UMEM Educational Pearls

Cyanide is one of the deadliest known poisons causing immediate toxic effects and lethality within seconds to minutes. Exposures are rare, most commonly by inhalational route (HCN gas) from structural fires due to combustion of synthetic materials or from ingestion of cyanide salts. Cyanide toxicity can also occur from dermal or parental (sodium nitroprusside) exposure. 

• Cyanide is a mitochondrial poison act by binding the heme portion of cytochrome oxidase a3 in the electron transport chain halting ATP production from oxygen shifting cellular respiration from aerobic to anaerobic metabolism causing a profound lactic acidosis > 8
•  Impaired peripheral oxygen delivery and utilization can cause “arterialization” of venous blood (cherry red skin), in which the concentration of venous oxygen resembles that of arterial blood 
• Clinical effects are profound but nonspecific, most frequently reported include unresponsiveness, respiratory failure, hypotension, cardiac arrest, and seizure
• There are no pathognomonic clinical symptoms or diagnostic blood tests for cyanide poisoning (good correlation of carboxyhemoglobin levels >10 with cyanide toxicity, lactate level >10), clinical suspicion is required
• Rapid administration of antidote is crucial. Survival is determined by timing of exposure, rapid recognition, and administration of antidote and supportive treatment. 

The preferred first line antidote is hydroxycobalamin (vitamin B12) available as Cyanokit, which has higher affinity for cyanide than cytochrome oxidase and binds to form harmless cyanocobalamin and is renally excreted. Limited studies reveal good survival rates in noncardiac arrest patients. Hydroxycobalamin has minimal side effects (red skin and urine, increased BP) and is well-tolerated with safer and simpler mechanism of action than Nithiodote (original antidote), containing sodium nitrite (CN preferentially binds methemoglobin to form cyanomethemoglobin) and thiosulfate (provides sulfur to convert cyanide to thiocynate for excretion). Sodium nitrite has numerous adverse effects causing hypotension and methemoglobin (contraindicated in smoke inhalation victims due to concern for carbon monoxide poisoning, G6PD deficiency, preexisting amenia), and hypersensitivity reactions. Sodium thiosulfate has less side effects and augments cyanide excretion but is considered less effective due to its slow onset, short half-life, low volume of distribution, and poor intracellular penetration.  

As of August 2025, the American Society of Health -System Pharmacists (ASHP) Drug Shortage lists Cyanokit as “limited availability” in the U.S. as manufacturing was suspended due to investigation of ongoing quality defect with concern for sterility and endotoxin content. Impacted batches were released and their numbers are listed in an FDA bulletin (see references). Healthcare providers should weigh the potential benefit of using Cyanokit against the risk of infection. Infusion set with 0.2 micron in line filter can be temporarily used for administration of Cyanokit 5 mg hydroxycobalmin to prevent potential infection.

References

Surviving Cyanide Poisoning: A case report highlighting the role of early antidote use. Hopes BC, Slob EM, et al. Toxicology Reports, Volume 15, December 2025.

Challenges in the diagnosis of acute cyanide poisoning. Parker-Cote JL, Rizer J, et al. Clin Toxicol. 2018 Jul:56(7):609-617.

American Society of Health -System Pharmacists (ASHP) Drug Shortage Detail-Hydroxocobalmin for injection 9/22/2025. 

February 6, 2025 Manufacturer letter to healthcare professional https://www.fda.gov/media/185400/download