Toxicology/original research
Prospective Study of Hydroxocobalamin for Acute Cyanide Poisoning in Smoke Inhalation

Presented in part at the 2005 annual meeting of the American College of Emergency Physicians, September 2005, Washington, DC.
https://doi.org/10.1016/j.annemergmed.2007.01.026Get rights and content

Study objective

To assess outcomes in patients treated with hydroxocobalamin at the fire scene or in the ICU for suspected smoke inhalation-associated cyanide poisoning.

Methods

Adult smoke inhalation victims with suspected cyanide poisoning as determined by soot in the face, mouth, or nose or expectorations and neurologic impairment received an intravenous infusion of hydroxocobalamin 5 g (maximum 15 g) at the fire scene or in the ICU in this observational case series conducted from 1987 to 1994. Blood cyanide specimens were collected before administration of hydroxocobalamin. The threshold for cyanide toxicity was predefined as greater than or equal to 39 μmol/L.

Results

The sample included 69 patients (mean age 49.6 years; 33 men), of whom 39 were comatose. Out-of-hospital deaths were excluded. Fifty of the 69 patients (72%) admitted to the ICU survived after administration of hydroxocobalamin. In the group in which cyanide poisoning was confirmed a posteriori (n=42), 67% (28/42) survived after administration of hydroxocobalamin. The most common adverse events were chromaturia (n=6), pink or red skin discoloration (n=4), hypertension (n=3), erythema (n=2), and increased blood pressure (n=2). No serious adverse events were attributed to hydroxocobalamin. Laboratory tests revealed transient alterations in renal and hepatic function consistent with the critical condition of the patients and mild anemia consistent with progressive hemodilution.

Conclusion

Empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had cyanide poisoning. Hydroxocobalamin was well tolerated irrespective of the presence of cyanide poisoning. Hydroxocobalamin appears to be safe for the out-of-hospital treatment of presumptive cyanide poisoning from smoke inhalation.

Introduction

Inhalation of smoke accounts for more fire-related morbidity and mortality than burns.1, 2 Hydrogen cyanide contributes significantly to smoke inhalation deaths and injuries and is the most common cause of acute cyanide poisoning in developed countries.3, 4, 5, 6 Treatment of acute cyanide poisoning entails supportive care and the administration of an antidote.7, 8 The ability to administer an antidote empirically outside of the hospital for presumptive cyanide poisoning allows for early intervention that can be lifesaving. The potential for serious adverse effects limits or prevents the use of some currently available cyanide antidotes as out-of-hospital empiric treatment, particularly for cyanide poisoning caused by smoke inhalation. Both 4-dimethylaminophenol (4-DMAP) and the cyanide antidote kit (consisting of amyl nitrite, sodium nitrite, and sodium thiosulfate) are generally considered unsuitable for out-of-hospital use in smoke inhalation victims because of the presence of hypoxemia of multiple causes, including concomitant carbon monoxide poisoning.4, 9, 10, 11, 12 The cyanide antidote kit and DMAP cause methemoglobinemia, which is potentially detrimental because it can further reduce the oxygen-carrying capacity of the blood. Although sodium thiosulfate can be used alone for suspected smoke inhalation cyanide poisoning, this component of the cyanide antidote kit is thought to have a relatively slow onset of action8 and has not been prospectively studied in the context of smoke inhalation.

The cyanide antidote hydroxocobalamin has been used regularly in France for out-of-hospital and inhospital treatment of cyanide poisoning since the 1980s and was formally licensed there in 1996. A natural form of vitamin B12, hydroxocobalamin detoxifies cyanide through the irreversible formation of cyanocobalamin, which is subsequently excreted in urine. Successful use of hydroxocobalamin for out-of-hospital and inhospital treatment of acute cyanide poisoning from smoke inhalation, ingestion, and occupational exposure has been documented in case reports and series,13, 14, 15, 16, 17, 18, 19 but data from prospective studies have not been reported to date.

This study was conducted to assess outcomes in patients treated with hydroxocobalamin in the out-of-hospital setting or ICU for smoke-inhalation-associated cyanide poisoning.

Section snippets

Study Design and Setting

This study was conducted in Paris, France, among fire victims initially treated by members of the Paris Fire Brigade for presumptive smoke inhalation-induced cyanide poisoning. The Paris Fire Brigade operates an out-of-hospital emergency medical service composed of 7 mobile ICUs staffed at any given time by a physician, nurse, and driver. The brigade is responsible for providing emergency medical services to Paris and its environs, totaling a 759-km2 area of 6,188,434 inhabitants (according to

Results

The sample included 69 patients (36 women and 33 men; median age 44 years [range 20 to 94 years]) (Table 1). All patients were victims of house fires in Paris or its environs and were subsequently admitted to the Toxicology Intensive Care Unit of the Fernand Widal Hospital. Mean (SD) time between the initial call for help and initiation of out-of-hospital care was 10.4 minutes (6.2 minutes). Fifteen victims who were examined at the fire scene by the Paris Fire Brigade and treated with

Limitations

The data from this study should be interpreted in the context of several limitations that prevent making inferences about hydroxocobalamin efficacy. These limitations include the absence of a contemporaneous control group, the open-label design, and the impact of multiple other interventions administered around the time of hydroxocobalamin treatment. Caution should be exercised in the interpretation of outcome data because of the presence in fire smoke of multiple toxicants, including carbon

Discussion

With a half-life of approximately 1 to 3 hours,6, 26, 27 cyanide disappears rapidly from blood. Technologic and logistic limitations make it difficult to analyze blood from smoke-inhalation victims within the time required for accurate measurement of peak cyanide concentrations. Research that has overcome these impediments to measure cyanide in blood sampled close to the time of smoke exposure demonstrates the presence of cyanide at toxic to lethal levels in the blood of many individuals

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      For example, a qualitative systematic review of actual fire reports/databases found that up to 87% of patients exposed to smoke inhalation may have cyanide poisoning [11]. A prospective study in France, designed to assess the patient outcomes with hydroxocobalamin for those who were victims of house fires, reported the presence of cyanide poisoning in 61% of patients [12]. Additionally, a multi-country observational study designed to understand cyanide concentrations among fire victims found that 72% of fire victims had cyanide concentrations above 10 µmol/l [13].

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    Supervising editor: E. Martin Caravati, MD, MPH

    Author contributions: All authors contributed to the design, conduct, or analysis of the study and the preparation of the article, and all approved the final version for submission. FJB takes responsibility for the paper as a whole.

    Funding and support: Data analysis for this study and medical writing assistance with the article were supported by EMD Pharmaceuticals, an affiliate of Merck KgaA. No pharmaceutical company was involved, financially or otherwise, in the design or conduct of the study. Drs. Baud and Borron have been consultants for EMD Pharmaceuticals.

    Reprints not available from the authors.

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