Correspondence

Acute Chemical Emergencies

N Engl J Med 2004; 350:2102-2104May 13, 2004

Article

To the Editor:

In their review of acute chemical emergencies, Kales and Christiani (Feb. 19 issue)1 mention intravenous dosages of nerve-agent antidotes, but not intramuscular autoinjectors: the MARK I kit (atropine, 2 mg, plus 2-pralidoxime chloride, 600 mg) and diazepam, 10 mg. Originally developed for military use, these autoinjectors are now stockpiled by civilian responders. Emergency physicians will probably see patients who have already been treated with them.

Benzodiazepines are the only anticonvulsant medications that are useful in patients with seizures from nerve agents. Trying the usual anticonvulsant drugs used for status epilepticus wastes valuable time. Although not specifically approved for this indication, midazolam is the most efficacious benzodiazepine in studies in animals.2 There is no evidence that thiosulfate is beneficial in mustard poisoning after skin lesions appear. Its usefulness in mass-casualty events is probably minimal.3

Treatment protocols and other information are always available at the Web site of the Chemical Casualty Care Division, U.S. Army Medical Research Institute of Chemical Defense (http://ccc.apgea.army.mil).

(The views expressed in this letter are those of the authors and are not necessarily those of the U.S. Army Medical Research and Materiel Command, the Department of the Army, or the Department of Defense.)

Jonathan Newmark, M.D., Col., M.C.
Charles G. Hurst, M.D., Col.(ret.), M.C.
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400
jonathan.newmark@amedd.army.mil

3 References

1
Kales SN, Christiani DC. Acute chemical emergencies. N Engl J Med 2004;350:800-808
Full Text | Web of Science | Medline

2
McDonough JH Jr, McMonagle J, Copeland T, Zoeffel D, Shih T-M. Comparative evaluation of benzodiazepines for control of soman-induced seizures. Arch Toxicol 1999;73:473-478
CrossRef | Web of Science | Medline

3
Sidell FR, Urbanetti JS, Smith WJ, Hurst CG. Vesicants. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical aspects of chemical and biological warfare. Textbook of military medicine series. Part 1. Warfare, weaponry, and the casualty. Washington, D.C.: Borden Institute, Walter Reed Army Medical Center, 1997:197-228.

To the Editor:

We agree with Kales and Christiani's emphasis on the recognition of four “toxidromes” that are applicable to most acute chemical emergencies. However, we were surprised that there was no mention of hydroxocobalamin as an antidote for severe cyanide toxicity. This drug has a cobalt ion, which allows it to chelate the cyanide and form cyanocobalamin (vitamin B₁₂), which is eliminated in the urine.1 Hydroxocobalamin reduces whole-blood cyanide levels and increases urinary cyanide excretion, and it has the added advantage of not causing methemoglobinemia or hypotension.2 Its efficacy and safety have also been proved in fire victims with cyanide intoxication.3

In Europe, hydroxocobalamin has been included in antidote kits in many paramedic units and hospital emergency rooms for the treatment of patients who have inhaled smoke during a fire or the victims of a chemical emergency in which cyanide intoxication is suspected. Similar measures have been proposed for the United States.4

Santiago Nogué-Xarau, M.D., Ph.D.
Hospital Clínic, E-08036 Barcelona, Spain
snogue@clinic.ub.es

Antonio Dueñas, M.D., Ph.D.
Hospital Universitario Río Hortega, E-47010 Valladolid, Spain

Guillermo Burillo, M.D.
Hospital Universitario de Canarias, E-38320 Tenerife, Spain

4 References

1
Duenas Laita A, Nogue Xarau S. Intoxicación por el humo de los incendios: tratamiento antidótico a base de vitaminas. Med Clin (Barc) 2000;114:658-660
Medline

2
Forsyth JC, Mueller PD, Becker CE, et al. Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. J Toxicol Clin Toxicol 1993;31:277-294
CrossRef | Medline

3
Baud FJ, Barriot P, Toffis V, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med 1991;325:1761-1766
Full Text | Web of Science | Medline

4
Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med 2001;37:635-641
CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Newmark and Hurst's comments. First, atropine, pralidoxime, and diazepam can be administered intramuscularly as therapy for exposure to nerve agents and are available as autoinjectors. Intramuscular dosing saves time during initial treatment by emergency responders and in the treatment of patients in whom gaining intravenous access is difficult. Second, although diazepam is the most frequently recommended benzodiazepine,1 lorazepam and midazolam are also effective in treating seizures from nerve agents, but barbiturates, phenytoin, and other anticonvulsant medications are not.2 Third, although thiosulfate has shown promise in animals for the treatment of mustard poisoning, the need to administer it before the development of skin lesions limits its usefulness.

We agree with Nogué-Xarau and colleagues that hydroxocobalamin (vitamin B_12a), which binds cyanide on an equimolar basis to form cyanocobalamin (vitamin B₁₂), is a safe and effective antidote for cyanide poisoning, available in Europe. In addition, thiosulfate, a slower-acting agent, may have a synergistic effect when administered after hydroxocobalamin. Cyanocobalamin can give up its cyanide to rhodanese, the enzyme that converts thiosulfate to thiocyanate, regenerating hydroxocobalamin to bind more cyanide in the case of large exposures.3 As a cyanide antidote, hydroxocobalamin is an investigational drug in the United States. Because hydroxocobalamin acts rapidly and can be administered safely by both emergency responders and hospital clinicians, the development and stockpiling of this medication might improve public health preparedness in the United States.4

Stefanos N. Kales, M.D., M.P.H.
David C. Christiani, M.D., M.P.H.
Harvard School of Public Health, Boston, MA 02115
skales@challiance.org

4 References

1
Prevention and treatment of injury from chemical warfare agents. Med Lett Drugs Ther 2002;44:1-4
Web of Science | Medline

2
Nerve agents. In: Managing hazardous material incidents (MHMI). Vol. 3. Medical management guidelines (MMGs). Atlanta: Agency for Toxic Substances and Disease Registry, 2001.

3
Aaron CK. Cyanide antidotes. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS, Howland MA, Hoffman RS, eds. Goldfrank's toxicologic emergencies. 6th ed. Stamford, Conn.: Appleton & Lange, 1998:1583-5.

4
Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med 2001;37:635-641
CrossRef | Web of Science | Medline

Citing Articles (1)