Phosgene Toxicity

Updated: Jul 28, 2021
Author: Paul P Rega, MD, FACEP; Chief Editor: Zygmunt F Dembek, PhD, MS, MPH, LHD 


Practice Essentials

Phosgene is a highly toxic substance that exists as a gas at room temperature. Owing to its poor water solubility, one of the hallmarks of phosgene toxicity is an unpredictable asymptomatic latent phase before the development of noncardiogenic pulmonary edema. See the image below.

Anteroposterior portable chest radiograph in a mal 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.

Signs and symptoms

According to the National Institute for Occupations Safety and Health (NIOSH), a toxic level that can place a person’s life and well-being in jeopardy can be as low as 2 parts per million (ppm).[1] Exposure to moderate-to-high concentrations of phosgene (>3-4 ppm) can produce an immediate irritant reaction that typically lasts 3-30 minutes and includes the following:

  • Lacrimation
  • Conjunctival irritation/burning
  • Burning sensation in mouth/throat
  • Throat swelling/changes in phonation - May reflect laryngeal edema

Respiratory manifestations, which can develop relatively early at greater than 4.8 ppm,[2] usually do not develop until after a latent period lasting 4-24 hours postexposure. They consist of the following signs and symptoms:

  • Cough - Initially dry, then increasing frothy white/yellow sputum
  • Chest tightness, chest pain, or substernal burning
  • Dyspnea - Exertional early on, subsequently becomes present at rest
  • Altered taste sensation - If the patient is a smoker, metallic or unpleasant taste to cigarettes

Other signs and symptoms of this phase, which result primarily from hypoxemia or volume depletion, include the following:

  • Lightheadedness
  • Palpitations
  • Angina
  • Headache
  • Anorexia
  • Nausea, and vomiting
  • Weakness
  • Anxiety and sense of impending doom

On physical examination, respiratory findings may include the following:

  • Crackles on auscultation - Herald the onset of pulmonary edema
  • Cyanosis - Late finding
  • Thin, frothy white/yellow secretions
  • Wheezing
  • Tachypnea
  • Stridor
  • Accessory muscle use for respiratory effort

Cardiovascular findings may include the following:

  • Tachycardia
  • Hypotension - Late finding secondary to inflammation-mediated fluid diversion out of vascular system and into lung interstitium

Skin findings may include the following:

  • Cyanosis from pulmonary injury and resultant hypoxemia
  • Chemical burns from liquefied phosgene (although it also is considered a frostbite hazard in the compressed liquid form)

Three patients in China were exposed to an unknown concentration of phosgene gas in an industrial accident. Their immediate symptom was eye irritation, and they were properly decontaminated. However, the symptoms of cough, chest tightness, and dyspnea did not occur until 8-12 hours later.[2]

In another recent incident, a young Indian worker was exposed to phosgene gas at a pesticide manufacturing factory. Initial symptoms consisted of lacrimation, nausea, and a burning sensation in the mouth and throat with a dry cough. Six hours post exposure he began experiencing breathlessness. Twenty-four hours after exposure, he developed acute respiratory distress (pulse, 130/minute; respiratory rate, 36/minute; blood oxygen saturation [SpO2], 80% on room air), which ultimately required invasive airway management.[3]

See Clinical Presentation for more detail.


No test is diagnostic.[1] In addition, for patients who are asymptomatic despite a known recent phosgene exposure, no combination of laboratory or radiographic studies has been shown to discriminate reliably between those who remain asymptomatic and those who are in the latent phase and will later develop life-threatening pulmonary edema.

Useful tests include the following:

  • Pulse oximetry: Hypoxemia heralds onset of pulmonary edema
  • Arterial blood gases
  • CBC: Baseline study
  • Electrolytes: Baseline study
  • Cardiac enzymes: If cardiogenic pulmonary edema is strongly suspected

Findings on chest radiography are as follows:

  • Initial films may be normal
  • Early changes include hyperinflation and hilar enlargement
  • Later changes are typical for noncardiogenic pulmonary edema

See Workup for more detail.


Treatment that should be performed in the prehospital setting includes the following:

  • Patients exposed to liquid phosgene: Decontamination
  • Patients with ocular exposure: Eye flushes with saline or plain water for at least 15 minutes
  • Patients with dyspnea or chest tightness: Supplemental oxygen, cardiac monitor, symptomatic therapy, and expeditious transportation to a healthcare facility

In case of asymptomatic patients with suspected exposure to phosgene, monitor the patient for a minimum of 8-12 hours (many authors recommend 12-24 h[1] ) because of the potential for delayed-onset pulmonary edema. Reassess patients at least every 2 hours during the first 6 hours after exposure. Criteria for discharge after this observation time are as follows:

  • No symptoms
  • Clear lung ausculatory examination
  • Normal respiratory rate
  • Normal oxygen saturation
  • Normal chest radiograph

Treatment for symptomatic patients is as follows:

  • Focus on airway, breathing, and circulation
  • Proceed rapidly to intubation if necessary
  • Provide supplemental oxygen for dyspnea, hypoxia, or crackles
  • Provide positive-pressure ventilation
  • High inspired concentrations of oxygen and high PEEP settings may be necessary
  • Treat bronchospasm with standard doses of inhaled bronchodilators and inhaled anticholinergic agents such as albuterol and ipratropium bromide

Corticosteroids have been studied in various animal models and human cases, and no clear-cut evidence shows they are advantageous to the patient.[2, 3]

See Treatment and Medication for more detail.


Phosgene (COCl2) is a highly toxic gas or liquid that is classified as a pulmonary irritant. Exposure to phosgene gas produces delayed-onset noncardiogenic pulmonary edema. Immediate symptoms may occur with concentrations as low as 2-3 ppm (throat and eye irritation).[1, 2] This can be followed by a latent period, the duration of which depends on exposure to the chemical. The major pulmonary effects follow. Exposures to 50 ppm may be rapidly fatal. Management of phosgene toxicity is supportive, as no specific antidote or effective elimination process exists.

Phosgene is produced and utilized across numerous industries for chemical synthetic processes. Large-scale exposure may occur through industrial accidents. Small-scale exposures most often occur when phosgene is released by heating chlorinated hydrocarbons. Phosgene has been used in the past as a chemical weapon by warring nations and extremist groups. It could potentially be used as a weapon of mass destruction by any group with simple chemical synthetic capabilities or with the means to sabotage an existing industrial phosgene source.

The British chemist John Davy first synthesized phosgene in 1812 by combining chlorine gas and carbon monoxide with activated charcoal as a catalyst (CO + Cl2 → COCl2).[2] Synonyms for phosgene include the following:

  • Carbonic dichloride
  • Carbon oxychloride
  • Carbonyl dichloride
  • Chloroformyl chloride
  • D-stoff
  • Green Cross

The United Nations/Department of Transportation number for phosgene is UN#1076. The American Chemical Society's Chemical Abstracts Service (CAS) registry number for phosgene is #75-44-5.

Although it is typically colorless as a gas, phosgene may appear as a white cloud under conditions of concentrated release due to slow hydrolysis with airborne water vapor. Phosgene has a boiling point of 8°C (47°F) and thus exists as a gas at room temperature. Below the boiling point, it exists as a colorless fuming liquid. Vaporization is still significant at lower temperatures, making inhalational exposure possible even in cold conditions.

Phosgene is usually transported as a compressed liquefied gas. Direct contact with this form of the substance may produce frostbite injuries.

Although phosgene is nonflammable, it is strongly reactive and demonstrates electrophilic properties. It reacts with alkalis, ammonia, amines, copper, and aluminum. It can also attack plastics and rubber materials. Because phosgene is poorly soluble in water, it reacts minimally with oropharyngeal and conducting airway tissues and as a result can penetrate deeply into the lung, where it exerts its effects at the alveolar-capillary membrane (see Pathophysiology).

The odor of newly mown hay characterizes phosgene gas, but this olfactory warning signal may not be appreciated by all individuals. Since the odor detection threshold concentration is approximately 0.5-1.5 ppm, which is at least 5 times the permissive exposure limit of 0.1 ppm[4] set by the National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Government Industrial Hygienists (ACGIH), significant exposure may occur before any unusual scent is perceived.

This odor detection threshold approaches the NIOSH-defined immediately dangerous to life and health (IDLH) level of 2 ppm.[4] As a result, the odor of newly mown hay is an insufficient warning signal for dangerously high phosgene levels.[5] Other pulmonary irritant gases, such as chlorine, are so noxious that exposed persons flee the immediate area of release, but persons exposed to phosgene may inadvertently remain in a highly contaminated area, unaware that they are in any danger.

Because phosgene is 4 times denser than air, it tends to remain close to the ground and to collect in low-lying areas. This distribution of contamination should be considered when planning evacuation routes in the event of a phosgene release. Children may be at risk for higher exposure levels as a result of increased gas distribution closer to the ground. Children may also be at higher risk for severe exposure to this irritant gas due to their larger minute volume-to-weight ratios and their larger lung surface area–to–body weight ratios. Older people who have an inability to escape rapidly from the exposure also are at greater risk than the average younger adult.

Phosgene is used in the synthesis of plastics, pharmaceutical agents, isocyanates, polyurethanes, dyes, and pesticides. It is also used in the uranium enrichment process and in the bleaching of sand for glass production. Industries in the United States produce over 1 billion pounds of phosgene per year.

Unfortunately, industrial accidents involving phosgene are not uncommon. A phosgene-containing pipe rupture in 1994 in Yeochon, Korea, resulted in multiple injuries and 3 deaths. In 2000, a phosgene gas leak from a Thai plastics factory killed 1 person and injured 814 others. A laboratory accident involving inadvertent phosgene release in Fuzhou, China, in 2004 killed 1 person and injured more than 260 others.

Small-scale exposures to phosgene have also occurred, as phosgene is a product of thermal decomposition of chlorinated hydrocarbons.[6] Such agents include refrigeration coolants, dry cleaning fluids (carbon tetrachloride), metal degreasing agents (trichloroethylene), and paint strippers (methylene chloride).[7] When these chlorinated hydrocarbons are exposed to heat from a source such as a welding torch, a fire, or a heat gun, phosgene may be liberated.

Phosgene as a chemical weapon

Phosgene was used as a chemical weapon in World War I, first by the Germans and subsequently by French, American, and British forces. The term Green Cross derives from the marking on German artillery shells containing phosgene.

The initial World War I deployment of phosgene occurred when the Germans released approximately 4000 cylinders of gas against the British near Ypres on December 19, 1915. Because trench warfare typified much of World War I, heavier-than-air gases such as phosgene readily inflicted casualties in these low-lying areas.

From December 1915 to August 1916, casualties from phosgene exposure occurred in 4.1% of gas-exposed troops. Fatality from phosgene exposure occurred in 0.7% of gas-exposed troops. In this conflict, phosgene was often combined with chlorine in liquid-filled shells, so it is difficult to state the number of casualties and deaths attributable solely to phosgene. Total casualties from chemical gas exposure occurred in 1.2 million troops and caused 100,000 deaths. Phosgene accounted for an estimated 80% of these cases.[8]

Between the world wars, phosgene was assigned the military designation CG and was classified as a nonpersistent agent because of its rapid evaporation. Although stockpiled, it was never used in WW II.[1] In military publications, it has been referred to as a choking agent, pulmonary agent, or irritant gas.

The extremist cult Aum Shinrikyo used this agent to attack the Japanese journalist Shouko Egawa in 1994. Egawa had been reporting on the cult's activities, and the cult retaliated against her by introducing phosgene into her Yokohama apartment through the mail slot while she slept.


Phosgene interacts with biological molecules through two primary reactions: hydrolysis to hydrochloric acid and acylation reactions.[2] Because phosgene is poorly soluble in water, the hydrolysis reaction (COCl2 + H2 O → CO2 + 2 HCl) contributes far less to the typical clinical presentation, but this reaction is likely responsible for the mucous membrane irritant effects observed with exposure to high concentrations of phosgene.

The acylation reactions occur with amino, hydroxyl, and sulfhydryl groups on biological molecules, which attack the highly electrophilic carbon molecule in phosgene. These reactions can result in membrane structural changes, protein denaturation, and depletion of lung glutathione. Acylation reactions may be particularly important with phospholipids such as phosphatidylcholine, which is a major constituent of pulmonary surfactant and lung tissue membranes.

Studies in animal models have shown that exposure to phosgene vastly increases alveolar leukotrienes, which are thought to be important mediators of phosgene toxicity to the alveolar-capillary interface. Phosgene exposure also increases lipid peroxidation and free radical formation. These processes may lead to increased arachidonic acid release and thus provide more substrate for lipoxygenase (ie, more leukotriene production).

Levels of proinflammatory cytokines, such as interleukin-6, are also found to be substantially higher 4-8 hours after phosgene exposure.[9] Sodium-potassium–adenosine triphosphatase (Na-K-ATPase) dysfunction, resulting in increased oxidative stress and depletion of antioxidants, has also been demonstrated in mice exposed to phosgene.[10]

In addition, studies have shown that phosphodiesterase activity increases postexposure, leading to decreased levels of cyclic adenosine monophosphate (cAMP). Normal cAMP levels are believed to be important for maintenance of tight junctions between pulmonary endothelial cells and thus for prevention of vascular leakage into the interstitium.

On a physiologic level, the most important clinical effect of phosgene toxicity is the development of noncardiogenic pulmonary edema resulting from increased pulmonary vascular permeability due to the damaged alveolar-capillary interface. Up to 1 L/h of serum may leak out the circulation and into the alveolar septa.

Similar to other pathologic processes resulting in noncardiogenic pulmonary edema, this state is characterized by heavy, wet lungs that have low compliance. Oxygenation and ventilation both suffer, and the work of breathing is dramatically increased.

Arterial blood gases after severe phosgene exposure demonstrate low PaO2, decreased oxygen saturation, and often a respiratory acidosis due to impaired gas exchange. Pulmonary function tests show a markedly decreased vital capacity and an overall restrictive pattern. Alveoli may collapse, resulting in significant ventilation/perfusion (V/Q) mismatch, unless the patient receives ventilatory support with positive end-expiratory pressure (PEEP)


Phosgene exposure may result from any of the following[11] :

  • Small-scale accidental exposure involving the heating of chlorinated hydrocarbons
  • Fire exposure
  • Industrial accident
  • Industrial sabotage
  • Release as a weapon of mass destruction by extremist groups

Current literature describes exposures caused by the combustion products from chlorinated chemicals (eg, methylene chloride, trichloroethylene).[6] For example, use of methylene chloride, a commonly used chemical paint remover, near a heat source allows the release of phosgene. Phosgene is a breakdown product of chloroform that is stored for more than 6 months, even if the chloroform is stabilized with amylene.

Welding metals recently treated with degreasers, such as trichloroethylene, may produce phosgene.[12, 13, 14] Solvents used for degreasing purposes should be stored more than 200 feet from a welding arc, as the exposure to ultraviolet light can create phosgene by photodegradation. Phosgene exposure can also occur during the manufacture of aniline dyes, coal tar, certain resins, pesticides, polyurethane, and some pharmaceuticals.[3]

Any release of phosgene as a weapon of mass destruction would likely produce large numbers of casualties presenting simultaneously with similar symptoms. However, a large industrial accident could result in similar patient arrival patterns.

The use of phosgene as chemical warfare in a traditional military conflict is essentially of historical interest. The development of more effective agents and improved personal protective equipment make phosgene an unlikely agent to be used in future battles. Even in World War I, the German army switched to mustard gas in 1917 because of the development of effective gas masks.


According to OSHA, millions of kilograms of phosgene are produced annually, with 10,000 workers at risk of exposure. This does not include the large number of people that may have mild-to-moderate exposures in their homes from using solvents (eg, methylene chloride) with heat guns to remove paint.

Nevertheless, clinically significant phosgene exposure occurs infrequently. Sporadic exposures in recent years are related to industrial accidents or isolated.[15] In view of currently available war gases, which are much more lethal than phosgene, and improved respiratory protection, military use of phosgene is no longer considered a significant threat.


One of the hallmarks of phosgene toxicity is an unpredictable asymptomatic latent phase before the development of noncardiogenic pulmonary edema. Typically, the latent phase lasts 3-24 hours, but it may be as short as 30 minutes or as long as 48 hours after phosgene exposure. The duration of the latent phase is an extremely important prognostic factor for the severity of the ensuing pulmonary edema.

Patients with a latent phase of less than 4 hours before the onset of pulmonary edema have a poor prognosis.[8] Increased physical activity may shorten the duration of the latent phase and worsen the overall clinical course. Unfortunately, there are no reliable historical or physical examination findings during the latent phase to predict its duration.

Patients who survive the first 48 hours after phosgene exposure have a generally excellent prognosis. Clinical and radiographic improvement often occurs in 3-5 days. Patients who remain significantly ill beyond 5 days should be evaluated for a concurrent disease process such as superimposed infection. No data suggest carcinogenicity or reproductive/developmental hazards in association with phosgene exposure.

Many patients report ongoing exertional dyspnea for months or even years after phosgene exposure despite normalized chest radiographs. Some patients may develop reactive airway dysfunction syndrome (RADS), which is an irritant-induced reactive airway process. These patients may benefit from follow-up pulmonary function testing 2-3 months after phosgene exposure, possibly to include a methacholine challenge test.

Chronic low level exposure to phosgene (< 0.1 ppm) in a cohort of almost 800 workers at a uranium enrichment facility during World War II resulted in no documented increase in all-cause mortality or respiratory causes of mortality in 35 years of follow-up when matched with unexposed control workers at the same facility.


The Occupational Safety and Health Administration permissible exposure limit (OSHA PEL) for the workplace is 0.1 ppm (0.4 mg/m) as an 8-hour time weighted average. The level immediately dangerous to life or health (IDLH) is 2 ppm. Even a short exposure to 50 ppm may result in rapid fatality.

Another means to assess exposure and potential complications is using the inhaled dose instead of concentration alone. An inhaled dose of greater than 25 ppm-min leads to subclinical biochemical lung alterations, greater than 150 ppm-min causes overt alveolar edema, greater than 300 ppm-min is possibly lethal, and the level with 50% mortality is about 500 ppm-min.[5]

Morbidity and mortality are related to the degree of pulmonary insult and subsequent hypoxemia. Delayed diagnosis may result from delayed signs and symptoms. Underlying medical conditions contribute to the patient's ability to withstand the hypoxic insult. Chronic bronchitis and emphysema have been reported as a result of phosgene exposure.[16]

Patient Education

In the case of isolated exposures, instruct patients to avoid future exposures and to educate others involved in similar practices. Patients should minimize exertion for several weeks. Determining factors for return to the emergency department should include cough recurrence, dyspnea (especially resting dyspnea), and chest discomfort.

Resources are available through the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (ATSDR). For patient education information, see Chemical Warfare, Personal Protective Equipment, and Carbon Monoxide Poisoning.[6]




The diagnosis of phosgene toxicity depends largely on a history of exposure.[15] Consider phosgene toxicity in patients involved in the manufacture of dyes, resins, coal tar, and pesticides. Query patients regarding occupation and any exposure to chemicals, especially around sources of heat.[17] In the work setting and at home, phosgene can be produced by the combustion of methylene chloride (paint remover) or trichloroethylene (a degreasing solvent).

Although phosgene gas has the odor of newly mown hay, do not rely on the presence of that odor to substantiate a suspected phosgene exposure. Some persons cannot detect the smell of this agent, and the threshold for olfactory detection is well above dangerous exposure levels. The odor detection threshold concentration is approximately 0.5-1.5 ppm, which is at least 5 times the permissive exposure limit of 0.1 ppm set by the National Institute for Occupational Safety and Health (NIOSH).[4]

Patients typically have an asymptomatic period of 30 minutes to 72 hours after exposure, but in most cases of significant exposure the latent period is less than 24 hours. The duration and concentration of exposure determine the time to symptom onset.  Phosgene toxicity is thought to be more severe with short-duration, high-concentration exposures than long-duration, low-concentration exposures.[18]  

Phosgene toxicity can produce an immediate irritant reaction likely caused by the hydrolysis of phosgene to hydrochloric acid on mucous membranes. This reaction occurs only in the presence of high concentrations of phosgene (>3-4 ppm), typically lasts 3-30 minutes, and does not have any prognostic value for the timing and severity of later respiratory symptoms. The most important aspect of this stage is a laryngeal irritant reaction causing laryngospasm, which may lead to sudden death

The immediate irritant reaction to phosgene gas includes the following:

  • Lacrimation
  • Conjunctival irritation/burning
  • Burning sensation in mouth/throat
  • Throat swelling/changes in phonation - May reflect laryngeal edema

If the patient was sweating or wearing wet clothing at the time of exposure, the irritant reaction may also include a burning sensation on the skin. Like the airway reaction, this is caused by the breakdown of phosgene to hydrochloric acid.

Respiratory manifestations, which usually develop 4-24 hours postexposure, consist of the following signs and symptoms:

  • Cough - Initially dry, then increasing frothy white/yellow sputum
  • Chest tightness, chest pain, or substernal burning
  • Dyspnea - Exertional early on, subsequently becomes present at rest
  • Altered taste sensation - If the patient is a smoker, metallic or unpleasant taste to cigarettes

Other signs and symptoms of this phase, which result primarily from hypoxemia or volume depletion, include the following:

  • Lightheadedness
  • Angina
  • Headache
  • Anorexia
  • Nausea, and vomiting
  • Weakness
  • Anxiety and sense of impending doom

Physical Examination

Physical examination is useful with patients with active symptoms. Patients who relate a recent exposure may be in the latent phase and have no specific findings related to the exposure.

Head, ears, eyes, nose, and throat (HEENT) examination in patients with symptomatic phosgene toxicity may reveal the following:

  • Conjunctival injection and lacrimation
  • Nasal mucosa hyperemia associated with rhinorrhea
  • Oropharyngeal hyperemia and salivation
  • Altered phonation

Significant injury may occur to the lower airways without upper airway involvement. Respiratory findings may include the following:

  • Crackles on auscultation - Herald the onset of pulmonary edema
  • Cyanosis - Late finding
  • Thin, frothy white/yellow secretions
  • Wheezing
  • Tachypnea
  • Stridor
  • Accessory muscle use for respiratory effort

Cardiovascular findings may include the following:

  • Tachycardia
  • Hypotension - Late finding secondary to inflammation-mediated fluid diversion out of vascular system and into lung interstitium

Skin findings may include the following:

  • Cyanosis from pulmonary injury and resultant hypoxemia
  • Chemical burns from liquefied phosgene (although it also is considered a frostbite hazard in the compressed liquid form)




Approach Considerations

In patients who are asymptomatic despite recent phosgene exposure, no combinations of laboratory or radiographic studies have been shown to discriminate reliably between those who remain asymptomatic and those who are in the latent phase and will later develop life-threatening pulmonary edema. Initial findings on chest radiography may be normal, but radiographic findings may evolve rapidly over the first few hours after phosgene exposure. Pulse oximetry measurements remain normal during the latent phase, but it is useful for following progression over several hours of observation. Increase the triage priority and level of intervention if the oxygen saturation begins to decline, as hypoxemia heralds the onset of pulmonary edema.

Arterial blood gas measurements may be normal during the latent phase but are useful for following progression of manifest illness after the onset of pulmonary edema. In addition, arterial blood gas measurements may be useful for making adjustments in respiratory care therapy (ventilator settings). Acidosis typically occurs, initially as a respiratory acidosis, but later becoming a mixed acidosis due to anaerobic metabolism in the wake of profound tissue hypoxia.

In patients who develop hypoxemia, a partial pressure of oxygen (pO2) as low as 23 mm Hg on 8 L/min of oxygen by face mask has been reported. Typical presenting pO2 levels are 50-60 mm Hg while breathing room air. The carboxyhemoglobin level is important for cases involving exposure to methylene chloride or when carbon monoxide exposure is suspected. Methemoglobinemia may suggest other causes.

A complete blood cell count (CBC) may be obtained as a baseline level or if pneumonia is high on the differential diagnosis list. An elevated white blood cell count is not specific because it may result from hypoxemic stress or an infectious process. The CBC may reveal hemoconcentration late in the disease process, due to third-spacing of fluid into lungs once pulmonary edema has occurred, but this test is of little value prognostically.

A 2009 study noted that levels of secreted phospholipase A2 (sPLA-IIA) found on bronchial alveolar lavage increased markedly after phosgene exposure, peaking at 6 hours, and correlated well with severity of lung injury in the study population. While not specific for phosgene exposure, measurement of sPLA-IIA in bronchial lavage is a potential future measurement for the progression of lung injury from phosgene exposure.[19]

Electrolytes may be obtained as baseline studies because of the anticipated large fluid shifts that occur. Cardiac enzymes (eg, creatine kinase-MB [CK-MB], troponin T, troponin I) may be obtained if cardiogenic pulmonary edema is high on the differential.

Chest Radiography

Initial findings on chest radiography may be normal. Radiographic findings may evolve rapidly over the first few hours after phosgene exposure, however. Using a low-energy exposure technique (50-80 kV) may facilitate early identification of evolving pulmonary edema, while the patient is still asymptomatic (as early as halfway through the latent period).

Early changes include hyperinflation and hilar enlargement. Later changes are typical for noncardiogenic pulmonary edema: fluffy "batwing" perihilar interstitial infiltrates. See the images below.

British machine-gunners in anti-phosgene masks, So British machine-gunners in anti-phosgene masks, Somme, 1915. Courtesy of the Imperial War Museum, London.
The chest radiograph of a 42-year-old woman chemic The chest radiograph of a 42-year-old woman chemical worker 2 hours after exposure to phosgene. Dyspnea progressed rapidly over the second hour; PO2 was 40 mm Hg breathing room air. This radiograph shows bilateral perihilar, fluffy, and diffuse interstitial infiltrates. The patient died 6 hours postexposure. Used with permission from Medical Aspects of Chemical and Biological Warfare, Textbook of Military Medicine, 1997, p 258.

In patients without preexisting cardiac disease, the heart silhouette should be normal. A chest radiograph may help exclude other possibilities in the differential diagnosis (pneumothorax, pneumonia, hemothorax, pleural effusion). Chest radiographs clear over several days as clinical improvement occurs.



Approach Considerations

Phosgene is a ubiquitous industrial product and exposures may occur at any time due to an accident, which is a more likely scenario than its use as a weapon. Emergency departments (EDs) should plan for such hazards in conjunction with local emergency planning committees/hazardous materials (HAZMAT) teams and to conduct appropriate training.

Prehospital and ED personnel should become educated about the hazards involved with liquid phosgene and should be trained in the appropriate personal protective equipment needed to work with phosgene-exposed patients. Prehospital personnel should be trained in the protection against exposure to phosgene gas at accident scenes.

Notify appropriate community authorities (HAZMAT, law enforcement, health department) of suspected phosgene exposure in a scenario where community health may be at risk.

In a case of suspected exposure to phosgene, monitor the patient for a minimum of 8-12 hours because of the potential for delayed-onset pulmonary edema. The patient must remain asymptomatic and have no chest x-ray changes or hypoxemia after observation to be released from the ED or inpatient ward.

Perform endotracheal (ET) intubation and mechanical ventilation based on the degree of respiratory failure and overall clinical picture. Lower tidal volumes and increased positive end-expiratory pressure (PEEP) may result in improved oxygenation and reduced mortality.

Management of phosgene toxicity is supportive. Bronchodilators are indicated for patients with evidence of bronchospasm. Corticosteroids (inhaled, systemic) have been recommended, but no solid evidence supports their efficacy. Prophylactic antibiotics and antifungals may be used because of the risk of superinfection. Pressor agents may be required to treat hypotension, bradycardia, and renal failure. Other agents (eg, leukotriene inhibitors, N -acetylcysteine, angiopoietin-1) have shown benefit in animal studies.[2, 20]

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.

Prehospital Care

Rescuer safety is paramount.[21] 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 and uphill from the exposure source).

To care for patients with liquid phosgene exposure, prehospital or HAZMAT personnel should be attired in at least level B protection, as follows:

  • Full face mask with either supplied air respirator or preferably self-contained breathing apparatus (SCBA) [22]
  • Butyl rubber gloves
  • Chemical protective suit
  • Chemical resistant protective overboots

The National Institute for Occupational Safety and Health (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.[23] Patients should use soap and water to wash their hair and all body surfaces, with care to avoid unnecessary hypothermic stress (especially in the very young and very old). Warm water, warm blankets, and dry uncontaminated clothing are essential. For more information on this topic, 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. Anticipate rapid in-transport deterioration of the patient with phosgene-induced pulmonary edema. Strongly consider pretransport intubation and mechanical ventilation.

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. 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.

If the patient reports dyspnea or chest tightness, begin therapy with supplemental oxygen. Severe exposures may require endotracheal intubation and suctioning. If a significant bronchospastic component is present, bronchodilators may be used with caution.[21, 23]

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.

Past wartime experience has demonstrated that in a mass casualty situation, patients with phosgene exposure should be triaged as requiring immediate care because of the impending need for intubation and PEEP to maintain distal airway opening.[24]

Emergency Department Care

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 Chemical, Biological, Radiological, Nuclear, and Explosives (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.

Be wary of discharging asymptomatic patients during the latent phase after phosgene exposure. Patients who later develop severe pulmonary edema may be completely asymptomatic shortly after exposure.

Asymptomatic patients require a minimum of 8 hours of observation, and many authors recommend 12-24 hours of observation before discharge. Enforce rest of asymptomatic patients during the latent period, as exertion worsens the clinical course of phosgene toxicity.

Criteria for discharge after this observation time are as follows:

  • No symptoms
  • Clear lung ausculatory examination
  • Normal respiratory rate
  • Normal oxygen saturation
  • Normal chest radiograph
  • Good support system (physical, mental)
  • Secure transportation

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. Reassess patients at frequent intervals—at least every 2 hours during the first 6 hours after exposure. Hourly reassessment would be preferred, and some authors recommend repeating vital signs and lung ausculatory examinations every 30 minutes.

Triage depends, in part, on the availability of high-level critical care and ventilators for patients with severe pulmonary edema. It is The possibility may arise that the number of victims may be greater than the number of immediately available ventilators. Upon knowledge of a phosgene attack having occurred, it is incumbent on local authorities (eg, medical, public health) to realize the potential for inadequate resources over time and secure additional resources through their local and state emergency management agencies, the Federal Emergency Management Agency (FEMA), and the Strategic National Stockpile (SNS). In the meantime, the exposed, asymptomatic victims, in order to preserve local resources, may be transferred, with appropriate personnel, to alternative venues where resources are more readily accessible, keeping and caring for the symptomatic victim in situ.

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

However, this triage scheme is, arguably, more an indication of poor planning than proper triage. To label a victim who has pulmonary edema, hypotension, and/or cyanosis as “expectant” is depriving that person of acute classic medical care because the local healthcare infrastructure is declaring there is virtually no hope of resources arriving in days, weeks, or months. This could be the case with a nuclear war or a 1918-like pandemic, but an intentional phosgene gas attack, while inflicting scores of casualties, is still a limited event encircled by untouched regional resources. Since phosgene toxicity has a latency period, there is time, albeit short and stressful, to marshal those resources expeditiously.

Ensure that 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 ED by staff members in appropriate protective equipment (level B or higher). A decontamination shower unit may be used.[21, 22]

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.

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.

In many cases, high inspired concentrations of oxygen and high 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 ventilation/perfusion 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.

Minimize fluid administration except when it is needed to correct hypotension. Pulmonary artery catheter monitoring may be required to maintain appropriate fluid balance while treating hypotension caused by fluid shifts. Avoid diuretics because the patient typically is volume-depleted from fluid shifts. Extracorporeal membrane oxygenation (ECMO) may be considered for patients with respiratory impairment refractory to supportive care.

Pharmacologic Treatment

Bronchodilators may improve existing bronchospasm. Prophylactic antibiotics have been recommended by some authors based on the findings of pneumonia and bronchitis in virtually all autopsy specimens. Corticosteroid administration postexposure remains controversial.

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.[25, 26] Nebulized sodium bicarbonate treatment theoretically may be beneficial; however, consider it as second line after the drugs noted above.

Tomelukast, a leukotriene receptor antagonist, prevents pulmonary edema in phosgene-exposed rabbits. Experimentally, ibuprofen has been shown to reduce phosgene-induced pulmonary edema.[27] In mouse studies, colchicine and cyclophosphamide have reduced neutrophil influx, lung injury, and mortality when administered 30 minutes following phosgene exposure.[28]

Intratracheal dibutyryl cyclic adenosine monophosphate (DBcAMP), a cyclic adenosine monophosphate (cAMP) analogue, inhibits the release of leukotrienes that contribute to the disease process.[29, 30] In phosgene-exposed rabbits, terbutaline and aminophylline (cAMP enhancers) limit the pulmonary capillary leakage. In addition, intratracheal N -acetylcysteine administered to rabbits 45 minutes postexposure reduces leukotriene formation and pulmonary edema.[31] Theoretically, nebulized N -acetylcysteine also should be effective.

Inpatient Care

Patients with phosgene-induced pulmonary edema should be admitted to a critical care setting. These include all phosgene-exposed persons with crackles on ausculatory examination, chest radiograph abnormalities consistent with pulmonary edema, hypoxemia, or tachypnea.

Patients with pulmonary edema will require ongoing supplemental oxygen therapy and likely will require positive pressure ventilation, either noninvasively through CPAP or BiPAP or invasively through endotracheal intubation and mechanical ventilation. Intubated patients are likely to require frequent suctioning due to copious secretions.

Patients with ongoing symptoms of dyspnea but no objective abnormalities on examination, radiograph, or vital signs should be hospitalized for observation until they declare themselves as either improving or worsening. Improvement typically occurs within 48-72 hours.[21] Improving patients may be discharged, and worsening patients should be admitted to a critical care setting for continued monitoring and supportive care.

Inpatients should be considered for bronchodilator therapy and possibly for systemic steroids as described above. Diuretics should probably be avoided, and antibiotics should be used only in the presence of a documented infection.


Patients with phosgene-induced noncardiogenic pulmonary edema require hospitalization in a critical care setting. If a local hospital cannot provide such care, then transfer must be arranged by direct physician-to-physician contact with a critical care provider at another institution. Critical care capable transport should be used (advanced cardiac life support [ACLS] ambulance or helicopter with capability for mechanical ventilation).

En route deterioration should be anticipated since the pulmonary edema is often rapidly progressive. For patients who are already significantly ill, consideration should be given to pretransfer intubation, sedation, and mechanical ventilation.


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 and a medical toxicologist.

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 Centers for Disease Control and Prevention (CDC) Chemical Emergencies Web page and the National Response Center (for reporting chemical spills).

Long-Term Monitoring

Patients may be discharged after an appropriate observation period (8-12 h if the patient has a clear chest radiograph, 24 h in a setting without chest radiography capability) if they are asymptomatic, have normal vital signs, and have a clear ausculatory examination. Patients need good follow-up care instructions with precautions to return if they develop symptoms. A preprinted patient information sheet and discharge instructions are available from CDC/Agency for Toxic Substances and Disease Registry (ATSDR ).

Discharged patients require no medications since they are asymptomatic. Previously diagnosed asthmatic patients should continue to take their inhaled steroids and inhaled bronchodilators as prescribed.

Instruct patients discharged from the hospital after recovery from pulmonary edema to avoid exertion and any pulmonary toxins that may precipitate a recurrence. Also, instruct patients to avoid circumstances similar to their exposure and to warn others of the same dangers.



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. 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.

Guidelines from the Centers for Disease Control and Prevention through the Agency for Toxic Substances and Disease Registry recommend intravenous corticosteroids in cases of severe phosgene exposure even if the patient is asymptomatic.[32] Some authors recommend both inhaled and systemic steroids for all phosgene-exposed patients, while others recommend steroids only in patients with pre-existing reactive airway disease. The recommended regimen is methylprednisolone 1 g IV with a taper over the following several days.[33]

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 the following:

  • Intratracheal isoproterenol
  • Parenteral ibuprofen
  • Intratracheal N -acetylcysteine
  • Parenteral aminophylline
  • Subcutaneous terbutaline
  • Colchicine
  • Parental leukotriene receptor blockers

Many of these agents and delivery routes show promise in terms of the following:

  • Decreased pulmonary edema
  • Increased levels of reduced glutathione
  • Decreased production of lipid peroxidation products
  • Decreased leukotriene production
  • Maintenance of tissue cyclic adenosine monophosphate (cAMP) levels

However, 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.


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. 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. Treatment lasting more than 1 week may require a taper to prevent abrupt steroid withdrawal.

Methylprednisolone (Solu-Medrol)

Methylprednisolone decreases inflammation by suppressing migration of polymorphonuclear neutrophils (PMNs) and reversing increased capillary permeability.

Beclomethasone (Beclovent, Vanceril)

Beclomethasone inhibits bronchoconstriction mechanisms, producing direct smooth muscle relaxation. It may decrease number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness.

Betamethasone (Celestone, Soluspan)

Betamethasone decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability.

Beta2 Agonists

Class Summary

Patients with hyperactive airways usually benefit from aerosolized bronchodilator therapy.

Albuterol (Proventil, Ventolin)

Albuterol relaxes bronchial smooth muscle by its action on beta 2-receptors. It has little effect on cardiac muscle contractility.


Class Summary

Vasopressors are used to treat hypotension, bradycardia, or renal failure.

Dopamine (Intropin)

Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect depends on the dose; lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Use low doses to protect renal function; use high doses to combat severe hypotension unresponsive to fluid administration.

Leukotriene antagonists

Class Summary

These agents reduce the inflammatory response elicited by the leukotriene cascade. Leukotriene antagonists are approved by the 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, this agent should be considered for first-line therapy. In the presence of food, bioavailability of oral zafirlukast is decreased by 40%. Administer on an empty stomach.