never be used as the sole initial vasopressor. 4, 1
• Introduce epinephrine as a third-line agent if MAP targets remain unmet despite norepinephrine plus vasopressin. 4, 1
• Add dobutamine 2.5–5 µg/kg/min when myocardial dysfunction or persistent tissue hypoperfusion ("cold shock") is evident despite adequate MAP and volume status, indicated by low cardiac output, cold extremities, or confusion. 4, 1

Lactate Monitoring

• Measure serum lactate immediately at sepsis recognition as a baseline metabolic marker. 1
• Repeat lactate measurement within 6 hours if the initial value is ≥ 2 mmol/L; use lactate normalization as a resuscitation endpoint to guide ongoing therapy. 1

Source Control

• Identify or exclude a specific anatomic infection source requiring emergent intervention within 12 hours of sepsis onset (e.g., abscess, infected device, bowel perforation). 4, 1, 2
• Perform definitive source-control procedures (drainage, debridement, removal of infected devices) as soon as medically and logistically feasible; inadequate source control is independently associated with increased mortality. 4, 1, 2
• Sample fluid or tissue from the suspected infection site whenever possible; examine by Gram stain, culture, and antibiogram. 4, 1

Respiratory Support

• Apply oxygen to achieve oxygen saturation ≥ 90%; if pulse oximetry is unavailable, administer oxygen empirically. 4, 2
• Place patients in semi-recumbent position with head of bed elevated 30–45 degrees to reduce aspiration risk and ventilator-associated pneumonia. 4, 2
• Consider non-invasive ventilation in patients with dyspnea and/or persistent hypoxemia despite oxygen therapy if medical staff is adequately trained. 4, 2
• If mechanical ventilation is required, use tidal volume 6 mL/kg predicted body weight and keep plateau pressures ≤ 30 cm H₂O to minimize ventilator-induced lung injury. 4, 5

Antimicrobial De-escalation

• Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, typically within 48–72 hours. 4, 1
• De-escalate to the most appropriate single agent within 3–5 days based on culture data and clinical improvement; de-escalation is a protective factor for mortality. 4, 1
• Plan a total antibiotic course of 7–10 days for most serious infections associated with sepsis. 1
• Extend antibiotic duration for slow clinical response, undrained infection 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. 4, 5
• Consider hydrocortisone 200 mg/day (e.g., 50 mg IV every 6 hours) only if hemodynamic stability cannot be attained despite adequate fluid resuscitation and vasopressor therapy. 4, 5
• Taper hydrocortisone when vasopressors are no longer required. 4, 5

Blood Product Management

• Target hemoglobin 7–9 g/dL unless there is tissue hypoperfusion, ischemic coronary disease, or acute hemorrhage. 4, 5
• Transfuse red blood cells only when hemoglobin falls below 7.0 g/dL. 4, 5

Prophylaxis

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

Common Pitfalls to Avoid

• Delaying antimicrobial administration beyond 1 hour directly increases mortality—this is the most critical error. 1, 2, 3
• Inadequate initial fluid resuscitation—the 30 mL/kg bolus is a minimum, not a maximum; many patients require more. 1, 2
• Failing to initiate vasopressors when MAP remains < 65 mmHg despite fluids—this prolongs tissue hypoperfusion and worsens outcomes. 1, 2
• Relying solely on MAP—normal MAP can coexist with severe tissue hypoperfusion; always monitor lactate, urine output, mental status, and skin perfusion. 1
• Using dopamine as first-line therapy—it is linked to more arrhythmias and worse outcomes compared with norepinephrine. 4
• Excessive fluid administration when vasopressor support is required—this risks fluid overload, especially in patients with abdominal pathology or ARDS. 1, 6
• Attempting extubation while patients still require vasopressors—this is an absolute contraindication. 5