carbon monoxide (co) & cyanide

context: smoke inhalation

Victims of house fires are at risk for both CO and Cyanide toxicity.

Hypoxia:
- Carbon Monoxide (CO) binds to Haemoglobin (Hb) with 200–250x higher affinity than Oxygen, forming Carboxyhaemoglobin (COHb). This reduces oxygen-carrying capacity.
- Shifts the oxyhaemoglobin dissociation curve to the Left, impairing oxygen release from Hb to tissues.
- Results in tissue hypoxia despite falsely normal or high SpO2 readings.
Cellular Toxicity: CO directly binds to cytochrome c oxidase, disrupting mitochondrial oxidative phosphorylation and causing direct cellular (neuronal) death, independent of its haemoglobin-binding effects.
Causes:
- Carbon combustion + inadequate ventilation (e.g., gas stoves, car exhaust, fires).
- Exposure to methylene chloride/bromide (metabolised to CO).

Early (< 4h): Headache (H/A), dizziness, nausea, ‘flu-like’ symptoms.
Continued Exposure / End-Organ Hypoxia:
- CNS: Ataxia, syncope, altered mental status, seizures, coma.
- Cardiac: Arrhythmias, myocardial ischaemia, cardiomyopathy.
- Respiratory: Pulmonary oedema (cardiogenic or ARDS), dyspnoea.
- Skin: Cherry-red skin (rare, late sign), skin bullae.
- Metabolic: Anion gap metabolic acidosis (AGMA), lactic acidosis.
- Ocular: Retinal haemorrhages.
Delayed Neurological Sequelae (DNSE): Can occur days to weeks later, including Parkinsonism, dementia, psychosis, apraxia.

Carboxyhaemoglobin (COHb) Level: Measured via CO-Oximetry (part of ABG/VBG).
- Normal: 1–2%.
- Smokers: 5–10%.
- Abnormal: > 10%.
Pulse Oximetry (SpO2): Unreliable; will falsely read normal or high as it cannot distinguish COHb from OxyHb.
Imaging: CT/MRI may show bilateral opacities in the globus pallidus.

Remove Source: Move patient to a well-ventilated area, remove from CO source.
100% Oxygen: Administer immediately (high-flow nasal cannula, non-rebreather mask, or intubate if coma/respiratory compromise).
- Reduces COHb half-life:
  - Room air: 250–320 minutes.
  - 100% FiO2: ~90 minutes.
  - Hyperbaric Oxygen (2.5 ATA): ~20 minutes.
Hyperbaric Oxygen (HBO): Consider (conflicting evidence, expert consensus).
- Potential Indications:
  - Presentation within 6 hours of exposure.
  - COHb level > 25%.
  - Neurological symptoms: Seizure, coma, syncope, altered mental status, ataxia.
  - Cardiac ischaemia or arrhythmia.
  - Pregnancy: COHb > 15% in pregnant woman or evidence of foetal distress.
- If patient has CO poisoning after smoke inhalation, treat for concurrent cyanide poisoning.

Hypoxia:
- Cyanide (CN) blocks mitochondrial cytochrome c oxidase (complex IV of the electron transport chain).
- This inhibits cellular aerobic respiration, forcing cells into anaerobic metabolism.
- Results in profound tissue hypoxia and severe lactic acidosis, despite adequate oxygen delivery to cells.
Causes:
- Inhalation: Combustion of nitrogen-containing materials (plastics, rubber, wool, silk, polyurethane) in fires.
- Ingestion: Cassava, apricot pits, bitter almonds.
- Iatrogenic: Intravenous nitroprusside infusion (especially in renal impairment).

Hallmarks: Coma, severe metabolic acidosis, cardiac instability.
Onset: Abrupt (minutes) for inhalation, hours for ingestion.
Symptoms: Headache, nausea, dizziness, confusion, syncope, seizures, coma, cardiac collapse, cardiac arrest.
Metabolic: Severe lactic acidosis (anion gap metabolic acidosis).
Cardiovascular: Non-specific arrhythmias, bradycardia, tachycardia, conduction blocks.
Venous Blood Gas (VBG): Venous arterialisation (high central/mixed venous oxygen saturation, as tissues cannot extract oxygen).
Arterial Blood Gas (ABG): Often high SaO2 (unlike CO toxicity) in early stages.
Odour: Characteristic ‘bitter almond’ smell (only detectable by ~50% of the population).

Purely Clinical: Based on hallmarks and suspicion (e.g., fire victim, nitroprusside infusion).
High Mixed/Central Venous Oxygen Saturation (> 90%): A strong indicator.
Lactate > 8-10 mmol/L in a fire victim.
Cyanide Levels: Rarely useful in acute emergency as results take too long to return.
- Levels > 2.4 mg/L often associated with coma.
- Levels > 3 mg/L often associated with death.

Supportive Care:
- Airway: Secure airway (intubate) if necessary.
- Oxygen: Administer 100% FiO2.
- Haemodynamics: Crystalloids and vasopressors for shock.
- Acidosis: Sodium bicarbonate for severe metabolic acidosis.
Specific Antidotes:
- Hydroxocobalamin (Cyanokit): Mainstay of management.
  - Mechanism: Binds directly to cyanide, forming non-toxic cyanocobalamin (Vitamin B12), which is renally excreted.
  - Dose: 5 g IV over 15 minutes. May repeat once if needed (total 10g).
  - Adverse Effects: Transient hypertension, chromaturia (red urine), anaphylactoid reactions.
- Nitrites (Sodium Nitrite / Amyl Nitrite): (Only if Hydroxocobalamin unavailable).
  - Mechanism: Induce methaemoglobinaemia. Methaemoglobin has a higher affinity for cyanide than cytochrome oxidase.
  - Dose (Sodium Nitrite): 3% solution, 10 mL IV over 2–4 minutes.
  - Pre-hospital: Amyl nitrite pearls (inhaled).
  - Adverse Effects: Hypotension, hypoxaemia (do not use if concomitant CO poisoning, as it worsens hypoxia).
- Sodium Thiosulfate: (Often given with nitrites or alone if Hydroxocobalamin unavailable).
  - Mechanism: Acts as a sulphur donor, converting cyanide to thiocyanate (less toxic, renally excreted).
  - Dose: 150–200 mg/kg IV over 10–20 minutes.
  - Adverse Effects: Hypernatraemia.

exam pearl

If a fire victim has a persistent lactic acidosis despite resuscitation, think Cyanide.

feature	methemoglobinemia	carbon monoxide (co)	cyanide (cn)
Scenario	Exposure to Dapsone, Septra, Nitrates, Benzocaine.	Combustion (fires, gas stoves) in poor ventilation.	Industrial fires (wool/plastic combustion), Lab exposure.
Pathology	$F e^{2 +} \to F e^{3 +}$ (cannot carry $O_{2}$ ).	CO binds Hb (blocks $O_{2}$ ).	Blocks Cytochrome C Oxidase (blocks use of $O_{2}$ ).
Skin/Blood	Cyanosis. “Chocolate Brown” blood.	Cherry Red skin (rare).	Normal / Pink.
SpO2 vs PaO2	Sat Gap: SpO2 ~85% but PaO2 Normal/High.	Normal SpO2 (falsely normal). PaO2 Normal.	High SpO2 (venous blood looks arterial).
Key Lab	MetHb > 1–2%.	CarboxyHb > 10%.	Lactate > 8 mmol/L.
Antidote	Methylene Blue (1–2 mg/kg).	100% Oxygen (Hyperbaric).	Hydroxocobalamin (5g).