Inhalational Agents

Thomas Burklow, MDThomas Burklow, MDDepartment of PediatricsDepartment of Pediatrics

Walter Reed Army Medical CenterWalter Reed Army Medical Center

Inhalational Agents as Inhalational Agents as Terrorist WeaponsTerrorist Weapons

Thomas R. Burklow, MDThomas R. Burklow, MD

LTC, MCLTC, MC

Division of Pediatric CardiologyDivision of Pediatric Cardiology



Historical notesHistorical notes First “chemical agent” 423 B.C., Sparta: Burning

mixture of pitch, naphtha, and sulfursulfur dioxide

1915, Ypres, Belgium: Germans release 150 tons of chlorine

1917, Verdun: Germans use phosgene in artillery shells



AgentsAgents

Phosgene (CG) Chlorine (CL) Diphosgene (DP) Chloropicrin (PS)



ToxicokineticsToxicokinetics

Absorbed almost exclusively by inhalation Penetrates readily to alveolar Not systemically absorbed



Toxicity: LCtToxicity: LCt5050 Toxicity:Lethal concentration-time product (i.e. dose) to

kill 50% of a group Ct50: agent concentration (mg/m3) multiplied by time

(minutes) The lower the LCt50, 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/m3 for 10 minutes is the equivalent

exposure dose of 100 mg/m3 for 5 minutes



ToxicityToxicity

Phosgene Odor threshold (“new mown hay”), 1.5 mg/ m3

Irritation threshold, 4 mg/ m3

3200 mg-min/m2

Chlorine Odor of “swimming pool water” 6000 mg-min/m2



Clinical effectsClinical 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.



Most prominent clinical symptom: Most prominent clinical symptom: DyspneaDyspnea

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)





TREATMENTTREATMENT

Medical Management of Chemical Casualties Handbook, 3rd Ed, 1998

Chlorine http://www.emedicine.com/emerg/topic851.htm

Phosgene http://www.emedicine.com/emerg/topic905.htm



General principles of inhalation General principles of inhalation agent managementagent 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



Phosgene: Prehospital CarePhosgene: 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



Phosgene: Emergency Phosgene: Emergency Department CareDepartment 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.



Pulmonary edemaPulmonary edema

Positive end-expiratory pressure via positive airway pressure mask or, in more severe cases, endotracheal intubation with positive pressure ventilation.



Phosgene inhalation caveatsPhosgene 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



ChlorineChlorine

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



Chlorine: Prehospital CareChlorine: 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.



Chlorine: Emergency Chlorine: Emergency Department CareDepartment 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.



Chlorine poisoning: Chlorine poisoning: BronchospasmBronchospasm

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.



Sodium bicarbonateSodium 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.



Other therapiesOther 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



Differential DiagnosisDifferential 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



Inhalational agents as Inhalational agents as terrorist weaponsterrorist 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



Inhalational agents as Inhalational agents as terrorist weaponsterrorist 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



The Washington Post The Washington Post November 12November 12thth 2001 2001



Industrial injuriesIndustrial 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.



Pediatric considerationPediatric 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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Inhalational Agents