What is the initial management of 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 at least two sets of blood cultures, and initiate aggressive fluid resuscitation with 30 mL/kg of crystalloid within the first three hours. 1

Immediate Actions (Within First Hour)

Obtain Cultures Before Antibiotics

• Draw at least two sets of blood cultures (both aerobic and anaerobic bottles) before starting antimicrobials, with at least one drawn percutaneously and one through each vascular access device (unless inserted <48 hours prior) 1
• Do not delay antimicrobials beyond 45 minutes while waiting for cultures 2
• Sample fluid or tissue from the suspected infection site when feasible 3

Antimicrobial Therapy

• Initiate IV broad-spectrum antimicrobials within one hour of recognition for both sepsis and septic shock 1
• Select one or more agents with activity against all likely bacterial pathogens (and potentially fungal or viral coverage) that penetrate adequately into the presumed source 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
• Consider healthcare-associated infection risk factors (hospitalization >1 week, previous antimicrobial therapy, healthcare setting acquisition) when selecting agents to cover multidrug-resistant organisms 4

Fluid Resuscitation

• Administer at least 30 mL/kg of IV crystalloid fluid within the first three hours for sepsis-induced hypoperfusion 1, 2
• Use crystalloids as the initial fluid of choice 1
• Continue fluid challenges as long as hemodynamic improvement occurs, guided by frequent reassessment using dynamic variables when available 1, 3

Hemodynamic Support

Vasopressor Therapy

• Initiate norepinephrine as the first-choice vasopressor when needed to maintain mean arterial pressure ≥65 mmHg 1, 2
• Add epinephrine when an additional agent is required to maintain adequate blood pressure 1
• 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 1

Additional Hemodynamic Measures

• Measure serum lactate levels as a marker of tissue hypoperfusion 2
• Guide resuscitation to normalize lactate in patients with elevated levels 1
• Add dobutamine infusion to vasopressor therapy if myocardial dysfunction is present (elevated cardiac filling pressures with low cardiac output) or ongoing signs of hypoperfusion persist despite adequate volume and MAP 1

Source Control and Diagnostic Imaging

• Perform imaging studies promptly to confirm the potential source of infection 1
• Implement source control interventions (drainage, debridement, removal of infected devices) as soon as possible after diagnosis, ideally within 12 hours when feasible 2, 3
• Remove intravascular access devices confirmed as the infection source after establishing alternative vascular access 2

Antimicrobial Optimization

Daily Reassessment

• Reassess antimicrobial therapy daily for potential de-escalation once pathogen identification and sensitivities are established 1
• Narrow therapy to the most appropriate single agent as soon as the susceptibility profile is known 1
• If combination therapy is used for septic shock, discontinue it within the first few days in response to clinical improvement and/or evidence of infection resolution 1

Duration of Therapy

• Limit antimicrobial treatment to 7-10 days for most serious infections associated with sepsis 1, 5
• Consider longer courses for slow clinical response, undrainable foci of infection, Staphylococcus aureus bacteremia, fungal/viral infections, or immunologic deficiencies including neutropenia 1
• Consider shorter courses for rapid clinical resolution following effective source control of intra-abdominal or urinary sepsis 1

Additional Supportive Care

• Target hemoglobin of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage 1, 2
• Use low tidal volume ventilation (6 mL/kg predicted body weight) for patients with sepsis-induced ARDS 2
• Maintain blood glucose ≤180 mg/dL using a protocolized approach 2
• Provide prophylaxis for deep vein thrombosis and stress ulcer prophylaxis in patients with bleeding risk factors 1

Critical Pitfalls to Avoid

• Never delay antimicrobials beyond one hour while obtaining cultures or imaging 1, 4
• Do not use inadequate initial fluid resuscitation—the full 30 mL/kg bolus is essential 1
• Avoid continuing broad-spectrum antibiotics without daily reassessment for de-escalation 1
• Do not miss occult sources requiring source control (abscesses, infected devices) 3
• Avoid hetastarch formulations for fluid resuscitation 1