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Toxicity, Phosgene: Treatment & Medication
Updated: Jul 10, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
- To avoid further exposures, hazardous materials (Hazmat) prehospital providers should always ensure that the environment is safe.
- A self-contained breathing apparatus (SCBA) should be worn at the exposure site. Remove the patient's clothes to prevent further contamination.
- If the eyes and skin are exposed, begin irrigation on site.
- In the field, standard management of ABCs usually is sufficient. Severe exposures may require ET intubation and suctioning. If a significant bronchospastic component is present, bronchodilators may be used with caution.
- Past wartime experience has demonstrated that, in a mass casualty situation, phosgene exposures should be classified as immediate because of the impending need for intubation and positive end-expiratory pressure (PEEP) to maintain distal airway opening.
Emergency Department Care
Always consider the need for decontamination in any toxic exposure to minimize the risk of poisoning hospital personnel. Inhalational exposure of phosgene should not occur unless in the proximity of the gas. If external decontamination has not been performed in the field, use personal protective equipment, as necessary, including dermal, eye, and facial protection. A decontamination shower unit may be used.
- Initiate humidified oxygen supplementation. Intubation with continuous positive airway pressure (CPAP) ventilation and pressure support is usually required to improve oxygenation. Frequent suctioning may improve conditions.
- Bronchodilators may improve existing bronchospasm. In animal studies, beneficial effect has been shown with the administration of numerous drugs, including leukotriene antagonists, ibuprofen, colchicine, cyclophosphamide, terbutaline, aminophylline, and N -acetylcysteine. Nebulized sodium bicarbonate treatment theoretically may be beneficial; however, consider it as second line after the drugs noted above.
- Avoid excessive fluid administration. Pulmonary artery catheter monitoring may be required to maintain appropriate fluid balance while treating hypotension caused by fluid shifts.
- In severe cases, extracorporeal membrane oxygenation (ECMO) may be considered refractory to supportive care.
- Minimize fluid administration except when it is needed to correct hypotension. Avoid diuretics because the patient typically is volume-depleted from fluid shifts.
- Avoid exertion during treatment and for several weeks after recovery.
- Prophylactic antibiotics have been recommended by some authors based on the findings of pneumonia and bronchitis in virtually all autopsy specimens.
- Corticosteroid administration postexposure has been recommended to reduce the degree of pulmonary edema by reducing the inflammatory response. Some sources recommend administration begin within 15 minutes or as soon as possible after exposure.
- No specific antidote or effective elimination process exists. During both world wars, the Germans and Russians believed that hexamethylene tetramine was the antidote. Subsequent studies have shown some preexposure benefit but no definite postexposure benefit.
- Tomelukast, a leukotriene receptor antagonist, prevents pulmonary edema in phosgene-exposed rabbits. Experimentally, ibuprofen has been shown to reduce phosgene-induced pulmonary edema. Colchicine and cyclophosphamide reduce neutrophil influx when administered to mice 30 minutes following phosgene exposure. These drugs reduce lung injury and mortality in mice.
- Intratracheal dibutyryl cyclic adenosine monophosphate (DBcAMP), a cyclic adenosine monophosphate (cAMP) analogue, inhibits the release of leukotrienes that contribute to the disease process. In phosgene-exposed rabbits, terbutaline and aminophylline (cAMP enhancers) limit the pulmonary capillary leakage. Also, intratracheal N -acetylcysteine (NAC), administered to rabbits 45 minutes postexposure, reduces leukotriene formation and pulmonary edema. Theoretically, nebulized NAC also should be effective.
Consultations
- Consult the regional poison control center and a medical toxicologist for additional useful information and patient care recommendations.
- Prolonged critical care management often is required for the pulmonary complications of phosgene exposure.
Medication
Management of phosgene toxicity is supportive. Oxygen, corticosteroids (inhaled, systemic), leukotriene inhibitors, IV fluids, and prophylactic antibiotics are recommended. The recommended steroid dose is much higher than the dose conventionally used in asthma. Prophylactic antibiotics and antifungals may be required because of the risk of superinfection. Pressor agents may be required to treat hypotension, bradycardia, and renal failure.
Corticosteroids
Reduce inflammatory response. Whether early administration of corticosteroids can prevent development of noncardiogenic pulmonary edema is unknown. The decision to administer corticosteroids must be made on clinical grounds.
Treatments lasting more than 1 week may require a taper to prevent abrupt steroid withdrawal.
Beclomethasone (Beclovent, Vanceril)
Inhibits bronchoconstriction mechanisms, producing direct smooth muscle relaxation; may decrease number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness.
Adult
10 puffs immediately followed by 5 puffs qh for 10 h; then 1 puff qh for at least 5 d
Pediatric
Not established
Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant
Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur (taper medication slowly if these changes occur)
Methylprednisolone (Solu-Medrol)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
Day 1: 1000 mg IV
Days 2-3: 800 mg IV
Days 4-5: 700 mg IV
Day 6: Reduce dose quickly if chest x-ray remains clear
Pediatric
Not established
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications; caution in viral, fungal, or tubercular skin infections
Betamethasone (Celestone, Soluspan)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
Begin with 20 mg IV; repeat q6h IV/IM for 24 h; reduce dose over next 5 d
Pediatric
Not established
Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of multiple complications, including severe infections (caution in tubercular or systemic fungal infections); monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications
Vasopressors
Used to treat hypotension, bradycardia, or renal failure.
Dopamine (Intropin)
Stimulates adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Use low dose to protect renal function; use high dose to combat severe hypotension unresponsive to fluid administration.
Adult
2-20 mcg/kg/min IV; titrate to effect
Pediatric
Administer as in adults
Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects
Documented hypersensitivity; pheochromocytoma or ventricular fibrillation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during the infusion; before infusion, correct hypovolemia with whole blood or plasma prn; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia
Leukotriene antagonists
Reduce the inflammatory response elicited by the leukotriene cascade. Leukotriene antagonists are approved by the Food and Drug Administration (FDA) only for chronic asthma management.
Zafirlukast (Accolate)
No human studies have evaluated the efficacy and safety of zafirlukast in patients exposed to phosgene. Nevertheless, given the known effects of leukotriene stimulation by phosgene, the results from animal studies, and the drug's safety profile, should be considered first line.
In the presence of food, bioavailability of oral zafirlukast is decreased by 40%. Administer on an empty stomach.
Adult
20 mg q12h PO asthma; however, given the pharmacokinetic profile and the exaggerated response caused by phosgene, an increased dosage can be assumed (consider 40-80 mg PO q12h for the initial 48 h)
Pediatric
Not established
Aspirin increases plasma levels; erythromycin decreases plasma levels; theophylline may decrease levels and may increase plasma theophylline levels; warfarin may result in clinically significant increases in half-life of warfarin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Severe liver disease; concomitant warfarin therapy; systemic eosinophilia, and symptoms consistent with Churg-Strauss syndrome have been reported during reduction in oral steroid therapy; efficacy and safety in humans exposed to phosgene have not been validated in clinical trials
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References
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Further Reading
Keywords
phosgene toxicity, phosgene exposure, phosgene poisoning, COCl2, carbonic dichloride, carbon oxychloride, carbonyl dichloride, chloroformyl chloride, d-stoff, green cross, CG, pulmonary irritant
