eMedicine Specialties > Emergency Medicine > Warfare - Chemical, Biological, Radiological, Nuclear and Explosives

CBRNE - Vesicants, Mustard: Hd, Hn1-3, H

Daniel J Dire, MD, FACEP, FAAP, FAAEM, Clinical Associate Professor, Department of Emergency Medicine, University of Texas-Houston

Updated: Dec 21, 2007

Introduction

Background

Mustard agents are vesicants (blister agents) used in warfare to produce casualties, degrade fighting efficiency, and force opposing troops to wear full protective equipment. Mustard agents are cytotoxic alkylating compounds and include nitrogen mustards (HN-1, HN-2, HN-3), sulfur mustards (H, HD, HT), and mustard-lewisite (HL). Mustard agents are oily liquids ranging from colorless (in pure state) to pale yellow to dark brown, depending on the type and purity. They have a faint odor of mustard, onion, garlic, or horseradish, but because of olfactory fatigue, do not rely on odor for detection. Volatility varies with the particular compound. Mustard agents are only slightly soluble in water and may persist for long periods. HN-1 is more volatile and less persistent than HD, but it is only one fifth as potent a vesicant to the skin. HN-3 is less volatile and more persistent than HD and has equal vesicant effects.

Mustard agents rapidly penetrate clothing and skin. Chemical protective mask with charcoal filters, chemical protective overgarments with charcoal, and butyl rubber chemical protective gloves and boots afford full protection against mustard agents.

More than 2 dozen nations may have the capability to manufacture offensive chemical weapons. Mustard agents are simple to manufacture and therefore can be a first choice for countries or terrorists who decide to have a capacity for chemical warfare agents. Mustard agents may be delivered by artillery shell, mortar shell, rockets, bombs, or aircraft spray. Since World War I, mustard use in at least 12 conflicts has been supported by evidence or allegations. Historically, mustard agents are the most widely used type of chemical warfare agent.

Mustard agents constitute both a vapor and a liquid threat. Mustard agents cause tissue damage within several minutes of contact. No immediate symptomatic or local reaction occurs to mustard vapor or liquid. Decontamination must be performed immediately after contact to prevent injury. A latent period occurs, ranging from 4-12 hours after mild exposure and 1-3 hours after severe exposure, prior to the onset of symptoms. More than 80% of mustard casualties are from vapor exposure, but more severe injuries are caused after contact with liquid mustard agents.

Mustards first were produced in 1822, but their harmful effects were not discovered until 1860. On July 12, 1917, the Germans delivered artillery shells containing HD on a World War I battlefield near Ypres, Belgium. More than 20,000 casualties resulted from this first use of mustard as a chemical warfare agent. Subsequently, mustard agents accounted for 80% of chemical casualties in World War I. Among 6980 cases of mustard burns during World War I, the location of the lesions were as follows: eyes, 86%; respiratory, 75%; scrotum, 42%; face, 27%; anus, 24%; legs, 11%; buttocks, 10%; hands, 4%; and feet, 1.5%. Fewer than 5% of casualties from mustard who reached medical treatment died. Mustard injuries were slow to heal and necessitated an average convalescent period of more than 6 weeks.

Italy allegedly used mustard against Abyssinia in the 1930s. Japan allegedly used mustard agents against the Chinese from 1937-1944.

Nitrogen mustard agents were synthesized in the late 1930s. Mechlorethamine (HN-2) became the prototypical mustard agent used as a cancer chemotherapeutic agent. Germans and Americans started the military production of nitrogen mustard agents in 1941 and 1943, respectively. They have not been used on the battlefield.

Toward the end of World War II, a German air attack on the Italian port of Bari struck a US ship loaded with mustard agent munitions. Large amounts of mustard agents were released to the atmosphere and into the harbor water. Many soldiers and sailors were exposed to the mustard-contaminated water. Of 617 US mustard casualties, 83 died.

During the Yemen War of 1963-1967, Egypt reportedly used mustard bombs against the royalist troops in North Yemen.

During the Iran-Iraq war from 1979-1988, approximately 5000 Iranian soldiers were reported killed by Iraqi chemical agents, 10-20% by mustard agents. Additionally, 40,000-50,000 individuals were injured resulting in many chronic medical problems.

After the February 1991 cease-fire ending the Persian Gulf War, United Nations inspection teams discovered mustard agents at Al Muthanna, Iraq.

In Sweden, recurring incidents of mustard agent exposures involve fisherman who encounter discarded chemical weapons that were dumped in the waters off the coast after World War II.

Developing nations and terrorist groups can easily obtain HD because of its low cost and availability. The US stockpile of mustard chemical warfare agents currently is undergoing destruction.

Pathophysiology

Mustard agents are lipophilic and are absorbed readily across intact skin and mucous membranes. The rapid penetration is enhanced by moisture, heat, and thin skin. The physical properties (low volatility and a freezing point of 14^o C) of sulfur mustard (H, HD, HT) make it a better weapon for use in warm or hot environments due to a greater risk of vapor inhalation. Approximately 20% of HD is absorbed by the skin, the remainder evaporates. Of the absorbed HD, 10-50% of the mustard dose binds to the skin as reacted (fixed) mustard, and the remaining 50-90% is distributed in the circulation as unreacted (free) mustard to almost all organs and tissues. Because of dilutional effects, systemic effects are observed only at high doses. Mustard is eliminated from the body in the urine as a by-product of alkylation.

No single mechanism or clear understanding exists for the biological damage caused by mustard agents. The toxic effects of mustards depend on their rapid covalent binding to a large number of biological molecules and in the formation of a reactive cyclic ethylene sulfonium ion. Mustard agent molecules contain 2 reactive binding groups. Mustards can bind to nucleophiles such as nitrogen in the base components of nucleic acids and sulfur in SH-groups in proteins and peptides. Mustards can destroy a large number of cellular substances by alkylation of DNA, which leads to DNA strand breaks and apoptosis.

Mustards also bind to cellular glutathione, a small peptide that is a major free radical scavenger.   Glutathione depletion leads to inactivation of enzymes, loss of calcium homeostasis, lipid peroxidation, cellular membrane breakdown, and cell death. Pretreatment of cells with N -acetylcysteine has shown benefit in some studies.

Mortality/Morbidity

The concentration-time product capable of killing 50% of exposures (LCt50) of mustard vapor is 1500 mg·min/m³, and the lethal dose to 50% of exposures (LD50) of liquid mustard on the skin is 100 mg/kg.

Mustards are mutagenic resulting in a slight increased incidence of lung cancer, bladder cancer, and leukemia.

Clinical

Physical

• The clinical presentation of exposure to a vesicant depends on the route of administration and the agent used.
• The eyes are most sensitive and vulnerable to mustard. Ocular effects precede cutaneous manifestations and occur at lower concentrations (as low as 1/10^th) than that required to affect the airways. HN causes more severe and earlier ocular lesions than HD.
  • Conjunctivitis follows an exposure time of approximately 1 hour to a concentration barely perceptible by odor that does not affect the skin or respiratory mucosa significantly.
  • In World War I, 75% of eye exposures were classified as mild conjunctivitis.
  • After mild exposure, a latent period of 4-12 hours is followed by lacrimation, a sensation of grit in the eyes, conjunctival injection, and edema (palpebral and bulbar). Recovery requires 1-2 weeks.
  • After heavy exposure, eye signs and symptoms appear after 1-3 hours, and severe lesions may appear. Blepharospasm is common.
  • A steamy haziness of the cornea or an orange-peel roughening of the cornea may occur. Spotty hemorrhagic discolorations of the iris may be observed. Temporary blindness is common, but permanent blindness is rare.
  • Mild corneal involvement demonstrates corneal erosions with fluorescein staining. Superficial corneal scarring and vascularization or iritis may occur.
  • With severe corneal involvement, dense corneal opacification with deep ulceration and vascularization occurs. Local necrosis of the cornea may rupture the globe. Panophthalmitis may occur and result in eye loss if appropriate therapy is not instituted.
  • Recovery from the ocular effects, especially with corneal involvement, may take months.
• Severity of cutaneous effects of mustard and the rapidity with which they develop are influenced by the degree of exposure and the weather. Hot, humid weather results in more severe lesions. Warm, moist areas, such as the perineum, external genitalia, axillae, antecubital fossae, and neck, are most susceptible.
  • The latent period from contact with liquid or vapor exposures is usually 6-12 hours but may be as short as 1 hour when the weather is hot and humid. The effects appear more rapidly from liquid agent than from vapor.
  • The initial cutaneous effect is erythema, resembling sunburn. Slight skin edema may occur with mild exposures, but in severe burns, edema is greater. Vapor exposures may not cause skin lesions. Systemic symptoms such as malaise, vomiting, and fever may develop approximately at onset of erythema.
  • Intense cutaneous pruritus is common, may last for several days, and may persist after healing.
  • Erythema is followed by vesication as a result of liquefaction necrosis in the epidermal basal cell keratinocytes. A liquid droplet with 10 mcg of mustard produces vesication. Vesicles are more concentrated in warm, moist areas such as the groin and axilla. Vesicles and bullae may be painful and are filled with yellow transudate that tends to coagulate. This fluid does not contain mustard and is not a risk to contacts. Reabsorption of the fluids takes place in approximately 1 week if the vesicles or bullae do not rupture. If rupture occurs, the burn is considered an open wound and is susceptible to secondary infection. Spontaneous healing occurs slowly with little scar formation.
  • Exposed areas of skin may develop a persistent brown pigmentation except at the site of actual vesication, where a temporary depigmentation is seen. The rate of healing typically is 1-2 weeks for facial lesions and up to 2-4 weeks or longer for other areas of the skin. Secondary infection may increase the severity of the lesions and delay healing.
  • Arsenical vesicants such as phenyldichloroarsine (PD) or chlorovinyldichloroarsine (L) often are mixed with mustard agents for chemical warfare weapons. When mixed as such, the resulting skin lesions are not more severe than either agent alone but tend to confuse and make the specific diagnosis difficult.
• A longer latent period (18-24 h) may occur before the onset of respiratory symptoms. In patients with eye symptoms, expect the development of respiratory effects. Inhalation of mustard vapors may damage the laryngeal and tracheobronchial mucosa. Single exposure to a low concentration of vapor does not cause significant injury. Repeated or chronic exposures may lead to the development of pulmonary fibrosis, chronic bronchitis, and bronchiectasis.
  • Respiratory effects develop slowly and reach maximal severity in several days. Symptoms begin in the upper airways and progress to the lower airways.  Early symptoms begin with hoarseness and loss of voice. This is followed by a cough, which subsequently becomes productive. Fever, dyspnea, rhonchi, and wet crackles may develop. Mild symptoms last 1-2 weeks. Recovery is slow, and coughing may persist for 1 or more months.
  • Moderate acute exposure leads to mucous membrane hyperemia, edema, and necrosis. Profuse, thin, mucopurulent rhinorrhea occurs; sinusitis may develop later. Mucosal findings range from small discrete ulcerations to extensive sloughing.
  • Pharyngitis usually appears 1-3 days after inhaling mustard vapors and may occur with nasal involvement in mouth breathers. The palate, uvula, tonsils, and pharynx are hyperemic and edematous. Multiple whitish ulcerations appear, varying in size according to severity of exposure. Laryngeal involvement resembles that of the pharynx. Edema and necrosis may lead to airway obstruction. Hoarseness, which almost always is present, may last 3-6 weeks or longer.
  • Severe inhalation exposures lead to a diphtherialike pseudomembrane, which may form a cast of the tracheobronchial tree. Mechanical obstruction from pseudomembrane formation and laryngospasm may cause death in the first 24 hours. Mild patchy pulmonary edema and focal atelectasis occur. Chemical pneumonitis may appear after the first 24 hours. Hemorrhagic pulmonary edema is not common and occurs only with severe damage. Suppurative bacterial bronchitis and bronchopneumonia are frequent complications; the latter is responsible for almost all deaths from vapor exposure.
  • In World War I, early mortality occurred in slightly more than 2% of US troops exposed to mustard and was caused almost entirely by pulmonary complications. Approximately 10% of the Iranian casualties treated in western European hospitals during the Iran-Iraq War developed progressive stenosis of the tracheobronchial tree.
• Liquid mustard ingestion leads to mucosal necrosis and hemorrhage. Initial symptoms include nausea, vomiting, painful diarrhea, and prostration. Severe gastrointestinal (GI) effects from mustard poisoning are relatively infrequent. Vomiting and bloody diarrhea beginning days after a high-dose exposure imply a poor prognosis.
• Moderate-to-severe liquid cutaneous, inhalational, or GI exposures cause systemic symptoms of nausea, vomiting, fever, malaise, and prostration.
  • Immediate bronchospasm and respiratory distress may occur.
  • The most severe patients also may present with CNS symptoms (eg, CNS depression) and parasympathetic effects such as bradycardia and other dysrhythmias.
  • Hemoconcentration and hypovolemic shock may occur due to fluid shifts and losses or GI hemorrhaging.
  • With systemic absorption of near lethal doses, hematopoietic and lymphatic tissue injuries occur, resulting in myelosuppression (leukopenia, thrombocytopenia, and anemia). The thymus, spleen, and lymph nodes may involute rapidly. The development of shock, thrombocytopenia, leukopenia, and hemorrhagic diathesis are grave prognostic signs. Bone marrow failure resulting in fulminant sepsis and bleeding is the most frequent cause of late deaths from mustard exposure.

Differential Diagnoses

Workup

Laboratory Studies

• No hospital laboratory test exists to identify or quantify mustard exposures, since mustard is biotransformed and bound to tissues within minutes of adsorption.
• Obtain a complete blood count, serum electrolytes, and coagulation studies; observe these periodically in all patients except those with isolated mild ocular or cutaneous involvement.
• Leukocytosis occurs during the first day. After large systemic adsorption, leukopenia may begin on day 3-5. A leukocyte count of 500 or less is an unfavorable prognostic sign.

Imaging Studies

• Chest radiographs: Mustards may cause a chemical pneumonitis. Secondary infection may lead to lobular or lobar consolidation. Radiographic appearance follows the characteristics of the type of secondary pneumonia.

Other Tests

• The US military has the capability of detecting mustard agents in the environment with the use of the M256A1, M272 water testing kit, miniature chemical agent monitor (MINICAMS), individual chemical agent detector (ICAD), M18A2, M21 remote sensing alarm, M90, M93A1 Fox, Bubbler, chemical agent monitor (CAM), depot area air monitoring system (DAAMS), and M8 or M9 chemical detection paper.

Treatment

Prehospital Care

• Patients contaminated with mustard agents endanger unprotected health care providers. Decontaminate patients exposed to mustard agents before transport and entry into medical treatment facilities to prevent vapor accumulation. Providers attending contaminated patients should have protective masks, butyl rubber gloves (latex gloves are NOT adequate), and chemical protective overgarments.
• Unless carried out within 1-2 minutes, decontamination of victims exposed to mustard agents does not prevent subsequent blistering. After that brief window, decontamination still should be carried out to prevent secondary contamination.
  • The first step is to cut away all of the victim's clothing. Also cut away and discard mustard-contaminated hair.
  • Exposed skin and scalp can be decontaminated using the military M291 or M258A1 skin decontamination kits. Alternately, use 0.5% aqueous chlorine solution to thoroughly wash the skin and hair. Wash off the decontamination solutions within 3-4 minutes with soap and water. If the victim already has erythematous skin, decontaminating the skin with just soap and water is recommended.

Emergency Department Care

• No specific treatment or antidote can reverse or prevent the cellular effects of mustard agents.
• Apply steroid ointments and antibiotic ointments and relegate their further use to an ophthalmologist. Ophthalmic ointments containing boric acid 5% provide lubrication.
  • Do not patch the eyes and do not allow the eyelids to stick together. Sterile petroleum jelly can be used to lubricate and prevent sealing of the eyelids.
  • Use cycloplegic eye drops (atropine or homatropine) 3 times a day in patients with severe blepharospasm and photophobia for pain and to prevent future synechiae formation. Keep patients in a darkened room.
  • Systemic narcotic analgesics are recommended for pain control. Do not use topical ophthalmic anesthetics.
  • Hospitalization seldom is required for mild eye exposures; early and prolonged hospitalization with ophthalmologist consultation is required for moderate and severe cases. The eyes usually recover within 2 weeks, but corneal scarring may lead to long-term visual dysfunction.
  • Mild mustard erythema requires no specific treatment. One animal study suggests rapid application of povidone-iodine ointment within 20 minutes of exposure may protect the skin from vesication. Topical steroid creams or sprays or calamine lotion may provide symptomatic relief of annoying pruritus. Address tetanus immunization in patients with cutaneous or ocular involvement.
• Debride ruptured vesicles or bullae. Cleanse the underlying skin with sterile saline. Small areas of involvement can be dressed with petroleum gauze. Facial lesions are best covered with bacitracin ointment and left open.
  • Applying a 1/8-inch thick layer of mafenide acetate or silver sulfadiazine burn cream may treat larger areas of involvement best. Clean and redress these larger wounds twice a day. Multiple or large areas of vesication are cleansed easily with whirlpool bathing. HD-induced lesions heal slowly, often ulcerate, and vesicate repeatedly.
  • Culture wounds that become infected similar to thermal burns and administer appropriate parenteral antibiotics.
  • Avoid overhydration, since fluid losses generally are less than with thermal burns.
  • Liberal uses of narcotic analgesics are warranted to treat painful skin lesions.
• Mild respiratory tract injury requires no specific treatment. Symptomatic treatment with antitussive medication and steam or cool mist inhalations may be tried. Hospitalization is required for moderate or severe respiratory tract injuries. Inhaled beta-agonists may benefit patients with bronchospasm. Patients with respiratory obstruction, hypoxia unresponsive to supplemental oxygen, or respiratory failure should undergo endotracheal intubation and mechanical ventilation. Direct antibiotic therapy for secondary bacterial pneumonia toward the specific organisms recovered and their antibiotic sensitivities.
• Treatment of systemic toxicity from mustard is supportive. Atropine sulfate (0.4-0.8 mg SC) may be used in reducing GI hyperactivity. General discomfort, restlessness, and pain may be treated with sedative and/or narcotic analgesics. Adequate nutrition and fluid and electrolyte replacement are mandatory for patients with severe poisonings who have vomiting, diarrhea, leukopenia, hemoconcentration, and shock. Patients with severe leukopenia require isolation and may require appropriate antibiotics.

Consultations

• Seek ophthalmologic consultation as soon as possible when eye involvement is present. Admit patients with corneal findings to the hospital.
• Involve plastic surgeons in the care of those with cutaneous injuries admitted to the hospital.
• Consult hematology and/or oncology specialists for patients with aplastic anemia, which is much more common after HN exposure.

Medication

The goals of pharmacotherapy are to neutralize toxicity, reduce morbidity, and prevent complications.

Cycloplegics and mydriatics

Instillation of long-acting cycloplegic agents can relax any ciliary muscle spasm that can cause a deep aching pain and photophobia.

Homatropine ophthalmic drops 2-5% (AK-Homatropine, Isopto-Homatropine)

Contains homatropine hydrobromide, which blocks action of certain parasympathetic nerves and cholinergic drugs; used in ophthalmology for mydriatic and cycloplegic effects; peripheral effects are much weaker than those of atropine; preferred to atropine for diagnostic purposes because its action is more rapid, less prolonged, and is controlled readily by physostigmine; effect is exerted in 15-30 min and passes off in 12-24 h; usually does not produce complete paralysis of accommodation in children.

Dosing

Adult

1-2 gtt q3-4h

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Regular ophthalmologic examination is required, since possibility of adverse effects on corneal permeability and danger of disruption of corneal epithelium with prolonged or repeated usage of benzalkonium chloride–preserved preparations cannot be excluded; caution when using over an extended period in patients with extensive ocular surface disease; caution in elderly patients (increased intraocular pressure may be present); toxic anticholinergic systemic adverse effects are possible, but incidence is rare when used sparingly (more common in children, especially infants); following administration, compressing lacrimal sac by digital pressure for 1-3 min minimizes systemic absorption; hypersensitivity is not uncommon and appears as conjunctivitis; systemic reactions have followed absorption of anticholinergics from eye drops, particularly in children; mydriatics and cycloplegics may increase intraocular pressure (caution in elderly patients and others in whom an increase may be encountered); tonometric
examination prior to drop instillation is advisable

Atropine ophthalmic drops 1% (Isopto, Atropair, Atropisol)

For use as long-acting mydriatic and cycloplegic; most potent ophthalmic parasympatholytic available; by paralyzing sphincter pupillae muscle, helps dilate pupil; also paralyzes ciliary muscle; effect lasts 7-10 d; also indicated to decrease GI motility.

Dosing

Adult

1 gtt bid

Pediatric

1 gtt bid or apply 1% ointment qd/bid

Interactions

Coadministration with other anticholinergics has additive effects

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypersensitivity is not uncommon and occurs as conjunctivitis; systemic toxicity may be produced by instillation of anticholinergic ophthalmic solution, particularly in infants; systemic absorption may be minimized by compressing lacrimal sac for 1-2 min following instillation; may increase intraocular pressure (caution in elderly patients and others in whom an increase may be encountered); tonometric examination prior to drop instillation is advisable; overdosage may cause systemic effects such as ataxia, incoherent speech, restlessness, hallucinations, disorientation, failure to recognize people, and tachycardia; psychotic reactions and behavioral disturbances have been encountered in children; physostigmine salicylate (1-2 mg IV/IM/SC) controls central and peripheral effects; excitement may be controlled by small doses of a short-acting barbiturate such as thiopentone sodium 100 mg

GI antispasmodic/antimotility agents

Thought to work centrally by suppressing conduction in vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.

Atropine sulfate injectable (Atropair, Isopto, Atropisol)

Acts at parasympathetic sites in smooth muscle and decreases GI motility.
Dosage may require reduction in elderly patients due to possible occurrence of cardiovascular and CNS adverse effects.

Dosing

Adult

0.3-1.2 mg IV/IM/SC q4-6h if needed

Pediatric

Not typically recommended (as antimotility agent) in children

Interactions

Levodopa, phenothiazine, and agents with cholinergic mechanisms decrease atropine anticholinergic effects; thiazides and amantadine increase atropine anticholinergic effects

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; concomitant acute MI and/or ischemia; thyrotoxicosis; tachycardia; coronary heart disease; congestive heart failure; cardiac arrhythmias; hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Overdosage may cause systemic effects such as ataxia, incoherent speech, restlessness, hallucinations, disorientation, failure to recognize people, and tachycardia; Down syndrome or in children with brain damage, because they may demonstrate a hyperreactive response to atropine; psychotic reactions and behavioral disturbances have been encountered in children; physostigmine salicylate (1-2 mg IV/IM/SC) controls central and peripheral effects; excitement may be controlled by small doses of a short-acting barbiturate such as thiopentone sodium 100 mg

Analgesics

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained burns.

Morphine sulfate (Duramorph, Astramorph, MS Contin)

DOC for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone; morphine sulfate administered IV may be dosed in a number of ways and commonly is titrated until desired effect is obtained.

Dosing

Adult

Initial dose: 0.1-0.2 mg/kg IV/IM/SC
Maintenance dose: 5-20 mg/70 kg IV/IM/SC q4h
Relatively hypovolemic patients: Start with 2 mg IV/IM/SC; reassess hemodynamic effects of dose

Pediatric

Neonates and infants <6 months: 0.05-0.1 mg/kg/dose IV/IM/SC q3-4h prn
Children: 0.1-0.2 mg/kg/dose IV/IM/SC q3-4h prn

Interactions

Phenothiazines may antagonize analgesic effects; TCAs, MAOIs, and other CNS depressants may potentiate adverse effects

Contraindications

Documented hypersensitivity; hypotension; potentially compromised airway in which establishing rapid airway control would be difficult

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid in respiratory depression, nausea, emesis, constipation, and urinary retention; caution in atrial flutter and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate

Meperidine (Demerol)

Narcotic analgesic with multiple actions similar to those of morphine; may produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine.

Dosing

Adult

25-75 mg PO/IV/IM/SC q3-4h prn

Pediatric

1-1.8 mg/kg (0.5-0.8 mg/lb) PO/IV/IM/SC q3-4h prn; not to exceed adult dose

Interactions

Cimetidine and protease inhibitors may increase toxicity; hydantoins may decrease effects

Contraindications

Documented hypersensitivity; concurrent MAOIs; upper airway obstruction or significant respiratory depression; during labor when delivery of premature infant anticipated

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with head injuries, since may increase respiratory depression and CSF pressure (use only if absolutely necessary); caution postoperatively and with history of pulmonary disease (suppresses cough reflex); substantially increased dose levels due to tolerance may aggravate or cause seizures even if no history of convulsive disorders; monitor closely for meperidine-induced seizure activity if seizure history

Hydrocodone bitartrate and acetaminophen (Vicodin ES)

Drug combination indicated for relief of moderate to severe pain.

Dosing

Adult

1-2 tab or cap PO q4-6h prn for pain

Pediatric

<12 years: 10-15 mg/kg/dose acetaminophen PO q4-6h prn; not to exceed 2.6 g/d of acetaminophen or 5 mg of hydrocodone bitartrate/dose
>12 years: 650 mg acetaminophen PO q4h; not to exceed 5 doses/d acetaminophen or 10 mg of hydrocodone bitartrate/dose

Interactions

Phenothiazines may decrease analgesic effects; CNS depressants or TCAs may increase toxicity

Contraindications

Documented hypersensitivity; elevated intracranial pressure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Tablets contain metabisulfite, which may cause hypersensitivity; caution in patients dependent on opiates, since this substitution may result in acute opiate-withdrawal symptoms; caution in severe renal or hepatic dysfunction

Bronchodilators

Primary action is to decrease muscle tone in both small and large airways in the lungs, thus increasing airflow and ventilation. This category includes beta-adrenergic, methylxanthine, and anticholinergic medications.

Albuterol (Proventil, Ventolin)

Bronchodilator in reversible airway obstruction due to asthma; relaxes bronchial smooth muscle by action on beta 2-receptors with little effect on heart rate.

Dosing

Adult

7.5 mg inhaled over 60-90 min divided tid; dilute 2.5 mg in 3 mL of saline or use premixed nebules

Pediatric

0.15 mg/kg inhaled q20min for 3 doses

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, or sympathomimetic agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, sensitivity to sympathomimetic amines, coronary insufficiency, and hypertension; excessive use may result in tolerance; adverse reactions may occur more frequently in children aged 2-5 y

Antibiotics

Topical and ophthalmic antibiotics routinely are used for dermal and ocular burns, respectively. Injured tissues lose many of their protective mechanisms and are at increased risk of infection.

Silver sulfadiazine (Silvadene)

Used topically for dermal burns and useful in prevention of infections from second-degree or third-degree burns; has bactericidal activity against many gram-positive and gram-negative bacteria, including yeast.

Dosing

Adult

Apply to a thickness of 1/16th inch qd/bid; continually cover burned area; remove all previous medication before applying each new dose

Pediatric

<2 months: Not recommended (may exacerbate bilirubin toxicity)
>2 months: Apply as in adults

Interactions

Reduces effectiveness of proteolytic enzymes

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Patients with G-6-PD deficiency and renal insufficiency

Toxoids

Used to induce active immunity against tetanus in selected patients.

Tetanus toxoid

Immunizing agents of choice for most adults and children >7 y are tetanus and diphtheria toxoids. Necessary to administer booster doses to maintain tetanus immunity throughout life.
Pregnant patients should receive only tetanus toxoid, not a diphtheria antigen-containing product.
In children and adults, may administer into deltoid or midlateral thigh muscles. In infants, preferred site of administration is mid thigh laterally.

Dosing

Adult

Primary immunization: 0.5 mL IM; give 2 injections 4-8 wk apart; third dose 6-12 mo after second injection
Booster dose: 0.5 mL q10y

Pediatric

Administer as in adults

Interactions

Patients receiving immunosuppressants, including corticosteroids or radiation therapy, may remain susceptible despite immunization because of poor immune response; cimetidine may enhance or augment delayed-hypersensitivity responses to skin-test antigens; avoid concurrent use with systemic chloramphenicol since it may impair amnestic response to tetanus toxoid; concurrent use of tetanus immune globulin may delay development of active immunity by several days (interaction is nevertheless clinically insignificant and does not preclude concurrent use)

Contraindications

Documented hypersensitivity; history of any type of neurologic symptoms or signs following administration of this product; FDA recommends that elective tetanus immunization be deferred during any outbreak of poliomyelitis because tetanus toxoid injections are an important cause of provocative poliomyelitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use to treat actual tetanus infections or for immediate prophylaxis of unimmunized individuals (use instead tetanus antitoxin, preferably human tetanus immune globulin); diminished antibody response to active immunization may be seen in patients receiving immunosuppressive therapy; better to defer primary diphtheria immunization until immunosuppressive therapy discontinued; routine immunization of symptomatic and asymptomatic HIV-infected persons is recommended

Antitussives

Indicated for control of excessive cough.

Guaifenesin and codeine (Robitussin AC, Guiatuss AC, Mytussin AC, Brontex liq)

Treats minor cough resulting from bronchial and throat irritation.

Dosing

Adult

5-10 mL PO q4-8h, not to exceed 60 mL/24 h

Pediatric

1-1.5 mg/kg codeine/d PO divided qid

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment

Corticosteroid creams

Indicated for inflammation of skin.

Hydrocortisone 1% (Cortaid, Dermacort, Westcort)

Adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. Has mineralocorticoid and glucocorticoid effects resulting in anti-inflammatory activity.

Dosing

Adult

Apply sparingly to affected areas bid/qid

Pediatric

Apply as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use, applying over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA suppression, hyperglycemia, and glycosuria

Follow-up

Further Inpatient Care

• Patients with moderate-to-severe cutaneous effects are best managed in a hospital burn unit. The period of recuperation is much longer than that for thermal burns.
• Those with severe leukopenia require infection isolation.
• Patients with significant pulmonary involvement usually require ICU admission.
• Topical combination therapy with zinc desferrioxamine and dexamethasone resulted in faster corneal reepithelization and less severe neovascularization in an animal model. Keratoplasty may be necessary to recover visual function.
• Granulocyte colony-stimulating factor and pegylated granulocyte colony-stimulating factor have been shown to reduce the duration of HD-induced neutropenia in an animal model.

Further Outpatient Care

• For 12 hours prior to discharge, observe patients who are exposed to mustard and who are initially asymptomatic.
• Chronic health problems may develop after mustard exposure including respiratory diseases (asthma, pulmonary fibrosis, bronchiectasis), skin lesions (dermal scarring), neoplasms (gastrointestinal cancers, chronic myelocytic leukemia, respiratory cancers, and skin cancers), and ocular problems (keratitis, corneal ulcers, conjunctivitis).

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Chemical Warfare and Personal Protective Equipment.

Miscellaneous

Medicolegal Pitfalls

• Failure to make the correct diagnosis

Special Concerns

• Mustard is classified as a mutagen and a carcinogen, but no association between a single exposure and cancer has been proven. Repeated symptomatic exposure over a period of years is established as a casual factor in an increased incidence of upper airway cancers.

Multimedia

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.

Image available at http://img.medscape.com/pi/emed/ckb/emergency_medicine/756148-829124-832060-832152.pdf.

References

1. Headquarters, Department of the Army. Field Manual 8-285, Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries. Washington, DC: Dec 22 1995.

2. Iyriboz Y. A recent exposure to mustard gas in the United States: clinical findings of a cohort (n = 247) 6 years after exposure. MedGenMed. 2004;6(4):4. [Medline]. [Full Text].

3. McManus J, Huebner K. Vesicants. Crit Care Clin. Oct 2005;21(4):707-18, vi. [Medline].

4. Morad Y, Banin E, Averbukh E, Berenshtein E, Obolensky A, Chevion M. Treatment of ocular tissues exposed to nitrogen mustard: beneficial effect of zinc desferrioxamine combined with steroids. Invest Ophthalmol Vis Sci. May 2005;46(5):1640-6. [Medline].

5. Pons P, Dart RC. Chemical incidents in the emergency department: if and when. Ann Emerg Med. Aug 1999;34(2):223-5. [Medline].

6. Richter MN, Wachtlin J, Bechrakis NE, Hoffmann F. Keratoplasty after mustard gas injury: clinical outcome and histology. Cornea. May 2006;25(4):467-9. [Medline].

7. Saladi RN, Smith E, Persaud AN. Mustard: a potential agent of chemical warfare and terrorism. Clin Exp Dermatol. Jan 2006;31(1):1-5. [Medline].

8. Sidell FR, Takafuji ET, Franz DR. Medical Aspects of Chemical and Biological Warfare. Washington, DC: Borden Institute; 1997:197-222.

9. Smith KJ, Hurst CG, Moeller RB, et al. Sulfur mustard: its continuing threat as a chemical warfare agent, the cutaneous lesions induced, progress in understanding its mechanism of action, its long-term health effects, and new developments for protection and therapy. J Am Acad Dermatol. May 1995;32(5 Pt 1):765-76. [Medline].

10. US Army Medical Research Institute of Chemical Defense. Medical Management of Chemical Casualties Handbook. 3^rd ed. Aug 1999.

Keywords

vesicants, mustard agents, blister agents, nitrogen mustards, HN-1, HN-2, HN-3, sulfur mustards, H, HD, HT, mustard-lewisite, HL, chemical warfare agent, nitrogen mustard agents, mustard exposure, vesicant exposure, decontamination of mustard agents, mutagenic agents, carcinogenic agents, mustard agent toxicity

Contributor Information and Disclosures

Author

Daniel J Dire, MD, FACEP, FAAP, FAAEM, Clinical Associate Professor, Department of Emergency Medicine, University of Texas-Houston
Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US
Disclosure: Nothing to disclose.

Medical Editor

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
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

CME Editor

John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School
John Halamka, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

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
Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Association of Military Surgeons of the US
Disclosure: Nothing to disclose.

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