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

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

Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Agents  Phosgene (CG)  Chlorine (CL)  Diphosgene (DP)  Chloropicrin (PS)

Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center Toxicokinetics  Absorbed almost exclusively by inhalation  Penetrates readily to alveolar  Not systemically absorbed

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

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

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.

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)

Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center

Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center TREATMENT  Medical Management of Chemical Casualties Handbook, 3 rd Ed, 1998  Chlorine   Phosgene 

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

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

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.

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.

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

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

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.

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.

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.

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.

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

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

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

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,

Thomas Burklow, MD Department of Pediatrics Walter Reed Army Medical Center The Washington Post November 12 th 2001

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 , 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.

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