Elsevier

Toxicology

Volume 214, Issue 3, 30 October 2005, Pages 221-231
Toxicology

Medical management of incidents with chemical warfare agents

https://doi.org/10.1016/j.tox.2005.06.028Get rights and content

Abstract

Successful management of incidents with chemical warfare agents strongly depends on the speed of medical help and the ability of helpers to react properly. Though the general principles of clinical toxicology, such as decontamination, stabilization, patient evaluation and symptomatic treatment are similar for many toxicants, chemical warfare agents deserve special attention because of their very high inhalative and cutaneous toxicity, rapid onset of the disease and multiple organ failures.

This article describes the medical management of mass casualties with blister agents, nerve agents and blood agents from the viewpoint of a clinical toxicologist. Characteristic diagnostic signs, decontamination procedures and therapeutic schemes for these agents are described. Treatment options are discussed. The importance of planning (e.g. antidote availability) and preparedness is emphasized.

Introduction

After the terrorist attacks of Matsumoto (1994), Tokyo (1995) and of September 11th, 2001 with the subsequent anthrax letters there is an increased awareness that terrorists might use chemical warfare agents or other very toxic materials in future homicidal attempts. Though prevention and mitigation are in the focus of planning activities, the medical toxicologist must be ready to treat poisoned victims in the case of a chemical incident according to the state of the art.

Some of the diagnostic and therapeutic experiences with chemical warfare agents are based on the outcome of their former use. The devastating effect of chemical warfare agents such as chlorine and mustard gas which even surprised the first users is well-known from World War I (Koch, 1921, Muntsch, 1939). The nerve agents were developed just before the second World War in search of insecticides by Schrader (Schrader, 1950). When they were used by the Iraq Forces during the Iraq–Iran War (1983–1988) nobody had much experience with their effects on humans. Also sulphur mustard claimed many deaths and 100,000 injured (Balali Mood, 1988) in the Iran–Iraq War. In 1995, Japanese terrorists used the nerve agent sarin in two terrorist assaults. The first one happened in Matsumoto (Okudera et al., 1997). The second attack was launched in the subway of Tokyo. More than 5000 persons needed medical care and 12 died (Nozaki et al., 1995, Ohbu et al., 1997).

The mechanism of action of selected chemical warfare agents will be briefly discussed in this paper. Diagnostic and therapeutic options in case of mass poisoning will be considered from the viewpoint of a clinical toxicologist in an emergency poison center.

Section snippets

Management principles of incidents with chemical warfare agents

Management of chemical incidents requires specific knowledge of the toxicants and their biological effects as well as clinical experiences in the diagnosis and treatment of intoxications. Compared to common medical emergencies, the management of chemical incidents is aggravated by requirements of decontamination and personal protection. Stockpiled antidotes and protective equipment must be immediately available (Table 1).

In the initial phase of a chemical mass casualty, the identity of the

Groups of chemical warfare agents

Chemical warfare agents include nerve agents, blister agents, blood agents and lung agents. Blister agents include sulphur mustard and nitrogen mustard. Nerve agents include tabun (GA), sarin (GB), soman (GD) and VX. Blood agents are hydrogen cyanide (AC) and cyanogen chloride (CK). Lung agents include phosgene and diphosgene (Helm and Weger, 1980).

General

The term blister agents seems to be very euphemistic and describes only one of the visible symptoms of a potentially systemic poisoning. Many other organs are damaged not just the skin. Organs with proliferating epithelia like eyes, lungs and the bone marrow may be severely damaged. Death ensues either due to bronchial obstruction, bronchopneumonia or bone marrow aplasia (Zilker and Felgenhauer, 2002). The blistering agent sulphur mustard has the highest military significance in the group. It

General

Nerve agents belong to the group of phosphororganic (OP) cholinesterase inhibitors, with some prominent of these compounds first synthesized by German chemists in the 1930s (Baselt, 2002). Their basic chemical structure which they all have in common, is described by the Schrader formula (Abou-Donia, 1995).

The structural diversity of OPs is due to different substituents at the phosphorus atom. R1 and R2 are alkyl-, alkoxy-, alkylthio- or amino-groups and X is a labile acyl residue (halide-,

General

The devastating action of cyanide gas has been dug into the memory of mankind by the inhuman use of it for the genocide of the Jewish people by the Nazis. As a matter of fact cyanide was used during WW I under the name of Vincennite as warfare agent (Paulet, 1962). Hydrogen cyanide gas has a high vapour pressure and low molecular weight which means that deadly concentrations in the open air are difficult to achieve. Nevertheless, a terrorist attack inside buildings cannot be excluded and could

References (64)

  • Balali Mood, M., 1988. Personal...
  • D. Barak et al.

    Evidence for P–N bond scission in phosphoroamidate nerve agent adducts of human acethylcholinesterase

    Biochemistry

    (2000)
  • P.G. Bardin et al.

    Intensive care management of acute organophosphate poisoning. A 7-year experience in the Western Cape

    S. Afr. Med. J.

    (1987)
  • R.C. Baselt

    Sarin

    Disposition of Toxic Drugs Chemicals in Man

    (2002)
  • F. Blodi

    Mustard gas keratopathy

    Int. Ophtalmol. Clin.

    (1971)
  • J. Borak et al.

    Agent of chemical warfare: sulphur mustard

    Ann. Emerg. Med.

    (1992)
  • J.G. Clement

    Toxicity of the combined nerve agent GB/GF in mice: efficacy of atropine and various oximes as antidotes

    Arch. Toxicol.

    (1994)
  • R.F. De Busk et al.

    Attempted suicide by cyanide. A report of two cases

    Calif. Med.

    (1969)
  • R.T. Dorr et al.

    Cancer Chemotherapy Handbook, Dermal Contamination

    (1980)
  • W.D. Erdmann et al.

    Ein neuer Esterase Reaktivator für die Behandlung von Vergiftungen mit Alkylphosphaten

    Dtsch. Med. Wochenschr.

    (1963)
  • F. Eyer et al.

    Human parathion poisoning

    Toxicol. Rev.

    (2003)
  • P. Eyer

    The role of oximes in the management of organophosphorus pesticide poisoning

    Toxicol. Rev.

    (2003)
  • P. Eyer et al.

    Reaction of 4-dimethylaminophenols with haemoglobin

    Arch. Exp. Path. Pharmak.

    (1971)
  • T. Garigan

    Medical Treatment of Chemical Warfare Casualities

    (1996)
  • W.J. Geeraets et al.

    Acute corneal injury by mustard gas

    South. Med. J.

    (1977)
  • W.M. Grant

    Mustard gas

  • D. Grob

    The manifestation and treatment of poisoning due to nerve gas and other organic phosphate anticholinesterase compounds

    Arch. Intern. Med.

    (1956)
  • U. Helm

    Nevenkampfstoffvergiftungen (Alkylphophatvergiftungen)

  • U. Helm et al.

    Grundzüge der Wehrtoxikologie

  • R.M. Joy
  • G. Kauert et al.

    Plasma-katecholamin-verlauf bei alkylphosphat-intoxikationen und deren therapie

    Klin. Wochenschr.

    (1990)
  • M. Kiese et al.

    Versuche am menschen zur kinetik der ferrihämoglobinbildung durch aminophenole und nitrit

    Arch. Exp. Path. Pharmak.

    (1968)
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