Published May 29, 2002

Thomas P.
Noeller, MD

Department of
Emergency Medicine

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Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Therapy and
Outcomes

References

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.

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 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.

Ricin
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

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.

Ricin
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.

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.

Ricin
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

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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