Background

Pulmonary agents (also referred to as toxic industrial chemicals and choking agents) hold historical significance as the forerunners of modern chemical warfare and still hold relevance today as likely chemical culprits given their availability. Chlorine and phosgene are produced and stored in large quantities worldwide, and could have devastating effects when vaporized. There are other agents which can produce chemical lung injury such as ammonia, hydrogen sulfide, zinc oxide, phosphorus smokes, and perfluoroisobutylene (by-product of Teflon). These agents are irritating to the lungs, but are less likely to be used in a chemical attack.

Chlorine becomes a gas at -34 ° C, and is therefore stored as a compressed liquid.  Phosgene becomes a toxic gas at 47 °F.  The extent of injury caused by either gas is a function of the duration and concentration of exposure.  Other variables that impact toxicity include respiratory rate and depth (minute ventilation) and possibly body position.

Exposures to 30ppm of chlorine will cause coughing; more serious damage to the lungs occurs at levels above 40 to 60ppm for more than 30 minutes. Phosgene is more surreptitious and toxicity may occur below its odor threshold of 0.4ppm with prolonged exposure. Additionally olfactory fatigue can occur so an individual may only transiently notice the warning odor. Phosgene IDHL (Immediately Dangerous to Life or Health) is 2ppm whereas chlorine IDHL is 100ppm.

Both gases react with moisture in the respiratory system and undergo hydrolysis. Chlorine causes lung damage through reactions to form hydrochloric and hypochlorous acids, which in turn react with sulfhydryl groups of cysteine and cause enzyme inhibition. In addition to this reaction, hydrolysis of chlorine results in free radical generation that can lead to direct cell injury and death. Phosgene also reacts with water to form carbon dioxide and hydrogen chloride. However, the major toxicity of phosgene is believed to occur through acylation in which phosgene interacts with sulfhydryl, amine, and hydroxyl groups causing protein and lipid denaturation, disruption of membrane structure and interference with enzyme function. Phosgene also disrupts the pulmonary surfactant layer.

Pulmonary Agent Signs and Symptoms

Both gases have the ability to cause asphyxia due to displacement of oxygen if released in a confined space. More commonly, the gases act as irritants and cause damage to the respiratory tract through the mechanisms described above. Lastly, the gases can cause a systemic inflammatory response.

Chlorine has an unpleasant odor and is highly irritating. Because chlorine undergoes more rapid hydrolysis when contacting mucous membranes, it causes more immediate symptoms in the moist areas of the eyes, mouth, and upper airways. Eye pain, blepharospasm, and lacrimation are common. Other symptoms may include headache, salivation, dyspnea, cough, hemoptysis, chest burning, and vomiting.

Physical examination may reveal tachycardia, tachypnea, and possibly cyanosis. If eye irritation is present, evaluation for corneal burns/abrasions should be done with fluorescein staining of the eye. In the presence of oropharyngeal erythema, there may be more significant distal injury requiring careful assessment of the airway.  Stridor, hoarseness, or aphonia may indicate laryngeal edema or laryngospasm. Oropharyngeal secretions may be copious.

Phosgene smells of fresh mown hay. It has more insidious effects, and early symptoms may be mild or absent. Typical onset of phosgene-induced symptoms occurs 2 to 6 hours after exposure and delayed symptoms have been described up to 15 hours post exposure. The major effects of phosgene are on peripheral airways, therefore dyspnea, chest tightness or pain, and cough are common symptoms. Development of hypoxia and pulmonary edema may occur hours after the onset of symptoms. Fluid shifts secondary to pulmonary edema may result in hypovolemia.  Early onset of pulmonary edema portends a grave prognosis.

Pulmonary Agent Decontamination

Safe removal from the toxic gas is the priority in chlorine or phosgene exposure. Respiratory protection for rescuers and providers in a potential exposure area is critical. Once the casualty is removed from the exposure area, decontamination should be continued with removal of all clothing. For toxic gas exposure, this removes the majority of risk from the gases.  Soap and water is adequate to complete decontamination.

Pulmonary Agent Diagnostics

There are no readily available diagnostic tests to confirm or quantify pulmonary agent toxicity. Standard tests such as arterial blood gases and chest x-rays (CXR) should be used to guide supportive care as needed. Arterial blood gases can be useful when needed to follow oxygenation, but may be normal in the early phases of phosgene exposure. PCO2 may be elevated in patients with obstructive pathophysiology and indicate a need for bronchodilators or corticosteroids.

Much like ABGs, CXR performed shortly after exposure may be normal but the patient may progress to frank pulmonary edema within a few hours. Fortunately the CXR can reveal pulmonary edema before clinical exam findings.  A baseline CXR may be useful for comparison when trying to detect subtle early findings of pulmonary edema. If the CXR is normal at 8 hours, it is unlikely the patient will develop pulmonary edema.³⁷