AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Diphosgene (DP, trichloromethylchloroformate) was a product of the chemical weapons race in World War I. It belongs to a class of chemicals termed lung-damaging agents or choking agents. These agents attack lung tissue directly, causing pulmonary edema. DP is described not only as a respiratory irritant but also as a lachrymator. The lacrimatory effect makes DP more easily detected than phosgene (CG). The mechanism of action is not well understood, but the chemical is believed to react directly upon the alveolar and capillary walls. The production of leukotrienes and the excessive accumulation of neutrophils may affect the alveolar sites sufficiently to cause pulmonary edema.

The Germans staged the first major successful chemical attack of the war using chlorine. Chlorine then was replaced by phosgene, which caused greater casualties. Gas masks of the era were designed to filter out phosgene. DP was created by combining phosgene with chloroform, which destroyed the gas filters, and it was first utilized in the field in May 1916. Blistering and nerve agents largely have replaced the pulmonary agents chlorine, phosgene, and DP.

In the field, DP rapidly vaporizes and breaks down into phosgene and chloroform. It is a colorless gas under standard temperatures and pressures, but it can also be found as an oily, colorless liquid. It emits an odor reminiscent of green corn or new mown hay. Its lethal dose is 3000 mg⋅min/cubic meter for 50% of exposed resting adults. Clinically, DP behaves in essentially the same manner as phosgene. The chloroform does not reach levels sufficient to cause toxicity, even of the liver, during tactical employment. DP is heavier than air and remains in low-lying areas for longer periods. Therefore, children are at increased risk for a greater absorption of the agent. Doses are cumulative, since DP is not detoxified in the body. Symptoms may be delayed for more than 3 hours after exposure with minimal contact, but in the presence of high concentrations, the effects will be immediate, especially with its strong lachrymator action.

DP deployment almost surely indicates a purposeful, not an accidental, event. Industrial accidents have occurred with both chlorine and phosgene but not with DP, which is not a normal product of manufacturing processes. It also is relatively unstable and degrades easily into phosgene and chloroform. DP must be transported in glass (instead of metal) containers. No automatic detectors are available for use in the field.

Pathophysiology

Like phosgene, the principal feature of DP is delayed pulmonary edema. Although the mechanism is not entirely clear, edema may be caused by direct alveolar damage when DP breaks down into hydrochloric acid and carbon dioxide in the presence of water. DP also causes irritation of the upper respiratory tract and rarely can cause airway obstruction. Respiratory effects occur at doses of 1-10 ppm. Doses greater than 25 ppm can be rapidly fatal. Toxicity varies with both the concentration of vapor and the length of exposure. Because of DP's low water solubility, patients often inhale significant amounts of vapor before symptoms appear.

CLINICAL

Section 3 of 11  

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• Clinical
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• Follow-up
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• Multimedia
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History

• History likely reveals multiple casualties with respiratory complaints.
• Patients report irritation of the eyes or the skin.
• Victims likely will have been involved in a mass gathering or military event within the last 24 hours. Patients may report explosions, smoke, or a gas cloud. Patients inconsistently report the odor of newly mown hay.
• Exposure to low concentrations of DP causes chest discomfort or dyspnea.
• Exposure to somewhat higher concentrations tends to cause lacrimation and irritation of the eyes and skin.
• Exposure to high concentrations can quickly cause pulmonary edema with cough, dyspnea, and production of frothy sputum. Signs include tachypnea, rales, and decreased oxygen saturations.
• Further cardiopulmonary decompensation can occur from noncardiogenic pulmonary edema, with respiratory failure, hypotension, and death.
• Direct eye exposure to DP liquid can cause corneal abrasions, ulcers, or perforation. Direct skin exposure to DP liquid can cause burns.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Noncardiogenic pulmonary edema, etiology other than DP (distinguish from DP by history of mass casualties, knowledge of direct terrorist or military attack, history of gas exposure, or delayed onset of pulmonary edema following symptom onset)

WORKUP

Section 5 of 11  

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• Follow-up
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Lab Studies

• An arterial blood gas measurement may be useful to determine the degree of hypoxemia or acidemia in patients where endotracheal tube placement is in question. No laboratory test confirms DP exposure.

Imaging Studies

• A chest radiograph may initially appear normal but eventually reveals pulmonary edema with significant exposure. Because of the possibility of delayed pulmonary edema, a baseline chest radiograph should be considered prior to discharge.

Other Tests

• An ECG can be obtained to help ensure that the patient does not have cardiogenic pulmonary edema or stress-induced ischemia.

TREATMENT

Section 6 of 11  

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Prehospital Care

• Scene responders need to ensure their own safety when possible to prevent becoming victims themselves.
• Remove patients from the scene and move them to fresh air or administer oxygen if necessary.
• Terminate exposure by removing their clothing. Begin skin decontamination with soap and water.
• Pulmonary edema may be precipitated by exertion. Enforce strict bedrest if possible.

Emergency Department Care

• Begin or continue care as discussed in Prehospital Care above.
• Minimize exertion on the part of the patient so as to lessen the risk of delayed pulmonary edema.
• Administer standard resuscitation measures.
• • Patients can present with airway obstruction, although this situation is rare.
  • Acute pulmonary edema is common, and patients may require positive end-expiratory pressure if they are clinically in respiratory distress or frank failure. Avoid use of diuretics.
  • Patients also can present with hypotension; perform standard resuscitation with crystalloid fluids as first-line agents and vasopressors as second-line agents.
• Give bronchodilators to patients with bronchospasm.
• • Systemic steroids likely are not beneficial routinely for DP exposure, except in patients with bronchospasm not controlled by bronchodilators.
  • Some literature suggests using inhalational steroids for phosgene poisoning, which may lessen the severity of pulmonary edema. Similar regimens possibly may be used for DP inhalation. However, initiate treatment within a short time of exposure (15 min). One regimen uses dexamethasone and another uses betamethasone or beclomethasone in doses higher than that prescribed for asthma therapy.
• Eyes should be copiously irrigated with standard solutions and then assessed for visual acuity and corneal damage.
• Contact with liquid DP may produce chemical burns and, after thorough decontamination, may be treated with standard burn therapy.
• Antibiotics are unnecessary, prophylactically or therapeutically, unless a secondary infection is present.

Consultations

• Consult an ophthalmologist for a significant eye injury.
• Consult a pulmonologist in the event of significant respiratory exposure.

MEDICATION

Section 7 of 11  

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In general, follow decontamination with soap and water by symptomatic treatment.

Drug Category: Bronchodilator

This agent is used to relieve significant bronchospasm.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Admit patients who require resuscitation or oxygen supplementation.
• For at least 12 hours, observe patients with likely exposure who have minor symptoms or are asymptomatic, since delayed pulmonary edema is the classic feature of DP exposure.
• Counsel all patients with significant exposure to avoid strenuous activities for 72 hours and to return if significant respiratory symptoms develop.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Chemical Warfare and Personal Protective Equipment.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Early discharge with patient return in respiratory failure is the major pitfall in DP exposure. Patients with significant toxicity reportedly have presented up to 72 hours after exposure.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.
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Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
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• Follow-up
• Miscellaneous
• Multimedia
• References

• Chemical Casualty Care Division USAMRICD. Medical Response to Chemical Warfare and Terrorism. 3^rd ed. 1997:i-xiv, 1-8.
• Choking Agents. Defense Treaty Inspection Readiness Program. Available at http://dtirp.dtra.mil/CBW/references/agents/AgentsCW_choking.cfm. Accessed June 13, 2007.
• Compton JAF. Diphosgene. In: Military Chemical and Biological Agents. 1987:124-134.
• Givens M. Phosgene and toxic gases. In: Keyes DC, Burstein LJ, et al, eds. Medical Response to Terrorism, Preparedness and Clinical Practice. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005.
• Lillie SH, Hanlon E, Kelly JM, eds. Potential Military Chemical/Biological Agents and Compounds (FM3-11.9). Jan 2005.
• Micromedex. PoisinDex [Web site]. Phosgene. Accessed September 8, 2000.
• Nelson LS. Simple asphyxiants and pulmonary irritants. In: Goldfrank's Toxicologic Emergencies. 6^th ed. 1998:1523-1538.
• Traub SJ. Respiratory agent attack (toxic inhalational injury). In: Ciottone GR, Anderson PD, Auf Der Heide E, Darling RG, Jacoby I, Noji E, Suner S, eds. Disaster Medicine. 3^rd ed. Philadelphia, PA: Mosby/Elsevier; 2006:chap 93; 573-575.
• Urbanetti JS. Toxic inhalation injury. In: Textbook of Military Medicine. Part 1. 1997:247-270.
• US Army. Diphosgene. General Reimer Digital Library [Web site]. Accessed September 27, 2000.

Article Last Updated: Aug 7, 2007