Sepsis — Causes, Warning Signs, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Sepsis is defined by the Sepsis-3 consensus (2016) as life-threatening organ dysfunction caused by a dysregulated host response to infection. It represents a medical emergency in which the body's immune response to infection, rather than the infection itself, causes widespread tissue injury and organ failure. Septic shock — the most severe form — is defined as sepsis with circulatory failure (vasopressor requirement to maintain mean arterial pressure above 65 mmHg) and elevated serum lactate above 2 mmol/L despite adequate fluid resuscitation, carrying a mortality rate of 40-50%. Globally, sepsis affects approximately 49 million people annually and causes approximately 11 million deaths — 20% of all global deaths. Sepsis is the most common cause of preventable death in hospitals and ICUs. In-hospital mortality from sepsis is 10-30%; septic shock mortality is 40-50%. Survivors face long-term complications including cognitive impairment, post-traumatic stress disorder, weakness, organ damage, and significantly increased 5-year mortality. Sepsis can develop from any infection — including seemingly minor ones — and can deteriorate rapidly from presentation to septic shock within hours.

Sepsis is most commonly caused by bacterial infections, though fungi, viruses (including influenza and COVID-19), and parasites can also cause sepsis. The most frequent sources of infection leading to sepsis are: respiratory (pneumonia — most common source in community-acquired sepsis); urinary tract (UTI, pyelonephritis — particularly gram-negative bacteria, E. coli); abdominal (peritonitis, biliary sepsis — cholangitis, appendicitis, perforated viscus); skin and soft tissue (cellulitis, necrotising fasciitis — rapidly fatal without surgical debridement); and bloodstream infection/bacteraemia (line-related — healthcare-associated sepsis). Common causative organisms: gram-negative bacteria (E. coli, Klebsiella, Pseudomonas, Enterobacter — endotoxin-mediated shock); gram-positive bacteria (Staphylococcus aureus including MRSA — exotoxin-mediated; Streptococcus pneumoniae; Group A Streptococcus — necrotising fasciitis, streptococcal toxic shock); fungi (Candida — particularly in immunocompromised and critical care patients). Risk factors for sepsis: extremes of age (neonates and elderly — immune senescence); immunocompromised state (HIV, chemotherapy, corticosteroids, biological therapy); chronic comorbidities (diabetes, chronic kidney disease, liver cirrhosis — all impair immune function); recent surgery, invasive procedures, or hospitalisation; indwelling catheters or IV lines; malnutrition; pregnancy and the puerperium; and homelessness/deprivation.

Sepsis can present deceptively — early sepsis may mimic a 'bad infection' before deteriorating rapidly. The UK Sepsis Trust 'Sepsis Six' awareness campaign uses the mnemonic for red flag symptoms: temperature above 38.3°C or below 36°C (hypothermia is ominous); respiratory rate above 22 breaths/minute; heart rate above 100 beats/minute; altered mentation (new confusion, agitation, or reduced consciousness); low blood pressure (systolic below 90 mmHg or decrease of more than 40 mmHg from baseline — a late and ominous sign); and mottled/cyanotic skin or not passed urine in 18 hours. High clinical suspicion is essential — sepsis can present without fever (particularly in elderly, immunocompromised, or those on steroids) and without obvious focus. The quick SOFA (qSOFA) bedside screening tool identifies patients at risk of organ dysfunction: respiratory rate above 22, altered mentation, and systolic BP below 100 mmHg — score 2+ warrants immediate investigation and treatment. SOFA (Sequential Organ Failure Assessment) scores across 6 organ systems (respiratory, coagulation, liver, cardiovascular, CNS, renal) — increase of 2+ points above baseline indicates organ dysfunction defining sepsis. Severe sepsis features include: oliguria/anuria, serum creatinine above 176 μmol/L, coagulopathy, elevated bilirubin, thrombocytopaenia, ileus, and metabolic acidosis. Septic shock: refractory hypotension requiring vasopressors + serum lactate above 2 mmol/L.

Sepsis is a clinical diagnosis supported by investigations — delays waiting for results must not defer treatment. Immediate blood tests: full blood count (leucocytosis or leucopenia — WBC above 12 or below 4 x10^9/L; thrombocytopaenia in severe sepsis); serum lactate (key prognostic marker — above 2 mmol/L signals tissue hypoperfusion; above 4 mmol/L indicates high mortality); blood cultures (two sets from separate sites before antibiotics — identify causative organism in 15-30% of cases; do not delay antibiotics beyond 1 hour to obtain cultures); C-reactive protein (CRP) and procalcitonin (PCT — elevated in bacterial sepsis; PCT also guides antibiotic duration and de-escalation); blood glucose (hyperglycaemia common in sepsis); renal function, liver function, coagulation (APTT/PT — elevated in DIC); and arterial blood gas (ABG — assess hypoxaemia, hypocapnia, metabolic acidosis, and base excess). Site-specific cultures and samples: urine microscopy and culture (suspected UTI); sputum, BAL, or respiratory sample (pneumonia); wound swabs; CSF (suspected meningitis — only after CT if papilloedema or focal neurology); and drain or fluid aspiration. Imaging: chest X-ray (pneumonia, pleural effusion); CT abdomen/pelvis (abdominal source of sepsis — urgent if intra-abdominal pathology suspected); ultrasound (biliary sepsis, renal obstruction). Echocardiogram (rule out endocarditis in bacteraemia). Blood cultures should always be taken before antibiotics if possible (within 45 minutes of sepsis recognition) but must never delay antibiotic administration beyond 1 hour.

Sepsis treatment follows time-sensitive evidence-based bundles. Surviving Sepsis Campaign 1-Hour Bundle (SSC 2018): (1) measure serum lactate — re-measure if above 2 mmol/L; (2) obtain blood cultures before administering antibiotics; (3) administer broad-spectrum intravenous antibiotics within 1 hour of sepsis recognition — every hour of delay in antibiotics increases mortality by 7-10%; (4) administer 30 mL/kg IV crystalloid (sodium chloride 0.9% or Hartmann's solution) for hypotension or lactate above 4 mmol/L — completed within 3 hours; (5) apply vasopressors (noradrenaline — first-line agent, maintains mean arterial pressure above 65 mmHg) if hypotension persists after fluid resuscitation or if initial MAP is below 65 mmHg. UK Sepsis Six (implemented within 1 hour): oxygen (target SpO2 above 94%); blood cultures; IV antibiotics; IV fluid bolus; serum lactate and FBC; urinary catheter and hourly urine output monitoring. Antibiotic selection: broad-spectrum empirical coverage based on suspected source — piperacillin-tazobactam + gentamicin covers gram-negative sepsis; add metronidazole for abdominal source; add glycopeptide (vancomycin, teicoplanin) for MRSA risk or healthcare-associated sepsis; antifungal (caspofungin) for Candida risk. Antibiotics should be de-escalated to the narrowest effective agent once culture and sensitivity results are available (typically 48-72 hours). Source control is essential: drainage of abscess, debridement of necrotising fasciitis, removal of infected prosthetic material, ERCP/PTC for biliary sepsis. Vasopressors (noradrenaline first-line; vasopressin added for refractory shock); inotropes (dobutamine for myocardial depression — cardiogenic component of sepsis); hydrocortisone 200 mg/day (for septic shock refractory to fluids and noradrenaline — reverses adrenal suppression). Organ support in ICU: mechanical ventilation (ARDS, respiratory failure — low tidal volume 6 mL/kg with plateau pressure below 30 cmH2O); renal replacement therapy (acute kidney injury stage 3); blood glucose control (target 6-10 mmol/L with insulin infusion). Procalcitonin-guided antibiotic duration reduces antibiotic exposure without worsening outcomes.

Septic shock — the most severe complication — occurs when sepsis-induced circulatory failure and cellular metabolic abnormalities are profound enough to substantially increase mortality (above 40% in-hospital mortality; defined by vasopressor requirement to maintain MAP above 65 mmHg and serum lactate above 2 mmol/L despite adequate fluid resuscitation). Multi-organ dysfunction syndrome (MODS) involves sequential or simultaneous failure of two or more organ systems — most commonly acute kidney injury (AKI — requiring renal replacement therapy in 5–20% of sepsis patients), acute respiratory distress syndrome (ARDS — occurs in 25–40% of septic shock patients; bilateral pulmonary infiltrates, PaO2/FiO2 below 200 mmHg, requiring invasive mechanical ventilation), hepatic dysfunction (elevated bilirubin, coagulopathy), and cardiovascular dysfunction (myocardial depression — septic cardiomyopathy). Disseminated intravascular coagulation (DIC) from endothelial activation and procoagulant cytokine storm causes simultaneous thrombosis and haemorrhage — prolonged PT/aPTT, thrombocytopenia, elevated D-dimer, and low fibrinogen. DIC carries high mortality. Acute mesenteric ischaemia and gut translocation can perpetuate systemic inflammation. Post-intensive care syndrome (PICS): survivors of severe sepsis frequently develop lasting physical, cognitive, and psychological sequelae — muscle wasting and weakness (ICU-acquired weakness), cognitive impairment resembling dementia, PTSD, depression, and anxiety are reported in 30–50% at 1 year. ICU-acquired weakness from critical illness polyneuropathy and myopathy is associated with prolonged mechanical ventilation. Mortality varies by source of infection, pathogen, age, and comorbidities — overall 30-day mortality in sepsis is 15–30% and above 40% in septic shock.

Vaccination is the most effective sepsis prevention strategy: influenza vaccine annually; pneumococcal vaccine (PCV20, PPSV23) for high-risk individuals (elderly, immunocompromised, splenectomised, chronic disease); meningococcal vaccine; Haemophilus influenzae type b; and hepatitis B. Aseptic technique for all invasive procedures — central venous catheters, urinary catheters, and peripheral cannulae should be inserted using sterile technique and removed as soon as no longer needed. Hand hygiene (WHO five moments of hand hygiene) is the most effective simple measure to prevent healthcare-associated infection. Antibiotic stewardship reduces emergence of resistant organisms causing sepsis. Post-splenectomy patients require lifelong penicillin prophylaxis and vaccination against encapsulated organisms (pneumococcus, meningococcus, Haemophilus). Wound care and early recognition of surgical site infections. Diabetic foot care to prevent entry of infection. Public awareness: early recognition of sepsis symptoms by patients and carers enables earlier presentation and treatment, which is the most significant factor in improving sepsis survival.

Sepsis is a medical emergency — call 999 or the local emergency number immediately for any person (including children) who is unwell with suspected infection AND any of the following: extreme shivering, muscle pain, or feeling 'the worst ever'; skin that is mottled, bluish, or very pale; not passed urine in 12-18 hours (or no wet nappy in a child); changed mental status — confusion, slurred speech, or difficulty staying awake; breathes very fast or has difficulty breathing; feels faint, dizzy, or collapses. In hospitals and emergency departments: use NEWS2 (National Early Warning Score) or equivalent triggering systems; a NEWS2 of 5 or above warrants immediate senior review and sepsis screening. Do not wait for lab results before starting treatment in a patient with suspected sepsis who looks clinically unwell — the '1-hour bundle' should be initiated on clinical suspicion. Sepsis can deteriorate from presentation to septic shock in 1-2 hours without treatment.