What is the recommended early goal‑directed therapy (sepsis bundle) for an adult with suspected sepsis or septic shock?

Sepsis Bundle: Early Goal-Directed Therapy for Adults with Suspected Sepsis or Septic Shock

For adults with suspected sepsis or septic shock, immediately initiate aggressive fluid resuscitation with at least 30 mL/kg IV crystalloid within the first 3 hours, administer broad-spectrum IV antimicrobials within 1 hour of recognition, target mean arterial pressure ≥65 mmHg, and achieve source control within 12 hours when feasible. 1, 2

Immediate Recognition and Initial Actions (Hour 0-1)

Sepsis and septic shock are medical emergencies requiring immediate treatment. 1

• Obtain at least 2 sets of blood cultures before antibiotics (one percutaneously, one through any vascular access device present >48 hours), but do not delay antimicrobials if this causes significant delay 2
• Measure serum lactate immediately to confirm tissue hypoperfusion 2
• Administer IV antimicrobials within 1 hour of recognition for both sepsis and septic shock 2
• Use empiric broad-spectrum antibiotics covering gram-negative organisms, gram-positives, and anaerobes if complicated infection, with an antipseudomonal beta-lactam as the primary agent 2

Fluid Resuscitation (Hours 0-3)

Give at least 30 mL/kg of IV crystalloid fluid within the first 3 hours of recognizing sepsis-induced hypoperfusion (defined as hypotension persisting after initial fluid challenge or blood lactate ≥4 mmol/L). 1, 2

• Administer fluid challenges of 1,000 mL of crystalloids or 300-500 mL of colloids over 30 minutes 1
• More rapid and larger volumes may be required in sepsis-induced tissue hypoperfusion 1
• Following initial fluid resuscitation, guide additional fluids by frequent reassessment of hemodynamic status 1

Hemodynamic Targets (Hours 0-6)

Target the following parameters during resuscitation:

• Mean arterial pressure ≥65 mmHg via crystalloid fluid boluses and vasopressors if needed 1, 2
• Urine output ≥0.5 mL/kg/hour as a marker of adequate perfusion 1, 2
• Use dynamic variables over static variables to predict fluid responsiveness when available 1

Evolution of CVP and ScvO2 Targets

The original Rivers protocol 3 targeted central venous pressure (CVP) 8-12 mmHg and central venous oxygen saturation (ScvO2) ≥70%, which reduced mortality from 46.5% to 30.5%. However, the 2016 Surviving Sepsis Campaign guidelines moved away from mandatory CVP and ScvO2 targets, instead recommending frequent clinical reassessment including heart rate, blood pressure, respiratory rate, temperature, and urine output. 1 This shift reflects evidence that filling pressures do not reliably predict fluid responsiveness and that ScvO2 is characteristically high in septic patients due to decreased oxygen extraction. 1

Source Control (Within 12 Hours)

Identify and treat the anatomic source within 12 hours of diagnosis whenever feasible. 2

• Obtain imaging promptly to identify drainable sources requiring intervention 2
• Perform source control (drainage of any purulent collections) within the first 12 hours if feasible 4
• Failing to identify and control the source of infection within 12 hours significantly worsens outcomes 2

Antimicrobial Management

Initial Therapy

• For septic shock, consider combination empirical therapy using at least two antibiotics of different antimicrobial classes aimed at the most likely bacterial pathogens 4
• Empiric combination therapy should not be administered for more than 3-5 days 4

De-escalation (Days 3-5)

• Reassess antimicrobial regimen daily for potential de-escalation 4
• De-escalate to the most appropriate single therapy once susceptibility profile is known 4
• Daily evaluation is mandatory to identify opportunities for de-escalation 5

Duration

• Standard duration is 7-10 days, with the shorter end appropriate for most cases with good clinical response 4
• Extend to 10-14 days for slow clinical response, undrainable foci, certain pathogens (e.g., Staphylococcus aureus), or immunologic deficiencies including neutropenia 4

Additional Supportive Care

Blood Products

• Transfuse red blood cells only when hemoglobin decreases to <7.0 g/dL (target 7.0-9.0 g/dL) once tissue hypoperfusion has resolved, unless extenuating circumstances exist (myocardial ischemia, severe hypoxemia, acute hemorrhage) 1

Corticosteroids

• Do not use IV hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 1
• If hemodynamic stability is not achievable, suggest IV hydrocortisone alone at 200 mg/day 1

Mechanical Ventilation (if ARDS develops)

• Target tidal volume of 6 mL/kg predicted body weight 1
• Maintain plateau pressures ≤30 cm H₂O 1
• Use higher PEEP strategies for moderate to severe ARDS 1

Critical Pitfalls to Avoid

• Do not delay antimicrobials beyond 1 hour while waiting for cultures or imaging 2
• Do not continue combination therapy beyond 3-5 days without strong reason 5
• Do not extend antibiotics beyond 10 days without clear indication (slow response, undrainable focus, specific pathogens, immunocompromise) 4, 5
• Do not fail to perform source control within 12 hours when feasible 4, 2
• Do not use static measures like CVP alone to guide fluid therapy; use dynamic assessment and clinical parameters 1

Evidence Context

The original Rivers EGDT study 3 demonstrated dramatic mortality reduction (46.5% to 30.5%), but subsequent trials showed that the specific protocol elements (CVP/ScvO2 targets) were less important than the overall concept of early recognition and aggressive early treatment. 6, 7, 8 The key elements that consistently improve outcomes are: immediate recognition, rapid antimicrobial administration, aggressive early fluid resuscitation, and timely source control. 9, 6, 7