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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Inhalational Agents as Terrorist Weapons Thomas R. Burklow, MD LTC, MC Division of Pediatric Cardiology
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Historical notes First “chemical agent” 423 B.C., Sparta: Burning mixture of pitch, naphtha, and sulfur sulfur dioxide 1915, Ypres, Belgium: Germans release 150 tons of chlorine 1917, Verdun: Germans use phosgene in artillery shells
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Agents Phosgene (CG) Chlorine (CL) Diphosgene (DP) Chloropicrin (PS)
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Toxicokinetics Absorbed almost exclusively by inhalation Penetrates readily to alveolar Not systemically absorbed
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Toxicity: LCt 50 Toxicity:Lethal concentration-time product (i.e. dose) to kill 50% of a group Ct 50 : agent concentration (mg/m 3 ) multiplied by time (minutes) The lower the LCt 50, less of the agent is required, and thus more potent is the agent Does not take into account physiological factors Case example exposure to 50 mg/m 3 for 10 minutes is the equivalent exposure dose of 100 mg/m 3 for 5 minutes
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Toxicity Phosgene Odor threshold (“new mown hay”), 1.5 mg/ m 3 Irritation threshold, 4 mg/ m 3 3200 mg-min/m 2 Chlorine Odor of “swimming pool water” 6000 mg-min/m 2
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Clinical effects Exposure clinical latent period (up to 24 hrs) pulmonary edema Creates defects in the alveolar-capillary barrier, but the exact mechanism is unknown Early symptoms may result from irritation of mucosal membranes (conjunctivitis and irritation of larynx) by phosgene or chlorine.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Most prominent clinical symptom: Dyspnea Initially unaccompanied by objective signs of pulmonary damage Hypoxemia, tachypnea, decreased pulmonary compliance Cyanosis may become clinically evident Profound pulmonary edema (pulmonary sequestration of plasma-derived fluid accumulates up to 1 liter/hr)
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center TREATMENT Medical Management of Chemical Casualties Handbook, 3 rd Ed, 1998 Chlorine http://www.emedicine.com/emerg/topic851.htm Phosgene http://www.emedicine.com/emerg/topic905.htm
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center General principles of inhalation agent management Decontamination Vapor: fresh air, supplemental oxygen Liquid: copious water irrigation Management Termination of exposure ABCs of resuscitation Rest and observation Oxygen with or without positive airway pressure Monitor for delayed pulmonary edema
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Phosgene: Prehospital Care Full personal protective equipment for toxic vapor exposures, including Level A suits and self- contained breathing apparatus. Not expected to pose a significant risk of contamination. ABC’s Inhalational bronchodilator treatment
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Phosgene: Emergency Department Care Appropriate ED care also depends on careful attention to the ABCs. Ongoing reassessment is a key. Toxic effects may not be apparent in the first few hours. Noncardiogenic pulmonary edema may develop 4-6 hours after exposure.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Pulmonary edema Positive end-expiratory pressure via positive airway pressure mask or, in more severe cases, endotracheal intubation with positive pressure ventilation.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Phosgene inhalation caveats No specific antidote Diuretics Limited role Reduces fluid loss into the lungs via the damaged alveolar-capillary membrane May cause hypotension in hypovolemic patients receiving positive pressure ventilation. Steroids Not effective Bronchodilator therapy Benefits patients with hyperactive airways
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Chlorine Poisoning is common in the US. Common inhalational irritant One third of the morbidity cases following acute irritant exposure involving both adults and children. Toxic effects after inhalation exposure usually are mild to moderate, and death is uncommon. Large amounts of chlorine are produced in the industrial sector
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Chlorine: Prehospital Care Remove victims from the toxic environment. Chlorine gas exposure represents a low risk for cross-contamination Decontamination at the scene if eye or skin involvement is found. Copious amounts of water may be used. Remove the patient's clothing if it has been contaminated with liquid chlorine.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Chlorine: Emergency Department Care ABC’s Monitor for laryngospasm Irrigate the eyes and skin; wash skin with a mild soap and water. Use a pH reagent strip for assess any eye injury. Continue irrigation of the eye until the pH returns to near 7. Evaluate the cornea with fluorescein staining under a slit lamp.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Chlorine poisoning: Bronchospasm Beta agonists such as albuterol. Ipratropium may be added to the treatment. May require terbutaline or aminophylline. Nebulized lidocaine (4% topical solution) may provide analgesia and reduce coughing.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Sodium bicarbonate In the past, several authors advocated nebulized sodium bicarbonate. Most recommendations are based on anecdotal experience, and little supporting clinical data are available. The mechanism of action is believed to be the neutralization of hydrochloric acid formed in the airways. Theoretically, an exothermic reaction may occur. Animal studies suggest nebulized sodium bicarbonate may cause chemical pneumonitis.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Other therapies Corticosteroids: Inhaled and parenteral steroids have been used with many patients exposed to chlorine gas, but no strong clinical evidence supports their use. Fluid management Diuretics
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Differential Diagnosis Riot control agents More intense irritation than phosgene or chlorine. Not accompanied by odor of phosgene Nerve agents Production of profuse secretions Lack of cholinergic effects: profuse secretions; miosis, Effects not delayed Vesicants Predominately affects central rather than peripheral airways Dyspnea accompanied by airway necrosis and obstruction Pulmonary parenchymal damage usually manifests as hemorrhage rather than edema
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Inhalational agents as terrorist weapons “Weapon of opportunity” Actually terrorist potential uncertain 1995, the FBI uncovered a terrorist effort to release a chlorine gas bomb in the Disneyland theme park in California
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Inhalational agents as terrorist weapons Not stockpiled by the US military US produces over a billion pounds a year for industrial use Chlorine: 20.6 billion ton-miles shipped by rail, 1985-1995
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center The Washington Post November 12 th 2001
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Industrial injuries Accidental industrial accidents Hamburg, Germany 1928: accidental factory release of phosgene. The gas cloud spread over 10 km, killing and injuring hundreds of people American Association of Poison Controls Centers' National Data Collection System 1988-1992, Chlorine Categorized outcome in 21,437 cases 40 resulted in a major effect 2091 resulted in a moderate effect 17,024 resulted in a minor effect 2099 had no effect.
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Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Pediatric consideration Higher number of respirations per minute in children results in exposure to a relatively greater dosage. The high vapor density of the gases places their highest concentration close to the ground in the lower breathing zone of children. Having less fluid reserve increases the child's risk of rapid dehydration or frank shock with pulmonary edema
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