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 blood cultures, while simultaneously initiating aggressive fluid resuscitation with 30 mL/kg of 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 prior) 1
• Critical caveat: Do not delay antibiotics beyond 45 minutes while waiting to obtain cultures 2
• Obtain other appropriate cultures based on suspected source (urine, sputum, wound, cerebrospinal fluid) 1

2. Measure Serum Lactate

• Obtain lactate level immediately as a marker of tissue hypoperfusion 2
• Use lactate normalization as a resuscitation target in patients with elevated levels 1, 2

3. Initiate Antimicrobial Therapy

• Timing is critical: Administer IV antimicrobials within one hour of recognition for both sepsis and septic shock 1
• Each hour of delay increases mortality risk by approximately 8% 3
• Use empiric broad-spectrum therapy covering all likely pathogens (bacterial, and consider fungal or viral if indicated) 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

For sepsis without shock: Monotherapy with broad-spectrum coverage is typically adequate 1

4. Begin Fluid Resuscitation

• Administer at least 30 mL/kg of IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion 1, 2, 4
• Crystalloids are preferred over colloids for initial resuscitation 1
• Avoid hetastarch formulations 1
• Continue fluid challenges as long as hemodynamic improvement occurs based on dynamic or static variables 1
• Consider adding albumin only if patients require substantial ongoing crystalloid to maintain adequate mean arterial pressure 1

Hemodynamic Support

Vasopressor Therapy

• Initiate vasopressors if hypotension persists despite adequate fluid resuscitation 2
• Target mean arterial pressure (MAP) ≥65 mmHg 1, 2
• Norepinephrine is the first-choice vasopressor 1, 2
• Add epinephrine if 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 used as initial vasopressor 1
• Dopamine is not recommended except in highly selected circumstances 1

Inotropic Support

• Add dobutamine 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 and Imaging

• Perform imaging studies promptly to confirm potential infection source 1
• Implement source control interventions as soon as possible after diagnosis 2
• Remove intravascular access devices if confirmed as the infection source (after establishing alternative access) 2

Antimicrobial Selection Strategy

Empiric Coverage Considerations

• Select agents with activity against likely pathogens based on:
  • Suspected infection source 1, 5
  • Local resistance patterns and hospital antibiogram 5, 3
  • Recent healthcare exposure (consider multidrug-resistant organisms if hospitalized >1 week or recent antimicrobial therapy) 4, 5
  • Patient-specific risk factors for resistant pathogens 4

Special Pathogen Coverage

• Consider 1,3-β-D-glucan assay, mannan, and anti-mannan antibody assays if invasive candidiasis is in the differential 1, 2
• Include anaerobic coverage for intra-abdominal infections or other sources where anaerobes are likely 3

Dosing Optimization

• Optimize antimicrobial dosing based on pharmacokinetic/pharmacodynamic principles 1
• Consider loading doses for all patients, then individualize subsequent dosing based on renal/hepatic function 5
• Use extended or continuous infusion of beta-lactams when appropriate 5

Daily Reassessment and De-escalation

Antimicrobial Stewardship

• Reassess antimicrobial therapy daily for potential de-escalation 1
• Narrow therapy once pathogen identification and sensitivities are established or adequate clinical improvement is noted 1
• If combination therapy was used for septic shock, discontinue 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, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency including neutropenia 1
• Shorter courses are appropriate with rapid clinical resolution after effective source control (particularly intra-abdominal or urinary sepsis, uncomplicated pyelonephritis) 1

Additional 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
• Consider prone positioning if PaO₂/FiO₂ ratio <100 mmHg in experienced facilities 1
• Elevate head of bed unless contraindicated 1

Metabolic Management

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

Corticosteroids

• Avoid IV hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 1

Prophylaxis

• Provide deep vein thrombosis prophylaxis 1
• Use stress ulcer prophylaxis in patients with bleeding risk factors 1

Common Pitfalls to Avoid

• Never delay antimicrobials while waiting for cultures or imaging - the one-hour window is critical for mortality reduction 1, 4
• Do not use sustained systemic antimicrobial prophylaxis in severe inflammatory states of noninfectious origin (severe pancreatitis, burn injury) 1
• Avoid inadequate initial spectrum - it is better to start broad and de-escalate than to start narrow and escalate after clinical deterioration 5, 3
• Do not continue combination therapy beyond 3-5 days - de-escalate to single-agent therapy once susceptibilities are known 1
• Recognize that not all suspected sepsis is infection - a substantial fraction have noninfectious conditions, but this determination should not delay initial treatment in critically ill patients 6