What is the initial management for a patient with sepsis?

Initial Management of Sepsis

Administer IV broad-spectrum antibiotics within one hour of recognizing sepsis or septic shock, immediately after obtaining blood cultures, while simultaneously initiating aggressive fluid resuscitation with 30 mL/kg of crystalloid within the first three hours. 1, 2

Immediate Recognition and Assessment (First 15 Minutes)

• Calculate a NEWS2 score to stratify risk of severe illness or death from sepsis 1
• Measure serum lactate immediately as a marker of tissue hypoperfusion—elevated lactate (>2 mmol/L) indicates need for aggressive resuscitation 1, 2
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but do not delay antimicrobial therapy beyond 45 minutes to obtain cultures 1, 2
• Identify potential source through focused history (recent procedures, indwelling devices, immunosuppression) and targeted imaging to confirm infection source 1

Antimicrobial Therapy (Within 1 Hour)

The timing of antibiotics is risk-stratified based on severity: 1

• High risk (NEWS2 ≥7 or septic shock): Antibiotics within 1 hour 1, 2
• Moderate risk: Antibiotics within 3 hours 1
• Low risk: Antibiotics within 6 hours 1

For septic shock specifically, use combination therapy with at least two antibiotics from different antimicrobial classes targeting the most likely bacterial pathogens 1, 2. This typically means an extended-spectrum beta-lactam (piperacillin-tazobactam 4.5g IV q6h or a carbapenem) plus coverage for MRSA (vancomycin or linezolid) if healthcare-associated infection or risk factors present 3, 4.

Critical caveat: The 2024 NICE guidelines 1 represent a shift from universal 1-hour targets, acknowledging that not all sepsis patients require the same urgency and that overly aggressive antibiotic administration can cause harm through overtreatment of non-infectious conditions 5. However, the Surviving Sepsis Campaign 1 maintains the 1-hour target for both sepsis and septic shock as a strong recommendation. In clinical practice, err on the side of earlier administration for any patient appearing critically ill.

Fluid Resuscitation (First 3 Hours)

• Administer 30 mL/kg of IV crystalloid as initial fluid challenge for sepsis-induced hypoperfusion 1, 2
• Use crystalloids (normal saline or balanced solutions) as first-line fluids—avoid hydroxyethyl starches entirely 1, 6
• Consider albumin only if patients continue requiring substantial crystalloid to maintain adequate mean arterial pressure 1
• Continue fluid challenges as long as hemodynamic improvement occurs, guided by dynamic variables (pulse pressure variation, stroke volume variation) rather than static measures (CVP) when available 1, 6

Hemodynamic Support and Vasopressors

If hypotension persists despite adequate fluid resuscitation:

• Target mean arterial pressure (MAP) ≥65 mmHg 1, 2
• Norepinephrine is the first-choice vasopressor 1, 2, 6
• Add epinephrine as second agent if additional support needed 1, 6
• Vasopressin 0.03 U/min can be added to norepinephrine to raise MAP or decrease norepinephrine dose, but should not be used as initial vasopressor 1
• Avoid dopamine except in highly selected circumstances (e.g., patients with low risk of arrhythmias and bradycardia) 1
• Add dobutamine if myocardial dysfunction present (elevated filling pressures with low cardiac output) or ongoing hypoperfusion despite adequate volume and MAP 1

Lactate-Guided Resuscitation

• Remeasure lactate within 2-6 hours if initially elevated 1, 6
• Guide ongoing resuscitation to normalize lactate—persistently elevated lactate indicates inadequate tissue perfusion requiring continued aggressive management 1, 6

Source Control

• Identify and control the anatomic source of infection as rapidly as possible 2, 6
• Implement source control interventions (drainage of abscesses, debridement of infected tissue, removal of infected devices) as soon as medically and logistically practical, ideally within 12 hours 2, 3, 6
• Remove intravascular access devices if confirmed as infection source after establishing alternative access 2

Antimicrobial De-escalation (Days 3-5)

• Reassess antimicrobial therapy daily for potential narrowing of spectrum 1, 3, 4
• Discontinue combination therapy within 3-5 days once clinical improvement occurs and/or culture results available 1, 3
• Narrow to targeted therapy based on culture results and sensitivities within 24-48 hours 1, 2
• Total duration typically 7-10 days for most serious infections, though shorter courses appropriate for rapid clinical resolution with effective source control 1, 7, 4

Common Pitfalls to Avoid

Do not delay antibiotics to obtain imaging—imaging should be performed promptly but never at the expense of timely antimicrobial administration 1. Do not use hetastarch—it increases mortality and should be completely avoided 1, 6. Do not continue combination therapy beyond 3-5 days—prolonged broad-spectrum coverage increases resistance and toxicity without benefit 1, 3. Do not target CVP or SCVO2 as primary resuscitation endpoints—these static measures are poor predictors of fluid responsiveness 6.