In the January 2012 WMSHP Newsletter, Chelsey Timmer, a PGY1 pharmacy resident at Spectrum Health, writes about therapy for suspected cyanide poisoning.

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Use of Cyanokit^® for Suspected Cyanide Poisoning

Chelsey Timmer, Pharm.D.

Poisoning due to cyanide can cause severe harm and death within minutes to hours. For this reason, it is critical that clinicians are aware of common sources of cyanide exposure. Exposed patients must be quickly assessed for signs and symptoms of toxicity, and clinicians must be able to identify how and when to appropriately use the available cyanide antidotes.

The major source of cyanide exposure in the United States is via smoke inhalation from structural fires^1,2,3. Cyanide gas is produced when materials such as wool, silk, polyurethane, and synthetic polymers combust². During a fire, inhaled cyanide gas can rapidly diffuse into tissues, causing signs and symptoms of toxicity within minutes. Other sources of cyanide poisoning include intentional ingestion in an attempt to commit suicide, accidental ingestion, and occupational or industrial exposures to the chemical. The anti-hypertensive medication sodium nitroprusside, which contains 44% cyanide by molar weight, can also lead to cyanide accumulation in select patient populations such as those with a defect in cyanide metabolism or renal dysfunction¹.

Cyanide binds to the ferric ion of cytochrome oxidase a₃, a component of the mitochondria that is essential for oxidative phosphorylation. When cyanide levels rise, the normal elimination pathway is overwhelmed, oxidative phosphorylation is inhibited, and levels of lactate rise to cause a metabolic acidosis^1,4. This may manifest initially as an anxiety, headache, giddiness, tachycardia, and tachypnea. As the toxicity progresses, hypotension, arrhythmias, seizures, and coma may occur^1,3.

It is imperative that practitioners recognize that cyanide exposure needs to be assessed and promptly treated. The two antidote kits currently available for treatment are the cyanide antidote kit and Cyanokit^®. Quick Drug References are available on Insite for both products^5,6. The cyanide antidote kit consists of 3 drugs: amyl nitrite, sodium nitrite, and sodium thiosulfate. Amyl nitrite is to be administered via inhalation while IV access is obtained; if IV access is already established, sodium nitrite should be administered first. Amyl nitrite and sodium nitrite work to oxidize hemoglobin to methemoglobin. Cyanide will preferentially bind to methemoglobin, freeing cytochrome oxidase a₃ and allowing the resumption of ATP generation and cellular respiration. Sodium thiosulfate is administered immediately following sodium nitrite. It facilitates excretion by acting as a sulfhydral group donor to cyanide. This forms the compound thiocyanate, which is renally eliminated^1,5.

The cyanide antidote kit is associated with multiple adverse events as well as administration difficulties, making it the non-preferred treatment for cyanide poisoning. The major side effect is hypotension, due to both the nitrites and the sodium thiosulfate portions of the kit. Sodium nitrite should be administered slowly over at least two minutes, and sodium thiosulfate over at least 10 minutes to minimize the risk of hypotension. The production of excessive amounts of methemoglobin can also be concerning in patients who may already have low levels of functioning hemoglobin due to concurrent carbon monoxide poisoning. Patients should be observed for signs of methemoglobinemia, including a blue color of the skin or mucus membranes, vomiting, shock, and coma⁵.

Cyanokit^®, which contains hydroxocobalamin, is the preferred treatment for suspected cyanide poisoning due to its comparative ease of administration and less severe side effects. Hydroxocobalamin works by binding to cyanide to form cyanocobalamin (vitamin B₁₂). Cyanocobalamin is renally eliminated, freeing cytochrome oxidase a₃ for cellular respiration. Each Cyanokit® contains two 2.5 g vials of hydroxocobalamin, two sterile transfer spikes, and one sterile intravenous infusion set. The starting dose for adults is 5 g (two 2.5 g vials), which should be reconstituted in 200 mL 0.9% sodium chloride. A second dose of 5 g may be administered if signs and symptoms of cyanide poisoning persist. For children, the starting dose is 70 mg/kg IV. The first dose should be administered over 15 minutes, the second dose over 15 minutes to 2 hours⁶.

Side effects of hydroxocobalamin include discoloration of skin and body fluids as well as hypertension. In a prospective, open-label trial, diastolic blood pressure increased by an average of 10 mmHg, while systolic increased an average of 7.5 mmHg. This transient increase may actually benefit patients who are hypotensive due to cyanide poisoning. Blood pressure returned to baseline without treatment in all patients³. Red discoloration of the skin and urine are the most common side effects of hydroxocobalamin. Skin redness may last up to 2 weeks, urine redness up to 5 weeks⁶. Hydroxocobalamin can also interfere with colorimetric laboratory tests, including bilirubin, creatinine, magnesium, serum iron, oxyhemoglobin and methemoglobin¹.

Whether or not to empirically treat fire victims for cyanide poisoning is a long-debated issue, with some clinicians arguing that cyanide poisoning is over-diagnosed and treated, and others in favor of treating all patients who have potential symptoms of cyanide poisoning². One reasonable approach is to administer hydroxocobalamin to any patient who has been in a structural fire and has mental status changes. If it is an available service, toxicology should also be consulted for these patients.

References

1. Hammel J. A review of acute cyanide poisoning with a treatment update. Crit Care Nurse. 2011 Feb;31(1):72-82.
2. Barillo DJ. Diagnosis and treatment of cyanide toxicity. J Burn Care Res. 2009;30(1):148-152.
3. Borron SW, Baud FJ, Barriot P, Imbert M, Bisumth C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007 Jun;49(6):794-801.
4. Hall AH, Dart R, Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning? Ann Emerg Med. 2007 Jun;49(6):806-813.
5. Posey J, Thomas W. Amyl nitrite, sodium nitrite, sodium thiosulfate kit (Cyanide Antidote Kit®). Spectrum Health Drug Quick Reference. Updated 2011 Jan; pp 1-2.
6. Posey J, Thomas W. Hydroxocobalamin (Cyanokit®). Spectrum Health Drug Quick Reference. Updated 2011 Jan; pp 1-2.