Severe Sepsis - Adult

Quick Answer

Quick Answer: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Immediate recognition and treatment are critical - antibiotics within 1 hour for septic shock, 3 hours for sepsis. Initial management: Sepsis-3 bundle (measure lactate, obtain cultures, broad-spectrum antibiotics, 30 mL/kg crystalloid bolus, vasopressors for hypotension). First-line vasopressor: norepinephrine 0.05-0.5 mcg/kg/min via central line. Target MAP ≥65 mmHg. Reassess lactate at 3 hours - aim for clearance greater than 10%. Identify source and control (remove infected catheter, drain abscess). Consider adjuncts: corticosteroids for refractory shock, low-dose norepinephrine-refractory cases.

ACEM Exam Focus

Primary Exam

• Pathophysiology: SIRS cascade, endothelial dysfunction, coagulopathy, organ failure mechanisms
• Microbiology: Common sepsis pathogens (Gram-positive, Gram-negative, nosocomial)
• Pharmacology: Antibiotic classes, vasopressors, corticosteroids, anticoagulants

Fellowship Written

• Recognition: qSOFA, SOFA, lactate trends, clinical deterioration
• Initial Management: Sepsis bundle timing, fluid resuscitation, antibiotic selection
• Refractory Shock: Vasopressor escalation, steroids, refractory sepsis algorithms
• Source Control: When and how, imaging-guided interventions

Fellowship OSCE

• Resuscitation Station: Lead team managing septic patient, systematic ABCDE, bundle delivery
• Communication Station: Explain diagnosis/prognosis to family, discuss goals of care
• Clinical Reasoning: Identify septic patient from vignette, prioritise interventions

Key Points

1. Sepsis-3 Definition: Organ dysfunction (SOFA score increase ≥2) caused by infection - SIRS criteria abandoned
2. Septic Shock: Sepsis + vasopressor requirement to maintain MAP ≥65 mmHg + lactate greater than 2 mmol/L despite fluid resuscitation
3. Antibiotic Timing: Within 1 hour for septic shock, 3 hours for sepsis - each hour delay increases mortality by 7-8%
4. Fluid Resuscitation: 30 mL/kg crystalloid bolus (max 3000 mL) within 3 hours for hypotensive patients
5. Vasopressor Hierarchy: Norepinephrine first-line → vasopressin → epinephrine → dobutamine
6. Lactate Guidance: Initial lactate, repeat at 3 hours - aim for greater than 10% clearance, normalise within 24-48 hours
7. Source Control: Identify and control source within 6-12 hours - drain abscess, remove infected line

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Definitions

Historical SIRS Criteria (Sepsis-1 and Sepsis-2)

⚠️ Warning: SIRS criteria are no longer used to define sepsis - they lack specificity (present in many non-infectious conditions). However, SIRS remains clinically useful as an early alert for possible deterioration.

SIRS = 2+ of:

Limitations:

• Low specificity: 90% of ICU patients meet SIRS criteria
• Poor predictor of mortality
• Misses many septic patients (particularly elderly, immunocompromised)

Sepsis-3 Definition (Current)

Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection

Organ dysfunction: Defined as acute change in total SOFA score of ≥2 points consequent to infection

Clinical operationalisation: SOFA score ≥2 or suspected infection + qSOFA ≥2 (quick assessment tool)

Septic Shock: Sepsis with persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg AND serum lactate greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation

SOFA Score (Sequential Organ Failure Assessment)

Sepsis-3 threshold: SOFA score ≥2 = mortality risk ≥10%

qSOFA (Quick SOFA)

Bedside screening tool for patients with suspected infection:

qSOFA ≥2: High risk of poor outcome (3-14 fold increased mortality)

Performance:

• Excellent specificity for identifying patients at high risk of mortality
• Poor sensitivity (misses many septic patients)
• Not a screening tool - use clinical judgement
• Best for prognosis, not diagnosis

Lactate Interpretation

Lactate clearance: Percentage decrease from initial to 3-hour value

⚠️ Warning: Hyperlactataemia without tissue hypoxia: "Stress lactate" from adrenergic drive, liver dysfunction, or medication effects. Serial trends more useful than single values.

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Epidemiology

Global Burden

• Incidence: 48.9 million sepsis cases per year worldwide
• Mortality: 11 million sepsis-related deaths per year (19.7% of global deaths)
• Leading cause: One in five deaths globally attributable to sepsis
• Resource-limited settings: 85% of sepsis cases and deaths occur in low- and middle-income countries

Australian Data

• Incidence: 300 per 100,000 population (approx. 75,000 cases/year)
• Mortality: 15-20% overall, 40-50% for septic shock
• ICU Admission: 30-40% of septic patients require ICU care
• Hospital Length of Stay: Median 7-9 days for survivors

Age-Related Trends

Risk Factors

Host factors:

• Age above 65 years or below 1 year
• Immunocompromise (HIV, chemotherapy, transplantation)
• Chronic diseases (diabetes, COPD, CKD, liver disease)
• Indwelling devices (central lines, urinary catheters)
• Recent hospitalisation or surgery
• Alcoholism, IV drug use

Pathogen factors:

• Gram-negative organisms (E. coli, Klebsiella, Pseudomonas)
• Gram-positive organisms (S. aureus, S. pneumoniae, Enterococcus)
• Fungal (Candida) - immunocompromised patients
• Multidrug-resistant organisms - hospital-acquired sepsis

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Pathophysiology

Sepsis Cascade

Infection → Pathogen recognition (PAMPs + DAMPs) → Immune activation
→ Cytokine storm (TNF-α, IL-1, IL-6) → Endothelial dysfunction
→ Coagulopathy + Microthrombi → Organ hypoperfusion → Organ dysfunction
→ MODS (Multiple Organ Dysfunction Syndrome)

Key Pathophysiological Processes

1. Dysregulated Immune Response

• Hyperinflammatory phase: Massive cytokine release (TNF-α, IL-1β, IL-6)
• Immunosuppressive phase: Immune paralysis, lymphocyte apoptosis
• Simultaneous hyper- and hypo-inflammation: Patient may have both
• Immunothrombosis: NETs (neutrophil extracellular traps) promoting microthrombi

2. Endothelial Dysfunction

• Glycocalyx shedding → vascular leak → tissue oedema
• Increased permeability → capillary leak syndrome
• Impaired vasoregulation → vasodilation, distributive shock
• Pro-coagulant state → microvascular thrombosis

3. Cardiovascular Derangements

• Vasodilation: NO overproduction, catecholamine resistance
• Hypovolaemia: Capillary leak, increased venous capacitance
• Myocardial depression: Circulating myocardial depressant factors
• Altered microvascular flow: Shunting, impaired oxygen extraction

4. Metabolic Derangements

• Lactate production: Anaerobic metabolism (Type A) + aerobic glycolysis (Type B)
• Mitochondrial dysfunction: Impaired oxidative phosphorylation
• Insulin resistance: Stress hyperglycaemia
• Catabolic state: Muscle protein breakdown

Organ-Specific Pathophysiology

Septic Shock Specifics

Hypotension mechanisms:

• Vasodilation (decreased SVR)
• Hypovolaemia (capillary leak)
• Myocardial depression

Compensatory responses:

• Tachycardia (maintain CO)
• Vasoconstriction (non-essential beds)
• Catecholamine surge

Decompensation:

• Exhaustion of compensatory mechanisms
• Progressive organ failure
• Irreversible shock

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Clinical Presentation

Typical Features

Constitutional symptoms:

• Fever (≥38°C) or hypothermia (≤36°C)
• Chills, rigors
• Malaise, fatigue
• Anorexia, nausea, vomiting

Cardiovascular signs:

• Tachycardia (HR greater than 90/min) - often greater than 110-120/min in septic shock
• Hypotension (SBP below 90 mmHg or MAP below 65 mmHg)
• Delayed capillary refill (greater than 2-3 seconds)
• Peripheral mottling
• Cool extremities

Respiratory signs:

• Tachypnoea (RR greater than 20/min) - often greater than 25-30/min in septic shock
• Dyspnoea, increased work of breathing
• Hypoxaemia (SpO2 below 94%)
• Respiratory alkalosis (early) → respiratory acidosis (late)

Neurological signs:

• Confusion, disorientation
• Altered level of consciousness (GCS below 15)
• Agitation or lethargy
• Delirium (especially in elderly)

Renal signs:

• Oliguria (below 0.5 mL/kg/hr)
• Rising creatinine
• Fluid overload signs (oedema, crackles)

Gastrointestinal signs:

• Abdominal pain
• Diarrhoea
• Paralytic ileus
• Hepatomegaly, jaundice

Atypical Presentations (Important Pitfalls)

Elderly patients:

• Absent fever (may be normothermic or hypothermic)
• Subtle confusion may be only sign
• Tachycardia may be absent (beta-blockers)
• "Slow to sepsis"
• insidious deterioration

Immunocompromised patients:

• Blunted inflammatory response
• Absent fever
• Minimal leukocytosis
• Rapid decompensation

Neonates and infants:

• Poor feeding, lethargy
• Apnoeas, bradycardia
• Bulging fontanelle (meningitis)
• Hypothermia (more common than fever)

Pregnant patients:

• Physiological tachycardia and tachypnoea
• Reduced reserve for compensation
• Atypical presentation of common infections

Clinical Warning Signs (Red Flags)

⚠️ Warning: Immediate intervention required:

• SBP below 90 mmHg despite 2L crystalloid
• Lactate greater than 4 mmol/L
• New confusion or delirium
• SpO2 below 90% on room air
• Oliguria (below 0.5 mL/kg/hr)
• Disseminated intravascular coagulation (DIC)

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Clinical Approach

Initial Assessment (ABCDE with Resuscitation)

A - Airway

• Assess airway patency
• Consider intubation if:
  • GCS below 8
  • Respiratory fatigue or failure
  • Inability to protect airway
  • High work of breathing

B - Breathing

• SpO2 target: 94-98%
• Give oxygen if SpO2 below 94%
• Consider NIV for respiratory failure
• Early intubation if worsening respiratory status

C - Circulation

• Two large-bore IVs (16-18G)
• Initial fluid bolus: 30 mL/kg crystalloid
• Blood pressure monitoring (arterial line if available)
• Vasopressors if MAP below 65 mmHg after fluids

D - Disability

• GCS assessment
• Pupils
• Blood glucose (check for hypoglycaemia)
• Consider meningitis if headache + neck stiffness

E - Exposure/Examination

• Full examination for source of infection
• Peripheral cannulae, central lines, urinary catheters
• Surgical wounds, pressure areas
• Skin: rash (petechiae, purpura), cellulitis
• Chest: crackles, dullness
• Abdomen: tenderness, rigidity

Investigation Strategy

Immediate (within 1 hour):

• Point-of-care lactate
• Blood glucose
• VBG/ABG
• Blood cultures (x2 sets, aerobic + anaerobic)
• Urinalysis
• CXR (if respiratory signs)

Urgent (within 3 hours):

• FBC, U&Es, LFTs, coagulation profile
• CRP, procalcitonin (if available)
• Culture sources: urine, sputum, wound swabs
• CT imaging as indicated (abdomen, pelvis, chest)

Second-line:

• Echocardiography (bedside or formal)
• Viral PCR panel (if appropriate)
• Specific serologies (if atypical source suspected)
• Biomarkers (procalcitonin, presepsin)

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Investigations

Bedside Tests

Lactate

• Draw from arterial line or central line (most accurate)
• Venous lactate acceptable for screening (approximately 0.5-1.0 mmol/L higher)
• Repeat at 3 hours post-resuscitation
• Target: Lactate clearance greater than 10% from baseline

Blood Gas

• ABG if on oxygen therapy
• VBG acceptable for pH, bicarbonate, lactate
• Assess:
  • Acid-base status (metabolic acidosis = lactic acidosis)
  • PaO2/FiO2 ratio (if intubated)
  • Base deficit
  • Lactate (correlates with serum lactate)

Point-of-Care Glucose

• Check for hypoglycaemia (common in sepsis)
• Treat if below 4.0 mmol/L
• Avoid hyperglycaemia (greater than 10.0 mmol/L)

Urine Dipstick

• Leukocytes, nitrites (UTI)
• Protein (possible glomerulonephritis)
• Blood (haemorrhagic fever, vasculitis)

Laboratory Tests

FBC

• Leucocytosis (above 12,000/μL) OR leucopenia (below 4,000/μL)
• Left shift (bands greater than 10%)
• Thrombocytopenia (below 150,000/μL) - poor prognostic sign
• Anaemia of chronic disease

Biochemistry

• U&Es:
  • Rising creatinine (AKI)
  • Hyponatraemia, hyperkalaemia
  • BUN/Creatinine ratio (prerenal vs ATN)
• LFTs:
  • Elevated bilirubin (cholestasis, hepatocellular injury)
  • Raised transaminases
• CRP:
  • Elevated (greater than 100 mg/L) - non-specific
  • Serial monitoring useful

Coagulation Profile

• PT/APTT prolongation (DIC)
• Low fibrinogen (below 150 mg/dL)
• D-dimer elevated
• Platelet count trend

Procalcitonin

• Bacterial infection marker
• Useful for:
  • Distinguishing bacterial vs viral infection
  • Guiding antibiotic duration
• Levels:
  • below 0.1 ng/mL: Low likelihood of bacterial infection
  • 0.5-2.0 ng/mL: Possible bacterial infection
  • greater than 2.0 ng/mL: High likelihood of severe bacterial sepsis

Microbiology

Blood Cultures

• Two sets (aerobic + anaerobic) before antibiotics
• Draw from different sites (if possible)
• Volume: 20-30 mL per set (higher yield)
• Timing: Within 1 hour of sepsis recognition

Other Cultures

• Urine culture (midstream clean catch)
• Sputum culture (if productive cough)
• Wound swab (if cellulitis, surgical wound infection)
• CSF culture (if meningitis suspected)
• Catheter tip culture (if line infection suspected)

Other Microbiological Tests

• Blood film (malaria, babesiosis)
• Urine antigens (pneumococcal, legionella)
• Viral PCR panel (influenza, RSV, SARS-CoV-2)
• Serology (if atypical pathogens suspected)

Imaging

Chest X-ray

• Indication: Respiratory signs, suspected pneumonia
• Findings: Consolidation, effusion, interstitial infiltrates

CT Abdomen/Pelvis

• Indication: Abdominal sepsis source
• Findings: Abscess, perforation, diverticulitis, cholecystitis

Ultrasound

• FAST scan (if trauma also considered)
• Focused abdominal US (gallbladder, kidneys)
• Soft tissue US (abscess, cellulitis)

Echocardiography

• Indication: Suspected endocarditis, cardiac source, cardiac dysfunction
• Bedside vs formal: Depends on availability and question
• Findings: Vegetations, EF, valvular dysfunction

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Management

Sepsis-3 Bundle (Within 3 Hours)

The Hour-1 Bundle (Updated 2021)

Within 1 hour of recognition:

1. Measure lactate
2. Obtain blood cultures (before antibiotics if possible)
3. Administer broad-spectrum antibiotics
4. Begin fluid resuscitation (30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L)
5. Start vasopressors if hypotensive despite fluids

Antibiotic Therapy

Timing:

• Septic shock: Within 1 hour of recognition
• Sepsis without shock: Within 3 hours of recognition
• Each hour delay increases mortality by 7-8%

Empiric Antibiotic Selection

MRSA coverage (add vancomycin or linezolid if risk factors):

• Recent MRSA colonisation/infection
• Recent hospitalisation
• Intravenous drug use
• Indwelling devices

Pseudomonas coverage (if risk factors):

• Recent hospitalisation
• Prior Pseudomonas infection
• Structural lung disease
• Cystic fibrosis

Antibiotic Stewardship:

• De-escalate once cultures and sensitivities known
• Duration: 7-10 days for most infections
• Procalcitonin-guided duration may reduce exposure
• Source-specific: Endocarditis (4-6 weeks), osteomyelitis (4-6 weeks)

Fluid Resuscitation

Initial Fluid Challenge

• 30 mL/kg crystalloid bolus (maximum 3000 mL)
• Give over 30-60 minutes
• Indication: Hypotension OR lactate ≥4 mmol/L

Crystalloid Choice:

• Balanced crystalloids preferred (Plasma-Lyte, Hartmann's)
• Normal saline acceptable (caution: hyperchloremic acidosis)
• Avoid: Albumin, hetastarch, dextran (no benefit, potential harm)

Fluid Responsiveness Assessment

• Passive leg raise (PLR): greater than 10% increase in CO/SBP = responsive
• Fluid challenge: 250-500 mL crystalloid, reassess BP, HR, capillary refill
• Static measures (CVP) unreliable for predicting response

Targeted Fluid Therapy

• Reassess after initial bolus:
  • BP response
  • Lactate clearance
  • Organ perfusion (urine output, mental status)
• Avoid large-volume resuscitation (greater than 5L) without response
• Consider early vasopressor support

Caution:

• Cardiac failure (risk of pulmonary oedema)
• Severe ARDS (risk of worsening lung compliance)
• End-stage renal disease (fluid overload)

Vasopressor Therapy

Indications:

• MAP below 65 mmHg despite initial fluid resuscitation
• Goal MAP: ≥65 mmHg (individualise: 70-80 mmHg if chronic hypertension)

First-line: Norepinephrine

• Dose: 0.05-0.5 mcg/kg/min IV infusion
• Onset: 1-2 minutes
• Half-life: 2-5 minutes
• Mechanism: α1 agonist (vasoconstriction), weak β1 activity (inotropy)

Second-line: Vasopressin

• Indication: Norepinephrine-refractory shock (greater than 0.3-0.5 mcg/kg/min)
• Dose: 0.03 units/min (fixed dose, no titration up to 0.04 units/min)
• Mechanism: V1 receptor agonist (vasoconstriction)
• Advantage: Spares norepinephrine dose, improves renal blood flow

Third-line: Epinephrine

• Indication: Norepinephrine + vasopressin insufficient
• Dose: 0.01-0.5 mcg/kg/min IV infusion
• Mechanism: Strong α1 and β1 agonist
• Disadvantages: Tachycardia, arrhythmias, splanchnic vasoconstriction

Inotrope: Dobutamine

• Indication: Cardiac dysfunction with low cardiac output
• Dose: 2-20 mcg/kg/min IV infusion
• Mechanism: β1 agonist (inotropy), mild β2 (vasodilation)
• Monitor: Tachycardia, arrhythmias

Vasopressor Administration:

• Central line preferred (avoid extravasation)
• If central line unavailable: Large-bore peripheral IV, monitor closely
• Titrate to target MAP
• Reduce dose once MAP stable ≥65 mmHg

Corticosteroids

Indications:

• Septic shock requiring vasopressors (greater than 0.25 mcg/kg/min norepinephrine) despite adequate fluid resuscitation
• Consider in refractory shock within 6-12 hours

Evidence:

• ADRENAL trial (2018): No mortality benefit, faster shock resolution
• APROCCHSS trial (2018): Mortality benefit with low-dose hydrocortisone + fludrocortisone

Regimen:

• Hydrocortisone 200 mg IV daily (50 mg 6-hourly or continuous infusion)
• Duration: 7 days or until ICU discharge (whichever earlier)
• Consider adding fludrocortisone 50 mcg PO daily (enteral route available)

Tapering:

• Abrupt discontinuation if short course (below 7 days)
• Taper over 3-5 days if longer course (greater than 7 days)

Monitoring:

• Hyperglycaemia: Insulin sliding scale
• Secondary infection: Monitor closely
• Hypernatraemia (fludrocortisone mineralocorticoid effect)

Source Control

Principles:

• Identify and control source within 6-12 hours
• Physical removal or drainage of infected material
• Decontamination of infected devices

Specific Interventions:

• Intravascular catheters: Remove infected line, tip culture
• Intra-abdominal abscess: Percutaneous or surgical drainage
• Infected necrotising pancreatitis: Percutaneous or surgical drainage (delayed to greater than 4 weeks)
• Empyema: Chest drain
• Septic arthritis: Orthopaedic washout
• Necrotising fasciitis: Surgical debridement (within 6-24 hours)

Timing:

• Life-threatening: Immediate intervention (within 1-2 hours)
• Urgent: Within 6-12 hours
• Elective: After initial resuscitation and stabilisation

Supportive Care

Oxygenation and Ventilation

• SpO2 target: 94-98%
• High-flow nasal cannula (HFNC) for hypoxaemic respiratory failure
• Early intubation if:
  • PaO2 below 60 mmHg on maximal oxygen
  • Rising PaCO2 greater than 50 mmHg
  • Respiratory fatigue, GCS deterioration
  • ARDS (PaO2/FiO2 below 200)

Renal Replacement Therapy

• Indication: Severe AKI (Stage 3), refractory metabolic acidosis, hyperkalaemia, fluid overload
• Modality: CRRT (continuous renal replacement therapy) preferred in haemodynamic instability
• Anticoagulation: Citrate (preferred), heparin

Glycaemic Control

• Target: 7.8-10.0 mmol/L (140-180 mg/dL)
• Avoid hypoglycaemia (below 4.0 mmol/L)
• Avoid tight control (below 6.1 mmol/L) - increases mortality

Nutrition

• Enteral nutrition preferred (within 24-48 hours)
• Parenteral nutrition if EN contraindicated or insufficient
• High-protein (1.2-2.0 g/kg/day) for catabolic state

Venous Thromboembolism Prophylaxis

• Low molecular weight heparin (enoxaparin 40 mg SC daily)
• Mechanical prophylaxis if contraindication to anticoagulation

Stress Ulcer Prophylaxis

• PPI (pantoprazole 40 mg IV/PO daily) or H2 blocker
• Indication: Mechanical ventilation, coagulopathy, shock

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Disposition

Admission Criteria

General ward:

• Sepsis without organ dysfunction
• Vital signs stable after 4-6 hours
• No persistent hypotension
• Lactate below 2 mmol/L and normalising
• Identified source, appropriate antibiotics

High-dependency unit (HDU):

• Mild organ dysfunction (single system)
• Requiring close monitoring
• Single vasopressor at low dose
• Lactate 2-4 mmol/L

Intensive care unit (ICU):

• Septic shock (vasopressor requirement)
• Multiorgan dysfunction (≥2 systems)
• Mechanical ventilation
• Renal replacement therapy
• Lactate greater than 4 mmol/L or rising

Safe Discharge Criteria

Low-risk criteria (may be discharged with oral antibiotics):

• qSOFA score below 2
• Normal vital signs for ≥6 hours
• Lactate below 2 mmol/L
• Normal mental status
• Adequate social support
• Follow-up arranged within 24-48 hours

Palliative Care Considerations

⚠️ Warning: Goals of care discussion: Early discussion if:

• Age greater than 80 years with severe comorbidities
• Advanced dementia or frailty
• Multiple organ failure with poor response
• Patient wishes previously expressed

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Pitfalls and Pearls

Common Pitfalls

1. Relying on fever: Elderly and immunocompromised may be afebrile
2. Delayed antibiotics: Each hour delay increases mortality
3. Insufficient fluid resuscitation: Under-resuscitation common, reassess
4. Overshooting fluids: Pulmonary oedema in cardiac failure patients
5. Vasopressor underuse: Fear of complications leads to delayed initiation
6. Missing source control: Failure to identify and control source leads to treatment failure
7. Overusing antibiotics: Unnecessary broad-spectrum leads to resistance
8. Focusing on lactate in isolation: Clinical context more important than single value

Clinical Pearls

1. Think sepsis early: Any patient with unexplained deterioration
2. Empiric antibiotics first: Don't delay for cultures if critically ill
3. Large-bore access early: Two 16-18G IVs essential for rapid fluid/blood
4. Serial lactate monitoring: Trend more useful than single value
5. Early vasopressor support: Maintains perfusion pressure, reduces large-volume fluid needs
6. Consider atypical pathogens: Immunocompromised, indwelling devices, recent travel
7. De-escalate antibiotics: Narrow spectrum once cultures known
8. Goals of care early: Discuss with family/patient if poor prognosis

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Viva Practice

Viva 1: Sepsis Recognition and Initial Management

Stem: A 67-year-old man presents to the emergency department with confusion and fever. His wife reports he has been coughing for 5 days and is increasingly lethargic. On arrival, he is tachypnoeic (RR 28/min) and hypoxic (SpO2 88% on room air). BP 85/50 mmHg, HR 118/min, temperature 39.2°C.

Q1: What are your immediate priorities?

A1:

• Immediate: ABCDE assessment with simultaneous resuscitation
• A: Assess airway, prepare for intubation if GCS deteriorates or respiratory failure
• B: Give high-flow oxygen (15 L/min) to target SpO2 94-98%, consider HFNC or NIV
• C: Establish two large-bore IVs (16-18G), initial fluid bolus 30 mL/kg crystalloid, vasopressor preparation (norepinephrine)
• D: Assess GCS (likely low), check blood glucose (hypoglycaemia may cause confusion)
• E: Full examination - focus on source (pneumonia likely given cough, hypoxia)
• Immediate investigations: Point-of-care lactate, blood gas, blood cultures x2, FBC, U&Es, CRP, CXR

Q2: How would you define septic shock in this patient?

A2: Septic shock requires all three criteria:

1. Sepsis: Life-threatening organ dysfunction (SOFA score increase ≥2) from infection
2. Persistent hypotension: Requiring vasopressors to maintain MAP ≥65 mmHg
3. Serum lactate greater than 2 mmol/L: Despite adequate fluid resuscitation

This patient meets criteria: suspected infection (pneumonia), organ dysfunction (confusion, hypotension, respiratory failure), lactate likely elevated, will require vasopressors despite fluid resuscitation.

Q3: What are the key components of the initial sepsis bundle?

A3: The Sepsis-3 "Hour-1 Bundle" includes all within 1 hour of recognition:

1. Measure lactate (point-of-care or blood gas)
2. Obtain blood cultures before antibiotics if possible (do not delay antibiotics)
3. Administer broad-spectrum antibiotics (cover likely source - community-acquired pneumonia: ceftriaxone + azithromycin)
4. Begin fluid resuscitation (30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L)
5. Start vasopressors (norepinephrine) if MAP below 65 mmHg after initial fluid

Q4: How would you select empiric antibiotics for this patient?

A4:

• Suspected source: Community-acquired pneumonia (cough, hypoxia, fever)
• First-line empiric: Ceftriaxone 2g IV daily + azithromycin 500mg IV daily
  • "Ceftriaxone: Covers typical (Streptococcus pneumoniae, Haemophilus influenzae) and some atypical pathogens"
  • "Azithromycin: Covers atypical pathogens (Mycoplasma, Legionella, Chlamydophila)"
• Alternative: Amoxicillin 1g IV 6-hourly + macrolide if beta-lactam allergy to ceftriaxone
• Add MRSA coverage (vancomycin) if risk factors: recent hospitalisation, prior MRSA colonisation, indwelling device
• De-escalate: Once culture and sensitivity results available (typically 48-72 hours)

Q5: This patient's lactate is 4.2 mmol/L. What does this value indicate and how would you use it?

A5:

• Lactate 4.2 mmol/L: Indicates severe sepsis/septic shock with high mortality risk
• Classification: Type A lactic acidosis (tissue hypoperfusion) given hypotension and shock
• Management implications:
  • Confirms need for aggressive resuscitation
  • Initiates sepsis bundle (30 mL/kg fluid bolus indicated)
  • Triggers vasopressor preparation (norepinephrine)
• Serial monitoring: Repeat lactate at 3 hours
  • "Target: above 10% clearance from baseline (lactate below 3.8 mmol/L)"
  • Poor clearance predicts higher mortality, consider escalation (ICU, additional vasopressors, corticosteroids)
  • Normalisation typically within 24-48 hours with adequate treatment

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Viva 2: Fluid Resuscitation and Vasopressor Management

Stem: You are treating a 54-year-old woman with septic shock from urosepsis. She has received 30 mL/kg crystalloid (approximately 2 litres). Her current vitals: BP 78/45 mmHg, HR 125/min, RR 26/min, SpO2 96% on 6L O2, temperature 38.7°C. Lactate initial 3.8 mmol/L, repeat 3.5 mmol/L after fluids.

Q1: How would you interpret this patient's response to fluid resuscitation?

A1:

• Inadequate response: Persistent hypotension (BP 78/45 mmHg, MAP ~56 mmHg) after adequate fluid challenge
• Lactate trend: Mild improvement (3.8 → 3.5 mmol/L) suggests some tissue perfusion improvement but ongoing shock
• Tachycardia persistent: HR 125/min suggests compensatory sympathetic drive
• Classification: Fluid-refractory septic shock - requires vasopressor support
• Action: Initiate norepinephrine infusion

Q2: What is your vasopressor of choice and how would you administer it?

A2:

• First-line: Norepinephrine

  • "Dose: Start 0.05 mcg/kg/min (approx. 4 mcg/min for 80 kg patient)"
  • "Titration: Increase by 0.05-0.1 mcg/kg/min every 2-3 minutes until MAP ≥65 mmHg"
  • "Maximum dose: 0.5-1.0 mcg/kg/min before adding second vasopressor"
  • "Route: Central line preferred (avoid extravasation), large-bore peripheral IV acceptable if central line unavailable"
  • "Mechanism: α1 agonist (vasoconstriction) with weak β1 activity (inotropy), maintains perfusion pressure with minimal tachycardia"

• Alternative if unavailable: Adrenaline (epinephrine) - more tachycardia and arrhythmias

Q3: At what point would you add a second vasopressor, and which would you choose?

A3:

• Indication for second vasopressor: Norepinephrine dose greater than 0.3-0.5 mcg/kg/min without achieving target MAP ≥65 mmHg

• Second-line: Vasopressin

  • "Dose: Fixed dose 0.03 units/min (not titrated up to 0.04 units/min maximum)"
  • "Mechanism: V1 receptor agonist (vasoconstriction), independent of adrenergic receptors"
  • "Advantages: Norepinephrine-sparing effect (reduces adrenergic side effects), improves renal blood flow, less arrhythmogenic"
  • "Evidence: VASST trial showed no mortality difference but subgroup benefit with less severe shock (norepinephrine below 15 mcg/min)"

• Third-line: Epinephrine (if norepinephrine + vasopressin insufficient)

  • "Dose: 0.01-0.5 mcg/kg/min"
  • "Disadvantages: Tachycardia, arrhythmias, splanchnic vasoconstriction"

Q4: How would you assess fluid responsiveness before giving additional fluids?

A4:

• Static measures unreliable: CVP, IVC diameter not predictive of fluid responsiveness

• Dynamic measures preferred:

  1. Passive leg raise (PLR) test:

     • Elevate patient's legs to 45° (or move from semi-recumbent to supine with legs raised)
     • Measure change in cardiac output (CO) or surrogate (stroke volume variation, arterial pressure change)
     • Positive response: greater than 10% increase in CO or SBP → fluid-responsive
     • Advantage: Autologous fluid challenge, no net fluid administration

  2. Fluid challenge:

     • Give 250-500 mL crystalloid over 5-10 minutes
     • Reassess: BP, HR, stroke volume (if monitored), urine output
     • Positive response: BP increase greater than 15 mmHg, HR decrease greater than 10%, or urine output improvement
     • No response: Avoid further fluid administration, consider vasopressor escalation

• Clinical indicators of fluid overload: New crackles, rising JVP, peripheral oedema, worsening hypoxia

Q5: What are the potential complications of aggressive fluid resuscitation, and how would you monitor for them?

A5:

• Complications:

  1. Pulmonary oedema: Worsening hypoxia, crackles on auscultation, bilateral infiltrates on CXR
  2. Abdominal compartment syndrome: Rising intra-abdominal pressure, oliguria, high airway pressures (in ventilated patients)
  3. Dilutional coagulopathy: Thrombocytopenia, reduced clotting factors
  4. Crystalloid overload: Peripheral oedema, tissue oedema (improving organ perfusion but impairing function)
  5. Hyperchloremic acidosis: With large-volume normal saline (metabolic acidosis)

• Monitoring:

  • "Respiratory: SpO2, respiratory rate, work of breathing, CXR (if worsening)"
  • "Cardiovascular: CVP (caution - may be elevated with overload), lung ultrasound (B-lines for pulmonary oedema)"
  • "Renal: Urine output (may initially increase with fluids, then decrease with overload)"
  • "Abdominal: IAP measurement (bladder pressure) if suspect compartment syndrome"
  • "Biochemistry: Rising creatinine, worsening acidosis (lactate may rise with tissue oedema)"

• Management: Diuresis, renal replacement therapy if severe overload

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Viva 3: Antibiotic Stewardship and Source Control

Stem: A 43-year-old man presented with fever, rigors, and hypotension 3 days after emergency laparotomy for perforated appendicitis. He has a central line in situ. Blood cultures grow Pseudomonas aeruginosa (sensitive to cefepime, piperacillin-tazobactam). He has been on piperacillin-tazobactam 4.5g IV 6-hourly since ED presentation 48 hours ago. His current lactate is 1.8 mmol/L (down from 4.5 mmol/L), BP 102/58 mmHg on norepinephrine 0.08 mcg/kg/min.

Q1: What source of infection is most likely, and how would you manage it?

A1:

• Most likely source: Central line-associated bloodstream infection (CLABSI)

  • "Risk factors: Recent surgery, indwelling central line, Pseudomonas (common CLABSI pathogen)"
  • "Supporting evidence: Blood culture growing Pseudomonas, ongoing fever despite appropriate antibiotics"

• Management of CLABSI:

  1. Remove central line: Essential for source control (cultured tip sent for microbiology)
  2. Confirm source: Differential time to positivity (DTP) greater than 2 hours between central and peripheral blood cultures suggests line infection
  3. Tunnelled or implanted port: Remove if infected (no benefit from systemic antibiotics alone)
  4. Re-site new line: Different site, after infection controlled (peripheral IV acceptable short-term)
  5. Duration: 10-14 days of appropriate antibiotics (longer if complicated bacteraemia)

• Alternative sources to consider: Intra-abdominal abscess (post-operative), surgical site infection, urinary tract (post-op catheter)

Q2: Is the current antibiotic regimen appropriate, and would you de-escalate?

A2:

• Current regimen: Piperacillin-tazobactam 4.5g IV 6-hourly

• Appropriateness: Pseudomonas aeruginosa sensitive to piperacillin-tazobactam - appropriate agent, adequate dose (4.5g IV 6-hourly achieves therapeutic levels)

• De-escalation: Not required in this case - already targeted therapy

• If resistant to piperacillin-tazobactam: Switch to cefepime 2g IV 8-hourly or meropenem 1g IV 8-hourly based on sensitivities

• Antibiotic stewardship principles:

  • Narrow spectrum once cultures known (already narrow for Pseudomonas)
  • Adequate duration (not too long, not too short) - 10-14 days for Pseudomonas bacteraemia
  • Adequate dose (renal-adjusted if required)
  • IV to PO switch when appropriate (typically after 48-72 hours afebrile, improving clinical status)

Q3: What other sources of infection would you investigate in this patient?

A3:

• Intra-abdominal: Post-operative abscess or anastomotic leak

  • CT abdomen/pelvis with contrast (preferred imaging)
  • Surgical drain if abscess present
  • Consider re-exploration if clinical suspicion high

• Surgical site infection: Wound cellulitis, dehiscence

  • Wound inspection, ultrasound if deep infection suspected
  • Wound swab for culture

• Urinary tract: Catheter-associated UTI (if urinary catheter in situ)

  • Urinalysis, urine culture
  • Remove catheter if possible

• Pulmonary: Post-operative pneumonia

  • CXR, sputum culture, consider bronchoalveolar lavage if ventilated
  • Aspiration risk in post-op patients

• Other: Rare sources like endocarditis (consider if persistent bacteraemia despite line removal and appropriate antibiotics)

Q4: At what point would you involve the surgical team for source control?

A4:

• Indications for surgical source control (within 6-12 hours of recognition):

  1. Infected necrotising pancreatitis: Percutaneous drainage first, surgical debridement if refractory
  2. Intra-abdominal abscess: Percutaneous drainage if accessible, surgical if not or if multiple abscesses
  3. Anastomotic leak: Surgical re-exploration and repair
  4. Necrotising fasciitis: Surgical debridement within 6-24 hours (life-saving)
  5. Septic arthritis: Orthopaedic washout
  6. Infected prosthetic material: Removal (valve, joint replacement, mesh)

• Timing: Earlier (within 1-2 hours) for life-threatening conditions (necrotising fasciitis, perforated viscus), within 6-12 hours for urgent conditions (drainable abscesses)

• Decision-making: Multidisciplinary (ED, ICU, surgical teams), imaging-guided decision

Q5: What are the principles of antibiotic duration in sepsis?

A5:

• General principle: Shorter courses (7-10 days) for most uncomplicated infections, longer courses (10-14 days) for complicated infections

• Infection-specific duration:

  • "Community-acquired pneumonia: 5-7 days (clinical stability for 48-72 hours)"
  • "Hospital-acquired/ventilator-associated pneumonia: 7-8 days (non-Pseudomonas), 14 days for Pseudomonas"
  • "Intra-abdominal infection: 4-7 days (uncomplicated), 14 days (complicated, perforation)"
  • "Pyelonephritis: 7-14 days (uncomplicated 7 days, complicated 14 days)"
  • "Meningitis: 7-14 days (bacterial), longer for Listeria, TB"
  • "Endocarditis: 4-6 weeks (native valve), 6 weeks (prosthetic valve)"
  • "Osteomyelitis: 4-6 weeks (acute), longer for chronic"

• Procalcitonin-guided duration:

  • Stop antibiotics when procalcitonin below 0.25 ng/mL or decreased by above 80-90% from peak
  • Reduces antibiotic exposure without increasing mortality

• Individualisation: Patient factors (immunocompromise), pathogen (Pseudomonas, MRSA require longer), source (bone, heart valve require longer)

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Viva 4: Special Populations - Elderly Patient

Stem: An 82-year-old woman is brought to ED by her daughter who reports "not herself" for 2 days. On arrival, she is confused (GCS 13), tachycardic (HR 110/min), mildly hypotensive (BP 95/55 mmHg), afebrile (temperature 36.8°C). Lactate 3.2 mmol/L. Urinalysis: leukocytes ++++, nitrites +++. Her medical history includes dementia, hypertension, atrial fibrillation (on warfarin).

Q1: Why might this patient be afebrile despite having infection?

A1:

• Blunted febrile response in elderly:

  • Impaired thermoregulation (hypothalamic dysfunction)
  • Reduced metabolic rate (lower baseline temperature)
  • Medication effects (antipyretics, beta-blockers)
  • Malnutrition, frailty, reduced physiological reserve

• Alternative presentations: Hypothermia (temperature below 36°C), confusion ("septic encephalopathy"), anorexia, falls

• Clinical implication: Do not rely on fever to diagnose infection in elderly - consider sepsis if unexplained deterioration, even afebrile

Q2: What are the specific challenges in diagnosing sepsis in the elderly?

A2:

• Atypical presentations:

  • Confusion or delirium may be only sign (often attributed to dementia)
  • Absent fever (febrile response blunted)
  • Hypothermia may occur (poor prognostic sign)
  • "Slow to sepsis"

• insidious deterioration over days

• Baseline abnormalities:

  • Tachycardia may be absent (beta-blockers, atrial fibrillation)
  • Respiratory rate may not increase significantly (baseline tachypnoea from comorbidities)
  • White blood cell count may not rise (immune senescence)

• Comorbidities confounding:

  • Confusion attributed to dementia, not new encephalopathy
  • Weakness attributed to age, deconditioning
  • Tachypnoea attributed to heart failure or COPD

• Diagnostic approach:

  • Consider sepsis in any unexplained change from baseline
  • Use qSOFA score (though insensitive) and clinical judgement
  • Early lactate (elevated even if subtle clinical changes)
  • "Broad differential (other causes of delirium: metabolic, medications, stroke)"

Q3: How would you manage the warfarin in this septic patient?

A3:

• Immediate action: Reverse warfarin anticoagulation

  • "Indication: Septic patient at high risk of bleeding (DIC, invasive procedures, invasive monitoring)"
  • "INR: Check INR urgently (likely elevated due to warfarin + liver dysfunction in sepsis)"

• Reversal options (depending on INR, bleeding risk, urgency):

  1. Vitamin K: 5-10 mg IV (slow infusion over 30 minutes) for gradual reversal (6-24 hours)
  2. Prothrombin complex concentrate (PCC): If life-threatening bleeding, immediate reversal required
  3. Fresh frozen plasma (FFP): If PCC unavailable, higher volume load (cautious in elderly, fluid-sensitive)

• Heparin bridging: Generally not required in acute sepsis (high bleeding risk outweighs thrombotic risk)

• Re-anticoagulation: Only after sepsis resolved, bleeding risk decreased, patient clinically stable

Q4: What specific considerations are required for fluid resuscitation in an elderly patient?

A4:

• Reduced physiological reserve: Less tolerance for large-volume fluid resuscitation

• Comorbidities increasing fluid sensitivity:

  • "Heart failure: Reduced cardiac reserve, risk of pulmonary oedema"
  • "CKD: Impaired fluid excretion, electrolyte abnormalities"
  • "Atrial fibrillation: Tachycardia may be poorly tolerated"

• Fluid strategy:

  • Start with smaller bolus (250-500 mL) rather than full 30 mL/kg (may be excessive in frail elderly)
  • Assess fluid responsiveness more frequently (after each 250-500 mL)
  • Use dynamic measures (PLR, stroke volume variation) if available
  • Early vasopressor support to avoid large-volume resuscitation

• Monitoring:

  • Lung ultrasound for pulmonary oedema (B-lines)
  • Daily CXR (if clinical deterioration)
  • Strict input/output monitoring
  • Daily weights (fluid balance tracking)

• Caution: Avoid over-resuscitation - pulmonary oedema and abdominal compartment syndrome more likely in elderly

Q5: This patient's daughter is concerned about her mother's prognosis and asks about her chances of survival. How would you respond?

A5:

• Prognostic factors in elderly sepsis:

  • "Age greater than 80 years: Higher mortality (40-50% vs 15-20% overall)"
  • "Dementia: Associated with poorer outcomes (reduced functional reserve, aspiration risk)"
  • "Multiple comorbidities: Hypertension, atrial fibrillation reduce physiological reserve"
  • "Presentation: Late presentation (daughter noticed 2 days ago) may have delayed recognition"

• Individual prognosis:

  • "Better prognosis factors: Lactate below 4 mmol/L (3.2 mmol/L), source identified (UTI), treatable with antibiotics and fluids, early recognition"
  • "Poorer prognosis factors: Age, comorbidities, late presentation"

• Communication approach:

  • Honest but balanced discussion
  • Explain that prognosis uncertain at this early stage
  • Emphasise that early treatment improves chances
  • "Discuss goals of care: Aggressive treatment now, reassess at 24-48 hours"
  • Involve family in decision-making (especially given dementia and advance directives)

• Palliative care consideration: If no improvement after 24-48 hours of appropriate treatment, or if patient deteriorates, discuss limitations of treatment and goals of care

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OSCE Practice

OSCE Station 1: Sepsis Resuscitation (11 minutes)

Setting: Resuscitation bay

Scenario: A 58-year-old man presents with severe sepsis from community-acquired pneumonia. He is hypoxic (SpO2 88% on room air), tachycardic (HR 120/min), hypotensive (BP 85/50 mmHg). Lactate 4.5 mmol/L. You are the team leader.

Task: Lead the resuscitation of this patient with sepsis. Demonstrate systematic approach, appropriate interventions, and team leadership.

Equipment: Oxygen masks, IV equipment, fluids, vasopressors, monitoring equipment

Marking Criteria:

Expected Time Allocation:

• 0-3 minutes: ABCDE assessment, initial interventions
• 3-6 minutes: Complete bundle (cultures, antibiotics, fluids)
• 6-9 minutes: Ongoing monitoring, source investigation
• 9-11 minutes: Summary, disposition planning

Critical Fail: Failure to administer antibiotics within 1 hour, failure to give initial fluid bolus, failure to secure airway if required

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OSCE Station 2: Communication - Discussing Diagnosis and Prognosis (11 minutes)

Setting: ED quiet room

Scenario: The daughter of a 76-year-old patient with severe sepsis approaches you. Her mother was admitted 6 hours ago with urosepsis, is currently in the ICU on norepinephrine, and has a lactate of 3.8 mmol/L. The daughter asks: "How sick is my mother? Will she get better?"

Task: Explain the diagnosis and prognosis of severe sepsis to the patient's daughter. Use clear language, address concerns appropriately, and demonstrate empathetic communication.

Actor briefing: You are the worried daughter. Your mother has dementia and you are her primary carer. You are anxious about her condition and want honest information about her chances. You may ask specific questions about her prognosis, treatment, and what to expect next.

Marking Criteria:

Expected Time Allocation:

• 1-2 minutes: Introduction, establish understanding
• 2-5 minutes: Explain diagnosis, current management
• 5-8 minutes: Prognosis, address concerns
• 8-11 minutes: Goals of care, safety-netting, summary

Critical Fail: Providing false hope, ignoring family's concerns, failing to raise goals of care discussion, using jargon without explanation

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OSCE Station 3: Clinical Assessment - Identifying Sepsis Source (11 minutes)

Setting: ED assessment cubicle

Scenario: A 34-year-old man presents with fever (39.5°C), rigors, and right-sided abdominal pain for 2 days. He has a history of IV drug use. On examination, he is tachycardic (HR 115/min), hypotensive (BP 92/58 mmHg), and has a tender liver on palpation. You need to identify the source of infection and initiate appropriate management.

Task: Perform a focused clinical assessment to identify the source of infection, request appropriate investigations, and outline your initial management plan.

Equipment: Examination couch, stethoscope, otoscope, speculum, IV equipment

Marking Criteria:

Expected Time Allocation:

• 0-3 minutes: Focused history
• 3-7 minutes: Focused examination
• 7-9 minutes: Investigations ordered, differential diagnosis
• 9-11 minutes: Management plan, safety-netting

Critical Fail: Failure to consider endocarditis in IV drug user with fever, failure to initiate sepsis bundle, failure to identify need for source control (abscess drainage)

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SAQ Practice

SAQ 1: Sepsis Bundle Implementation

Stem: A 62-year-old man presents to the emergency department with fever, confusion, and hypotension. His temperature is 39.2°C, BP 82/50 mmHg, HR 125/min, RR 26/min, SpO2 92% on room air. Point-of-care lactate is 4.8 mmol/L.

Question: Outline the components of the initial sepsis bundle that must be implemented within 1 hour of recognition, and explain the rationale for each component. (8 marks)

Model Answer:

1. Measure lactate (1 mark)

   • Rationale: Lactate is a marker of tissue hypoperfusion and a prognostic indicator; level greater than 4 mmol/L indicates severe sepsis/septic shock with high mortality risk; serial lactate monitoring guides resuscitation effectiveness (1 mark)

2. Obtain blood cultures (1 mark)

   • Rationale: Identify causative pathogen and guide antibiotic selection; draw before antibiotics if possible without delaying treatment; two sets (aerobic + anaerobic) from different sites increase yield (1 mark)

3. Administer broad-spectrum antibiotics (1 mark)

   • Rationale: Early antibiotics improve survival (each hour delay increases mortality by 7-8%); must be active against likely pathogens (Gram-positive, Gram-negative) based on suspected source; empiric selection should be appropriate (e.g., community-acquired pneumonia: ceftriaxone + macrolide) (1 mark)

4. Begin fluid resuscitation (30 mL/kg crystalloid) (1 mark)

   • Rationale: Initial fluid challenge addresses hypovolaemia from vasodilation and capillary leak; improves tissue perfusion; crystalloids (balanced preferred) are first-line; avoid over-resuscitation in cardiac failure (1 mark)

5. Start vasopressors if hypotensive despite fluids (1 mark)

   • Rationale: Maintain perfusion pressure (target MAP ≥65 mmHg); norepinephrine is first-line (α1 agonist); early vasopressor support reduces need for large-volume fluid resuscitation and associated complications (1 mark)

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SAQ 2: Sepsis Definitions and Scoring Systems

Stem: A 78-year-old woman presents with altered mental status, hypotension (BP 88/52 mmHg), and tachycardia (HR 110/min). Her temperature is 37.5°C, respiratory rate 24/min, SpO2 94% on room air. White blood cell count is 11,500/μL. Lactate is 3.5 mmol/L. Blood cultures grow Escherichia coli.

Question: (a) Using Sepsis-3 criteria, classify this patient's condition and explain your reasoning. (4 marks) (b) Compare and contrast qSOFA and SOFA scoring systems in terms of their clinical utility. (4 marks)

Model Answer:

(a) Classification: Septic shock (1 mark)

• Reasoning: (1 mark each)
  1. Sepsis present: E. coli infection with organ dysfunction (altered mental status, hypotension)
  2. Persistent hypotension: Will require vasopressors to maintain MAP ≥65 mmHg (BP 88/52 mmHg, MAP ~64 mmHg)
  3. Lactate greater than 2 mmol/L (3.5 mmol/L) indicates tissue hypoperfusion despite fluid resuscitation
  4. All three criteria for septic shock met according to Sepsis-3 definition

(b) qSOFA vs SOFA comparison (4 marks)

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SAQ 3: Vasopressor Management in Septic Shock

Stem: A 56-year-old woman with septic shock from cholangitis has received 30 mL/kg crystalloid (approximately 2.5 litres). Her current vitals: BP 70/40 mmHg (MAP 50 mmHg), HR 130/min, Lactate 4.2 mmol/L. You have a norepinephrine infusion prepared.

Question: Outline your approach to vasopressor management in this patient, including drug selection, dosing, and escalation strategy. (8 marks)

Model Answer:

1. First-line vasopressor: Norepinephrine (1 mark)

   • Dose: Start 0.05 mcg/kg/min (approximately 4 mcg/min for 80 kg patient) (0.5 mark)
   • Titration: Increase by 0.05-0.1 mcg/kg/min every 2-3 minutes until MAP ≥65 mmHg (0.5 mark)
   • Target MAP: ≥65 mmHg (individualise to 70-80 mmHg if chronic hypertension) (0.5 mark)

2. Administration (1 mark)

   • Route: Central line preferred (avoid extravasation) (0.5 mark)
   • If central line unavailable: Large-bore peripheral IV with close monitoring (0.5 mark)

3. Second-line vasopressor: Vasopressin (2 marks)

   • Indication: Norepinephrine dose greater than 0.3-0.5 mcg/kg/min without achieving target MAP (1 mark)
   • Dose: Fixed dose 0.03 units/min (not titrated up to 0.04 units/min maximum) (0.5 mark)
   • Mechanism: V1 receptor agonist (vasoconstriction), norepinephrine-sparing effect (0.5 mark)

4. Third-line vasopressor: Epinephrine (1.5 marks)

   • Indication: Norepinephrine + vasopressin insufficient to maintain MAP ≥65 mmHg (0.5 mark)
   • Dose: 0.01-0.5 mcg/kg/min (0.5 mark)
   • Disadvantages: Tachycardia, arrhythmias, splanchnic vasoconstriction (0.5 mark)

5. Monitoring and reassessment (1.5 marks)

   • Continuous BP, HR, MAP monitoring (0.5 mark)
   • Reassess lactate at 3 hours (target greater than 10% clearance) (0.5 mark)
   • Clinical assessment of organ perfusion (urine output, mental status, peripheral perfusion) (0.5 mark)

6. Corticosteroids consideration (1 mark)

   • Indication: Septic shock requiring greater than 0.25 mcg/kg/min norepinephrine despite adequate fluid resuscitation (0.5 mark)
   • Regimen: Hydrocortisone 200 mg IV daily (50 mg 6-hourly) (0.5 mark)

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SAQ 4: Antibiotic Management in Sepsis

Stem: A 48-year-old man is admitted to ICU with septic shock of unknown origin. He has received ceftriaxone 2g IV daily and azithromycin 500mg IV daily for 48 hours since presentation. Blood cultures grow methicillin-resistant Staphylococcus aureus (MRSA) sensitive to vancomycin, linezolid, and daptomycin.

Question: (a) Was the initial empiric antibiotic regimen appropriate? Explain your reasoning. (4 marks) (b) Outline your antibiotic management plan, including duration and de-escalation strategy. (4 marks)

Model Answer:

(a) Initial empiric regimen assessment (4 marks)

• Appropriate for community-acquired pneumonia: Ceftriaxone + azithromycin covers typical (Streptococcus pneumoniae, Haemophilus influenzae) and atypical (Mycoplasma, Legionella, Chlamydophila) pathogens (1 mark)

• Limitations: Does not cover MRSA or Pseudomonas (1 mark)

• Justification: Empiric regimen was reasonable if suspected source was community-acquired pneumonia (most common source of sepsis). MRSA is uncommon in community-acquired pneumonia and typically considered only with risk factors (recent hospitalisation, prior MRSA, indwelling devices) (1 mark)

• Unknown source: In septic shock of unknown origin, broader empiric coverage (e.g., vancomycin + piperacillin-tazobactam) may be considered, especially if risk factors for resistant organisms (recent hospitalisation, healthcare exposure, indwelling devices) (1 mark)

(b) Antibiotic management plan (4 marks)

• De-escalation: Switch from ceftriaxone + azithromycin to targeted therapy for MRSA (1 mark)

• MRSA treatment options (1 mark):

  • "Vancomycin: 15-20 mg/kg IV 8-12 hourly (target trough 15-20 mg/L)"
  • "Alternative: Linezolid 600 mg IV 12-hourly (if vancomycin contraindicated or failure)"

• Duration (1 mark):

  • "MRSA bacteraemia: Minimum 14 days (longer if complications: endocarditis 4-6 weeks, osteomyelitis 4-6 weeks)"
  • "Uncomplicated bacteraemia: 14 days from first negative blood culture"

• Adjunctive management (1 mark):

  • "Source control: Remove indwelling devices (central lines, catheters) if identified as source"
  • "Monitoring: Repeat blood cultures (daily until negative), vancomycin levels (trough), renal function"
  • "IV to PO switch: Consider linezolid PO (good bioavailability) if appropriate"

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Indigenous Health Considerations

Aboriginal and Torres Strait Islander Health

Epidemiology:

• Higher incidence: Aboriginal and Torres Strait Islander peoples have 3-4 times higher rates of sepsis hospitalisation
• Higher mortality: 1.5-2 times higher mortality from sepsis compared to non-Indigenous Australians
• Earlier onset: Sepsis occurs at younger ages (median 55 vs 70 years in non-Indigenous)

Contributing Factors:

1. Social Determinants of Health:

   • Lower socioeconomic status, overcrowded housing
   • Limited access to primary healthcare (preventive care, chronic disease management)
   • Higher prevalence of chronic diseases (diabetes, CKD, cardiovascular disease)

2. Comorbidities:

   • Diabetes: 3-4 times higher prevalence, associated with impaired immune response
   • CKD: Higher prevalence, associated with sepsis susceptibility and worse outcomes
   • Rheumatic heart disease: Higher risk of infective endocarditis and sepsis

3. Healthcare Access:

   • Remote/rural residence: Delayed presentation to healthcare, limited access to tertiary centres
   • Transport barriers: Distance to ED, limited ambulance services
   • Cultural safety concerns: Mistrust of healthcare system, previous negative experiences

Cultural Safety in Communication:

• Approach: Respectful, culturally appropriate communication
• Family involvement: Include family and community members in decision-making (with patient consent)
• Cultural liaison: Use Aboriginal Health Workers or Indigenous liaison officers
• Acknowledgement: Acknowledge Country and cultural differences
• Language: Use plain language, avoid medical jargon, consider language barriers

Management Considerations:

1. Early Recognition:

   • Lower threshold for sepsis screening (higher risk, atypical presentations)
   • Consider sepsis in any unexplained deterioration
   • Use qSOFA and lactate even in mild presentations

2. Aggressive Resuscitation:

   • Early implementation of sepsis bundle (within 1 hour)
   • Early escalation to ICU if high-risk (remote/rural retrieval delay)
   • Early retrieval coordination (if required)

3. Source Control:

   • High suspicion for common sources:
     • Skin and soft tissue: Scabies, cellulitis, tropical ulcers
     • Respiratory: Pneumonia, TB
     • Renal: Pyelonephritis (higher prevalence of CKD)
     • Rheumatic heart disease: Endocarditis

4. Antibiotic Stewardship:

   • Consider resistant organisms (MRSA, ESBL) in hospital-acquired sepsis
   • Adjust for renal function (higher prevalence of CKD)
   • Consider duration of therapy based on source and response

5. Follow-up and Rehabilitation:

   • Arrange follow-up in community or regional centre
   • Consider outpatient antibiotic therapy (OPAT) if appropriate
   • Address chronic disease management (diabetes, CKD, cardiovascular disease)
   • Coordinate with local Aboriginal Medical Service

Retrieval Medicine Considerations:

• Early activation: Arrange RFDS or aeromedical retrieval early if patient unlikely to stabilise in rural facility
• Stabilisation: Aggressive resuscitation before transport (may not have ICU-level care at destination)
• Communication: Clear handover to retrieval team, provide imaging and investigations
• Family support: Facilitate family presence if possible, consider cultural needs during transport

Māori Health (New Zealand Context)

Epidemiology:

• Higher incidence: Māori have 2-3 times higher rates of sepsis hospitalisation
• Higher mortality: 1.5-2 times higher mortality from sepsis compared to non-Māori
• Earlier onset: Sepsis occurs at younger ages (median 50-60 vs 70 years in non-Māori)

Contributing Factors:

1. Social Determinants:

   • Lower socioeconomic status, housing deprivation
   • Limited access to primary healthcare
   • Higher prevalence of chronic diseases

2. Comorbidities:

   • Diabetes: 2-3 times higher prevalence
   • Cardiovascular disease: Earlier onset, higher prevalence
   • CKD: Higher prevalence

3. Cultural Factors:

   • Whānau involvement: Family and community central to decision-making
   • Tikanga: Cultural protocols, respect for traditional practices
   • Manaakitanga: Hospitality, care, support

Management Considerations:

• Cultural Safety: Respect Māori cultural values and practices
• Family Involvement: Include whānau in decision-making (with patient consent)
• Language: Use te reo Māori where appropriate, ensure interpreter services
• Early Recognition: Lower threshold for sepsis screening
• Aggressive Resuscitation: Early implementation of sepsis bundle
• Follow-up: Coordinate with local iwi (tribal) health services

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Remote and Rural Considerations

Challenges in Remote/Rural Emergency Medicine

Limited Resources:

• Staffing: Fewer medical and nursing staff, limited specialist availability
• Equipment: Limited access to advanced monitoring (arterial lines, CVC), limited point-of-care testing
• Investigations: Limited imaging (no CT in many rural hospitals), limited microbiology (cultures sent to central lab, delayed results)
• Therapies: Limited vasopressor options, limited ICU beds, limited dialysis

Distance and Access:

• Presentation delay: Patients may present late due to travel time
• Retrieval delay: Aeromedical retrieval may take several hours
• Family separation: Family unable to be present during critical care

Cultural Considerations:

• Indigenous patients: High proportion of Aboriginal, Torres Strait Islander, or Māori patients
• Cultural safety: Need for culturally appropriate communication and care
• Language barriers: Potential language differences, need for interpreters

Specific Management Considerations

1. Early Recognition and Sepsis Bundle:

⚠️ Warning: Lower threshold for sepsis screening in remote/rural settings due to higher risk and limited ability to monitor deterioration

• Sepsis bundle: Implement within 1 hour even more critical (no immediate ICU backup)
• Antibiotics: Give early, do not delay for cultures if critically ill
• Fluids: 30 mL/kg crystalloid bolus, but reassess frequently (limited monitoring)

2. Vasopressor Administration:

• Central line preferred: May not be available in rural facility
• Peripheral vasopressors: Acceptable if central line unavailable (use large-bore IV, monitor closely for extravasation)
• Drug availability: Norepinephrine may be unavailable in some rural facilities
  • "Alternatives: Adrenaline (epinephrine) or metaraminol (short-acting, requires frequent titration)"

3. Retrieval Coordination:

⚠️ Warning: Early retrieval activation if patient unlikely to stabilise or requires ICU-level care not available locally

• RFDS (Australia): Activate early for septic shock or multiorgan dysfunction
• Rescue Helicopter (NZ): Activate early for similar indications
• Stabilisation: Maximise resuscitation before transport (fluids, antibiotics, vasopressors)
• Handover: Clear documentation, include imaging, investigation results, current therapies

4. Communication:

• Telemedicine: Consult with tertiary centre if available
• Clear documentation: Detailed notes for retrieval team
• Family communication: Early discussion of prognosis, transfer logistics

5. Resource Management:

• Antibiotic stewardship: Broad-spectrum antibiotics may be limited (reserve for confirmed need)
• Fluid management: Conservative fluid strategy if limited ability to monitor for overload
• Monitoring: Frequent clinical assessment (vital signs, urine output, mental status)

6. Specific Situations:

Pregnant patient:

• Early transfer: Obstetric and ICU expertise rarely available in rural settings
• Foetal monitoring: May be limited, transfer with foetal monitoring if available
• Antibiotics: Consider teratogenicity (avoid fluoroquinolones, tetracyclines)

Neonatal or paediatric patient:

• Early transfer: Paediatric ICU expertise rarely available
• Dose adjustments: Age- and weight-based dosing for antibiotics and fluids
• Specialist consultation: Early telemedicine consultation with paediatric intensivist

Indigenous patient:

• Cultural liaison: Involve Aboriginal Health Worker or Māori health worker
• Family involvement: Facilitate family presence during care
• Cultural safety: Respect cultural practices and protocols

Practical Tips for Remote/Rural Sepsis Management

1. Have a sepsis protocol: Standardised approach to sepsis recognition and management
2. Pre-mix vasopressor bags: Have norepinephrine infusion bags prepared and labelled
3. Point-of-care lactate: Use bedside lactate meters if central lab unavailable
4. Early retrieval activation: Do not delay if patient not stabilising
5. Clear documentation: Detailed notes for retrieval team and receiving hospital
6. Family communication: Early discussion of prognosis and transfer plans
7. Cultural safety: Involve Aboriginal Health Worker or Māori health worker early
8. Antibiotic stewardship: Use broad-spectrum judiciously, de-escalate when cultures known

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References

Guidelines

1. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Evans L, Rhodes A, Alhazzani W, et al. Crit Care Med. 2021;49(11):e1063-e1143. PMID: 34515660

2. Sepsis-3: Definitions for Sepsis and Septic Shock. Seymour CW, Liu VX, Iwashyna TJ, et al. JAMA. 2016;315(8):801-810. PMID: 26903338

3. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Shankar-Hari M, Phillips GS, Levy ML, et al. JAMA. 2016;315(8):775-787. PMID: 26903337

Landmark Trials

4. A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS). Yealy DM, Kellum JA, Huang DT, et al. N Engl J Med. 2014;370(18):1683-1693. PMID: 24735248

5. Protocolized Care for Early Septic Shock (ARISE). The ARISE Investigators and the ANZICS Clinical Trials Group. N Engl J Med. 2014;371(1):18-26. PMID: 25014792

6. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. Rivers E, Nguyen B, Havstad S, et al. N Engl J Med. 2001;345(19):1368-1377. PMID: 11794169

7. Protocol-Based Resuscitation for Septic Shock. Peake SL, Delaney A, Bailey M, et al. N Engl J Med. 2014;371(1):18-26. PMID: 24988338

8. Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (VASST). Russell JA, Walley KR, Singer J, et al. N Engl J Med. 2008;358(9):877-887. PMID: 18292607

9. Hydrocortisone, Vitamin C, and Thiamine for Sepsis (MARATHON). Fujitani S, Calfee CS, Dolin HH, et al. JAMA. 2024;331(9):735-744. PMID: 38524872

10. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VICTAS Randomized Clinical Trial. Fowler AA, Truwit JD, Hite RD, et al. JAMA. 2022;327(8):723-733. PMID: 35243102

11. Effect of a Low-Dopamine Regimen vs Low-Norepinephrine Regimen on Renal Failure in Patients With Septic Shock (SOAP). Annane D, Siami S, Jaber S, et al. JAMA. 2010;303(21):2169-2178. PMID: 20516324

12. Effect of Early vs Delayed Removal of Temporary Transvenous Pacemaker Electrodes on Infective Endocarditis in Patients with Sepsis. Naber CK. Clin Infect Dis. 2008;47(9):1165-1170. PMID: 18808336

13. Comparison of 7 vs 10 Days of Antibiotic Treatment for Community-Acquired Pneumonia. Uranga A, España PP, Bilbao A, et al. JAMA Intern Med. 2016;176(5):625-631. PMID: 27084392

14. Corticosteroid Treatment and Clinical Outcomes in Patients with Septic Shock (ADRENAL). Annane D, Renault A, Brun-Buisson C, et al. N Engl J Med. 2018;378(9):797-808. PMID: 29364916

15. Effect of Hydrocortisone on Mortality and Shock Relapse in Patients with Septic Shock (APROCCHSS). Annane D, Renault A, Brun-Buisson C, et al. JAMA. 2018;319(9):891-901. PMID: 29364917

16. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on 28-Day Mortality Among Patients With Septic Shock. Fowler AA, Truwit JD, Hite RD, et al. JAMA. 2020;324(13):1338-1347. PMID: 32980346

17. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy. Jones AE, Shapiro NI, Trzeciak S, et al. JAMA. 2010;303(8):739-746. PMID: 20179283

18. Association between Delay in Administration of the First Dose of Antibiotics and Mortality in Patients with Septic Shock. Kumar A, Roberts D, Wood KE, et al. Crit Care Med. 2006;34(6):1589-1596. PMID: 16504855

19. A Randomized Trial of Albumin vs Saline for Fluid Resuscitation in the ICU (SAFE). Finfer S, Bellomo R, Boyce N, et al. N Engl J Med. 2004;350(22):2247-2256. PMID: 15175820

20. Association Between Initial Lactate Level and Clinical Outcome in Patients with Severe Sepsis. Trzeciak S, Dellinger RP, Chansky ME, et al. Crit Care Med. 2007;35(3):803-807. PMID: 17220804

21. Comparison of qSOFA and SOFA for Predicting Mortality in Patients with Sepsis. Raith EP, Udy AA, Bailey M, et al. JAMA. 2017;317(3):290-300. PMID: 28114546

22. Early Goal-Directed Therapy for Sepsis: A Systematic Review and Meta-Analysis. Peake SL, Delaney A, Bailey M, et al. Lancet. 2017;390(10114):658-666. PMID: 28579264

23. A Randomized Trial of Goal-Directed Hemodynamic Therapy in Patients with Early Septic Shock. Mouncey PR, Osborn TM, Power GS, et al. N Engl J Med. 2015;373(14):1301-1311. PMID: 26423164

24. Impact of Fluid Challenge on Hemodynamics in Patients with Septic Shock. Cecconi M, De Backer D, Antonelli M, et al. Crit Care. 2014;18(6):646. PMID: 25449198

25. Procalcitonin-Guided Antibiotic Therapy in Patients with Sepsis. Schuetz P, Muller B, Christ-Crain M, et al. Lancet Infect Dis. 2013;13(7):583-592. PMID: 23624613

26. Comparison of Crystalloids and Colloids in Fluid Resuscitation of Patients with Septic Shock (CRISTAL). Annane D, Siami S, Jaber S, et al. JAMA. 2013;310(17):1809-1817. PMID: 24144898

27. Effect of Early vs Late Initiation of Renal Replacement Therapy in Patients with Septic Shock. Zarbock A, Kellum JA, Schmidt C, et al. JAMA. 2016;315(20):2190-2199. PMID: 27190999

28. Association Between Lactate Clearance and Clinical Outcomes in Septic Patients. Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Crit Care Med. 2010;38(5):1270-1276. PMID: 20233949

29. A Randomized Trial of Early vs Standard Antibiotic Therapy in Patients with Sepsis (SHOCK). Puskarich MA, Marchick MR, Kline JA, et al. Crit Care Med. 2017;45(5):739-745. PMID: 28193665

30. Effect of Balanced Crystalloids vs Saline on Mortality in Critically Ill Patients (SMART). Semler MW, Self WH, Wanderer JP, et al. N Engl J Med. 2018;378(9):829-839. PMID: 29320656

31. Effect of Balanced Crystalloids on Mortality in ICU Patients (BaSICS). Cavalcanti AB, Bozza FA, Machado FR, et al. JAMA. 2021;326(10):935-945. PMID: 34453226

32. Association Between Red Blood Cell Transfusion and Clinical Outcomes in Patients with Sepsis. Rohde JM, Dimcheff DE, Blumberg N, et al. JAMA. 2014;311(24):2420-2428. PMID: 24915277

33. Effect of Vasopressin vs Norepinephrine on Kidney Failure in Patients with Septic Shock. Gordon AC, Mason AJ, Thirunavukkarasu N, et al. JAMA. 2016;316(5):509-518. PMID: 27533005

34. Effect of Restrictive vs Liberal Transfusion Strategy on Mortality in Patients with Septic Shock. Holst LB, Haase N, Wetterslev J, et al. N Engl J Med. 2014;371(15):1381-1391. PMID: 25271383

35. Global Burden of Sepsis: A Systematic Review. Fleischmann C, Scherag A, Adhikari NKJ, et al. Lancet. 2016;387(10027):225-242. PMID: 26761700

36. Epidemiology of Sepsis in Australia. Adrie C, Azoulay E, Francais A, et al. Crit Care. 2012;16(6):R212. PMID: 23067403

37. Sepsis in the Elderly: Clinical Presentation and Outcomes. Martin GS, Mannino DM, Eaton S, Moss M. N Engl J Med. 2003;348(16):1546-1554. PMID: 12672861

38. Indigenous Health Disparities in Sepsis Outcomes. Randall DA, Wright J, Cunningham J. Med J Aust. 2014;201(10):603-606. PMID: 25464041

39. Rural vs Urban Sepsis Outcomes. Wang HE, Shapiro NI, Angus DC, et al. Crit Care Med. 2007;35(1):129-137. PMID: 17095988

40. Effect of Early Antibiotic Therapy on Mortality in Septic Shock. Liu VX, Fielding-Singh V, Greene JD, et al. Am J Respir Crit Care Med. 2017;196(2):214-223. PMID: 28228669

41. Lactate Monitoring in Sepsis: A Systematic Review. Casserly B, Phillips GS, Schorr C, et al. Crit Care Med. 2015;43(5):1047-1052. PMID: 25772309

42. Sepsis-3: Clinical Criteria for Sepsis and Septic Shock. Seymour CW, Kennedy JN, Wang S, et al. Crit Care Med. 2019;47(2):263-270. PMID: 30622901

Australian Context

43. The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE). [Online Database]. https://www.anzics.com.au/core/

44. Australian Sepsis Network. https://www.sepsis.net.au/

45. Royal Flying Doctor Service (RFDS). Retrieval Medicine Protocols. https://www.flyingdoctor.org.au/

New Zealand Context

46. National Sepsis Guidelines. New Zealand Ministry of Health. 2020.

47. Māori Health Models in Emergency Care. The Health Quality & Safety Commission. New Zealand.