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)

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. Administer Antimicrobials Within One Hour

• This is a strong recommendation with moderate quality evidence and directly impacts mortality 1
• 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
• Select agents with good penetration into the presumed source of infection 1

4. 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
• 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
• Reassess hemodynamic status frequently after initial bolus 3

Hemodynamic Support (If Hypotension Persists)

Vasopressor Therapy

• Norepinephrine is the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg 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
• Add dobutamine if myocardial dysfunction is present (elevated filling pressures with low cardiac output) or ongoing hypoperfusion 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 devices confirmed as infection source after establishing alternative access 2

Antimicrobial Selection Considerations

Pathogen Coverage

• Cover gram-positive and gram-negative organisms empirically 4
• Add anaerobic coverage for intra-abdominal infections or when anaerobes are likely pathogens 4
• Consider 1,3-β-D-glucan assay, mannan, and anti-mannan antibody assays if invasive candidiasis is in the differential 1, 2
• Consider antifungal or antiviral therapy based on clinical context 1

Risk Factors for Resistant Organisms

• Healthcare-associated infection 3
• Hospitalization >1 week 3
• Previous antimicrobial therapy 3
• Known colonization with multidrug-resistant organisms 5

Dosing Optimization

• Use loading doses for all patients initially 5
• Optimize subsequent dosing based on pharmacokinetic/pharmacodynamic principles 1
• Consider extended or continuous infusion of beta-lactams 5
• Implement therapeutic drug monitoring when available 5

Early Reassessment and De-escalation

Daily Antimicrobial Review

• 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 and septic shock 1
• Longer courses are appropriate for slow clinical response, undrainable foci, S. aureus bacteremia, fungal/viral infections, or immunologic deficiencies including neutropenia 1
• Shorter courses are appropriate with rapid clinical resolution after effective source control of intra-abdominal or urinary sepsis 1

Common Pitfalls to Avoid

• Do not delay antibiotics while waiting for cultures - the mortality risk increases approximately 8% for each hour delay 4
• Do not use sustained systemic antimicrobial prophylaxis in severe inflammatory states of noninfectious origin (severe pancreatitis, burn injury) 1
• Do not routinely use combination therapy for ongoing treatment of most serious infections once shock has resolved 1
• Avoid inadequate initial spectrum - better to start broad and de-escalate than to start narrow and miss resistant organisms 5
• Do not continue empiric broad-spectrum therapy beyond 3-5 days without reassessment 1, 6