New Cyanide Drug Effective but Costly

Dr. Bukata is the medical director of the emergency department at San Gabriel Valley Medical Center in San Gabriel, CA, a clinical professor in the department of emergency medicine at Los Angeles County/USC Medical Center, and the editor of Emergency Medical Abstracts.

Smoke inhalation is associated with more fire-related deaths than burns, and cyanide in smoke is frequently the culprit in victims of collapse. Traditional cyanide antidote kits are available for use in the hospital, but these kits do not lend themselves to prehospital use because of their complexity. They contain amyl nitrite, sodium nitrite, and sodium thiosulfate, and the methemoglobinemia that is produced is also potentially dangerous.

Recently the FDA approved a new cyanide treatment that is considerably safer and associated with substantially fewer adverse effects than the traditional kits. Cyanokit, produced by Dey, L.P., a U.S. affiliate of Merck KGaA of Darmstadt, Germany, has been available in the United States since March. Used in France since the 1980s and formally licensed there in 1996, the active ingredient is a precursor of vitamin B12, hydroxocobalamin, which detoxifies cyanide through the irreversible formation of cyanocobalamin, which is subsequently excreted in the urine.

Given the apparent safety of hydroxocobalamin, its empiric prehospital use for presumptive cyanide toxicity appears attractive. But like many breakthrough drugs, there is a catch. According to Dr. Leon Gussow’s column in the August issue of Emergency Medicine News (2007;29[8]:18), the drug costs $650 per dose, so the cost-effectiveness of this remedy becomes an issue. He nicely makes the case that giving sodium thiosulfate at a cost of about $6 is much more cost-effective.

Both thiosulfate treatment and hydroxocobalamin are associated with side effects. The manufacturer of the Cyanokit notes that the most common adverse reactions (>5%) are transient, including chromaturia, erythema, rash, increased blood pressure, nausea, headache, decreased lymphocyte percent, and injection site reactions. Allergic reactions have been observed, and usage may interfere with some clinical laboratory evaluations.

It is likely that this new product will be carried by all paramedic squads, and it is important to be aware of its availability, side effects, and efficacy. The following French study details the effect of hydroxocobalamin in 69 smoke inhalation victims suspected of having cyanide poisoning (39 were comatose) between 1987 and 1994. Ultimately cyanide poisoning was present in 42, and 67 percent of those survived with treatment.

Prospective Study of Hydroxocobalamin for Acute Cyanide Poisoning in Smoke Inhalation

Borron SW, et al Ann Emerg Med 2007;49(6):794

BACKGROUND: Hydroxocobalamin is a naturally occurring form of vitamin B12 that detoxifies cyanide via irreversible binding to form cyanocobalamin. Unlike some other cyanide antidotes, hydroxocobalamin does not produce serious adverse effects and is therefore suitable for prehospital administration.

METHODS: This seven-year observational case series from France examined the effects of treatment with IV hydroxocobalamin (5 g/dose to a maximum of 15g) after obtaining blood specimens for measurement of cyanide levels in 69 adult victims of smoke inhalation with suspected cyanide poisoning. The study excluded patients who died in the prehospital setting.

RESULTS: Significant concomitant carbon monoxide poisoning was identified in 83 percent of the patients, and at the time of treatment, 96 percent were neurologically impaired, and 57 percent were comatose. Cyanide poisoning was ultimately confirmed in 67 percent of patients with an available blood level (42/63). Survival was 72 percent overall, 71 percent in patients with pretreatment neurologic impairment, and 67 percent in patients with confirmed cyanide toxicity. There were three survivors among six patients with a blood cyanide level at least twice the potentially lethal concentration, and two among 15 patients found in cardiac arrest (both of whom recovered without neurologic sequelae). An adverse event possibly related to hydroxocobalamin treatment was reported in 27 percent of the patients, none of which was considered serious.

CONCLUSIONS: Prehospital treatment with hydroxocobalamin may be safe and well tolerated in smoke inhalation victims with and without cyanide poisoning. In this series of patients who did not die in the field, two-thirds of the patients with confirmed cyanide toxicity survived.

Pneumococcal Vaccine Proves Highly Effective

Our addiction to antibiotics for treating febrile children continues. Although studies have suggested some modest decline in the frequency of prescribing of contraindicated antibiotics, this is offset because the antibiotics prescribed now are more likely than in the past to be broad-spectrum. The next paper may be of help in weaning some physicians and parents from their dependence on antibiotics. It specifically notes that in a large group of children having blood cultures who were immunized with just one injection of the pneumococcal vaccine, none had a positive culture for this bug. Hopefully these compelling results will allow physicians to feel comfortable getting off the occult bacteremia protocols of the past in which children with high fevers got CBCs and, if the white cell count was over 15,000, blood cultures. Those days should be long over.

Souce: Emergency Medicine News:Volume 29(12)December 2007p 17-19,24,25