Crit Care Nurse 2003 Oct; 23(5): 15-20
Cover Article
CE Article
Chemical Warfare
Toxicity of Nerve Agents
Tina Martin, RN, MSN, FNP
Sharon Lobert, RN, PhD
Tina Martin is an instructor in the school of nursing and a family nurse practitioner in the division of neurology at the University of Mississippi Medical Center in Jackson, Miss. She teaches in both the undergraduate and graduate programs in the school of nursing.
Sharon Lobert is a professor in the University of Mississippi Medical Center School of Nursing and teaches in the graduate and doctoral programs.
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This article has been designated for CE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives:
- Recognize common nerve agents utilized in chemical warfare
- Describe properties and clinical manifestations of various nerve agents
- Identify management for patients exposed to nerve agents
Concerns about threats to public safety have escalated dramatically since the events of September 11, 2001. These concerns include the possibility of the deliberate release of deadly nerve agents developed since the 1930s as weapons of chemical warfare.1 Among these agents are the organophosphates, VX, and the G agents (tabun, sarin, and soman). Immediate care, including decontamination, could save lives. In the following summary, we report information essential for emergency department and critical care nurses about the action of nerve agents and the clinical signs and symptoms of exposure to these agents. We explain the use of decontamination procedures, antidotes, and the care of patients exposed to nerve agents. This article is meant to provide an overview of issues related to nerve-agent poisoning. Detailed protocols for treatment may be specified in agency policies and procedures.
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Properties of Nerve Agents
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Nerve agents differ in their water solubility and volatility.1,2 The relative differences in these properties influence an agent’s potential as a biological hazard. For example, more volatile compounds are readily inhaled. In general, nerve agents enter the body via the respiratory tract; however, some agents that are easily dissolved by organic solvents rather than water may be absorbed through the skin. Understanding these properties will help nurses evaluate signs and symptoms and initiate appropriate decontamination procedures and emergency care.
V agents
V agents are sulfur-containing organophosphates. VX, the most common form, is an oily, odorless, amber liquid at room temperature. It does not readily evaporate and in order to be dispersed, it must be aerosolized into tiny droplets. It can persist on the ground for 2 to 6 days.1 Degradation products continue to have some activity. Water-dispersed V agents can enter the body via the skin or mucous membranes or, most efficiently, be inhaled as a vapor.
G agents
GA (tabun) is a cyanide-containing agent, whereas both GB (sarin) and GD (soman) contain fluorine.3 GA is an oily, colorless to brown liquid that gives off a colorless vapor that has a fruity odor. GA was the first nerve agent discovered in the late 1930s in Germany, and it was produced in quantity in the early 1940s. It is readily soluble in organic solvents and can penetrate skin; although generally it enters the body as a vapor via the respiratory tract. Its main site of action is the respiratory system. However, it can also impair vision. GA evaporates 20 times more slowly than does water, and in its liquid form, it may persist 1 to 2 days under ambient conditions.1
GB (sarin), the agent used in a terrorist attack in Japan in 1995, is a colorless, odorless liquid.2,4 It evaporates at the same rate as does water. Because it is the most volatile of the G agents, it is more of a vapor hazard than a contact hazard. The few known degradation products are relatively stable and relatively nontoxic.1
GD (soman) is a colorless liquid that gives off a colorless vapor with a fruity or camphor odor.1,2 It evaporates at about one quarter the rate of water. GD is intermediate between GA and GB in volatility; however, its volatility is high enough to make it a vapor hazard.
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Action of Nerve Agents
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Nerve agents inhibit the enzyme acetylcholinesterase by causing irreversible phosphorylation of the enzyme’s active site.3 This enzyme is essential for normal muscle and glandular function. It degrades the neurotransmitter acetylcholine at its site of release, permitting smooth and coordinated muscle contractions and maintaining normal glandular secretions (see Figure
). The clinical signs and symptoms of exposure to a nerve agent are, therefore, signs and symptoms of enhanced or excessive cholinergic activity. The activities of both nicotinic and muscarinic receptors of the autonomic nervous system are affected. Nicotinic and muscarinic receptors are found at the synapses, where preganglionic neurons can stimulate postganglionic neurons, and at the postganglionic effector cells of the autonomic nervous system. In addition, nicotinic receptors can be found at the neuromuscular junctions of skeletal muscle and at other nonautonomic sites. Excessive cholinergic activity causes muscle contractions to become uncoordinated and sustained. Inappropriate levels of acetylcholine lead to the uncontrolled release of copious secretions from mucus-forming cells of the gastrointestinal and respiratory tracts and from the glands that produce tears, saliva, and sweat.
Cholinergic signs and symptoms due to acetylcholinesterase inhibition occur quite quickly, depending on the dose: signs and symptoms of eye exposure occur in less than 2 to 3 minutes; those of respiratory exposure, in 2 to 5 minutes. Absorption through the skin can cause death in 1 to 2 minutes. Death due to inhalation of lethal doses can occur in less than 15 minutes.3
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Autonomic and Central Nervous System Effects
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Nerve agents affect both the autonomic and the central nervous systems.3,5 The extent of the signs and symptoms may be localized or generalized, depending on the exposure dose.
Muscarinic Effects
Increased cholinergic muscarinic activity affects the muscles of the eye, resulting in miosis, eye pain, and blurred vision. Indications of muscarinic activity also include respiratory signs such as copious secretions (saliva and nasal mucus) and bronchoconstriction. Gastrointestinal signs and symptoms include nausea and vomiting, abdominal cramps, epigastric distress, and diarrhea. Additional signs are hyperemia, excessive tearing, sweating, bradycardia, frequent urination, and incontinence.3
Nicotinic Effects
Cholinergic nicotinic effects include excessive activity of striated muscles, leading to muscle fatigue, weakness, twitching, and cramps. Generalized muscle weakness affecting respiratory function may cause dyspnea and lead to death. Sympathetic effects cause vasoconstriction leading to pallor and transient elevation of blood pressure followed by hypotension.3
Central Nervous System Effects
Acute effects on the central nervous system lead to serious depression of the respiratory and circulatory centers. Dyspnea, cyanosis, and hypotension may occur. Seizures, loss of consciousness, and coma may ensue. Delayed effects on the central nervous system due to chronic exposure may be manifested as behavioral changes (giddiness, anxiety, restlessness, emotional lability) or insomnia, nightmares, depression, drowsiness, difficulty concentrating, slowness of recall, confusion, slurred speech, or ataxia.3
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Clinical Manifestations
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It is critical that healthcare providers recognize the clinical manifestations of exposure to chemical warfare agents in order to initiate decontamination and treatment that could save lives. Furthermore, the safety of healthcare personnel depends on early recognition of exposure. Rapid recognition of exposure to nerve agents and early detection of signs and symptoms are imperative to prevent further injury. Emergency department nurses may be the first to encounter the clinical signs and symptoms, and critical care nurses will be responsible for managing ongoing care. Detailed health histories must be obtained from patients because many patients and their families may not be aware of initial exposure. One key to recognizing exposure to a nerve agent is the appearance of multiple patients with similar signs and symptoms.
The route of exposure and the dose of a nerve agent determine the onset and severity of signs and symptoms. Inhaled nerve agents can produce a rapid onset of signs and symptoms. Often, signs and symptoms such as rhinorrhea, increased secretions, bronchoconstriction, and eye pain may be misinterpreted as evidence of an upper respiratory tract illness or allergy. Objective signs include miosis, wheezing, and dyspnea. Furthermore, patients may report visual disturbances.2,5,6
Gastrointestinal symptoms are often associated with oral or dermal exposure to nerve agents. These symptoms may include nausea, vomiting, diarrhea, increased gastrointestinal mobility, increased secretions, indigestion, or chest tightness. Cardiovascular findings may be detected from an electrocardiogram showing bradycardia and atrioventricular conduction blocks.2,4–6 Lethal doses of a nerve agent often lead to immediate loss of consciousness, seizures, copious secretions, muscle fasciculations (twitching), and flaccidity.2,5,6
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Management
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Decontamination
Treatment begins with the rapid removal of the agent through a decontamination process. Personal protective equipment must be used by healthcare providers to prevent secondary contamination. The Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry recommend that healthcare personnel use chemical protective attire and butyl rubber gloves. A positive-pressure self-contained breathing apparatus should be worn when exposure is from a nerve agent vapor or liquid.2,6 Latex gloves are not considered adequate protection because many nerve agents have nonpolar properties that allow them to penetrate the latex barrier. Ideally, the contaminant should be identified, but doing so may be impossible. A decontamination area located outside the hospital must be established to prevent injury to hospital personnel and patients. Patients do not enter the emergency department until complete decontamination has been verified.5,6
Effective skin decontamination involves removal of the liquid or aerosolized agent by removing all clothing and thoroughly cleansing the skin with soap and water. Alternatively, a 0.5% solution of hypochloride (1:9 ratio of household bleach to water) may be used. Isotonic sodium chloride solution or water may be used to flush eyes, mucous membranes, and wounds.1,2,4–6 The clothing and used solution are considered contaminated and require double bagging and disposal in a closed container.1,2
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Antidotes
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Currently, in the United States, the only available antidotes used to treat exposure to nerve agents are atropine and pralidoxime (see Table). The Centers for Disease Control and Prevention has developed recommendations for prehospital management of persons exposed to nerve agents that consist of the development of a local and state disaster response team. Team members may include paramedics, firefighters, and police officers.7 Proper training of these personnel is essential because, in all likelihood, they will be the first responders to a disaster scene.8 If antidotes are used in the prehospital treatment of nerve agent exposure by emergency medical services, the Centers for Disease Control and Prevention recommends use of single-dose prefilled autoinjectors.7 One autoinjector intramuscularly delivers 2 mg of atropine and another delivers 600 mg of pralidoxime chloride.2
Atropine, an anticholinergic drug, is administered to counteract the muscarinic effects resulting from excess acetylcholine that builds up at the nerve endings in the absence of functional acetylcholinesterase (see Figure
). Hospital management of toxic effects of nerve agents includes an initial dose of 2 to 4 mg of atropine intravenously. Depending on the severity of the signs and symptoms, the dose may be repeated every 5 to 10 minutes until the signs and symptoms improve. After the administration of atropine, patients should be monitored for flushing, warmth, tachycardia, urinary hesitancy, blurred vision, and drowsiness.1,3,5 The usual dose for infants and children is 0.02 to 0.1 mg/kg.2,3,5,8,9
Pralidoxime chloride is used as an adjunct to atropine and should be given as soon as possible to counteract the nicotinic effects. Pralidoxime chloride is an oxime that reactivates acetylcholinesterase and gradually restores skeletal muscle function. The therapeutic dose of pralidoxime is 15 mg/kg administered slowly intravenously. Pralidoxime is usually given as a 1- to 2-g dose in 100 to 150 mL of isotonic sodium chloride solution intravenously for 15 to 30 minutes. The dose may be repeated if signs or symptoms warrant it. Blood pressure should be monitored carefully during the infusion because severe hypertension has been associated with the rapid administration of pralidoxime. Adverse effects of pralidoxime include tachycardia, diplopia, nausea, vomiting, and dizziness. The initial dose for a child is 15 mg/kg.1,2,3,5
Diazepam is usually administered for seizure prophylaxis or control. Seizures may be manifested by a range of clinical signs from muscular fasciculation to paralysis. Diazepam is usually initially given as a 5-mg dose and subsequently given in 5-mg increments up to a cumulative total of 20 mg intravenously or endotracheally.2,4,9 The dose for a child more than 5 years old is 1 mg intravenously.2,4
Antidotes should be administered as soon as possible, but respiratory distress or failure may ensue despite administration of medication because of bronchconstriction, increased airway secretions, and increased airway resistance. Supplemental oxygen, suctioning, and careful monitoring of patients’ vital signs, electrolyte levels, and cardiac rhythm are essential. Mechanical ventilation may be necessary. Often, signs and symptoms improve after the administration of the antidotes; however, the duration of the signs and symptoms depends on the route and degree of exposure to the nerve agent.2,5,8
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Long-term Effects
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Neuropsychological effects may persist for several weeks to months, especially if the acute cholinergic effects were severe. A detailed discussion of the long-term neurological and neuropsychological effects of exposure to nerve agents is beyond the scope of this article (see Brown and Brix10). Patients may experience impaired memory and difficulty concentrating, anxiety, irritability, and depression.5,9,10 Symmetric sensorimotor neuropathy may occur a few weeks after exposure. Long-term effects may be difficult to distinguish from post-traumatic stress disorder.10
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Conclusion
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Early recognition of the signs and symptoms of exposure to nerve agents is critical for initiating decontamination procedures and treating with antidotes. Understanding the course and potential outcomes of the illness is an important responsibility for emergency department and critical care nurses. We all hope never to encounter these life-threatening exposures; however, the preparedness of healthcare providers may make the difference between life and death.
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References
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- Munro NB, Watson AP, Ambrose KR, Griffin GD. Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning. Environ Health Perspect. 1990;89:205–215.[Medline]
- Nerve agents: Tabun (GA) CAS 77-81-6; Sarin (GB) CAS 107-44-8; Soman (GD) CAS 96-64-0; and VX CAS 5078.69-9. Available at: http://www.ATSDR.cdc.gov/mmgd4.pdf. Accessed July 7, 2003.
- Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J. Ellenhorn’s Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997:1267–1282.
- DeLorenzo RA. Exposed: signs, symptoms and EMS management of nerve-agent poisoning. J Emerg Med Serv JEMS. June 2001;26:48–57.
- Pfaff BL. Emergency department management of nerve agent exposure. Int J Trauma Nurs. 1998;4:71–78.[Medline]
- Centers for Disease Control and Prevention. Public health emergency preparedness and response. Available at: http://www.bt.cdc.gov. Accessed July 7, 2003.
- Centers for Disease Control and Prevention. CDC recommends: prevention guidelines system. Available at: http://www.phppo.cdc.gov/cdcrecommends. Accessed July 7, 2003.
- Greenfield RA, Brown BR, Hutchins JB, et al. Microbiological, biological, and chemical weapons of warfare and terrorism. Am J Med Sci. 2002;323:326–340.[Medline]
- Evison D, Hinsley D, Rice P. Chemical weapons. BMJ. 2002;324:332–335.[Free Full Text]
- Brown MA, Brix KA. Review of health consequences from high-, intermediate- and low-level exposure to organophosphorus nerve agents. J Appl Toxicol. 1998;18:393–408.[Medline]
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Properties of Nerve Agents
Action of Nerve Agents
