Sepsis — Symptoms, Causes & Treatment | MyMedicPlus

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis-3 definition, 2016 — replaces previous SIRS-based criteria). The dysregulated immune response causes simultaneous excessive inflammation and immunosuppression, leading to multi-organ failure. Septic shock: the most severe form of sepsis — vasoplegic hypotension requiring vasopressors to maintain mean arterial pressure (MAP) above 65 mmHg despite adequate fluid resuscitation (30 mL/kg crystalloid) plus serum lactate above 2 mmol/L; hospital mortality for septic shock is approximately 40%. Sepsis affects 49 million people and causes 11 million deaths annually worldwide — accounting for 20% of all global deaths. In the UK, an estimated 245,000 cases of sepsis occur annually, causing approximately 48,000 deaths. Sepsis is the final common pathway of many severe infections and must be recognised and treated within 1 hour of presentation — every hour of delay in antibiotic administration increases mortality by approximately 7%.

Bacterial infections are the most common cause: gram-negative organisms (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa — typically from urinary, respiratory, or abdominal sources) and gram-positive organisms (Staphylococcus aureus including MRSA, Streptococcus pneumoniae, Group A Streptococcus — from skin, respiratory, or soft tissue sources). Source of infection: urinary tract infections (most common in community-onset sepsis), respiratory tract (pneumonia — most common in hospital-acquired sepsis), abdominal and biliary tract (bowel perforation, cholangitis, diverticulitis), skin and soft tissue (cellulitis, necrotising fasciitis), intravascular catheters (CLABSI — central line-associated bloodstream infection). Fungal sepsis (Candida species) occurs in immunocompromised patients, those with prolonged antibiotic exposure, and ICU patients with central venous catheters. Risk factors: extremes of age (neonates and elderly), immunosuppression (chemotherapy — neutropenic sepsis is an oncological emergency; long-term corticosteroids; biological agents; HIV/AIDS), invasive devices (urinary catheters, central venous catheters, mechanical ventilation), recent surgery, diabetes, chronic renal failure, liver cirrhosis, malnutrition, and frailty.

Early systemic signs: fever (above 38°C) or hypothermia (below 36°C — a sign of severe sepsis and poor prognosis), tachycardia (above 90 bpm), tachypnoea (above 20 breaths per minute), leukocytosis (above 12×10⁹/L) or leukopenia (below 4×10⁹/L). Organ dysfunction (the hallmark of sepsis, distinguishing it from uncomplicated infection): altered consciousness or confusion (brain — cerebral hypoperfusion), hypotension (MAP below 65 mmHg — cardiovascular failure), oliguria (urine output below 0.5 mL/kg/hour for 2 hours — acute kidney injury), elevated creatinine (above 176.8 mcmol/L), coagulopathy (INR above 1.5 or aPTT above 60 seconds — DIC risk), elevated bilirubin (above 34 mcmol/L — hepatic dysfunction), and hyperlactataemia (above 2 mmol/L — tissue hypoperfusion). qSOFA score (quick SOFA): respiratory rate above 22/min + altered mentation (GCS below 15) + systolic BP below 100 mmHg — a score of 2 or above at the bedside predicts poor outcome and triggers immediate senior medical review and sepsis bundle initiation. Skin: mottled (livedo reticularis) or blotchy appearance — a sign of peripheral vasoconstriction and impaired skin perfusion indicating severity.

Sepsis-3 diagnostic criteria: suspected or confirmed infection PLUS a SOFA (Sequential Organ Failure Assessment) score increase of 2 or more points from baseline — SOFA assesses 6 organ systems (respiratory, coagulation, liver, cardiovascular, CNS, and renal). Two sets of blood cultures from different peripheral sites before antibiotics (takes only 10 minutes — never delay antibiotics more than 10 minutes to obtain them). Lactate measurement: guides resuscitation and prognosis — lactate above 2 mmol/L indicates tissue hypoperfusion even without hypotension; above 4 mmol/L — approximately 40% mortality; target lactate clearance of more than 10% per hour with resuscitation. Full blood count (CBC — leukocytosis or leukopenia), CRP, procalcitonin (PCT — above 0.25 ng/mL suggests bacterial infection; useful for antibiotic de-escalation decisions), coagulation screen (INR, fibrinogen, D-dimer for DIC assessment), LFTs, renal function (creatinine, eGFR, urea), urinalysis and urine culture, chest X-ray (pneumonia, ARDS), and culture of all clinically suspected infection sites (wound swabs, sputum, drain fluid, CSF if meningitis suspected). CT scan of abdomen for abdominal source (perforation, abscess, cholangitis).

Hour-1 sepsis bundle (Surviving Sepsis Campaign 2018): (1) Measure blood lactate — repeat if initial above 2 mmol/L; (2) Blood cultures x2 from different sites before antibiotics (never delay antibiotics more than 10 minutes for cultures); (3) Broad-spectrum IV antibiotics within 1 hour of recognition — meropenem 1 g IV + metronidazole 500 mg IV (intra-abdominal source), co-amoxiclav 1.2 g IV (urinary source), tazocin 4.5 g IV (respiratory), vancomycin + meropenem (MRSA risk, healthcare-associated); delays in antibiotics increase mortality by approximately 7% per hour; (4) 30 mL/kg IV crystalloid bolus (Hartmann's or normal saline) for hypotension or lactate above 4 mmol/L — reassess after each 500 mL aliquot for fluid responsiveness; (5) Vasopressors (norepinephrine — first choice, target MAP above 65 mmHg; add vasopressin 0.03 units/min or hydrocortisone 200 mg/day as steroid-sparing agents in refractory septic shock). Source control: surgical or percutaneous drainage of abscesses, debridement of necrotising fasciitis, removal of infected catheters, ureteric stenting for obstructive uropathy — within 6 hours where possible. De-escalate antibiotics within 48–72 hours based on culture results and clinical response — antimicrobial stewardship reduces emergence of resistance. Glycaemic control: insulin infusion targeting 6–10 mmol/L in ICU patients with septic shock.

Acute respiratory distress syndrome (ARDS — bilateral inflammatory lung injury causing severe hypoxic respiratory failure requiring mechanical ventilation — occurs in 10–40% of sepsis cases); acute kidney injury (AKI — affects 50% of patients in septic shock, requiring renal replacement therapy — CVVHDF — in approximately 25%); disseminated intravascular coagulation (DIC — consumptive coagulopathy causing simultaneous thrombosis and haemorrhage — elevated D-dimer, falling fibrinogen, prolonged INR/aPTT, thrombocytopaenia — life-threatening); hepatic dysfunction (elevated bilirubin and transaminases from ischaemia and direct inflammation); septic cardiomyopathy (myocardial depression from inflammatory cytokines — reduced ejection fraction in 40–50% of septic shock patients, usually reversible); ICU-acquired weakness (critical illness neuromyopathy — prolonged ventilator dependence and rehabilitation need in 25–50% of critically ill sepsis survivors); post-sepsis syndrome: cognitive impairment, PTSD, depression, chronic fatigue, and new or worsened physical disability persist in up to 50% of sepsis survivors for months to years after discharge — constituting a significant long-term morbidity burden. In-hospital mortality: approximately 20–30% for sepsis, 40% for septic shock. Long-term mortality: 1-year mortality after sepsis is approximately 40–50%, driven by underlying comorbidity and post-sepsis immune dysfunction.

Prevention: hand hygiene (WHO 5-moments — the single most effective infection control measure, reducing healthcare-associated infections by 50%); IV catheter care bundles (CLABSI prevention — maximal sterile barrier, chlorhexidine skin prep, daily catheter-need assessment, prompt removal when no longer required); ventilator care bundle (VAP prevention — head-of-bed elevation 30–45 degrees, oral chlorhexidine 0.12%, subglottic secretion drainage, daily sedation holds, spontaneous breathing trials); urinary catheter care (CAUTI prevention — sterile insertion, closed drainage, daily review of indication — urinary tract infection is the most common community-onset sepsis source); antimicrobial stewardship (appropriate antibiotic choice, dose, duration, and de-escalation reduces emergence of resistant organisms); influenza and pneumococcal vaccination for high-risk groups (elderly, immunocompromised, COPD, diabetes, chronic heart and liver disease); surgical site infection prevention bundles (pre-operative antiseptic skin preparation, antibiotic prophylaxis within 60 minutes of incision, normothermia, glycaemic control); early recognition of deteriorating ward patients using NEWS2 (score above 5 = Red Alert — requires immediate critical care review and hourly monitoring).

Sepsis is a medical emergency — call 999/112/911 or go to the nearest emergency department immediately if you suspect it. The 'Sepsis Six' warning signs (UK Sepsis Trust): slurred speech or confusion; extreme shivering, muscle pain, or feels like you have the worst flu ever; passing no urine in a day; severe breathlessness; feels like you are going to die; and skin mottled or discoloured. If someone with a known infection develops any of these features, assume sepsis until proven otherwise. Time is critical — every hour without treatment increases mortality by approximately 7%. Seek urgent same-day assessment (call 111 or go to urgent care) for: high fever with chills and rigors following a urinary tract infection, chest infection, skin wound, or dental procedure; a wound or skin area becoming rapidly hot, red, swollen, and painful (cellulitis or necrotising fasciitis); and fever in an immunocompromised person (on chemotherapy, steroids, biological agents, or with haematological malignancy) — even low-grade fever may indicate neutropenic sepsis requiring emergency admission and broad-spectrum antibiotics within 1 hour.