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Sepsis and Septic Shock: Anaesthetic Management

LONG QUESTION — MD Anaesthesiology

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1. INTRODUCTION AND DEFINITIONS (Sepsis-3, 2016)

The old terms "severe sepsis" and SIRS-based criteria are no longer used in Sepsis-3.

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2. EPIDEMIOLOGY AND ETIOLOGY

• ~88% of cases are community-onset (within 48 h of admission); 12% hospital-onset
• 53% are culture-positive; equal split between gram-positive and gram-negative organisms
• Common gram-positives: S. aureus, Streptococcus spp., Enterococcus (13.6% MRSA/VRE)
• Common gram-negatives: E. coli, Klebsiella, Pseudomonas (13.2% resistant strains)
• Most common infection sites: urinary tract (49%), respiratory (33%), intra-abdominal (14%), skin/soft tissue (10%)
• Mortality of septic shock: 35–40% at 28 days (improving over time due to bundle-based care)

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3. PATHOPHYSIOLOGY

3a. Immune and Inflammatory Response

• Cytokine storm: TNF-α, IL-1β, IL-6 → systemic inflammation
• Complement activation
• Procoagulant cascade: microthrombi, DIC
• Immunosuppression: lymphocyte apoptosis, T-cell exhaustion, delayed adaptive immunity

3b. Cardiovascular Pathophysiology

• Massive vasodilation → ↓ SVR → relative hypovolemia
• Early/hyperdynamic phase: ↑ CO, warm extremities, bounding pulse, wide pulse pressure
• Later phase: myocardial depression (septic cardiomyopathy), ↓ contractility despite ↑ CO from tachycardia
• Endothelial activation → capillary leak → third spacing → absolute hypovolemia
• Microcirculatory failure and maldistribution of blood flow → tissue hypoxia despite potentially normal global DO₂

3c. Respiratory

• Cytokine-mediated endothelial damage → high-permeability pulmonary oedema → ARDS
• ↑ Dead space, ↓ FRC, V/Q mismatch, intrapulmonary shunting

3d. Renal

• Sepsis is the commonest cause of AKI in ICU (up to 66% of critically ill patients)
• Mechanisms: renal hypoperfusion, direct tubular toxicity from cytokines, microvascular thrombosis

3e. Coagulation

• DIC: consumption of clotting factors and platelets → simultaneous bleeding and thrombosis
• Elevated INR, thrombocytopenia, elevated D-dimer, fibrinogen depletion

3f. Metabolic / Endocrine

• Lactic acidosis: impaired oxygen extraction at tissue level, Warburg effect, mitochondrial dysfunction
• Relative adrenocortical insufficiency ("critical illness-related corticosteroid insufficiency", CIRCI)
• Hyperglycemia from stress response; hypoglycemia in late/hepatic failure
• Hypocalcaemia, hypomagnesaemia

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4. CLINICAL FEATURES

SOFA Score (Sequential Organ Failure Assessment)

1. Respiratory — PaO₂/FiO₂
2. Coagulation — Platelets
3. Liver — Bilirubin
4. Cardiovascular — MAP / vasopressor requirements
5. CNS — Glasgow Coma Scale
6. Renal — Creatinine / urine output

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5. DIAGNOSIS AND MONITORING

Investigations

• Blood cultures (at least 2 sets, including from all lines) — before antibiotics
• FBC, CMP, LFTs, coagulation profile, blood gas (lactate)
• Procalcitonin (PCT) — not for initiating antibiotics but useful for de-escalation
• Urine culture, wound swabs, sputum/BAL culture
• Chest X-ray, CT scan (source identification)
• Echocardiography (assess cardiac function, preload, tamponade)
• Serum lactate — serial monitoring for adequacy of resuscitation (target < 2 mmol/L)

Monitoring in Anaesthesia / ICU

• Invasive arterial line (beat-to-beat BP monitoring, ABG sampling)
• Central venous catheter (CVP, drug delivery, ScvO₂)
• Urinary catheter (urine output; target ≥ 0.5 mL/kg/h)
• Cardiac output monitoring: echocardiography (TTE/TOE), pulse contour analysis (PiCCO, LiDCO), pulmonary artery catheter (selected cases)
• Temperature monitoring (core and peripheral)

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6. ANAESTHETIC MANAGEMENT

6a. Pre-operative / Pre-induction Assessment and Stabilisation

The 1-Hour Bundle (SSC 2021)

1. Blood cultures drawn (before antibiotics)
2. Empiric broad-spectrum antibiotics administered within 1 hour of recognition
3. Lactate measurement (if ≥ 4 mmol/L → treat as septic shock)
4. Crystalloid 30 mL/kg IV (within 3 hours if hypotensive or lactate ≥ 4)
5. Vasopressors if MAP < 65 mmHg despite fluid resuscitation

• Optimize volume status (avoid both under- and over-resuscitation; use dynamic indicators — PPV, SVV, echo-guided assessment)
• Secure central venous and arterial access
• Insert urinary catheter
• Correct coagulopathy (FFP if INR > 1.5 in bleeding patient, platelets if < 50,000/μL with surgery planned)
• Correct hypocalcaemia, hypomagnesaemia
• Identify and communicate airway concerns

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6b. Induction of Anaesthesia

• Severe cardiovascular collapse on induction (loss of sympathetic drive + vasodilation from agents + PPV-induced preload reduction)
• Difficult airway (oedema, coagulopathy, limited mouth opening from source)
• Full stomach (ileus, emergency surgery) → aspiration risk

Approach

• Treat as RAPID SEQUENCE INDUCTION (RSI) in almost all emergency cases
• Pre-oxygenate with 100% O₂ for 3–5 minutes (or 8 vital-capacity breaths)
• Have vasopressors immediately available (phenylephrine, ephedrine, norepinephrine infusion)
• Positioning: slight head-up or supine with left lateral tilt if pregnant

Choice of Induction Agents

Neuromuscular Blockade for RSI

• Suxamethonium 1.5 mg/kg (if no contraindications — hyperkalaemia is a concern in established AKI/rhabdomyolysis; check K+ first)
• Rocuronium 1.2–1.6 mg/kg (equivalent onset to suxamethonium when used at higher doses; reversible with sugammadex 16 mg/kg)

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6c. Maintenance of Anaesthesia

• Volatile agents (sevoflurane, isoflurane) at reduced MAC — may cause vasodilatation; titrate carefully
• TIVA with propofol infusion at reduced rates; ketamine infusion as adjunct for haemodynamic support
• Opioids: Titrate carefully; fentanyl or morphine acceptable; avoid bolus doses that cause histamine release (morphine)
• Avoid nitrous oxide — immunosuppression, bowel distension, increases homocysteine

Haemodynamic Targets During Anaesthesia

• MAP ≥ 65 mmHg (higher targets, e.g., 75–80 mmHg, in chronic hypertensives)
• CVP: less reliable; use dynamic measures (PPV > 13% → fluid-responsive)
• ScvO₂ ≥ 70% (or SvO₂ ≥ 65%)
• Lactate clearance ≥ 10% per 2 hours — target normalization

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6d. Fluid Management

• Crystalloids (balanced solutions — Ringer's Lactate or PlasmaLyte preferred over NS; avoid large volumes of NS → hyperchloraemic acidosis)
• Initial resuscitation: 30 mL/kg within 3 hours
• Reassess with dynamic fluid responsiveness indicators before each fluid bolus: PPV, SVV, passive leg raise test, mini-fluid challenge (250 mL over 5 min → assess CO response)
• Albumin (4–5%) may be considered when large volumes of crystalloid required (SSC: weak recommendation)
• Avoid: hetastarch (HES) / gelatins — increased AKI and mortality in sepsis
• Target: adequate preload, not a CVP target

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6e. Vasopressors and Inotropes

Key principle: Norepinephrine is the cornerstone. Vasopressin is added early rather than escalating NE beyond 0.25 μg/kg/min. Dopamine is largely abandoned.

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6f. Corticosteroids

• Hydrocortisone 200 mg/day (IV continuous infusion or 50 mg q6h bolus) is recommended in refractory septic shock (shock persisting despite adequate fluids and vasopressors)
• Mechanism: anti-inflammatory, restores vasopressor sensitivity (upregulates α-adrenergic receptors), corrects CIRCI
• Do NOT use ACTH stimulation test to guide steroid use (ADRENAL and APROCCHSS trials, 2018)
• Taper steroids when vasopressors are no longer required
• CORTICUS trial: no benefit in non-refractory shock; hence restrict to refractory cases

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6g. Respiratory Management / Mechanical Ventilation

Lung-Protective Ventilation (ARDS Net protocol)

• Tidal volume: 6 mL/kg ideal body weight (NOT actual body weight)
• Plateau pressure: ≤ 30 cmH₂O
• PEEP: apply adequate PEEP to maintain alveolar recruitment (PEEP titration — ARDSNet table or decremental PEEP trial)
• FiO₂: target SpO₂ 92–96% / PaO₂ 55–80 mmHg
• Permissive hypercapnia (PaCO₂ 45–60 mmHg) acceptable if pH ≥ 7.20
• I:E ratio: 1:2 (avoid air trapping)

Advanced Respiratory Interventions

• Prone positioning: ≥ 12 hours/day recommended for moderate-severe ARDS (P/F ratio < 150) — improves V/Q matching, recruits dorsal lung
• Neuromuscular blockade: facilitates proning; intermittent bolus preferred over continuous infusion
• VV-ECMO: for severe refractory ARDS (P/F < 80 despite optimal ventilation) in centres with expertise
• Recruitment manoeuvres: selective use
• High-flow nasal cannula (HFNC): may delay intubation in moderate hypoxia, but monitor closely

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6h. Antibiotic and Source Control

• Cultures first — do not delay antibiotics waiting for results, but culture BEFORE first dose
• Broad-spectrum empirical antibiotics within 1 hour of septic shock recognition
• Empirical regimens by source:
  • Unknown/undifferentiated: piperacillin-tazobactam ± vancomycin (MRSA coverage)
  • Hospital-acquired/Pseudomonas risk: cefepime or meropenem
  • Abdominal source: meropenem or piperacillin-tazobactam + metronidazole
  • Urinary source: ceftriaxone (community-acquired)
  • Skin/SSTI: vancomycin + pip-tazo
• De-escalation at 48–72 hours based on culture sensitivity
• Duration: typically 7–10 days; PCT-guided de-escalation reduces overuse
• Source control: drain abscesses, debride necrotic tissue, remove infected lines/catheters — ideally within 6–12 hours of diagnosis

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6i. Blood Products and Targets

• Red cell transfusion threshold: Hb < 7 g/dL in ICU (restrictive strategy)
  • Exception: Hb < 9 g/dL permissible in early septic shock, active ischaemia (ACS), or neurologic injury
• FFP: only for documented coagulopathy with active bleeding or planned invasive procedure; do not transfuse prophylactically
• Platelets: transfuse if < 50,000/μL with active bleeding or surgery planned; < 10,000/μL prophylactically
• Cryoprecipitate / fibrinogen concentrate: for DIC with fibrinogen < 1.5 g/L

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6j. Glycaemic Control

• Target blood glucose 140–180 mg/dL (7.8–10 mmol/L) using insulin infusion protocol
• Avoid tight glycaemic control (< 80–110 mg/dL) — NICE-SUGAR trial showed increased mortality with intensive insulin therapy due to hypoglycaemia
• Hourly glucose monitoring during insulin infusion

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6k. Sedation and Analgesia in the Mechanically Ventilated Septic Patient

• Follow ABCDEF bundle (Assess, Both SAT+SBT, Choose wisely, Delirium, Early mobility, Family)
• Analgesia-first approach: treat pain before sedation (fentanyl/morphine)
• Light sedation preferred (RASS –1 to 0 target) over deep sedation
• Daily sedation interruption (DSI/SAT) + daily spontaneous breathing trial (SBT)
• Preferred sedatives: propofol (short-term) or dexmedetomidine (reduces delirium, promotes cooperative sedation, facilitates extubation)
• Avoid benzodiazepine infusions (midazolam) — associated with increased delirium, prolonged ICU stay

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6l. Renal Replacement Therapy

• Indicated for severe AKI (KDIGO stage 3, oliguria/anuria > 12h, uraemia, refractory acidosis/hyperkalaemia, fluid overload)
• CRRT (continuous) preferred over IHD in haemodynamically unstable patients
• No proven benefit from early initiation of RRT in uncomplicated AKI (STARRT-AKI trial)

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6m. Post-operative and ICU Care

• Admission to ICU within 6 hours of diagnosis
• Thromboprophylaxis: UFH or LMWH (dose-adjust for renal function); mechanical if anticoagulation contraindicated
• Stress ulcer prophylaxis: PPI or H₂ blocker in mechanically ventilated patients
• Early enteral nutrition within 24–48 hours via NGT; avoid parenteral nutrition in first 7 days if gut functioning
• Head of bed elevation 30–45° (VAP prevention)
• Oral hygiene / chlorhexidine mouth care (VAP prevention)

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7. ORGAN FAILURE MANAGEMENT SUMMARY

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8. SPECIAL CONSIDERATIONS IN SEPTIC OBSTETRIC PATIENT

• Sepsis is a leading cause of maternal mortality
• Septic abortion, chorioamnionitis, pyelonephritis, endometritis are common sources
• Physiological changes of pregnancy alter presentation: tachycardia and hypotension may be masked or exaggerated
• Aortocaval compression — left lateral tilt, especially if gravid uterus
• Airway oedema in pregnancy + sepsis — plan for difficult airway
• Avoid etomidate; ketamine preferred for haemodynamically unstable obstetric patient
• Consult obstetrics urgently; fetal monitoring; expedite delivery if fetal compromise

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9. PROGNOSIS AND OUTCOMES

• Hospital mortality: ~20–25% for sepsis, 35–40% for septic shock
• Sepsis survivors face significant long-term morbidity: PTSD, cognitive impairment, physical disability, recurrent infections
• Post-Sepsis Syndrome: a constellation of physical, psychological, and cognitive sequelae affecting up to 50% of survivors
• Discharge planning should include screening for economic/social support, physical rehabilitation, and psychological follow-up (SSC 2021)

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10. KEY EXAMINATION POINTS (Quick Review)

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REFERENCES

• Barash, Cullen, and Stoelting's Clinical Anesthesia, 9e, Chapter 57 (Critical Care Medicine / Septic Shock), pp. 4828–4832
• Harrison's Principles of Internal Medicine, 22e (2025), Chapter 315 (Sepsis and Septic Shock), pp. 2359–2366
• Evans L et al: Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 49:e1063, 2021
• Singer M et al: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:801, 2016
• NICE-SUGAR Study Investigators: Intensive versus Conventional Glucose Control in Critically Ill Patients. NEJM 2009
• Weiss SL et al: Surviving Sepsis Campaign International Guidelines for Children 2026. Pediatr Crit Care Med, 2026 [PMID: 41869844]

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