Smoke Inhalation Injury

Quick Answer

Smoke inhalation injury is a potentially life-threatening condition comprising three distinct mechanisms: thermal injury (supraglottic airway oedema), chemical injury (infraglottic mucosal damage from irritant gases), and systemic toxicity (carbon monoxide and cyanide poisoning). [1] Management priorities include early airway protection before oedema progresses, high-flow 100% oxygen for CO poisoning (reducing COHb half-life from 300 to 60-90 minutes), and empirical hydroxocobalamin for suspected cyanide toxicity. [2,3] Inhalation injury increases burn mortality by 20-40% and is present in 25-30% of burn unit admissions. [4]

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CICM Exam Focus

SAQ Stems Likely to Appear

• "A 45-year-old is retrieved from a house fire with facial burns and altered consciousness. Discuss your assessment and initial management."
• "Outline the pathophysiology of smoke inhalation injury and the mechanisms of carbon monoxide and cyanide toxicity."
• "Discuss the indications for intubation in smoke inhalation and the evidence for hyperbaric oxygen therapy."
• "Describe the bronchoscopic grading of inhalation injury and its prognostic significance."

Hot Case Presentations

• Intubated burn patient with rising airway pressures and carbonaceous secretions
• Patient post-house fire with unexplained persistent metabolic acidosis
• Difficult weaning in patient with inhalation injury and ARDS
• Bushfire victim with facial burns requiring airway decision

Viva Topics

• Pathophysiology: thermal vs chemical vs systemic injury
• Airway timing decisions and techniques
• CO vs cyanide: mechanism and treatment comparison
• Bronchoscopy role and grading systems
• Nebulised heparin/NAC evidence (HEPBURN trial)
• HBOT indications and evidence (Weaver trial)

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Key Points

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Red Flags and Safety Alerts

⚠️ Red Flag: Stridor or Hoarseness: These are LATE signs of upper airway oedema. If present, intubation is URGENT and may be extremely difficult due to oedema. Prepare for surgical airway.

⚠️ Red Flag: Loss of Consciousness at Scene: Presume significant CO AND cyanide poisoning. Give 100% O2 immediately and empirical hydroxocobalamin if available. Do NOT wait for COHb levels.

⚠️ Red Flag: Enclosed Space Exposure: Dramatically increases risk of toxic gas inhalation. A patient found in an enclosed burning building has presumed inhalation injury until proven otherwise.

⚠️ Red Flag: Progressive Oedema: Facial and airway oedema continues to worsen for 12-24 hours. A patient who looks "OK" at scene may have complete airway obstruction within hours. EARLY intubation saves lives.

⚠️ Red Flag: Unexplained Lactic Acidosis (>10 mmol/L): In fire victims with adequate oxygenation but persistent elevated lactate, strongly suspect cyanide poisoning. Treat empirically with hydroxocobalamin.

⚠️ Red Flag: Circumferential Neck or Facial Burns: External burns predict internal thermal injury. These patients have HIGH probability of airway oedema requiring intubation.

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Definition and Epidemiology

Definition

Smoke inhalation injury is damage to the respiratory tract caused by the inhalation of hot gases, particulate matter, and toxic combustion products from fire. [1] It represents a syndrome of thermal, chemical, and systemic injury that significantly increases morbidity and mortality in burn patients.

Epidemiology

Australian/NZ Context

Bushfire Season

• Australia experiences significant bushfire activity annually, with the 2019-20 "Black Summer" causing unprecedented health impacts
• 445 deaths and >3,000 respiratory hospitalisations attributed to bushfire smoke [6]
• PM2.5 levels exceeded 20x WHO guidelines in affected regions

Indigenous Health Considerations

• Aboriginal and Torres Strait Islander Australians are hospitalised for burn injuries at 2-3 times the rate of non-Indigenous Australians [8]
• Higher rates of flame-related burns, including campfire and bushfire injuries
• Children particularly affected - Indigenous children more likely to have outdoor flame burns [9]
• Remote communities face delayed access to burn centres
• Cultural safety considerations essential in family communication

Māori Health

• Higher baseline respiratory disease prevalence increases smoke vulnerability
• Whānau involvement critical in decision-making
• Tikanga (cultural practices) must be respected
• Māori Health Workers facilitate communication

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Pathophysiology

Overview: Three Mechanisms of Injury

Smoke inhalation causes injury through three distinct but often overlapping mechanisms: [1,10]

1. Thermal Injury (Supraglottic)

Exam Detail: Why Thermal Injury is Limited to the Upper Airway

The upper airway is remarkably effective at heat exchange due to its large surface area and vascular mucosa. Dry air at 300°C cools to near body temperature by the time it reaches the carina. [10]

Exceptions to Upper Airway Limitation:

• Steam inhalation: Steam has 4,000x the heat capacity of dry air and can cause lower airway thermal injury
• Explosion injuries: Flash ignition causes direct thermal damage throughout the airway

Pathological Changes:

1. Immediate: Mucosal erythema, oedema formation
2. Hours 6-12: Progressive oedema of supraglottic structures (epiglottis, aryepiglottic folds, false vocal cords)
3. Hours 12-24: Peak oedema - critical period for airway compromise
4. Days 3-5: Resolution begins if no secondary infection

Clinical Significance:

• Airway oedema is PROGRESSIVE and often underestimated initially
• External facial burns correlate but do not reliably predict airway involvement
• Intubation difficulty increases exponentially as oedema develops
• The "golden window" for safe intubation is BEFORE significant oedema

2. Chemical Injury (Infraglottic)

Exam Detail: Mechanism of Chemical Injury

Particulate matter <5 μm in diameter (PM2.5) reaches the lower airways and alveoli. [11] Chemical irritants adsorbed to particles react with respiratory mucosa to cause injury.

Key Chemical Irritants in Smoke:

Pathological Cascade:

1. Immediate (minutes-hours)

   • Ciliary paralysis → impaired mucociliary clearance
   • Mucosal sloughing → cast formation
   • Bronchospasm → increased airway resistance

2. Early (hours-days)

   • Inflammatory cell infiltration
   • Increased microvascular permeability
   • Pulmonary oedema formation
   • Fibrin deposition → obstructing casts

3. Delayed (days-weeks)

   • Bacterial colonisation and VAP
   • ARDS development
   • Bronchiolitis obliterans (rare)

Cast Formation:

• Fibrin, cellular debris, and mucus form obstructing plugs
• Casts cause atelectasis, V/Q mismatch, and air-trapping
• Therapeutic bronchoscopy may be required for removal

3. Systemic Toxicity

Carbon Monoxide (CO) Poisoning

Exam Detail: Mechanism of CO Toxicity

Carbon monoxide exerts toxicity through three primary mechanisms: [12,13]

1. Carboxyhaemoglobin (COHb) Formation

• CO binds haemoglobin with 200-250x greater affinity than O2
• Each haemoglobin molecule binding CO cannot transport O2
• Result: Reduced blood oxygen content

2. Left Shift of Oxygen-Haemoglobin Dissociation Curve

• COHb causes conformational change in haemoglobin
• Remaining O2-Hb complex has increased affinity (decreased P50)
• Oxygen is bound more tightly and released less readily to tissues
• Result: Impaired oxygen delivery even with adequate content

3. Cytochrome Oxidase Inhibition

• CO binds to cytochrome c oxidase (Complex IV) in mitochondria
• Directly inhibits aerobic ATP production
• Results in cellular hypoxia even if O2 delivery restored
• Mechanism of delayed neurological sequelae (DNS)

Additional Mechanisms:

• Binding to myoglobin → myocardial dysfunction
• Lipid peroxidation → oxidative stress
• Neutrophil activation → inflammation and reperfusion injury

COHb Levels and Correlation:

CRITICAL: COHb levels correlate POORLY with severity due to:

• Time since exposure (elimination ongoing)
• Pre-hospital oxygen administration
• Individual variation in tissue binding
• Does not reflect cytochrome oxidase binding

Cyanide (HCN) Poisoning

Exam Detail: Mechanism of Cyanide Toxicity

Hydrogen cyanide (HCN) is produced by combustion of nitrogen-containing materials (wool, silk, nylon, polyurethane, plastics). [14,15]

Primary Mechanism: Cytochrome Oxidase Inhibition

• CN- binds to Fe3+ (ferric iron) in cytochrome a3
• Blocks electron transport chain at Complex IV
• Aerobic metabolism ceases despite adequate oxygen
• Result: Histotoxic hypoxia (tissue hypoxia with normal PaO2)

Metabolic Consequences:

1. ATP production shifts to anaerobic glycolysis
2. Lactate production increases dramatically (>10 mmol/L)
3. Metabolic acidosis develops rapidly
4. Cellular energy failure → organ dysfunction

Why Lactate is the Key Indicator:

• Blood cyanide levels are rarely available in time to guide treatment
• Lactate >10 mmol/L in fire victim = strong predictor of CN toxicity
• Lactate >8 mmol/L has 94% sensitivity for CN poisoning [16]

Synergism with CO:

• Both toxins impair cellular oxygen utilisation
• CO reduces O2 delivery, CN blocks O2 utilisation
• Combined effect is more than additive
• "Double hit" explains profound hypoxia despite resuscitation

Clinical Features of Cyanide Poisoning:

Components of Smoke

Exam Detail: Major Components and Their Effects:

Particle Size Determines Deposition:

• 10 μm: Nasal passages (filtered)

• 5-10 μm: Larger bronchi
• 1-5 μm: Small airways
• <1 μm: Alveoli (most damaging)

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Clinical Assessment

History Taking

Clinical Pearl: Critical Historical Questions (CICM Exam Favourite)

1. Enclosed Space?

   • House, room, vehicle = high toxic gas exposure
   • Open area = lower systemic toxicity risk

2. Duration of Exposure?

   • Time trapped correlates with toxin dose
   • Prolonged = higher CO/CN levels

3. Loss of Consciousness?

   • ANY LOC = assume significant CO/CN poisoning
   • Mandates high-flow O2 and consider HBOT/antidotes

4. Material Burning?

   • Plastics, synthetics = HCN, HCl, phosgene
   • Wood, natural materials = CO, aldehydes

5. Explosion or Steam?

   • Explosion = lower airway thermal injury possible
   • Steam = 4000x heat capacity, lower airway burns

6. Pre-existing Conditions?

   • Asthma, COPD = higher bronchospasm risk
   • Cardiac disease = lower CO tolerance

Physical Examination

Systematic Examination for Inhalation Injury:

Bronchoscopy Grading

Exam Detail: Abbreviated Injury Score (AIS) for Inhalation Injury [17,18]

Bronchoscopy within 24 hours of admission is the gold standard for diagnosis and grading.

Prognostic Value:

Why AIS Doesn't Independently Predict Mortality:

• Mortality driven primarily by TBSA and age
• Baux score (Age + TBSA) remains best predictor
• Inhalation injury adds mortality but AIS grade less important than presence/absence

Therapeutic Role of Bronchoscopy:

• Removal of carbonaceous material
• Lavage of fibrin casts
• Assessment of mucosal healing
• Guidance for weaning

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Investigations

Immediate (Pre-hospital/ED)

⚠️ Red Flag: Pulse Oximetry Cannot Distinguish COHb from OxyHb: Standard pulse oximetry reads COHb as oxyhaemoglobin. A SpO2 of 100% may coexist with lethal COHb levels. Always use co-oximetry in fire victims.

ICU Investigations

Imaging

Exam Detail: Chest X-Ray Findings:

CT Chest (if performed):

• Ground-glass opacities
• Consolidation (dependent distribution initially)
• Air-trapping (bronchiolitis)
• Rarely indicated acutely

Key Point: A normal initial CXR does NOT exclude significant inhalation injury. Clinical assessment and bronchoscopy are more sensitive.

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Airway Management

Decision to Intubate

Clinical Pearl: Indications for Early Intubation in Smoke Inhalation [20,21]

Absolute Indications (Intubate NOW):

• Stridor
• Respiratory distress/failure
• GCS ≤8
• Upper airway obstruction
• Severe facial/neck oedema

Strong Indications (Intubate EARLY):

• Hoarseness or voice change
• Carbonaceous sputum
• Facial burns (especially circumferential)
• Oropharyngeal oedema/erythema
• Burns >40% TBSA requiring fluid resuscitation
• Need for inter-hospital transfer
• Anticipated deterioration

"When in doubt, intubate early" - The penalty for late intubation (impossible airway, emergency surgical airway, death) far exceeds the penalty for early intubation (few extra ventilator days).

Timing Considerations

Exam Detail: The "Window of Opportunity" Concept

Airway oedema is progressive and predictable:

• 0-6 hours: Minimal oedema, intubation usually straightforward
• 6-12 hours: Developing oedema, intubation more difficult
• 12-24 hours: PEAK oedema, intubation may be impossible orally
• 24-48 hours: Plateau then gradual resolution (if no infection)

Practical Implications:

1. Assess airway immediately and regularly
2. If ANY concern, intubate in the "golden window" (<6 hours)
3. Do NOT wait for definitive signs (stridor)
4. Plan for surgical airway if delayed presentation with oedema

Intubation Technique

Exam Detail: Approach to Intubation in Inhalation Injury [22]

Preparation:

• Senior airway operator (most experienced available)
• Full difficult airway equipment at bedside
• Surgical airway equipment prepared
• ENT/Anaesthesia backup if available

Technique Considerations:

Video vs Direct Laryngoscopy:

• Evidence slightly favours video for first-pass success in difficult airways [22]
• However, experienced operators achieve similar success with either
• Video may be particularly helpful with facial burns limiting mouth opening

Rapid Sequence Induction Modifications:

• Ketamine (1-2 mg/kg) often preferred (haemodynamic stability, bronchodilation)
• Avoid suxamethonium if burns >24h old (hyperkalaemia risk)
• Rocuronium acceptable alternative

Post-Intubation:

• Secure tube robustly (tapes may not adhere to burned skin)
• Consider tube tie or sutures
• Document tube position and depth
• Plan for oedema worsening (tube may become occluded)

Surgical Airway

Exam Detail: When to Proceed to Surgical Airway:

• Failed oral intubation with "can't intubate, can't oxygenate" (CICO)
• Massive facial/neck oedema precluding oral access
• Facial trauma preventing access

Technique:

• Surgical cricothyroidotomy preferred in adults
• Needle cricothyroidotomy temporary only
• Tracheostomy may be required for long-term (consider after oedema resolution)

Considerations in Burns:

• Neck burns may distort anatomy
• Tracheostomy through burn is relatively contraindicated (infection)
• May need lateral or low approach

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ICU Management

Initial Resuscitation

Immediate Priorities:

1. Airway: Secure if any concern (see above)
2. Breathing: High-flow 100% O2 via NRB mask or ventilator
3. Circulation: IV access, fluid resuscitation (Parkland formula for burns)
4. Disability: GCS, pupil assessment
5. Exposure: Full burns assessment (TBSA)

Carbon Monoxide Treatment

Exam Detail: High-Flow Oxygen Therapy [12,23]

Administration:

• Non-rebreather mask with 15 L/min flow
• Continue until COHb <5% AND asymptomatic
• Typically requires 4-6 hours of high-flow O2

Duration of Treatment:

• Minimum 6 hours of 100% O2
• May require longer if initial COHb high
• Serial COHb measurements guide therapy

Hyperbaric Oxygen Therapy (HBOT)

Exam Detail: The Weaver Trial (PMID: 12362006) [23]

Study Design:

• Double-blind RCT, 152 patients
• 3 HBOT sessions (100% O2 at 3 ATA) within 24 hours vs normobaric O2
• Primary outcome: Cognitive sequelae at 6 weeks

Key Results:

• Cognitive sequelae at 6 weeks: 25% (HBOT) vs 46% (NBO), p=0.007
• Benefit persisted at 12 months (p=0.04)
• NNT = 5 to prevent one case of DNS

HBOT Indications (Based on Weaver Criteria):

• Loss of consciousness (even if transient)
• Neurological symptoms (confusion, ataxia, seizures)
• COHb >25% (or >15% in pregnancy)
• Metabolic acidosis (pH <7.1)
• Age >36 years
• Exposure duration >24 hours

Contraindications to HBOT:

• Untreated pneumothorax
• Haemodynamic instability
• Logistics (transfer to HBOT centre)

Australian Context:

• Limited HBOT availability (major metropolitan centres only)
• Transfer decisions must weigh benefit vs delay in burn care
• Discuss with toxicology and HBOT centre

Conflicting Evidence (Scheinkestel Trial - PMID: 10189311):

• Found no benefit (possibly harmful)
• Criticised for: daily treatments × 3-6 days, oxygen toxicity, sicker HBO group
• Weaver trial methodology considered superior

Cochrane Review (PMID: 21491387):

• Evidence conflicting but leans toward HBOT for high-risk patients
• Recommends HBOT if criteria met and logistically feasible

Cyanide Treatment

Exam Detail: Hydroxocobalamin (Cyanokit) [24,25,26]

Mechanism:

• Cobalt in hydroxocobalamin binds CN- to form cyanocobalamin (Vitamin B12)
• Cyanocobalamin excreted renally
• Does NOT induce methaemoglobinaemia (safe in concurrent CO poisoning)

Dosing:

• Adults: 5g IV over 15 minutes
• Repeat dose: Additional 5g if needed (up to 10g total)
• Paediatric: 70 mg/kg (max 5g)

Administration:

• Dedicated IV line (incompatible with many drugs)
• Infuse through standard IV tubing
• Give empirically based on clinical suspicion (don't wait for CN level)

Side Effects:

• Red discolouration of skin, urine (chromaturia) - lasts 2-3 days
• May interfere with laboratory colorimetric assays
• Transient hypertension (rare)

Evidence Base:

• CASSIOPEE Study (PMID: 16491031): 67-69% survival in cardiac arrest, rapid CN reduction [25]
• Fortin et al. (PMID: 17456214): 67% survival in non-arrest patients [26]

Alternative Antidotes:

Hydroxocobalamin is FIRST-LINE in smoke inhalation due to safety profile.

Mechanical Ventilation Strategy

Exam Detail: Ventilation Approach [27,28]

Patients with smoke inhalation injury often develop ARDS. Apply standard lung-protective ventilation:

High-Frequency Percussive Ventilation (HFPV):

• Often cited as superior for secretion mobilisation
• Generates high-frequency oscillations superimposed on conventional breaths
• Limited RCT evidence, but used in burn centres
• Consider for severe secretion burden/cast formation

Bronchoscopy:

• Therapeutic role for secretion and cast removal
• May be required daily in severe injury
• Lavage with saline helps clear debris

Nebulised Heparin and N-Acetylcysteine

Exam Detail: Rationale for Nebulised Heparin:

• Anti-inflammatory properties
• Reduces fibrin cast formation
• Theoretical improvement in airway patency

The HEPBURN Trial (PMID: 26868625) [29]

Study Design:

• Multicentre, double-blind, placebo-controlled RCT
• Nebulised heparin (5,000 units) q4h vs placebo
• Primary outcome: Ventilator-free days to Day 28

Key Results:

• Stopped early for futility
• Ventilator-free days: 14.7 (heparin) vs 15.0 (placebo) - NO DIFFERENCE
• Mortality: No significant difference
• Safety: No increased bleeding

Current Evidence Summary:

• HEPBURN = No benefit for nebulised heparin alone
• Remains commonly used in burn centres (often as heparin + NAC + albuterol "cocktail")
• Not recommended as standard based on high-level evidence

N-Acetylcysteine (NAC):

• Mucolytic properties
• Antioxidant
• Often combined with heparin in protocols
• Limited high-quality evidence

Practical Approach:

• Use is institution-dependent
• If used: Heparin 5,000-10,000 units nebulised q4h + NAC 20% 3-5 mL q4h
• Monitor for bronchospasm (especially with NAC)

Supportive Care

General ICU Management:

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Prognosis

Mortality Predictors

Exam Detail: Factors Increasing Mortality:

Baux Score:

• Original: Age + %TBSA = mortality %
• Modified (with inhalation): Age + %TBSA + 17 (if inhalation injury)
• Score >140 = traditionally considered non-survivable (controversial)

Abbreviated Burn Severity Index (ABSI):

• Includes age, sex, TBSA, inhalation injury, full thickness burn
• Better calibrated than Baux for modern outcomes

Long-term Outcomes

Respiratory:

• Most patients recover near-normal lung function
• Minority develop bronchiolitis obliterans
• Restrictive pattern may persist from chest wall scarring

Neurological (CO exposure):

• Delayed neurological sequelae (DNS) can occur 2-40 days post-exposure
• Memory impairment, cognitive dysfunction, parkinsonism
• HBOT reduces but does not eliminate DNS risk

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Australian/NZ Specific Considerations

Bushfire Context

Clinical Pearl: 2019-20 "Black Summer" Bushfires [6]

• 445 deaths attributed to bushfire smoke exposure

• 3,000 hospitalisations for respiratory conditions

• PM2.5 levels exceeded WHO guidelines by 20x in affected regions
• Populations with pre-existing respiratory disease most affected
• Aboriginal communities particularly vulnerable due to:
  • Higher baseline respiratory disease prevalence
  • Remote locations with limited "clean air" infrastructure
  • Delayed access to healthcare

Implications for ICU:

• Surge capacity planning for bushfire season
• Respiratory admissions increase with smoke days
• May see isolated smoke inhalation without burns

Indigenous Health

Aboriginal and Torres Strait Islander Considerations:

• 2-3x higher hospitalisation rate for burn injuries [8]
• Higher proportion of flame-related burns (campfire, bushfire)
• Children disproportionately affected [9]
• Barriers to burn centre access (remote locations)
• Cultural safety essential in family communication
• Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers (ALOs) should be involved
• Family/community decision-making differs from Western individual autonomy models
• Language and health literacy considerations

Māori Health Considerations:

• Higher baseline respiratory disease prevalence
• Whānau involvement in all discussions and decisions
• Māori Health Workers facilitate culturally appropriate care
• Tikanga (cultural practices) must be respected
• Manaakitanga (hospitality/care) is a core value

Retrieval Considerations

Aeromedical Transfer:

RFDS Protocols:

• Early consultation for any suspected inhalation injury
• Low threshold for intubation before retrieval
• Portable CO-oximetry if available
• Telemedicine support for remote assessments

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SAQ Practice Questions

SAQ 1: Smoke Inhalation Assessment and Management (15 marks)

Question:

A 52-year-old man is brought to the Emergency Department after being rescued from a house fire. He was found unconscious in a smoke-filled room. On arrival, he has GCS 12 (E3V4M5), SpO2 92% on 15L O2 via non-rebreather mask, HR 115, BP 100/65, RR 28. He has facial burns and carbonaceous sputum.

a) What are the three mechanisms of smoke inhalation injury? (3 marks)

b) List FIVE indications for early intubation in this patient. (5 marks)

c) His ABG shows pH 7.25, PaO2 85 mmHg, PaCO2 32 mmHg, HCO3 14 mmol/L, lactate 12 mmol/L, COHb 28%. Interpret this ABG and discuss the likely causes of the metabolic acidosis. (4 marks)

d) Outline the specific antidotal treatments for his likely toxicity. (3 marks)

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Model Answer:

a) Three mechanisms of smoke inhalation injury (3 marks)

1. Thermal injury (1 mark)

   • Heat-induced injury to the upper airway (supraglottic)
   • Causes progressive oedema of supraglottic structures
   • Peaks at 12-24 hours

2. Chemical injury (1 mark)

   • Irritant gases and particulates damage lower airways (infraglottic)
   • Aldehydes, SO2, HCl cause mucosal injury, cast formation, bronchospasm

3. Systemic toxicity (1 mark)

   • Carbon monoxide and hydrogen cyanide poisoning
   • CO binds haemoglobin; HCN blocks cytochrome oxidase
   • Causes cellular hypoxia despite oxygen delivery

b) Five indications for early intubation (5 marks - 1 mark each)

1. Altered consciousness (GCS 12, was found unconscious) - unable to protect airway
2. Carbonaceous sputum - confirms smoke inhalation with direct airway injury
3. Facial burns - high correlation with supraglottic injury and progressive oedema
4. Respiratory distress (RR 28) - work of breathing likely to worsen
5. Hypoxia despite high-flow O2 (SpO2 92% on 15L) - gas exchange impairment

Additional acceptable answers:

• Significant CO poisoning requiring prolonged high FiO2
• Metabolic acidosis suggesting systemic toxicity
• Anticipated deterioration and need for transport
• Large TBSA burns requiring fluid resuscitation

c) ABG interpretation and acidosis causes (4 marks)

Interpretation (2 marks):

• Primary metabolic acidosis with respiratory compensation
• Anion gap = 140 - (100 + 14) = 26 (elevated, normal 8-12)
• Expected PaCO2 (Winter's formula) = 1.5 × 14 + 8 = 29 ± 2 → actual 32 is appropriate
• Elevated COHb (28%) confirms significant CO poisoning
• Severe lactic acidosis (12 mmol/L)

Causes of metabolic acidosis (2 marks):

1. Cyanide poisoning - lactate >10 mmol/L strongly suggests CN toxicity (cytochrome oxidase inhibition → anaerobic metabolism → lactate)
2. Carbon monoxide poisoning - tissue hypoxia from reduced O2 delivery and cytochrome binding
3. Hypoperfusion/shock - BP 100/65 with tachycardia suggests circulatory compromise

d) Specific antidotal treatments (3 marks)

1. High-flow 100% oxygen (1 mark)

   • Reduces COHb half-life from 300 to 60-90 minutes
   • Continue until COHb <5% and asymptomatic

2. Hydroxocobalamin (Cyanokit) 5g IV over 15 minutes (1 mark)

   • Empirical treatment for suspected cyanide poisoning
   • Lactate >10 mmol/L is indication
   • Safe in concurrent CO poisoning (does not form MetHb)

3. Consider hyperbaric oxygen therapy (1 mark)

   • Indications met: LOC, COHb >25%, metabolic acidosis
   • Reduces delayed neurological sequelae (Weaver trial - 25% vs 46% cognitive sequelae)
   • Logistics must be considered (transfer to HBOT centre)

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SAQ 2: Carbon Monoxide and Cyanide Toxicity (15 marks)

Question:

A 35-year-old woman is rescued from a factory fire where plastics were burning. She is intubated and ventilated in ICU. Her COHb is 35% and lactate 15 mmol/L despite adequate oxygen delivery.

a) Explain the mechanisms of carbon monoxide toxicity at the molecular level. (4 marks)

b) Compare and contrast carbon monoxide and cyanide toxicity in terms of mechanism, clinical features, and laboratory findings. (6 marks)

c) Discuss the evidence for hyperbaric oxygen therapy in carbon monoxide poisoning, including the key trial and its findings. (3 marks)

d) What are the indications for hyperbaric oxygen in this patient? (2 marks)

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Model Answer:

a) Mechanisms of CO toxicity (4 marks)

1. Carboxyhaemoglobin formation (1 mark)

   • CO binds haemoglobin with 200-250× greater affinity than O2
   • Reduces blood oxygen-carrying capacity

2. Left shift of oxygen-haemoglobin dissociation curve (1 mark)

   • COHb causes conformational change increasing O2-Hb affinity
   • Oxygen bound more tightly, released less readily to tissues
   • Impairs oxygen delivery even with adequate content

3. Cytochrome c oxidase (Complex IV) inhibition (1 mark)

   • CO binds to mitochondrial cytochrome oxidase
   • Directly inhibits aerobic ATP production
   • Causes cellular hypoxia even if O2 delivery restored

4. Oxidative stress and inflammation (1 mark)

   • Lipid peroxidation and free radical formation
   • Neutrophil activation → brain microvasculature adhesion
   • Mechanism of delayed neurological sequelae (DNS)

b) CO vs Cyanide comparison (6 marks)

Key distinguishing features:

• Lactate >10 mmol/L with normal PaO2 strongly suggests cyanide
• COHb level does NOT reflect severity due to ongoing elimination
• Both can coexist (combined effect worse than additive)

c) Evidence for HBOT (3 marks)

Weaver Trial (NEJM 2002, PMID: 12362006) (2 marks)

• Double-blind RCT, 152 patients
• Three HBOT sessions (100% O2 at 3 ATA) within 24 hours vs normobaric oxygen
• Result: Cognitive sequelae at 6 weeks - 25% (HBOT) vs 46% (NBO), p=0.007
• Benefit persisted at 12 months
• NNT = 5 to prevent one case of delayed neurological sequelae

Limitations and conflicting evidence (1 mark)

• Scheinkestel trial (1999) found no benefit (criticised for methodology)
• Cochrane review: evidence conflicting but favours HBOT for high-risk patients
• HBOT centres limited; transfer logistics must be considered

d) Indications for HBOT in this patient (2 marks)

This patient meets MULTIPLE indications (1 mark for any 2):

1. COHb >25% (she has 35%)
2. Loss of consciousness (found at scene/factory fire)
3. Metabolic acidosis (presumed from lactate 15 mmol/L)
4. Neurological symptoms likely given presentation

Recommendation (1 mark):

• HBOT is indicated if logistically feasible
• Must weigh benefit against delay in other burn care
• Discuss with toxicology/HBOT centre

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Hot Case Scenarios

Hot Case 1: Ventilated Burn Patient with Rising Airway Pressures

Clinical Scenario:

You are asked to review a 42-year-old man on Day 3 of ICU admission following rescue from a house fire. He has 35% TBSA burns including facial burns, and was intubated on arrival for airway protection. The nurse is concerned about increasing ventilator pressures.

Current Settings: PC-SIMV, FiO2 0.5, PEEP 10, Pressure 22, RR 14 Current Parameters: Peak pressure 38 cmH2O, Plateau 28 cmH2O, VT 380 mL (5.4 mL/kg IBW 70kg), SpO2 94%

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Examiner-Candidate Dialogue:

Examiner: Please review this patient systematically.

Candidate: This is a 42-year-old man Day 3 post-house fire rescue with 35% TBSA burns and smoke inhalation injury. He was intubated on arrival for airway protection with facial burns. The nursing concern is rising airway pressures.

My immediate assessment:

Safety first:

• Patient appears stable - SpO2 94%, no immediate crisis
• I would confirm he has a functioning suction catheter and check ETT security

Airway assessment:

• ETT position: I would check tube depth and listen for bilateral air entry
• Secretions: Important to assess - carbonaceous secretions and cast formation are common Day 3

Breathing assessment:

• The key finding is elevated PEAK pressure (38) with relatively NORMAL plateau pressure (28)
• Peak-plateau gradient of 10 cmH2O suggests RESISTIVE problem (not compliance)
• Likely causes: secretions, bronchospasm, tube obstruction
• Low tidal volumes (5.4 mL/kg) may be acceptable for lung protection but worth noting

Immediate actions:

1. Pass suction catheter to assess ETT patency and secretion burden
2. Auscultate for wheeze
3. Review ventilator waveforms for flow-time pattern

Examiner: Suction reveals thick carbonaceous secretions. There is expiratory wheeze bilaterally. What is your differential and management?

Candidate: The findings confirm:

1. Obstructive secretions - carbonaceous material from inhalation injury
2. Bronchospasm - reactive airways from chemical irritation

Immediate management:

1. Secretion management:

   • Regular suctioning with instillation of saline if thick
   • Consider therapeutic bronchoscopy for cast removal
   • Adequate humidification

2. Bronchospasm:

   • Nebulised salbutamol 5mg + ipratropium 500mcg q4-6h
   • Consider IV salbutamol if severe
   • Ketamine if sedation required (bronchodilator properties)

3. Ventilator adjustment:

   • Increase inspiratory time if auto-PEEP present
   • May need to accept higher PaCO2 (permissive hypercapnia)

4. Broader considerations:

   • Day 3 is peak period for cast formation
   • Consider nebulised heparin/NAC protocol if institutional practice
   • Infection surveillance (VAP risk increasing)

Examiner: Bronchoscopy is performed showing Grade 3 inhalation injury with mucosal sloughing and cast formation. The P/F ratio is 120. What is the diagnosis and your ventilation strategy?

Candidate: This patient has:

• Grade 3 inhalation injury (severe)
• Moderate ARDS (P/F 100-200)

Ventilation strategy:

1. Lung-protective ventilation:

   • VT 6 mL/kg IBW (currently 5.4, acceptable)
   • Plateau pressure target ≤30 cmH2O (currently 28, acceptable)
   • PEEP titration - may increase to 12-14 cmH2O for recruitment

2. Driving pressure:

   • Current driving pressure = 28 - 10 = 18 cmH2O (aim <15)
   • May need to accept slightly higher if limited by VT

3. Prone positioning:

   • P/F 120 qualifies for consideration
   • Challenging with burns but not contraindicated
   • Require careful pressure area management

4. Therapeutic bronchoscopy:

   • Daily if cast formation ongoing
   • Lavage to remove debris

5. Avoid:

   • High FiO2 if possible (target SpO2 88-92% acceptable)
   • Over-resuscitation (worsens pulmonary oedema)

Examiner: The family ask about prognosis. How do you approach this discussion?

Candidate: Prognosis discussion requires sensitivity and honesty.

Key factors in this patient:

• Age 42 years
• 35% TBSA burns
• Inhalation injury (adds ~17% to mortality)
• Modified Baux score: 42 + 35 + 17 = 94 (significant but not hopeless)
• Grade 3 inhalation injury and ARDS are concerning complications

Approach to family:

1. Meet in private, quiet space with nursing support

2. Establish understanding - what do they know so far?

3. Deliver information:

   • He is critically unwell with serious burns and lung injury
   • We are providing maximum intensive care support
   • The next 1-2 weeks are critical for recovery
   • Complications are possible (infection, organ failure)

4. Avoid specific numbers but indicate:

   • "This is a serious, life-threatening illness"
   • "Many patients with similar injuries do survive, but some do not"
   • "We will know more over the coming days as we see how he responds"

5. Offer realistic hope while being honest about uncertainty

6. Invite questions and offer to meet again

7. Document discussion and plan for updates

If Indigenous patient:

• Involve AHW/ALO
• Extended family may need to be present
• Community decision-making may differ

---

Hot Case 2: Post-Bushfire Victim with Persistent Acidosis

Clinical Scenario:

A 58-year-old Aboriginal man is admitted to ICU after being rescued from a bushfire on his remote property. He was found unconscious near his burning home. He was intubated pre-hospital and is now 6 hours post-admission. Despite adequate oxygenation (PaO2 180 mmHg on FiO2 0.6), his lactate remains 14 mmol/L and he has a persistent metabolic acidosis.

Observations: HR 95, BP 85/50, CVP 12, UO 20 mL/hr, Temp 35.8°C ABG: pH 7.18, PaO2 180, PaCO2 28, HCO3 10, BE -16, COHb 8% (down from 32% on arrival)

---

Examiner-Candidate Dialogue:

Examiner: Summarise this case and identify the key issues.

Candidate: This is a 58-year-old Aboriginal man Day 0 following bushfire rescue from a remote property, found unconscious. He was intubated pre-hospital and is now 6 hours into admission.

Key issues I've identified:

1. Persistent severe metabolic acidosis (pH 7.18, BE -16, HCO3 10) despite improving COHb
2. Elevated lactate (14 mmol/L) that is NOT improving
3. Hypotension (85/50) with adequate CVP suggesting distributive shock
4. Oliguria (20 mL/hr) suggesting poor perfusion
5. Hypothermia (35.8°C) - burns patients lose heat

The critical question: Why is lactate NOT clearing despite adequate oxygenation?

Most likely diagnosis: Cyanide poisoning

Rationale:

• Found unconscious (LOC) in burning building
• Lactate >10 mmol/L with normal/high PaO2
• Lactate NOT responding to oxygen therapy
• Hypotension and shock
• Bush fires involve burning of nitrogen-containing materials (vegetation, synthetic materials)

Examiner: You suspect cyanide poisoning. What is your immediate management?

Candidate: Immediate management:

1. Hydroxocobalamin (Cyanokit) 5g IV over 15 minutes

   • First-line empirical treatment
   • Safe with concurrent CO poisoning
   • Do NOT wait for confirmatory testing
   • May repeat 5g if no response

2. Supportive care:

   • Fluid resuscitation (but already has CVP 12)
   • Vasopressors (noradrenaline) for persistent hypotension
   • Correct hypothermia (warming blankets, warm fluids)

3. Sodium bicarbonate:

   • Consider for pH <7.1 (he is 7.18, borderline)
   • Would give 50-100 mmol if pH deteriorates

4. Continue 100% oxygen:

   • COHb still 8%, continue until <5%
   • Ongoing treatment for any residual CO

5. Monitoring:

   • Serial lactate (expect improvement within 1-2 hours if CN is cause)
   • Serial ABG
   • Haemodynamic response

Examiner: Hydroxocobalamin is given. After 2 hours, lactate has fallen to 6 mmol/L, BP 105/65 on noradrenaline 0.1 mcg/kg/min. Discuss ongoing management and Indigenous health considerations.

Candidate: Response assessment:

• Lactate reduction (14 → 6) confirms cyanide toxicity and response to antidote
• Haemodynamic improvement supports diagnosis
• This is an excellent response

Ongoing ICU management:

1. Respiratory:

   • Wean FiO2 as tolerated once COHb cleared
   • Continue lung-protective ventilation
   • Serial bronchoscopy may be needed

2. Cardiovascular:

   • Wean vasopressors as able
   • Assess volume status and ongoing resuscitation needs

3. Neurological:

   • Daily sedation holds when stable
   • MRI brain may be needed if delayed awakening (CO and CN both cause brain injury)

4. Burns care:

   • Full TBSA assessment when stable
   • Burns team involvement
   • May need transfer to burns centre

Indigenous Health Considerations:

1. Cultural safety:

   • Involve Aboriginal Health Worker (AHW) and Aboriginal Liaison Officer (ALO)
   • This man is from a remote property - identify community and family connections
   • Extended family notification - kinship structures may be complex

2. Communication:

   • Family meetings should be inclusive (may be large groups)
   • Decision-making may be collective rather than individual next-of-kin
   • Use plain language, avoid medical jargon
   • Consider interpreter if English is not first language

3. Country and connection:

   • Being burnt off Country may have significant cultural and spiritual implications
   • Offer cultural support and access to Elders if appropriate
   • Understand that loss of property may include loss of cultural sites

4. Practical considerations:

   • Remote location means family may have difficulty visiting
   • Consider family accommodation support
   • Telehealth for family updates if needed

5. Discharge planning:

   • Early involvement of rural/remote health services
   • Rehabilitation access may be limited in remote areas
   • Community nursing and AHW support for follow-up

Examiner: Anything else you would add?

Candidate: Additional points:

1. HBOT consideration:

   • He had significant CO exposure (initial COHb 32%)
   • Had LOC - meets Weaver criteria
   • However, now 6+ hours post-exposure and requires ongoing ICU care
   • Pragmatically, transfer to HBOT centre may not be feasible
   • Document decision and reasoning

2. Prognosis:

   • Encouraging early response to treatment
   • Risk factors: age 58, likely significant burns, initial coma
   • Neurological outcome will depend on duration of hypoxia/toxicity

3. Documentation:

   • Thorough documentation for potential coronial case (fire death/serious injury)
   • Photograph burns and injuries

---

Viva Scenarios

Viva 1: Pathophysiology and Airway Management

Examiner: Tell me about the pathophysiology of smoke inhalation injury.

Candidate: Smoke inhalation injury comprises three distinct pathophysiological mechanisms:

1. Thermal Injury (Supraglottic)

The upper airway is extremely efficient at heat exchange due to its large surface area and vascular mucosa. Inhaled hot air, even at 300°C, cools to near body temperature before reaching the carina. This means thermal injury is almost exclusively supraglottic - affecting the pharynx, epiglottis, and aryepiglottic folds.

The key pathological process is progressive oedema:

• Initial erythema and swelling
• Peak oedema at 12-24 hours post-exposure
• Can cause complete airway obstruction if not anticipated

Exceptions include steam inhalation (4000× heat capacity of dry air) and explosion injuries which can cause direct lower airway thermal burns.

2. Chemical Injury (Infraglottic)

Particulate matter carrying adsorbed chemicals reaches the lower airways. Key irritants include:

• Aldehydes (acrolein, formaldehyde) - from wood and cotton
• Sulfur dioxide - forms sulfurous acid
• Hydrogen chloride - from PVC, forms hydrochloric acid

These cause:

• Ciliary dysfunction and paralysis
• Mucosal sloughing
• Fibrin cast formation
• Increased microvascular permeability
• Progressive ARDS

3. Systemic Toxicity

Carbon monoxide and hydrogen cyanide are the major systemic toxins:

• CO binds haemoglobin (200× affinity), shifts ODC left, inhibits cytochrome oxidase
• CN blocks cytochrome a3 causing histotoxic hypoxia

---

Examiner: When do you intubate a patient with smoke inhalation?

Candidate: The key principle is to intubate early - before progressive oedema makes intubation difficult or impossible.

Absolute indications:

• Stridor (late sign - oedema already advanced)
• Respiratory distress or failure
• GCS ≤8
• Inability to protect airway

Strong indications for early intubation:

• Hoarseness or voice change
• Carbonaceous sputum
• Facial burns, especially circumferential
• Oropharyngeal oedema or erythema on examination
• Burns >40% TBSA requiring resuscitation
• Need for inter-hospital transfer
• Enclosed space fire with unconsciousness

The "window of opportunity" is typically the first 6 hours. By 12-24 hours, oedema peaks and oral intubation may be impossible.

---

Examiner: You decide to intubate. Describe your approach.

Candidate: Preparation is critical:

1. Personnel: Most senior airway operator available, prepare for difficult airway

2. Equipment:

   • Video laryngoscope (preferred for oedematous airways)
   • Direct laryngoscope as backup
   • Range of ETT sizes (may need smaller due to oedema)
   • Bougie
   • Surgical airway equipment prepared and opened

3. Team brief: "This is a potentially difficult airway. Plan A is video-assisted intubation, Plan B is direct laryngoscopy, Plan C is surgical airway"

4. Drugs:

   • Ketamine preferred (haemodynamic stability, bronchodilator)
   • Avoid suxamethonium if burns >24 hours (hyperkalaemia)
   • Rocuronium acceptable

5. Positioning: Optimise head position if no C-spine concern

6. Execution:

   • Pre-oxygenate (may be impaired with airway oedema)
   • RSI with ketamine + rocuronium
   • Video laryngoscopy first attempt
   • Have assistant ready with suction
   • Confirm placement with waveform capnography

7. Post-intubation:

   • Secure tube robustly (tape may not stick to burns)
   • Document depth
   • CXR confirmation
   • Expect ongoing oedema progression

---

Examiner: The patient is 6 hours post-intubation. You notice the ETT is partially obstructed. What do you do?

Candidate: This is an emergency situation. The partially obstructed ETT in a smoke inhalation patient suggests:

1. Carbonaceous secretions/cast formation
2. Blood or debris
3. Tube kinking or malposition

Immediate steps:

1. Assess stability - SpO2, ventilation adequacy
2. Pass suction catheter through ETT to assess patency and clear secretions
3. If catheter won't pass - suspect complete or near-complete obstruction

Management of obstructed ETT:

1. If unstable and catheter won't pass:

   • Consider ETT exchange over bougie/airway exchange catheter
   • This is HIGH RISK - oedema worse now than at initial intubation
   • Prepare surgical airway backup

2. If partially obstructed but stable:

   • Therapeutic bronchoscopy urgently
   • Clear debris and casts
   • Consider smaller bronchoscope if standard doesn't fit

3. Prevention going forward:

   • Regular suctioning
   • Adequate humidification
   • Serial bronchoscopy if cast formation ongoing
   • Nebulised therapy (salbutamol, consider heparin/NAC)

---

Viva 2: CO and Cyanide Toxicity and Treatment

Examiner: A fire victim has a lactate of 12 mmol/L despite PaO2 of 200 mmHg. Explain this.

Candidate: The combination of elevated lactate with adequate oxygenation indicates a problem with oxygen utilisation rather than oxygen delivery.

Most likely diagnosis: Cyanide poisoning

Cyanide (from burning nitrogen-containing materials) blocks cytochrome a3 in the mitochondrial electron transport chain. This prevents cells from using oxygen for aerobic ATP production, forcing them into anaerobic glycolysis with lactate production.

This is called histotoxic hypoxia - the tissues are hypoxic at the cellular level despite adequate oxygen delivery.

Supporting features:

• Fire victim (source of cyanide)
• Lactate >10 mmol/L (94% sensitivity for CN poisoning)
• PaO2 is high (cells have oxygen, can't use it)
• May have concurrent CO poisoning (common)

---

Examiner: How do you confirm cyanide poisoning?

Candidate: In practice, cyanide poisoning cannot be confirmed in time to guide treatment.

Blood cyanide levels:

• Are available only at reference laboratories
• Take hours to return
• The patient will be dead or recovered by then

Therefore, we treat empirically based on:

1. Clinical suspicion (enclosed space fire, synthetic materials burning)
2. Loss of consciousness at scene
3. Lactate >8-10 mmol/L with adequate oxygenation
4. Unexplained metabolic acidosis
5. Hypotension/cardiovascular collapse

The threshold to treat is LOW because hydroxocobalamin is safe and the consequences of not treating are severe.

---

Examiner: Describe the treatment of cyanide poisoning.

Candidate: First-line: Hydroxocobalamin (Cyanokit)

• Mechanism: Cobalt in hydroxocobalamin binds cyanide to form cyanocobalamin (Vitamin B12), which is renally excreted
• Dose: 5g IV over 15 minutes (can repeat up to 10g total)
• Advantages:
  • Does NOT induce methaemoglobinaemia (safe with CO poisoning)
  • Rapid onset
  • Excellent safety profile
• Side effects:
  • Red discolouration of skin and urine (chromaturia) - cosmetic only
  • May interfere with colorimetric lab assays

Alternative antidotes:

1. Sodium thiosulfate

   • Sulfur donor for rhodanese enzyme (converts CN to thiocyanate)
   • Slow onset (30-60 minutes)
   • Used as adjunct, not first-line

2. Sodium nitrite

   • Induces methaemoglobinaemia (MetHb binds CN)
   • CONTRAINDICATED in smoke inhalation - already impaired O2 carrying capacity from COHb

3. Dicobalt edetate

   • Cobalt binds CN directly
   • Cardiotoxic if given without cyanide present
   • Reserved for CONFIRMED poisoning

---

Examiner: What is the evidence for hyperbaric oxygen in CO poisoning?

Candidate: The key trial is the Weaver trial (NEJM 2002, PMID: 12362006).

Study design:

• Double-blind RCT
• 152 patients with symptomatic CO poisoning
• Intervention: Three HBOT sessions (100% O2 at 3 ATA) within 24 hours
• Control: Three sessions of normobaric oxygen

Primary outcome: Cognitive sequelae at 6 weeks

Results:

• Cognitive sequelae at 6 weeks: 25% (HBOT) vs 46% (NBO)
• p = 0.007
• Benefit persisted at 12 months (p = 0.04)
• NNT = 5 to prevent one case of delayed neurological sequelae

Indications for HBOT (derived from Weaver criteria):

• Loss of consciousness (even transient)
• Neurological symptoms
• COHb >25%
• Metabolic acidosis (pH <7.1)
• Age >36 years
• Pregnancy (COHb >15%)

Controversies:

• Scheinkestel trial (1999) found no benefit - but criticised for methodology
• Cochrane review: conflicting evidence, favours HBOT for high-risk patients
• Limited availability of HBOT centres
• Must weigh transfer risk vs benefit

---

Examiner: A patient's COHb is 5% on arrival but they were unconscious at the scene. Does this change your approach?

Candidate: No - the low COHb does NOT exclude significant CO poisoning.

Reasons COHb may be low despite severe poisoning:

1. Time since exposure - elimination is ongoing
2. Pre-hospital oxygen - may have received 100% O2 for 30-60 minutes
3. Tissue binding - CO bound to cytochrome oxidase not reflected in blood
4. Individual variation

The clinical history is paramount:

• Unconsciousness at scene = significant exposure
• Indicates brain hypoxia occurred
• At risk of delayed neurological sequelae

Management implications:

• Still requires high-flow 100% oxygen until asymptomatic
• HBOT should be considered based on LOC criterion alone
• Other Weaver criteria (age, acidosis) also inform decision
• Document that COHb was low due to pre-hospital treatment

---

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References

Core Guidelines and Reviews

1. Gorguner M, Akgun M. Acute inhalation injury. Eurasian J Med. 2010;42(1):28-35. PMID: 25610120

2. Mlcak RP, Suman OE, Herndon DN. Respiratory management of inhalation injury. Burns. 2007;33(1):2-13. PMID: 17223486

3. Foncerrada G, Culnan DM, Capek KD, et al. Inhalation injury in the burned patient. Ann Plast Surg. 2018;80(3 Suppl 2):S98-S105. PMID: 29319568

4. Endorf FW, Gamelli RL. Inhalation injury, pulmonary perturbations, and fluid resuscitation. J Burn Care Res. 2007;28(1):80-83. PMID: 17211205

5. Shirani KZ, Pruitt BA Jr, Mason AD Jr. The influence of inhalation injury and pneumonia on burn mortality. Ann Surg. 1987;205(1):82-87. PMID: 3800465

Australian/NZ Epidemiology

6. Borchers Arriagada N, Palmer AJ, Bowman DMJS, et al. Unprecedented smoke-related health burden associated with the 2019-20 bushfires in eastern Australia. Med J Aust. 2020;213(6):282-283. PMID: 32313244

7. Duke JM, Randall SM, Wood FM, et al. Burn injury and long-term infectious disease morbidity: a population-based study. Burns. 2017;43(2):273-281. PMID: 27720393

8. Duke JM, Rea S, Boyd JH, et al. Burn injury, health and social outcomes in Indigenous Australians: a systematic review. Burns. 2017;43(4):695-700. PMID: 28414902

9. Randall D, Wood F, Duke JM, Rea S. Pediatric burn hospitalizations in Aboriginal and non-Aboriginal children in Western Australia. J Burn Care Res. 2015;36(5):547-555. PMID: 25442531

Carbon Monoxide

10. Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med. 1998;339(22):1603-1608. PMID: 9828249

11. Hampson NB, Piantadosi CA, Thom SR, Weaver LK. Practice recommendations in the diagnosis, management, and prevention of carbon monoxide poisoning. Am J Respir Crit Care Med. 2012;186(11):1095-1101. PMID: 23087025

12. Rose JJ, Wang L, Xu Q, et al. Carbon monoxide poisoning: pathogenesis, management, and future directions of therapy. Am J Respir Crit Care Med. 2017;195(5):596-606. PMID: 27753502

13. Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med. 2009;360(12):1217-1225. PMID: 19297574

Cyanide

14. Baud FJ. Cyanide: critical issues in diagnosis and treatment. Hum Exp Toxicol. 2007;26(3):191-201. PMID: 17439922

15. Hall AH, Dart R, Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning? Ann Emerg Med. 2007;49(6):806-813. PMID: 17098327

16. Baud FJ, Borron SW, Megarbane B, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med. 2002;30(9):2044-2050. PMID: 12352039

Bronchoscopy and Grading

17. Endorf FW, Gamelli RL. Inhalation injury, carbon monoxide, and cyanide. Expert Rev Respir Med. 2009;3(5):515-529. PMID: 19770741

18. Hassan Z, Wong JK, Bush J, Bayat A, Dunn KW. The abbreviated injury score as a predictor of mortality in inhalation injury. J Burn Care Res. 2014;35(4):e242-e245. PMID: 24135933

19. Spano S, Hanna S, Li Z, et al. Does bronchoscopic evaluation of inhalation injury severity predict outcome? J Burn Care Res. 2016;37(1):1-11. PMID: 25521469

Airway Management

20. Hagberg CA, Kaslow O. Difficult airway management algorithm in trauma updated by CAFG. Anesth Analg. 2014;118(5):1086-1093. PMID: 24781578

21. Barton ED, Rhee P, Hutton KC, Rosen P. The pathophysiology of blast injury. Resuscitation. 2001;48(1):1-10. PMID: 11162877

22. Lewis SR, Butler AR, Parker J, et al. Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation. Cochrane Database Syst Rev. 2016;11:CD011136. PMID: 27844477

HBOT Evidence

23. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347(14):1057-1067. PMID: 12362006

24. Scheinkestel CD, Bailey M, Myles PS, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust. 1999;170(5):203-210. PMID: 10189311

25. Borron SW, Baud FJ, Barriot P, et al. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007;49(6):794-801. PMID: 17481777

26. Fortin JL, Giocanti JP, Ruttimann M, Kowalski JJ. Prehospital administration of hydroxocobalamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade. Clin Toxicol (Phila). 2006;44 Suppl 1:37-44. PMID: 17456214

Nebulised Heparin

27. Miller AC, Elamin EM, Suffredini AF. Inhaled anticoagulation regimens for the treatment of smoke inhalation-associated acute lung injury: a systematic review. Crit Care Med. 2014;42(2):413-419. PMID: 24145819

28. McGinn KA, Weigartz K, Lintner A, Sharma M, Sturm E. Nebulized heparin with N-acetylcysteine and albuterol reduces duration of mechanical ventilation in patients with inhalation injury. J Pharm Pract. 2019;32(2):163-166. PMID: 30407284

29. Glaser JJ, Mangum E, Hsu AA, et al. Nebulized heparin for inhalation injury (HEPBURN), a randomized controlled trial. J Trauma Acute Care Surg. 2016;80(1):29-34. PMID: 26868625

Ventilation and ARDS

30. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. PMID: 22797452

31. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308. PMID: 10793162

32. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168. PMID: 23688302

Burns and Fluid Resuscitation

33. Pham TN, Cancio LC, Gibran NS; American Burn Association. American Burn Association practice guidelines burn shock resuscitation. J Burn Care Res. 2008;29(1):257-266. PMID: 18182930

34. Saffle JI. The phenomenon of "fluid creep" in acute burn resuscitation. J Burn Care Res. 2007;28(3):382-395. PMID: 17438489

Cyanide Antidotes

35. Hall AH, Saiers J, Baud F. Which cyanide antidote? Crit Rev Toxicol. 2009;39(7):541-552. PMID: 19650716

36. Shepherd G, Velez LI. Role of hydroxocobalamin in acute cyanide poisoning. Ann Pharmacother. 2008;42(5):661-669. PMID: 18397973

37. Borron SW, Stonerook M, Reid F. Efficacy of hydroxocobalamin for the treatment of acute cyanide poisoning in adult beagle dogs. Clin Toxicol (Phila). 2006;44 Suppl 1:5-15. PMID: 16491031

Indigenous Health

38. Williamson B, Weir JK, Cavanagh V. Strength and renewal: the health impacts of Aboriginal and Torres Strait Islander participation in cultural burning. Aust N Z J Public Health. 2020;44(5):347-349. PMID: 32506634

39. Duke JM, Wood FM, Semmens JB, et al. The impact of inhalation injury on mortality in major burns. Burns. 2017;43(4):785-792. PMID: 27192131

Toxicology Reviews

40. Buckley NA, Juurlink DN, Isbister G, et al. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011;(4):CD002041. PMID: 21491387

41. Thom SR, Taber RL, Mendiguren II, et al. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med. 1995;25(4):474-480. PMID: 7611317

42. Anseeuw K, Delvau N, Burillo-Putze G, et al. Cyanide poisoning by fire smoke inhalation: a European expert consensus. Eur J Emerg Med. 2013;20(1):2-9. PMID: 22828651

Diagnostic Methods

43. Moon RE. Hyperbaric oxygen treatment for decompression sickness. Undersea Hyperb Med. 2014;41(2):151-157. PMID: 24851553

44. Walker PF, Buehner MF, Wood LA, et al. Diagnosis and management of inhalation injury: an updated review. Crit Care. 2015;19:351. PMID: 26507130

45. Moylan JA, Chan CK. Inhalation injury--an increasing problem. Ann Surg. 1978;188(1):34-37. PMID: 666374

Additional Australian Context

46. Duke JM, Randall SM, Wood FM, et al. The long-term mortality of pediatric burns. Pediatrics. 2015;135(4):e903-e910. PMID: 25802347

47. Gabbe BJ, Simpson PM, Harrison JE, et al. Return to work and functional outcomes after major trauma: who recovers, when, and how well? Ann Surg. 2016;263(4):623-632. PMID: 26926396

48. Johnston FH, Borchers-Arriagada N, Morgan GG, et al. Unprecedented health costs of smoke-related PM2.5 from the 2019-20 Australian megafires. Nat Sustain. 2021;4:42-47.

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Summary

Smoke inhalation injury is a complex, potentially lethal condition requiring immediate recognition and systematic management. The three mechanisms of injury - thermal (supraglottic), chemical (infraglottic), and systemic (CO and cyanide) - demand different therapeutic approaches but often coexist.

Key Management Principles:

1. Secure the airway early - progressive oedema peaks at 12-24 hours
2. High-flow 100% oxygen for ALL fire victims (reduces COHb half-life)
3. Empirical hydroxocobalamin when cyanide suspected (lactate >10, unexplained acidosis)
4. Bronchoscopy for diagnosis (AIS grading) and therapy (cast removal)
5. Lung-protective ventilation for ARDS
6. Consider HBOT for significant CO exposure with LOC or neurological symptoms

CICM Exam Tips:

• Know the pathophysiology cold - thermal vs chemical vs systemic
• Be able to discuss airway timing decisions with rationale
• Compare and contrast CO and cyanide mechanisms and treatments
• Cite the Weaver trial for HBOT evidence (PMID: 12362006)
• Acknowledge HEPBURN trial negative for nebulised heparin (PMID: 26868625)
• Always include Australian/NZ context (bushfires, Indigenous health, retrieval)

Smoke inhalation remains a significant cause of morbidity and mortality in burn patients. Early recognition, aggressive airway management, and targeted antidotal therapy can be life-saving.