What is the initial management for a patient with sepsis?

Initial Management of Sepsis

Administer IV broad-spectrum antimicrobials 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. 1

Immediate Actions (Within First Hour)

Obtain Cultures Before Antibiotics

• Draw at least two sets of blood cultures (aerobic and anaerobic) before starting antimicrobials, but do not delay antibiotics beyond 45 minutes to obtain them 1, 2
• Obtain cultures from other suspected sources (urine, sputum, wounds) as clinically indicated 1

Antimicrobial Therapy

• Administer IV antibiotics within one hour of sepsis recognition—this is a strong recommendation with moderate quality evidence 1
• Use empiric broad-spectrum therapy covering all likely pathogens including bacterial, and potentially fungal or viral organisms 1
• For septic shock specifically, consider combination therapy using at least two antibiotics from different antimicrobial classes targeting the most likely bacterial pathogens 1, 2
• For sepsis without shock, monotherapy with broad-spectrum coverage is typically adequate 1

Important caveat: The 2024 NICE guidelines suggest a more nuanced approach based on risk stratification—one hour for high-risk patients (NEWS2 ≥7), three hours for moderate risk, and six hours for low risk 1. However, the Surviving Sepsis Campaign's one-hour target remains the international standard for both sepsis and septic shock 1.

Fluid Resuscitation

• Administer at least 30 mL/kg of IV crystalloid within the first three hours for sepsis-induced hypoperfusion 1, 3
• Use crystalloids (normal saline or lactated Ringer's) as the fluid of choice 1, 3
• Avoid hetastarch formulations entirely 1
• Consider adding albumin only if patients continue requiring substantial crystalloid to maintain adequate mean arterial pressure 1

Hemodynamic Monitoring and Targets

• Measure serum lactate levels immediately as a marker of tissue hypoperfusion 2, 3
• Target mean arterial pressure (MAP) ≥65 mmHg 1, 2
• If lactate is elevated (>2 mmol/L), remeasure within 2-4 hours to guide ongoing resuscitation 1, 3

Vasopressor Support (If Hypotension Persists)

First-Line Vasopressor

• Norepinephrine is the first-choice vasopressor to maintain MAP ≥65 mmHg 1, 2
• Initiate vasopressors if hypotension persists despite adequate fluid resuscitation 1

Additional Vasopressor Options

• Add epinephrine when an additional agent is needed to maintain adequate blood pressure 1, 2
• Vasopressin (0.03 U/min) can be added to norepinephrine to raise MAP or decrease norepinephrine dose, but should not be used as the initial vasopressor 1
• Avoid dopamine except in highly selected circumstances (e.g., patients with low risk of arrhythmias and absolute or relative bradycardia) 1

Inotropic Support

• Add dobutamine infusion to vasopressor therapy if myocardial dysfunction is present (elevated cardiac filling pressures with low cardiac output) or if signs of hypoperfusion persist despite adequate volume and MAP 1

Source Control

• Identify the anatomic source of infection as rapidly as possible through clinical examination and imaging studies 1, 2
• Implement source control interventions (drainage of abscesses, debridement of infected tissue, removal of infected devices) as soon as medically and logistically practical, ideally within 6-12 hours of diagnosis 2, 3
• Remove intravascular access devices if confirmed as the infection source after establishing alternative access 2

Antimicrobial Stewardship (After Initial Management)

De-escalation Strategy

• Reassess antimicrobial therapy daily once pathogen identification and sensitivities are available 1
• Narrow to the most appropriate single therapy within 3-5 days if combination therapy was used 1
• Duration of therapy typically 7-10 days for most serious infections associated with sepsis 1, 2
• Longer courses (>10 days) are appropriate for slow clinical response, undrainable foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiency including neutropenia 1
• Shorter courses may be appropriate with rapid clinical resolution after source control of intra-abdominal or urinary sepsis 1

Common Pitfalls to Avoid

Delaying antibiotics for diagnostic workup: While cultures should be obtained first, never delay antibiotics beyond one hour to complete imaging or other diagnostics 1, 4. The mortality risk increases approximately 8% for each hour delay 5.

Inadequate initial fluid resuscitation: The 30 mL/kg crystalloid bolus is a minimum—some patients require more rapid administration and greater volumes 1. Continue fluid challenges as long as hemodynamic improvement occurs 1.

Using dopamine as first-line vasopressor: Norepinephrine has superior outcomes and should always be first choice 1.

Prolonged combination antibiotic therapy: If combination therapy is initiated for septic shock, de-escalate within the first few days based on clinical improvement and culture results 1. Extended combination therapy increases toxicity and resistance without improving outcomes 1.

Inadequate spectrum of initial antibiotics: Empiric therapy must cover all likely pathogens based on the suspected source, local resistance patterns, and patient risk factors for multidrug-resistant organisms 1, 6. Failure to cover the causative pathogen significantly increases mortality 4, 5.