CHAPTER 2-159: WARFARE AGENTS—CHEMICAL

Chemical warfare has a long history that may have reached its zenith during World War I with the battlefield use of chlorine, phosgene, and mustard gases. More recently, Iraq used chemical agents in its war with Iran and against its own Kurdish population. In 1995, Aum Shinrikyo, a terrorist cult, released the nerve agent sarin in the Tokyo subway system during rush hour. It is also alleged that nerve agents were used in Syria.

Chemical warfare agents are divided into groups largely on the basis of their mechanism of toxicity (Table II–64): nerve agents, vesicants or blister agents, blood agents or cyanides, choking agents, and incapacitating agents. Presenting symptoms and the clinical circumstances may help identify the agent and lead to effective treatment as well as proper decontamination.

1. Nerve agents include GA (tabun), GB (sarin), GD (soman), GF, and VX. These potent organophosphorus agents cause inhibition of acetylcholinesterase and subsequent excessive muscarinic and nicotinic stimulation (Organophosphorus and Carbamate Insecticides).

2. Vesicants (blister agents). Nitrogen and sulfur mustards are hypothesized to act by alkylating cellular DNA and depleting glutathione, leading to lipid peroxidation by oxygen free radicals; lewisite combines with thiol moieties in many enzymes and also contains trivalent arsenic.

3. Choking agents include chlorine and lacrimator agents. These gases and mists are highly irritating to mucous membranes. In addition, some may combine with the moisture in the respiratory tract to form free radicals that lead to lipid peroxidation of cell walls. Phosgene causes less acute irritation but may lead to delayed pulmonary injury due to deeper pulmonary inspiration (Phosgene).

4. Cyanides (blood agents) include cyanide, hydrogen cyanide, and cyanogen chloride (Cyanide). These compounds have high affinity for metalloenzymes such as cytochrome aa3, thus inhibiting cellular respiration and leading to a metabolic acidosis.

5. Incapacitating agents. A variety of agents have been considered, including strong antimuscarinic compounds such as BZ and scopolamine (see "Anticholinergics"), stimulants such as amphetamines and cocaine, hallucinogens such as LSD, and CNS depressants such as opioids. A form of fentanyl gas mixed with an inhalational anesthetic may have been used by Russian authorities in 2002 in an attempt to free hostages being held in a Moscow theater.

Vary widely and also depend on the physical properties of the agents as well as the route and duration of exposure. Apart from the mechanism of toxicity of the chemical weapon, the following are important for consideration:

1. Physical state of the chemical. Agents delivered as aerosols and in large droplets generally have more persistence and can accumulate on surfaces. Gases tend to disperse, whereas vaporized forms of liquids may reliquefy in a cooler environment, leading to the potential for delayed dermal exposure. The use of high–molecular-weight thickeners to decrease evaporation of substances has been shown to increase agent persistence.

2. Volatility. Highly volatile agents (eg, hydrogen cyanide) vaporize rapidly and can be easily inhaled, whereas chemicals with low volatility (eg, VX) can remain in the environment for long periods.

3. Environmental factors. The presence of wind and rain can reduce the effectiveness of chemical weapon delivery by increasing dispersion and dilution. Cold weather may reduce vapor formation but increase the persistence of the liquid form of some agents. Gases and vapors heavier than air may accumulate in low-lying areas.

4. Agent decomposition (see Table II–64). Some warfare agents produce toxic by-products when exposed to acidic environments. GA may produce hydrogen cyanide and carbon monoxide. GB and GD produce hydrogen fluoride under acidic conditions. Lewisite is corrosive to steel and in nonalkaline conditions may decompose to trisodium arsenate. VX forms the toxic product EA2192 when it undergoes alkaline hydrolysis.

1. Nerve agents are potent cholinesterase-inhibiting organophosphorus compounds. Symptoms of muscarinic and nicotinic overstimulation include abdominal pain, vomiting, diarrhea, excessive salivation and sweating, bronchospasm, copious pulmonary secretions, muscle fasciculations and weakness, and respiratory arrest. Seizures, bradycardia, or tachycardia may be present. Severe dehydration can result from volume loss caused by sweating, vomiting, and diarrhea.

2. Vesicants (blister agents). The timing of onset of symptoms depends on the agent, route, and degree of exposure.

   1. Skin blistering is the major cause of morbidity and can lead to severe tissue damage.

   2. Ocular exposure causes tearing, itching, and burning and can lead to severe corneal damage, chronic conjunctivitis, and keratitis. Permanent blindness usually does not occur.

   3. Pulmonary effects include cough and dyspnea, chemical pneumonitis, and chronic bronchitis.

3. Choking agents can cause varying degrees of mucous membrane irritation, cough, wheezing, and chemical pneumonitis. Phosgene exposure may also present with delayed pulmonary edema that can be severe and sometimes lethal.

4. Cyanides cause dizziness, dyspnea, confusion, agitation, and weakness, with progressive obtundation and even coma. Seizures and hypotension followed by cardiovascular collapse may occur rapidly. The effects of these agents tend to be all or nothing in a gas exposure, so if patients survive the initial insult, they can be expected to recover.

5. Incapacitating agents. The clinical features depend on the agent (see Item I.E above).

   1. Antimuscarinics. As little as 1.5 mg of scopolamine can cause delirium, poor coordination, stupor, tachycardia, and blurred vision. BZ (3-quinuclidinyl benzilate, or QNB) is about three times more potent than scopolamine. Other signs include dry mouth, flushed skin, and dilated pupils.

   2. LSD and similar hallucinogens cause dilated pupils, tachycardia, CNS stimulation, and varying degrees of emotional and perceptual distortion.

   3. CNS stimulants can cause acute psychosis, paranoia, tachycardia, sweating, and seizures.

   4. CNS depressants generally cause somnolence and depressed respiratory drive (with apnea possible).

Is based mainly on symptoms as well as the setting in which the exposure occurred.

1. Specific levels

   1. Nerve agents. Plasma and red blood cell cholinesterase activity is depressed, but interpretation may be difficult because of wide inter-individual variability and broad normal ranges (Organophosphorus and Carbamate Insecticides).

   2. Pulmonary agents and vesicants. There are no specific blood or urine levels that will assist in diagnosis or management.

   3. Cyanides. Cyanide levels will be elevated, but rapid testing is not widely available. Suspect cyanide poisoning if a patient has severe metabolic acidosis, especially if mixed venous oxygen saturation is greater than 90%.

2. Other laboratory tests include CBC, electrolytes, glucose, BUN, creatinine, arterial blood gases, amylase/lipase and liver transaminases, chest radiography, and ECG monitoring. In addition, obtain serum lactate and mixed venous oxygen saturation if cyanide poisoning is suspected.

3. Methods of detection. The military has developed various devices to detect commonly known chemical warfare agents encountered in liquid or vapor forms. These devices include individual soldier detection systems such as M8 and M9 paper, which identify persistent and nonpersistent nerve or blister agents. These tests are sensitive but not specific. More sophisticated chemical agent detector kits, such as the M256 and M256A1 kits, which can identify a larger number of liquids or vapors, are also available. Systems that monitor air concentrations of various agents also have been used, such as the US military's CAM (Chemical Agent Monitor), ICAM (Improved Chemical Agent Monitor), and ACADA (Automatic Chemical Agent Detector/Alarm). Complexity and portability vary widely among detection methods: M9 paper may simply indicate that an agent is present, whereas the Chemical Biological Mass Spectrometer Block II analyzes air samples with a mass spectrometer. Further development of such systems is under way in both the private and governmental/military sectors.

For expert assistance in management of chemical agent exposures and to access pharmaceutical antidote stockpiles that may be needed, contact your local or state health agency or a local poison control center (1-800-222-1222). In addition, if an act of terrorism is suspected, contact the Federal Bureau of Investigation (FBI).

1. Emergency and supportive measures. Caution: Rescuers and health care providers should take measures to prevent direct contact with the skin or clothing of contaminated victims because secondary contamination and serious illness may result (see Section IV).

   1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Monitor patients closely; airway injury may result in abrupt obstruction and asphyxia. Muscle weakness caused by nerve agents may cause abrupt respiratory arrest. Delayed pulmonary edema may follow exposure to less soluble gases such as phosgene.

   2. Treat hypotension, seizures, and coma if they occur.

2. Specific drugs and antidotes

   1. Nerve agents (Organophosphorus and Carbamate Insecticides)

      1. Atropine. Give 0.5–2 mg IV initially and repeat the dose as needed. Initial doses may also be given IM. The most clinically important indication for continued atropine administration is persistent wheezing or bronchorrhea. Note: Atropine will reverse muscarinic but not nicotinic (muscle weakness) effects.

      2. Pralidoxime (2-PAM, Protopam) is a specific antidote for organophosphorus agents. It should be given immediately (to potentially improve muscular weakness and fasciculations) as a 1- to 2-g initial bolus dose (20–40 mg/kg in children) IV over 5–10 minutes, followed by a continuous infusion. It is most effective if started early, before irreversible phosphorylation of cholinesterase, but may still be effective if given later. Initial doses can be given by the IM route if IV access is not immediately available. Note: Oximes such as HI-6, obidoxime, and P2S may be available in other countries for cholinesterase regeneration. The availability of these agents in the United States is currently very limited.

      3. Benzodiazepines. Anticonvulsant therapy may be beneficial even before the onset of seizures and should be considered as soon as exposure is recognized. The initial diazepam dose is 5–10 mg IV in adult patients (0.1–0.3 mg/kg in children), while the dose of lorazepam is 1–2 mg IM or IV in adults (0.05–0.1 mg/kg in children). See Benzodiazepines (Diazepam, Lorazepam, and Midazolam).

   2. Vesicants. Treat primarily as a chemical burn (Caustic and Corrosive Agents).

      1. British anti-lewisite (BAL), a chelating agent used in the treatment of arsenic, mercury, and lead poisoning, originally was developed for the treatment of lewisite exposures. Topical BAL has been recommended for eye and skin exposure to lewisite; however, preparations for ocular and dermal use are not widely available.

      2. Sulfur donors such as sodium thiosulfate have shown promise in animal models of mustard exposures when given before or just after an exposure. The role of this antidote in human exposures is not clear.

   3. Choking agents. Treatment is mainly symptomatic, with the use of bronchodilators as needed for wheezing. Hypoxia should be treated with humidified oxygen, but caution should be exercised in treating severe chlorine or phosgene exposure because excessive oxygen administration may worsen the lipid peroxidation caused by oxygen free radicals. Steroids may be indicated for patients with underlying reactive airways disease.

   4. Cyanides. Hydroxocobalamin (Cyanokit) chelates cyanide to form cyanocobalamin (vitamin B₁₂), which is then renally excreted. The initial dose is 5 g (2 vials) given IV over 15 minutes. The pediatric dose is 70 mg/kg. If hydroxocobalamin is not available, the older cyanide antidote package (Nithiodote and others) can be used instead. It consists of sodium nitrite, which produces cyanide-scavenging methemoglobinemia, and sodium thiosulfate, which accelerates the conversion of cyanide to thiocyanate. Amyl nitrite may also be included in older kits.

   5. Incapacitating agents

      1. Antimuscarinic delirium may respond to physostigmine.

      2. Stimulant toxicity and bad reactions to hallucinogens may respond to lorazepam, diazepam, and other benzodiazepines.

      3. Treat suspected opioid toxicity with naloxone.

3. Decontamination. Note: Rescuers should wear appropriate chemical-protective clothing, as some agents can penetrate clothing and latex gloves. Butyl chemical-protective gloves should be worn, especially in the presence of mustard agents. Preferably, a well-trained hazardous materials team should perform initial decontamination before transport to a health care facility (see Section IV). Decontamination of exposed equipment and materials may also be necessary but can be difficult because agents may persist or even polymerize on surfaces. Currently, the primary methods of decontamination are physical removal and chemical deactivation of the agent. Gases and vapors in general do not require any further decontamination other than simple physical removal of the victim from the toxic environment. Off-gassing is unlikely to cause a problem unless the victim was thoroughly soaked with a volatile liquid.

   1. Physical removal involves removal of clothing, dry removal of gross contamination, and flushing of exposed skin and eyes with copious amounts of water. The M291 kit employed by the US military for individual decontamination on the battlefield uses ion-exchange resins and adsorbents to enhance physical removal of chemical agents before dilution and chemical deactivation. It consists of a carrying pouch that contains six individual pads impregnated with a resin-based powder. The M258A1 kit contains two types of packets for removal of liquid chemical agents, one for the G-type nerve agents (Packet 1) and the other for nerve agent VX and liquid mustard (Packet 2).

   2. Chemical deactivation of chemical agents. Nerve agents typically contain phosphorus groups and are subject to deactivation by hydrolysis, whereas mustard and VX contain sulfur moieties subject to deactivation via oxidation reactions. Various chemical means of promoting these reactions have been used.

      1. Oxidation. Dilute sodium or calcium hypochlorite (0.5%) can oxidize susceptible chemicals. This alkaline solution is useful for both organophosphorus compounds and mustard agents. Caution: Dilute hypochlorite solutions should not be used for ocular decontamination or for irrigation of wounds involving the peritoneal cavity, brain, or spinal cord. A 5% hypochlorite solution is used for equipment.

      2. Hydrolysis. Alkaline hydrolysis of phosphorus-containing nerve agents is an effective means of decontamination of personnel exposed to these agents (VX, tabun, sarin, soman). Dilute hypochlorite is slightly alkaline. The simple use of water with soap to wash an area may also cause slow hydrolysis.

4. Enhanced elimination. There is no role for these procedures in managing illness caused by chemical warfare agents.