Sepsis Bundle Components
The sepsis bundle consists of immediate, time-sensitive interventions that must be initiated within the first hour of sepsis recognition, including: obtaining blood cultures before antibiotics, administering broad-spectrum antibiotics within 1 hour, delivering 30 mL/kg crystalloid fluid resuscitation for hypotension or lactate >4 mmol/L, measuring serum lactate immediately, and applying vasopressors (norepinephrine first-line) for persistent hypotension targeting MAP ≥65 mmHg. 1, 2, 3
Immediate Recognition and Diagnostic Actions (Hour 1)
Measure serum lactate immediately upon sepsis recognition—this serves as an objective marker of tissue hypoperfusion and predicts mortality. 1, 2, 3 Remeasure lactate within 6 hours if initially elevated, targeting clearance of at least 10% every 2 hours during the first 8 hours. 1, 2, 3
Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before antimicrobial therapy—this showed an independent mortality reduction with risk-adjusted odds ratio of 0.76 (95% CI 0.70-0.83, P<0.0001). 1, 3 However, never delay antibiotic administration beyond 1 hour to obtain cultures; obtain them quickly but prioritize antibiotic timing. 1, 2, 3
Administer effective IV broad-spectrum antimicrobials within the first hour of sepsis recognition—this is the single most critical intervention affecting mortality. 1, 3 For emergency department admissions, the target is within 3 hours; for non-ED ICU admissions, within 1 hour. 2, 3 Compliance with this timing demonstrated a risk-adjusted odds ratio for mortality of 0.86 (95% CI 0.79-0.93, P<0.0001). 3
Fluid Resuscitation (First 3 Hours)
Deliver at least 30 mL/kg IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion (hypotension and/or lactate >4 mmol/L). 1, 2, 3 More rapid administration and greater amounts may be needed in some patients. 4, 1 Use crystalloids as first-line fluid; avoid hetastarch formulations entirely. 4, 3
Continue fluid challenges as long as hemodynamic improvement occurs based on either dynamic or static variables. 4, 2 Clinical indicators of adequate tissue perfusion include: normal capillary refill time, absence of skin mottling, warm and dry extremities, well-felt peripheral pulses, return to baseline mental status, and urine output >0.5 mL/kg/hour in adults or >1 mL/kg/hour in children. 4
Critical pitfall to avoid: Do not aggressively fluid resuscitate patients with documented ventricular dysfunction, as this worsens outcomes. 3
Vasopressor Support
Use norepinephrine as the first-choice vasopressor to maintain MAP ≥65 mmHg if hypotension persists after initial fluid resuscitation. 4, 2, 3 Epinephrine should be added when an additional agent is needed to maintain adequate blood pressure. 4, 5 Epinephrine acts on both alpha and beta-adrenergic receptors, providing direct myocardial stimulation, increased heart rate, and peripheral vasoconstriction with onset <5 minutes. 5
Vasopressin (0.03 U/min) can be added to norepinephrine to either raise MAP to target or decrease norepinephrine dose, but should not be used as the initial vasopressor. 4 Dopamine is not recommended except in highly selected circumstances. 4, 3
Dobutamine should be administered or added to vasopressor in the presence of myocardial dysfunction (elevated cardiac filling pressures and low cardiac output) or ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate MAP. 4
Corticosteroid Therapy
Administer intravenous hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) to adult patients requiring escalating dosages of epinephrine or dopamine in septic shock. 4, 1, 2, 3, 6 However, avoid using intravenous hydrocortisone if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. 4
Ventilation and Positioning
Apply oxygen to achieve oxygen saturation ≥90%; if no pulse oximeter is available, administer oxygen empirically in patients with severe sepsis or septic shock. 4
Place patients in semi-recumbent position (head of bed raised to 30-45°). 4, 1 Unconscious patients should be placed in the lateral position with airway kept clear. 4
For mechanically ventilated patients, use low tidal volume ventilation and maintain inspiratory plateau pressures <30 cm H₂O—this demonstrated a risk-adjusted odds ratio for mortality of 0.70 (95% CI 0.62-0.78, P=0.0001). 4, 1, 2, 3
Use non-invasive ventilation in patients with dyspnea and/or persistent hypoxemia despite oxygen therapy if staff is adequately trained. 4
Glucose Control
**Maintain blood glucose above lower limit of normal but <150 mg/dL (8.3 mmol/L)**; commence insulin when two consecutive levels are >180 mg/dL. 1, 2, 3 This showed a risk-adjusted odds ratio for mortality of 0.67 (95% CI 0.62-0.71, P=0.0001). 3
Source Control
Drain or debride the source of infection as soon as possible through surgical intervention, percutaneous drainage, or device removal. 4, 1 Perform detailed patient history and thorough clinical examination to identify the infection source; use imaging techniques when available. 4 Sample fluid or tissue from the site of infection and examine by Gram stain, culture, and antibiogram whenever possible. 4
Antimicrobial Stewardship
Reassess antimicrobial regimen daily for potential de-escalation. 1 Empiric combination therapy should not continue beyond 3-5 days. 1 This balances adequate initial coverage with minimizing resistance and toxicity.
Transfusion Threshold
Target hemoglobin of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage. 4, 2
Performance Improvement
Hospitals must have performance improvement programs for sepsis, including routine screening of acutely ill, high-risk patients. 1 Discuss goals of care and prognosis with patients and families as early as feasible, but no later than 72 hours of ICU admission. 1
Evidence of Bundle Effectiveness
Complete bundle compliance is associated with 25-30% reduction in mortality, with a number needed to treat of 15 patients to save one life. 3, 7 One study showed complete bundle compliance associated with 31% lower risk of mortality (adjusted IRR 0.69,95% CI 0.53-0.91). 7 Another demonstrated mortality decrease from 37% to 30.8% over 2 years with bundle implementation. 4
Common implementation challenge: Bundle compliance remains suboptimal worldwide, ranging from 18-52% for the resuscitation bundle and 10-36% for the management bundle across different studies. 4, 3 The most common delays occur in IV fluid administration, inotrope administration, and timely antibiotic delivery. 4