What are the Sepsis Six recommendations according to NICE (National Institute for Health and Care Excellence) guidelines?

Sepsis Six According to NICE Guidelines

The "Sepsis Six" is not explicitly defined in current NICE guidelines; instead, NICE 2024 recommends a risk-stratified approach using NEWS2 scores to determine the urgency of interventions, with antibiotic timing based on risk level (high risk: 1 hour, moderate risk: 3 hours, low risk: 6 hours) rather than a universal one-hour bundle for all patients. 1

Understanding the Evolution Away from Universal "Sepsis Six"

The traditional "Sepsis Six" bundle approach has been replaced by NICE with a more nuanced, risk-stratified framework. The 2024 NICE guidance moved away from the blanket one-hour antibiotic administration target for all suspected sepsis cases, recognizing that this approach was "not always practical and could be potentially harmful" 1. This represents a significant departure from earlier sepsis management paradigms.

NICE 2024 Risk Stratification Using NEWS2

NICE mandates using NEWS2 (National Early Warning Score 2) to categorize patients into risk levels that guide intervention timing: 1

Risk Categories:

• High risk: NEWS2 score ≥7 or presence of mottled/ashen appearance, non-blanching rash, or cyanosis 1
• Moderate risk: NEWS2 score 5-6 1
• Low risk: NEWS2 score 1-4 1
• Very low risk: NEWS2 score 0 1

NEWS2 Components (Six Physiological Parameters):

The NEWS2 score incorporates: respiratory rate, oxygen saturation (with adjustment for hypercapnic patients), supplemental oxygen requirement, systolic blood pressure, pulse rate, level of consciousness (Alert vs CVPU), and temperature 1.

NICE-Recommended Interventions by Risk Level

For High-Risk Patients (NEWS2 ≥7):

Antibiotic Administration: Give IV antibiotics within 1 hour of calculating the NEWS2 score 1

Blood Cultures: Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but do not delay antimicrobials if cultures cannot be obtained 1

Lactate Measurement: Measure serum lactate as a marker of tissue hypoperfusion 1

Fluid Resuscitation: Administer IV crystalloid fluids (the NICE guidance references Surviving Sepsis Campaign recommendations of 30 mL/kg within 3 hours for sepsis-induced hypoperfusion) 1

Oxygen Therapy: Provide supplemental oxygen to maintain adequate saturation 1

Urine Output Monitoring: Monitor urine output as part of hemodynamic assessment 1

Monitoring Frequency: Re-calculate NEWS2 and re-evaluate risk every 30 minutes 1

For Moderate-Risk Patients (NEWS2 5-6):

Antibiotic Administration: Give IV antibiotics within 3 hours of calculating NEWS2 score 1

Same diagnostic and supportive measures as high-risk patients, but with less urgent timeframes 1

Monitoring Frequency: Re-calculate NEWS2 every hour 1

For Low-Risk Patients (NEWS2 1-4):

Antibiotic Administration: Give IV antibiotics within 6 hours of calculating NEWS2 score 1

Monitoring Frequency: Re-calculate NEWS2 every 4-6 hours 1

Critical Caveats and Clinical Judgment

These timeframes represent maximum times until prescription, not targets to work toward 1. Clinical judgment must override scoring systems when the patient's condition is deteriorating or not improving despite interventions 1.

Consider evaluating risk as higher than the NEWS2 score suggests if: 1

• The patient's condition is deteriorating
• No improvement has occurred since previous NEWS2 calculation
• No improvement has occurred since previous interventions

Interpret NEWS2 scores within the context of: 1

• The patient's underlying physiology
• Pre-existing comorbidities
• Baseline physiological abnormalities (e.g., patients with chronic respiratory disease may have chronically low oxygen saturations)

Source Control and Antimicrobial Strategy

Source Control: Perform imaging studies promptly to confirm infection source and implement source control interventions (drainage, debridement, device removal) as soon as possible 1

Antimicrobial Selection: Use broad-spectrum empiric therapy covering all likely pathogens (bacterial, fungal, viral) based on the presumed source and local resistance patterns 1

De-escalation: Review antibiotic choice and narrow spectrum when microbiological results are available, ideally within 1 hour of receiving results 1

Duration: Target 7-10 days for most serious infections, with daily assessment for de-escalation 1

Community and Pre-Hospital Settings

In remote/rural locations with transfer times >1 hour: Administer antibiotics to high-risk patients before hospital transfer according to local guidelines 1

Ambulance services: Should have mechanisms to give antibiotics to high-risk patients when handover times exceed one hour 1

Alert receiving hospitals for patients aged ≥16 with consecutive NEWS2 scores ≥5 or significant clinical concern 1

Key Differences from Traditional "Sepsis Six"

The NICE approach differs from the traditional Surviving Sepsis Campaign bundle by: 1

• Risk stratification rather than universal one-hour targets
• Emphasis on antimicrobial stewardship to reduce potential antibiotic-related harm
• Standardization through NEWS2 rather than varied early warning scores
• Explicit recognition that not all suspected sepsis requires immediate antibiotics

This approach aims to balance the urgency of treating true sepsis against the harms of over-treatment with antibiotics and excessive fluid administration in patients with non-infectious inflammatory conditions 1.