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, simultaneously with aggressive fluid resuscitation of at least 30 mL/kg crystalloid and obtaining blood cultures. 1

Immediate Actions (Within First Hour)

Antimicrobial Therapy

• Start IV antibiotics within 60 minutes of sepsis recognition, covering all likely bacterial, fungal, and potentially viral pathogens with broad-spectrum agents that penetrate the presumed infection source 1
• Obtain at least two sets of blood cultures (aerobic and anaerobic bottles) before antibiotics—one drawn percutaneously and one through each vascular access device—but do not delay antimicrobials beyond 45 minutes waiting for cultures 1, 2
• 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 local resistance patterns and prior antimicrobial exposure when selecting agents, particularly if healthcare-associated infection or prior hospitalization >1 week 3

Fluid Resuscitation

• Administer 30 mL/kg IV crystalloid bolus within the first 3 hours for sepsis-induced hypoperfusion 1, 2
• Continue fluid challenges as long as hemodynamic parameters improve based on dynamic or static variables 1
• Avoid hetastarch formulations entirely 1

Diagnostic Workup

• Measure serum lactate immediately as a marker of tissue hypoperfusion 1, 2
• Obtain imaging studies promptly to confirm potential infection source 1
• Consider 1,3-β-D-glucan assay, mannan, and anti-mannan antibody assays if invasive candidiasis is in the differential 1, 2

Hemodynamic Support

Vasopressor Management

• Norepinephrine is the first-choice vasopressor to maintain mean arterial pressure (MAP) ≥65 mmHg 1, 2
• Add epinephrine as the second agent if additional support is needed 1
• 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 1
• Add dobutamine if myocardial dysfunction is present (elevated cardiac filling pressures with low cardiac output) or ongoing hypoperfusion despite adequate volume and MAP 1

Resuscitation Targets

• Target MAP ≥65 mmHg in patients requiring vasopressors 1, 2
• Guide resuscitation to normalize lactate in patients with elevated levels 1

Source Control

• Implement source control interventions (drainage, debridement, device removal) as soon as possible after diagnosis, ideally within 12 hours if feasible 2, 3
• Remove intravascular access devices confirmed as infection source after establishing alternative access 2

Antimicrobial Optimization

Dosing Strategies

• Use loading doses (initial higher dose) for all patients regardless of organ dysfunction 4, 5
• Optimize subsequent doses based on pharmacokinetic/pharmacodynamic principles and specific drug properties 1
• Consider extended or continuous infusion of beta-lactams to achieve therapeutic levels 4, 5
• Implement therapeutic drug monitoring when available 4, 5

De-escalation and Duration

• Reassess antimicrobial therapy daily for potential de-escalation once pathogen identification and sensitivities are available 1
• Narrow therapy to the most appropriate single agent as soon as susceptibility profiles are known 1
• If combination therapy is used for septic shock, discontinue within the first few days in response to clinical improvement 1
• Duration of 7-10 days is adequate for most serious infections associated with sepsis 1, 6, 7
• Consider longer courses only for slow clinical response, undrainable foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiency including neutropenia 1

Supportive Care

Respiratory Management

• Use low tidal volume ventilation (6 mL/kg predicted body weight) for sepsis-induced ARDS 2
• Consider recruitment maneuvers for severe refractory hypoxemia 1
• Elevate head of bed unless contraindicated 1

Metabolic Management

• Target hemoglobin 7-9 g/dL in absence of tissue hypoperfusion, ischemic coronary disease, or acute hemorrhage 1, 2
• Maintain blood glucose ≤180 mg/dL using protocolized insulin approach 1, 2

Corticosteroids

• Avoid IV hydrocortisone in adult septic shock if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 1

Critical Pitfalls to Avoid

• Never delay antibiotics beyond 1 hour while waiting for cultures or imaging—sepsis is a time-dependent emergency like myocardial infarction 1, 4
• Do not use sustained systemic antimicrobial prophylaxis in severe inflammatory states of noninfectious origin (severe pancreatitis, burns) 1
• Avoid routine combination therapy for ongoing treatment of most serious infections without shock, including bacteremia 1
• Do not routinely use combination therapy for neutropenic sepsis/bacteremia 1
• Ensure broad-spectrum coverage initially—inadequate initial antimicrobial therapy significantly increases mortality 4, 5