CG
Signs and Symptoms: eye and airway irritation, dyspnea, chest tightness, and delayed pulmonary edema.
Detection: odor of newly mown hay or freshly cut grass or corn. Neither the M256A1 detector kit nor chemical-agent detector paper (M8 paper, M9 paper) is designed to identify phosgene, but the MINICAMS, Monitox Plus, Draeger tubes, Individual Chemical Agent Detector (ICAD), M18A2, M90, and M93A1 Fox will detect small concentrations of this gas.
Decontamination: vapor - fresh air; liquid - copious water irrigation.
Management: termination of exposure, ABCs of resuscitation, enforced rest and observation, oxygen with or without positive airway pressure for signs of respiratory distress, other supportive therapy as needed. Summary Review and Summary - Therapy
Inhalation of selected organohalides, oxides of nitrogen (NOx), and other compounds can result in varying degrees of pulmonary edema, usually after a symptom-free period that varies in duration with the amount inhaled. Chemically induced, acute lung injury by these groups of agents involves a permeability defect in the blood-air barrier (the alveolar-capillary membrane); however, the precise mechanisms of toxicity remain an enigma. The United States produces over a billion pounds of phosgene (CG) per year for industrial uses; however, we do not stockpile this agent for military use.
Perfluoroisobutylene (PFIB) is a toxic pyrolysis product of tetrafluoroethylene polymers encountered in military materiel (e.g., Teflon®, found in the interior of many military vehicles). The oxides of nitrogen (NOx) are components of blast weapons or may be toxic decomposition products. Smokes (e.g., HC) contain toxic compounds that cause the same effects as phosgene. The remainder of this chapter will deal solely with phosgene because it is the prototype of this class of agents; however, the principles of medical management of phosgene exposure also apply to casualties from compounds such as PFIB or NOx.
John Davy first synthesized phosgene in 1812. Subsequent development as a potential chemical warfare agent led to the first battlefield use of phosgene (in shells filled solely with phosgene) at Verdun in 1917 by Germany. Later, both sides in the conflict employed phosgene either alone or in mixed-substance shells, usually in combination with chlorine. Although military preparations for World War II included the manufacture and stockpiling of phosgene-filled munitions, phosgene was not used during that war, and the United States Armed Forces do not currently stockpile this agent.
PHYSICOCHEMICAL CHARACTERISTICS
Phosgene is transported as a liquid. Military dispersion during World War I followed the explosion of liquid filled shells with subsequent rapid vaporization and formation of a white cloud due to its slight solubility in an aqueous environment. It spontaneously converted to a colorless, low-lying gas four times as dense as air. Because of its relatively low boiling point (7.5oC), phosgene was often mixed with other substances. It has a characteristic odor of sweet, newly-mown hay.
Physical Properties of Phosgene
The immediately-dangerous-to-life-and-health (IDLH) concentration of phosgene is 2.0 parts per million (ppm). The M256A1 kit, M272 water-testing kit, M8 paper, M9 paper, Chemical Agent Monitor (CAM), Automated Continuous Air Monitoring System (ACAMS), M8A1 automatic chemical-agent detector alarm, and Depot Area Air Monitoring System (DAAMS) are all incapable of detecting phosgene (CG); however, the following detectors have the capacity to detect it at the threshold limits given:
| DETECTOR |
CG |
| MINICAMS |
50 ppbv |
| Monitox Plus |
0.25 TWA |
| Draeger |
0.02 - 0.6 ppm |
| ICAD |
25.0 mg/m3 |
| M18A2 |
12.0 mg/m3 |
| M90 |
>50 ppm |
| M93A1 Fox |
115 mg/m3 |
Because the odor of phosgene may be faint or lost after accommodation, olfactory detection of the odor of newly mown hay is not a reliable indicator of phosgene exposure. The eye irritation, coughing, sneezing, hoarseness, and other central respiratory effects seen after exposure to high concentrations are also unreliable guides to phosgene exposure, especially at lower but still lethal concentrations when they may be transient or entirely absent.
The activated charcoal in the canister of the chemical protective mask adsorbs phosgene, and the mask affords full protection from this gas.
The pulmonary agents are absorbed almost exclusively by inhalation. Because they are gases, they readily penetrate to the level of the respiratory bronchioles and the alveoli, that is, to the peripheral compartment of the respiratory tree. However, most of these agents are essentially consumed by reactions occurring at the alveolar-capillary membrane or more proximally in the respiratory tract and are not systemically distributed to a clinically significant extent.
The odor threshold for phosgene is about 1.5 mg/m3, and phosgene irritates mucous membranes at 4 mg/m3. The LCt50 of phosgene is approximately 3200 mg·min/m3, which is half the LCt50 (6,000 mg·min/m3) of chlorine, the first gas used on a large scale in World War I. Since only half as much phosgene is required to kill half of an exposed group, phosgene is thus twice as potent as chlorine. That it is less potent than almost all of the subsequently developed chemical warfare agents should not lead to an underestimation of its danger; deaths have occurred after the inhalation of only a few breaths of high concentrations of phosgene. Perfluoroisobutylene is ten times more toxic than phosgene.
TOXICODYNAMICS (MECHANISM OF ACTION)
Chemicals that are highly reactive or highly soluble in aqueous solutions (or both) tend to act in the conducting, or central compartment, of the respiratory tract. Most of the pulmonary agents are relatively insoluble and nonreactive compared to centrally acting irritants such as ammonia and hydrochloric acid, which cause pronounced irritation of the epithelial cells lining the upper airway on inhalation. Additionally, at low concentrations, they are essentially consumed by deposition and reaction in the conducting airways before having the chance to reach the peripheral portion of the respiratory tract. Peripherally acting agents such as phosgene, oxides of nitrogen, and PFIB are still largely unreacted by the time they reach the alveoli and the alveolar-capillary membranes, where they then undergo acylation reactions and are essentially consumed at that site, causing the damage that may eventually lead to pulmonary edema (see the section on toxicodynamics). However, it should be emphasized that the distinction between centrally and peripherally acting agents is not a strict either/or dichotomy. Centrally acting irritants such as hydrochloric acid (and the chemical warfare vesicants sulfur mustard and Lewisite, to be discussed in a subsequent chapter) when administered in high enough concentrations will not be entirely used up by reactions in the nasopharynx, trachea, bronchi, and large to medium-sized bronchioles. Enough of these agents may remain to act peripherally to cause pulmonary edema. Similarly, high concentrations of peripherally acting agents can release enough hydrochloric acid to cause significant central airway irritation and epithelial damage. Moreover, agents such as chlorine are approximately midway between the two poles of this spectrum. Chlorine-exposed soldiers in World War I usually exhibited both central airway damage and pulmonary edema, even from moderate concentrations of the gas.
Phosgene is only slightly soluble in water and aqueous solutions; however, once dissolved, it rapidly hydrolyzes to form carbon dioxide and hydrochloric acid. The early onset ocular, nasopharyngeal, and central airway irritation from high concentrations of phosgene results from the release of hydrochloric acid during phosgene hydrolysis by water in the upper airways. However, the carbonyl group (C=O) of phosgene can undergo acylation reactions with amino (-NH2), hydroxyl (-OH), and sulfhydryl (-SH) groups, and these reactions account for the major pathophysiological effects of phosgene. Acylation occurs at alveolar-capillary membranes and leads to leakage of fluid from those capillaries into the interstitial portions of the lung. This effect is from direct contact of phosgene with these membranes; phosgene exposure by other routes, e.g., intravenous administration, does not cause this damage. Mechanism of Injury for Phosgene
Phosgene-induced leakage of fluid from capillaries into the pulmonary interstitium is normally opposed by lymphatic drainage from the parenchyma, but as the fluid leakage increases, normal drainage mechanisms become progressively overwhelmed. After an asymptomatic or latent period of 20 minutes to 24 hours or longer, fluid eventually reaches alveoli and peripheral airways, leading to increasingly severe dyspnea and clinically evident pulmonary edema.
(Mild Exposure, Extreme Exposure)
Phosgene produces pulmonary edema following a clinical latent period of variable length that depends primarily on the intensity of exposure (i.e., the Ct), but also partly on the physical activity of the exposed individual. After the latent period, the patient experiences worsening respiratory distress that at first is unaccompanied by objectively verifiable signs of pulmonary damage, but may progress relentlessly to pulmonary edema and death.
During the time preceding the appearance of shortness of breath, individuals exposed to particularly high concentrations of organohalides may report symptoms associated with mucous membrane irritation. Exposure to large quantities of phosgene may irritate moist mucous membranes, presumably because of the generation of hydrochloric acid from the hydrolysis of phosgene. Transient burning sensation in the eyes with lacrimation and chemical conjunctivitis may coexist with mild, early onset cough and a substernal ache with a sensation of pressure. Irritation of the larynx by very large concentrations of the agent may lead to sudden laryngeal spasm and death.
A clinical latent period during which the patient is asymptomatic may follow low Ct exposure or the transient irritation associated with substantial phosgene exposure. This asymptomatic period may persist up to 24 hours after organohalide inhalation. The duration of this latent period is shorter following high Cts and is shortened by physical exertion following exposure.
The most prominent symptom following the clinical latent period is dyspnea, perceived as shortness of breath, with or without chest tightness. These sensations reflect hypoxemia, increased ventilatory drive, and decreased lung compliance, all of which result from the accumulation of fluid in the pulmonary interstitium and peripheral airways. Fine crackles appear at the lung bases, but these may not be clearly audible unless auscultation is conducted after a forced expiration. Later, auscultation reveals coarse crackles and râles in all lung fields, and increasing quantities of thin, watery secretions are noted. The buildup of fluid in the lungs has two clinically pertinent effects. First, developing pulmonary edema interferes with oxygen delivery to alveolar capillaries and may lead to hypoxemia, and if a sufficient percentage of hemoglobin is unoxygenated, cyanosis will become apparent. Secondly, the sequestration of plasma-derived fluid (up to one liter per hour) in the lungs may lead to hypovolemia and hypotension, interfering with oxygen delivery to the brain, kidneys, and other crucial organs. Death results from respiratory failure, hypoxemia, hypovolemia, or a combination of these factors. Hypoxia and hypotension may progress particularly rapidly and suggest a poor prognosis. The development of symptoms and signs of pulmonary edema within four hours of exposure is an especially accurate indicator of a poor prognosis; in the absence of immediately available intensive medical support, such patients are at high risk of death. Complications include infection of damaged lungs and delayed deaths following such respiratory infections.
Phosgene is distinguished by its odor, its generalized mucous membrane irritation in high concentrations, dyspnea, and pulmonary edema of delayed onset.
Riot-control agents produce a burning sensation predominantly in the eyes and upper airways. This irritation is typically more intense than that caused by phosgene and is unaccompanied by the distinctive odor of phosgene.
Nerve agents induce the production of watery secretions as well as respiratory distress; however, their other characteristic effects distinguish nerve agent toxicity from organohalide inhalation injury.
The respiratory toxicity associated with vesicants is usually delayed but predominantly affects the central, rather than the peripheral airways. Vesicant inhalation severe enough to cause dyspnea typically causes signs of airway necrosis, often with pseudomembrane formation and partial or complete upper airway obstruction. Finally, pulmonary parenchymal damage following vesicant exposure usually manifests itself as hemorrhage rather than pulmonary edema.
No commonly available laboratory tests exist for the specific identification or quantification of phosgene inhalation; however, an increase in the hematocrit may reflect the hemoconcentration induced by transudation of fluid into the pulmonary parenchyma. Arterial blood gases may show a low PaO2 or PaCO2, which are early, nonspecific warnings of increased interstitial fluid in the lung.
Peak expiratory flow rate may decrease early after a massive phosgene exposure. This nonspecific test helps to assess the degree of airway damage and the effect of bronchodilator therapy. Decreased lung compliance and carbon monoxide diffusing capacity are particularly sensitive indicators of interstitial fluid volume in the lung, but are complex tests for hospital use only.
Early findings on chest x-ray are hyperinflation, followed later by pulmonary edema without cardiovascular changes of redistribution or cardiomegaly. Ventilation profusion ratio (V/Q) scanning is very sensitive but is nonspecific and for hospital use only.
Terminate exposure as a vital first measure. This may be accomplished by physically removing the casualty from the contaminated environment or by isolating him from surrounding contamination by supplying a properly fitting mask. Decontamination of liquid agent on clothing or skin terminates exposure from that source.
Execute the ABCs of resuscitation as required. Establishing an airway is especially crucial in a patient exhibiting hoarseness or stridor; such individuals may face impending laryngeal spasm and require intubation. Establishing a clear airway also aids in interpretation of auscultatory findings. Steps to minimize the work of breathing must be taken. Because of the always present danger of hypotension induced by pulmonary edema or positive airway pressure, accurate determination of the casualty's circulatory status is vital not just initially, but also at regularly repeated intervals and whenever indicated by the clinical situation.
Enforce rest. Even minimal physical exertion may shorten the clinical latent period and increase the severity of respiratory symptoms and signs in an organohalide casualty, and physical activity in a symptomatic patient may precipitate acute clinical deterioration and even death. Strict limitation of activity (i.e., forced bed rest) and litter evacuation are mandatory for patients suspected of having inhaled any of the edematogenic agents. This is true whether or not the patient has respiratory symptoms and whether or not objective evidence of pulmonary edema is present.
Prepare to manage airway secretions and prevent/treat bronchospasm. Unless superinfection is present, secretions present in the airways of phosgene casualties are usually copious and watery. They may serve as an index to the degree of pulmonary edema and do not require specific therapy apart from suctioning and drainage. Antibiotics should be reserved for those patients with an infectious process documented by sputum gram staining and culture. Bronchospasm may occur in individuals with reactive airways, and these patients should receive theophylline, or beta-adrenergic bronchodilators. Steroid therapy is also indicated for bronchospasm as long as parenteral administration is chosen over topical therapy, which may result in inadequate distribution to damaged airways. Methylprednisolone, 700-1000 mg or its equivalent, may be given intravenously in divided doses during the first day and then tapered during the duration of the clinical illness. The increased susceptibility to bacterial infection during steroid therapy mandates careful surveillance of the patient. No human studies have shown any benefit from steroids. Thus, steroids are not recommended in individuals without evidence of overt or latent reactive airway disease.
Prevent/treat pulmonary edema. Positive airway pressure provides some control over the clinical complications of pulmonary edema. Early use of a positive pressure mask may be beneficial. Positive airway pressure may exacerbate hypotension by decreasing thoracic venous return, necessitating intravenous fluid administration and perhaps judicious use of the pneumatic anti-shock garment.
Prevent/treat hypoxia. Oxygen therapy is definitely indicated and may require supplemental positive airway pressure administered via one of several available devices for generating intermittent or continuous positive pressure. Intubation with or without ventilatory assistance may be required, and positive pressure may need to be applied during at least the end-expiratory phase of the ventilator cycle.
Prevent/treat hypotension. Sequestration of plasma-derived fluid in the lungs may cause hypotension that may be exacerbated by positive airway pressure. Urgent intravenous administration of either crystalloid or colloid (which in this situation appear equally effective) may need to be supplemented by the judicious application of the pneumatic anti-shock garment. The use of vasopressors is a temporary measure until fluids can be replaced.
Patients seen within 12 hours of exposure: A patient with pulmonary edema only is classified immediate if intensive pulmonary care is immediately available. In general, a shorter latent period portends a more serious illness. A delayed patient is dyspneic without objective signs and should be observed closely and retriaged hourly. An asymptomatic patient with known exposure should be classified minimal and observed and retriaged every two hours. If this patient remains asymptomatic 24 hours after exposure, discharge the patient. If exposure is doubtful and the patient remains asymptomatic 12 hours following putative exposure, consider discharge. An expectant patient presents with pulmonary edema, cyanosis, and hypotension. A casualty who presents with these signs within six hours of exposure generally will not survive; a casualty with the onset of these signs six hours or longer after exposure may survive with immediate, intensive medical care.
Patients seen more than 12 hours after exposure: A patient with pulmonary edema is classified immediate provided he will receive intensive care within several hours. If cyanosis and hypotension are also present, triage the patient as expectant. A delayed patient is dyspneic and should be observed closely and retriaged every two hours. If the patient is recovering, discharge him 24 hours after exposure. An asymptomatic patient or patient with resolving dyspnea is classified minimal. If the patient is asymptomatic 24 hours after exposure, discharge him. A patient with persistent hypotension despite intensive medical care is expectant.
If the patient had only eye or upper airway irritation and is asymptomatic with normal physical examination 12 hours later, he may be returned to duty. If the patient's original complaint was dyspnea only, yet physical examination, chest x-ray, and arterial blood gases are all normal at 24 hours, he may be returned to duty. If the patient presented initially with symptoms and an abnormal physical examination, chest x-ray, or arterial blood gas, he requires close supervision but can be returned to duty at 48 hours if physical examination, chest x-ray, and arterial blood gases are all normal at that time.
