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sepsis

life-threatening organ dysfunction caused by a dysregulated host response to infection — the sepsis six must be completed within 1 hour

infectious diseasescommonacute

About This Page

This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

The Bottom Line

  • Sepsis = life-threatening organ dysfunction due to dysregulated host response to infection (Sepsis-3 definition)
  • Septic shock = sepsis + persistent hypotension requiring vasopressors + lactate >2 mmol/L despite fluid resuscitation
  • NEWS2 score ≥5 or any red flag criterion → trigger sepsis pathway
  • Sepsis Six within 1 hour: 1) Blood cultures, 2) Serum lactate, 3) Urine output monitoring (catheterise), 4) IV antibiotics, 5) IV fluids (500 mL crystalloid stat), 6) Oxygen (target SpO₂ ≥94%)
  • Each hour delay in antibiotics increases mortality by ~8% — time is critical

Overview

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis-3, 2016). It represents a spectrum from uncomplicated infection through sepsis to septic shock with multi-organ failure. Any infection can cause sepsis, but the commonest sources are respiratory (pneumonia), urinary, abdominal (peritonitis, biliary), and skin/soft tissue. Early recognition and the "Sepsis Six" bundle within 1 hour of recognition are critical to survival.

Epidemiology

Sepsis affects approximately 250,000 people per year in the UK, with around 48,000 deaths — more than lung, bowel, and breast cancer combined. Mortality from septic shock remains approximately 40%. Groups at highest risk include extremes of age, immunocompromised patients, those with indwelling devices, chronic disease (diabetes, CKD, liver disease), post-surgical patients, and pregnant/postpartum women. Neutropenic sepsis in chemotherapy patients is a specific emergency requiring immediate broad-spectrum antibiotics.

Clinical Features

Symptoms
Fever OR hypothermia (temperature >38°C or <36°C)
Rigors and chills
Feeling "flu-like" or generally very unwell — out of proportion to apparent illness
Confusion or altered mental state
Breathlessness
"I feel like I'm going to die" — patients' own assessment should not be ignored
Reduced urine output
Signs
Tachycardia (HR >90 bpm) — often the earliest sign
Tachypnoea (RR >20)
Hypotension (systolic <90 or MAP <65 or systolic drop >40 from baseline)
Mottled, cyanosed, or ashen skin
Non-blanching rash (meningococcal sepsis)
Warm peripheries (early sepsis — vasodilation). Cold peripheries (late — vasoconstriction, shock)
Altered consciousness, GCS <15
NEWS2 score ≥5 (or 3 in a single parameter)

Investigations

First-line
Blood cultures (×2 sets from 2 sites)Take BEFORE antibiotics — but do NOT delay antibiotics to wait for results
Serum lactate>2 mmol/L suggests tissue hypoperfusion. >4 mmol/L = high risk of death and organ failure
FBC, U&Es, LFTs, CRP, coagulationOrgan dysfunction assessment. Raised WCC or neutropenia; rising creatinine (AKI); deranged LFTs; prolonged INR (DIC)
Blood gas (VBG/ABG)Metabolic acidosis (raised lactate, low bicarbonate), hypoxia
Second-line
Urine MC&SCommon source — dip and send before or with antibiotics
CXRIf respiratory source suspected (pneumonia)
Wound swab / drain fluid / CSFCulture from suspected source
Specialist
CT imagingIf intra-abdominal source suspected (abscess, perforation, biliary)
ProcalcitoninRising levels support bacterial infection; can guide antibiotic duration
1
The Sepsis Six — ALL within 1 hour
  • 1. Take blood cultures (before antibiotics, from 2 peripheral sites)
  • 2. Measure serum lactate
  • 3. Give IV antibiotics (broad-spectrum, per local guidelines — e.g. Tazocin, meropenem)
  • 4. Give IV fluids: 500 mL crystalloid stat (reassess, repeat up to 30 mL/kg)
  • 5. Give high-flow oxygen (target SpO₂ ≥94%, 88–92% in COPD)
  • 6. Measure urine output (catheterise — target ≥0.5 mL/kg/h)
2
Source control
  • Identify and treat the source: drain abscess, remove infected device, operate on perforation
  • Source control within 6–12 hours improves outcomes
  • Image if source unclear: CT abdomen/pelvis, echocardiogram if endocarditis suspected
3
Septic shock / escalation
  • If hypotension persists after 30 mL/kg fluid resuscitation → vasopressors (noradrenaline first-line) — ITU referral
  • Refractory shock: consider hydrocortisone 200 mg/day IV (Surviving Sepsis Campaign recommendation)
  • Monitor: NEWS2, urine output, lactate clearance (aim >20% fall every 2 hours)
  • Senior review if lactate not falling, hypotension persists, or clinical deterioration
4
Neutropenic sepsis
  • Defined as: temperature ≥38°C (or signs of sepsis) + neutrophil count <0.5 × 10⁹/L (usually post-chemotherapy)
  • Treat as medical emergency — IV piperacillin-tazobactam (Tazocin) within 1 hour (NICE NG151)
  • Do NOT wait for blood results — treat empirically based on clinical suspicion

Complications

  • Multi-organ dysfunction: AKI, ARDS, hepatic failure, DIC, cardiac dysfunction — each additional organ failure increases mortality
  • Septic shock: Persistent hypotension despite fluids — mortality ~40%
  • DIC: Consumptive coagulopathy — bleeding and thrombosis simultaneously
  • ARDS: Non-cardiogenic pulmonary oedema — refractory hypoxaemia requiring ventilatory support
  • Long-term: Post-sepsis syndrome (fatigue, cognitive impairment, PTSD, recurrent infections)
UKMLA Exam Tips
  • 1Sepsis Six within 1 HOUR — learn the 6 components. This is tested frequently
  • 2Each hour delay in antibiotics increases mortality by ~8% — antibiotics are the single most time-critical intervention
  • 3Blood cultures BEFORE antibiotics — but NEVER delay antibiotics to wait for culture results
  • 4Lactate >2 = tissue hypoperfusion. Lactate >4 = septic shock territory until proven otherwise
  • 5Neutropenic sepsis: fever + neutrophils <0.5 in a chemo patient → Tazocin within 1 hour. Do NOT wait for results
  • 6NEWS2 ≥5: triggers urgent clinical review. NEWS2 ≥7 or 3 in single parameter: emergency response
  • 7Sepsis can present with hypothermia (<36°C) — especially in elderly, immunocompromised, and neonates. Do not dismiss
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Verified Sources & References

NICE NG51 — Sepsis
Surviving Sepsis Campaign 2021