PassFinals
Infectious Disease

Sepsis

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, in which inflammatory signalling and microvascular failure injure organs remote from the infected site.

Definition

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, the Sepsis-3 definition NICE NG253 adopts. Research operationalises organ dysfunction as a rise of 2 or more SOFA (Sequential Organ Failure Assessment) points, but UK bedside practice uses NEWS2. Septic shock is sepsis needing vasopressors to hold mean arterial pressure at 65 mmHg or more, with lactate over 2 mmol/L despite fluids.

Epidemiology

Any infection can cause sepsis. NICE's 2025 review lists age 75 or over, ethnic minority background, frailty, multimorbidity, impaired immunity, surgery or an invasive procedure within 6 weeks, indwelling catheters, repeated antibiotics and breached skin. Communication difficulties, drug or alcohol misuse, homelessness and deprivation raise the chance sepsis is missed.

Pathophysiology

Pathogen components and damaged host cells trigger widespread cytokine release. Vasodilation and capillary leak drop systemic vascular resistance and intravascular volume, while microthrombi and endothelial injury disrupt capillary flow. Oxygen delivery falls and cellular oxygen use is impaired, so lactate rises. Organs fail in the order their reserve runs out.

First principles

Sepsis is infection plus organ dysfunction

Most infections stay localised. Sepsis is the subset where the host response turns dysregulated and damages organs, so the diagnosis needs new dysfunction of circulation, breathing, brain or kidneys. The old SIRS (systemic inflammatory response syndrome) criteria were retired in 2016 because almost any unwell patient meets two. Fever is neither necessary nor sufficient.1,2,3

NEWS2 grades urgency, it does not diagnose sepsis

NEWS2 (National Early Warning Score 2) adds points for respiratory rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse, consciousness or new confusion, and temperature. It measures physiological disturbance from any cause. A high score in an infected patient signals danger without proving sepsis, and a low score never overrides a worried clinician.4,5

The antibiotic clock is risk-stratified, not a universal hour

Only high risk carries the 1 hour deadline. Moderate risk allows 3 hours and low risk 6 hours, and that time exists only to reach a specific diagnosis. Once the decision to treat is made, no further delay is acceptable. The Sepsis Six is a UK Sepsis Trust care bundle, not a NICE recommendation.6,7,8

Fluid is titrated in 250 mL steps

Vasodilation and capillary leak make the septic circulation fluid-responsive early and fluid-intolerant later. NICE therefore gives 250 mL, reassesses, and repeats only while the patient improves, capped at 1,000 mL before senior input. More fluid past that point worsens oedema and gas exchange without restoring perfusion.6

Antibiotics cannot drain an abscess

No antimicrobial sterilises an undrained collection, an obstructed infected ureter or a colonised line. Source control runs alongside resuscitation. Examine for a focus, consider urinalysis and chest X-ray in everyone, and image the abdomen and pelvis if nothing emerges. Involve surgery or interventional radiology early rather than after failure.9

Presentation

Suspect sepsis when possible infection is joined by new physiological, neurological, respiratory, renal or circulatory deterioration. Temperature may be normal or low, so NEWS2 and clinical context, not fever, drive the decision.3,5,6,10

Cardinal features

  • Suspected or confirmed infection with new deterioration from baseline
  • Tachycardia, tachypnoea, hypoxia or a new oxygen requirement
  • Hypotension, prolonged capillary refill, mottled or ashen skin, or cyanosis
  • New confusion or reduced GCS, sometimes reported only by family as altered behaviour
  • Reduced urine output or acute kidney injury
  • Fever, rigors or hypothermia, although normal temperature does not exclude sepsis

Red flags

  • NEWS2 of 7 or more: IV antibiotics and a fluid bolus within 1 hour
  • Any single NEWS2 parameter scoring 3: high-priority review by a Foundation Year 2 (FY2) doctor or above
  • NEWS2 of 5 or 6 with lactate over 2 mmol/L or acute kidney injury: manage as high risk
  • Mottling, cyanosis or a non-blanching petechial or purpuric rash: treat as a higher band than the score
  • No response within 1 hour of any intervention: senior decision maker in person, critical care, consultant informed
  • A drainable or obstructed source: refer to surgery or interventional radiology now
  • Neutropenia, pregnancy or recent pregnancy, or age under 16: a different NICE pathway applies

Investigations

Structured observations and NEWS2

Measure temperature, heart rate, respiratory rate, blood pressure, consciousness and oxygen saturation, then read NEWS2 against the person's usual physiology and previous scores. Ask family what has changed and how much urine has been passed in 18 hours.

Expected finding: Interpret against baseline: beta-blockers blunt tachycardia, older people may throw a new arrhythmia instead, and NEWS2 of 0 is very low risk rather than no risk.

5,4

Venous blood gas with lactate, blood panel and cultures

At high and moderate risk send a venous gas including glucose and lactate, with blood cultures, FBC, CRP, U&E, creatinine, LFTs and clotting. Culture the suspected focus too, but never let sampling push a high-risk patient past the 1 hour deadline.

Expected finding: Lactate over 2 mmol/L or acute kidney injury at moderate risk means treating as high risk. Acidosis, cytopenia, deranged LFTs or coagulopathy indicate organ dysfunction. Negative cultures do not exclude sepsis.

6,11

Urinalysis and chest X-ray, then targeted imaging

Consider urinalysis and chest X-ray in everyone. If no source emerges after examination and initial tests, image the abdomen and pelvis. Image elsewhere when a line, joint, spine or central nervous system focus is suspected.

Expected finding: Consolidation, pyuria, a collection, perforation or obstruction identifies the source and, if drainable, triggers immediate surgical or radiological referral.

9

Serial NEWS2 and active reconsideration of the diagnosis

Recalculate NEWS2 every 30 minutes at high risk, hourly at moderate, every 4 to 6 hours at low risk, and with routine observations at very low risk. Recalculate after any deterioration.

Expected finding: Rising blood pressure, clearing consciousness, better urine output and a falling NEWS2 indicate response. Persistent abnormality means escalation, and prompts review for haemorrhage, PE, MI, pancreatitis, DKA or adrenal crisis.

5,3

Management

StepDetailSource
Recognise possible sepsis, assess face to face and grade the riskAny possible infection with new abnormality of behaviour, circulation or breathing needs face-to-face observations: temperature, heart rate, respiratory rate, blood pressure, consciousness, oxygen saturation. Examine for a source, mottling, cyanosis or a non-blanching rash. NEWS2 of 7 or more is high risk, 5 to 6 moderate, 1 to 4 low, 0 very low.3,5NICE NG253, 1.1.1 to 1.3.7 and 1.6.2
Override the score when the patient looks worse than the numberA single parameter scoring 3 needs high-priority review by a Foundation Year 2 (FY2) doctor or above to fix the band. Mottling, cyanosis, purpura, deterioration or failure to improve since the last score all justify managing at a higher risk level.5NICE NG253, 1.6.2 to 1.6.4
High risk: bloods, cultures and IV antibiotics within 1 hourArrange urgent assessment by an FY2 doctor or above. Send the venous gas, cultures and blood panel. Give a broad-spectrum IV antibiotic within 1 hour of the first NEWS2, calculated on emergency department arrival or ward deterioration. Refer to the senior clinical decision maker, ST3 or above in adults.6,1NICE NG253, 1.8.2, 1.8.3 and terms used
Choose the empirical antibiotic: chest or urinary sourceSevere pneumonia: IV co-amoxiclav 1.2 g every 8 hours plus clarithromycin 500 mg every 12 hours, or levofloxacin 500 mg every 12 hours if penicillin-allergic. Urinary source: co-amoxiclav 1.2 g every 8 hours, ceftriaxone 1 to 2 g once daily, or gentamicin 5 to 7 mg/kg once daily.12,13NICE NG250 and NG111 antibiotic tables
Choose the empirical antibiotic: abdominal, unknown, skin or brain sourceAbdominal or unidentified source: IV piperacillin with tazobactam 4.5 g every 8 hours. Severe cellulitis: co-amoxiclav 1.2 g every 8 hours, adding vancomycin 15 to 20 mg/kg every 8 to 12 hours if MRSA is likely. Suspected meningitis: ceftriaxone 2 g every 12 hours, plus amoxicillin 2 g every 4 hours if Listeria risk factors exist.11,14,15,16,17,18,19,20NICE NG253 1.9.7, NG141, NG240 1.6.5 to 1.6.6, plus manufacturers' prescribing information
Adjust for the local formulary, allergy, renal function and monitoringThese are common UK choices, not a national protocol: check your trust's antimicrobial guideline, usually MicroGuide, for the agreed first-line agent. Reduce doses in renal impairment, avoid beta-lactams after anaphylaxis, and monitor gentamicin and vancomycin levels. Neutropenic sepsis gets piperacillin with tazobactam 4.5 g every 6 hours immediately.11,21,16NICE NG253 1.9.2, NICE CG151
Resuscitate with 250 mL boluses and set the oxygen targetWithin 1 hour of identifying high risk, give 250 mL of a balanced crystalloid such as Hartmann's over 10 to 15 minutes, or 0.9% sodium chloride if none is available. Reassess, repeat to a maximum of 1,000 mL, then get senior advice. Target saturations 94% to 98%, or 88% to 92% if at risk of hypercapnic respiratory failure.6,11NICE NG253, 1.8.4 to 1.8.9 and 1.10.1
Moderate and low risk: use the 3 and 6 hour windows properlyAt moderate risk, an FY2 doctor or above must review the patient and the lactate within 1 hour. Broad-spectrum antibiotics may then be deferred for up to 3 hours to reach a specific diagnosis, after senior discussion. Low risk allows up to 6 hours. Lactate over 2 mmol/L or acute kidney injury converts moderate risk to high risk.6,7NICE NG253, 1.8.16 to 1.8.23
Find and control the sourceRun source-finding in parallel with treatment: urinalysis and chest X-ray in everyone, further tests tailored to the examination, and abdominal and pelvic imaging if no source is found. If drainage, decompression, debridement or line removal could control the infection, involve surgery or interventional radiology early.9NICE NG253, 1.11.1 to 1.11.4
Escalate non-response and septic shockIf a high-risk patient has not responded within 1 hour of any intervention, the senior clinical decision maker attends in person. Contact critical care and inform the consultant. For shock persisting after 1,000 mL, discuss vasopressors with critical care. A peripheral start needs a visible cannula watched for extravasation.6NICE NG253, 1.8.11 to 1.8.15
Narrow the antibiotic, plan discharge and check the population pathwayOnce the source or microbiology is known, narrow the antibiotic rather than continuing broad-spectrum cover. Before discharge, explain the diagnosis or the remaining uncertainty, the warning signs and how to get urgent help, and tell the GP. Pregnancy uses NG255, under-16s NG254, neutropenic sepsis CG151.11,22,23,24,25,21,10NICE NG253, 1.9.1, 1.8.27 and update information

Illustrations

Dysregulated host responseDiagram showing infection triggering excessive inflammatory signalling, causing vasodilation, capillary leak and microvascular dysfunction distant from the original site.PassFinals · original
Risk-stratified sepsis pathwayInfographic showing NEWS2 risk bands, the one-hour high-risk pathway, the maximum three-hour moderate-risk window, the maximum six-hour low-risk window, fluids, source control and escalation.PassFinals · original
Purpuric rash in severe sepsisNon-blanching purpuric rash and skin microvascular injury in severe sepsis and meningococcal disease; the same rash may be harder to detect on darker skin tones.Gley A.I. and Shkurba A.V., Wikimedia Commons · Public domain

Differentials

Cardiogenic or hypovolaemic shock

Shock with no convincing infective source, and a cardiac or haemorrhagic cause.

Anaphylaxis

Onset within minutes of exposure, with urticaria, angioedema, wheeze or airway compromise.

Pulmonary embolism or myocardial infarction

Cardiopulmonary symptoms with thrombotic or coronary risk factors and supportive ECG, troponin or imaging.

Diabetic ketoacidosis or adrenal crisis

Acidosis, hypotension and altered consciousness explained by ketones, glucose, sodium and potassium.

Pancreatitis, burns or other non-infective inflammation

Systemic inflammation with a clear non-infective trigger and negative infection assessment.

Complications

  • Septic shock with persistent hypoperfusion
  • Acute kidney injury and multi-organ dysfunction
  • Acute respiratory distress syndrome and respiratory failure
  • Coagulopathy and disseminated intravascular coagulation
  • Delirium, longer-term cognitive impairment and post-sepsis syndrome
  • Death

Prognosis

Outcome depends on how early infection is recognised, how fast antibiotics and source control follow, and how many organs fail. Septic shock carries hospital mortality above 40%. Survivors commonly develop post-sepsis syndrome, usually improving over 6 to 18 months.

Guidelines

  • Suspected sepsis in people aged 16 or over: recognition, assessment and early management (NG253) (NICE, 2025)
  • Statement on the initial antimicrobial treatment of sepsis (v2.0) (Academy of Medical Royal Colleges, 2022)

References

  1. NICE NG253, Terms used in this guideline (NG253)Published 19 Nov 2025
  2. Singer M and others, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA 2016;315(8):801-810 (Sepsis-3)Published 23 Feb 2016
  3. NICE NG253, Could this be sepsis? (NG253)Published 19 Nov 2025
  4. Royal College of Physicians, National Early Warning Score (NEWS) 2 (RCP NEWS2)Published 19 Dec 2017
  5. NICE NG253, Evaluating risk of severe illness or death from sepsis (NG253)Published 19 Nov 2025
  6. NICE NG253, Managing suspected sepsis (NG253)Published 19 Nov 2025
  7. Academy of Medical Royal Colleges, Statement on the initial antimicrobial treatment of sepsis (v2.0) (AoMRC sepsis statement v2.0)
  8. UK Sepsis Trust, information for healthcare professionals and the Sepsis Six (UK Sepsis Trust)
  9. NICE NG253, Finding and controlling the source of infection (NG253)Published 19 Nov 2025
  10. NHS, sepsis (NHS sepsis)Updated 14 May 2026
  11. NICE NG253, Antibiotic therapy, intravenous fluid and oxygen (NG253)Published 19 Nov 2025
  12. NICE NG250, Pneumonia: diagnosis and management, antibiotic choice for adults (NG250)
  13. NICE NG111, Pyelonephritis (acute): antimicrobial prescribing (NG111)Published 31 Oct 2018
  14. NICE NG141, Cellulitis and erysipelas: antimicrobial prescribing (NG141)Published 27 Sept 2019
  15. NICE NG240, Meningitis (bacterial) and meningococcal disease (NG240)Published 19 Mar 2024
  16. Summary of product characteristics, piperacillin 2 g/tazobactam 250 mg powder for solution for infusion (emc SmPC piperacillin with tazobactam)Updated 1 Jun 2022
  17. Summary of product characteristics, ceftriaxone 1 g powder for solution for injection or infusion (emc SmPC ceftriaxone)Updated 12 Aug 2020
  18. Summary of product characteristics, amoxicillin 1 g powder for solution for injection or infusion (emc SmPC amoxicillin)Updated 24 Jul 2023
  19. BNF, piperacillin with tazobactam (BNF piperacillin with tazobactam)
  20. BNF, ceftriaxone (BNF ceftriaxone)
  21. NICE CG151, Neutropenic sepsis: prevention and management in people with cancer (CG151)Published 19 Sept 2012
  22. NICE NG253, Information and support for all people with suspected sepsis (NG253)Published 19 Nov 2025
  23. NICE NG253, Update information (NG253)Published 19 Nov 2025
  24. NICE NG254, Suspected sepsis in under 16s (NG254)
  25. NICE NG255, Suspected sepsis in pregnant or recently pregnant people (NG255)

Evidence checked: 2026-08-05

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.