What is the initial management of sepsis?

Initial Management of Sepsis

Administer IV broad-spectrum antimicrobials within 1 hour of recognizing sepsis and simultaneously begin aggressive fluid resuscitation with at least 30 mL/kg of crystalloid within the first 3 hours. 1, 2

Immediate Actions (First Hour)

Antimicrobial Therapy - The Most Critical Intervention

• Start IV broad-spectrum antibiotics within 1 hour of recognition - this is non-negotiable for both sepsis and septic shock 3, 1, 2
• Each hour of delay in antimicrobial administration decreases survival by 7.6% on average 3, 2
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but do not delay antibiotics more than 45 minutes to obtain cultures 1, 2
• Use empiric broad-spectrum therapy covering all likely pathogens including gram-positive, gram-negative, and potentially fungal or viral pathogens based on clinical syndrome and local resistance patterns 3, 1

Fluid Resuscitation - Start Immediately

• Administer a minimum of 30 mL/kg of IV crystalloid fluid within the first 3 hours for sepsis-induced hypoperfusion (hypotension or lactate >4 mmol/L) 3, 1, 2
• Use crystalloids (either balanced crystalloids or normal saline) as the fluid of choice - never use hydroxyethyl starches as they increase acute kidney injury and mortality 3, 2
• Continue fluid challenges of 500-1000 mL over 30 minutes as long as hemodynamic parameters improve (increased blood pressure, decreased heart rate, improved mental status, improved urine output) 3
• Consider adding albumin when patients require substantial amounts of crystalloids to maintain adequate mean arterial pressure 3, 2

Hemodynamic Monitoring and Targets

• Measure lactate levels immediately and repeat within 6 hours if initially elevated 1
• Target mean arterial pressure (MAP) ≥65 mmHg 3, 1, 2
• Monitor urine output targeting ≥0.5 mL/kg/hour 3
• Assess tissue perfusion by capillary refill, skin mottling, temperature of extremities, and mental status 1

Vasopressor Support (If Hypotension Persists Despite Fluids)

• Use norepinephrine as the first-choice vasopressor to maintain MAP ≥65 mmHg 3, 1, 2
• Add epinephrine when an additional agent is needed to maintain adequate blood pressure 3, 2
• Vasopressin 0.03 units/minute can be added to norepinephrine to raise MAP or decrease norepinephrine dose, but should not be used as the initial vasopressor 3
• Avoid dopamine except in highly selected circumstances (patients with low risk of tachyarrhythmias and absolute or relative bradycardia) 3

Source Control

• Identify or exclude a specific anatomic diagnosis of infection requiring emergent source control as rapidly as possible 3, 1, 2
• Implement required source control intervention (drainage, debridement, device removal) as soon as medically and logistically practical after diagnosis 3, 1, 2
• Remove intravascular access devices that are a possible source of sepsis after other vascular access has been established 3

Ongoing Management (First 6 Hours)

Reassessment and De-escalation

• Reassess antimicrobial therapy daily for de-escalation once pathogen identification and sensitivities are established 3, 1, 2
• Narrow antimicrobial therapy once adequate clinical improvement is noted 3, 1
• Guide resuscitation to normalize lactate in patients with elevated lactate levels 1

Respiratory Support

• Apply supplemental oxygen to achieve oxygen saturation >90% 1
• Place patients in semi-recumbent position (head of bed raised 30-45°) 1
• Consider non-invasive ventilation for dyspnea and/or persistent hypoxemia despite oxygen therapy if staff is adequately trained 1

Critical Pitfalls to Avoid

• Never delay antibiotics while waiting for cultures or imaging - the 1-hour window is absolute 1, 2
• Never use hydroxyethyl starches - they increase mortality and acute kidney injury 3, 2
• Do not rely solely on central venous pressure (CVP) to guide fluid resuscitation - the original early goal-directed therapy protocol with CVP targets is no longer recommended 4
• Do not use low-dose dopamine for renal protection - it is ineffective 3
• Stop fluid administration if no hemodynamic improvement occurs or if signs of fluid overload develop (pulmonary crackles, worsening oxygenation) 3

Special Considerations

For Patients with Renal Dysfunction or Dialysis Dependence

• Be particularly vigilant for fluid overload as these patients cannot excrete excess volume 5
• Arrange for urgent dialysis or continuous renal replacement therapy if signs of fluid overload develop during resuscitation 5

For Neutropenic Patients

• Consider combination therapy with an aminoglycoside in severe sepsis despite increased renal toxicity 3
• Knowledge of local microbiology and resistance patterns is crucial for antimicrobial selection 3