Sepsis Bundle Components
The sepsis bundle consists of time-sensitive interventions divided into a 3-hour bundle (initial resuscitation) and a 6-hour bundle (extended management), with the core components being: obtain blood cultures, measure lactate, administer broad-spectrum antibiotics within 1 hour, and begin aggressive fluid resuscitation with 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L. 1, 2
3-Hour Bundle (Initial Resuscitation)
Blood Cultures and Laboratory Testing
- Obtain at least two sets of blood cultures (aerobic and anaerobic bottles) before antibiotic administration, with at least one drawn percutaneously and one through each vascular access device (unless inserted <48 hours ago) 2, 3
- Measure serum lactate level immediately—elevated lactate >2 mmol/L indicates more severe disease and need for aggressive resuscitation 2, 3
- Obtain complete blood count to assess for leukocytosis (>12,000/μL), leukopenia (<4,000/μL), or >10% immature forms 2, 3
- Draw comprehensive metabolic panel to evaluate renal function (creatinine), hepatic function (bilirubin), and electrolyte abnormalities 2
- Check coagulation studies (INR, PTT) to assess for coagulopathy—INR >1.5 or PTT >60 seconds indicates severe sepsis 2, 3
- Consider procalcitonin as an adjunctive test to determine likelihood of bacterial infection 2
Antibiotic Administration
- Administer broad-spectrum IV antibiotics within 1 hour of recognition for patients with possible septic shock or high likelihood of sepsis 1, 2, 4
- For patients with suspected infection but low likelihood and no shock signs, antibiotics may be initiated within 3 hours with close monitoring 1
- Empiric antibiotics must cover all likely pathogens (including gram-positive, gram-negative, and anaerobes when indicated) and penetrate adequately into the presumed infection source 2, 4
- Use combination therapy for neutropenic patients, suspected multidrug-resistant pathogens, or patients with respiratory failure and septic shock 2
Fluid Resuscitation
- Administer 30 mL/kg IV crystalloid solution rapidly for patients with hypotension (systolic BP <90 mmHg or MAP <70 mmHg) or elevated lactate ≥4 mmol/L 2, 3
- Crystalloid solutions are first-line because they are well-tolerated and cost-effective 1
- In resource-limited settings, aggressive fluid resuscitation with >4 L during the first 24 hours may be required for adequate resuscitation 1
- Target clinical endpoints: >10% increase in systolic/mean arterial pressure, >10% reduction in heart rate, improvement in mental status, improved peripheral perfusion (decreased mottling, improved capillary refill), and urine output ≥0.5 mL/kg/hr 1, 3
Source Identification
- Obtain prompt imaging studies (ultrasound, CT, or X-ray) to identify potential infection sources requiring drainage or surgical intervention 2
- Look for specific signs: mottled or ashen appearance, non-blanching petechial or purpuric rash, cyanosis of skin/lips/tongue, decreased capillary refill, peripheral cyanosis 1, 3
6-Hour Bundle (Extended Management)
Vasopressor Therapy
- Initiate norepinephrine as first-line vasopressor if hypotension persists despite fluid resuscitation 1, 2, 3
- Target mean arterial pressure (MAP) ≥65 mmHg 1, 2, 3
- Consider adding epinephrine if inadequate response to norepinephrine 1
- Start low-dose steroids (hydrocortisone 200 mg/day as 50 mg IV every 6 hours or continuous infusion) if no response to norepinephrine or epinephrine ≥0.25 µg/kg/min for at least 4 hours 1
Lactate Monitoring
- Remeasure lactate if initial level was elevated (>2 mmol/L)—guide resuscitation to normalize lactate as a marker of tissue hypoperfusion 2, 3
- Serial lactate measurements are essential to assess response to therapy 2
Source Control
- Implement source control measures (drainage, debridement, device removal) as soon as possible after initial resuscitation, ideally within 12 hours when feasible 2, 4
Ongoing Monitoring and Risk Stratification
NEWS2 Score Assessment
- Calculate NEWS2 score using six physiological parameters: respiratory rate, oxygen saturation, supplemental oxygen requirement, systolic blood pressure, pulse, consciousness level (Alert vs CVPU), and temperature 1
- Interpret scores in context of underlying physiology and comorbidities: Score ≥7 = high risk; score 5-6 = moderate risk; score 1-4 = low risk; score 0 = very low risk 1
- A score of 3 in any single parameter may indicate increased sepsis risk 1
- Re-calculate NEWS2 score every 30 minutes for high-risk patients, every hour for moderate-risk patients, and every 4-6 hours for low-risk patients 1
Continuous Monitoring
- Monitor vital signs closely: heart rate, blood pressure, respiratory rate, temperature, oxygen saturation 1
- Assess organ function using Sequential Organ Failure Assessment (SOFA) score—an increase of ≥2 points defines sepsis 1, 3
- Target urine output ≥0.5 mL/kg/hr as marker of adequate renal perfusion 2, 3
- Monitor for signs of deterioration: worsening mental status, increasing vasopressor requirements, persistent elevated lactate 1
De-escalation and Duration
- Reassess antimicrobial regimen daily for potential de-escalation based on clinical improvement and culture results 2, 4
- Narrow therapy once pathogen identification and sensitivities are established 4
- Typical duration is 7-10 days, but longer courses may be necessary for slow clinical response 4
Critical Pitfalls to Avoid
- Never delay antibiotic administration beyond 1 hour from recognition of sepsis or septic shock—each hour delay increases mortality 2, 4, 5
- Do not use lactic acid to diagnose sepsis during active labor (per CMS guidance) 1
- Avoid fluid overload in patients with generalized peritonitis, which may aggravate gut edema and increase intra-abdominal pressure 1
- Do not fail to obtain blood cultures before antibiotics when feasible—but never delay antibiotics if obtaining cultures would cause significant delay 2, 4
- Recognize that 18-32% of patients initially diagnosed with sepsis have noninfectious mimics requiring different treatments 6
- In children with compensated shock and profound anemia (particularly with malaria), aggressive fluid boluses may be harmful—use cautious fluid administration with close monitoring 1