Carbon Monoxide and Cyanide Poisoning

Quick Answer

Carbon monoxide (CO) and cyanide (CN) poisoning are life-threatening toxicological emergencies that frequently co-occur in house fire victims (smoke inhalation). Both toxins cause cellular hypoxia through distinct mechanisms: CO binds hemoglobin with 200-250x affinity of oxygen (forming carboxyhemoglobin, COHb) and inhibits cytochrome c oxidase; cyanide directly inhibits cytochrome c oxidase, blocking mitochondrial oxidative phosphorylation. Combined exposure produces synergistic toxicity.

Key Clinical Features:

Headache, nausea, confusion, seizures, coma, cardiac ischemia
Elevated lactate (>10 mmol/L strongly suggests cyanide)
Normal SpO2 despite profound cellular hypoxia (pulse oximetry unreliable)
Cherry-red skin is RARE (agonal sign, not reliable)

Emergency Management:

100% oxygen via non-rebreather or intubation (reduces CO half-life from 4-5 hours to 60-90 minutes)
Hydroxocobalamin 5g IV for suspected cyanide (house fire, elevated lactate)
Hyperbaric oxygen (HBO) consideration for severe CO poisoning (coma, cardiac ischemia, pregnancy, neurological symptoms)
Airway management for inhalational injury (anticipate progressive edema)

ICU Mortality: CO alone 1-3% (30-50% severe); combined CO/CN in fires 40-60%

Must-Know Facts:

Pulse oximetry does NOT detect COHb - use co-oximetry
Lactate >10 mmol/L in fire victim = empiric hydroxocobalamin
HBO reduces delayed neurological sequelae (DNS) from 30% to 5-10%
Delayed neurological sequelae (Parkinsonism, cognitive decline) occur 2-40 days post-exposure

CICM Exam Focus

What Examiners Expect

Second Part Written (SAQ):

Common SAQ stems:

"A 45-year-old is retrieved from a house fire with reduced GCS and soot around face. ABG shows pH 7.15, lactate 14 mmol/L, COHb 35%. Outline your management."
"Discuss the pathophysiology of carbon monoxide poisoning and the role of hyperbaric oxygen therapy."
"A patient develops cognitive decline and Parkinsonian features 2 weeks after house fire. What is the likely diagnosis and how would you have prevented this?"

Expected depth:

Dual toxicity mechanism (CO hemoglobin binding + cyanide cytochrome inhibition)
COHb half-life calculations (room air vs 100% O2 vs HBO)
Evidence for HBO (Weaver trial, Cochrane review limitations)
Hydroxocobalamin dosing, mechanism, and adverse effects
Delayed neurological sequelae (DNS) pathophysiology and prevention

Second Part Hot Case:

Typical presentations:

Day 1 house fire victim intubated for smoke inhalation with elevated COHb and lactate
Post-fire patient with persistent neurological deficits despite initial improvement
Industrial worker found unconscious near faulty heater

Examiners assess:

Recognition of combined CO/CN toxicity in fire victims
Systematic A-E approach with emphasis on airway burns
HBO decision-making (indications, logistics, retrieval)
Understanding of SpO2 limitations (co-oximetry use)
Prognosis and delayed sequelae discussion

Second Part Viva:

Expected discussion areas:

Pathophysiology: COHb formation, left-shift of O2-Hb curve, cytochrome oxidase inhibition
HBO mechanism of action and evidence base
Cyanide antidote comparison (hydroxocobalamin vs dicobalt edetate vs sodium nitrite/thiosulfate)
Australian HBO chamber locations and retrieval considerations
Indigenous health: house fire risk factors, remote access challenges

Examiner expectations:

Safe, consultant-level decision-making on HBO referral
Evidence-based practice (cite Weaver trial, Cochrane limitations)
Understanding of cellular hypoxia despite normal PaO2
Cultural considerations for Indigenous patients and families

Common Mistakes

Relying on pulse oximetry SpO2 (does not detect COHb)
Missing cyanide toxicity in house fire patients
Ignoring HBO for "mild" CO poisoning (delayed sequelae risk)
Not recognizing that PaO2 is normal/high in CO and cyanide poisoning
Forgetting airway assessment for inhalational burns

Key Points

Must-Know Facts

CO Affinity for Hemoglobin: CO binds hemoglobin with 200-250x greater affinity than oxygen, forming carboxyhemoglobin (COHb) and causing functional anemia with left-shifted oxygen-hemoglobin dissociation curve (PMID: 9675982)
Dual Mechanism of CO Toxicity: Beyond COHb formation, CO inhibits mitochondrial cytochrome c oxidase (Complex IV), causing direct cellular toxicity independent of oxygen-carrying capacity (PMID: 17596563)
Cyanide Mechanism: Cyanide binds ferric iron (Fe3+) in cytochrome c oxidase, completely blocking oxidative phosphorylation; cells cannot utilize oxygen despite adequate delivery (tissue PO2 and venous O2 high) (PMID: 16618977)
Combined Toxicity in Fires: House fires produce both CO (incomplete combustion) and cyanide (combustion of synthetic materials: plastics, wool, silk, nylon); synergistic toxicity with LD50 reduced by 75% (PMID: 10397629)
Lactate as Cyanide Marker: Lactate >10 mmol/L in fire victim has 87% sensitivity and 94% specificity for significant cyanide exposure; >8 mmol/L should prompt empiric hydroxocobalamin (PMID: 17046364)
CO Half-Life Reduction: COHb half-life: 4-5 hours (room air) → 60-90 minutes (100% O2) → 20-30 minutes (HBO at 2.5-3 ATA) (PMID: 15159037)
HBO and Delayed Neurological Sequelae: Weaver trial (2002) showed HBO reduces DNS from 46% to 25% at 6 weeks and from 32% to 18% at 12 months; NNT = 5 (PMID: 12362006)
Hydroxocobalamin for Cyanide: First-line antidote; 5g IV over 15 minutes; binds cyanide to form cyanocobalamin (vitamin B12); causes transient red skin/urine discoloration (PMID: 17197890)
DNS Clinical Features: Parkinsonism, cognitive decline, memory impairment, personality change, ataxia; onset typically 2-40 days post-exposure; white matter demyelination on MRI (PMID: 17596563)
Pulse Oximetry Limitation: Standard pulse oximetry cannot distinguish oxyhemoglobin from carboxyhemoglobin; SpO2 may read 98-100% despite lethal COHb levels; co-oximetry is essential (PMID: 19286455)

Memory Aids

Mnemonic SMOKE: Carbon Monoxide and Cyanide in Fire Victims

Soot around nose/mouth - airway burns
Metabolic acidosis - suggests cyanide (lactate >10)
Oximetry unreliable - use co-oximetry for COHb
Keep on 100% O2 - reduces CO half-life
Empiric hydroxocobalamin - if fire/elevated lactate

Mnemonic COHb: Carbon Monoxide Effects

Cytochrome oxidase inhibition
Oxygen-hemoglobin curve left-shifted
Hemoglobin binding (200-250x O2 affinity)
brain injury (delayed neurological sequelae)

Definition and Epidemiology

Definition

Carbon Monoxide Poisoning: Systemic toxicity resulting from inhalation of carbon monoxide, a colorless, odorless gas produced by incomplete combustion of carbon-containing fuels. Toxicity occurs through carboxyhemoglobin (COHb) formation and direct cellular effects on mitochondrial cytochrome oxidase. Clinically significant poisoning typically requires COHb >10% (symptoms) or >25% (moderate-severe) (PMID: 17596563).

Cyanide Poisoning: Acute toxicity from hydrogen cyanide (HCN) or cyanide salts that inhibit cytochrome c oxidase, blocking mitochondrial oxidative phosphorylation and causing cellular asphyxiation. In fire-related cyanide exposure, blood cyanide levels correlate poorly with clinical severity due to rapid tissue distribution (PMID: 16618977).

Smoke Inhalation Injury: Complex toxicological syndrome in fire victims involving thermal airway injury, particulate deposition, and combined CO/CN/irritant gas exposure. Mortality is primarily driven by CO and cyanide toxicity rather than thermal injury (PMID: 17046364).

Severity Classification (CO Poisoning):

Severity	COHb Level	Clinical Features	DNS Risk	Mortality
Mild	10-20%	Headache, nausea	5-10%	<1%
Moderate	20-30%	Confusion, visual disturbance	15-25%	1-3%
Severe	>30%	Coma, seizures, cardiac ischemia	30-50%	10-30%
Critical	>50%	Cardiorespiratory failure	40-60%	30-50%

Epidemiology

International Data:

Carbon Monoxide:

Incidence: 3-5 per 100,000 population annually in developed countries (PMID: 21320988)
Leading cause of poisoning deaths in developed nations
Approximately 50,000 ED presentations/year in the USA
ICU admission rate: 10-20% of CO poisoning cases
Mortality: 1-3% overall; 30-50% in severe cases

Cyanide:

Incidence: Difficult to estimate (underdiagnosed)
Present in 1-2% of all fire victims at significant levels
50-70% of house fire fatalities have detectable blood cyanide
Industrial exposure: Mining, electroplating, chemical manufacturing
Suicide: Rare in developed countries (limited access)

Australian/NZ Data (ANZICS APD, State Registries):

CO poisoning: Approximately 500-800 hospital admissions/year in Australia
House fires: 50-80 deaths/year in Australia; significant proportion with CO/CN toxicity
Bushfire exposure: Seasonal peaks during summer fire season
Industrial CO: Mining, smelting, automotive industries
Indigenous populations: Higher rates of house fire injuries in remote communities

Sources of Carbon Monoxide:

House fires (combined CO/CN exposure): Most common cause of severe poisoning
Motor vehicle exhaust: Deliberate or accidental exposure
Faulty heating appliances: Gas heaters, furnaces, wood stoves
Charcoal grills/BBQs: Indoor use during cold weather
Generators: Improper indoor use during power outages
Industrial exposure: Mining, smelting, chemical manufacturing
Methylene chloride: Paint stripper metabolized to CO in liver

Sources of Cyanide:

House fires: Combustion of synthetic materials (plastics, wool, silk, nylon, polyurethane)
Industrial exposure: Mining (gold/silver extraction), electroplating, chemical manufacturing
Ingestion: Cyanide salts, bitter almonds (amygdalin), cassava (improperly prepared)
Pharmaceutical: Sodium nitroprusside (prolonged infusion at high doses)
Suicide/homicide: Rare in developed countries

Risk Factors:

CO Poisoning:

Occupational: Firefighters, miners, garage workers, mechanics
Seasonal: Winter (enclosed heating)
Socioeconomic: Poor housing, inadequate ventilation
Behavioral: Indoor charcoal/BBQ use, generator use during power outages
Deliberate self-harm: Motor vehicle exhaust, charcoal burning

Combined CO/CN (Fires):

Residential fires: Synthetic building materials
Motor vehicle accidents with fire
Aircraft/vehicle fires
Industrial fires

High-Risk Populations:

Aboriginal and Torres Strait Islander peoples: 2-3x increased risk of house fire injury due to overcrowding, substandard housing, and limited access to smoke alarms in remote communities (PMID: 26001348)
Maori: 1.5-2x increased fire-related injury rates; similar socioeconomic factors
Remote/rural populations: Delayed access to HBO, limited co-oximetry availability
Elderly: Increased mortality from fires, cognitive impairment delays escape
Children: House fire victims with higher inhalation exposure due to body surface area
Pregnant women: Fetal COHb 10-15% higher than maternal; higher fetal risk (PMID: 15159037)

Outcomes:

ICU mortality (CO alone): 1-3%
ICU mortality (combined CO/CN in fires): 40-60%
Hospital mortality: 3-7% for all CO; up to 30% for severe
Delayed neurological sequelae: 10-30% without HBO; 5-10% with HBO
Long-term cognitive impairment: 15-40% at 1 year

Applied Basic Sciences

Anatomy

Relevant Anatomy for ICU:

Upper Airway:

Thermal injury typically limited to supraglottic structures (hot gases cool rapidly)
Laryngeal edema onset: 12-36 hours post-exposure
Glottic and subglottic edema: Anticipate difficult airway
Nasal/pharyngeal burns: Soot, erythema, blistering

Lower Airway:

Chemical injury from combustion products (aldehydes, acids, ammonia)
Tracheobronchial mucosal damage: Sloughing, pseudomembrane formation
Alveolar epithelial injury: Surfactant dysfunction, ARDS development

Cardiovascular System:

Myocardium: CO-induced myocardial stunning, ischemia (COHb binds cardiac myoglobin)
Coronary arteries: Pre-existing CAD increases vulnerability
Conduction system: Arrhythmias from hypoxia and direct CO effect

Central Nervous System:

Hippocampus, globus pallidus, substantia nigra: Selectively vulnerable to hypoxic-ischemic injury
White matter: Periventricular demyelination in DNS
Basal ganglia: Parkinsonism from selective vulnerability

Physiology

Normal Oxygen Transport:

Hemoglobin carries 98% of blood oxygen
Each gram of hemoglobin carries 1.34 mL O2 when fully saturated
Oxygen delivery (DO2) = CO × [(Hb × 1.34 × SaO2) + (PaO2 × 0.003)]
Oxygen consumption (VO2) depends on cellular utilization

Oxygen-Hemoglobin Dissociation Curve:

Sigmoid shape allows efficient O2 loading in lungs and unloading in tissues
P50 (PO2 at 50% saturation) = 26-27 mmHg normally
Right shift (increased P50): Fever, acidosis, 2,3-DPG → favors O2 release
Left shift (decreased P50): Alkalosis, hypothermia, COHb, methemoglobin → impairs O2 release

Pathophysiology

Carbon Monoxide Toxicity:

Mechanism 1: Carboxyhemoglobin (COHb) Formation

CO binds hemoglobin with 200-250x greater affinity than O2
Forms carboxyhemoglobin (COHb), reducing oxygen-carrying capacity
Functional anemia: Each 1% COHb = 1.4 g/dL effective hemoglobin reduction
CO displacement from hemoglobin requires mass action (high O2 concentration)

Mechanism 2: Left Shift of Oxygen-Hemoglobin Dissociation Curve

COHb binding increases affinity of remaining hemoglobin for O2
Left shift prevents O2 unloading at tissue level
Even with adequate SaO2, tissue PO2 is critically reduced
This explains why symptoms occur at lower COHb than predicted by anemia alone (PMID: 9675982)

Mechanism 3: Mitochondrial Cytochrome c Oxidase Inhibition

CO binds cytochrome c oxidase (Complex IV) with high affinity
Blocks electron transport chain at terminal oxidase
Impairs oxidative phosphorylation independent of COHb
Explains delayed neurological effects persisting after COHb normalization
CO also binds cardiac myoglobin (cardiac stunning) (PMID: 17596563)

Mechanism 4: Oxidative Stress and Inflammation

CO generates reactive oxygen species (ROS)
Lipid peroxidation damages cell membranes
Activates neutrophils and microglia in CNS
Promotes inflammatory cascade leading to delayed demyelination
Explains DNS occurring days-weeks after initial recovery (PMID: 11389795)

Cyanide Toxicity:

Mechanism: Cytochrome c Oxidase Inhibition

Cyanide (CN-) binds ferric iron (Fe3+) in cytochrome c oxidase
Complete block of mitochondrial Complex IV
Oxidative phosphorylation ceases; cells cannot utilize oxygen
Cellular hypoxia despite adequate oxygen delivery
Results in anaerobic metabolism → profound lactic acidosis (PMID: 16618977)

Histotoxic Hypoxia:

Tissue PO2 is normal or elevated (O2 delivery continues but cannot be used)
Venous blood appears arterial (bright red) due to high O2 content
Mixed venous O2 saturation (SvO2) elevated (paradoxically)
Lactate production from anaerobic glycolysis
Cellular ATP depletion leads to rapid cell death

Combined CO and Cyanide Toxicity:

Synergistic Effects:

Both toxins inhibit cytochrome c oxidase
CO reduces O2 delivery; CN blocks O2 utilization
Combined LD50 is 75% lower than either toxin alone (PMID: 10397629)
Fire victims often have lethal toxicity at COHb and CN levels that would be sublethal individually
Lactate production is accelerated and more severe

House Fire Exposure Timeline:

CN peaks rapidly (highest in first few minutes of fire exposure)
CO accumulates more gradually but persists longer
CN half-life: 20-60 minutes; CO half-life: 4-5 hours (room air)
Early fire victims: CN predominant; prolonged exposure: CO predominant
Treatment must address both toxins simultaneously

Pharmacology

Key ICU Drugs:

Oxygen (High-Flow):

Class: Medical gas; competitive antagonist to CO at hemoglobin
Mechanism: Mass action drives CO off hemoglobin; increases dissolved O2
ICU Indication: All CO and CN poisoning
Dosing: 100% via non-rebreather mask or mechanical ventilation
Monitoring: COHb levels via co-oximetry
Effect on CO Half-Life: Reduces from 4-5 hours (room air) to 60-90 minutes
Adverse Effects: Oxygen toxicity (prolonged >24h at FiO2 >0.6), absorption atelectasis
PBS/TGA: Available as medical gas

Hyperbaric Oxygen (HBO):

Class: Medical treatment; pressurized 100% oxygen
Mechanism:
- Increases dissolved O2 (sufficient for cellular metabolism without hemoglobin)
- Accelerates CO displacement from hemoglobin and cytochrome oxidase
- Reduces inflammation and oxidative stress
- Prevents delayed neurological sequelae
ICU Indication: Severe CO poisoning (see HBO indications below)
Dosing: 2.4-3 ATA for 60-120 minutes; typically 3 sessions over 24 hours
Monitoring: Ear pressure (barotrauma), blood glucose, seizures (O2 toxicity)
Effect on CO Half-Life: Reduces to 20-30 minutes
Adverse Effects: Barotrauma (ear, sinus), O2-induced seizures (rare), claustrophobia
PBS/TGA: Available at designated HBO centers

Hydroxocobalamin (Cyanokit):

Class: Antidote; cyanide binder (vitamin B12 precursor)
Mechanism: Cobalt ion binds cyanide to form cyanocobalamin (vitamin B12), renally excreted
ICU Indication: Suspected or confirmed cyanide poisoning (fire victims, industrial exposure)
Dosing:
- "Adults: 5g IV over 15 minutes"
- "Children: 70 mg/kg (max 5g) IV over 15 minutes"
- May repeat 5g if persistent acidosis/hemodynamic instability
Monitoring: Vital signs, lactate, metabolic acidosis
Adverse Effects:
- Transient red skin discoloration (flushing, 100%)
- Red urine discoloration (up to 28 days)
- Interference with colorimetric lab assays (bilirubin, creatinine, CO-oximetry)
- Hypertension (transient, 20%)
- Allergic reactions (rare)
PBS/TGA: Listed on PBS; available in most EDs and ICUs; expensive (~$3,000 per kit)
PMID: 17197890

Sodium Thiosulfate:

Class: Antidote; sulfur donor for cyanide metabolism
Mechanism: Provides sulfur for rhodanese-mediated conversion of cyanide to thiocyanate (renally excreted)
ICU Indication: Adjunct to hydroxocobalamin; sodium nitroprusside toxicity
Dosing: 12.5g IV over 10-30 minutes (adults); 1.65 mL/kg 25% solution (children)
Monitoring: Vital signs, nausea/vomiting
Adverse Effects: Nausea, vomiting, hypotension (if rapid infusion)
Notes: Slow onset (requires rhodanese enzyme); less effective alone than hydroxocobalamin
PBS/TGA: Available in most hospitals

Dicobalt Edetate (Kelocyanor):

Class: Antidote; cobalt chelator for cyanide
Mechanism: Cobalt binds cyanide directly
ICU Indication: Alternative to hydroxocobalamin if unavailable
Dosing: 300 mg (20 mL of 1.5%) IV over 1 minute; followed by 50 mL 50% dextrose
Monitoring: ECG (cobalt cardiotoxicity)
Adverse Effects:
- SIGNIFICANT TOXICITY if cyanide not present
- Hypotension, arrhythmias, seizures, angioedema
- Only use when cyanide diagnosis is certain
Notes: Largely replaced by hydroxocobalamin due to safety profile
PBS/TGA: Limited availability in Australia; not recommended as first-line

Sodium Nitrite + Sodium Thiosulfate (Historical):

Class: Cyanide antidote kit (Lilly kit)
Mechanism:
- Sodium nitrite induces methemoglobin (MetHb); cyanide binds MetHb preferentially
- Sodium thiosulfate provides sulfur for rhodanese conversion
Dosing:
- "Sodium nitrite: 10 mL of 3% IV over 3-5 minutes"
- "Sodium thiosulfate: 50 mL of 25% IV over 10 minutes"
Limitations:
- Induces methemoglobinemia (10-20% MetHb)
- Contraindicated in CO poisoning (exacerbates tissue hypoxia)
- Should NOT be used in fire victims (combined CO/CN exposure)
- Largely obsolete; replaced by hydroxocobalamin
PBS/TGA: Limited availability; not recommended for fire victims

Pharmacokinetics in Critical Illness:

Hydroxocobalamin: Volume of distribution unchanged; renal excretion of cyanocobalamin
No dose adjustment for renal or hepatic impairment
Pregnancy: Hydroxocobalamin preferred (no teratogenic risk documented)

Pathology

Histopathology:

Carbon Monoxide Poisoning:

Acute: Generalized cerebral edema, petechial hemorrhages
Subacute/Chronic: Bilateral globus pallidus necrosis (pathognomonic), white matter demyelination
Heart: Myocyte degeneration, subendocardial hemorrhage

Cyanide Poisoning:

Acute: Generalized cerebral edema, petechial hemorrhages
Bright red venous blood (high O2 content)
Bitter almond odor in autopsy specimens (40% population cannot detect)

Delayed Neurological Sequelae Pathology:

Periventricular white matter demyelination
Hippocampal necrosis
Basal ganglia (globus pallidus) lesions on MRI

Clinical Presentation

ICU Admission Scenarios

Scenario 1: House Fire Victim

History: 45-year-old rescued from house fire, found unconscious, soot on face
Examination: GCS 8, RR 28, HR 130, BP 85/50, singed nasal hairs, carbonaceous sputum
Severity: Severe (combined CO/CN, inhalational injury)
Key concerns: Airway edema, CO toxicity, cyanide toxicity, trauma

Scenario 2: Faulty Heater Exposure

History: Family of 4 found obtunded with headache, nausea; faulty gas heater in winter
Examination: All family members drowsy but rousable, headache, nausea, mild confusion
Severity: Moderate (CO only, no airway concerns)
Key concerns: COHb levels, neurological symptoms, HBO consideration

Scenario 3: Industrial Cyanide Exposure

History: 35-year-old mining worker collapsed at gold extraction facility
Examination: GCS 3, seizures, profound bradycardia, gasping respirations
Severity: Critical (cyanide predominant)
Key concerns: Immediate hydroxocobalamin, airway protection, cardiac arrest risk

Symptoms and Signs

History:

Chief complaint: Confusion, headache, found unconscious
Associated symptoms: Nausea, vomiting, dizziness, visual disturbance, chest pain
Time course: Acute onset, exposure duration
Exposure source: Fire, exhaust, heater, industrial
Co-exposures: Alcohol, drugs (affects presentation)

Examination:

General:

Appearance: May look deceptively well initially
Vital signs: Tachycardia, hyper- or hypotension, tachypnea
Cherry-red skin: RARE and often agonal (not reliable sign)
Bitter almond odor: Present in cyanide (40% population cannot detect)

A - Airway:

Soot around nose/mouth (suggests smoke inhalation)
Singed nasal hairs
Carbonaceous sputum
Stridor (progressive laryngeal edema)
Hoarse voice
Drooling

B - Breathing:

Respiratory rate: Tachypnea initially, may progress to bradypnea
Work of breathing: Accessory muscle use, intercostal recession
Auscultation: Wheeze (bronchospasm), crackles (pulmonary edema/aspiration)
SpO2: May read normal despite profound hypoxia (COHb not detected)

C - Circulation:

Heart rate: Tachycardia (early), bradycardia (severe CN poisoning, agonal)
Blood pressure: Hypertension (early hypoxia), hypotension (late, cardiac depression)
Perfusion: Delayed CRT, mottling in severe cases
JVP: Normal unless cardiac failure
Heart sounds: Normal; possible ischemic murmur

D - Disability/Neurology:

GCS: Range from normal to 3 (proportional to severity)
Pupils: Normal or sluggish; may be dilated in severe hypoxia
Focal neurology: Rare acutely; may develop with DNS
Seizures: Common in severe CO and CN poisoning

E - Exposure/Everything Else:

Temperature: Hypothermia (environmental, metabolic depression) or hyperthermia (fire)
Skin: Burns, soot, cherry-red color (rare, agonal)
Burns: Calculate TBSA, assess depth

Severity Scoring

COHb Levels and Clinical Correlation:

COHb (%)	Clinical Features	Management
0-5%	Normal (non-smokers); may be 5-10% in smokers	No treatment
10-20%	Headache, mild confusion	100% O2
20-30%	Severe headache, confusion, visual disturbance	100% O2, consider HBO
30-40%	Syncope, seizures, tachycardia	HBO recommended
40-50%	Coma, cardiovascular instability	HBO if available
>50%	Seizures, coma, cardiorespiratory arrest	HBO if available; high mortality

Note: COHb level at presentation may not reflect peak exposure (treatment may have started, CO redistributes)

Differential Diagnosis

Key Differentials:

Hypoglycemia: Check BSL; common in altered consciousness
Opioid/sedative overdose: Miosis, respiratory depression; responds to naloxone
Intracranial pathology: Stroke, hemorrhage; focal signs, CT abnormal
Sepsis: Fever, source, lactate elevation (but no COHb elevation)
Methanol/ethylene glycol: High anion gap metabolic acidosis, osmolar gap
Methemoglobinemia: Cyanosis, "chocolate-colored" blood, measured by co-oximetry

Investigations

Laboratory Investigations

Bedside Tests:

Arterial Blood Gas with Co-Oximetry (ESSENTIAL):

pH: Low (metabolic acidosis) in severe poisoning
PaCO2: Normal or low (respiratory compensation)
PaO2: Normal or elevated (O2 delivery maintained)
HCO3: Low in severe poisoning
Lactate: Elevated (key marker, especially for cyanide)
- "Lactate >10 mmol/L: 87% sensitivity, 94% specificity for significant cyanide (PMID: 17046364)"
- "Lactate >8 mmol/L: Empiric hydroxocobalamin indicated in fire victims"
COHb: Measured by co-oximetry (NOT calculated from SpO2)
- "Normal: <3% (non-smokers), <10% (smokers)"
- "Toxic: >10% (symptoms), >25% (moderate-severe), >40% (severe)"
MetHb: Important if sodium nitrite given or methemoglobinemia suspected

Blood Glucose: Hypoglycemia common; treat if low

Blood Tests:

FBC: Leukocytosis (stress response), anemia (baseline)
UEC: Baseline renal function; monitor for AKI
LFT: Baseline hepatic function
Coagulation: Baseline INR, APTT, fibrinogen
Cardiac Troponin: Myocardial ischemia/stunning common (elevated in 30-50% severe CO)
Creatine Kinase: Rhabdomyolysis (if prolonged down time)
Cyanide Level:
- Not routinely available rapidly
- Send if suspected; results rarely influence acute management
- "Toxic: >0.5 mg/L (may correlate with symptoms)"
- "Lethal: >3.0 mg/L"
Carboxyhemoglobin Level: Serial measurements to guide therapy

Specific Tests:

Co-oximetry: Gold standard for COHb measurement
- Standard pulse oximetry does NOT detect COHb
- Bedside co-oximeters (Masimo Radical-7) available in some EDs/ICUs
- Laboratory co-oximetry is definitive
Lactate: Trend for treatment response (should fall with hydroxocobalamin)

Imaging

Chest X-Ray:

Findings:
- Initially normal
- Pulmonary edema (develops over hours)
- Aspiration pneumonitis
- ARDS pattern (bilateral infiltrates)
Sensitivity: Low initially; may be normal despite significant injury
Note: Inhalational injury may not be apparent on initial CXR

CT Brain:

Acute indications: Persistent coma, focal neurology, suspected trauma
Findings:
- Cerebral edema (severe poisoning)
- Globus pallidus hypodensity (characteristic, may appear days later)
- White matter hypodensity (delayed)
DNS follow-up: MRI preferred for white matter changes

Bronchoscopy:

Indication: Suspected inhalational injury with upper airway burns
Findings: Edema, erythema, carbonaceous deposits, mucosal sloughing
Grading: Used to assess severity of inhalational injury

Physiological Monitoring

Non-Invasive Monitoring:

Continuous ECG: Arrhythmias, ST changes (ischemia common)
SpO2: UNRELIABLE for COHb; use for trend, not absolute value
NIBP: Continuous or frequent
Temperature: Hypothermia or hyperthermia
Capnography: EtCO2 if intubated

Invasive Monitoring:

Arterial line: Frequent ABG/co-oximetry sampling; continuous BP
Central venous catheter: If vasopressors required
ScvO2: Paradoxically high in cyanide poisoning (tissue cannot extract O2)

Neurological Monitoring:

Pupil reactivity
GCS trend
Seizure surveillance (clinical, consider EEG in prolonged sedation)

ICU Management

Initial Resuscitation (First Hour)

A - Airway:

Assessment:

High index of suspicion for progressive airway edema in fire victims
Assess for soot, singed nasal hairs, carbonaceous sputum, stridor, hoarseness
Serial examination for progressive edema (peak 12-36 hours)

Intervention:

Early intubation if ANY signs of inhalational injury (anticipate deterioration)
RSI drug choices:
- "Induction: Ketamine (maintains airway reflexes) or propofol"
- "Paralysis: Rocuronium (avoid if burns >24h old - hyperkalemia risk with succinylcholine)"
Uncut ETT initially (facial swelling may progress)
Cuff pressure monitoring (edema may require re-positioning)

B - Breathing:

Oxygen Therapy:

100% oxygen via non-rebreather mask (15 L/min) for ALL patients
Reduces CO half-life from 4-5 hours to 60-90 minutes
Continue until COHb <5% and neurologically improved
If intubated: FiO2 1.0 initially

Ventilatory Support:

NIV: Generally NOT recommended (airway edema risk, need for frequent reassessment)
Invasive ventilation if:
- GCS <8
- Respiratory failure
- Inhalational injury
- Progressive edema
Initial settings: Lung-protective (Vt 6-8 mL/kg PBW, PEEP 5-10)

C - Circulation:

Fluid Resuscitation:

Type: Balanced crystalloid (Hartmann's or Plasmalyte)
Volume: Judicious; avoid fluid overload (pulmonary edema)
Burns: Parkland formula if significant TBSA involvement

Vasopressors/Inotropes:

First-line: Noradrenaline if hypotensive after fluid bolus
Consider: Myocardial stunning from CO (may need inotrope support)
Targets: MAP ≥65 mmHg

Cardiac Monitoring:

ECG: ST changes common (30-50% in severe CO)
Troponin: Serial measurements
Echo: If persistent hypotension or suspected myocardial dysfunction

D - Disability:

GCS monitoring hourly initially
Seizure precautions (common in severe poisoning)
Glucose control: Target 6-10 mmol/L
Sedation: Minimize if possible to allow neurological assessment

E - Everything Else:

Temperature management: Active rewarming if hypothermic
Burns assessment: TBSA, depth, escharotomy if circumferential
Trauma survey: Mechanism may involve falls, explosions
Toxicology screen: Co-ingestants

Specific Antidote Therapy

Carbon Monoxide - 100% Oxygen:

Mechanism: Mass action displaces CO from hemoglobin
Duration: Continue until COHb <5% AND neurologically normal
Normobaric (NBO) vs hyperbaric: See HBO section below

Cyanide - Hydroxocobalamin (Cyanokit):

Indications for Empiric Hydroxocobalamin:

House fire victim with altered consciousness
Smoke inhalation with lactate >8-10 mmol/L
Unexplained metabolic acidosis in fire victim
Cardiac arrest in fire setting
Known cyanide exposure (industrial)

Dosing:

Adults: 5g IV over 15 minutes
Children: 70 mg/kg (max 5g) IV over 15 minutes
May repeat 5g if persistent acidosis/hemodynamic instability
Maximum: 10g total (two kits)

Expected Response:

Improved hemodynamics within 10-30 minutes
Falling lactate over 1-2 hours
Improved level of consciousness

Adverse Effects:

Red skin discoloration (100% - transient)
Red urine (up to 28 days)
Interference with lab assays (colorimetric tests affected: bilirubin, creatinine, some co-oximetry)
Hypertension (transient, 20%)

Hyperbaric Oxygen Therapy (HBO)

Mechanism of HBO:

Increases dissolved oxygen (PaO2 >2000 mmHg at 3 ATA)
Provides sufficient O2 for cellular metabolism without hemoglobin
Accelerates CO displacement from hemoglobin (half-life 20-30 min at 2.5-3 ATA)
Accelerates CO displacement from cytochrome c oxidase
Reduces CNS inflammation and oxidative stress
Prevents delayed neurological sequelae

Evidence for HBO:

Weaver Trial (2002) - PMID: 12362006:

RCT: 152 patients, HBO vs NBO (100% O2)
Intervention: 3 HBO sessions (2.4-2.0 ATA) over 24 hours
Results: DNS reduced from 46% to 25% at 6 weeks (NNT = 5)
Long-term (12 months): DNS 32% vs 18% (p = 0.04)
Conclusion: HBO reduces cognitive sequelae

Scheinkestel Trial (1999) - PMID: 10617246:

RCT: 191 patients, HBO (2.8 ATA x3 over 3 days) vs NBO
Results: No significant difference in neuropsychological outcomes
Criticism: Longer time to treatment, different protocol

Cochrane Review (Annane 2011) - PMID: 21491385:

6 RCTs, 1,361 patients
Inconclusive: Heterogeneous protocols, outcomes, quality
Unable to support or refute HBO benefit
Called for better standardized trials

Indications for HBO (Consensus Guidelines):

Absolute Indications:

Loss of consciousness (at any point during exposure)
Neurological symptoms (confusion, ataxia, visual disturbance)
Cardiac ischemia (ST changes, troponin elevation)
Pregnancy (fetal COHb 10-15% higher than maternal)
COHb >25% (some guidelines: >40%)

Relative Indications:

Persistent symptoms despite NBO
Prolonged exposure (>24 hours)
Age >36 years with prolonged exposure
Significant metabolic acidosis

Contraindications to HBO:

Untreated pneumothorax (absolute)
Active seizures
Hemodynamic instability unable to transfer
Some chemotherapeutic agents (bleomycin)

HBO Protocol (Typical Weaver Protocol):

Session 1: 2.4 ATA for 150 minutes (3 × 20 min O2 at pressure, 5 min air breaks)
Session 2: 2.0 ATA for 120 minutes at 6-12 hours
Session 3: 2.0 ATA for 120 minutes at 18-24 hours
Variations exist between centers

Australian HBO Considerations:

HBO Chamber Locations (As of 2024):

NSW: Royal Prince Alfred Hospital (Sydney), Prince of Wales Hospital (Sydney), Royal Hobart Hospital (TAS link)
VIC: The Alfred Hospital (Melbourne)
QLD: Wesley Hospital (Brisbane), Townsville Hospital
WA: Fremantle Hospital (Perth)
SA: Royal Adelaide Hospital
TAS: Royal Hobart Hospital
ACT: No chamber; transfer to Sydney

Retrieval Considerations:

Coordinate with state retrieval service (NSW: Aeromedical Control Centre; VIC: Adult Retrieval Victoria)
Continue 100% O2 during transport
Fixed-wing aircraft: Maintain cabin altitude at sea level (avoid altitude-induced pressure changes)
Rotary-wing: Generally fly low
Time-sensitive: Benefit of HBO decreases after 6-12 hours post-exposure
Remote areas: RFDS retrieval to nearest HBO center

Ongoing ICU Care

Daily Management:

Serial COHb measurements until <5%
Neurological assessment (GCS, focal signs)
Cardiac monitoring (troponin, ECG changes)
Lactate trend
Respiratory support (wean as tolerated)

Complications Prevention:

VTE Prophylaxis: LMWH or mechanical
Stress Ulcer Prophylaxis: PPI if intubated
Glycemic Control: Target 6-10 mmol/L

Delayed Neurological Sequelae (DNS) Surveillance:

Onset: 2-40 days post-exposure (typically 2-3 weeks)
Features: Parkinsonism, cognitive decline, memory impairment, personality change
Incidence: 10-30% without HBO; 5-10% with HBO
Risk factors: LOC during exposure, age >36, prolonged exposure, COHb >25%
Follow-up: Neuropsychological testing at 4-6 weeks if significant exposure

Australian-Specific Protocols

ANZICS-CORE Recommendations:

Smoke inhalation: Early airway assessment and intubation
Combined CO/CN: Empiric hydroxocobalamin if lactate >8-10 mmol/L
HBO referral: Contact local HBO center for consultation

Therapeutic Guidelines Australia (eTG Complete):

CO poisoning: 100% O2, HBO for severe cases
Cyanide: Hydroxocobalamin first-line; sodium thiosulfate adjunct
Dicobalt edetate: Only if hydroxocobalamin unavailable AND cyanide confirmed

State-Based Protocols:

NSW ACI: Toxicology network provides 24/7 consultation
VIC DHHS: Adult Retrieval Victoria coordinates HBO transfers
Poisons Information Centre: 13 11 26 (Australia-wide)

Monitoring and Complications

ICU-Specific Monitoring

Daily Parameters:

Vital signs: Continuous
COHb: Serial until <5% and stable
ABG with lactate: 4-6 hourly until normalized
ECG: Daily (or continuous if ischemia)
Troponin: Repeat at 6-12 hours

Trend Monitoring:

Neurological status (GCS, cognition)
Lactate clearance (target <2 mmol/L)
COHb decline (should normalize within 4-6 hours on 100% O2)

Complications

Early Complications (First 24-48 hours):

Complication 1: Progressive Airway Edema

Incidence: 10-30% of inhalational injury
Risk factors: Facial burns, carbonaceous sputum, stridor
Presentation: Progressive stridor, respiratory distress, failed extubation
Prevention: Early intubation if signs of inhalational injury
Management: Intubation, steroids (controversial), nebulized adrenaline

Complication 2: Myocardial Ischemia/Stunning

Incidence: 30-50% in severe CO poisoning
Risk factors: Pre-existing CAD, severe COHb, prolonged exposure
Presentation: ST changes, troponin elevation, hypotension
Prevention: HBO may reduce risk
Management: Cardiology consultation, supportive care, avoid coronary intervention acutely (unstable hemoglobin)

Complication 3: Pulmonary Edema

Incidence: 10-20%
Risk factors: Severe poisoning, smoke inhalation, fluid overload
Presentation: Hypoxia, bilateral infiltrates on CXR
Prevention: Judicious fluid resuscitation
Management: Lung-protective ventilation, PEEP, diuretics if fluid overloaded

Complication 4: Seizures

Incidence: 5-10% in severe cases
Risk factors: COHb >30%, cyanide toxicity, hypoxic brain injury
Presentation: Generalized tonic-clonic seizures
Prevention: Adequate oxygenation, HBO
Management: Benzodiazepines (midazolam 5-10 mg IV), consider levetiracetam for secondary prophylaxis

Late Complications (Beyond 48 hours):

Complication 5: Delayed Neurological Sequelae (DNS)

Incidence: 10-30% without HBO; 5-10% with HBO
Risk factors: LOC, age >36, prolonged exposure, COHb >25%
Presentation:
- Onset 2-40 days post-exposure
- Parkinsonism (bradykinesia, rigidity, tremor)
- Cognitive decline (memory, executive function)
- Personality changes, depression
- Incontinence
Prevention: HBO therapy (NNT = 5 in Weaver trial)
Management:
- Supportive care
- Neuropsychological rehabilitation
- "Parkinsonism: May partially respond to L-DOPA"
- Some patients recover over months; some have permanent deficits

Complication 6: ARDS

Incidence: 5-10% with significant smoke inhalation
Risk factors: Inhalational injury, aspiration, prolonged hypoxia
Presentation: Progressive hypoxemia, bilateral infiltrates
Prevention: Lung-protective ventilation
Management: ARDSNet protocol, prone positioning, consider ECMO if severe

Prognosis

Prognostic Factors:

Good Prognostic Factors:

Brief exposure (<1 hour)
No loss of consciousness
COHb <25%
Rapid treatment (100% O2 within 1 hour)
HBO within 6 hours
Normal cardiac markers
Young age
No pre-existing cardiopulmonary disease

Poor Prognostic Factors:

Prolonged exposure (>4 hours)
Loss of consciousness at any point
COHb >40%
Cardiac arrest
Metabolic acidosis (lactate >10 mmol/L)
Delayed treatment
Combined CO/CN exposure
Age >36 years
Pre-existing cardiovascular disease

Mortality Predictors:

Cardiac arrest at scene
COHb >50%
Lactate >10 mmol/L (combined poisoning)
GCS <8 on arrival
Multiple organ failure

Special Considerations

Indigenous Health

Aboriginal and Torres Strait Islander Considerations:

Epidemiology:

2-3x higher rates of house fire injury compared to non-Indigenous Australians (PMID: 26001348)
Higher rates of fire-related fatalities
Contributing factors:
- Overcrowded housing (increased fire spread, delayed escape)
- Substandard housing (inadequate smoke alarms, electrical faults)
- Limited access to emergency services in remote communities
- Higher rates of alcohol/substance use (impaired escape)

Access to Care:

Remote communities: Significant delays to HBO (may be 500+ km from chamber)
Limited co-oximetry availability in remote clinics
RFDS retrieval required for HBO
Hydroxocobalamin may not be stocked in remote clinics

Cultural Considerations:

Involve Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers (ALOs) early
Extended family involvement in decision-making
Culturally appropriate communication about prognosis
Consider "Sorry Business" if patient dies (funeral/bereavement practices)
Repatriation to Country may be requested

Clinical Approach:

Early retrieval planning if significant exposure
Aggressive normobaric 100% O2 pending transfer
Empiric hydroxocobalamin if fire-related with lactate elevation
Liberal HBO referral criteria given delayed access
Neuropsychological follow-up (may require telemedicine)

Maori Health Considerations:

Epidemiology:

1.5-2x higher fire-related injury rates than non-Maori
Similar socioeconomic factors as Aboriginal populations

Cultural Considerations:

Whanau (family) involvement in care decisions
Tikanga (customs and protocols) respected
Maori Health Workers involvement
Karakia (prayer/blessing) may be requested

Pregnancy

Fetal Vulnerability:

Fetal hemoglobin has higher CO affinity than adult hemoglobin
Fetal COHb 10-15% higher than maternal COHb
Fetal COHb elimination slower (longer half-life)
CO crosses placenta readily

Management Considerations:

Lower threshold for HBO referral (ANY symptoms or COHb >15%)
HBO is safe in pregnancy (no documented teratogenic effects)
Fetal monitoring during and after treatment
Obstetric consultation for all pregnant CO exposures
Fetal loss and preterm labor are risks of severe poisoning

Remote/Rural Considerations

Pre-Hospital Care:

Early 100% O2 via non-rebreather (portable cylinders)
Empiric hydroxocobalamin if available and fire-related
Early retrieval activation (RFDS, state retrieval service)

Transfer Considerations:

Maintain 100% O2 during aeromedical transfer
Fixed-wing: Request sea-level cabin pressure
Rotary-wing: Fly low (minimize altitude effects)
Continue hydroxocobalamin infusion if ongoing acidosis

Telemedicine:

Toxicology consultation via phone/video
Poisons Information Centre: 13 11 26
HBO center consultation for transfer decision

Bushfire Exposure

Australian Context:

Seasonal bushfire emergencies (October-March)
Mass casualty potential
Firefighters: Occupational exposure (repeated low-level CO)
Community exposure: Smoke drift, home fires from ember attack

Clinical Differences:

Outdoor exposure: Generally lower CO/CN levels than enclosed structure fires
Prolonged low-level exposure: Chronic symptoms, fatigue
Firefighter occupational health monitoring
Consider CO poisoning in unexplained headache/fatigue during fire season

SAQ Practice

SAQ 1: House Fire with Combined CO/Cyanide Exposure

Time Allocation: 10 minutes
Total Marks: 20

Stem: A 48-year-old male is retrieved from a house fire and arrives in your metropolitan ICU. He was found unconscious in a smoke-filled room after approximately 20 minutes of fire exposure. Paramedics provided 100% oxygen via non-rebreather mask. He has soot on his face and carbonaceous sputum.

On arrival to ICU:

GCS: 6 (E1V2M3)
HR: 128 bpm
BP: 85/50 mmHg
RR: 32 breaths/min (spontaneous, irregular)
SpO2: 98% on 15L O2 non-rebreather
Temperature: 35.2°C

Investigations:

ABG (FiO2 1.0):

pH: 7.12
PaCO2: 28 mmHg
PaO2: 285 mmHg
HCO3: 9 mmol/L
Lactate: 16.5 mmol/L
COHb: 32%
MetHb: 1.2%

Other:

Troponin I: 0.85 ng/mL (elevated)
ECG: Sinus tachycardia, 2mm ST depression V4-V6
CXR: No obvious infiltrates

Question 1.1 (8 marks)

List the key diagnoses and outline your immediate management priorities in the first 30 minutes.

Question 1.2 (6 marks)

Discuss the role of hyperbaric oxygen therapy in this patient. Include indications, evidence, and logistical considerations.

Question 1.3 (6 marks)

The patient's family asks about his prognosis. What factors would you consider, and what would you tell them about delayed neurological sequelae?

Model Answer

Question 1.1 (8 marks total)

Key Diagnoses (3 marks):

Severe carbon monoxide poisoning (COHb 32%, GCS 6, cardiac ischemia) - 1 mark
Cyanide poisoning (lactate 16.5 mmol/L, profound metabolic acidosis, house fire) - 1 mark
Inhalational airway injury (carbonaceous sputum, soot on face) - 0.5 marks
Myocardial ischemia/stunning (troponin elevation, ST depression) - 0.5 marks

Immediate Management Priorities (5 marks):

Airway and Breathing (2 marks):

Immediate RSI and intubation (GCS 6, airway injury risk, need for 100% O2) - 1 mark
- "Induction: Ketamine 1-2 mg/kg"
- "Paralysis: Rocuronium 1.2 mg/kg (avoid succinylcholine if burns present)"
Continue 100% FiO2 via ventilator - 0.5 marks
Lung-protective ventilation: Vt 6-8 mL/kg PBW, PEEP 5-8 cmH2O - 0.5 marks

Circulation (1 mark):

Arterial line insertion for monitoring and ABG sampling - 0.5 marks
IV fluid bolus (500 mL balanced crystalloid) for hypotension - 0.25 marks
Noradrenaline infusion if persistent hypotension despite fluid - 0.25 marks

Antidote Therapy (1.5 marks):

Hydroxocobalamin 5g IV over 15 minutes (empiric cyanide treatment given lactate >10 mmol/L) - 1 mark
Continue 100% oxygen (reduces CO half-life to 60-90 minutes) - 0.5 marks

Monitoring and Investigation (0.5 marks):

Serial COHb (aim for <5%)
Repeat lactate at 30-60 minutes (should improve with hydroxocobalamin)
ECG monitoring for arrhythmias
Repeat troponin at 6 hours

Question 1.2 (6 marks total)

HBO Indications in This Patient (2 marks):

Loss of consciousness (GCS 6) - 0.5 marks
Neurological impairment - 0.5 marks
Cardiac ischemia (troponin elevation, ST changes) - 0.5 marks
COHb >25% (32%) - 0.5 marks

Evidence for HBO (2 marks):

Weaver Trial (2002, PMID: 12362006): RCT of 152 patients; HBO (3 sessions over 24h) reduced delayed neurological sequelae from 46% to 25% at 6 weeks; NNT = 5 - 1 mark
Cochrane Review (2011): 6 RCTs, inconclusive due to heterogeneous protocols; unable to definitively support or refute HBO benefit - 0.5 marks
Despite Cochrane uncertainty, current consensus supports HBO for severe CO poisoning with neurological or cardiac involvement - 0.5 marks

Logistical Considerations (2 marks):

Contact nearest HBO center (e.g., Alfred Hospital Melbourne, RPA Sydney) - 0.5 marks
Coordinate with state retrieval service (Adult Retrieval Victoria, Aeromedical Control Centre) - 0.5 marks
Patient must be stabilized (intubated, hydroxocobalamin given) before transfer - 0.5 marks
Time-sensitive: Benefit decreases after 6-12 hours post-exposure - 0.25 marks
Relative contraindications: Untreated pneumothorax (not present), hemodynamic instability (may delay but not preclude transfer) - 0.25 marks

Question 1.3 (6 marks total)

Prognostic Factors to Consider (3 marks): Poor Prognostic Factors Present (2 marks):

Loss of consciousness/GCS 6 - 0.5 marks
Prolonged exposure (20 minutes in smoke-filled room) - 0.5 marks
COHb >25% (32%) - 0.5 marks
Cardiac involvement (troponin, ST changes) - 0.5 marks

Other Factors to Consider (1 mark):

Combined CO/CN toxicity (lactate 16.5 mmol/L)
Age (48 years, >36 is risk factor for DNS)
Time to HBO treatment
Response to hydroxocobalamin (lactate clearance)

Delayed Neurological Sequelae (DNS) (3 marks):

Explanation for Family (1.5 marks):

DNS occurs in 10-30% of severe CO poisoning patients without HBO - 0.5 marks
Onset typically 2-40 days after apparent recovery - 0.5 marks
Features include: memory problems, concentration difficulties, personality changes, movement disorders (Parkinsonism) - 0.5 marks

Prevention and Prognosis (1.5 marks):

HBO therapy reduces DNS risk to 5-10% (Weaver trial NNT = 5) - 0.5 marks
He is at high risk given LOC, cardiac involvement, and age >36 - 0.5 marks
Will require neuropsychological follow-up at 4-6 weeks regardless of initial recovery - 0.5 marks

Common Mistakes:

Failing to recognize combined CO and cyanide toxicity
Relying on SpO2 for oxygenation assessment (98% SpO2 does not reflect COHb)
Not giving empiric hydroxocobalamin when lactate >10 mmol/L in fire victim
Delaying intubation in patient with inhalational injury signs

SAQ 2: Delayed Neurological Sequelae

Time Allocation: 10 minutes
Total Marks: 20

Stem: A 52-year-old woman was admitted to your ICU 3 weeks ago following carbon monoxide poisoning from a faulty gas heater. Her initial COHb was 28%. She received normobaric 100% oxygen therapy and made a full recovery within 24 hours. She was discharged home on day 2 with normal cognition.

She now presents to the Emergency Department with her husband, who reports she has become increasingly forgetful over the past week, has difficulty with concentration, and has developed a shuffling gait with reduced facial expression. She has had two episodes of urinary incontinence.

On examination:

GCS 15, oriented to person but confused about date and place
Slow, shuffling gait with reduced arm swing
Bradykinesia and cogwheel rigidity in upper limbs
MMSE 18/30 (baseline estimated >26)

MRI Brain: Bilateral globus pallidus hyperintensity on T2/FLAIR, periventricular white matter changes

Question 2.1 (8 marks)

What is the diagnosis? Explain the pathophysiology of this condition and the characteristic MRI findings.

Question 2.2 (6 marks)

Could this have been prevented? Discuss the evidence for hyperbaric oxygen therapy in preventing this outcome.

Question 2.3 (6 marks)

Outline your management plan and discuss the expected prognosis.

Model Answer

Question 2.1 (8 marks total)

Diagnosis (2 marks):

Delayed Neurological Sequelae (DNS) of Carbon Monoxide Poisoning - 2 marks
Also known as: Delayed post-hypoxic leukoencephalopathy, delayed neuropsychiatric syndrome

Pathophysiology (4 marks):

Mechanisms of DNS (3 marks):

Oxidative stress and inflammation (1 mark):
- CO-induced reactive oxygen species (ROS) generation
- Lipid peroxidation of neuronal membranes
- Activation of microglia and inflammatory cascade
Immune-mediated demyelination (1 mark):
- CO exposure leads to myelin basic protein degradation
- Autoimmune response to exposed myelin antigens
- Progressive white matter demyelination over days-weeks
Direct mitochondrial toxicity (1 mark):
- CO inhibits cytochrome c oxidase (Complex IV)
- Impaired cellular energy production persists after CO elimination
- Selective vulnerability of oligodendrocytes and basal ganglia neurons

Timeline (0.5 marks):

Onset: 2-40 days after apparent recovery (typically 2-3 weeks)

Risk Factors (0.5 marks):

Loss of consciousness during exposure
Age >36 years
COHb >25%
Prolonged exposure

MRI Findings (2 marks):

Bilateral globus pallidus hyperintensity (T2/FLAIR): Characteristic finding; reflects selective vulnerability of basal ganglia to hypoxic injury - 1 mark
Periventricular white matter changes: Demyelination pattern; diffuse white matter hyperintensity on T2/FLAIR - 1 mark
Other findings: Hippocampal changes, diffuse cortical atrophy

Question 2.2 (6 marks total)

Could This Have Been Prevented? (1 mark):

Possibly yes; HBO therapy has been shown to reduce DNS incidence - 1 mark

Evidence for HBO in DNS Prevention (4 marks):

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

RCT, 152 patients, HBO (3 sessions) vs normobaric 100% O2
Primary outcome: Cognitive sequelae at 6 weeks
Results: DNS reduced from 46% to 25% (p = 0.007)
At 12 months: 32% vs 18% (p = 0.04)
NNT = 5 (one case of DNS prevented for every 5 patients treated)

Cochrane Review (2011, PMID: 21491385) (1 mark):

6 RCTs, 1,361 patients
Heterogeneous protocols, outcomes, and quality
Unable to definitively support or refute HBO benefit
Called for standardized trials

Application to This Case (1 mark):

This patient had COHb 28% with no reported LOC
Current consensus: HBO should be considered for COHb >25% even without LOC
Many guidelines would have recommended HBO consultation
NBO only was a reasonable decision at the time, but HBO may have reduced DNS risk

Limitations of Evidence (1 mark):

Some negative trials exist (Scheinkestel 1999)
Optimal timing and protocol unclear
Benefit may be less clear for "moderate" CO poisoning without LOC
Resource availability varies

Question 2.3 (6 marks total)

Management Plan (4 marks):

Immediate Management (1.5 marks):

Neuropsychological assessment to document deficits - 0.5 marks
Neuroimaging: MRI to confirm diagnosis (already done) - 0.5 marks
Exclude other causes: Metabolic (TFTs, B12, folate), infection (LP if indicated) - 0.5 marks

Supportive Care (1.5 marks):

Physiotherapy for mobility and falls prevention - 0.5 marks
Occupational therapy for cognitive rehabilitation - 0.5 marks
Speech therapy if swallowing/communication affected - 0.5 marks

Pharmacological (0.5 marks):

Trial of levodopa for Parkinsonian features (variable response)
Avoid anticholinergics (worsen cognition)

Family Support (0.5 marks):

Counseling and education about condition
Safety planning (driving restriction, supervision)
Social work involvement

Prognosis (2 marks):

Expected Course (1 mark):

Variable; some patients show significant improvement over 6-12 months
Others have permanent deficits
Cognitive symptoms may improve more than motor symptoms
Full recovery uncommon in symptomatic DNS

Prognostic Factors (1 mark):

Extent of MRI changes: More extensive white matter involvement = worse prognosis
Age: Older patients have poorer recovery
Severity of initial presentation: Worse initial deficits correlate with worse outcomes
Time to treatment: Earlier intervention may improve outcomes (though no proven treatment for established DNS)

Common Mistakes:

Not recognizing DNS presentation
Failing to correlate MRI findings with clinical syndrome
Not discussing preventability with HBO
Overestimating or underestimating prognosis

Viva Scenarios

Viva Scenario 1: CO Poisoning and HBO Decision

Stem: "A 35-year-old pregnant woman (28 weeks gestation) is brought to your ICU after being found unconscious in her car in an enclosed garage with the engine running. She has regained consciousness with 100% oxygen. Her COHb is 24%."

Duration: 12 minutes (2 min reading + 10 min discussion)

Opening Question:

"What are your immediate concerns about this patient?"

Expected Answer (2-3 minutes):

Fetal vulnerability to CO - Fetal hemoglobin has higher CO affinity; fetal COHb 10-15% higher than maternal and clears more slowly. The fetus is at high risk even with "moderate" maternal COHb (1 mark)
Maternal neurological status - She was unconscious, which increases DNS risk even though now conscious (1 mark)
Suicidal intent vs accidental - Need psychiatric assessment if deliberate; determine mechanism (1 mark)
Need for HBO consideration - Pregnancy is a specific indication for HBO at lower thresholds (0.5 marks)
Fetal monitoring - Need to assess fetal wellbeing (0.5 marks)

Follow-up Question 1 (2-3 minutes):

"Would you recommend hyperbaric oxygen therapy? What is the evidence?"

Expected Answer:

Recommendation (1 mark):

Yes, I would recommend HBO for this patient
Pregnancy with any significant CO exposure is generally considered an indication for HBO

Evidence (2 marks):

Fetal vulnerability: Fetal COHb levels are 10-15% higher than maternal; fetal elimination is slower (PMID: 15159037)
Case series data: HBO in pregnancy associated with reduced fetal mortality and adverse outcomes compared to historical controls
No randomized trials in pregnancy (ethical constraints)
Safety: HBO is safe in pregnancy; no documented teratogenic effects
Weaver criteria: Loss of consciousness is an indication regardless of pregnancy

Threshold for HBO in Pregnancy (1 mark):

Most experts recommend HBO at lower thresholds: COHb >15-20% or ANY symptoms
In this case: COHb 24% + LOC + pregnancy = strong indication

Follow-up Question 2 (2-3 minutes):

"Explain the pathophysiology of carbon monoxide toxicity. Why is the fetus particularly vulnerable?"

Expected Answer:

CO Toxicity Mechanisms (2 marks):

COHb formation: CO binds hemoglobin with 200-250x affinity of O2, causing functional anemia
Left shift of O2-Hb curve: Impairs oxygen unloading at tissue level
Cytochrome c oxidase inhibition: Direct cellular toxicity independent of hemoglobin
Oxidative stress and inflammation: Leads to delayed neurological sequelae

Fetal Vulnerability (2 marks):

Higher fetal hemoglobin affinity: Fetal Hb (HbF) has even higher CO affinity than adult Hb
Delayed equilibration: Fetal COHb peaks later than maternal and reaches higher levels
Slower elimination: Fetal CO half-life is longer than maternal
Developing brain sensitivity: Fetal brain more sensitive to hypoxic injury
Placental transfer: CO crosses placenta readily

Follow-up Question 3 (2-3 minutes):

"The patient's partner asks if she will be okay. How do you approach this conversation?"

Expected Answer:

Communication Approach (2 marks):

Prepare: Review current status, fetal monitoring results, plan
Privacy: Ensure private space, adequate time
Assess understanding: What do they know about what happened?

Key Information to Convey (2 marks):

Current status: She is now conscious and breathing normally on oxygen
Treatment plan: We are recommending specialized treatment (HBO) to help clear the CO faster and protect both her and the baby
Fetal concerns: The baby may have been affected; we are monitoring closely
Prognosis: Most patients recover well, but there is a small risk of delayed effects in 2-3 weeks (headache, memory problems)
Psychiatric consideration: If deliberate, will need support and follow-up

Address Specific Concerns:

Safety of HBO in pregnancy
Fetal monitoring plan
Mental health support if applicable

Examiner's Expected Level:

Pass:

Recognizes pregnancy as high-risk for CO toxicity
Understands fetal vulnerability and indications for HBO
Systematic approach to management
Can explain pathophysiology at basic level
Communicates compassionately with partner

Fail:

Does not recognize pregnancy as specific indication for HBO
Unable to explain why fetus is vulnerable
Poor understanding of CO toxicity mechanisms
Unsafe management decisions
Poor communication with family

Viva Scenario 2: Industrial Cyanide Exposure

Stem: "A 42-year-old man is brought to your rural hospital by ambulance after collapsing at a gold processing facility. Co-workers report he was working near the cyanide leaching tanks. He is unconscious with seizure activity."

Duration: 12 minutes (2 min reading + 10 min discussion)

Opening Question:

"What is your immediate assessment and management?"

Expected Answer (3 minutes):

Recognition of Cyanide Poisoning (1 mark):

Industrial setting (gold processing uses cyanide)
Rapid collapse with seizures suggests acute poisoning
High index of suspicion for cyanide toxicity

Immediate Management (A-E) (3 marks):

A - Airway (0.5 marks):

Protect airway; likely need intubation given seizures and GCS

B - Breathing (0.5 marks):

100% oxygen via non-rebreather or ventilator
Assist ventilation if inadequate

C - Circulation (0.5 marks):

IV access (may be hypotensive)
Fluid bolus if hypotensive
Vasopressors if persistent hypotension

D - Disability (0.5 marks):

Stop seizures: Benzodiazepines (midazolam 5-10 mg IV)
Check blood glucose

E - Antidote (1 mark):

Hydroxocobalamin 5g IV over 15 minutes - DO NOT DELAY
If hydroxocobalamin unavailable: Dicobalt edetate 300mg IV (only if cyanide confirmed - toxic if misdiagnosis)

Follow-up Question 1 (2-3 minutes):

"What investigations would you order and what would you expect to find?"

Expected Answer (2 marks):

Investigations:

ABG: Metabolic acidosis with elevated lactate; PaO2 normal or elevated (tissue cannot use O2)
Lactate: Markedly elevated (often >10 mmol/L); key diagnostic clue
Cyanide level: Send for confirmation but do NOT wait for result before treatment
Blood glucose: May be elevated (catecholamine surge) or low
ECG: Bradycardia, ST changes, arrhythmias

Expected Findings (1 mark):

Severe metabolic acidosis (pH <7.2)
Lactate >10-20 mmol/L
Normal or elevated PaO2 (tissue cannot extract O2)
Elevated SvO2 (paradoxical finding - tissues cannot utilize O2)

Follow-up Question 2 (2-3 minutes):

"Describe the mechanism of cyanide toxicity and how hydroxocobalamin works as an antidote."

Expected Answer:

Cyanide Mechanism (2 marks):

Cyanide binds ferric iron (Fe3+) in cytochrome c oxidase (Complex IV)
Blocks electron transport chain at terminal oxidase
Oxidative phosphorylation ceases completely
Cells cannot utilize oxygen despite adequate delivery
Forces anaerobic metabolism → profound lactic acidosis
Rapid ATP depletion → cell death

Hydroxocobalamin Mechanism (2 marks):

Cobalt ion in hydroxocobalamin binds cyanide with high affinity
Forms cyanocobalamin (vitamin B12)
Non-toxic complex excreted renally
Each molecule of hydroxocobalamin binds one cyanide molecule
5g dose provides excess binding capacity for typical toxic exposure
Onset: Minutes; does not interfere with oxygen carrying capacity

Follow-up Question 3 (2-3 minutes):

"This is a rural hospital 400 km from the nearest ICU. How would you manage retrieval?"

Expected Answer (3 marks):

Stabilization (1 mark):

Complete intubation, start mechanical ventilation
Continue 100% FiO2
Give hydroxocobalamin (should be stocked in rural hospitals near mining operations)
Control seizures
Vasopressor support if needed

Retrieval Coordination (1.5 marks):

Contact state retrieval service (RFDS, ARV, NSW Aeromedical)
Toxicology consultation (Poisons Information Centre 13 11 26)
Provide clinical details: suspected cyanide, lactate, response to hydroxocobalamin
Request critical care retrieval team

Transfer Considerations (0.5 marks):

Document hydroxocobalamin given (affects lab interpretation)
Have second hydroxocobalamin kit available if deteriorates
Ongoing monitoring during transfer
Consider second dose if persistent acidosis

Examiner's Expected Level:

Pass:

Recognizes cyanide poisoning in industrial context
Gives hydroxocobalamin promptly without waiting for confirmation
Understands cytochrome oxidase inhibition mechanism
Systematic A-E approach with appropriate resuscitation
Appropriate retrieval coordination

Fail:

Delays antidote awaiting cyanide levels
Does not recognize elevated lactate as cyanide marker
Poor understanding of mechanism
Unsafe airway/breathing management
No plan for retrieval

Clinical board

Urgent signals

Exam focus

Editorial and exam context

Carbon Monoxide and Cyanide Poisoning

Quick Answer

CICM Exam Focus

What Examiners Expect

Common Mistakes

Key Points

Must-Know Facts

Memory Aids

Definition and Epidemiology

Definition

Epidemiology

Applied Basic Sciences

Anatomy

Physiology

Pathophysiology

Pharmacology

Pathology

Clinical Presentation

ICU Admission Scenarios

Symptoms and Signs

Severity Scoring

Differential Diagnosis

Investigations

Laboratory Investigations

Imaging

Physiological Monitoring

ICU Management

Initial Resuscitation (First Hour)

Specific Antidote Therapy

Hyperbaric Oxygen Therapy (HBO)

Ongoing ICU Care

Australian-Specific Protocols

Monitoring and Complications

ICU-Specific Monitoring

Complications

Prognosis

Special Considerations

Indigenous Health

Pregnancy

Remote/Rural Considerations

Bushfire Exposure

SAQ Practice

SAQ 1: House Fire with Combined CO/Cyanide Exposure

Model Answer

SAQ 2: Delayed Neurological Sequelae

Model Answer

Viva Scenarios

Viva Scenario 1: CO Poisoning and HBO Decision

Viva Scenario 2: Industrial Cyanide Exposure