In this episode I’ll discuss cyanide toxicity.
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Cyanide is a rapidly lethal toxin. It causes death within minutes to hours of exposure.
Cyanide inhibits oxidative phosphorylation in the mitochondria, shutting down aerobic metabolism. Oxygen supply remains adequate but cells are unable to utilize the oxygen.
Cyanide is present in low background levels in the environment and is safely metabolized to thiocyanate by the liver. The capacity to metabolize cyanide is limited, and just ~0.5mg/kg is enough to be fatal.
Cyanide toxicity is relatively rare. Domestic fires, industrial accidents, and sodium nitroprusside are more common possible causes of cyanide poisoning.
Fabrics, upholstery, and melamine (often used as a coating on shelves and cabinets) can all give off cyanide when burned.
Cyanide is used in the extraction of gold and silver, and the production of nylon.
The antihypertensive sodium nitroprusside contains cyanide. Cyanide toxicity may occur in patients who receive prolonged infusions of sodium nitroprusside, have chronic renal failure, or in pediatric patients. Significant toxicity has resulted from rates higher than 2 mcg/kg/min.
A patient with cyanide toxicity generally presents with cardiovascular and CNS depression despite normal oxygenation. Most symptoms are non-specific although cherry-red skin coloring is sometimes present.
About half of the population detects a bitter almond odor after inhaling cyanide.
Treatment
As with the treatment of any poisoning patient, the following 4 essential steps must be considered:
1. Supportive care
2. Decontamination
3. Antidote therapy
4. Enhance elimination
Supportive care
While supportive care to treat cardiovascular and CNS depression is essential, no amount of supportive care can change the fact that the patient’s mitochondria can’t produce energy. Decontamination and antidote strategies should be considered simultaneously with supportive care.
Decontamination
There is a possibility for caregivers to be contaminated with cyanide due to “off-gassing”. This is more likely to happen if the cyanide toxicity is from a dermal exposure and remains on the patient’s clothing or skin.
GI decontamination with activated charcoal (AC) is indicated in oral cyanide exposures based on animal studies which report decreased mortality among rats given AC after lethal potassium cyanide ingestions. 50 g of AC can be given enterally as long as the patient is not at risk of aspiration.
Antidote therapy
Hydroxycobalamin combines with cyanide to form the harmless substance cyanocobalamin (vitamin B12). Hydroxycobalamin is given at a dose of 5 g IV, with a half dose repeated if the clinical situation warrants it.
Hydroxycobalamin is relatively safe, causing rash, headache, and a temporary reddish discoloration of the skin, plasma, urine, and mucous membranes.
Hydroxycobalamin will interfere with many lab tests. Most significantly it will interfere with co-oximetry measurements of total hemoglobin, carboxyhemoglobin, methemoglobin, and oxyhemoglobin. This may be significant in smoke inhalation victims, as carbon monoxide poisoning and cyanide poisoning may both occur from smoke inhalation.
The old cyanide antidote kit containing nitrites is no longer manufactured.
Enhance elimination
To enhance elimination use sodium thiosulfate to provide sulfur donors for the liver enzyme responsible for cyanide metabolism (Rhodanese). This allows excess cyanide to be eliminated. The onset of action of this effect is too slow (up to 30 minutes) to rely on sodium thiosulfate alone for treatment of cyanide toxicity. The dose of sodium thiosulfate is 0.4 mg/kg IV up to a maximum of 12.5 g.
Should cyanide antidote therapy be given to all smoke inhalation victims?
Given that cyanide is produced as a result of domestic fires, smoke inhalation victims may have concomitant cyanide poisoning. Although the antidote hydroxycobalamin is safe, it is costly at $900 USD per 5 gram dose.
I agree with the author of a 2007 editorial on hydroxycobalamin for smoke inhalation who concluded:
“”A call for routine empiric administration of hydroxocobalamin to smoke inhalation victims seems unwarranted until we have more data. For now, clinicians should assess patients individually and use cautious judgement. It appears reasonable to consider empiric hydroxocobalamin for victims who are comatose, in cardiac arrest, or have clear signs of cardiovascular extremis…
…While we should be cautious about embracing hydroxocobalamin too rapidly or too broadly for smoke inhalation at least pending further data. Nevertheless, we should not dismiss its potential importance for this indication, nor its clear advantages as a first-line antidote for other forms of cyanide poisoning.
It may be possible to further identify smoke inhalation victims who have cyanide toxicity by checking for an elevated lactate and low end tidal CO2 measurement. These two findings would be present in cyanide toxicity due to the lack of aerobic respiration. Such patients may represent a cohort that should receive empiric hydroxycobalamin therapy.
Further recommendations for which smoke inhalation victims are to receive cyanide antidote treatment are likely to be based on expert opinion, as there have been no clinical trials published using hydroxycobalmin in smoke inhalation victims since the drug’s approval in the US in 2007. According to clinicaltrials.gov there are no other trials underway.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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