The Cleveland Clinic

Published May 29, 2002

Thomas P.
Noeller, MD

Thomas P. Noeller, MD

Department of
Emergency Medicine

Print Article

Copyright 2002
The Cleveland Clinic Foundation



Chapter Outline




Signs and


Therapy and


National Guidelines

CDC Emergency Room Procedures in Chemical Hazard Emergencies—A Job Aid

ATSDR: Managing Hazardous Materials Incidents


Based on recent terrorist attacks and intelligence reports of chemical weapons stockpiles in Iraq, the former Soviet Union, and other countries, health care professionals now realize the need to educate themselves on the recognition and management of chemical weapons exposures.

According to the Organization for the Prohibition of Chemical Weapons and the Chemical Weapons Convention, substances are considered chemical weapons if they, through a "chemical effect on living processes, may cause death, temporary loss of performance, or permanent injury to people and animals." A chemical warfare agent must be highly toxic but not so toxic so as to make it too difficult to handle. The substance must be capable of being stored for long periods in containers without degradation and without corroding the packaging material. It must be relatively resistant to water, air, and heat so that it does not lose effect when dispersed.1

Chemical agents are likely to be deployed in an overt attack, causing rapid onset of symptoms and mass casualties. Police, fire, and emergency medical services personnel would likely be the first to respond and to determine at least that an attack has occurred, if not the specific agent used. Immediate management would require hazardous materials (HazMat) units and large-scale decontamination and treatment facilities. Specific management requires a working knowledge of clinical syndromes and toxicologic mechanisms.

According to military intelligence and various government agencies, at least 10 countries have the capability of producing and disseminating biologic or chemical weapons.2 It is either unknown or unpublished how many terror organizations have the capability to procure, manufacture, or effectively deploy these agents. Most experts now agree, however, that the nation is facing a real threat.

Countries such as Iran, Iraq, Pakistan, Libya, Cuba, China, and North Korea, as well as the US and several of its allies are known to have manufactured large quantities of chemical warfare agents.3 Terror organizations such as the Aum Shinrikyo, which executed the sarin gas attack in a Tokyo subway in 1995, have already demonstrated their willingness to use chemical and biologic agents.4

Because panic and paranoia are undesirable, preparation is the best response to the threat of chemical terrorism. Governmental agencies, health departments, and the Centers for Disease Control and Prevention (CDC) have identified the most likely agents to be used in a chemical attack (Table 1), and they have plans in place to address such events.5 These plans emphasize the important role of the frontline medical providers in recognizing and reporting suspected biologic and chemical weapons exposures.

Nerve Agents
A variety of nerve agents were developed between 1930 and 1960 for use in bombs and other military devices. Much work went into refining these agents to increase their potency and environmental persistence. The first known nerve agent, developed in Germany in the 1930s, was called tabun. Sarin was next, followed by soman in the late 1930s and early 1940s. American scientists dubbed these first agents G agents, so tabun is also known as GA, sarin as GB, and soman as GD. The V agents were developed in the 1950s as more stable versions of the G agents. VX is more potent than sarin, and because it is more stable, less volatile, and less water-soluble, it can persist in the environment up to several weeks after release.

Nerve agents affect transmission of nerve impulses by inhibiting cholinesterase. They are all highly toxic organophosphate compounds that irreversibly bind to cholinesterase, resulting in accumulation of acetylcholine at the nerve synapses and neuromuscular junctions. An initial overstimulation of cholinergic receptors precipitates a cholinergic crisis, followed by paralysis. The cholinergic crisis is characterized by central nervous system (CNS) symptoms and muscarinic and nicotinic effects, the onset and severity of which are determined by the dose, route of exposure, and properties of the specific agent involved.

Blistering Agents
Otherwise known as mustard agents, blistering agents are so named because they cause burns and blisters. These sulfide-based compounds have devastating effects on the skin, mucous membranes, and respiratory tract. They were first developed in the 19th century and used in World War I. Most recently, they were used extensively by Iraq in their war with Iran in the 1980s.

Blistering agents are essentially colorless and odorless. Their name derives from initial attempts at manufacturing that left a residual mustard odor. Some claim that these agents now have the odor of rotten onions. However, the sense of smell is significantly diminished after only a few breaths, and injury can be induced by concentrations so low as to escape olfactory detection.

These compounds work by binding to a variety of molecules via a reactive sulfonium ion. They have a particularly high affinity for nucleic acids and sulfur and sulfhydryl groups in proteins. They act as alkylating agents, affecting biologic processes such as cell division and deoxyribonucleic acid (DNA) synthesis.

Hydrogen Cyanide
Reports of hydrogen cyanide use by Iraq in their war against Iran and against the Kurds prompts a discussion of this agent as a possible chemical terror weapon. Hydrogen cyanide is most dangerous if inhaled. Because it is highly volatile, high concentrations are difficult to achieve unless it is released into a confined space. Once inhaled, clinical effects can be immediate. Cyanide compounds work by binding to and inhibiting cytochrome aa3 in the electron transport chain, effectively stopping cellular respiration and resulting in tissue hypoxia and lactic acidosis.

An extract from castor beans, ricin is a potent cytotoxin that inhibits protein synthesis. It has been manufactured and stored as a potential chemical weapon by Iraq.

Pulmonary Agents
Chlorine and phosgene gas have been used as chemical warfare agents since World War I. Chlorine gas is described as greenish-yellow with a strong pungent odor.6 Phosgene gas forms a white cloud and is reported to have the odor of freshly mown hay.7 Both are heavier than air, making them effective trench-warfare agents. They exert their pathophysiologic effects by reacting with water, forming hydrochloric acid. Mucous membrane exposure leads to severe irritation and pain. Inhalation results in direct alveolar endothelial damage, possibly leading to non-cardiogenic pulmonary edema.8,9

Nerve Agents
The onset of symptoms may be within a few minutes or up to 18 hours, depending on the degree of exposure.10 Common CNS effects are agitation, confusion, delirium, hallucinations, seizures, and coma. Muscarinic effects tend to be the most prominent, eg, salivation, lacrimation, urinary incontinence, diarrhea, gastrointestinal distress, and emesis, and are easily remembered using the mnemonic SLUDGE. Bradycardia, bronchospasm, bronchorrhea, and miosis also occur. Nicotinic effects resulting from acetylcholine stimulation of nicotinic receptors in sympathetic ganglia include tachycardia, hypertension, and pallor. Nicotinic stimulation at the neuromuscular junction causes muscle fasciculations, pain, and weakness particularly involving the respiratory muscles. Death results most directly from respiratory failure caused by respiratory muscle paralysis, loss of airway control, and profuse bronchorrhea.

The impact of a nerve agent release would depend on the agent used, the method of release, and the environmental concentration. Those in closest proximity or downwind of a vapor release would be expected to have the highest mortality rates. Others in the surrounding area would display varying degrees of symptoms. Inhalational exposure to sarin, the most volatile agent, may result in death in only a few minutes. A 2-mm2 to 3-mm2 area of dermal exposure to VX is potentially fatal.

Blistering Agents
Generally, no immediate symptoms occur, and presentation may be delayed 2 to 24 hours after exposure.10 Once symptoms do occur, eye irritation, lacrimation, cough, hoarseness, and a burning sensation on the skin would likely be the first indication of exposure. Skin damage is characterized first by generalized painful inflammation, followed by blistering and desquamation.

Death is most likely to result from direct lung injury or sepsis. Coughing, hoarseness, and chest discomfort may be the first symptoms, followed by evidence of pulmonary edema and respiratory failure. Effects on tissues such as bone marrow and the immune system may be delayed for 5 to 10 days, and the increased risk of neoplasm resulting from DNA alkylation may not manifest for months or years.11

Hydrogen Cyanide
After exposure to high concentrations of hydrogen cyanide, death is practically instantaneous. Lower concentrations may produce tachypnea, restlessness, headache, and palpitations followed by seizures, coma, and death. The clinical syndrome essentially mimics hypoxemia and hypoxia, with the exception that cyanosis is absent.

Clinical effects may be observed following either ingestion or inhalation. Inhalation exposure is characterized by cough, chest tightness, dyspnea, fever, and profuse sweating.12 Airway necrosis and lung injury follows over the next 2 to 3 days, manifested by hemoptysis and pulmonary edema. Ingestion of ricin from a contaminated food source would result in hemorrhagic gastroenteritis, shock, and death.

Pulmonary Agents
Clinical effects of chlorine and phosgene exposure are dose-dependent. Low levels can produce tearing, rhinorrhea, coryza, and salivation. Higher-level exposures will result in more severe respiratory effects: coughing, dyspnea, wheezing, and chest discomfort. Physical examination may reveal tachypnea, tachycardia, hypoxemia, rales, wheezes, and rhonchi. Non-pulmonary effects include lightheadedness, muscle pain and weakness, and abdominal discomfort.

The diagnosis of chemical agent exposure is largely made on clinical grounds based on the presenting syndrome. Hydrogen cyanide exposure might be confirmed in the appropriate clinical setting when a high venous partial pressure of oxygen (PO2) relative to arterial PO2 is noted, resulting from the inability of tissues to use oxygen. Clinical response to appropriate antidotes should also help confirm the specific diagnosis.
Nerve Agents
Efficient deployment of HazMat teams is critical to control a nerve agent attack. All major cities and emergency medical services have plans and equipment in place to address such emergencies, but the physician must be aware of principles involved in handling a patient or multiple patients exposed to one of these agents. Caregivers must first protect themselves by using isolation suits and butyl rubber gloves, because secondary contamination of even small amounts of these substances, especially VX, may result in lethal consequences.

Remember that these compounds are organic and have limited solubility in water. They penetrate latex gloves, resulting in dermal exposure to anyone observing only basic barrier precautions. Patients must be decontaminated by removing their clothing and washing with soap and water in appropriate decontamination facilities. VX is particularly oily and water-insoluble, so exposed patients must be decontaminated using alcohol, ethers, or acetate solutions.

Treatment for nerve agent exposure involves large amounts of atropine and significant critical care resources. Patients with only minimal inhalational exposures resulting in mild rhinorrhea, miosis, or blurred vision may need observation only. All other patients with symptoms will require atropine in doses starting at 2 mg. In severely affected patients, a starting dose of 6 mg is appropriate. Some patients may require up to 40 mg of atropine, potentially exhausting hospital supplies. Although atropine is effective in treating the muscarinic effects, it does nothing for the nicotinic effects. Thus, the goal of atropine therapy is the resolution of bronchorrhea.

Anyone requiring atropine should also receive the antidote to organophosphates, pralidoxime chloride. This compound reverses the binding of the organophosphate to acetylcholinesterase, reactivating the enzyme. However, it works only if aging has not taken place. Aging is the process by which the temporary phosphorylated bond between the organophosphate and acetylcholinesterase undergoes alkyl group hydrolysis, resulting in a permanent covalent bond. Once aging has taken place, only regeneration of new enzyme will result in clinical improvement, a process that may take days or weeks. Soman undergoes aging in 2 minutes, sarin in 5 hours.11 Therefore, early administration of pralidoxime is critical. Appropriate starting doses are 600 mg for mild to moderate symptoms and up to 1,800 mg for severely affected individuals.12

Military personnel have been trained in the use of autoinjectors containing 2 mg of atropine and 600 mg of pralidoxime for immediate intramuscular injection. These autoinjectors may be available for civilian use in the event of nerve agent attacks.

Blistering Agents
Treatment for blistering agent exposure is largely supportive, as there is no known antidote. Decontamination is important to prevent further exposure to the patients and health care providers. Off-gassing poses a potential danger to responders, particularly in hot weather, and necessitates respiratory protection. The patient's clothes must be removed and sealed, the patient washed with soap and water, eyes flushed, and hair shaved. Decontamination facilities set up by HazMat teams would likely be necessary for multiple patients, and suitable barrier precautions would be provided to health care staff.

Burn units would be the most appropriate for managing the most severely affected patients because the initial syndrome and subsequent complications, such as local and systemic infection, are similar to those of more common burn injuries.

Hydrogen Cyanide
Treatment for cyanide poisoning is based on its mechanism of action. First, sodium nitrite is given intravenously at a dose of 10 mL of a 3% solution over 2 to 3 minutes. The pediatric dose is 0.2 mL/kg up to 10 mL. Because the dose is based on available hemoglobin, it must be adjusted for anemia (charts are provided in the kit). Amyl nitrite capsules are available for inhalation, but are relatively inefficient and should be given only until intravenous access is achieved.

The nitrites convert hemoglobin to methemoglobin, which has a higher binding affinity for cyanide than does cytochrome oxidase. Cyanomethemoglobin is then converted to thiocyanate via rhodanese, regenerating methemoglobin in the process. Because rhodanese requires a sulfur substrate to exert its effect, sodium thiosulfate is given at a dose of 12.5 g intravenously after the sodium nitrite. Thiocyanate is then easily eliminated in the urine.

Hydroxocobalamin (vitamin B12) has been investigated as an antidote for cyanide intoxication, but is not yet approved by the US Food and Drug Administration for this indication.13 It combines with cyanide to form cyanocobalamin, a nontoxic compound easily excreted in the urine. It also has the benefit of avoiding the potential adverse effects of nitrite-induced methemoglobinemia.

There is no specific antidote for ricin, so treatment is largely supportive. Aggressive gut decontamination with activated charcoal might be considered if, for some reason, ricin ingestion is suspected.

Pulmonary Agents
There is no specific antidote for phosgene or chlorine gas exposure, so treatment is largely supportive. Because pulmonary toxicity can result in significant morbidity, attention should immediately be paid to the ABCs of resuscitation (airway, breathing, circulation). Initial decontamination methods should be carried out as in all suspected chemical agent exposures. Supportive therapy consisting of supplemental oxygen and ventilatory assistance via bilevel positive airway pressure or endotracheal intubation and positive end-expiratory pressure may be appropriate. Aggressive pulmonary toilet should be used to control excessive secretions. Although minimal laboratory work is necessary, arterial blood gas analysis may reveal the degree of hypoxemia and ventilatory failure. A chest radiograph should be performed. Bronchospasm may respond to inhaled or parenteral beta-receptor-agonists. Aminophylline, which was used in World War I with some success, is considered controversial because current evidence to support its use is lacking. There is no evidence that steroids or prophylactic antibiotics have a place in the management of pulmonary toxicity resulting from phosgene or chlorine gas exposure.6,7

Asymptomatic patients exposed to these gases should be observed for 4 to 6 hours for the development of signs of pulmonary edema because the clinical effects of moderate exposures may be delayed.6

Although it is not known whether or when a biologic or chemical attack will take place, clinicians can improve the medical community's readiness for such a situation by disseminating reliable information to others. Many resources provide information on chemical and biologic terrorism; one would want to focus on reliable sources because, unfortunately, times like these spawn a few who seek to spread fear and panic through misinformation.

For more information, readers are referred to the CDC web site, the Agency for Toxic Substances and Disease Registry and the World Health Organization. These web sites are excellent resources for the most up-to-date information on the management of chemical weapons exposures. They provide not only a listing of common agents, their properties and toxic effects, but current information on management of exposed patients. The CDC web site and the ATDSR web site provide guidelines for management of HazMat situations in both the pre-hospital and emergency department settings, emphasizing agent identification, decontamination, and prevention of secondary contamination of health care providers. Since information in this area is evolving rapidly, readers are encouraged to visit these sites often to obtain the most current information available.

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  1. Organization for the Prohibition of Chemical Weapons. Convention on the prohibition of the development, production, stockpiling and use of chemical weapons and on their destruction. Accessed 2/5/02.

  2. Department of Defense. Chemical and Biological Defense Program Annual Report to Congress and Performance Plan. July 2001. Accessed 1/23/02.

  3. Central Intelligence Agency. Unclassified Report to Congress on the Acquisition of Technology Relating to Weapons of Mass Destruction and Advanced Conventional Munitions, 1 January Through 30 June 2000.
    publications/bian/bian_feb_2001.htm#5. Accessed 2/13/02.

  4. Okumura T, Takasu N, Ishimatsu S. Report on 640 victims of the Tokyo sarin attack. Ann Emerg Med. 1996;28:129-135.

  5. Centers for Disease Control and Prevention. Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup. MMWR. 2000;49(RR-4):1-14.

  6. Noltkamper D, O'Malley GF. CBRNE - Lung-damaging agents, chlorine. eMedicine J. 2001;2(10)

  7. Arnold JL. CBRNE - Lung-damaging agents, phosgene. eMedicine J. 2001:2(10)

  8. Centers for Disease Control and Prevention. International chemical safety cards: chlorine.
    ipcs0126.asp. Accessed January 24, 2002.

  9. Centers for Disease Control and Prevention. International chemical safety cards: Phosgene.
    Pulmonary/ipcs0007.asp. Accessed January 24, 2002.

  10. Sidell FR, Takafuji ET, Franz DR, eds. Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General, TMM Publications, 1997.

  11. Organization for the Prohibition of Chemical Weapons. Chemical warfare agents. Based on A FOA Briefing Book on Chemical Weapons. Stockholm, 1992. Accessed 10/31/01.

  12. White SR, Eitzen EM Jr. Hazardous materials exposure. In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergency Medicine: A Comprehensive Study Guide, 5th ed. New York: McGraw-Hill, 2000:1201-1215.

  13. Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med. 2001;37:635-641.