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CBRNE - Lung-Damaging Agents, Phosgene: Treatment & Medication

Author: Joy C Wethern, DO, Resident Physician PGY3, Department of Emergency Medicine, Carl R Darnall Army Medical Center, Ft Hood, Texas
Coauthor(s): Kermit D Huebner, MD, FACEP, Research Director, Carl R Darnall Army Medical Center
Contributor Information and Disclosures

Updated: May 27, 2009

Treatment

Prehospital Care

No specific antidote exists for phosgene poisoning, but supportive care options are numerous.

• Rescuer safety is paramount. Little risk exists of secondary exposure or contamination from patients who have been exposed only to phosgene gas, but any patient exposed to liquid phosgene requires decontamination to protect prehospital and in-hospital care providers and resources. Knowing the ambient temperature is important. If the environment where exposure occurred is warmer than the boiling point of phosgene (47°F), then it is likely that exposure was only to the gas form, and extensive decontamination should not be required. The patient should be removed from further exposure to the gas (taken upwind of the exposure source).
• To care for patients with liquid phosgene exposure, prehospital or HAZMAT personnel should be attired in at least level B protection (full face mask with either supplied air respirator or preferably self-contained breathing apparatus (SCBA), butyl rubber gloves, chemical protective suit, chemical resistant protective overboots). NIOSH recommends this level of protection for known phosgene concentrations in excess of 1 ppm or any situation with unknown phosgene levels. Decontamination of patients exposed to liquid phosgene should start with clothing removal and bagging/tagging of contaminated apparel. Patients should use soap and water to wash their hair and all body surfaces, with care to avoid unnecessary hypothermic stress. Warm water, warm blankets, and dry uncontaminated clothing are essential. Also see CBRNE - Chemical Decontamination.
• Because of the latency of symptom onset, all patients with suspected phosgene exposure should be transported to a medical facility for evaluation.
• Priorities for care remain airway, breathing, and circulation. If patients are being treated and transported shortly after the exposure incident, it is unlikely that that they will be severely symptomatic due the latent period associated with phosgene. If the patient reports dyspnea or chest tightness, begin therapy with supplemental oxygen. Enforce rest (litter evacuation, not walking) since any exertion shortens the latent period and worsens toxicity. Keep patients calm, warm, and quiet to minimize the work of breathing.
• Any patient with ocular exposure to phosgene should begin eye flushes with copious amounts of saline or plain water for at least 15 minutes. This treatment should be started in the prehospital setting. Contact lenses should be removed.

Emergency Department Care

• Triage
  • Triage is a relatively simple matter when only a few patients are involved, but in the event of a CBRNE attack or large-scale industrial accident, triage becomes much more difficult since any one medical facility would rapidly be overwhelmed by large patient volumes.
  • The numbers of "worried well" who have not actually been exposed are likely to be large in any CBRNE event, but they create a particular problem for triage of phosgene exposures because the "worried well" and the "soon to be sick" who are in the latent phase before pulmonary edema may appear identical on presentation.
  • Asymptomatic patients require a minimum of 6 hours of observation, and many authors recommend 12-24 hours of observation before discharge. Patients who are eligible for discharge after this observation time should be asymptomatic with a clear lung ausculatory examination, normal respiratory rate, normal oxygen saturation, and normal chest radiograph.
  • While triage is always a dynamic process, this statement is particularly true for the triage of phosgene-exposed persons, who require frequent reassessment and retriage (every 1-2 h). Some authors recommend repeating vital signs and lung ausculatory examinations every 30 minutes. The first physical sign of pulmonary edema, crackles on the ausculatory examination, typically appears at half the time of the greatest symptomatic involvement (ie, a patient who develops crackles at 3 h postexposure can be expected to be severely ill at 6 h postexposure).
  • Triage depends on the availability of high-level critical care and ventilators for patients with severe pulmonary edema. If the number of patients who require ventilators outstrips the number of available ventilators, then patients who present with symptomatic pulmonary edema would likely be triaged as expectant.
  • When a true mass casualty situation exists, one triage scheme that has been recommended for phosgene exposed persons is as follows:
    • Minimal: Asymptomatic patients - Observe, retriage every 2 hours
    • Delayed: Symptoms of dyspnea without any signs on physical examination (normal vital signs, normal oxygen saturation) - Observe, retriage every hour
    • Immediate (if critical care resources are available): Signs of pulmonary edema (crackles on lung ausculatory examination, vital sign abnormalities, chest radiograph infiltrate)
    • Expectant: Patients with pulmonary edema accompanied by hypotension or cyanosis
• Ensure patients have been decontaminated in the prehospital setting. If patients exposed to liquid phosgene present for care before decontamination, ensure that they are decontaminated outside of the emergency department by staff members in appropriate protective equipment (level B or higher).
• Focus on airway, breathing, and circulation. For a stridorous patient who appears to have phosgene-induced laryngospasm, proceed rapidly to pharmacologically facilitated endotracheal intubation. If orotracheal intubation is impossible, be prepared for a surgical airway. Intubated patients may have copious airway secretions that require frequent suctioning. For patients not in need of emergent intubation, provide supplemental oxygen if they have symptoms of dyspnea and/or signs of tachypnea, hypoxia, or crackles on lung ausculatory examination.
• Enforce rest for all patients exposed to phosgene to minimize work of breathing since exertion shortens the latent period and worsens the clinical course.
• For patients with pulmonary edema and worsening respiratory status (hypoxemia, hypercapnia, increased work of breathing), provide airway support with positive pressure ventilation. Initially alert patients may do well with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP), but if their clinical status declines further, they may require intubation and mechanical ventilation for support. Frequently high inspired concentrations of oxygen and high positive end-expiratory pressure (PEEP) settings are required to treat the severe hypoxemia associated with phosgene-induced noncardiogenic pulmonary edema. This therapeutic measure is intended to recruit collapsed alveoli to participate in gas exchange, thereby decreasing V/Q mismatch and improving oxygenation. However, patients will require careful monitoring of cardiovascular status because high PEEP settings may depress cardiac output by decreasing venous return.
• For patients with significant wheezing or preexisting reactive airway disease and bronchospasm, treat with standard doses of inhaled bronchodilators and inhaled anticholinergic agents such as albuterol and ipratropium bromide.
• For patients with ocular exposures to phosgene, continue the irrigation begun in the prehospital setting for a total time of at least 15 minutes. Test the patient's visual acuity and perform a slit lamp examination. Topical anesthetics may be required to attenuate blepharospasm and permit an adequate examination. Stain the corneas with fluorescein to check for any corneal epithelial defects. Refer the patient to an ophthalmologist.

Consultations

• Notify the local/state health department.
• If decontamination needs surpass hospital capabilities, request help from the local hazardous materials team.
• Discuss management with the regional poison control center.
• Notify law enforcement if industrial sabotage or an intentional release of phosgene is suspected. The Federal Bureau of Investigation (FBI) is the lead agent for investigating possible terrorist actions and weapons of mass destruction events.
• Internet sources for more information include the following: Centers for Disease Control and Prevention, Chemical Emergencies; and National Response Center (for reporting chemical spills).

Medication

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)⁵ 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.

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.

Systemic corticosteroids

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

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

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

Aerosolized bronchodilator therapy

Patients with hyperactive airways usually benefit from aerosolized bronchodilator therapy.

Albuterol (Proventil, Ventolin)

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

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