Sepsis and septic shock

Respiratory

Pneumonia — the most common source overall

Abdominal

Cholangitis, perforation, appendicitis, diverticulitis, ischaemic bowel

Urinary

Pyelonephritis, obstructed infected stone, catheter-associated infection

Skin and soft tissue

Cellulitis, necrotising fasciitis, diabetic foot infection, pressure ulcers

Device / line related

Central venous catheter, prosthetic joint, pacemaker, peritoneal dialysis catheter

CNS and other

Meningitis, endocarditis, septic arthritis, postpartum and post-surgical infection

Non-bacterial

Influenza, dengue, severe malaria, invasive candidiasis, COVID-19

• Roughly 49 million cases and 11 million sepsis-related deaths annually worldwide (GBD estimates).
• Around 85% of the burden occurs in low- and middle-income countries.
• Neonates, young children, pregnant and postpartum women, and older adults are disproportionately affected.

• Age extremes and frailty
• Immunosuppression: chemotherapy, corticosteroids, biologics, HIV, asplenia, transplant
• Diabetes, CKD, cirrhosis, malignancy
• Indwelling devices, recent surgery or instrumentation
• Pregnancy and the postpartum period
• Injection drug use and alcohol dependence
• Prior hospitalisation and multidrug-resistant colonisation

1. 1Pathogen-associated molecular patterns activate innate immune receptors; tissue injury releases damage-associated patterns.
2. 2Massive cytokine release (TNF-α, IL-1β, IL-6) triggers endothelial activation and glycocalyx shedding.
3. 3Nitric oxide overproduction causes pathological vasodilatation and vasoplegia.
4. 4Coagulation activation with impaired fibrinolysis produces microvascular thrombosis and consumptive coagulopathy.
5. 5Mitochondrial dysfunction impairs oxygen utilisation even when delivery is restored (cytopathic hypoxia).
6. 6Concurrent immunosuppressive phase increases risk of secondary infection.

Normal physiology → mechanism → tissue change → clinical picture

1. 1Normal physiology: local inflammation contains infection while systemic perfusion and coagulation stay regulated.
2. 2Mechanism: uncontrolled systemic inflammatory and coagulation activation with endothelial barrier failure.
3. 3Tissue change: capillary leak, interstitial oedema, microthrombi, maldistributed blood flow.
4. 4Organ effect: hypoxaemia (ARDS), reduced GFR (AKI), cholestasis, ileus, encephalopathy, myocardial depression.
5. 5Clinical manifestation: fever or hypothermia, tachypnoea, hypotension, mottling, oliguria, confusion, raised lactate.

• Fever, rigors or feeling very cold
• Extreme malaise, 'worst ever' feeling, myalgia
• Breathlessness
• Reduced urine output
• Confusion, drowsiness, slurred speech
• Source-specific symptoms: cough, dysuria, abdominal pain, wound pain

• Tachypnoea, tachycardia, hypotension, narrow then widening pulse pressure
• Fever > 38 °C or hypothermia < 36 °C
• Mottled skin, prolonged capillary refill > 3 s, cold or paradoxically warm peripheries
• Altered mental state, GCS drop
• Oliguria < 0.5 mL/kg/h
• Purpura fulminans or non-blanching rash in meningococcal disease

1. 1Screen every unwell patient for infection plus organ dysfunction (NEWS2, qSOFA, or local sepsis screening tool).
2. 2Start the hour-1 bundle in parallel with diagnostics — do not sequence them.
3. 3Identify the source clinically, then confirm with targeted imaging (chest radiograph, ultrasound, CT).
4. 4Take cultures from blood plus the suspected site before antimicrobials if this causes no meaningful delay.
5. 5Quantify organ dysfunction with SOFA components: PaO2/FiO2, platelets, bilirubin, MAP/vasopressors, GCS, creatinine and urine output.
6. 6Escalate to critical care for vasopressor need, lactate > 4 mmol/L, or persisting dysfunction.
7. 7Reassess perfusion within 1-2 hours and again after each intervention; plan source control within 6-12 hours where needed.

Sepsis (Sepsis-3)

Suspected or confirmed infection PLUS acute increase in SOFA ≥ 2 points

Septic shock

Sepsis PLUS vasopressors to maintain MAP ≥ 65 mmHg PLUS lactate > 2 mmol/L after adequate fluid

qSOFA (bedside screen)

RR ≥ 22, altered mentation, SBP ≤ 100 mmHg — ≥ 2 indicates higher risk, not a diagnosis

Paediatric

Use age-specific vital sign thresholds and paediatric sepsis criteria — adult scores are not valid

Initial

• Lactate, blood cultures ×2 sets, FBC, CRP, urea and electrolytes, creatinine, liver function, coagulation screen, blood gas, glucose, urinalysis.

Source identification

• Site-specific cultures (urine, sputum, wound, CSF, pleural or ascitic fluid), chest radiograph, ultrasound or CT for occult source.

Severity / monitoring

• Repeat lactate at 2-4 h, urine output hourly, SOFA scoring, echocardiography or fluid-responsiveness assessment in shock.

Stewardship

• Procalcitonin where used for de-escalation, cultures for resistance profile, antimicrobial levels for vancomycin or aminoglycosides.

Haemorrhagic / hypovolaemic shock

Rule in: bleeding source, low haemoglobin, responds to blood. Rule out: infection focus and fever.

Cardiogenic shock

Rule in: raised JVP, pulmonary oedema, low cardiac output on echo. Rule out: warm vasodilated periphery with low SVR.

Anaphylaxis

Rule in: rapid onset after exposure, urticaria, wheeze, angio-oedema. Rule out: gradual onset with fever.

Pulmonary embolism

Rule in: acute RV strain, hypoxaemia with clear lungs. Rule out: consolidation with purulent secretions.

Adrenal crisis

Rule in: steroid dependence, hyponatraemia, hyperkalaemia, fluid-refractory hypotension. Rule out: response to antimicrobials and fluids alone.

Toxic / drug reaction

Rule in: serotonin syndrome, neuroleptic malignant syndrome, withdrawal features. Rule out: identified microbiological source.

• SOFA score across six organ systems quantifies dysfunction and tracks trajectory.
• Lactate > 2 mmol/L indicates hypoperfusion; > 4 mmol/L marks high mortality risk.
• Vasopressor dose requirement and lactate clearance at 6 hours are strong prognostic markers.

Immediate (hour-1 bundle)

• Oxygen to maintain saturations; secure airway if obtunded
• Two large-bore cannulae; balanced crystalloid, at least 30 mL/kg for hypoperfusion, given in reassessed boluses
• Broad-spectrum antimicrobials within 1 hour of recognition, guided by source and local resistance
• Noradrenaline if MAP remains < 65 mmHg during or after fluid resuscitation — start peripherally rather than delay
• Serial lactate and urine output; involve critical care early

Source control

• Drain abscesses, remove infected devices, relieve obstruction, debride necrotic tissue — ideally within 6-12 hours.

Refractory / organ support

• Add vasopressin as second agent; consider hydrocortisone in vasopressor-refractory shock
• Dobutamine or inotropes for septic cardiomyopathy with low output
• Lung-protective ventilation (6 mL/kg predicted body weight) for ARDS; prone positioning for severe hypoxaemia
• Renal replacement therapy for refractory acidosis, hyperkalaemia, fluid overload or uraemia

Supportive

• VTE prophylaxis, stress ulcer prophylaxis where indicated, glucose 8-10 mmol/L target, early enteral nutrition, delirium prevention, transfuse at Hb < 70 g/L unless bleeding or ischaemia.

Monitoring / stewardship

• De-escalate antimicrobials on culture results; typical 7-day course for most sources with adequate control; daily reassessment of lines, drains and organ support.

Linked drug entities

• ceftriaxone — common empirical backbone; add cover for MRSA, Pseudomonas or anaerobes per risk
• noradrenaline — first-line vasopressor targeting MAP ≥ 65 mmHg
• enoxaparin — VTE prophylaxis unless contraindicated
• paracetamol — antipyresis; avoid masking trends, watch hepatic dose limits in liver disease

Early

• Septic shock, ARDS, AKI, disseminated intravascular coagulation, ischaemic hepatitis, stress cardiomyopathy, ileus.

Intermediate

• Nosocomial and secondary infection, critical illness myopathy and neuropathy, pressure injury, delirium, thromboembolism.

Late

• Post-sepsis syndrome: fatigue, cognitive impairment, PTSD, functional dependence; increased 1-year mortality; digital or limb loss after severe vasopressor exposure.

• Hospital mortality roughly 15-25% for sepsis and above 30-40% for septic shock, varying widely with resources and comorbidity.
• Each hour of delay to effective antimicrobials is associated with measurably increased mortality.
• Lactate clearance and reversal of organ dysfunction within 24-48 hours predict survival.
• Survivors face persistent excess mortality and functional decline for 1-2 years — plan rehabilitation.

• Vaccination (pneumococcal, influenza, COVID-19, meningococcal, Hib) in at-risk groups
• Hand hygiene, care bundles for lines and catheters, timely device removal
• Prompt treatment of localised infection and diabetic foot surveillance
• Antimicrobial stewardship to limit resistance
• Sepsis screening tools embedded at triage and on wards

• Discharge summary documenting pathogen, antimicrobial course, and outstanding investigations
• Screen for post-sepsis physical, cognitive and psychological sequelae at 4-6 weeks
• Reassess immunisation, source-related surgery, and device replacement plans
• Rehabilitation referral for weakness or functional decline

Pregnancy / postpartum

Lower vital-sign thresholds, consider chorioamnionitis and endometritis, avoid teratogenic agents, urgent obstetric input

Neonates / children

Age-specific thresholds; fluid boluses 10-20 mL/kg with reassessment; early inotropes in resource-limited settings

Elderly

Hypothermia and delirium instead of fever; lower reserve; involve ceiling-of-care discussions early

CKD / dialysis

Careful fluid strategy, adjust antimicrobial dosing, consider dialysis-catheter infection

Cirrhosis

Consider spontaneous bacterial peritonitis; albumin for large-volume paracentesis; lactate may be unreliable

Neutropenic

Treat as emergency with anti-pseudomonal beta-lactam within 1 hour; consider fungal cover if persistent fever

• Surviving Sepsis Campaign international guidelines (2021)
• WHO clinical management of severe acute respiratory infection (2023)
• National sepsis pathway applicable to your service

• Balanced crystalloids are generally favoured over 0.9% saline for large-volume resuscitation.
• Restrictive versus liberal fluid strategies after initial resuscitation remain under active study.
• Vitamin C, thiamine and steroid combinations have not shown consistent mortality benefit.

• Surviving Sepsis Campaign 2021 (guideline, global).
• Sepsis-3 consensus definitions (JAMA 2016).
• DrZep editorial summary, demo dataset v0.1.