Phosgene Exposure Medication

  • Author: Joy C Crandall, DO; Chief Editor: Robert G Darling, MD, FACEP   more...
 
Updated: Mar 22, 2012
 

Medication Summary

Most of the data regarding medication use in phosgene poisoning are derived either from anecdotal experience in case reports or from studies involving animal models. Case reports are plagued by the absence of a control group and frequently by the lack of any documentation regarding level of phosgene exposure. Animal studies are useful for elucidating pathophysiological mechanisms and providing initial measures of treatment efficacy, but the applicability of such studies to the treatment of human phosgene toxicity is unknown. Human phosgene toxicity cases occur in too sporadic and sudden a fashion to allow randomized clinical trials, and clearly intentional exposure of human subjects to phosgene would be unethical.

Multiple authors agree on the need for aerosolized bronchodilator therapy for patients with reactive airway disease or asthma diagnoses prior to phosgene exposure and for patients who are actively wheezing.

Diuretics were recommended for many years, but most recent authors seem disinclined to recommend their use and note that they may actually be harmful in phosgene toxicity. Volume overload is not a feature of phosgene-related noncardiogenic pulmonary edema. In fact, patients are often hypotensive and intravascularly dry, since they are losing fluid from the vascular space into the lung interstitium due to the breakdown of the alveolar-capillary interface. Positive pressure ventilation may further depress venous return and decrease cardiac preload and may require vigorous support with isotonic crystalloid.

Recommendations for steroid use in phosgene toxicity vary widely. No data support the use of steroids to treat human phosgene exposure, but one animal study demonstrated that intravenous methylprednisolone 30 mg/kg completely blocked pulmonary edema and the associated increased leukotriene synthesis in phosgene-exposed rabbits. Two caveats about this study are that this protocol involved pretreatment with methylprednisolone before phosgene exposure rather than the postexposure scenario, which practicing clinicians face, and that this study was not designed to test whether the methylprednisolone actually resulted in a survival benefit.

Medical management guidelines for phosgene exposure from the CDC through the Agency for Toxic Substances and Disease Registry (ATSDR)[6] recommend starting intravenous corticosteroids in cases of severe exposure even if the patient is asymptomatic. Some authors recommend both inhaled and systemic steroids for all phosgene-exposed patients, while others recommend steroids only if the patient has a prior diagnosis of reactive airway disease. Dosing recommendations from authors who advocate steroids suggest methylprednisolone 1 g IV on the day of exposure, followed by a taper over the following several days.[7]

Prophylactic antibiotics are not recommended in phosgene-induced pulmonary edema. Antibiotic therapy should be reserved for patients who have clinical findings consistent with pneumonia such as a sputum culture with a likely culprit organism.

A variety of studies have been completed in rabbits and mice using postexposure administration of intratracheal isoproterenol, parenteral ibuprofen, intratracheal N -acetylcysteine, parenteral aminophylline, subcutaneous terbutaline, colchicine, and parental leukotriene receptor blockers. While many of these agents and delivery routes show promise in terms of decreased pulmonary edema, increased levels of reduced glutathione, decreased production of lipid peroxidation products, decreased leukotriene production, and maintenance of tissue cAMP levels, these favorable laboratory end points have not necessarily been tied to clinical end points of improved survival. None of these agents has Food and Drug Administration (FDA) approval for treatment of noncardiogenic pulmonary edema associated with toxic inhalations.

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Systemic corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune system to diverse stimuli.

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Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol)

 

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

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Aerosolized bronchodilator therapy

Class Summary

Patients with hyperactive airways usually benefit from aerosolized bronchodilator therapy.

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Albuterol (Proventil, Ventolin)

 

Relaxes bronchial smooth muscle by action on beta 2-receptors with little effect on cardiac muscle contractility.

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Contributor Information and Disclosures
Author

Joy C Crandall, DO  Brigade Surgeon, Department of Emergency Medicine, United States Army, 214th Fires Brigade, Fort Sill, Oklahoma

Joy C Crandall, DO is a member of the following medical societies: American College of Emergency Physicians and American Osteopathic Association

Disclosure: Nothing to disclose.

Coauthor(s)

Kermit D Huebner, MD, FACEP  Research Director, Carl R Darnall Army Medical Center

Kermit D Huebner, MD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, Association of Military Surgeons of the US, Society for Academic Emergency Medicine, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Mark Keim, MD  Senior Science Advisor, Office of the Director, National Center for Environmental Health, Centers for Disease Control and Prevention

Mark Keim, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rick Kulkarni, MD  Attending Physician, Department of Emergency Medicine, Cambridge Health Alliance, Division of Emergency Medicine, Harvard Medical School

Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: WebMD Salary Employment

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Robert G Darling, MD, FACEP  Adjunct Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director, Center for Disaster and Humanitarian Assistance Medicine

Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Telemedicine Association, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Elizabeth A Gray, MD, John W Love, MD, and Jeffery L Arnold, MD, to the development and writing of this article.

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Anteroposterior portable chest radiograph in a male patient who developed phosgene-induced adult respiratory distress syndrome. Notice the bilateral infiltrates and ground-glass appearance Image courtesy of Fred P. Harchelroad, MD, and Ferdinando L. Mirarchi, DO.
 
 
 
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