Initial effects after mild to moderate exposures to chlorine include ocular and nasal irritation, followed by cough, and progressing to a choking sensation and substernal chest tightness Bronchospasm often occurs, especially in patients with a history of reactive airway disease Pulmonary edema may develop within 30 minutes to hours depending on the severity of exposure Mild to moderate exposures to phosgene may be initially asymptomatic with only the perception of a pleasant odor of newly mown hay Thus, lung-exposure time may be significant before victims remove themselves from the affected area Pulmonary edema occurs after a considerable delay, typically to hours, but up to 24 hours after low concentration exposures In these cases, delayed-onset shortness of breath or chest tightness precedes objective clinical or radiologic findings With high concentration exposures, early lacrimation may be followed by cough, dyspnea, and pulmonary edema The pulmonary edema may be so severe as to result in hypotension from hypovolemia The onset of shortness of breath or chest tightness within the first hours of exposure to phosgene portends the eventual development of massive pulmonary edema and a grave prognosis Management of exposure to pulmonary agents is primarily supportive Removal to fresh air generally suffices for decontamination Careful attention to control of pulmonary secretions, bronchospasm, and pulmonary edema as well as to aggressive treatment of secondary bacterial infection (often occurring to days after exposure) is required Animal studies suggest a modest benefit of steroid therapy in mitigating lung injury after chlorine inhalation; thus steroids may be considered for patients with chlorine exposure, especially as an adjunct to bronchodilators In addition, some symptomatic relief has also been reported for chlorine exposure with nebulized 3.75% sodium bicarbonate therapy, but the impact of this regimen on pulmonary damage is unknown Cyanide Compounds containing the cyanide ion (CN− ) have a long history as favored agents for homicide and suicide, but their efficacy as CWAs is limited by their volatility in open air and by their flammability However, if released nonexplosively in a crowded, closed room, they could have devastating effects Chemical agents containing cyanide include the liquids hydrocyanic acid (hydrogen cyanide, HCN; NATO Code AC) and cyanogen chloride (ClCN; NATO code CK), both of which rapidly vaporize after release Toxicology Some cyanide is normally present in human tissues and several pathways exist for its metabolism For example, cyanide reacts reversibly with metals such as ferric ion (Fe3+ ) and cobalt; in the body, the reaction of hydroxocobalamin with cyanide yields cyanocobalamin, or vitamin B12 The ability of the body to metabolize small quantities of cyanide, given sufficient time, accounts for the dependence of cyanide toxicity on conditions of concentration and exposure time The same amount of cyanide that will kill when given over a few minutes may be successfully metabolized by the body if administered over several hours Doses of cyanide large enough to overwhelm normal metabolism inhibit electron transport of the mitochondrial cytochrome chain The inactivation of this enzyme site results in cellular anoxia and a decreased arteriovenous oxygen difference (from inability of cells to use delivered oxygen), increased lactic acid (from accelerated glycolysis under anaerobic conditions), and metabolic acidosis Clinical Manifestations Clinical manifestations of cyanide poisoning relate to cellular anoxia; thus the heart and brain are most severely affected High concentrations of cyanide vapor initially produce tachypnea, hyperpnea, and hypertension within 10 to 15 seconds Anoxic injury to the CNS and myocardium soon follow, with unconsciousness and seizures (30 seconds after exposure), opisthotonus, trismus, facial muscle spasm, decerebrate posturing, bradycardia, dysrhythmias, hypotension, and eventually cardiac arrest (as early as to minutes after exposure) Exposure to low concentrations of vapor produces nonspecific effects such as headache, light-headedness, nausea, and ataxia “Classic” signs of cyanide poisoning are said to include severe dyspnea without cyanosis, flushing from increased oxygen content venous blood, and a bitter almond odor to breath and body fluids Noteworthy laboratory abnormalities in cyanide poisoning include an abnormally high mixed venous oxygen saturation with a resultant decreased arteriovenous oxygen content difference (one of the most useful laboratory indicators of cyanide poisoning), a high anion gap metabolic acidosis, and hyperlactatemia Both cyanide and nerve-agent casualties can collapse suddenly, stop breathing, and convulse Gasping, normal or dilated pupil size (as opposed to miosis), pink skin (instead of cyanosis), and normal secretions (as opposed to increased secretions) may lead to a clinical diagnosis of cyanide over nerve agent, but none of these signs is pathognomic The similarities between cyanide and nerve-agent casualties may be more apparent than the differences Management Management of cyanide poisoning begins with removal to fresh air Dermal decontamination is unnecessary if exposure has been only to vapor, but wet clothing should be removed and the underlying skin should be washed with soap and water Attention to the basics of intensive supportive care is critical and includes administration of 100% oxygen to all significantly symptomatic patients, mechanical ventilation as needed, circulatory support with crystalloid and vasopressors, correction of metabolic acidosis with IV sodium bicarbonate, and seizure control The cyanide-induced inhibition of cellular oxygen use might lead to the expectation that supplemental oxygen would not be of use in cyanide poisoning, but in fact, administration of 100% oxygen has been found to empirically exert a beneficial effect, possibly by affecting the interaction of cyanide with nitric oxide in mitochondria Symptomatic patients, especially those with severe manifestations, may further benefit from specific antidotal therapy Currently, two regimens are available in the United States The first, the original “cyanide antidote kit” utilizes a two-step process First, a methemoglobin-forming agent such as amyl nitrite or sodium nitrite is administered This causes dissociation of bound cyanide from the cytochrome oxidase and restores aerobic energy production Perhaps even more importantly, nitrites generate nitric oxide, which antagonizes the inhibition of cytochrome oxidase by cyanide The second step of the cyanide antidote kit is provision of a sulfur donor, sodium thiosulfate, which reacts irreversibly with cyanide to generate thiocyanate and sulfites, both of which are excreted in the urine Caution is warranted when using this cyanide antidote Nitrites result in vasodilation, which may enhance vital organ perfusion However, too rapid infusion may cause or exacerbate hypotension, and overproduction of methemoglobin may compromise oxygen-carrying capacity Thus, this therapy should be avoided in conscious patients with minimal symptoms and used with caution in patients, especially children, whose cyanide toxicity may be complicated by carbon monoxide poisoning (e.g., smoke-inhalation victims) However, a case study of adult smoke-inhalation victims treated with nitrites and sodium thiosulfate showed no complications of the nitrite therapy, and smoke inhalation should be regarded as a relative rather than an absolute contraindication to nitrite use The nitrite risk–benefit ratio becomes more favorable in the context of a severely intoxicated casualty of a terrorist cyanide vapor attack, and careful attention to proper dosing and rate of administration should allow safe use of this antidote Pediatric nitrite dosing depends on body weight and hemoglobin concentration The recommended initial pediatric dosage, assuming hemoglobin concentration of 12 g/dL, is 0.33 mL/kg of the standard 3% sodium nitrite solution, given slowly IV over to 10 minutes; the initial adult dosage is 10 mL Thiosulfate itself is efficacious, relatively benign, and also synergistic with oxygen administration The initial thiosulfate dose for children is 1.65 mL/kg of the standard 25% solution IV, and the initial adult dose is 50 mL Second treatments with one-half the initial dose of nitrite and thiosulfate may be given 30 minutes after the original dose if needed in severe cases The newer antidote available in the United States is hydroxocobalamin, available in Cyanokit This compound nonenzymatically and reversibly reacts with cyanide to form cyanocobalamin (vitamin B12 ) which is subsequently excreted It does not induce hypotension (in fact, it predictably raises the blood pressure) or methemoglobinemia and has been advocated as a replacement for the cyanide antidote kit, especially for smoke-inhalation victims However, the cyanide antidote kit has a well-documented record of efficacy Moreover, hydroxocobalamin must be given via the IV route; amyl nitrite, included in the cyanide antidote kit, can be given via inhalation to a patient without IV access The recommended initial dose of hydroxocobalamin is g in adults or 70 mg/kg in children, administered IV over 15 minutes (∼15 mL/min) A second 5-g dose (70 mg/kg in children) may be repeated in severely affected patients, with the second infusion rate ranging from 15 minutes to hours based on the condition of the patient The medication is dark red in color, and treatment results in reddening of skin and mucous membranes and red-colored urine that may last several days This phenomenon may also skew some common laboratory results that are based on colorimetric tests, such as creatinine, bilirubin, and hepatic transaminases, as well as cooximetry results To date, the superiority of one cyanide antidote over another has not been clearly demonstrated Newer compounds with oral availability are under investigation and include cobinamide, a cobalamin precursor with high cyanide affinity, and analogs of 3-methyl pyruvate, which like thiosulfate enhance conversion of cyanide to thiocyanate Because clinical distinction between cyanide and nerve-agent casualties may be difficult, any patient thought to have been exposed either to cyanide or to a nerve agent but who does not respond to antidotal therapy specific for the suspected agent should be given a trial of the antidotes for the other agent Riot-Control Agents ... administration should allow safe use of this antidote Pediatric nitrite dosing depends on body weight and hemoglobin concentration The recommended initial pediatric dosage, assuming hemoglobin concentration