1.2 Sepsis, Sepsis Six Protocol & Septic Shock
Key Takeaways
The Sepsis-3 consensus defines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, objectified by an acute change in total SOFA score of ≥2 points.
Under NICE NG253 (November 2025), an adult with suspected infection and NEWS2 of 7 or more is high risk: FY2-or-above review, venous lactate and blood cultures, IV antibiotics within 1 hour, and IV balanced crystalloid in 250 mL boluses up to 1,000 mL.
Septic shock is clinically defined by persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg AND serum lactate >2 mmol/L despite adequate fluid resuscitation.
Noradrenaline is the first-line vasopressor of choice in septic shock; balanced crystalloid resuscitation should avoid large unbuffered saline infusions to prevent hyperchloraemic metabolic acidosis.
Sepsis, Sepsis Six Protocol & Septic Shock
Sepsis represents one of the leading causes of acute in-hospital deterioration and mortality in the National Health Service (NHS). Rapid recognition and time-critical delivery of basic resuscitation bundles within the first hour markedly reduce mortality and progression to multi-organ failure.
Sepsis-3 Definitions & Pathophysiology
Sepsis is defined by the Sepsis-3 (Third International Consensus Definitions for Sepsis and Septic Shock) criteria. UK early management follows NICE NG253 (Suspected sepsis in people aged 16 or over, published November 2025, updated 2026), which replaced NG51 together with NG254 (under 16s) and NG255 (pregnant or recently pregnant people):
- Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection.
- Organ Dysfunction: An acute change in total Sequential Organ Failure Assessment (SOFA) score of ≥2 points attributable to the infectious insult. An acute SOFA increase of ≥2 points is associated with an in-hospital mortality of more than 10%.
The SOFA Score Domains
- Respiration: PaO2/FiO2 ratio (hypoxaemia).
- Coagulation: Platelet count (thrombocytopenia from consumption).
- Liver: Serum bilirubin elevation.
- Cardiovascular: Mean arterial pressure (MAP) or requirement for vasopressor support.
- Central Nervous System: Glasgow Coma Scale (GCS) score drop.
- Renal: Serum creatinine rise or acute oliguria.
Bedside Risk Stratification: qSOFA & NEWS2
The quick SOFA (qSOFA) bedside assessment tool identifies non-ICU patients with suspected infection at high risk of deterioration (score ≥2):
- Respiratory Rate: ≥ 22 breaths/min
- Altered Mentation: GCS < 15
- Systolic Blood Pressure: ≤ 100 mmHg
In NHS practice, qSOFA is a teaching and research tool rather than the escalation trigger. NICE NG253 stratifies adults with suspected or confirmed infection using the National Early Warning Score 2 (NEWS2), interpreted with clinical judgement: 7 or more = high risk, 5–6 = medium risk, 1–4 = low risk, 0 = very low risk of severe illness or death from sepsis. If a single parameter scores 3, request a high-priority review by a clinician with acute-care competencies (FY2 or above) to decide the risk level. Mottled or ashen skin, a non-blanching rash, or other causes for concern can raise the risk above that suggested by NEWS2 alone.
NICE NG253 Risk Bands & the "Sepsis Six"
NICE NG253 links each NEWS2 band to time-critical actions:
| NEWS2 band | Risk of severe illness or death | Key NICE NG253 actions |
|---|---|---|
| 7 or more (or a single parameter of 3 confirmed as high risk on review) | High | Urgent review by a clinician at FY2 level or above; venous blood gas with glucose and lactate, blood cultures, FBC, CRP, U&Es, creatinine, LFTs and clotting; broad-spectrum IV antibiotics within 1 hour of calculating NEWS2; IV fluid within 1 hour unless contraindicated; involve the senior decision-maker, and the consultant and critical care if there is no response within 1 hour of any intervention |
| 5–6 | Medium | The same blood tests; FY2-or-above review of the patient and venous lactate within 1 hour; antibiotics may be deferred for up to 3 hours while a more specific diagnosis is sought; treat as high risk if there is hypoperfusion (lactate over 2 mmol/L or acute kidney injury) |
| 1–4 | Low | Clinical assessment, look for alternative diagnoses and the source, and safety-net |
| 0 | Very low | Manage the infection on its own merits |
NG253 (2026 update) also suggests considering procalcitonin testing, alongside standard tests, in adults at medium or high risk.
Fluid Resuscitation Under NG253
- Use an isotonic crystalloid, preferably a balanced solution such as Hartmann's (0.9% saline only if a balanced solution is not available).
- Give an initial 250 mL bolus over 10–15 minutes, reassess after each bolus, and give further 250 mL boluses up to 1,000 mL in total (including fluid already given). If the person has not improved after 1,000 mL, get advice from a senior clinical decision-maker.
- NICE reduced the first bolus from 500 mL to 250 mL in 2025. The international Surviving Sepsis Campaign still describes up to 30 mL/kg in the first 3 hours, but UK exam answers follow NICE.
The UK Sepsis Trust "Sepsis Six"
The UK Sepsis Trust bundle, whose clinical tools were updated to match NICE, is the bedside checklist for high-risk patients and should be delivered within the first hour:
| Step | Action | Practical points |
|---|---|---|
| 1 | Inform a senior clinician | Confirm sepsis, consider alternative diagnoses and agree any treatment limits |
| 2 | Give oxygen if required | Titrate to SpO2 94–98% (88–92% if at risk of hypercapnic respiratory failure) |
| 3 | Send bloods, including cultures | Blood cultures (ideally before antibiotics but without delaying them), venous blood gas with lactate and glucose, FBC, U&Es, CRP, LFTs and clotting; sample other sites (urine, sputum, wound) |
| 4 | Consider IV antibiotics and source control | Broad-spectrum, per local guideline, within 1 hour for high-risk patients; call surgeons or radiology early for drainable sources |
| 5 | Consider IV fluids | Balanced crystalloid in 250 mL boluses with reassessment, up to 1,000 mL before senior review |
| 6 | Continue monitoring | NEWS2, hourly urine output (catheterise if needed; target above 0.5 mL/kg/h) and repeat lactate; escalate if not improving |
Important
Avoid Large Volumes of 0.9% Saline: Large volumes of 0.9% sodium chloride cause hyperchloraemic metabolic acidosis and are associated with more renal replacement therapy. NICE NG253 prefers balanced crystalloids (Hartmann's solution or Plasma-Lyte) for sepsis resuscitation.
Septic Shock: Definition & Hemodynamic Resuscitation
Septic shock is a clinical subset of sepsis wherein underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality (>40%).
Clinical Criteria for Septic Shock
- Persisting hypotension requiring vasopressors to maintain a Mean Arterial Pressure (MAP) ≥ 65 mmHg, AND
- Serum lactate > 2.0 mmol/L (18 mg/dL) despite adequate volume resuscitation.
Hemodynamic Targets & Drug Selection
- Target MAP: Maintain MAP ≥ 65 mmHg to ensure adequate vital organ perfusion pressure (cerebral, coronary, and renal).
- First-Line Vasopressor: Noradrenaline (norepinephrine) is the drug of choice. It acts predominantly as a potent alpha-1 adrenergic agonist to restore systemic vascular resistance, with modest beta-1 inotropic activity. It is ideally given through a central venous line; NICE NG253 accepts peripheral administration after a shared decision, following local policies on drug, dose, concentration and monitoring, so that treatment is not delayed.
- Second-Line Vasopressor: Vasopressin (at a fixed dose of 0.03 units/min) can be added to noradrenaline to either raise MAP or reduce noradrenaline dosage requirements.
- Inotrope Selection: If myocardial dysfunction persists with low cardiac output and hypoperfusion despite adequate volume and MAP, add an inotrope such as dobutamine.
- Corticosteroids: Intravenous hydrocortisone (200 mg/day) is suggested for septic shock with an ongoing vasopressor requirement (Surviving Sepsis Campaign 2021 example: noradrenaline 0.25 µg/kg/min or more for at least 4 hours).
Biomarkers & Serial Assessment
- Serum Lactate: Reflects anaerobic glycolysis secondary to tissue hypoperfusion, mitochondrial dysfunction, and accelerated aerobic glycolysis driven by adrenergic stimulation. Measuring serial lactate clearance is vital: failure to clear lactate by ≥20% every 2 hours during active resuscitation strongly correlates with worsening multi-organ dysfunction and death.
- Procalcitonin (PCT): Produced by parenchymal tissues in response to bacterial endotoxins and pro-inflammatory cytokines (IL-1β, TNF-α). Useful for confirming bacterial aetiology and guiding antibiotic discontinuation decisions (antimicrobial stewardship).
- C-Reactive Protein (CRP): Acute-phase reactant synthesized by the liver in response to IL-6. Highly sensitive for systemic inflammation, though non-specific; useful for tracking therapeutic response over 48–72 hours.
A 68-year-old man is admitted with severe community-acquired pneumonia. Over the past 2 hours, he has received 1,000 mL of balanced crystalloid in 250 mL boluses, with reassessment after each. On reassessment, his blood pressure is 82/48 mmHg (Mean Arterial Pressure 59 mmHg), heart rate is 114 bpm, respiratory rate is 24 breaths/min, and oxygen saturation is 95% on 4 L/min via nasal cannula. Repeat venous blood gas demonstrates a lactate of 3.4 mmol/L. His lungs have bilateral basal crackles and his jugular venous pressure is visible 3 cm above the sternal angle. What is the most appropriate next step in hemodynamic management?
Start a noradrenaline infusion targeting a MAP of at least 65 mmHg
Administer IV furosemide 40 mg to relieve developing pulmonary congestion
Administer a further rapid 2000 mL bolus of 0.9% normal saline
Infuse 500 mL of 20% human albumin solution over 30 minutes
A 71-year-old woman with severe chronic obstructive pulmonary disease (COPD) and documented chronic hypercapnic respiratory failure carries an oxygen alert card stating a target SpO2 of 88–92%. She presents with 2 days of dysuria and fever and is diagnosed with urosepsis. She is alert and speaking in full sentences. Her respiratory rate is 24 breaths/min, blood pressure is 118/72 mmHg, heart rate is 104 bpm, and SpO2 on room air is 85%. What is the most appropriate oxygen prescription during her initial assessment?
High-flow 100% oxygen via a 15 L/min non-rebreathe reservoir mask targeting 98–100%
Controlled oxygen via a 28% Venturi mask or nasal cannulae titrated to achieve target oxygen saturations of 88–92%
Withhold supplemental oxygen entirely until an arterial blood gas result is obtained to preserve hypoxic respiratory drive
Immediate endotracheal intubation and invasive mechanical ventilation before starting medical therapy
A junior doctor is using the quick Sequential Organ Failure Assessment (qSOFA) bedside tool to identify ward patients with suspected infection who are at heightened risk of poor clinical outcomes. Which of the following constellations of physiological signs represents a qSOFA score of 3?
Urine output 15 mL/h, Arterial blood gas pH 7.28, and Serum lactate 3.8 mmol/L
Heart rate 116 bpm, Temperature 39.1°C, and White blood cell count 18.5 x 10^9/L
Respiratory rate 18 breaths/min, Systolic blood pressure 90 mmHg, and Glasgow Coma Scale 15
Respiratory rate 24 breaths/min, Glasgow Coma Scale 13, and Systolic blood pressure 94 mmHg
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