Sepsis
Exam Tips
- In OSCEs, state explicitly: treat suspected sepsis as a time-critical emergency and give IV antibiotics within 1 hour after cultures if this does not delay treatment.
- Do not rely on fever alone; sepsis may present with normal or low temperature, especially in older or immunocompromised patients.
- Quote septic shock criteria accurately: vasopressor requirement to keep MAP at least 65 mmHg plus lactate greater than 2 mmol/L despite adequate fluids.
- Use a structured script: identify source, assess organ dysfunction, start sepsis bundle, then pursue source control and reassess response.
- Common UK exam pitfall: forgetting safety checks (drug allergy, renal dose adjustment, fluid overload risk, pregnancy/post-partum context).
- See Figure: SOFA/qSOFA concept map and Sepsis Six workflow (standard exam revision diagrams in acute care chapters).
Definition
Sepsis is a life-threatening syndrome in which infection triggers a dysregulated host response, causing acute organ dysfunction rather than a simple localized infection. In clinical practice, suspect it early in any unwell patient with possible infection and physiological deterioration, because delayed treatment rapidly increases mortality. Septic shock is the more severe subset, with persistent hypotension requiring vasopressors to maintain MAP at least 65 mmHg and lactate greater than 2 mmol/L despite adequate fluid resuscitation.
Pathophysiology
Sepsis results from a maladaptive interaction between pathogen factors (load, virulence, site) and host factors (age, frailty, comorbidity, immune status). Early innate immune activation releases pro-inflammatory mediators (for example TNF-alpha, IL-1, IL-6), endothelial injury, complement/coagulation activation, and nitric-oxide-mediated vasodilation; this coexists with compensatory anti-inflammatory pathways that can produce immune paralysis. The net effect is maldistributed microvascular flow, capillary leak, mitochondrial dysfunction, impaired oxygen utilization, and cellular apoptosis, leading to tissue hypoxia and multi-organ dysfunction (for example AKI, ARDS, encephalopathy, cholestatic liver injury). Coagulopathy (including DIC) further worsens organ perfusion through microthrombi and bleeding risk. See Figure: sepsis inflammatory-coagulation-microcirculatory cascade (critical care physiology diagrams).
Risk Factors
- Age extremes (infants under 1 year, older adults over 75 years)
- Frailty and multiple comorbidities
- Immunocompromise (for example diabetes, HIV, cirrhosis, asplenia, sickle cell disease)
- Iatrogenic immunosuppression (chemotherapy, oral corticosteroids, other immunosuppressants)
- Recent surgery, trauma, or invasive procedure (within about 6 weeks)
- Indwelling devices (urinary catheter, vascular line)
- Skin barrier breach (burns, wounds, cellulitis)
- Pregnancy, post-partum state, miscarriage or termination within 6 weeks
- Recent prolonged/repeated antibiotic exposure
- Intravenous drug use or harmful alcohol use
- Communication barriers/cognitive impairment that may delay recognition
Clinical Features
Symptoms
- Feeling very unwell with rapid deterioration from a suspected infection
- Fever, rigors, or sometimes hypothermic symptoms (feeling cold/shivery)
- Reduced urine output or no urine for many hours
- Breathlessness or increased work of breathing
- Confusion, agitation, drowsiness, or acute behavioural change
- Generalized malaise, severe weakness, poor oral intake
- Site-specific infective symptoms (for example cough/sputum, dysuria, abdominal pain, skin/soft tissue pain)
Signs
- Tachypnoea, hypoxia, or respiratory distress
- Tachycardia and hypotension; narrow pulse pressure in shock
- Fever or low core temperature
- Altered mental state (new confusion, reduced GCS/AVPU response)
- Oliguria and signs of dehydration/poor perfusion
- Mottled/cool peripheries or delayed capillary refill
- Non-blanching rash/purpura (consider meningococcal sepsis/DIC)
- Laboratory-supported organ dysfunction (for example rising creatinine, lactataemia, thrombocytopenia)
Investigations
Management
Lifestyle Modifications
- Time-critical escalation: urgent senior review, early warning score monitoring, and clear communication with patient/family about red-flag deterioration
- High-flow oxygen only if hypoxic, with target saturations adjusted to comorbidity (for example CO2 retainers may need lower targets)
- Strict fluid balance, hourly urine output monitoring, and early nutrition/physiotherapy after stabilization
- Safety-netting on discharge: return urgently for confusion, breathlessness, reduced urine output, fever/hypothermia, or worsening function
Pharmacological Treatment
Empirical IV broad-spectrum antibiotics (within 1 hour of suspected high-risk sepsis)
- Piperacillin with tazobactam 4.5 g IV every 6-8 hours
- Meropenem 1 g IV every 8 hours (severe sepsis/high resistance risk, per microbiology advice)
- Ceftriaxone 2 g IV once daily (or cefotaxime 2 g IV every 6-8 hours in selected protocols)
- Add vancomycin IV (weight- and level-guided) if MRSA/device-related risk
Take cultures first if possible but do not delay antibiotics. Choose regimen by likely source, local resistance, allergy history, pregnancy status, and recent microbiology. Check for immediate beta-lactam allergy/anaphylaxis risk; adjust doses for renal impairment; review at 24-48 hours for de-escalation/IV-to-oral switch.
IV fluid resuscitation
- Balanced crystalloid (for example Hartmann's or Plasma-Lyte) 500 mL bolus over less than 15 minutes, repeated with reassessment
- % sodium chloride IV when specifically indicated (for example hypochloraemic states or compatibility reasons)
Use dynamic reassessment (BP, lactate trend, urine output, capillary refill, bedside echo where available). Avoid uncritical large-volume fluids in heart failure, advanced CKD, or pulmonary oedema risk.
Vasopressor/inotrope support in septic shock (critical care)
- Noradrenaline infusion IV titrated to maintain MAP at least 65 mmHg
- Vasopressin infusion as adjunct in refractory vasodilatory shock (ICU protocol)
Requires monitored setting and usually central access. Correct hypovolaemia first; peripheral vasopressor use should be brief and protocolized to reduce extravasation injury.
Adjunctive corticosteroid for refractory shock
- Hydrocortisone 200 mg per 24 hours IV (for example 50 mg every 6 hours or continuous infusion)
Consider if shock persists despite adequate fluids and vasopressors. Monitor glucose, sodium, and secondary infection risk.
Thromboprophylaxis and supportive medicines
- Enoxaparin 40 mg SC once daily (dose-adjust for renal impairment/body weight)
- Paracetamol 1 g PO/IV every 4-6 hours as needed (maximum 4 g/day) for fever/discomfort
Avoid pharmacological VTE prophylaxis if active bleeding or severe coagulopathy; use mechanical prophylaxis where appropriate. Ensure antimicrobial stewardship and stop unnecessary agents promptly.
Surgical / Interventional
- Urgent source control: drainage of abscess/empyema, debridement of necrotizing soft tissue infection, removal/replacement of infected lines
- Relief of obstruction in infected systems (for example nephrostomy or ureteric stent in obstructed infected kidney)
- Early operative management for intra-abdominal sepsis when indicated (for example perforation, ischemic bowel, anastomotic leak)
Complications
- Septic shock with refractory hypotension
- Multi-organ dysfunction/failure (AKI, ARDS, cardiac dysfunction, hepatic dysfunction)
- Disseminated intravascular coagulation, thrombosis, or bleeding
- Secondary and recurrent infections due to immune dysregulation
- Neurological and cognitive impairment (including critical illness neuropathy/encephalopathy)
- Psychological morbidity (anxiety, PTSD, reduced quality of life)
- Death
Prognosis
Outcome depends on speed of recognition, burden of organ dysfunction, pathogen/source control, and patient reserve (age, frailty, comorbidity, immune status). Mortality is substantial and is highest in septic shock; lactate elevation, AKI, DIC, and persistent organ failure indicate poorer prognosis. Survivors have high early readmission risk and many develop post-sepsis physical, cognitive, and psychological sequelae requiring follow-up and rehabilitation.
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(3)
- Ergometrine maleate[contraindications]
- Lidocaine with cetrimide[cautions]
- Suxamethonium chloride[cautions]
✅NICE Guidelines(1)
- Sepsis[overview]
📖Textbook References(15)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 306)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 316, 317)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 311, 312)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1471)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 316)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 316)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 306)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 318)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 311, 312)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 489)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 307)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 594, 595)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 72, 73)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 73)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 73, 74)[context]