Chapter 57B: Toxic Pulmonary Inhalation

Fires kill more than 3200 and injure approximately 16,000 civilians annually in the United States^1,2 via thermal, chemical and systemic injury to the airway caused by toxic inhalation of carbon monoxide (CO), cyanide (CN), and other toxins. Toxic inhalation is the major cause of death from fires with 80% of cases related to CO poisoning.³ Complications of toxic inhalation include airway damage, pneumonia, and acute respiratory distress syndrome (ARDS).⁴ More than 50,000 patients a year visit the emergency department with CO poisoning in the United States.⁵

Particles greater than 5 μm in diameter are cleared by the nasopharynx,⁶ but in smoke inhalation, larger particles may lodge deeper in the airway as patients breathe through the mouth.⁴ Thermal injuries from fires primarily affect the upper airways, as air cools as it travels to the carina. Combustion results in decreased oxygen in ambient air and asphyxiation.

Damage to the airway and lung parenchyma result in free radical formation, inflammation, increased capillary permeability, and capillary leakage. Alveoli are filled with fluid and blood. Polymorphonuclear macrophages, IL-1, IL6, IL-8, and tumor necrosis factor-α activation result in atelectasis, bronchospasm, impaired mucociliary function, and in some cases, ARDS. ARDS results from alveolar and lung endothelium capillary injury. Initially inflammation leads to increased capillary endothelial permeability resulting in accumulation of fluid in the alveoli and pulmonary edema. This leads to intrapulmonary shunting as fluid-filled alveoli are perfused but not ventilated, resulting in hypoxemia.

Toxic inhalants can be divided into asphyxiants, irritants and systemic toxins. Asphyxiants induce hypoxia, which can result in headache, dizziness, nausea, dyspnea, altered mental status, cardiac ischemia, respiratory failure, syncope, coma, and seizures. Simple asphyxiants such as helium, argon, carbon dioxide, chlorofluorocarbon refrigerants, methane, and propane displace oxygen and result in oxygen deprivation. Systemic asphyxiants such as CO, CNs, and sulfides impair oxygen transport resulting in tissue hypoxia and reduced oxidative phosphorylation and hence ATP synthesis. Irritants such as ammonia, chlorine, nitrogen oxides, and sulfur dioxide, and systemic toxins such as hydrocarbons, organophosphates, and metal fumes can cause upper and lower airway burns and destruction resulting in respiratory distress and failure.

In all cases of toxic inhalation (Table 57B–1) priorities include securing the airway and insuring adequate oxygenation, treating shock with crystalloids and vasopressors, correcting acidemia, cardiac monitoring and administering antidotes if available.⁷ Tests and imaging should include complete blood count, complete metabolic panel, arterial blood gases (ABG), carboxyhemoglobin to rule out CO poisoning, chest radiograph and an ECG to look for arrhythmias and myocardial ischemia.

Any patient that has the potential to become hemodynamically unstable or have airway compromise should be monitored in the ICU. Patients who appear ill or those with serious comorbidities, other injuries such as hypoxia from smoke inhalation, airway compromise requiring mechanical intubation or burns should be admitted to the ICU. All toxic inhalation victims should receive high (FiO₂ 100%) supplemental oxygen, decontamination, airway protection, bronchodilators if necessary and close monitoring.^8,9 Hyperbaric oxygen is useful for CO, CN, and hydrogen sulfide toxicity as it increases the amount of dissolved oxygen in the blood and increases delivery of nonhemoglobin bound oxygen to tissues. Its use is limited by availability. The benefits of hyperbaric oxygen on noncomatose patients are inconclusive.¹⁰ Patients with burns in the mouth or difficulty speaking should be evaluated for early intubation. In these patients, laryngoscopy or bronchoscopy can be used to evaluate the extent of airway swelling, ulceration, and structural damage (Figure 57B–1).

Asphyxiants

CO is the most frequent cause of toxic inhalation in the United States. It is an odorless, colorless gas produced by incomplete combustion of hydrocarbons. Hypoxia results from hemoglobin having a 200-fold greater binding affinity to CO than to oxygen, causing decreased oxygen transport and unloading. Important sources of CO include motor vehicle exhaust, metal and chemical manufacturing, fires, stoves, cigarette smoke, and unvented space heaters. Elevated carboxyhemoglobin levels confirm the diagnosis. However, low carboxyhemoglobin levels do not exclude CO toxic exposure if there is a delay between exposure and testing; oxygen therapy lowers CO levels more rapidly. Severe CO toxicity causes lactic acidosis. The SaO₂ reported from standard ABG (SaO₂ value is calculated from the dissolved oxygen [PaO₂]) will be normal in the presence of CO toxicity; direct measurement of oxyhemoglobin with co-oximetry is needed to accurately detect the SaO₂, which will be lowered by carboxyhemoglobin. It is also important to note that most bedside pulse oximeters cannot differentiate carboxyhemoglobin from oxyhemoglobin and will display a normal SpO₂ (SpO₂ = pulse oximeter measurement of SaO₂) in the presence of low oxyhemoglobin.^11,12 Of note, the ABG findings seen with CO poisoning also occur with methemoglobinemia.

CN toxicity often occurs with CO poisoning and should be suspected in any smoke inhalation patient with elevated carboxyhemoglobin levels and severe lactic acidosis or with persistent neurologic symptoms despite low carboxyhemoglobin levels, for example, less than 30%.

CN is a colorless gas with a bitter almond smell. It is found in plastics, paints, lacquer, polyurethane, nylon, and rubber. It is also found in cigarette smoke. CN binds to ferric on cytochrome a3, arresting cellular respiration. CN toxicity causes persistent hypotension and severe lactic acidemia. There is no specific test to diagnose CN toxicity and suspicion is based on the smoke inhalation history and clinical findings as noted above under CO. Hydroxocobalamin, thiosulfate, and sodium nitrite are treatments for CN toxicity. Hydroxocobalamin directly binds CN, thiosulfate increases the detoxification of CN, and sodium nitrite results in methemoglobin formation increasing the affinity of CN away from the cytochromes and toward hemoglobin. Methemoglobin levels must be checked in these patients. In an event, nitrites should not be administered in patients with significant hypoxemia (eg, as a result of high carboxyhemoglobin levels) that cannot tolerate any further reductions in oxygen delivery (oxyhemoglobin) caused by methemoglobin generation.

Hydrogen sulfide is a colorless, flammable gas that is irritating to eyes and mucous membranes and has a rotten egg odor. It is formed from the decomposition of organic material including crude oil, petroleum, sewers, compost pics, cleaners, sulfur springs, and underground fields of natural gas. Toxicity causes central nervous system (CNS) and respiratory depression. There are no specific tests to diagnose hydrogen sulfide poisoning is suspicion based on the exposure history and clinical findings. There is no specific antidote for hydrogen sulfide toxicity. Patients should be monitored for ocular inflammation and scarring, and pulmonary edema. Any patient with significant exposure should be monitored for 24 hours for signs of CNS depression and respiratory distress. If these symptoms are present, the patient should be admitted to the intensive care unit. Supportive respiratory and cardiovascular management are primary. Sodium nitrite may have a benefit if administered early in patients without severe hypoxemia by inducing methemoglobin formation to attract hydrogen sulfide away from cytochromes to hemoglobin. Methemoglobin levels must be followed.

Irritants

Irritant inhalation is often a result of manufacturing accidents. Examples include ammonia, chlorine, nitrogen oxide, and sulfur dioxide. Symptoms depend on exposure and solubility. Highly soluble irritants cause upper airway burns whereas low soluble irritants cause lower airway destruction. No specific tests are available to detect irritant toxicity. Ammonia and chlorine have pungent odors, are highly corrosive and cause extensive airway damage, bronchoconstriction and pulmonary edema. Both are used in household cleaners. Ammonia is used in fertilizer and manufacturing. Chlorine is used as a bleach and in manufacturing paper, cloth, and pesticides.¹³

Nitrogen oxides are nonflammable and colorless gases that are found in vehicle exhaust, coal, oil, natural gas combustion, and in manufacturing. Exposure primarily causes lower respiratory tract damage and results in free radical generation, reduced immune function, methemoglobinemia, pulmonary edema, and bronchospasm.

There are no antidotes for ammonia, chlorine, nitrogen oxide, and sulfur dioxide exposure, although methylene blue is used to treat nitrous oxide induced methemoglobinemia.

Methemoglobin and Treatment of Methemoglobinemia

Methemoglobin is an altered form of hemoglobin where iron is oxidized from ferrous to a ferric state, rendering it unable to bind oxygen. It results in decreased oxygen carrying capacity of blood. Normal methemoglobin levels are 1% to 3%. Methemoglobinemia results in cyanosis which does not improve with oxygenation and ventilation. Levels above 15% cause cardiac, respiratory, and neurologic symptoms, and levels more than 70% are usually fatal. Sources of methemoglobin include nitrates, exhaust, cocaine, dapsone, metoclopramide, primaquine, rasburicase, and sulfonamides.

Pulse oximeters estimate oxygen saturation by comparing the absorbance of light at 2 wavelengths; oxyhemoglobin absorbs infrared light and deoxyhemoglobin absorbs red light. Methemoglobin and oxyhemoglobin absorbance characteristics are similar, thereby, falsely elevating pulse oximeter readings. Specialized pulse oximeters with co-oximetry measure light absorbance at 4 or more wavelengths enabling accurate measurements of oxyhemoglobin, methemoglobin, and carboxyhemoglobin.

The treatment for methemoglobinemia is methylene blue which rapidly reduces methemoglobin to hemoglobin. In high doses, methylene blue can actually induce methemoglobinemia. Methylene blue is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because it is ineffective and can cause severe hemolysis.

Systemic Toxins

Hydrocarbons are organic substances that have the potential to be inhaled as recreational drugs or in workplace accidents. Examples include: gasoline, motor oil, paint, glue, and solvents. Inhalation toxicity often results in pneumonitis. Organophosphates are found in insecticides, herbicides, nerve agents, fertilizers, and solvents. Organophosphates inhibit acetylcholinesterase, resulting in cholinergic overstimulation. Toxicity is a clinical diagnosis. Symptoms include sweating, lacrimation, rhinorrhea, salivation, bronchorrhea, miosis, weakness, fasciculations, paralysis, tachycardia, hypertension, and respiratory failure. Metal fumes released by welding cause flu-like illness. Symptoms are often transient and self-limited, and are more likely and severe after a period away from work.

Hydrocarbons and metal fume toxicities are treated with supportive care including supplemental oxygen, decontamination, airway protection and bronchodilators if necessary. Organophosphate antidotes include atropine and pralidoxime. It is essential to remove any contaminated clothing. Healthcare workers must also take precautions while decontaminating victims.