Septic Shock (Adult)

Overview

Septic shock is defined as a subset of sepsis characterized by profound circulatory, cellular, and metabolic abnormalities that substantially increase mortality.[1] Under the Sepsis-3 definitions, septic shock requires:

• Vasopressor requirement to maintain mean arterial pressure (MAP) ≥65 mmHg, AND
• Serum lactate greater than 2 mmol/L despite adequate fluid resuscitation

Clinical Pearl: Septic shock carries a mortality rate of 40-60%, compared to 10-20% for sepsis without shock. Early recognition and aggressive treatment within the first hour significantly improve survival.[2]

Sepsis-3 Definitions (2016):[1]

Exam Detail: MRCP/FRACP commonly test Sepsis-3 definitions, the Hour-1 bundle components, and vasopressor selection. FRCEM emphasizes early recognition using qSOFA and initial resuscitation priorities.

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Epidemiology

Incidence and Mortality

Demographics and Risk Factors

Age distribution:

• Bimodal: infants/young children and elderly (greater than 65 years)
• Median age of septic shock: 65-70 years
• Mortality increases with age (greater than 75 years: 50-70% mortality)

Risk factors for septic shock:[6]

• Extremes of age (> 1 year, greater than 65 years)
• Immunocompromise (chemotherapy, HIV, transplant, steroids)
• Chronic diseases (diabetes, CKD, cirrhosis, heart failure)
• Indwelling devices (catheters, lines, prostheses)
• Recent surgery or hospitalization
• Malignancy
• Malnutrition

Source of Infection

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Aetiology and Pathophysiology

Microbiology

Bacterial causes (85-90%):[7]

• Gram-negative: E. coli, Klebsiella, Pseudomonas, Acinetobacter (40-50%)
• Gram-positive: S. aureus (including MRSA), Streptococcus, Enterococcus (30-40%)
• Anaerobes: Bacteroides, Clostridium (5-10%)
• Polymicrobial: 10-20%

Non-bacterial causes:

• Fungal (Candida, Aspergillus): 5-10%, increasing in immunocompromised
• Viral (influenza, COVID-19, HSV): rare primary cause of septic shock
• Parasitic (malaria): endemic regions

Pathophysiology of Septic Shock

Inflammatory cascade:[8]

• Pathogen-associated molecular patterns (PAMPs) trigger innate immunity
• Pattern recognition receptors (TLRs, NOD-like receptors) activate
• Pro-inflammatory cytokines released (TNF-α, IL-1β, IL-6)
• Complement activation
• Neutrophil activation and endothelial damage

Endothelial dysfunction:

• Glycocalyx degradation
• Increased vascular permeability (capillary leak)
• Tissue edema
• Impaired microcirculation

Cardiovascular dysfunction:

• Vasodilation - Nitric oxide (NO) excess, loss of vascular tone
• Hypovolemia - Third-spacing from capillary leak
• Myocardial depression - Sepsis-induced cardiomyopathy (reversible)
• Distributive shock - Maldistribution of blood flow

Cellular and metabolic dysfunction:

• Mitochondrial dysfunction
• Impaired oxygen extraction (cytopathic hypoxia)
• Elevated lactate (anaerobic metabolism + impaired clearance)
• Multi-organ dysfunction

Clinical Pearl: Septic shock is primarily a distributive shock with profound vasodilation. However, hypovolemia (from capillary leak) and myocardial dysfunction often coexist, making it a "mixed" shock state.[8]

Hemodynamic Profile

Classic septic shock hemodynamics:

• Decreased systemic vascular resistance (SVR)
• Increased cardiac output (hyperdynamic phase) - initially
• Wide pulse pressure
• Warm peripheries (early "warm shock")
• Progresses to cold shock (vasoconstriction, low CO) if untreated

Echocardiographic findings:

• LV systolic dysfunction in 40-50% (septic cardiomyopathy)
• RV dysfunction in 30-40%
• Usually reversible within 7-10 days

Detailed Pathophysiological Mechanisms

Innate vs Adaptive Immunity in Sepsis

Innate immune response (hours):[28]

• Pattern recognition: PAMPs (LPS, peptidoglycan, flagellin) bind TLRs (Toll-like receptors)
  • "TLR4: Recognizes gram-negative LPS"
  • "TLR2: Recognizes gram-positive peptidoglycans"
  • "TLR5: Recognizes bacterial flagellin"
• Cytokine storm: TNF-α, IL-1β, IL-6, IL-8 released from macrophages
• Complement activation: C3a, C5a promote inflammation and neutrophil recruitment
• Neutrophil activation: Respiratory burst, NET formation, degranulation
• Collateral damage: Excessive innate response injures host tissues

Adaptive immune dysfunction (days):[29]

• T-cell exhaustion: PD-1 and CTLA-4 upregulation, impaired proliferation
• Lymphocyte apoptosis: Massive loss of CD4+ and CD8+ T cells
• Immunoparalysis: Transition from hyper-inflammation to immunosuppression
• Nosocomial infection risk: Secondary infections common (VAP, CLABSI, Candida)

Clinical Pearl: Sepsis is biphasic: Initial hyper-inflammatory phase (first 24-72h) followed by prolonged immunosuppression phase. This explains early ARDS/shock and later secondary infections.[29]

Endothelial Dysfunction Mechanisms

Glycocalyx degradation:[30]

• Heparan sulfate shedding (biomarker: syndecan-1 elevated)
• Loss of protective barrier function
• Increased microvascular permeability
• Leukocyte adhesion and extravasation

Endothelial activation:

• Increased expression of ICAM-1, VCAM-1, E-selectin
• Platelet adhesion and microthrombi formation
• Shift to pro-coagulant state

Vascular permeability:

• VE-cadherin disruption at adherens junctions
• Capillary leak syndrome
• Third-spacing of fluids (interstitial edema)
• Hypoalbuminemia exacerbates fluid shifts

Nitric oxide (NO) dysregulation:

• Excessive iNOS (inducible nitric oxide synthase) activation
• Profound vasodilation and hypotension
• Impaired vascular reactivity to catecholamines

Microcirculatory Failure

Microcirculatory alterations in sepsis:[31]

• Heterogeneous perfusion: Adjacent capillaries have vastly different flow
• Stopped-flow capillaries: Up to 50% of capillaries non-perfused
• Functional shunting: Blood bypasses capillary beds
• Increased diffusion distance: Edema increases O₂ diffusion distance

Mechanisms of microcirculatory dysfunction:

• Endothelial swelling and glycocalyx loss
• Leukocyte plugging
• Microthrombi formation
• Red cell deformability impairment
• Sympathetic overdrive causing precapillary vasoconstriction

Clinical correlation:

• Mottled skin and delayed capillary refill reflect microcirculatory failure
• Normal MAP does not guarantee adequate tissue perfusion
• Microcirculation monitored via sublingual videomicroscopy (research tool)

Mitochondrial Dysfunction

Cytopathic hypoxia:[32]

• Adequate oxygen delivery BUT impaired cellular oxygen utilization
• Mitochondrial electron transport chain (ETC) dysfunction
• Complex I and IV inhibition by inflammatory mediators (NO, peroxynitrite)

Consequences:

• Shift to anaerobic metabolism (lactate production)
• ATP depletion despite normoxia
• Cell death pathways activated (apoptosis, necroptosis)
• Organ dysfunction even after shock resolved

Biomarkers:

• Elevated lactate despite normal ScvO₂ (suggests mitochondrial dysfunction)
• Decreased venous-arterial CO₂ gap (V-aCO₂) correlates with outcomes

Coagulation Cascade in Sepsis

Pro-coagulant state:[33]

• Tissue factor (TF) expression: Endothelial cells and monocytes express TF
• Thrombin generation: Extrinsic pathway activation
• Platelet activation: Microthrombi formation in capillaries
• Fibrin deposition: DIC develops in 25-50% of septic shock

Anticoagulant failure:

• Protein C depletion (consumption + impaired synthesis)
• Antithrombin III depletion
• Tissue factor pathway inhibitor (TFPI) reduction

Fibrinolysis impairment:

• PAI-1 (plasminogen activator inhibitor-1) markedly elevated
• Impaired clot breakdown
• Microvascular thrombosis persists

Disseminated intravascular coagulation (DIC):[34]

• Consumption coagulopathy: Platelets ↓, fibrinogen ↓, PT/APTT ↑
• D-dimer markedly elevated
• Bleeding (GI, pulmonary) AND thrombosis (acral ischemia, purpura fulminans)
• ISTH DIC score: Diagnostic tool (platelets, D-dimer, PT, fibrinogen)

Therapeutic implications:

• Antithrombin III replacement not beneficial in sepsis[35]
• Recombinant activated protein C withdrawn (no benefit, bleeding risk)
• Fresh frozen plasma (FFP) only for active bleeding, NOT prophylactic

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Clinical Presentation

Recognition of Septic Shock

Symptoms suggesting infection:

• Fever or hypothermia
• Rigors, chills
• Localizing symptoms (cough, dysuria, abdominal pain, headache)
• Malaise, confusion

Signs of shock:

• Hypotension (SBP > 90 mmHg or MAP > 65 mmHg)
• Tachycardia (HR greater than 90 bpm)
• Tachypnoea (RR greater than 22/min)
• Altered mental status (confusion, agitation, obtundation)
• Oliguria (> 0.5 mL/kg/hr)
• Mottled skin, delayed capillary refill (greater than 3 seconds)
• Cool extremities (late sign, "cold shock")

qSOFA Score (Quick SOFA)[1]

Bedside screening tool for sepsis (≥2 criteria suggests sepsis):

Interpretation:

• qSOFA ≥2: High suspicion for sepsis, initiate workup and treatment
• qSOFA > 2: Does NOT exclude sepsis - clinical judgment required

Exam Detail: qSOFA is a screening tool, NOT diagnostic criteria. Sepsis diagnosis requires documented/suspected infection PLUS organ dysfunction (SOFA ≥2). qSOFA has moderate sensitivity but good specificity for identifying high-risk patients.[1]

SOFA Score (Sequential Organ Failure Assessment)[9]

Sepsis = SOFA score increase ≥2 points from baseline in setting of infection

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Investigations

Immediate Investigations (Hour-1 Bundle)[10]

Source Identification

Imaging based on suspected source:

• Chest X-ray: All patients (pneumonia, ARDS)
• CT abdomen/pelvis: Suspected intra-abdominal source
• CT head + lumbar puncture: Suspected CNS infection
• Echocardiography: Suspected endocarditis, assess cardiac function
• Ultrasound: Biliary, renal, pelvic sources

Cultures and specimens:

• Blood cultures ×2 sets (aerobic + anaerobic) from separate sites
• Urine culture and microscopy
• Sputum culture (if productive cough, intubated)
• Wound/abscess aspirate if applicable
• CSF if meningitis suspected
• Line tip cultures if CRBSI suspected

Clinical Pearl: Blood cultures should be obtained BEFORE antibiotics but must NOT delay antibiotic administration. If obtaining cultures will delay antibiotics by greater than 45 minutes, give antibiotics first.[10]

Serial Monitoring

Lactate clearance:

• Repeat lactate every 2-4 hours
• Target ≥10% decrease per 2 hours, or normalization (> 2 mmol/L)
• Failure to clear lactate associated with increased mortality[11]

Hemodynamic monitoring:

• Arterial line for continuous BP
• Central venous catheter for CVP and vasopressor administration
• Consider advanced monitoring (ScvO₂, cardiac output) if refractory shock

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Management

Hour-1 Bundle (Surviving Sepsis Campaign 2021)[10]

The Hour-1 Bundle must be initiated immediately upon sepsis recognition:

• Measure lactate level

  • If lactate greater than 2 mmol/L, remeasure within 2-4 hours

• Obtain blood cultures before antibiotics

  • Do NOT delay antibiotics if cultures will take greater than 45 minutes

• Administer broad-spectrum antibiotics

  • Within 1 hour of sepsis recognition (ideally > 30 minutes for septic shock)
  • Appropriate empiric coverage based on suspected source

• Begin rapid fluid resuscitation

  • 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
  • "Note: This is now a WEAK recommendation - individualize based on patient factors[10]"

• Apply vasopressors if hypotensive during or after fluid resuscitation

  • Target MAP ≥65 mmHg
  • Norepinephrine first-line

Clinical Pearl: Each hour delay in antibiotic administration increases mortality by 4-8%. For septic shock, aim for antibiotics within 30 minutes of recognition.[12]

Fluid Resuscitation

Initial resuscitation:[10,13]

• Type: Balanced crystalloids (Ringer's lactate, Plasma-Lyte) preferred over 0.9% saline
  • Balanced crystalloids associated with lower mortality and AKI vs saline[14]
• Volume: 30 mL/kg initial bolus (now WEAK recommendation)
  • May give less if evidence of fluid overload
  • May give more if ongoing losses or profound hypovolemia
• Rate: Rapid boluses (500 mL over 15-30 minutes), reassess after each bolus

Fluid responsiveness assessment:[15]

• Passive leg raise (PLR) with stroke volume monitoring
• Pulse pressure variation (greater than 13% suggests fluid responsive, if mechanically ventilated)
• Stroke volume variation
• Dynamic assessment preferred over static measures (CVP unreliable)

CLOVERS trial (2023):[16]

• Restrictive vs liberal fluid strategy in sepsis-induced hypotension
• No difference in 90-day mortality
• Supports individualized approach rather than mandatory 30 mL/kg

When to stop fluids:

• Signs of fluid overload (pulmonary edema, rising CVP)
• Fluid non-responsiveness
• Adequate perfusion achieved (lactate clearing, urine output improving)

Evidence Debate: The 30 mL/kg debate:

• Traditional teaching: 30 mL/kg crystalloid mandatory for all septic shock
• CLOVERS trial (2023): Restrictive strategy non-inferior to liberal[16]
• CLASSIC trial (2022): Restrictive strategy non-inferior[17]
• Current practice: 30 mL/kg is a reasonable starting point but NOT mandatory - individualize based on patient response, comorbidities, and fluid tolerance[10]

Vasopressor Therapy

Norepinephrine (first-line):[10,18]

• Mechanism: α1 agonist (vasoconstriction) + mild β1 (inotrope)
• Starting dose: 0.05-0.1 µg/kg/min
• Titrate to MAP ≥65 mmHg
• Maximum: 1-2 µg/kg/min (high doses suggest refractory shock)

Vasopressin (second-line adjunct):[19]

• Mechanism: V1 receptor agonist (vasoconstriction)
• Fixed dose: 0.03 units/min (do NOT titrate)
• Add when norepinephrine dose reaches 0.25-0.5 µg/kg/min
• Allows norepinephrine dose reduction
• May reduce mortality in less severe septic shock

Epinephrine (alternative/adjunct):

• Consider if inadequate response to norepinephrine + vasopressin
• Dose: 0.01-0.5 µg/kg/min
• More arrhythmogenic than norepinephrine
• Increases lactate (β2 effect) - complicates lactate monitoring

Dopamine:

• NOT recommended as first-line (higher arrhythmia risk vs norepinephrine)[20]
• May consider in highly selected patients (bradycardia)

Vasopressor administration:

• Central venous catheter preferred
• Peripheral administration safe in early resuscitation if central access delayed[21]
  • Use large vein (antecubital fossa)
  • Dilute concentration
  • Monitor for extravasation
  • Convert to central line when feasible

Advanced Hemodynamic Monitoring

Lactate-Guided Resuscitation

Lactate as resuscitation endpoint:[11,36]

• Superior to ScvO₂-guided therapy (PROCESS, ARISE, ProMISe trials)[37,38,39]
• Target: ≥10% reduction every 2 hours OR normalization (below 2 mmol/L)
• Lactate clearance ≥10% at 6h associated with 60-70% survival vs 30-40% without[11]

Lactate kinetics:

• Initial lactate greater than 4 mmol/L: 2-3× mortality risk
• Lactate normalization within 24 h: Excellent prognosis
• Persistently elevated lactate: Consider occult shock, mitochondrial dysfunction, seizures

ANDROMEDA-SHOCK trial (2019):[40]

• Capillary refill time (CRT) vs lactate-guided resuscitation
• CRT below 3 seconds non-inferior to lactate normalization
• Suggests multiple resuscitation targets acceptable

Limitations of lactate:

• Elevated in seizures, thiamine deficiency, medications (metformin, linezolid)
• Hepatic dysfunction impairs lactate clearance
• Epinephrine increases lactate via β2 effects (not necessarily tissue hypoxia)

Central Venous Oxygen Saturation (ScvO₂)

ScvO₂ monitoring:[13]

• Normal ScvO₂: 65-75% (central venous blood from SVC via CVC)
• Low ScvO₂ (below 65%): Suggests inadequate oxygen delivery vs demand

ScvO₂ interpretation:

Early Goal-Directed Therapy (EGDT) controversy:

• Rivers 2001: EGDT (targeting CVP 8-12, MAP ≥65, UO ≥0.5, ScvO₂ ≥70%) reduced mortality[13]
• PROCESS, ARISE, ProMISe (2014-2015): EGDT no better than usual care[37,38,39]
• Current practice: ScvO₂ useful adjunct but NOT mandatory target

Cardiac Output Monitoring

Indications for cardiac output (CO) monitoring:

• Refractory shock despite vasopressors
• Suspected septic cardiomyopathy
• Unclear volume status (fluid vs vasopressor escalation?)
• Guide inotrope therapy

Monitoring modalities:[41]

Hemodynamic phenotypes in septic shock:[43]

1. Hypovolemic phenotype: Low CO, low CVP → Needs more fluid
2. Vasoplegic phenotype: High CO, low SVR → Needs vasopressors
3. Cardiogenic phenotype: Low CO, high CVP, low EF → Needs inotropes
4. Mixed phenotype: Combination of above

Clinical application:

• Echocardiography first-line for phenotyping septic shock
• PAC rarely used (no mortality benefit despite physiologic data)[42]
• Pulse contour useful for trending CO during interventions

Microcirculation Assessment Tools

Sublingual videomicroscopy (research tool):[31]

• Handheld microscope images sublingual microcirculation
• Measures capillary density, perfusion, heterogeneity
• Research shows microcirculatory improvement predicts survival better than MAP
• Not routinely used clinically (lack of standardization)

Capillary refill time (CRT):[40]

• Simple bedside tool: Press sternum or fingernail 10 seconds, release, measure refill time
• Normal CRT: below 3 seconds
• Prolonged CRT: Marker of poor peripheral perfusion
• ANDROMEDA-SHOCK: CRT-guided resuscitation non-inferior to lactate

Skin mottling score:[44]

• Grade 0-5 based on mottling extent (knees, mid-thigh, inguinal)
• Score ≥3 associated with increased mortality
• Persistent mottling despite resuscitation: Poor prognosis
• Simple, reproducible bedside tool

Inotropic Support

Dobutamine:[10]

• Indication: Evidence of myocardial dysfunction despite adequate fluid and vasopressors
• Signs: Low ScvO₂ (> 70%), poor lactate clearance, echocardiographic LV dysfunction
• Dose: 2.5-20 µg/kg/min
• May cause hypotension (β2 vasodilation) - ensure adequate vasopressor coverage

Antibiotic Therapy

Principles:[10,22]

• Broad-spectrum empiric therapy within 1 hour
• Cover likely pathogens based on:
  • Suspected source of infection
  • Local resistance patterns
  • Patient risk factors (healthcare exposure, immunocompromise)
  • Recent antibiotic exposure
• De-escalate once culture results available

Empiric antibiotic recommendations by source:

Special considerations:

• MRSA risk: Add vancomycin (recent hospitalization, dialysis, IV drug use)
• Pseudomonas risk: Anti-pseudomonal beta-lactam (piperacillin-tazobactam, cefepime, meropenem)
• ESBL risk: Meropenem
• Fungal risk: Add echinocandin (immunocompromise, TPN, broad-spectrum antibiotics)

Clinical Pearl: In septic shock, combination antibiotic therapy (beta-lactam + aminoglycoside or fluoroquinolone) is recommended for initial empiric treatment. De-escalate to monotherapy once pathogen identified and patient stabilized.[10]

Source Control

Principles:[10]

• Identify and control source of infection as soon as feasible
• Aim for source control within 6-12 hours of diagnosis
• Balance urgency against patient stability

Source control interventions:

Corticosteroids

Indications:[10,23]

• Septic shock refractory to fluids and vasopressors
• Norepinephrine dose ≥0.25 µg/kg/min for greater than 4 hours

Regimen:

• Hydrocortisone 200 mg/day (50 mg IV q6h or 200 mg continuous infusion)
• Duration: Until vasopressor weaned, then taper
• Do NOT use ACTH stimulation test to guide treatment

Evidence:

• ADRENAL trial (2018): No mortality benefit, faster shock resolution[24]
• APROCCHSS trial (2018): Mortality benefit in most severe shock[25]
• Current recommendation: Consider in refractory shock (WEAK recommendation)

Additional Therapies

Blood products:[10]

• RBC transfusion: Target Hb greater than 7 g/dL (no benefit of higher threshold)
• Platelets: Transfuse if > 10,000/µL (prophylactic) or > 20,000/µL with bleeding risk
• FFP/coagulation factors: Only if active bleeding or invasive procedures

Renal replacement therapy:

• Initiate for standard indications (refractory hyperkalaemia, acidosis, fluid overload, uraemia)
• No benefit of early vs delayed initiation in absence of absolute indications[26]

Mechanical ventilation:

• Lung-protective ventilation if ARDS (VT 6 mL/kg IBW, plateau pressure > 30 cmH₂O)
• PEEP titration for oxygenation
• Conservative fluid strategy once shock resolved

Glucose control:

• Target glucose 7.8-10 mmol/L (140-180 mg/dL)
• Avoid hypoglycemia

DVT prophylaxis:

• LMWH or UFH (unless contraindicated)
• Mechanical prophylaxis if anticoagulation contraindicated

Stress ulcer prophylaxis:

• PPI or H2 blocker for mechanically ventilated patients

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Complications

Early Complications (0-72 Hours)

Sepsis-Induced Cardiomyopathy (Detailed)

Definition and incidence:[45]

• Reversible myocardial dysfunction in sepsis
• Occurs in 40-50% of septic shock patients
• Usually reversible within 7-10 days

Pathophysiology:

• Direct myocardial depressant effects of cytokines (TNF-α, IL-1β)
• Mitochondrial dysfunction in cardiomyocytes
• Coronary microvascular dysfunction
• Catecholamine desensitization (β-adrenergic receptor downregulation)
• Myocardial edema from capillary leak

Echocardiographic features:

• LV systolic dysfunction (EF below 50%) in 40-50%
• RV dysfunction (TAPSE below 16mm) in 30-40%
• Biventricular dilatation
• Global hypokinesis (NOT regional wall motion abnormalities)
• Diastolic dysfunction

Clinical presentation:

• Hypotension refractory to fluids and vasopressors
• Elevated BNP/NT-proBNP
• Pulmonary edema despite normal CVP
• Low ScvO₂ despite adequate MAP

Diagnosis:

• Echocardiography (TTE or TOE)
• Speckle-tracking strain imaging (more sensitive than EF)
• Elevated cardiac biomarkers (troponin, BNP)

Management:

• Optimize preload: Guided by dynamic indices
• Inotropic support: Dobutamine 2.5-20 µg/kg/min if low CO, elevated filling pressures
• Avoid excessive fluids: Risk of pulmonary edema
• Mechanical support: Rarely needed (IABP, ECMO) for refractory shock

Prognosis:

• Usually fully reversible within 7-10 days
• Paradoxically, presence of septic cardiomyopathy may predict BETTER survival[46]
  • Suggests adaptive response (heart "hibernating" to reduce O₂ demand)
  • Non-survivors often have preserved EF (inability to adapt)

Sepsis-Associated Encephalopathy (SAE)

Incidence and presentation:[47]

• Occurs in 70% of septic patients
• Spectrum: Delirium, confusion, obtundation, coma
• Independent predictor of mortality

Pathophysiology:

• Blood-brain barrier disruption
• Cerebral microcirculatory dysfunction
• Neuroinflammation (microglial activation)
• Neurotransmitter imbalance (acetylcholine, dopamine, serotonin)
• Cerebral edema
• Metabolic derangements (hypoglycemia, uremia, hepatic encephalopathy)

Clinical features:

• Altered consciousness (GCS variable)
• Delirium (hyperactive, hypoactive, mixed)
• Seizures (5-10%)
• Focal neurological signs (rare, suggest stroke/abscess)

Diagnosis:

• Exclusion of other causes (stroke, meningitis, drug effects)
• EEG: Diffuse slowing, triphasic waves (severity correlates with mortality)
• CT/MRI brain: Usually normal (rules out structural lesion)
• CSF: Normal (if LP performed)

Management:

• Treat underlying sepsis
• Optimize cerebral perfusion (maintain MAP ≥65 mmHg)
• Avoid sedation where possible
• Delirium management: Non-pharmacological first, haloperidol PRN

Prognosis:

• Usually resolves with sepsis treatment
• Persistent cognitive impairment in 30-50% of survivors at 1 year[48]

Critical Illness Polyneuropathy/Myopathy (CIP/CIM)

Incidence:[49]

• CIP: 50-70% of septic shock patients
• CIM: 25-50%
• Often coexist (critical illness polyneuromyopathy)

Pathophysiology:

• Microcirculatory failure to peripheral nerves/muscles
• Direct toxic effects of inflammatory mediators
• Hyperglycemia exacerbates nerve injury
• Corticosteroid + neuromuscular blocker combination increases CIM risk

Clinical features:

• Weakness (flaccid, symmetric, distal > proximal)
• Hyporeflexia or areflexia
• Muscle wasting
• Respiratory muscle weakness (difficult weaning)
• Preserved cranial nerves and consciousness

Diagnosis:

• Electromyography (EMG) and nerve conduction studies (NCS)
  • "CIP: Axonal neuropathy, reduced amplitudes"
  • "CIM: Myopathic pattern, short-duration low-amplitude potentials"
• Muscle biopsy (rarely needed): Myosin loss, necrosis

Management:

• Prevention: Tight glucose control (7.8-10 mmol/L), minimize steroids/NMB
• Early mobilization and physiotherapy
• Nutritional support
• No specific pharmacotherapy

Prognosis:

• Recovery slow (weeks to months)
• 50% recover completely, 30% partial recovery, 20% severe disability
• Prolongs ICU/hospital stay and ventilator days

Post-Sepsis Syndrome (Long-Term Outcomes)

Definition:[48,50]

• Constellation of physical, cognitive, and psychological sequelae after sepsis

Incidence:

• 50-70% of sepsis survivors experience at least one component

Cognitive impairment:[48]

• Executive dysfunction, memory deficits, attention problems
• Occurs in 30-50% at 1 year
• MRI shows brain atrophy, white matter changes
• Risk factors: Duration of delirium, severity of illness, hypotension

Physical impairment:

• Muscle weakness, fatigue, reduced exercise tolerance
• Activities of daily living (ADL) impairment in 40%
• Increased risk of falls, fractures, nursing home placement

Psychological sequelae:

• PTSD: 20-30% of survivors
• Depression: 30-40%
• Anxiety: 30-40%
• Intrusive memories, nightmares, avoidance behaviors

Functional disability:

• 25-50% unable to return to work within 1 year
• Reduced health-related quality of life
• Increased healthcare utilization post-discharge

Management:

• Post-ICU follow-up clinics
• Cognitive rehabilitation
• Physical therapy and exercise programs
• Psychological support and counseling
• Early identification and intervention

Late Complications

• Chronic critical illness
• Post-intensive care syndrome (PICS)
• Cognitive impairment
• Persistent organ dysfunction (CKD, chronic respiratory failure)
• Psychological sequelae (PTSD, depression, anxiety)

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Special Populations

Sepsis in Pregnancy

Epidemiology:

• Sepsis complicates 0.1-0.6% of pregnancies
• Leading cause of maternal mortality (10-15% of maternal deaths)
• Mortality: 5-15% (lower than non-pregnant, likely due to younger age)

Unique physiological changes affecting recognition:[51]

Sepsis-3 definitions apply BUT:

• qSOFA less sensitive (physiologic tachycardia, tachypnea)
• Consider lower threshold for lactate (greater than 2.5 mmol/L in pregnancy concerning)
• SOFA score not validated in pregnancy

Common sources in pregnancy:

• Chorioamnionitis (most common)
• Pyelonephritis
• Endometritis (postpartum)
• Septic abortion
• Mastitis
• Wound infection (post-cesarean)

Antibiotic choices in pregnancy:[52]

Empiric regimen for septic shock in pregnancy:

• Piperacillin-tazobactam 4.5g IV q6h + Azithromycin 500mg IV (covers chorioamnionitis including Ureaplasma)
• Add clindamycin 900mg IV q8h if necrotizing endometritis suspected
• Avoid fluoroquinolones and aminoglycosides where possible

Specific management considerations:

• Fluid resuscitation: Same 30 mL/kg target, but lower threshold for invasive monitoring
• Vasopressors: Norepinephrine first-line (same as non-pregnant)
• Source control: Urgent delivery if chorioamnionitis + fetal compromise
• Fetal monitoring: Continuous CTG if viable gestation
• Left lateral tilt: If greater than 20 weeks gestation to avoid aortocaval compression

Obstetric source control:

• Chorioamnionitis: Delivery (induction vs cesarean based on cervical favorability)
• Retained products of conception: Evacuation
• Septic abortion: Evacuation + antibiotics

Immunocompromised Patients

Neutropenic Sepsis

Definition:

• Neutrophil count below 0.5 × 10⁹/L + fever (greater than 38.3°C once, or greater than 38°C for greater than 1 hour)
• Absolute oncologic emergency

Risk stratification (MASCC score):[53]

• Low risk (MASCC ≥21): Consider outpatient oral antibiotics
• High risk (MASCC below 21): Inpatient IV antibiotics mandatory

Empiric antibiotic therapy:[54]

• Monotherapy: Piperacillin-tazobactam 4.5g IV q6h OR Meropenem 1g IV q8h
• Dual therapy (if MASCC below 21): Add aminoglycoside or ciprofloxacin
• Add vancomycin if:
  • Hemodynamic instability
  • Pneumonia
  • Skin/soft tissue infection
  • Known MRSA colonization
  • Mucositis
• Add antifungal (caspofungin, voriconazole) if:
  • Persistent fever greater than 4-7 days on antibiotics
  • Clinical/radiological evidence of invasive fungal infection

Granulocyte colony-stimulating factor (G-CSF):

• Consider if prolonged neutropenia expected
• May shorten duration of neutropenia
• Not routinely recommended

Source control challenges:

• Abscesses may not form (lack of neutrophils)
• Imaging (CT) critical for occult infections
• Typhlitis (neutropenic enterocolitis): Requires bowel rest, broad-spectrum antibiotics, ± surgical consultation

HIV/AIDS Sepsis

Risk factors for sepsis:

• CD4 below 200 cells/µL: High risk
• CD4 below 50 cells/µL: Very high risk (opportunistic infections)

Common organisms by CD4 count:

Empiric antibiotic therapy (CD4 below 200):

• Bacterial coverage: Piperacillin-tazobactam OR Ceftriaxone + Azithromycin
• Add PCP coverage: Trimethoprim-sulfamethoxazole 15-20 mg/kg/day (TMP component) + Prednisolone 40mg BD if PaO₂ below 70 mmHg
• Add Cryptococcus coverage: Liposomal amphotericin B + flucytosine if meningitis suspected

Special considerations:

• Antiretroviral therapy (ART): Continue if already on ART, don't start during acute sepsis (risk of immune reconstitution inflammatory syndrome, IRIS)
• Trimethoprim-sulfamethoxazole allergy: Pentamidine for PCP
• Steroid use: Essential for PCP with hypoxia

Solid Organ Transplant Recipients

Timing of infection post-transplant guides organisms:[55]

Empiric therapy:

• Bacterial: Meropenem 1g IV q8h + Vancomycin 25-30 mg/kg loading
• Add antifungal: Caspofungin 70mg loading, then 50mg daily
• Add antivirals: Ganciclovir 5 mg/kg IV q12h if CMV suspected
• Adjust immunosuppression: Reduce calcineurin inhibitors, maintain low-dose steroids

Listeria coverage:

• Add ampicillin 2g IV q4h if CNS infection (Listeria common in transplant)

Geriatric Sepsis

Epidemiology:

• Age greater than 65: 60% of sepsis cases, 80% of sepsis deaths
• Age greater than 85: Septic shock mortality 60-80%

Challenges in recognition:[56]

• Atypical presentation: Absence of fever in 20-30%, hypothermia common
• Baseline altered cognition: Difficult to detect delirium in dementia patients
• Comorbidities mask signs: Beta-blockers blunt tachycardia
• Frailty: Baseline hypotension, reduced physiologic reserve

Frailty and sepsis outcomes:[57]

• Clinical Frailty Scale (CFS) predicts mortality independent of age/SOFA
• CFS ≥7 (severely frail): 50-70% mortality
• Frailty assessment should inform goals of care discussions

Management modifications:

• Fluid resuscitation: Consider lower volumes (20 mL/kg) in frail elderly, high risk of pulmonary edema
• Vasopressor goals: MAP ≥65 mmHg may be too low if chronic hypertension (target higher, 70-75 mmHg)
• Antibiotic dosing: Renal dose adjustment common (age-related GFR decline)
• Polypharmacy: Review medications, stop nephrotoxins (NSAIDs, ACEi)

Goals of care:

• Early palliative care involvement
• Family meetings within 24-48 hours
• Discuss ceiling of treatment (ICU, intubation, RRT, CPR)
• Shared decision-making considering baseline function and frailty

Pediatric Considerations (Adult ICU Context)

Transition-age patients (16-18 years):

• May present to adult ED/ICU
• Use pediatric sepsis definitions if below 18 years (Phoenix Criteria 2024)[58]
• Weight-based dosing essential
• Consider congenital/genetic conditions (immunodeficiency, cystic fibrosis)

Key differences from adult sepsis:

• Fluid resuscitation: 20 mL/kg boluses (up to 40-60 mL/kg in first hour)
• Antibiotic dosing: Weight-based (see pediatric sepsis guidelines)
• Vasopressors: Norepinephrine first-line, but consider epinephrine if cold shock
• Hypoglycemia risk: Check glucose frequently

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Prognosis

Mortality Predictors

Survival Outcomes

Lactate clearance and outcomes:[11]

• Lactate clearance ≥10%/2 hours: 60-70% survival
• Lactate clearance > 10%/2 hours: 30-40% survival
• Lactate normalization within 24 hours: excellent prognosis

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Prevention

Primary Prevention

• Vaccination (pneumococcal, influenza, meningococcal)
• Infection control practices (hand hygiene, catheter care)
• Appropriate antibiotic stewardship
• Management of chronic diseases (diabetes, immunocompromise)

Secondary Prevention (Sepsis Survivors)

• Vaccination catch-up
• Chronic disease optimization
• Education on early sepsis recognition
• Follow-up for late complications

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Key Guidelines

• Surviving Sepsis Campaign 2021: International Guidelines for Management of Sepsis and Septic Shock[10]
• Sepsis-3 (2016): Third International Consensus Definitions for Sepsis and Septic Shock[1]
• NICE 2024: Sepsis: Recognition, Diagnosis and Early Management[27]
• IDSA 2023: Antimicrobial Therapy Guidelines

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Exam Scenarios

SAQ Practice Question 1: Sepsis-Induced Cardiomyopathy

Scenario: A 52-year-old woman with community-acquired pneumonia and septic shock has been resuscitated with 3 litres of crystalloid and is on norepinephrine 0.4 µg/kg/min and vasopressin 0.03 units/min. Her MAP is 68 mmHg, lactate 3.8 mmol/L (was 6.2 mmol/L on admission 6 hours ago). Bedside echocardiography shows global LV hypokinesis with EF 35%, dilated IVC (2.5 cm, below 50% collapsibility). ScvO₂ is 62%.

(a) What is the most likely cause of her ongoing shock? (2 marks)

Model Answer: Sepsis-induced cardiomyopathy with myocardial dysfunction.[45] The echocardiographic findings (global LV hypokinesis, reduced EF 35%) indicate impaired cardiac output. The low ScvO₂ (below 70%) confirms inadequate oxygen delivery despite adequate MAP, suggesting low cardiac output state. The dilated IVC indicates high filling pressures/fluid overload.

(b) Outline your immediate management. (4 marks)

Model Answer:

1. Inotropic support: Dobutamine 2.5-10 µg/kg/min to improve cardiac output and oxygen delivery[10]
2. Avoid further fluids: Dilated IVC indicates fluid overload; additional fluids will worsen pulmonary edema without improving CO
3. Monitor response: Repeat ScvO₂ and lactate within 2 hours; target ScvO₂ greater than 70%, lactate clearance ≥10%
4. Diuresis: Consider furosemide if pulmonary edema develops (cautiously, as may worsen hypotension)
5. Continue vasopressors: Maintain MAP ≥65 mmHg while improving cardiac output

(c) What is the typical prognosis for sepsis-induced cardiomyopathy? (2 marks)

Model Answer: Sepsis-induced cardiomyopathy is usually reversible within 7-10 days.[45] Paradoxically, presence of septic cardiomyopathy may predict better survival - it represents an adaptive response (myocardial "hibernation" reducing oxygen demand).[46] Recovery of LV function correlates with sepsis resolution and survival.

(d) List three differential diagnoses that should be excluded. (2 marks)

Model Answer:

1. Acute coronary syndrome: Check troponin, ECG (though troponin often elevated in sepsis without ACS)
2. Pulmonary embolism: May cause RV dysfunction, hypotension, elevated lactate
3. Pre-existing cardiomyopathy: Review past echocardiograms if available
4. Massive pericardial effusion/tamponade: Echo should exclude
5. Acute valvular pathology: Endocarditis, papillary muscle rupture (less likely)

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SAQ Practice Question 2: Fluid Strategy in Septic Shock

Scenario: A 65-year-old man with intra-abdominal sepsis secondary to perforated diverticulitis presents with septic shock (BP 78/45 mmHg, lactate 5.2 mmol/L). He weighs 80 kg. The ED consultant has ordered "30 mL/kg crystalloid as per Surviving Sepsis Campaign guidelines."

(a) Calculate the recommended initial fluid bolus and state the preferred fluid type. (2 marks)

Model Answer:

• Volume: 30 mL/kg × 80 kg = 2,400 mL (2.4 litres)
• Fluid type: Balanced crystalloid (Ringer's lactate or Plasma-Lyte) preferred over 0.9% saline[10,14]
• Balanced crystalloids associated with lower mortality and less acute kidney injury vs saline (BaSICS trial 2021)[14]

(b) Describe the recent evidence that challenges mandatory 30 mL/kg fluid boluses in all septic shock patients. (3 marks)

Model Answer:

• CLOVERS trial (2023):[16] Restrictive vs liberal fluid strategy in sepsis-induced hypotension - no difference in 90-day mortality
• CLASSIC trial (2022):[17] Restrictive strategy non-inferior to liberal strategy in ICU patients with septic shock
• Conclusion: The Surviving Sepsis Campaign 2021 downgraded the 30 mL/kg recommendation from STRONG to WEAK - suggests individualizing fluid therapy based on patient response, comorbidities (heart failure, ESRD), and fluid tolerance rather than mandatory fixed volumes[10]

(c) How would you assess fluid responsiveness in this patient? (3 marks)

Model Answer: Dynamic assessments (preferred):[15]

1. Passive leg raise (PLR) with stroke volume monitoring: Raise legs 45° for 60 seconds, measure change in stroke volume (via echo or pulse contour analysis); greater than 10-15% increase suggests fluid responsive
2. Pulse pressure variation (PPV): If mechanically ventilated; greater than 13% suggests fluid responsive
3. Stroke volume variation (SVV): If mechanically ventilated; greater than 10-12% suggests fluid responsive

Static measures (less reliable):

• CVP, PAOP unreliable predictors of fluid responsiveness
• Clinical assessment: JVP, lung auscultation, peripheral edema

Why dynamic > static: Static measures reflect preload at one moment but don't predict if additional fluid will increase cardiac output. Dynamic measures assess position on Frank-Starling curve.

(d) List four clinical scenarios where you would give LESS than 30 mL/kg initial fluid. (2 marks)

Model Answer:

1. Pulmonary edema/acute heart failure: Risk of respiratory decompensation
2. End-stage renal disease (ESRD): Inability to excrete fluid, risk of volume overload
3. Elderly/frail patients: Higher risk of fluid intolerance, pulmonary edema
4. Evidence of fluid overload: Elevated JVP, pulmonary crackles, peripheral edema on presentation
5. Rapid improvement after initial bolus: If BP improves after 1 litre, may not need full 30 mL/kg

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SAQ Practice Question 3: Antibiotic Selection in Septic Shock

Scenario: A 45-year-old woman with known IV drug use presents with fever (39.8°C), rigors, and hypotension (BP 82/50 mmHg). Examination reveals a new pansystolic murmur loudest at the left sternal edge. Lactate is 4.1 mmol/L. You suspect infective endocarditis.

(a) What are the two most important immediate investigations before starting antibiotics? (2 marks)

Model Answer:

1. Blood cultures (×3 sets from separate sites): Essential for organism identification and antibiotic sensitivities; critical in endocarditis for prolonged targeted therapy[10]
2. Echocardiography (transthoracic then transesophageal): TTE first-line to identify vegetations, valve destruction, abscess; TOE more sensitive (90% vs 60% for TTE) and should follow if TTE negative but clinical suspicion high

(b) Outline your empiric antibiotic regimen. Justify your choice. (4 marks)

Model Answer: Empiric regimen for suspected native valve endocarditis with septic shock in IVDU:

1. Vancomycin 25-30 mg/kg IV loading dose (covers MRSA - very common in IVDU)
2. Gentamicin 1 mg/kg IV q8h (synergy for Gram-positives, covers some Gram-negatives)
3. Consider adding meropenem 1g IV q8h if concern for Gram-negative or Pseudomonas (particularly if prosthetic valve)

Justification:

• IVDU: High risk of S. aureus (including MRSA) - most common organism in IVDU endocarditis (60-70%)
• Vancomycin provides MRSA coverage
• Gentamicin provides synergy against streptococci and staphylococci, reduces bacteremia duration
• Right-sided endocarditis (tricuspid) common in IVDU - often S. aureus
• Also covers streptococci (S. viridans, S. bovis), enterococci

(c) Once blood cultures grow Methicillin-Sensitive S. aureus (MSSA), how would you modify your antibiotics? (2 marks)

Model Answer:

• Switch vancomycin to flucloxacillin 2g IV q6h (or nafcillin/oxacillin)
• Beta-lactams (flucloxacillin) superior to vancomycin for MSSA endocarditis - faster bactericidal activity, better tissue penetration, lower mortality
• Continue gentamicin for first 3-5 days for synergy (then stop to avoid nephro-/ototoxicity)
• Total duration: 4-6 weeks IV antibiotics for native valve endocarditis

(d) State two absolute contraindications to this patient being treated solely with medical therapy. (2 marks)

Model Answer: Indications for urgent cardiac surgery (within 24-48h):

1. Heart failure secondary to severe valvular regurgitation (acute pulmonary edema, cardiogenic shock)
2. Perivalvular abscess or fistula formation (complicated endocarditis)
3. Persistent bacteremia despite 48-72h appropriate antibiotics (suggests uncontrolled infection)
4. Large vegetations (greater than 10mm) with recurrent emboli despite antibiotics
5. Fungal endocarditis (almost always requires surgery)

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SAQ Practice Question 4: Vasopressor Choice in Septic Shock

Scenario: You are managing a 68-year-old man with hospital-acquired pneumonia and septic shock. After 2.5 litres of balanced crystalloid, his MAP is 58 mmHg and lactate is 4.8 mmol/L. You plan to start vasopressors.

(a) Which vasopressor is first-line in septic shock? State the mechanism of action and starting dose. (3 marks)

Model Answer:

• Norepinephrine is first-line vasopressor[10,18]
• Mechanism: α1-adrenergic agonist (peripheral vasoconstriction) + mild β1-adrenergic agonist (positive inotropy and chronotropy)
• Starting dose: 0.05-0.1 µg/kg/min IV, titrated to MAP ≥65 mmHg
• Maximum dose: Up to 1-2 µg/kg/min (higher doses suggest refractory shock)

(b) At what norepinephrine dose would you add a second vasopressor? Which agent would you add and why? (3 marks)

Model Answer:

• Threshold: Add second vasopressor when norepinephrine reaches 0.25-0.5 µg/kg/min[10,19]
• Agent: Vasopressin 0.03 units/min IV (fixed dose, do NOT titrate)
• Rationale:
  • Vasopressin is depleted in septic shock (relative vasopressin deficiency)
  • Acts via V1 receptors causing vasoconstriction (non-adrenergic mechanism)
  • Allows reduction in norepinephrine dose (norepinephrine-sparing effect)
  • "VANISH trial: May reduce mortality in less severe shock, reduces renal replacement therapy[19]"
  • Combination therapy targets different vasoconstrictor pathways

(c) Despite norepinephrine 0.6 µg/kg/min and vasopressin 0.03 units/min, his MAP remains 60 mmHg. What is your next step? (2 marks)

Model Answer: Add third vasopressor:

• Epinephrine 0.01-0.05 µg/kg/min (α and β agonist - vasoconstriction + inotropy)[10]
• Alternative: Consider other adjuncts (hydrocortisone, methylene blue, angiotensin II - if available)

Reassess for reversible causes:

• Volume status (echocardiography, fluid responsiveness assessment)
• Cardiac function (septic cardiomyopathy - may need inotropes)
• Source control (is infection source adequately treated?)
• Adrenal insufficiency (consider hydrocortisone)

(d) Why is dopamine NOT recommended as a first-line vasopressor in septic shock? (2 marks)

Model Answer:

• Higher arrhythmia risk compared to norepinephrine (SOAP II trial)[20]
• No mortality benefit vs norepinephrine
• Dopamine may increase myocardial oxygen demand
• Less predictable dose-response (low dose = β, medium dose = β + α, high dose = α)
• Surviving Sepsis Campaign 2021: Norepinephrine preferred over dopamine[10]
• Exception: May consider in highly selected patients with bradycardia + hypotension

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OSCE Station 1: Hour-1 Bundle in Septic Shock

Scenario: You are the ED registrar. A 58-year-old woman presents with fever, confusion, and hypotension. Observations: BP 85/50 mmHg, HR 122, RR 26, SpO₂ 94% on air, temp 39.1°C, GCS 13/15. You suspect septic shock.

Task: Outline to the examiner the Hour-1 Bundle for sepsis management. Demonstrate how you would initiate this in the first 60 minutes.

Marking Criteria (10 marks):

Model Performance:

"This patient meets criteria for septic shock under Sepsis-3 definitions: suspected infection (fever, confusion), hypotension requiring likely vasopressor support, and I would expect lactate greater than 2 mmol/L.

I would immediately initiate the Hour-1 Bundle:

1. Measure lactate - Arterial or venous gas within 15 minutes. If lactate greater than 2 mmol/L, I will remeasure in 2-4 hours to assess clearance.

2. Blood cultures - Two sets (aerobic + anaerobic) from separate sites before antibiotics. However, I will NOT delay antibiotics beyond 45 minutes waiting for cultures.

3. Broad-spectrum antibiotics within 1 hour - For septic shock, I aim for below 30 minutes. Given unknown source, I would give:

   • Piperacillin-tazobactam 4.5g IV STAT
   • Gentamicin 5mg/kg IV (assuming normal renal function)

4. Fluid resuscitation - Balanced crystalloid (Ringer's lactate) 30 mL/kg. For a 70 kg patient, that's approximately 2 litres. I would give this as sequential 500 mL boluses over 15-30 minutes, reassessing after each bolus for signs of fluid overload or ongoing shock.

5. Vasopressors - If she remains hypotensive (MAP below 65 mmHg) during or after initial fluid resuscitation, I will start norepinephrine 0.05-0.1 µg/kg/min via a large peripheral cannula (antecubital fossa) while arranging central venous access.

6. Source identification:

   • Portable chest X-ray (pneumonia?)
   • Urine dipstick and culture (UTI?)
   • Abdominal examination and consider CT abdomen/pelvis if intra-abdominal source
   • Blood tests: FBC, U&E, LFT, coagulation, CRP, procalcitonin

7. Early ICU referral - This patient will need ICU-level care given septic shock. I would inform the ICU consultant early and arrange transfer once initial resuscitation complete.

All of this must happen within the first hour of sepsis recognition to improve survival."

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OSCE Station 2: Antibiotic De-escalation

Scenario: You are the ward registrar. A 62-year-old man was admitted 5 days ago with E. coli bacteremia from a urinary source (complicated UTI with perinephric abscess, drained). He was started on meropenem 1g IV q8h. Blood cultures from Day 1 grew E. coli sensitive to meropenem, ceftriaxone, gentamicin, and co-amoxiclav; resistant to amoxicillin and trimethoprim. He is now clinically improving, afebrile for 48 hours, eating and drinking, CRP falling from 310 to 85. The microbiology consultant has asked you to "de-escalate antibiotics."

Task: Explain to the examiner your de-escalation plan and the principles of antimicrobial stewardship.

Marking Criteria (10 marks):

Model Performance:

"This patient is clinically improving from E. coli bacteremia and now is an ideal candidate for antibiotic de-escalation, which is a key principle of antimicrobial stewardship.

De-escalation plan:

1. Stop meropenem - This is unnecessarily broad-spectrum. Meropenem is a carbapenem reserved for ESBL-producing organisms, carbapenem-resistant Enterobacteriaceae, or severe Pseudomonas infections. This E. coli is ceftriaxone-sensitive, so meropenem is overkill.

2. Switch to ceftriaxone 2g IV once daily - This provides adequate coverage for ceftriaxone-sensitive E. coli bacteremia, is narrow-spectrum, and has once-daily dosing convenience.

3. Plan oral step-down - Once he's been afebrile for 48 hours and tolerating oral intake well, I would switch to oral ciprofloxacin 500mg BD (if sensitive) or co-amoxiclav 625mg TDS. This allows earlier discharge.

4. Total duration - For E. coli bacteremia from urinary source with complicated UTI (perinephric abscess), I would recommend 14 days total antibiotics, given the abscess was drained. If the abscess was NOT drained, he may need 3-4 weeks.

Antimicrobial stewardship principles:

• Start broad, narrow quickly: Initial empiric therapy should be broad, but once sensitivities are known, de-escalate to narrowest effective spectrum.

• Reduce antimicrobial resistance: Meropenem selects for carbapenem-resistant organisms. Unnecessary use drives resistance.

• Reduce C. difficile risk: Broad-spectrum antibiotics (especially meropenem, piperacillin-tazobactam, fluoroquinolones, clindamycin) increase C. difficile infection risk 2-3×.

• Reduce drug toxicity: All antibiotics have side effects. Shorter durations and narrower spectrums reduce adverse events.

• Improve outcomes: Antibiotic stewardship has been shown to reduce mortality, length of stay, and costs.

In summary, I would switch from meropenem to ceftriaxone IV now, then to oral ciprofloxacin in 2-3 days, for a total of 14 days given the complicated UTI with abscess."

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OSCE Station 3: Breaking Bad News - Septic Shock Prognosis

Scenario: You are the ICU registrar. A 78-year-old woman with metastatic pancreatic cancer was admitted 48 hours ago with neutropenic sepsis and septic shock. Despite maximal therapy (norepinephrine 1.2 µg/kg/min, vasopressin, epinephrine, broad-spectrum antibiotics including antifungals), her lactate is rising (now 9.2 mmol/L), she is anuric, and her SOFA score is 18. The consultant has asked you to speak to her daughter about prognosis and goals of care.

Task: Conduct a goals-of-care discussion with the daughter (actor). Explain the current situation, prognosis, and discuss treatment escalation vs palliation.

Marking Criteria (10 marks):

Model Performance:

[Candidate introduces self, checks identity, offers private room]

"Thank you for meeting with me. I'm Dr. [Name], one of the intensive care registrars looking after your mother. Before we start, can I ask what the team has told you so far about your mother's condition?"

[Establishes baseline understanding]

"I'm afraid I have some very serious news. Your mother came in with a severe infection - we call it septic shock - which means her blood pressure is very low and her organs are failing despite all the support we're giving her.

Over the past 48 hours, we've been giving her maximum treatment: strong antibiotics, three different medications to support her blood pressure, breathing support on the ventilator, and kidney dialysis. However, despite all of this, her condition is deteriorating.

Her lactate - a blood test that shows how well her organs are functioning - has been rising, which is a very worrying sign. Her kidneys have stopped working, her liver is failing, and her heart is struggling.

[Pause - allow information to sink in]

I need to be honest with you. Based on her current condition - the severity of her septic shock, her underlying cancer, and the fact she's not responding to maximum treatment - her chance of survival is very low. We estimate less than 10-20% of patients in this situation survive, and those who do often have severe brain injury or need long-term dialysis.

[Pause - assess understanding]

Did your mother ever talk to you about what she would want if she became very unwell like this? Did she have any advance directives or wishes about intensive care treatment?"

[Daughter responds - explore patient values, what made life meaningful to her]

"Given how unwell she is, we need to think carefully about what further treatment is in her best interests. We have two broad options:

Option 1: Continue current treatment - keep her on the ventilator, continue the blood pressure medications, continue dialysis. However, I need to be clear: even with all of this, she is very unlikely to survive. And if we did more aggressive treatments like CPR if her heart stops, this would cause significant suffering with almost no chance of benefit.

Option 2: Shift the focus of care from aggressive life-prolonging treatment to ensuring she is comfortable and pain-free. We would continue antibiotics and keep her comfortable, but we wouldn't start new aggressive treatments or perform CPR if her heart stops. This is called palliative care, and our focus would be on dignity and comfort in her remaining time.

What are your thoughts? What do you think your mother would have wanted?"

[Allow family to process, ask questions]

"Whatever you decide, we will support you. We can involve our palliative care team to help ensure she's comfortable. Would you like to speak to other family members before making a decision? We can arrange a family meeting with the consultant later today.

I'm so sorry this is happening. Do you have any questions for me right now?"

[Offer support, arrange follow-up, involve chaplain/social work as appropriate]

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Scenario: A 68-year-old man presents with fever, confusion, and hypotension (BP 85/50 mmHg). His lactate is 4.2 mmol/L. After 2 litres of crystalloid, his BP is 80/45 mmHg and lactate is 4.5 mmol/L. Which is the most appropriate next step?

A) Administer another 2 litres of crystalloid
B) Start norepinephrine infusion
C) Administer hydrocortisone 200 mg IV
D) Perform passive leg raise to assess fluid responsiveness
E) Start dobutamine infusion

Answer

Answer: B) Start norepinephrine infusion

This patient meets criteria for septic shock (vasopressor requirement + lactate greater than 2 mmol/L despite fluid resuscitation). After adequate initial fluid resuscitation (2L = approximately 25-30 mL/kg for a 70 kg patient), persistent hypotension requires vasopressor initiation.[10]

Norepinephrine is first-line for septic shock. The target is MAP ≥65 mmHg. Further fluids may cause harm without benefit in a fluid non-responder. Hydrocortisone is considered for refractory shock (after vasopressors started). Dobutamine is for myocardial dysfunction, not initial shock management.

SBA Question 2

Scenario: A 55-year-old woman with community-acquired pneumonia develops septic shock. Blood cultures are pending. Which is the most appropriate empiric antibiotic regimen?

A) Amoxicillin 1g IV q8h
B) Ceftriaxone 2g IV q24h + Azithromycin 500mg IV q24h
C) Vancomycin 1g IV q12h alone
D) Metronidazole 500mg IV q8h
E) Fluconazole 400mg IV q24h

Answer

Answer: B) Ceftriaxone 2g IV q24h + Azithromycin 500mg IV q24h

For community-acquired pneumonia with septic shock, empiric therapy should cover typical (S. pneumoniae) and atypical (Legionella, Mycoplasma) pathogens. The combination of a beta-lactam (ceftriaxone) plus a macrolide (azithromycin) or fluoroquinolone provides appropriate coverage.[22]

Amoxicillin alone is inadequate for severe CAP. Vancomycin alone doesn't cover gram-negatives or atypicals. Metronidazole covers anaerobes (not primary CAP pathogens). Fluconazole is antifungal.

SBA Question 3

Scenario: Which of the following is part of the Sepsis-3 definition of septic shock?

A) Systolic blood pressure > 90 mmHg
B) Lactate greater than 2 mmol/L despite adequate fluid resuscitation
C) Heart rate greater than 100 bpm
D) White cell count greater than 12,000/µL
E) Temperature greater than 38.5°C

Answer

Answer: B) Lactate greater than 2 mmol/L despite adequate fluid resuscitation

The Sepsis-3 definition of septic shock requires BOTH:[1]

• Vasopressor requirement to maintain MAP ≥65 mmHg (not just SBP > 90 mmHg), AND
• Serum lactate greater than 2 mmol/L despite adequate fluid resuscitation

SBP > 90 mmHg was part of older (Sepsis-2) definitions. Heart rate, WCC, and temperature are not part of the septic shock definition (though may be present).

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Viva Scenario

Examiner: "A 72-year-old diabetic man is brought to the emergency department with fever, rigors, and confusion. His observations show BP 75/40 mmHg, HR 125, RR 28, SpO₂ 92% on air, temperature 39.2°C. His lactate is 5.8 mmol/L. Walk me through your management."

Candidate approach:

Recognition and resuscitation: "This patient has septic shock based on:

• Clinical signs of infection (fever, rigors)
• Hypotension (MAP approximately 52 mmHg) requiring likely vasopressor support
• Elevated lactate (5.8 mmol/L)
• Organ dysfunction (confusion, hypoxia)

I would initiate the Hour-1 bundle immediately:

• Measure lactate - already done (5.8 mmol/L), will repeat in 2 hours

• Blood cultures - I would take 2 sets from separate sites before antibiotics

Broad-spectrum antibiotics - Given unknown source in an elderly diabetic, I would give:

• Piperacillin-tazobactam 4.5g IV STAT
• Plus gentamicin 5mg/kg IV for synergy
• Add vancomycin if MRSA risk factors present

Fluid resuscitation - I would start with 500 mL crystalloid (balanced solution like Ringer's lactate) over 15 minutes, then reassess

Vasopressors - Given profound hypotension, I would start norepinephrine early rather than waiting for 30 mL/kg fluids, targeting MAP ≥65 mmHg"

Examiner: "After 1.5 litres of crystalloid, his BP is 82/50 (MAP 61) and lactate is now 5.2 mmol/L. Norepinephrine is running at 0.3 µg/kg/min. What next?"

Candidate: "The patient has refractory shock requiring high-dose norepinephrine. I would:

• Add vasopressin 0.03 units/min as second-line vasopressor to allow norepinephrine reduction

• Source control - I need to identify and control the infection source:

  • Chest X-ray (may have pneumonia)
  • Urine dipstick and culture (UTI common in diabetics)
  • CT abdomen/pelvis if intra-abdominal source suspected

• Consider hydrocortisone 50 mg IV q6h given refractory shock on high-dose vasopressors

• Central venous access for reliable vasopressor delivery and CVP/ScvO₂ monitoring

• Arterial line for continuous BP monitoring

• Reassess fluid status - Passive leg raise to assess if more fluid would help, but avoid fluid overload

• Consider echocardiography to assess cardiac function - may need inotropes if septic cardiomyopathy present"

Examiner: "His chest X-ray shows right lower lobe consolidation. What changes to your antibiotic regimen?"

Candidate: "With confirmed pneumonia as the source, I would:

• Continue piperacillin-tazobactam which covers typical pneumonia pathogens including Pseudomonas

• Add azithromycin 500 mg IV to cover atypical pathogens (Legionella, Mycoplasma) which are important in severe CAP

• Consider adding vancomycin if:

  • Necrotizing pneumonia suspected
  • Recent influenza (risk of S. aureus superinfection)
  • MRSA colonization known

• Review antibiotic choice when culture results available - de-escalate if possible

I would also consider urinary Legionella and pneumococcal antigens to help identify the pathogen early."

Viva Scenario 2: Antibiotic Stewardship in Septic Shock

Examiner: "A 58-year-old woman was admitted 4 days ago with E. coli urosepsis and septic shock. Blood cultures grew E. coli sensitive to ceftriaxone, gentamicin, and co-amoxiclav, resistant to amoxicillin. She was started on piperacillin-tazobactam and gentamicin. She's now improving - off vasopressors for 48 hours, lactate normalized, CRP falling from 280 to 120. What would you do with her antibiotics?"

Candidate approach:

"This patient is improving with appropriate source control and antibiotic therapy. Now is the time for de-escalation and antibiotic stewardship.[10,22]

De-escalation principles:

• Switch from broad-spectrum to narrow-spectrum based on culture sensitivities
• Change from IV to oral when clinical improvement + able to tolerate oral
• Shorten duration to minimum effective (avoid unnecessarily prolonged courses)

For this patient:

1. Stop gentamicin: She's clinically improved, no longer septic shock, and gentamicin has completed its role (synergy in first 48-72h). Prolonged aminoglycosides risk nephrotoxicity and ototoxicity.

2. De-escalate to ceftriaxone: E. coli is ceftriaxone-sensitive, so I would switch from piperacillin-tazobactam (covers Pseudomonas, anaerobes unnecessarily) to ceftriaxone 2g IV daily.

3. Plan oral switch: Once she's afebrile for 24-48h, tolerating oral, I would consider oral step-down to ciprofloxacin 500mg BD or co-amoxiclav 625mg TDS, depending on sensitivities.

4. Total duration: For uncomplicated E. coli bacteremia from urinary source, 7-14 days total is appropriate. If she has a structural abnormality (abscess, obstruction), may need longer.

Antimicrobial stewardship benefits:

• Reduces antimicrobial resistance
• Reduces C. difficile risk
• Reduces drug toxicity (nephrotoxicity, hepatotoxicity)
• Reduces costs
• Improves patient outcomes"

Examiner: "Why not just continue piperacillin-tazobactam for the full course since it's working?"

Candidate: "While piperacillin-tazobactam is effective, continuing unnecessarily broad-spectrum antibiotics has several harms:

1. Selection pressure for resistance: Piperacillin-tazobactam selects for ESBL-producing organisms, carbapenem-resistant Enterobacteriaceae, and multi-drug resistant Pseudomonas.

2. C. difficile risk: Broad-spectrum beta-lactams increase C. difficile infection risk 2-3×, particularly piperacillin-tazobactam.

3. Microbiome disruption: Prolonged broad-spectrum therapy causes dysbiosis, which impairs gut immunity and increases secondary infection risk.

4. Unnecessary anti-Pseudomonal coverage: This patient's E. coli is ceftriaxone-sensitive. Piperacillin-tazobactam's anti-Pseudomonal and anaerobic coverage is unnecessary, exposing her to broader resistance risk without benefit.

The principle is: Start broad, narrow quickly based on cultures. De-escalation is a core tenet of antimicrobial stewardship and Surviving Sepsis Campaign guidelines.[10]"

Viva Scenario 3: Refractory Septic Shock

Examiner: "A 45-year-old man with alcoholic cirrhosis presents with spontaneous bacterial peritonitis and septic shock. Despite 4 litres of crystalloid, norepinephrine 0.8 µg/kg/min, vasopressin 0.03 units/min, and appropriate antibiotics, his MAP is 58 mmHg and lactate is 7.2 mmol/L. What are your next steps?"

Candidate approach:

"This is refractory septic shock - hypotension and hyperlactatemia despite high-dose vasopressors. I need to systematically address potential causes and escalate therapy.[10]

Immediate actions:

• Echocardiography (TTE) to assess:
  • Cardiac function (septic cardiomyopathy? cirrhotic cardiomyopathy?)
  • Volume status (IVC collapsibility, LV end-diastolic volume)
  • RV function (RV strain from massive PE?)
• Passive leg raise with stroke volume monitoring
• If fluid-responsive, give additional boluses cautiously (risk of ascites worsening)

2. Add third vasopressor - Epinephrine:

   • Start epinephrine 0.01-0.05 µg/kg/min
   • Provides additional vasoconstriction (α1) and inotropy (β1)
   • Aware it will increase lactate (β2 effect)

3. Corticosteroids:

   • Hydrocortisone 50mg IV q6h (or 200mg continuous infusion)
   • Indicated in refractory shock on high-dose vasopressors[23,24,25]
   • May improve shock reversal (ADRENAL, APROCCHSS trials)

4. Source control reassessment:

   • Has ascitic tap been done? (SBP diagnosis confirmed?)
   • Repeat paracentesis if large-volume ascites (risk of abdominal compartment syndrome)
   • CT abdomen to exclude secondary infection source (abscess, bowel perforation)

5. Cardiac output monitoring:

   • If echo shows low cardiac output + high filling pressures → Consider dobutamine
   • Dose: 2.5-10 µg/kg/min, titrate to ScvO₂ greater than 70% or lactate clearance

6. Correct metabolic derangements:

   • Correct hypocalcemia (common in cirrhosis, worsens shock) - target iCa²⁺ greater than 1.0 mmol/L
   • Thiamine 200mg IV (alcoholic, may have deficiency causing lactic acidosis)
   • Measure cortisol (relative adrenal insufficiency in cirrhosis)

7. Consider mechanical circulatory support:

   • If refractory despite above, discuss ECMO candidacy (unlikely in decompensated cirrhosis)

8. Goals of care discussion:

   • Cirrhosis + refractory septic shock: Very high mortality (70-90%)
   • Early palliative care involvement
   • Discuss ICU ceiling of treatment with patient/family"

Examiner: "His echo shows hyperdynamic LV (EF 70%), dilated IVC, no RV strain. What does this tell you?"

Candidate: "This is consistent with hyperdynamic circulatory failure - the vasoplegic phenotype of septic shock:[43]

• High cardiac output (hyperdynamic LV)
• Profound vasodilation (requiring massive vasopressor doses)
• Cirrhosis exacerbates this (baseline splanchnic vasodilation, portosystemic shunting)

Management changes:

• He does NOT need inotropes (cardiac function preserved)

• Focus on vasopressor escalation

• Consider adding methylene blue 1.5-2 mg/kg IV bolus (rescue vasopressor for refractory vasoplegia)[59]

  • Inhibits guanylate cyclase, reducing NO-mediated vasodilation
  • Can cause transient increase in pulmonary artery pressure (caution if RV dysfunction)
  • Anecdotal reports of success in refractory shock

• Consider angiotensin II (if available) as rescue vasopressor[60]

  • Approved for distributive shock refractory to catecholamines + vasopressin
  • Restores vascular tone via AT1 receptor
  • "Dose: 20 ng/kg/min, titrate to MAP"

• Terlipressin (vasopressin analogue): Sometimes used off-label in cirrhotic shock, but limited evidence in septic shock

The dilated IVC suggests he may be fluid-overloaded. I would avoid further fluids and focus on vasopressors."

Viva Scenario 4: Lactate Clearance vs ScvO₂

Examiner: "Explain the evidence for lactate-guided versus ScvO₂-guided resuscitation in septic shock."

Candidate:

"This is an important area where evidence has evolved significantly.

Historical context - Rivers EGDT (2001):[13]

• Early goal-directed therapy targeted CVP 8-12, MAP ≥65, UO ≥0.5, ScvO₂ ≥70%
• Single-center RCT showed 16% absolute mortality reduction (46.5% → 30.5%)
• ScvO₂ below 70% triggered interventions: fluids, RBC transfusion (target Hb greater than 10), dobutamine
• Became standard of care for a decade

PROCESS, ARISE, ProMISe trials (2014-2015):[37,38,39]

• Three large multicenter RCTs comparing EGDT vs usual care
• No mortality difference in any trial
• EGDT group received more fluids, more blood transfusions, more dobutamine - no benefit
• Suggested improvements in usual care (earlier antibiotics, earlier fluids) made EGDT targets redundant

Lactate-guided resuscitation:[11,36]

• Lactate greater than 2 mmol/L marker of tissue hypoperfusion
• Target: ≥10% reduction every 2 hours OR normalization (below 2 mmol/L)
• Jansen 2010 trial: Lactate-guided therapy reduced mortality vs no lactate monitoring
• Simpler than ScvO₂ (requires only peripheral/arterial blood, not central line)

ANDROMEDA-SHOCK trial (2019):[40]

• Lactate normalization vs capillary refill time (CRT) below 3 seconds
• CRT-guided resuscitation non-inferior to lactate
• Suggests multiple resuscitation endpoints acceptable

Current evidence summary:

• ScvO₂ monitoring: No longer mandatory, EGDT protocol abandoned
• Lactate monitoring: Recommended by Surviving Sepsis Campaign 2021[10]
  • Measure lactate initially
  • If greater than 2 mmol/L, remeasure within 2-4 hours
  • Target lactate clearance or normalization
• Clinical endpoints: Ultimately most important (BP, urine output, mentation, perfusion)

Why did ScvO₂ fail?

• Not specific for tissue hypoxia (elevated in mitochondrial dysfunction, septic shunting)
• Invasive (requires central line)
• Interventions to raise ScvO₂ (transfusions, dobutamine) may cause harm
• Usual care improved, so additional ScvO₂ monitoring redundant

Current practice:

• Use lactate as resuscitation guide
• Combine with clinical assessment (MAP, urine output, skin perfusion, mentation)
• ScvO₂ can be adjunct in refractory shock with central line in situ, but not mandatory"

---

Patient Explanation (Layperson Level)

"You have a very serious condition called septic shock. This happens when an infection spreads through your body and causes your organs to start failing. Your blood pressure has dropped very low, and your body is struggling to deliver oxygen to your vital organs.

We are treating this aggressively with:

• Antibiotics through your vein - These are powerful medications to kill the bacteria causing the infection. We give them directly into your bloodstream so they work faster.

• Fluids - We're giving you fluids to help raise your blood pressure and improve blood flow to your organs.

• Medications to raise your blood pressure - Called vasopressors, these help squeeze your blood vessels to maintain blood pressure when fluids alone aren't enough.

• Finding the source - We're doing tests and scans to find where the infection started so we can treat it directly. Sometimes this requires procedures to drain infected fluid.

This is a life-threatening condition that requires treatment in the intensive care unit (ICU). We will monitor you very closely, with machines tracking your heart, blood pressure, oxygen levels, and other vital signs continuously.

The next 24-48 hours are critical. We expect your blood pressure to stabilize as the treatment takes effect. We'll regularly check blood tests to see if the infection is coming under control and if your organs are recovering.

With prompt treatment, many people recover from septic shock, but it is a serious illness and some patients do not survive. We are doing everything possible to give you the best chance of recovery."

---

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples (Australia)

Epidemiology of sepsis in Indigenous Australians:[61,62]

• 2-3× higher sepsis hospitalization rates vs non-Indigenous Australians
• 1.5-2× higher sepsis mortality
• Younger age at presentation (median 10-15 years younger)
• Higher rates of Gram-positive sepsis (S. aureus, GAS)

Risk factors for increased sepsis burden:

• Chronic diseases: Diabetes (3× higher), CKD (4× higher), rheumatic heart disease (10-20× higher), bronchiectasis
• Crowded housing: Facilitates transmission of Strep A, S. aureus, meningococcus
• Remote location: Delayed presentation, limited access to healthcare
• Social determinants: Lower socioeconomic status, food insecurity, inadequate housing

Common infection sources in Indigenous populations:

• Skin and soft tissue infections: S. aureus (including CA-MRSA), GAS (including invasive GAS)
• Pneumonia: S. pneumoniae, H. influenzae, S. aureus
• Rheumatic heart disease endocarditis: Streptococcus viridans, S. aureus
• Melioidosis: Burkholderia pseudomallei (endemic in Northern Australia)
• Post-streptococcal glomerulonephritis: Can present with AKI in sepsis

Antibiotic modifications for Indigenous populations:

• CA-MRSA coverage: Lower threshold to add vancomycin or linezolid for skin/soft tissue sepsis
• Melioidosis coverage (Top End, Kimberley, Cape York): Meropenem or ceftazidime (if soil exposure, diabetes, wet season)
• Penicillin-resistant pneumococcus: Use higher-dose ceftriaxone (2g q12h vs q24h)

Cultural safety in critical illness:[63]

• Family involvement: Extended family central to decision-making, not just immediate family
• Communication: Use interpreters if language barriers (Aboriginal English, Kriol, traditional languages)
• Spiritual/cultural practices: Accommodate smoking ceremonies, traditional healers, cultural rituals
• End-of-life care: Return to Country extremely important, discuss early if prognosis poor
• Mistrust of healthcare system: Acknowledge historical trauma, build trust through respectful communication

Remote and rural challenges:

• Delayed presentation: Patients may travel 200-500+ km to hospital
• Limited diagnostics: Many remote clinics lack CT, blood culture capability
• Retrieval considerations: RFDS coordination, stabilization before transfer
• Workforce shortages: High staff turnover, reliance on locums/agency staff
• Follow-up challenges: Arrange telehealth, visiting specialists, outreach clinics

Māori and Pacific Islander Peoples (New Zealand)

Epidemiology:[64]

• Māori: 1.5-2× higher sepsis admission rates vs non-Māori
• Pacific Islander: 2-2.5× higher sepsis admission rates
• Higher mortality in Māori and Pacific Islander populations

Risk factors:

• Rheumatic fever and RHD: 10× higher in Māori, 20× higher in Pacific children
• Diabetes: 2-3× higher in Māori and Pacific adults
• Respiratory disease: Higher rates of bronchiectasis, COPD
• Crowded housing: Facilitates transmission (meningococcal, GAS, pneumococcus)
• Socioeconomic deprivation: Delayed healthcare seeking

Cultural considerations for Māori patients:[65]

• Whānau (family) involvement: Essential in decision-making, not individual autonomy alone
• Tikanga (cultural protocols): Karakia (prayer), mirimiri (massage), rongoā (traditional medicine)
• Manaakitanga (hospitality/care): Provide culturally safe environment, accommodate whānau at bedside
• Ukaipō (place of sustenance): Return to ancestral lands important if dying
• Tapu and noa: Respect cultural protocols around body, illness, death

Communication strategies:

• Use Māori health workers/navigators if available
• Explain concepts using Te Ao Māori (Māori worldview) frameworks
• Family hui (meetings) for goals of care discussions
• Visual aids and interpreters if needed

Pacific Islander cultural considerations:

• Aiga/Fāmili (family): Collective decision-making, matai (chief) may have final say
• Fa'aaloalo (respect): Formal greetings, respectful communication
• Lotu (prayer/faith): Spiritual beliefs central, accommodate religious leaders
• Language diversity: Samoan, Tongan, Cook Island Māori, Niuean - use interpreters

---

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