You are in: eMedicine Specialties > Emergency Medicine > WARFARE - CHEMICAL, BIOLOGICAL, RADIOLOGICAL, NUCLEAR AND EXPLOSIVES CBRNE - Vesicants, Organic Arsenicals: L, ED, MD, PD, HLArticle Last Updated: Jun 19, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Geoffrey M Fitzgerald, MD, Consulting Staff, Concord Emergency Medical Associates Coauthor(s): Timothy Vollmer, MD, Consulting Staff, Department of Emergency Medicine, Geisinger Medical Center Editors: Fred Henretig, MD, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, Director, Section of Clinical Toxicology, Professor, University of Pennsylvania School of Medicine, Children's Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Robert G Darling, MD, FACEP, Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Director, Center for Disaster and Humanitarian Assistance Medicine Author and Editor Disclosure Synonyms and related keywords: chemical warfare, vesicant, blistering agents, lewisite, L, ethyldichloroarsine, ED, methyldichloroarsine, MD, phenyldichloroarsine, PD, arsenic poisoning, arsenic ingestion INTRODUCTIONSection 2 of 11
  BackgroundVesicants are a class of chemical weapons named for their ability to cause vesicular skin lesions. The 4 organic arsenicals are lewisite (L), methyldichloroarsine (MD), phenyldichloroarsine (PD), and ethyldichloroarsine (ED). These agents, together with the mustard agents and phosgene oxime, make up the vesicant class. Although not as well known as the mustards, the organic arsenicals are a group of potent vesicants that medical planners should not overlook. Interest in organic arsenicals dates back to the mid-19th century. While investigating possible new fumigants, European chemists discovered that chloroarsines (ie, arsenic-chloride compound in which 1 of the chlorine atoms is replaced by an organic radical) tended to be destructive both to insects and to human tissue. With the start of World War I, both sides employed chemists to create chemical warfare (CW) agents. The trench warfare stalemate created a tactical need for a chemical weapon that was both short acting (eg, nonpersistent, volatile) and lethal. To fill this need, German chemists delivered the first weaponized organic arsenical, MD. Two additional organic arsenicals, PD and ED, soon augmented MD. While MD, PD, and ED were being deployed on the battlefields of Europe in 1917 and 1918, a team of American researchers, lead by Captain Lewis of the US Army Medical Corps, was working on the fourth and final organic arsenical. Lewisite, as it was named, never was deployed in World WarI. Although mustard vesicants have been used in numerous regional wars since 1918, organic arsenical weapons have had limited use. L may have been used by Italy against Ethiopia in 1935 and again by Japan in China from 1937-1944. Today, arsenicals still are considered a threat, not so much from large nation states but from smaller, less developed nations and/or by terrorist organizations. The relative ease of production coupled with their effectiveness against an unprotected population make organic arsenicals a continued threat in the 21st century. PathophysiologyThe exact mechanism of biological activity and toxicity of the organic arsenicals is unknown. DNA alkylation and/or inhibition of glutathione-scavenging pathways are 2 postulated mechanisms of action. What is certain is that a blistering reaction occurs on any tissue that an arsenical contacts, whether it is skin, eye, or pulmonary tissue. The onset of symptoms after arsenical exposure occurs in seconds as compared to 4-8 hours for mustard exposure. Either a liquid or vapor (ie, gaseous form of a substance at temperatures below boiling point) can cause toxicity. The organic arsenicals tend to have high volatility at room temperature and thus pose a significant vapor threat to exposed personnel. Animal data and limited human trials demonstrated that organic arsenicals readily penetrate the skin. Within seconds of contact, the chemical fixes itself to the epidermis and dermis. Pain is immediate. Since the agent penetrates deeper, destruction of subcutaneous tissue results. Protease digestion of anchoring filament at the epidermal-dermal junction occurs. The separation of dermis from epidermis together with capillary leakage causes fluid-filled vesicles. Vapor contact with the conjunctiva may be the victims' first symptom. Severe conjunctival irritation and blepharospasm result upon eye contact. More severe exposure can cause loosening of corneal epithelial cells and swelling and edema of the cornea. The respiratory tract's mucosa and submucosa are susceptible to vapor exposure. Mucosal damage starts in the nose and descends down the respiratory mucosa in a dose-dependent fashion. Immediate pain, lacrimation, and irritation accompany the damage. Damaged respiratory mucosa slough off, filling the airways with debris. Damage to the lung parenchyma causes the secretion of blood and mucous that, with the pseudomembranes, can cause asphyxiation. In animal studies, large doses of L caused this "dry land drowning" within 10 minutes. The gastrointestinal tract also is susceptible. PD vapor in particular produces a phenyl radical that causes vomiting. Vomiting usually develops within 1-2 minutes after exposure to PD. The immediate onset of symptoms following exposure makes severe or systemic toxicity to organic arsenical unlikely. However, if a victim does not have protective gear or cannot move out of a contaminated area, prolonged contact may lead to multiorgan involvement. Blood-borne arsenicals can trigger increased permeability of capillaries throughout the body. Leakage of proteins and plasma then can cause third space fluid shifts, hypovolemia, and shock. Intravascular hemolysis of erythrocytes with subsequent hemolytic anemia may result. FrequencyUnited StatesOrganic arsenical weapons never have been used within the US. Other sources of arsenic poisoning are common, and arsenic ingestion is the most common cause of acute metal poisoning in the US. Inorganic arsenic is found in insecticides, rodenticides, and herbicides and is used in mining and smelting industries. InternationalAny nation or terrorist group that has access to a basic pesticide production facility can produce these agents with relative ease. The former Soviet Union is known to have combined sulfur mustard (H) and L into a binary weapon known as HL. Mortality/MorbidityAlthough vesicants have a relatively low mortality rate when compared to other CW agents, survivors usually require prolonged care and rehabilitation. These requirements placed a tremendous burden on the medical infrastructure during World War I. CLINICALSection 3 of 11
HistoryVictims of an L attack may remember observing puddles of a brown liquid or of smelling an odor similar to geranium. MD and ED reportedly smell like rotting fruit. Almost instantaneous pain and irritation of the skin, eyes, and nasal pharynx follow exposure. The patient usually relates a history of trying to remove himself or herself from the noxious stimuli.
PhysicalPhysical signs of organic arsenical exposure are similar to those of mustard agents. The major difference is the time of onset of signs. Organic arsenicals cause immediate signs, whereas signs of mustard exposure appear after a latent period of several hours.
CausesOrganic arsenical exposure can be caused by military CW attack or potentially from terrorist incident. DIFFERENTIALSSection 4 of 11
CBRNE - Irritants: Cs, Cn, Cnc, Ca, Cr, Cnb, PS CBRNE - Lung-Damaging Agents, Phosgene CBRNE - Vesicants, Mustard: Hd, Hn1-3, H
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| Drug Name | Dimercaprol (BAL in oil) |
|---|---|
| Description | Packaged in 3-mL ampules with 100 mg/mL. Formerly supplied as an ophthalmic and dermatologic ointment during World War II; these preparations are no longer available. |
| Adult Dose | 4-5 mg/kg (approximately 1 mL/50 lb) IM, not to exceed 4 mL; repeat q4h for a total of 4 doses; in severe exposure, additional doses can be administered as 2 mg/kg qd for 3-4 d |
| Pediatric Dose | Administer as in adults |
| Contraindications | In pregnant women, only use in life-threatening toxicities |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | High incidence of adverse effects; 4 mg/kg dose is estimated to have a 14% chance of adverse reaction; reactions can include nausea, vomiting, burning sensation of mouth and eyes, lacrimation, rhinorrhea, salivation, burning of the extremities, dental pain, chest pain, anxiety, agitation, hypertension, and tachycardia; adverse effects usually peak 10-30 min after administration and usually subside within 1 h; treatment for BAL overdose is supportive |
Pain is common and can be severe.
| Drug Name | Morphine sulphate (Duramorph, Astramorph, MS Contin) |
|---|---|
| Description | Mechanism of action is via the opiate receptors. |
| Adult Dose | Starting dose: 0.1 mg/kg IV/IM/SC Maintenance dose: 5-20 mg/70 kg IV/IM/SC q4h |
| Pediatric Dose | Administer as in adults using weight-based dosing |
| Contraindications | Documented hypersensitivity; respiratory depression |
| Interactions | Phenothiazines may antagonize analgesic effects of opiate agonists; TCAs, MAOIs, and other CNS depressants may potentiate adverse effects of morphine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate |
Cutaneous exposure can produce severe pruritus.
| Drug Name | Diphenhydramine (Benylin, Benadryl) |
|---|---|
| Description | For symptomatic relief of symptoms caused by release of histamine in allergic reactions. |
| Adult Dose | 25-50 mg PO qid 10-50 mg IV, not to exceed 400 mg/d |
| Pediatric Dose | 5 mg/kg/d PO/IV divided qid |
| Contraindications | Documented hypersensitivity; neonates |
| Interactions | Potentiates effect of CNS depressants; due to alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur |
Cutaneous damage caused by vesicants can leave the victim susceptible to bacterial infection.
| Drug Name | Silver sulfadiazine 1% (Silvadene) |
|---|---|
| Description | Useful in prevention of infections. Has bactericidal activity against many gram-positive and gram-negative bacteria, including yeast. |
| Adult Dose | Apply 1/16-inch thin film of ointment to cleansed and débrided burn wound bid; reapply if removed accidentally |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; neonates <2 mo and late pregnancy |
| Interactions | Effect of proteolytic enzymes is reduced when used concomitantly with this product; leukopenia increased with concomitant cimetidine |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | G-6-PD deficiency and impaired renal or hepatic function; not recommended in nursing mothers |
| Media file 1: Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html. | |
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CBRNE - Vesicants, Organic Arsenicals: L, ED, MD, PD, HL excerpt
Article Last Updated: Jun 19, 2006
