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 crystalloid. 1

Immediate Actions (Within First Hour)

1. Obtain Cultures Before Antibiotics

• Draw at least two sets of blood cultures (both aerobic and anaerobic bottles) before starting antimicrobials 1
• One set should be drawn percutaneously and one through each vascular access device (unless inserted <48 hours ago) 1
• Critical caveat: Do not delay antibiotics beyond 45 minutes waiting for cultures 2
• Sample fluid or tissue from the suspected infection source when feasible 3

2. Administer Antimicrobials Within One Hour

• Strong recommendation: Give IV antimicrobials within one hour of recognition for both sepsis and septic shock 1
• Use empiric broad-spectrum therapy covering all likely pathogens (bacterial, and potentially fungal or viral) 1
• For septic shock specifically, consider combination therapy using at least two antibiotics from different antimicrobial classes 1, 2
• Ensure adequate tissue penetration to the presumed infection source 1

3. Initiate Aggressive Fluid Resuscitation

• Administer at least 30 mL/kg of IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion 1, 2, 3
• Some patients may require more rapid administration and greater fluid volumes 1
• Continue fluid challenges as long as hemodynamic improvement occurs based on dynamic or static variables 1
• After initial resuscitation, guide further fluids by frequent reassessment of hemodynamic status 2, 3

Hemodynamic Support

Vasopressor Therapy

• Target mean arterial pressure (MAP) ≥65 mmHg 1, 2
• Norepinephrine is the first-choice vasopressor 1, 2
• Add epinephrine when an additional agent is needed 1
• Vasopressin (0.03 U/min) can be added to norepinephrine to raise MAP or decrease norepinephrine dose, but should not be the initial vasopressor 1
• Dopamine is not recommended except in highly selected circumstances 1

Inotropic Support

• Add dobutamine in the presence of myocardial dysfunction (elevated cardiac filling pressures with low cardiac output) or ongoing hypoperfusion despite adequate volume and MAP 1

Monitoring and Assessment

Lactate Measurement

• Measure serum lactate as a marker of tissue hypoperfusion 2
• Guide resuscitation to normalize lactate in patients with elevated levels 1, 2

Imaging Studies

• Perform imaging promptly to confirm potential infection source 1

Source Control

• Implement source control interventions as soon as possible after diagnosis, ideally within 12 hours when feasible 2, 3
• Drain or debride infection sources when possible 3
• Remove intravascular access devices confirmed as the infection source after establishing alternative access 2

Antimicrobial Optimization

Daily Reassessment

• Reassess antimicrobial regimen daily for potential de-escalation 1, 3
• Narrow therapy once pathogen identification and sensitivities are established or adequate clinical improvement is noted 1
• De-escalate combination therapy within the first few days in response to clinical improvement 1

Duration of Therapy

• 7-10 days is adequate for most serious infections associated with sepsis 1
• Longer courses are appropriate for slow clinical response, undrainable foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiencies 1
• Shorter courses may be appropriate with rapid clinical resolution after effective source control 1

Special Considerations for Antimicrobial Selection

• Consider 1,3-β-D-glucan assay, mannan, and anti-mannan antibody assays if invasive candidiasis is in the differential 1, 2
• Optimize dosing strategies based on pharmacokinetic/pharmacodynamic principles 1
• Consider higher risk of resistant pathogens if healthcare-associated infection, hospitalization >1 week, or previous antimicrobial therapy 4

Common Pitfalls to Avoid

• Never delay antimicrobials beyond one hour while waiting for diagnostic workup in high-risk patients 1, 3
• Avoid inadequate initial fluid resuscitation—the 30 mL/kg is a minimum, not a maximum 1
• Do not continue combination therapy beyond 3-5 days without reassessment 1
• Avoid hetastarch formulations for fluid resuscitation 1
• Do not use sustained systemic antimicrobial prophylaxis in severe inflammatory states of noninfectious origin (e.g., severe pancreatitis, burn injury) 1