Perspective

Most simple asphyxiations are workplace related and usually occur during the use of liquefied gas while the employee is breathing through an airline respirator or working in a confined space.¹ Since the advent of catalytic converters, most deaths from the intentional inhalation of automotive exhaust result from simple asphyxiation, due to hypoxia, and not from carbon monoxide (CO) poisoning.²

Principles of Disease

Most simple asphyxiants are inert and produce toxicity only by displacement of oxygen and lowering of the fraction of inspired oxygen (FIO₂). Exposed patients remain asymptomatic if the FIO₂ is normal. Carbon dioxide and nitrogen, both constituents of air, produce narcosis at elevated partial pressures, but their predominant toxicologic effect is simple asphyxiation.

Clinical Features

Acute effects occur within minutes of onset of hypoxia and are the manifestations of ischemia. A fall in the FIO₂ from normal, 0.21 (i.e., 21%), to 0.15 results in autonomic stimulation (e.g., tachycardia, tachypnea, and dyspnea) and cerebral hypoxia (e.g., ataxia, dizziness, incoordination, and confusion). Dyspnea is not an early finding because hypoxemia is not as potent a stimulus for this sensation, or for breathing, as are hypercarbia and acidosis. Lethargy from cerebral edema is expected as the FIO₂ falls below 0.1 (10%), and life is difficult to sustain at an FIO₂ below 0.06 (6%).³ Because removal from exposure terminates the simple asphyxiation and allows restoration of oxygenation and clinical improvement, most patients present with resolving symptoms. However, failure to improve suggests complications of ischemia (e.g., seizures, coma, and cardiac arrest) and is associated with a poor prognosis.

Diagnostic Strategies and Differential Considerations

A consistent history, an appropriate spectrum of complaints, and a rapid resolution on removal from exposure are generally sufficient to establish the diagnosis. Minimally symptomatic or asymptomatic patients do not require chest radiography or arterial blood gas (ABG) analysis. Definitive diagnosis ultimately requires scene investigation by a trained and suitably outfitted team. Determination of the exact nature of the gas is of limited clinical value but may have important public health implications. Because the presenting complaints offered by most exposed patients are nonspecific and protean (e.g., dizziness, syncope, and dyspnea), the differential diagnosis is extensive.

Management and Disposition

Management rarely requires specific therapy other than removal from exposure, supportive care, and possibly administration of supplemental oxygen. Neurologic injury or cardiorespiratory arrest should be managed with standard resuscitation protocols. Patients with manifestations of mild poisoning who recover after removal from the exposure can be observed briefly and discharged. Patients at risk for complications of hypoxia, such as those presenting with significant symptoms (e.g., coma) or with exacerbating medical conditions (e.g., cardiac disease), should be observed for the development or progression of posthypoxic complications.

Perspective

The pulmonary irritant gases are a large group of agents that produce a common toxicologic syndrome when they are inhaled in moderate concentrations. Although many of these agents can be found in the home, significant poisoning from consumer products is uncommon because of restrictions designed to reduce their toxicity. However, catastrophes such as the 1984 release of methyl isocyanate in Bhopal, India, which resulted in more than 2000 fatalities and 250,000 injuries, remain as an environmental risk. On a different scale, industrialization has increased ambient levels of sulfur dioxide, ozone, and oxides of nitrogen. These irritant gases frequently exacerbate chronic pulmonary disease.

Principles of Disease

Irritant gases dissolve in the respiratory tract mucus and alter the air-lung interface by invoking an irritant or inflammatory response. When these gases are dissolved, most of them produce an acid or alkaline product, but several generate oxygen-derived free radicals that produce direct cellular toxicity (Fig. 159-1). The clinical effects of pulmonary irritants can be predicted by their water solubility (see Table 159-1).

Clinical Features

Highly water-soluble gases have their greatest impact on the mucous membranes of the eyes and upper airway. Exposure results in immediate irritation, with lacrimation, nasal burning, and cough. Although their pungent odors and rapid symptom onset tend to limit significant exposure, massive or prolonged exposure can result in life-threatening laryngeal edema, laryngospasm, bronchospasm, or acute respiratory distress syndrome (ARDS) (formerly known as noncardiogenic pulmonary edema).⁴ Poorly water-soluble gases do not readily irritate the mucous membranes at low concentrations, and some have pleasant odors (e.g., phosgene’s odor is similar to that of hay). Because there are no immediate symptoms, prolonged breathing in the toxic environment allows time for the gas to reach the alveoli. Even moderate exposure causes irritation of the lower airway, alveoli, and parenchyma and causes pulmonary endothelial injury after a 2- to 24-hour delay. Initial symptoms consistent with acute respiratory distress syndrome may be mild, only to progress to overt respiratory failure and acute respiratory distress syndrome during the ensuing 24 to 36 hours.⁵

Gases with intermediate water solubility tend to produce syndromes that are a composite of the clinical features manifested with the other gases, depending on the extent of exposure. Massive exposure is most often associated with rapid onset of upper airway irritation and more moderate exposure with delayed onset of lower airway symptoms.⁶

Diagnostic Strategies and Differential Considerations

The evaluation of upper airway symptoms is usually done through physical examination but may require laryngoscopy. After exposure, swelling may occur rapidly or may be delayed, so normal findings on oropharyngeal or laryngeal evaluation may not exclude subsequent deterioration. Radiographic and laboratory studies have little role in the evaluation of upper airway symptoms.

Oxygenation and ventilation are assessed by serial chest auscultation, pulse oximetry, and capnometry supplemented as needed by chest radiography and ABGs in patients with cough, dyspnea, hypoxia, or abnormal findings on physical examination. No clinical test can identify the specific irritant, and identification is not generally necessary for patient care, although knowing the causative agent may allow refinement of the observation period.

Bronchospasm, cough, chest tightness, and acute conjunctival irritation frequently follow allergen exposure, but the history generally suggests the diagnosis. ARDS occurs after many physiologic insults, including trauma and sepsis, highlighting the need for accurate history taking.⁵

Management

Signs of upper airway dysfunction (e.g., hoarseness and stridor) mandate direct visualization of the larynx and immediate airway stabilization, if necessary. Given the potential rapidity of airway deterioration, early and frequent reassessment should be performed.

Bronchospasm generally responds to inhaled beta-adrenergic agonists; the role of ipratropium is not yet defined. Other than as a standard treatment of a comorbid condition, such as asthma, there is no clear indication for corticosteroids.⁷

Patients exposed to chlorine or hydrogen chloride gas receive symptomatic relief from nebulized 2% sodium bicarbonate solution.⁶ Because the inflammatory cascade is not altered, however, the component of lung injury mediated by free radicals probably continues and causes delayed deterioration. Patients receiving inhalational bicarbonate therapy require extensive discharge instructions for signs and symptoms of pulmonary irritation or admission to the hospital.

Diagnosis of acute respiratory distress syndrome indicates the need for aggressive supportive care, including manipulations of the patient’s airway pressures (e.g., continuous positive airway pressure and positive end-expiratory pressure). Exogenous surfactant and nitric oxide may have a beneficial role in toxin-induced acute respiratory distress syndrome, despite little support for use in other forms of the syndrome.

Disposition

Patients exposed to highly water-soluble gases can be discharged if they are asymptomatic or improve with symptomatic therapy. After exposure to intermediate or poorly water-soluble gases, asymptomatic patients should be observed for increasing dyspnea for several hours before final disposition. Patients with substantial exposure to these agents or those in high-risk situations (e.g., underlying pulmonary disease, extremes of age, and poor follow-up) should be observed for 24 hours and may require hospitalization. All patients should be instructed to return if symptoms recur.

Perspective

Annually, approximately 4000 people are injured or die in residential fires in the United States. Many of these casualties do not suffer serious cutaneous burns but rather die of smoke inhalation. This is a variant of irritant injury in which heated particulate matter and adsorbed toxins injure normal mucosa, similar to other irritant gases. In addition, CO and cyanide are systemic toxins often discussed with the smoke inhalation syndrome because of their common origin.

Principles of Disease

Even at temperatures between 350 and 500° C, air has such a low heat capacity that it rarely produces lower airway damage. However, the greater heat capacity of steam (approximately 4000 times that of air) or heated soot suspended in air (i.e., smoke) can transfer heat and cause injury deep within the respiratory tract.

The nature of the fuel determines the composition of its smoke, and because fires involve variable fuels and burning conditions, the character of fire smoke is almost always undefined to the clinician. Irritant toxins produced by the fire are adsorbed onto carbonaceous particles that are deposited in the airways. The irritant substances damage the mucosa through mechanisms similar to those of the irritant gases, including generation of acids and free radical formation.

Clinical Features

Most smoke-associated morbidity and mortality relate to respiratory tract damage. Thermal and irritant-induced laryngeal injury may produce cough or stridor, but these findings are often delayed. Soot and irritant toxins in the airways can produce early cough, dyspnea, and bronchospasm. Subsequently, a cascade of airway inflammation results in acute lung injury with failure of pulmonary gas exchange. The time between smoke exposure and the onset of clinical symptoms is highly variable and dependent on the degree and nature of the exposure. Singed nasal hairs and soot in the sputum suggest substantial exposure but are neither sufficiently sensitive nor specific to be practical.⁸

CO inhalation should be routinely considered in these patients. Patients who are exposed to filtered or distant smoke (e.g., in a different room) or to relatively smokeless combustion (e.g., engine exhaust) inhale predominantly CO, cyanide, and metabolic poisons and do not sustain smoke exposure.

Diagnostic Strategies and Differential Considerations

With the obvious exposure history, the differential diagnosis is limited. Although it is often unclear whether inhalational injuries are thermal or irritant, the differentiation is clinically irrelevant. CO and cyanide should be considered in every case.

Early death is caused by asphyxia, airway compromise, or metabolic poisoning (e.g., CO). Airway patency should be evaluated early. If evidence of significant airway exposure is present, such as carbonaceous sputum or hoarse voice, the airway should be examined by direct or fiberoptic laryngoscopy. Simply observing the patient for deterioration can result in airway compromise requiring rapid and, by then, very difficult airway intervention. Signs of alveolar filling or hyperinflation on chest radiography, abnormal flow-volume loop or diffusing capacity for CO on pulmonary function testing, or abnormal distribution and clearance of radiolabeled gas on ventilation scans can help predict lower airway injury.⁹

Metabolic acidosis, particularly when it is associated with a serum lactate level greater than 10 mmol/L, suggests concomitant cyanide poisoning.¹⁰ Oxygenation should be assessed by co-oximetry because blood gas analysis and pulse oximetry may be inaccurate in CO-poisoned patients (see later).