Epidemiology

Fires are common events in the United States. It is estimated that fire departments respond to fire alarms every 20 seconds.¹ In 2007, more than 1 million fire incidents and nearly 3500 deaths were reported, with civilian fatalities occurring every 153 minutes on average.¹ An estimated 50% to 80% of fire-related deaths are the result of smoke inhalation. Incident after incident, most of the victims of fires in commercial buildings, such as clubs, escape burns but suffer from smoke inhalation

Smoke inhalation injuries related to fire result from the toxic gases generated. Deaths from smoke inhalation have increased in recent years because of the abundant use of newer synthetic material in building and furnishings.²

Pathophysiology

Deaths from fires are most often caused by smoke inhalation.^3,4 The injury from smoke inhalation is a result of direct thermal injury to the airway and lung parenchyma, as well as mucosal irritation, corrosive injuries, and asphyxiation from toxic gases. Toxic gases can be classified as irritant gases and asphyxiants. The danger from such toxic gases predominates in exposed fire victims. Smoke is composed of a complex mixture of suspended small particles, fumes, and gases. More than 400 toxic compounds have been demonstrated in the smoke of a typical house fire. Polyvinyl chloride, a component of many plastic goods, generates at least 75 different toxic products when burned. Of these toxic substances, carbon monoxide (CO) appears to be the most common fatal substance associated with fire victims.^5,6

Thermal inhalation injuries are usually localized to the upper airway. Irritant gases, depending on their water solubility, affect either the upper or lower airway. Highly water-soluble agents such as ammonia, hydrogen chloride, and sulfur dioxide predominantly affect the upper airway. Their solubility directly correlates with rapid adverse upper airway symptoms. Agents with lower water solubility, such as phosgene and nitrogen dioxide, which do not produce immediate irritation, will be inhaled deeper in the pulmonary system and result in injury to the alveoli; victims typically have delayed noncardiogenic pulmonary edema.

Asphyxiants further compound the injury in smoke inhalation victims. Simple asphyxiants, such as carbon dioxide and methane, will produce an oxygen-deprived environment. Systemic asphyxiants, such as CO, cyanide, and hydrogen sulfide (H₂S), will prevent utilization of oxygen by cells. Either mechanism will promote an anaerobic state and the development of lactic acidosis.

CO is a colorless, odorless, nonirritating gas produced by the incomplete combustion of hydrocarbons and petroleum distillates, whether from a fire, fuel source, or automobile exhaust or from the metabolism of methylene chloride, a solvent commonly used as a paint stripper. One of the major mechanisms of CO toxicity is its affinity to bind hemoglobin, with an affinity estimated to be approximately 250 times greater than that of oxygen, which results in reduction in oxyhemoglobin. The impairment in delivery of oxygen is exacerbated by displacement of the oxygen dissociation curve to the left. Furthermore, CO interferes with cellular respiration by binding to mitochondrial cytochrome oxidase and is involved in the formation of oxygen free radicals and subsequent lipid peroxidation. All the aforementioned mechanisms produce oxidative stress on the brain, the main organ affected by CO; excitatory amino acids such as glutamate are activated, which results in neuronal injury and cell death. Areas of the brain that are highly sensitive to hypoxemia, such as the basal ganglia, appear to sustain the most injury. CO is known to bind to myoglobin as well, a feature that contributes to impairment in myocardial contractility. Fetal hemoglobin is more sensitive to the binding of CO; levels are reported to be approximately 10% higher than maternal levels, with a half-life five times longer. Over time, carboxyhemoglobin will dissociate, with its half-life on room air being approximately 4 to 6 hours. With 100% oxygen, the half-life decreases to approximately 90 minutes, and in the setting of hyperbaric oxygen therapy, it is about 20 minutes.

Cyanide is a highly toxic chemical. Hydrogen cyanide is a common by-product of the pyrolysis of wool, silk, and plastics. Cyanogenic compounds such as nitriles are used in industry as solvents and adhesives and are metabolized by the body to cyanide. Acetonitrile, which in the past was commercially available as an artificial nail glue remover, has resulted in fatality when accidentally ingested.⁷ With increasing concern about terrorism, it is high on the potential lists of chemical agents. Its mechanism is binding of the cytochrome aa₃ site on the electron transport system of mitochondria. The result is an inability to use oxygen and subsequent cellular asphyxia.

H₂S is the by-product of certain industries, such as paper factories, petroleum refineries, and dehairing of hides. It is produced naturally from decay of organic matter and from sulfur hot springs. These products have the characteristic “rotten egg” odor. Like cyanide, it is a potent inhibitor of the cytochrome oxidase system. The human nose is exquisitely sensitive to the odor of H₂S, and it is easily detected at levels as low as 0.13 parts per million (ppm). Irritation of mucous membranes occurs at levels of approximately 50 to 100 ppm, and such levels are also capable of causing bronchospasm, blepharospasm, and laryngeal edema. At levels greater than 500 ppm, a phenomenon classically described as a “rapid knockdown” effect occurs, which includes immediate loss of consciousness with the potential for cardiovascular collapse and respiratory arrest. Sulfhemoglobin may result from exposure to H₂S. Clinically, it may produce cyanosis. Unfortunately, it is an extremely stable compound and is eliminated only when the red blood cells are removed from the circulation. Recently, H₂S was a popular means of suicide in Japan.⁸ Bath sulfur, a product readily available, is added to water to mimic the water of natural sulfur hot springs. However, when the bath sulfur is combined with acid, such as toilet bowl cleaner, a lethal H₂S gas is liberated. Any sulfur-containing substance, including laundry detergent, is a suitable substitute for bath sulfur. Reports of suicide in the United States with this method have been described in the media.

Methemoglobin is the oxidized form of hemoglobin and can result from exposure to oxidizing agents, such as nitrites and nitrates, as well as from smoke inhalation.⁹ In this oxidized state, hemoglobin is no longer capable of carrying oxygen. Cyanosis is typically seen at levels approximately of 15% to 20%. Levels greater than 70% are usually lethal.

Presenting Signs and Symptoms

Victims of smoke inhalation will typically be in various degrees of respiratory distress and altered mental status. Hoarseness, stridor, and aphonia may be early signs of impending respiratory arrest. Attention to vital signs is imperative. Hypoxemia despite supplemental oxygen is a poor prognostic sign and needs to be addressed immediately. Carboxyhemoglobinemia and methemoglobinemia will give false readings on pulse oximetry unless newer pulse oximetry instruments that can detect these hemoglobinopathies are used. In a normal patient, the pulse oximetry instrument is calibrated to measure the differences in light absorption between the red and infrared wavelengths. With oxyhemoglobin, the majority of light absorption is in the red wavelength region. With carboxyhemoglobinemia, the peak wavelength of light absorption is similar to that of oxyhemoglobin, and the instrument does not detect differences between the two. With methemoglobinemia, as its concentration increases, the pulse oximetry instrument interprets equal light absorption between the red and infrared wavelengths. As a result, the instrument interprets this ratio automatically as 85%.

Many of the toxicants associated with smoke inhalation can cause hypotension as result of either third spacing, peripheral vasodilation, or myocardial depression or arrhythmia. Seizure may be one of the early signs and results from either secondary hypoxemia, acidosis, or toxic gases and compounds.

Differential Diagnosis and Medical Decision MakinG

As a means of better understanding this complex problem, dividing smoke inhalation injury into toxidromes (toxic syndromes) may help identify clinically significant smoke inhalation. Aside from the potential concomitant thermal injuries associated with structural fires, these major toxidromes involve irritant gases, simple asphyxiants, systemic asphyxiants, and methemoglobinemia (Table 136.1).

Irritant gases can be divided into highly water-soluble and poorly water-soluble agents. Moderately water-soluble gases, such as chlorine, behave more like the highly water-soluble agents and are thus combined with the highly water-soluble agents. Highly water-soluble agents are very irritating to the mucous membranes, eyes, and upper airway, and affected individuals experience symptoms immediately. As with thermal injuries, early orotracheal intubation should be a priority in any individual with any degree of respiratory distress. These individuals can deteriorate rapidly. Generally, most individuals will be able to remove themselves from such an environment; however, if they are injured, incapacitated, or involuntarily confined, their outcome may be lethal. A prime example is the 1984 incident in Bhopal, India, where approximately 20,000 lb of isocyanate leaked from a nearby storage tank. By the time that the leak was discovered, the fumes covered nearly 5 square miles. It is estimated more than 200,000 individuals were victimized by the irritant gas and thousands of people died.

Poorly water-soluble gases have very poor warning properties, and thus they are inhaled deeper in the pulmonary system and affect the alveoli. Two examples of such agents are phosgene and nitrogen dioxide. The hallmark of these inhalation injuries is delayed pulmonary edema.

The asphyxiant toxidromes can be divided in simple and systemic. As asphyxiants, these agents affect the availability or utilization of oxygen by cells and therefore tissues and organs. Simple asphyxiants are generally inert gases, such as carbon dioxide, but they may be flammable, such as methane, and create an explosive hazard. Simple asphyxiants displace oxygen and thus create a hypoxic environment. Symptoms depend on the severity of the hypoxia and the duration of exposure. Because of the underlying mechanism, an excess of deoxyhemoglobin, cyanosis is usually present. Systemic asphyxiates impair the body’s ability to use oxygen by interfering with the transportation of oxygen, such as with methemoglobinemia, or by interfering with the utilization of oxygen at the cellular level, such as with cyanide. CO impairs both the transportation and utilization of oxygen.

The diagnosis of cyanide toxicity is generally based on a high index suspicion from the history. The victim will appear in a shocklike state. The classic bitter almond odor of cyanide is rarely detected. Hypoxia is a late finding because of its underlying pathophysiology. Oxygen is available, but the cells and tissues are unable to use it. Because cyanide assay is not immediately available in most institutions, indirect evaluation of the difference in the oxygen content of arterial and venous blood can provide valuable insight.⁴ A small arterial (PaO₂)-venous (PvO₂) oxygen gap would support the diagnosis. Severe lactic acidosis should prompt further investigation of cyanide toxicity. A lactic acid level greater than 10 mmol/L has been correlated with a cyanide level of approximately 40 mmol/L, a level considered significant and warranting immediate action.

Methemoglobinemia is the result of oxidation of the iron in hemoglobin. Normal hemoglobin has iron in the 2+ state. When it is exposed to an oxidizing agent, the iron is converted to the 3+ state. In this oxidized state, it is unable to bind oxygen. A methemoglobin level of approximately 1.5 g/dL can produce cyanosis. The body normally reduces iron by various physiologic pathways, primarily via reduced nicotinamide adenine dinucleotide (NADH) methemoglobin reductase and by a minor pathway, reduced nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase. This latter pathway is dependent on a functional glucose-6-phosphate dehydrogenase (G6PD) system. It is the pathway that is the target of administration of methylene blue, the treatment of methemoglobinemia.

Treatment

The priority of treatment is supporting and stabilizing the primary survey—the ABCs (airway, breathing, and circulation). Aggressive airway management is essential, including high-flow supplemental oxygen and early orotracheal intubation and ventilator management if necessary.

Close monitoring is imperative to observe for the potential for rapid clinical deterioration. Good supportive care is vital and includes fluid resuscitation, anticonvulsant therapy, and correction of metabolic abnormalities, especially metabolic acidosis.

Hydroxocobalamin (Cyanokit) is a new cyanide antidote approved by the Food and Drug Administration in December 2006. It has essentially replaced the older antidote, which used sodium nitrite to generate a controlled methemoglobinemia, follow by the administration of sodium thiosulfate, a substrate required by the liver enzyme rhodanase to then detoxify the formation of cyanomethemoglobin. Use of hydroxocobalamin is indicated in any individual with cyanide toxicity or suspected cyanide toxicity. By mechanism, it binds to cyanide to form cyanocobalamin, which is vitamin B₁₂. It appears to be safe, with just a few clinically significant adverse effects, such as allergic reactions and transient hypertension. Generalized erythema and red chromaturia because of the dark red nature of the antidote once reconstituted are commonly reported. Unfortunately, laboratory studies that depend on colorimetric analysis are affected and will give false readings. Its clinical significance is unknown. Because of its safety profile, this antidote can be administered empirically at the scene of a fire to victims and fire rescuers who may be deemed at risk for toxic exposure to cyanide.¹⁰ In at least one animal study evaluating the effect of hydroxocobalamin on mice poisoned with sodium sulfide (at a lethal dose for 90% of the population [LD₉₀]), the antidote resulted in improved survival following its administration.¹¹

Methylene blue is the antidote for the treatment of methemoglobinemia. It is indicated in victims who are symptomatic and usually with methemoglobin levels greater than 20% to 30%. One contraindication to its use is G6PD deficiency. With multiple dosing, methylene blue may itself generate methemoglobinemia or cause hemolysis. Other therapeutic options for the treatment of methemoglobinemia are exchange transfusion or hyperbaric oxygen (HBO) therapy.

Treatment of CO toxicity is primarily supportive with 100% supplemental oxygen. HBO therapy has been studied clinically for years, but its role in treating CO toxicity remains controversial.^12,13 If considering HBO, generally accepted indications would include the following: loss of consciousness at the scene, comatose state, seizure, myocardial ischemia, and levels greater than 30% in adults and greater 15% in infants, children, or pregnant women.

Follow-Up, Next Steps in Care, and Patient Education

All smoke inhalation patients should be evaluated in an emergency department. If symptomatic, all will require admission. Depending on the severity of their exposure and injuries, they should be admitted to a monitor setting, including the intensive care unit if needed.

Patients with a brief exposure who are asymptomatic for a minimum of 6 hours can be discharged with good instructions to the patient and family member regarding the signs and symptoms of early respiratory distress, as long as they have the ability to access 911.

Patients in whom phosgene or nitrogen dioxide gases may be involved in the exposure should be admitted, despite being asymptomatic, and be observed for minimum of 24 hours with frequent assessment for signs and symptoms of delayed pulmonary edema.