* This is a professional Version *
- Pulmonary Chemical Warfare Agents
- Systemic Asphyxiants
- Nerve Agents
- Anticholinergic Compounds
- Incendiary Agents and Hydrogen Fluoride (HF)
- Riot-Control Agents
- Symptoms and Signs
- Resources In This Article
- Drugs Mentioned In This Article
Chemical Warfare Agents
Chemical warfare (CW) agents are chemical MCWs developed by governments for wartime use and include
Although incapacitating agents are sometimes referred to as nonlethal, in high doses, these agents can cause serious injury or death.
Toxic industrial chemicals (TICs) are chemicals produced for industrial uses that are capable of causing mass casualties. Some chemicals (eg, chlorine, phosgene, cyanide compounds) have both industrial and CW uses and are called dual-use agents.
Toxic CW agents are divided into four major classes:
Because pulmonary agents include substances that also affect primarily the upper respiratory tract rather than lung parenchyma, some experts prefer to call this class “agents with acute local effects on the respiratory tract.” Because most TICs capable of generating mass casualties affect the respiratory tract, they are discussed with pulmonary CW agents.
Systemic asphyxiants , specifically cyanide compounds and hydrogen sulfide, interfere with mitochondrial energy transport, blocking cellular respiration. They are distributed in the blood (and are thus termed blood agents in military references) and thus affect most tissues.
Vesicants damage the dermoepidermal junction, causing pain and typically blistering. Many can affect the lungs if inhaled.
Nerve agents inhibit the enzyme acetylcholinesterase, causing excess cholinergic stimulation and cholinergic crisis (eg, diarrhea, urination, miosis, bronchorrhea, bronchoconstriction, emesis, lacrimation, salivation).
Incapacitating agents can be divided into
In addition to their chemical designations, most CW agents also have a one- to three-letter North Atlantic Treaty Organization (NATO) code.
Incendiary agents, designed to create light and flame, may also cause thermal burns in large numbers of casualties. Hydrogen fluoride (HF) may likewise cause chemical burns. Some of these burns require specific management apart from the typical management of thermal burns.
Pulmonary agents include traditional CW “choking” agents such as chlorine, phosgene, diphosgene, and chloropicrin and some vesicants such as sulfur mustard, lewisite, and phosgene oxime (which also affect the skin) as well as military smokes, products of combustion, and many toxic industrial chemicals. Most of these compounds are gases or highly volatile liquids.
Toxic CW agents that affect the respiratory tract are divided into 2 types depending on which part of the tract is predominantly affected (see Table: Representative Type 1, Type 2, and Mixed-Effect Chemicals With Acute Local Effects on the Respiratory Tract):
Type 1 agents usually are those with inhaled particles (eg, smoke), which tend to settle out before reaching the alveoli, or highly water-soluble and/or highly reactive chemicals, which dissolve into respiratory mucosa before reaching the alveoli. Type 1 agents cause necrosis and sloughing of the respiratory epithelium in the large airways, which may cause partial or total airway obstruction. Chemical pneumonitis and secondary bacterial pneumonitis may occur as a consequence of type 1 local damage. High doses of type 2 agents also can cause type 1 (large-airway) effects, although the type 1 effects are more likely to be transient.
Type 2 agents usually are lower-solubility and/or less-reactive chemicals, which travel to the alveoli before dissolving. These agents damage pulmonary capillary endothelium, causing fluid leakage into interstitial spaces and alveoli; pulmonary edema may result. With some type 2 agents (eg, oxides of nitrogen and HC smoke [hexachloroethane plus zinc oxide]), acute pulmonary edema may be followed days to weeks later by progressive and potentially irreversible pulmonary fibrosis. The mechanism is presumed to be immunologic. High doses of type 1 agents can also cause pulmonary edema.
Mixed-effect agents act in both large airways and alveoli in low to moderate doses.
Representative Type 1, Type 2, and Mixed-Effect Chemicals With Acute Local Effects on the Respiratory Tract
Initial exposure to type 1 agents causes sneezing, coughing, and laryngospasm (eye irritation can also occur). Patients with airway obstruction have hoarseness, wheezing, and inspiratory stridor. With a high dose of a type 1 agent, chest tightness or shortness of breath may subsequently develop as a result of incipient pulmonary edema.
With type 2 agents, symptoms and signs are usually delayed several hours following exposure. Patients initially complain of chest tightness or shortness of breath. Physical findings may be minimal except for rare expiratory crackles and dullness to percussion. Time of onset is shorter with higher doses; development of dyspnea within 4 h of exposure suggests a potentially lethal dose.
Clinical diagnosis is used to recognize exposure and distinguish type of damage (not necessarily the type of agent, because both types can cause similar effects depending upon the dose). Patients with an initially noisy chest and prominent symptoms are presumed to have type 1 involvement (large airways). Delayed onset of shortness of breath with a relatively quiet chest suggests type 2 damage. Although a high dose of type 2 agent may initially cause coughing, sneezing, and wheezing, these signs typically decrease over time; the patient then appears well until developing progressive shortness of breath.
Chest x-ray may be normal initially. Scattered opacities due to chemical or secondary pneumonitis may develop with type 1 damage. Eventually, as pulmonary edema becomes radiographically evident, Kerley B lines and fluffy interstitial infiltrates due to type 2 damage will be visible.
Bronchoscopy can confirm type 1 damage but may miss early type 2 damage.
Laboratory testing is not helpful in initial diagnosis, but pulse oximetry and/or ABG measurements can help monitor for clinical deterioration.
Severe signs of type 1 damage (eg, severe wheezing, inspiratory stridor, soot around the nose or mouth due to smoke inhalation) should lower the threshold for early intubation. With a type 2 agent, it is important to re-triage patients frequently. Initially asymptomatic patients also require monitoring for deterioration; even mild symptoms are grounds for prompt transport to a medical facility because such patients often deteriorate further. Most patients with shortness of breath due to early pulmonary edema can be triaged as delayed for medical treatment; they can usually tolerate a short delay if more immediate casualties require treatment. However, such patients should have highest priority (urgent) for evacuation because they may require definitive, life-saving treatment in a pulmonary intensive care unit.
For type 1: Early intubation and bronchodilators, sometimes inhaled corticosteroids, and antibiotics for documented secondary bacterial infection
For type 2: O 2 and positive-pressure ventilation (continuous positive airway pressure in conscious patients; positive end-expiratory pressure in ventilated patients), bronchodilators, and rarely corticosteroids
It is important to treat the damage rather than the agent because some agents cause both type 1 and type 2 effects even at low doses and since at high doses both types of damage will occur. Decontamination of vapor or gas exposure is not indicated, and there are no specific antidotes for these agents.
For type 1 effects, give warm, humidified 100% O 2 by face mask. Bronchoscopy may be both diagnostic and therapeutic, via the removal of necrotic debris from the large airways. Early intubation and assisted ventilation may be needed. Bronchodilators may help by increasing the caliber of airways. Inhaled corticosteroids may decrease the inflammation that often accompanies large-airway damage. For management of smoke inhalation, see Smoke Inhalation.
For type 2 effects, patients should be admitted to an ICU. O 2 should be given via continuous positive airway pressure (CPAP) in conscious patients or via positive end-expiratory pressure (PEEP) in intubated patients. Positive-pressure ventilation may help force fluid from the alveolar spaces back into the pulmonary capillaries. A central line may help monitor pulmonary pressures so that they can be controlled without inducing hypovolemic shock. For guidelines for the hospital treatment of pulmonary edema, see Pulmonary Edema : Treatment. Although bronchodilators are indicated mainly to dilate large airways in cases of type 1 damage, recent evidence suggests that they act via independent pathways to alleviate type 2 damage as well. Corticosteroids do not relieve pulmonary edema but oral corticosteroids may be indicated early for patients exposed to HC smoke or to oxides of nitrogen in an effort to prevent late-onset pulmonary fibrosis.
Prophylactic antibiotics do not help either type of injury. Antibiotics should be given only after diagnosis of bacterial infection is made, including isolating an organism and determining antibiotic sensitivities.
Systemic asphyxiants include
Systemic asphyxiants have also been called blood agents because they are systemically distributed via the blood. However, their site of action is not the blood but rather at the cellular level throughout the body.
Although cyanide salts have been used to murder via ingestion, mass casualties would more likely result from inhalation of hydrogen cyanide or cyanogen chloride, which are highly volatile liquids or gases at ambient temperatures. Cyanides are also products of combustion of numerous household and industrial contents, and patients with smoke inhalation may also have cyanide poisoning. Cyanide has a characteristic bitter-almonds odor, but ability to detect this odor is conferred by a single gene that is absent in half the population.
Hydrogen sulfide is always a gas at ambient temperatures. Exposure is thus usually by inhalation. Hydrogen sulfide can be produced by mixing sulfur-containing household chemicals with acids; this combination has been used for suicide (termed detergent suicide), and residual gas can affect rescuers, causing multiple casualties. Hydrogen sulfide is also produced when manure decomposes. Large farm manure pits often contain lethal quantities of the gas, which may cause multiple casualties as would-be rescuers without proper protective gear succumb. Hydrogen sulfide has a characteristic rotten egg odor, but high concentrations damage olfactory fibers so that this odor will not be perceived in the most lethal environments.
Cyanides and hydrogen sulfides both enter mitochondria, where they inactivate cytochrome oxidase, an enzyme needed for oxidative phosphorylation (cellular respiration). Suppression of oxidative phosphorylation leads to cellular anoxia, with ATP depletion, inability to extract oxygen from blood delivered to tissues, and lactic acidosis resulting from the body's attempts to generate energy nonoxidatively. All organs and tissues are affected, but neurons are more sensitive than muscle; central apnea is the usual mechanism of death.
Cyanide initially causes gasping, tachycardia, and hypertension. Loss of consciousness and convulsions may occur in as little as 30 sec. Tetanus-like signs, including trismus (lockjaw), risus sardonicus (grimacing), and opisthotonus (neck arching), may occur. The skin may be flushed, but about half of casualties are cyanotic. Apnea usually precedes bradycardia and hypotension, and decorticate posturing may be noted prior to death.
Hydrogen sulfide in high doses also causes abrupt loss of consciousness with convulsions. Direct damage to myocardium may be prominent. Continued exposure to initially sublethal concentrations may induce eye irritation with conjunctivitis and corneal abrasions and ulcerations (gas eye), irritation of nasal and pharyngeal mucous membranes, headache, weakness, ataxia, nausea, vomiting, chest tightness, and hyperventilation. Some of these manifestations appear to be a reaction to the offensive odor of the compound. A green discoloration or darkening of coins carried by the patient should lead to a heightened suspicion of hydrogen-sulfide poisoning.
Severely affected patients must be treated before testing is available, so diagnosis is mainly clinical. Laboratory findings include a decreased arteriovenous O 2 difference (due to higher-than-usual venous O 2 content) and high-anion-gap acidemia with increased lactate.
All unconscious patients with a pulse are potentially salvageable and should be triaged for immediate medical treatment. Because patients with inhalational exposure usually do not get worse after removal from the contaminated environment, conscious patients who are reporting decreasing symptoms may be triaged as delayed (ie, able to tolerate a short delay while immediate casualties are being treated).
Attention should be given to airway, breathing, and circulation. Water with or without soap suffices for skin decontamination; patients exposed only to vapor or gas usually do not require decontamination.
Cyanide casualties require prompt antidotal therapy with inhaled amyl nitrite 0.2 mL (1 ampule) for 30 sec of each min; 3% Na nitrite 10 mL at 2.5 to 5 mL/min IV (in children, 10 mg/kg), then 25% Na thiosulfate 25 to 50 mL at 2.5 to 5 mL/min IV. Where available, hydroxocobalamin 5 to 10 g IV may be given instead. Antidotes may be effective even in apneic patients. In the absence of antidotes, ventilation and administration of 100% O 2 may be life-saving. However, unprotected mouth-to-mouth resuscitation may expose the rescuer to cyanide in the patient’s breath. Cyanide casualties resulting from smoke inhalation may also have carbon monoxide poisoning; previous concerns about administering nitrites in this situation are probably overstated. Hyperbaric O 2 has not been proven to improve outcomes in patients poisoned with cyanide.
Hydrogen-sulfide casualties are managed with supportive care, including administration of 100% O 2 . Amyl nitrite and especially Na nitrite may be of use, but there is no indication for Na thiosulfate or hydroxocobalamin. Hyperbaric O 2 has not proven to be of benefit.
Vesicants are blistering agents and include
These agents also affect the respiratory tract: mustards are predominantly type 1 agents, phosgene oxime is a type 2 agent, and lewisite is a mixed agent (see Representative Type 1, Type 2, and Mixed-Effect Chemicals With Acute Local Effects on the Respiratory Tract).
Sulfur mustard has been variously described as smelling like mustard, garlic, horseradish, or asphalt. Lewisite may have a geranium-like odor, and phosgene oxime has been described simply as irritating. The perceptions of these odors are so subjective that they are not reliable indicators of the presence of these compounds.
Sulfur mustard and nitrogen mustard alkylate many cellular components, including DNA, and also release inflammatory cytokines. They have similar acute local effects on the skin, eyes, and airways; at lethal concentrations, they suppress bone marrow. Damage to cells in the basal layer of the epidermis results in separation of the epidermis from the dermis or, at high doses, in direct necrosis and sloughing of the epidermis. Blister fluid does not contain active sulfur mustard. Type 1 damage to the large airways involves sloughing of airway mucosa as pseudomembranes. Pulmonary edema (type 2 damage) may occur at high doses. Mustards may also induce nausea, presumably via a cholinergic mechanism. Bone marrow suppression may lead to sepsis a week or two after exposure. Long-term effects can include eye changes (eg, chronic keratitis) and cancer of the skin and respiratory tract.
Lewisite causes skin damage similar to that caused by sulfur mustard, although the mechanism of damage is different and involves effects on glutathione and sulfhydryl groups in enzymes as well as inhibition of pyruvate dehydrogenase. In the respiratory tract, the arsenic moiety of lewisite leads to leakage of pulmonary capillaries and pulmonary edema; with high doses, systemic hypotension—so-called lewisite shock—may occur. Unlike the mustards, lewisite does not cause immunosuppression.
Phosgene oxime causes urticaria and then tissue necrosis by mechanisms that are currently unclear.
Mustard compounds cause intense and increasing skin pain, erythema, and blister formation after a latent period. The latent period is inversely correlated with dose but is usually at least a few hours (and up to 36 h). Blisters caused by sulfur mustard sometimes resemble a string of pearls around a centrally unaffected area; blisters caused by nitrogen mustard are less likely to show this pattern. Blisters may become large and pendulous. Painful chemical conjunctivitis causing reflex lid closure occurs earlier than skin symptoms but still after a delay often of hours. The cornea may become cloudy. Respiratory manifestations include cough, laryngospasm, hoarseness, wheezing, and inspiratory stridor. Chest tightness and dyspnea may occur with severe exposure. Nausea may occur after moderate to high doses.
Lewisite causes pain within a minute or so of skin exposure. Erythema is often noticeable in 15 to 30 min, and blisters develop after several hours. The blisters usually form at the center of the erythematous area and spread peripherally. Pain is usually not so severe as that caused by mustard and begins to subside after blisters form. Irritation of mucosal membranes and large airways occurs soon after inhalation and leads to coughing, sneezing, and wheezing. Later, after a few hours, type 2 symptoms (chest tightness and shortness of breath) occur.
Skin contact with phosgene oxime causes intense, "nettling" pain and blanching within 5 to 20 sec. The affected skin then turns gray with an erythematous border. Between 5 and 30 min after exposure, edema leads to wheal formation (urticaria). During the next 7 days, the skin becomes dark brown and then black as necrosis of skin and underlying subcutis and muscle occurs. If not surgically excised, the lesion may persist for more than 6 mo. In the respiratory tract, phosgene oxime causes pulmonary edema even at low doses.
Pain occurring at or shortly after exposure suggests that lewisite or phosgene oxime is the agent; the early onset of skin changes distinguishes phosgene oxime. Delayed onset of pain (sometimes until a day after exposure) suggests sulfur mustard. Clinical diagnosis can be confirmed by laboratory tests, but these tests are available only from specialized laboratories.
Patients exposed to mustard should have regular CBC with differential for the first 2 wk to monitor for lymphopenia and neutropenia.
All casualties with potential skin or eye exposure to vesicants should be prioritized for immediate decontamination. Skin decontamination within 2 min is ideal, but decontamination up to 15 or 20 min after exposure can potentially decrease the size of the eventual blisters. However, even patients arriving after this time should still be decontaminated as soon as possible to stop continuing absorption and thus accumulation of a lethal dose, which for mustard and lewisite is about 3 to 7 g. However, except for patients with impending airway compromise, most patients exposed to vesicants can tolerate a short delay in treatment while more immediate casualties are being stabilized.
Eye and skin decontamination should occur as soon as possible, preferably using Reactive Skin Decontamination Lotion (RSDL®). A 0.5% solution of sodium hypochlorite is less effective but still useful if RSDL® is unavailable. Physical or mechanical decontamination can be tried, but soap and water are minimally effective.
Skin lesions are managed as thermal burns (see Initial wound care). However, because fluid loss in patients exposed to vesicants is lower than in patients with thermal burns, less fluid should be used than is called for in the Brooke or Parkland fluid-replacement formulas. Scrupulous hygiene is important to prevent secondary infection. Antibiotic ointment should be applied to the edges of the eyelids to prevent lid adhesion.
Supportive respiratory care, including attention to airway and breathing, is indicated for patients with respiratory manifestations (see Pulmonary Chemical Warfare Agents : Treatment). Because nausea is cholinergic in origin, it can be treated with atropine (eg, 0.1 to 1.3 mg IV q 1 to 2 h prn).
Bone-marrow suppression requires reverse isolation and treatment with colony-stimulating factors.
There are 2 types of nerve agents:
G-series agents, or G agents, include GA (tabun), GB (sarin), GD (soman), and GF (cyclosarin), which were developed by Nazi Germany before and during World War II. V-series agents include VX; these compounds were synthesized after World War II. All nerve agents are organophosphorus esters, as are organophosphate (OP) pesticides (see Organophosphate and Carbamate Poisoning). However, nerve agents are far more potent; the LD 50 (the amount required to cause death in half of people receiving that dose) of VX is approximately 3 mg.
At room temperature, G agents are watery liquids with high volatilities and pose both skin-contact and inhalational hazards. VX is a liquid with the consistency of motor oil and that evaporates relatively slowly. None of these agents has a pronounced odor or causes local skin irritation.
Nerve agents inhibit the enzyme acetylcholinesterase (AChE), which hydrolyzes the neurotransmitter acetylcholine (ACh) once ACh has finished activating receptors in neurons, muscles, and glands. ACh receptors are present in the CNS, autonomic ganglia, skeletal-muscle fibers, smooth-muscle fibers, and exocrine glands.
The binding of nerve agent to AChE is essentially irreversible without treatment; treatment with an oxime can regenerate the enzyme as long as the bond has not been further stabilized (a process termed aging) over time. Most nerve agents, like OP insecticides, take hours to age fully, but GD (soman) can age essentially completely within 10 min of binding. Inhibition of AChE leads to an excess of ACh at all of its receptors (cholinergic crisis) first causing increased activity of the affected tissue, followed eventually in the CNS and in skeletal muscle by fatigue and failure of the tissue.
The clinical manifestations depend on the state of the agent, route of exposure, and dose. Vapor exposure to the face causes local effects such as miosis, rhinorrhea, and bronchoconstriction within seconds, progressing to the full range of systemic manifestations of cholinergic excess. However, if vapor is inhaled, collapse will occur within seconds. Liquid exposure to the skin first causes local effects (local twitching, fasciculations, sweating). Systemic effects occur after a latent period that can be as long as 18 h after exposure to a very small droplet; even fatal doses usually take up to 20 to 30 min to cause symptoms and signs, which may include sudden collapse and convulsions without warning.
Patients exhibit parts or all of the cholinergic toxidrome ( Common Toxic Syndromes (Toxidromes) and Symptoms and Treatment of Specific Poisons). Overstimulation and eventual fatigue of the CNS lead to agitation, confusion, unconsciousness, and seizures, progressing to failure of the respiratory center in the medulla. Overstimulation and eventual fatigue of skeletal muscles cause twitching and fasciculations that progress to weakness and paralysis. Overstimulation of cholinergically activated smooth muscle leads to miosis, bronchospasm, and hyperperistalsis (with nausea, vomiting, and cramping), and overstimulation of exocrine glands causes excessive tearing, nasal secretions, salivation, bronchial secretions, digestive secretions, and sweating. Death is usually due to central apnea, but direct paralysis of the diaphragm, bronchospasm, and bronchorrhea can also contribute.
Diagnosis is made clinically, although laboratory analysis of erythrocyte cholinesterase or plasma cholinesterase levels as well as more specialized laboratory tests can confirm nerve-agent exposure.
All people with suspicious liquid on their skin need to be prioritized for immediate decontamination of the affected area. Patients can then be triaged for medical treatment based on their symptoms and signs. All patients exposed to nerve agents who have significant difficulty breathing or systemic effects should be triaged as immediate for medical treatment.
Attention to A irway, B reathing, C irculation, Immediate D econtamination, and D rugs (the ABCDDs) is paramount. Bronchoconstriction may be so severe that ventilation may be impossible until atropine is given (see Table: Symptoms and Treatment of Specific Poisons).
Two drugs are given, atropine and 2-pyridine aldoxime methyl chloride (2-PAM—also called pralidoxime). Atropine blocks the action of ACh. 2-PAM reactivates AChE that has been phosphorylated by nerve agents (or OP insecticides) but that has not yet undergone aging. 2-PAM reverses the peripheral effects of nerve agents, most importantly the paralysis of respiratory muscles, but has less pronounced effects in the CNS (eg, to reverse respiratory depression) and on smooth muscles and so is always given with atropine.
For prehospital care, 2 autoinjectors for intramuscular use are typically used, one containing 2.0 or 2.1 mg of atropine and another containing 600 mg of 2-PAM. Newer autoinjectors combine both drugs in one autoinjector. The drugs are given into the belly of a large muscle (eg, thigh) before establishing IV access. Once IV access is obtained, subsequent doses are given IV.
Adult patients with significant difficulty breathing or with systemic effects should promptly receive three 2.0-mg or 2.1-mg doses of atropine and three 600-mg doses of 2-PAM followed immediately by 2 to 4 mg of diazepam (also available as 2-mg autoinjectors) or 1 to 2 mg of midazolam (which is better absorbed intramuscularly than diazepam). Patients with less severe signs and symptoms can be given one autoinjector repeated in 3 to 5 min if symptoms have not resolved; a benzodiazepine is not automatically given unless 3 autoinjectors are required to be given all at once. Additional 2-mg doses of atropine are given every 2 to 3 min until muscarinic effects (airway resistance, secretions) resolve. Additional 600-mg doses of 2-PAM may be given hourly as needed for the control of skeletal-muscle effects (twitching, fasciculations, weakness, paralysis). Additional doses of benzodiazepines are given as needed for seizures. Note that paralyzed patients may have seizures in the absence of visible convulsions. Transition to IV administration should be done at the first opportunity. Dosages are adjusted downward for children.
Decontaminate all suspicious liquid on skin as soon as possible using Reactive Skin Decontamination Lotion (RSDL®); a 0.5% hypochlorite solution may also be used, as may soap and water. Possibly contaminated wounds require inspection, removal of all debris, and copious flushing with water or saline. Severe symptoms and death may occur after skin decontamination because decontamination may not completely remove nerve agents that are passing through the skin.
Anticholinergic drugs have been used as incapacitating agents, designed not to cause serious injury or death but rather to cause sufficient disorientation to prevent military personnel from carrying out their missions. One anticholinergic CW agent is 3-quinuclidinyl benzilate, NATO code BZ.
BZ is a solid that can be disseminated by heat-generating artillery rounds without being inactivated. It can persist in the environment for 3 to 4 wk. Mass casualties due to BZ exposure would likely result from inhalation of aerosolized BZ, although the compound can also be dissolved in a solvent and placed on an environmental surface from which it can be absorbed through the skin following contact.
BZ binds to muscarinic cholinergic receptors in the CNS, smooth muscle, and exocrine glands and blocks acetylcholine (ACh) at these sites. The decrease in cholinergic stimulation produces the anticholinergic toxidrome (see Table: Common Toxic Syndromes (Toxidromes)).
Patients have dry mouth and skin and dilated pupils (causing blurring of vision) and may develop hyperthermia. Cholinergic blockade in the CNS causes first lethargy and then characteristic anticholinergic illusions and hallucinations; hallucinations may be visual or auditory and are typically concrete and easily describable (eg, voices of known contacts, imaginary television programs, sharing of imaginary cigarettes, odd shapes) in contrast to the abstract, geometric, and ineffable nature of psychedelic hallucinations. Anticholinergic visual hallucinations may also be lilliputian (ie, items hallucinated decrease in size over time—eg, a cow transforms into a dog and then into a mouse or a butterfly). Speech may be slurred, and patients exhibit stereotypical picking or plucking motions (woolgathering) and may confabulate. Stupor and coma may last hours to days, with gradual recovery.
Diagnosis is made by recognizing the typical anticholinergic toxidrome. No common laboratory tests detect BZ exposure. Although many drugs and plants have anticholinergic effects (see Table: Common Toxic Syndromes (Toxidromes)), the simultaneous appearance of an anticholinergic toxidrome in many individuals who did not all ingest an anticholinergic drug or plant suggests an intentional or CW exposure. Physostigmine, a cholinergic drug, can be used as a diagnostic challenge; reduction of anticholinergic manifestations after physostigmine is given strongly suggests an anticholinergic compound.
Patients are usually quiet but may become disruptive and may need to be reassured and in some cases restrained. Patients with elevated body temperature require cooling (see Cooling techniques). Most patients do not require drug treatment, but those who are disruptive or who are markedly distressed as a result of hallucinations may benefit from being given physostigmine slowly; dose is 0.5 to 20 mg IV in adults and 0.02 mg/kg IV in children (see Table: Symptoms and Treatment of Specific Poisons) Exceeding recommended doses may cause cholinergic effects, including seizures.
Military incendiary agents are designed to illuminate the battlefield, to start fires, to create smoke to obscure terrain and personnel, or for combinations of these effects. Agents include thickened gasoline (napalm), thermite (TH), white phosphorus (WP), and magnesium.
Hydrofluoric acid, used in industry and in other applications, is often confused with hydrochloric acid; for this reason, it is recommended that it be referred to as HF. Any of these compounds can create mass casualties.
Napalm has a jelly-like consistency; the other incendiary agents are usually weaponized as powdered solids. HF can exist at ambient temperatures as a liquid or a vapor. The most common routes of exposure are percutaneous, ocular, and inhalational.
Incendiary agents cause thermal burns. Some of them may be used in exploding projectiles which cause shrapnel that may lodge in tissue. White phosphorus may continue to burn on skin or clothing as long as it has access to air, and because magnesium will burn under water, it will continue to burn within tissue. White phosphorus is toxic and may also cause systemic effects, due to uncoupling of oxidative phosphorylation in hepatocytes, hyperphosphatemia, hypocalcemia (from binding of calcium to phosphorus), renal injury, and hyperkalemia (from hypocalcemia or from renal damage).
HF penetrates deeply and quickly into exposed tissue but generates hydronium ions relatively slowly. The fluoride released from the dissociation of hydrogen fluoride binds avidly to calcium and magnesium and may produce systemic effects due to hypocalcemia, hypomagnesemia, and hyperkalemia; coagulopathy and fatal cardiac dysrhythmias may occur.
Thermal burns due to incendiary agents have manifestations similar to those of other thermal burns.
The onset of pain after HF exposure depends on the concentration of HF; pain may appear within an hour but typically occurs after 2 or 3 h. However, once pain occurs, it is often deep and intense. Affected skin is erythematous but does not seem as severely affected as the intense pain would suggest.
Most incendiary burns are readily apparent. However, burns due to low concentrations of HF may appear deceptively innocuous, and a high index of suspicion must be maintained for deep tissue injury and systemic toxicity. WP burns may glow or smoke when exposed to air.
See Burns for the general management of thermal burns.
For WP burns, the affected areas are flooded with water or smothered to avoid exposure to air. WP particles are removed mechanically (they often adhere tightly to skin) and placed in water. Smoking trails may be good indicators of the location of small particles. A bicarbonate solution may be used to flood the burns and to wet the burn dressings, but cupric sulfate (CuSO 4 ) is no longer recommended for these burns.
Mg reacts with water to generate highly flammable gas and with carbon dioxide to produce magnesium oxide and carbon. Burning or smoking Mg particles in the skin or subcutis should be removed as promptly as possible. If not all particles can be removed at once (eg, because of the number of wounds), oil can be used to cover wounds until removal can be accomplished.
Patients exposed to HF require prompt decontamination by copious flushing with water; a topical skin decontamination product (RSDL®) has not been tested in patients with skin exposures to HF. However, because HF penetrates quickly, significant local and systemic effects may occur even after thorough decontamination. Ca gluconate or Ca carbonate paste is applied to local burns. Sometimes local injection of 10% Ca gluconate is also given; some clinicians give Ca gluconate intra-arterially. Patients with significant exposure are hospitalized to undergo cardiac monitoring and treatment with CaCl or Ca gluconate ( Symptoms and Treatment of Specific Poisons).
Riot-control agents are compounds that were initially developed for crowd control but that have also been used in military conflicts. They are also referred to as harassing agents, tear agents, or lacrimators and are often incorrectly called tear gas, but in fact they do not exist as gases or vapors. Instead, they are solids that can be dispersed as liquids (by dissolving the solid agent to form a solution and then spraying the solution) or as aerosols (small particles released explosively or as smoke). Like anticholinergic agents, they are intended to cause incapacitation rather than serious injury or death, although deaths due to pulmonary edema (acute lung injury) have occurred. Military versions of these agents include chloroacetophenone (CN, also marketed as Mace®), chlorobenzylidenemalononitrile (CS), dibenzoxazepine (CR), and diphenylaminoarsine (adamsite, or DM, a so-called vomiting agent). Oleoresin capsicum (OC, pepper spray) is a more recently developed riot-control agent used primarily for law enforcement and personal protection. Chloropicrin (PS) is a compound used during World War I that is occasionally regarded as a riot-control agent, although it is more properly classified as a pulmonary agent.
CN and CS alkylate enzymes such as lactic dehydrogenase; this mechanism may be responsible for transient tissue injury that resolves with rapid replacement of the inactivated enzymes. Release of cytokines such as bradykinin contributes to the pain caused by these compounds, as does generation of hydrochloric acid at high doses. CR appears to have a similar mechanism of action. DM is thought to exert its effects partly via the oxidation of its arsenic moiety from As(III) to As(V) and the subsequent release of chlorine. OC causes pain by binding to transient receptor potential vanilloid (TRPV1) receptors in neurons that are then stimulated to release neurokinin A, calcitonin -gene-related peptide, and substance P. These compounds induce neurogenic inflammation associated with pain, capillary leakage, edema, mucous production, and bronchoconstriction.
Although there are minor differences between compounds, most riot-control agents cause nearly immediate irritation and pain involving the eyes, mucous membranes, and skin, which may also become briefly erythematous. Respiratory effects resulting from inhalation are typically obviously audible (eg, coughing, sneezing, and wheezing) due to type 1 damage, although type 2 damage (delayed-onset shortness of breath due to incipient acute lung injury) can occur with high doses. Deaths are usually due to pulmonary edema resulting from high doses delivered in confined spaces. The largely obsolete agent DM may cause either immediate or delayed-onset irritation along with vomiting.
Effects of all of the riot-control agents typically resolve within a half an hour, although agent left on the skin may cause blisters. Reactive airways dysfunction syndrome (RADS) can occur long after exposure and persist indefinitely, although it is impossible to predict which patients will develop this complication.
Diagnosis is made by history, signs (lacrimation, blepharospasm, erythema, type 1 respiratory signs), and symptoms (transient irritation and pain with, at high doses, delayed-onset shortness of breath or chest tightness). Chest x-rays are usually clear and not needed unless patients develop dyspnea, which suggests pulmonary edema. Laboratory studies do not contribute to diagnosis.
At the first sign of exposure or potential exposure, masks are applied when available. People are removed from the affected area when possible.
Decontamination is by physical or mechanical removal (brushing, washing, rinsing) of solid or liquid agents. Water may transiently exacerbate the pain caused by CS and OC but is still effective, although fat-containing oils or soaps may be more effective against OC. Eyes are decontaminated by copious flushing with sterile water or saline or (with OC) open-eye exposure to wind from a fan. Referral to an ophthalmologist is needed if slit-lamp examination shows impaction of solid particles of agent.
Most effects resulting from riot-control agents are transient and do not require treatment beyond decontamination, and most patients do not need observation beyond 4 h. However, patients should be instructed to return if they develop effects such as vesication or delayed-onset shortness of breath.
The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.
Drug NameSelect Trade
midazolamNo US brand name
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