Smoke Inhalation Injury

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Practice Essentials

Smoke inhalation is the leading cause of death due to fires. It produces injury through several mechanisms, including thermal injury to the upper airway, irritation or chemical injury to the airways from soot, asphyxiation, and toxicity from carbon monoxide (CO) and other gases such as cyanide (CN). See the image below.



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Smoke inhalation in pediatric victims. Note the many hallmarks of smoke inhalation complexed with burn injury (ie, facial burns, carbonaceous particle....

Signs and symptoms

Findings on physical examination may include the following:

Symptoms of lower respiratory tract injury include the following:

Cyanosis may be present. However, cyanosis is an unreliable indicator of hypoxia because neither carbon monoxide nor CN cause cyanosis.

Findings in patients exposed to asphyxiants may include the following:

See Clinical Presentation for more detail.

Diagnosis

Studies may include the following:

Carboxyhemoglobin levels in the blood and the corresponding clinical manifestations are as follows[1] :

Blood carboxyhemoglobin levels may underestimate the degree of CO intoxication because of oxygen administered to the patient before arrival to the hospital. The use of nomograms to extrapolate levels to the time of rescue has been shown to have prognostic value.

See Workup for more detail.

Management

When a patient presents with smoke inhalation, immediate assessment of the patient’s airway, breathing, and circulation should be done.[2] Provide IV access, cardiac monitoring, and supplemental oxygen in the setting of hypoxia. Some patients manifest bronchospasm and may benefit from the use of bronchodilators. When upper airway injury is suspected, elective intubation should be considered. Airway edema can progress over the next 24-48 hours and may make later intubation difficult if not impossible. Studies have shown that initial evaluation is not a good predictor of the airway obstruction that may ensue later secondary to rapidly progressing edema.[2]

Although controlled studies assessing the effects of steroids on various forms of chemical pneumonitis are disappointing, steroids have been suggested as having some value in exposure to the following[3] :

Patients with smoke inhalation should be monitored for 4-6 hours in the ED. Those who are at low risk for injury and whose vital signs and physical examination findings remain normal can usually be discharged with close follow-up and instructions to return if symptoms develop. Patients with any of the following should be strongly considered for hospitalization:

Mechanical ventilation may be necessary in patients with declining lung function, oxygenation levels, and ventilation. It is given as follows:

Neurologic abnormalities and a history of loss of consciousness are the primary clinical features used to define severe CO toxicity and are indications for hyperbaric oxygen (HBO) therapy. In addition, HBO use is indicated in patients with any of the following:

See Treatment and Medication for more detail.

Background

Smoke inhalation injury was described as early as the first century CE, when Pliny reported the execution of prisoners by exposure to the smoke of greenwood fires. Smoke—the vaporous colloidal system formed when a material undergoes combustion or pyrolysis—comprises a collection of noxious gases, airborne solid particles, and airborne liquid particles. The distribution of those particles in the respiratory tract after inhalation is determined by their size and by the person’s breathing mechanics and tidal volume.

During fires, smoke inhalation victims are unable to efficiently breathe through the nasopharynx, thereby decreasing inspiratory air filtration and enabling a greater amount of particle distribution in the airway. This subsequently leads to nasopharyngeal irritation and severe lung injury.

Inhalation injury from smoke in fires may account for as many as 60-80% of fire-related deaths in the United States, many of which are preventable.[4, 5] Excellent care rendered at today's burn centers has greatly reduced the mortality from surface burns,[6] while the mortality from pulmonary injury has been increasing.

Many victims of fire accidents have both smoke inhalation and thermal injury. In fact, the co-presence of bronchopulmonary injury with cutaneous burns that exceed 30% of the total body surface area causes the mortality rate to increase more than 70%.[7] Other studies have shown that the incidence of inhalation injury increases with increasing burn size.[2]

Smoke inhalation may produce injury through several mechanisms. Heated air from a fire can cause significant thermal injury to the upper airway. Particulate matter produced during combustion (soot) can mechanically obstruct and irritate the airways, causing reflex bronchoconstriction. Noxious gases released from burning materials include carbon monoxide (CO) and hydrogen cyanide (CN).

Smoke may also contain aldehydes from combustion of furniture and cotton, and a variety of chemicals released by burning of rubber and plastics, including the following:

Smokes and obscurants long have been used by the military as a means of hiding troops, equipment, and certain areas from view of the opposing forces and from engagement by weapons with electro-optical control systems. Although smokes typically are not used as direct chemical agents, they may produce toxic injury to skin, eyes, and all parts of the respiratory tract.[8] Smokes are also produced inadvertently in industry by explosion, by mechanical generation, or as a by-product of a chemical interaction.

Smokes associated with the military, industry, or both, include the following:

The chemical property of smoke combined with burn injury induces a complex pathophysiologic process that results in hypoxic insult, early airway edema, and bronchoconstriction.[9]

Diagnosis of inhalation injury is not always straightforward, owing to poorly sensitive screening tests and, in many cases, the delay in manifestation of clinically significant symptoms until 24-72 hours after injury. In treatment of smoke inhalation, the most immediate concern is reversing cellular asphyxia and carbon monoxide (CO) and CN toxicity (see Treatment).

Although children are less likely than adults to experience significant smoke inhalation, it remains a serious and life-threatening problem in the pediatric population. Management of a child with burns and a coexistent inhalation injury requires a cohesive team of pediatric intensive care physicians, nurses, and burn specialists.

Children with burns have traditionally been cared for in adult burn units, but the increased availability of physicians, nurses, and ancillary staff trained in the care of severely ill pediatric patients makes the pediatric intensive care unit a superior environment. Understanding that children are not merely small adults is critical to preventing therapeutic errors and disastrous iatrogenic complications.

Exposure to metal fumes and fluorocarbons—systemic toxins typically released during industrial fires—is rare in the pediatric population. Children are less likely to be affected by systemic toxins than by toxins from household products and products of smoke, including CO and CN poisoning.

Pathophysiology

The 3 primary mechanisms that lead to injury in smoke inhalation are thermal damage, asphyxiation, and pulmonary irritation. The combination of these mechanisms can explain the pathophysiologic responses that alter the airway microenvironment with parenchymal damage and predispose smoke inhalation victims to respiratory insufficiency.

Thermal damage

Thermal damage is usually limited to the oropharyngeal area, in part due to the poor conductivity of air. In addition, heat dissipation in the upper airways and laryngeal reflexes help protect the lower lung areas from direct thermal injury. Animal experiments have shown that 142°C inhaled air cools to 38°C by the time it reaches the carina. Steam, volatile gases, explosive gases, and the aspiration of hot liquids provide some exceptions, as moist air has a much greater heat-carrying capacity than dry air.

Asphyxiation

Tissue hypoxia can occur via several mechanisms. Combustion in a closed space can consume significant amounts of oxygen, decreasing the ambient concentration of oxygen to as low as 10-13%. For victims in that setting, the decrease in fraction of inspired oxygen (FIO2) leads to hypoxia, even if they have adequate circulation and oxygen-carrying capacity. If sufficiently severe, hypoxia can lead to multiorgan dysfunction, which substantially raises morbidity and mortality.

Carbon monoxide

Carbon monoxide (CO) is a colorless, odorless gas produced by the incomplete combustion of carbon-containing compounds, such as wood, coal, and gasoline. It is a major component of the smoke produced in open fires.

CO causes tissue hypoxia by decreasing the oxygen-carrying capacity of the blood. Hemoglobin binds CO with an affinity more than 200 times greater than the affinity for oxygen. Other mechanisms contribute, as well.[10] CO causes a left shift in the oxyhemoglobin saturation dissociation curve, which reduces the ability of hemoglobin to unload oxygen.

The heart is particularly affected because CO binds with the heme molecules in myoglobin, decreasing facilitated diffusion of oxygen into muscle. Interaction of CO with myocardial myoglobin results in decreased myocardial contractility.

A classic study demonstrated that dogs breathing 13% CO died within 1 hour after carboxyhemoglobin (CO-Hgb) levels reached 54% to 90%. However, exchange transfusion with blood containing 80% CO-Hgb to otherwise healthy dogs resulted in no toxic effects, despite resultant CO-Hgb levels of 57-64%. This further supports the notion that CO toxicity is not dependent on CO-Hgb formation or, in other words, solely upon a relative anemia.[11]

The literature suggests that hypoxic encephalopathy secondary to CO poisoning results from a reperfusion injury in which the products of lipid peroxidation and free radical formation contribute to morbidity and mortality. The therapeutic effect of hyperbaric oxygen therapy in these patients is attributed to improvement in mitochondrial oxidative metabolism, impairment of adherence of neutrophils to cerebral vasculature (decreases inflammation), and preservation of adenosine triphosphate activity.

Cyanide

CN gas can be produced by combustion of the following:

The incomplete combustion of nitrogen-containing materials releases hydrogen CN (HCN), a colorless gas with a bitter almond odor that is detectable by 40% of the population. The burning of cotton generates 130 µg HCN/g; of paper, 1100 µg HCN/g; and of wool, 6300 µg HCN/g.[12] CN is 20 times more toxic than CO and can cause immediate respiratory arrest.

CN directly stimulates chemoreceptors of carotid and aortic bodies, leading to a brief period of hyperpnea.[12] CN is a small lipophilic molecule and a chemical asphyxiant that interferes with cellular metabolism by binding to the ferric ion on cytochrome a3, subsequently halting cellular respiration. Affected cells convert to anaerobic metabolism, and lactic acidosis ensues.

The organs most sensitive to cellular hypoxia are the central nervous system (CNS) and the heart. The CNS reacts to low concentrations of CN by promoting hyperventilation, thereby increasing exposure.

Consider CN toxicity in all patients with smoke inhalation who have CNS or cardiovascular findings. CN toxicity is difficult to confirm but is frequently concomitant with CO toxicity. Its presence can be inferred by the presence of lactic acidosis in the right clinical setting. Even mild degrees of CN poisoning can cause delayed neurological sequelae in survivors and permanent disability including the following:

Methemoglobinemia

Methemoglobinemia occurs in fire due to heat denaturation of hemoglobin, oxides produced in fire, and methemoglobin-forming materials such as nitrites. Methemoglobinemia is less common in smoke inhalation injury than CN and CO toxicity. The pathophysiologic consequences of methemoglobin formation are a decrease in the oxygen-carrying capacity of the blood and a shift of the oxyhemoglobin dissociation curve to the left, similar to carboxyhemoglobin.

Pulmonary irritation

Pulmonary injury from smoke inhalation is characterized by both hyperinflation and atelectasis. Debris from cellular necrosis, inflammatory exudate, and shed epithelium combine with carbonaceous material to narrow airways that are already compromised by edema. Reflex bronchoconstriction further exacerbates the obstruction.

Both inspiratory and expiratory resistance are increased, and the premature closure of small airways occurs, producing hyperinflation and air trapping. Surfactant production and activity are both impaired, leading to alveolar collapse and segmental atelectasis.

Low-pressure pulmonary edema plays an important role in the development of lung injury from smoke inhalation. Damage to the alveolar capillary membrane increases its permeability, and intravascular leakage into the pulmonary interstitium ensues. Eventually, increased lymphatic flow may be overwhelmed, resulting in alveolar edema. Alveoli fill with thick, bloody fluid. Loss of compliance, further atelectasis, and increasing edema can result in severe ventilation-perfusion mismatch and hypoxia.

Pulmonary injury may also occur as a direct result of hypoxia. The decrease in ambient oxygen tension that occurs during fires in closed spaces depends on the substances that are burned. Gasoline self-extinguishes when oxygen concentrations fall below 15%. Other substances may continue to undergo thermal decomposition, further decreasing ambient oxygen tension. Even small decrements in oxygen tension have a potentiating effect on inhaled asphyxiant gases, such as CO and HCN, resulting in severe lactic acidosis and a high fatality rate.

Inhalation of toxic products triggers a cascade of effects in the lower lung areas, such as the following[13] :

Activation of polymorphonuclear neutrophils (PMNs), resident alveolar macrophages, increased activity of systemic interleukin (IL)–1, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) and neutrophilic infiltration are suggested to mediate the physiopathologic changes that subsequently lead to atelectasis and impaired mucociliary function.[7] In addition, humoral mediators such as prostanoids and leukotrienes produce reactive oxygen species and proteolytic enzymes, which contribute to the development of pulmonary edema and the formation of airway fibrin clots and hypoxemia.

Supporting the importance of the inflammatory response in tissue destruction, some studies have shown that administration of the cyclooxygenase inhibitor ibuprofen reduced the lung lymph flow in animals with smoke inhalation.[14, 15]

The direct injury is a consequence of the size of the particle, its solubility in water, and its acid-base status. Ammonia produces alkaline injury, while sulfur dioxide and chlorine gas cause acid injuries. Other chemicals act via different mechanisms; for instance, acrolein causes free radical formation and protein denaturation.[16]

The solubility of the substance in water determines the location of injury and timing of symptoms. Highly soluble substances such as acrolein, sulfur dioxide, ammonia, and hydrogen chloride cause injury to the upper airway and cause immediate symptoms. Substances with intermediate solubility, such as chlorine and isocyanates, cause both upper and lower respiratory tract injury with more delayed symptoms. Phosgene (a colorless gas with oxidant properties) and oxides of nitrogen have low water solubility and cause diffuse parenchymal injury, with symptoms sometimes delayed up to a day or more.

Days after the injury, the risk of bacterial infection increases markedly. Ciliary function is impaired, leading to accumulation of airway debris. Macrophages within the alveoli are destroyed, allowing bacteria to proliferate. Disruption of the epithelial barrier by ulcerations and necrosis further facilitates the development of pneumonia.

Smokes associated with the military or industry

Smokes and obscurants long have been used by the military as a means of hiding troops, equipment, and certain areas from view of the opposing forces and from engagement by weapons with electro-optical control systems. Although smokes typically are not used as direct chemical agents, they may produce toxic injury to skin, eyes, and all parts of the respiratory tract.[8] Smokes also are produced in industry by explosion, by mechanical generation, or as a by-product of a chemical interaction.

Smokes associated with the military, industry, or both, include the following:

Oxides of nitrogen

NOx are components of photochemical smog, usually approximately 0.053 ppm. Nitrogen dioxide exists as a mixture of nitrogen dioxide, a reddish brown gas, and nitrogen tetroxide, a colorless gas. Other forms of nitrogen oxide include nitrous oxide, which is a common anesthetic or (when inhaled without oxygen) asphyxiant, and nitric oxide, which quickly decomposes to nitrogen dioxide in the presence of moisture.

Inhalation of nitric oxide causes the formation of methemoglobin. Inhalation of nitrogen dioxide results in the formation of nitrite, which leads to a fall in blood pressure, production of methemoglobin, and cellular hypoxia. Inhalation of high concentrations causes rapid death without the formation of pulmonary edema.

More severe exposures result in production of yellow frothy fluid in the nasal passages, mouth, and trachea and marked pulmonary edema, which may be fatal. The symptoms following the inhalation of NOx are mostly due to nitrogen dioxide.

Zinc oxide

Zinc oxide is a constituent of HC smoke, also termed "white smoke," which was developed by the French and US Chemical Warfare Service after World War I. A number of reports have been published on various lung abnormalities occurring in military personnel and firefighters exposed to smoke from HC smoke bombs during training drills.

HC smoke is created by combustion of a mixture of equal amounts of hexachloroethane, zinc oxide, and approximately 7% grained aluminum or aluminum powder. When ignited, these release zinc chloride, and the pyrotechnic mixture of zinc chloride and hexachloroethane rapidly absorbs moisture from the air to form a grayish white smoke.

Other chemicals also are released in the combustion process, such as chlorinated hydrocarbons (eg, phosgene and carbon tetrachloride), chlorine gas, CO, and several other compounds. These most likely contribute to the observed respiratory effects.

HC has a sweetish acrid odor, even at moderate concentrations. HC exposure can produce a gradual decrease in total lung capacity, vital capacity, and diffusion capacity of carbon monoxide (DLCO). It also is associated with the development of pulmonary edema, increased airway resistance, and decreased compliance. These changes were found to be reversible with cessation of episodic exposure.[17]

While upper respiratory tract damage can occur from HC, the mean diameter of the primary smoke particles is approximately 0.1 micrometers, allowing them to reach the alveoli. In a retrospective cohort study of 20 patients, Hsu et al reported significant impairment of pulmonary function within 3-21 days following acute exposure.[18] Follow up in 1-2 months showed significant improvement with mild-to-moderate exposures, whereas severe exposures led to interstitial fibrosis and continued functional limitation.

In a study by Conner et al performed with guinea pigs, exposure to ultrafine HC particles (0.05 µm) in increasing degrees was associated with a dose-response elevation in protein, neutrophils, and angiotensin-converting enzyme found in lavage fluid.[19] A direct relationship also was observed with alkaline phosphatase, acid phosphatase, and lactate dehydrogenase in lavage fluid. Centriacinar inflammation was seen histologically, indicating evidence of pulmonary damage.

An interesting study by Marrs et al involving mice, rats, and guinea pigs demonstrated a positive association of alveologenic carcinoma in a dose-response trend to HC smoke as well as a variety of inflammatory changes.[20] These researchers concluded that hexachloroethane and zinc, as well as carbon tetrachloride (which may be present in HC smoke), may be animal carcinogens in certain circumstances. This raises the suspicion of HC as a potential human carcinogen.

Hepatotoxicity has also been described in humans exposed to HC smokes in enclosed spaces during military training.[21] The toxic effects appear to be primarily due to the chlorinated compounds produced by combustion: tetrachloromethane, tetrachloroethylene, hexachlorobenzene, and carbon tetrachloride. This last compound is well known for its hepatotoxicity. Acute exposure causes elevated liver enzyme levels by day 1 or 2, with a peak around day 18-21. Liver function test results should normalize by 6 weeks.

Metal fume fever

Metal fume fever (MFF) is a well-documented acute disease induced by intense inhalation of metal oxides. MFF is primarily associated with the inhalation of zinc oxide fumes that are produced when zinc-oxide coated steel (galvanized) or zinc containing alloys (eg, brass) is exposed to high temperatures. Keyes found that 1 in 5 welders has experienced MFF by age 30 years.[22]

MFF is a self-limited syndrome characterized by fever, myalgias, headache, and nausea. Symptoms develop 4-12 hours after exposure and typically last several hours; severe cases generally resolve in 1-2 days. Observation is usually all that is necessary.

The exact pathology of MFF is not well understood but likely involves the deposition of fine metal particulates in the alveoli. A study by Kuschner et al on human volunteers showed that pulmonary cytokines such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and interleukin 8 (IL-8) may play important initial roles in mediating metal fume fever.[23]

Red phosphorus

After World War II, RP smoke was developed in an attempt to avoid the toxicity associated with the manufacturing of white phosphorus. RP is 95% phosphorus in a 5% butyl rubber base and provides an adequate tank screen on the battlefield.

When RP is oxidized, it forms a mixture of phosphorous acids. When these acids are exposed to water vapor, they in turn form polyphosphoric acids, which may be responsible for the toxic injuries to the upper airways. Most of these injuries are mild irritations. No human deaths have been reported from exposure to either white phosphorus or RP smokes.

Most of the pathologic consequences associated with phosphorus are from elemental white phosphorus fumes or vapor. Contact with elemental phosphorus can cause burns to body surfaces.

A well-described condition termed phossy jaw is associated with longer-term occupational exposures to airborne phosphorus fumes. This disease is a degenerative condition affecting the entire oral cavity including soft tissue, teeth, and bones. Massive necrosis of teeth, bone, and soft tissue can lead to life-threatening infections. Treatment typically consists of soft tissue and bone debridement, abscess drainage, and reconstructive surgery.

White phosphorus and RP smokes may cause respiratory tract irritation after 2-15 minutes of exposure. This probably is caused by the polyphosphoric acids that react with moist mucosal membranes. Respiratory tract irritation has been observed at concentrations of 187 mg phosphorus pentoxide equivalents per cubic meter for 5 minutes or longer. Intense congestion, edema, and hemorrhages were observed in lung tissue following a 1-hour exposure at varying concentrations in studies using rats, mice, and goats.

Sulfur trioxide

The smoke-producing agent FS, also known as sulfuric oxide, chlorosulfonic acid, or sulfuric anhydride, is typically a colorless liquid, which can exist as ice, fiberlike crystals, or gas. When it is exposed to air, it rapidly takes up water and forms white fumes. The smoke consists of 50% sulfur trioxide and 50% chlorosulfonic acid.

FS usually is dispersed by spray atomization. The sulfur trioxide evaporates from spray particles, reacts with surrounding moisture, and forms sulfur acid. The sulfur acid condenses into droplets that produce a dense white cloud. FS is extremely corrosive, which led to its disuse in by the military. However, it has industrial use as an intermediate in the production of sulfuric acid, as well as other chemicals and explosives.[24]

Toxicity from FS is that of an acidic irritation to mucosal membranes and even skin. The corrosive effect of acid on mucosa and keratinized skin causes significant irritations and chemical burns.

Titanium tetrachloride

Titanium tetrachloride, known as FM, is a colorless-to–pale yellow liquid that has fumes with a strong odor. Upon contact with water, it rapidly forms hydrochloric acid and titanium compounds. It is used to make titanium metal, white pigment in paints, and other products. It breaks down rapidly in the environment.

FM readily hydrolyzes in the presence of water or moist air via an exothermic reaction that occurs in 2 stages. First, FM reacts to form a highly dispersed particulate smoke. This smoke reacts with more moisture in the air to form hydrolytic products of FM such as hydrochloric acid, titanium oxychlorides, and titanium dioxide. Generation of the smoke has been used as screens in military operations. The formation of hydrochloric acid makes it irritating and corrosive.

When FM liquid is exposed to the air, it produces white fumes. These white fumes can come into contact with skin, resulting in a mild epithelial irritation that usually subsides within 24 hours. When mixed with water, FM produces both heat and hydrochloric acid, which can work synergistically to produce deep thermal burns.

The same pathophysiologic effects that occur with FS smoke occur with FM smoke, since both generate corrosive and irritating acids.

Oil fog

SGF2 is another type of chemical smoke obscurant used in the military. SGF2 is generated by injecting a light petroleum-based lubricating oil onto a heated engine exhaust manifold, causing the oil to vaporize and eventually recondense in the atmosphere. Any industry that generates an oil mist also may produce similar exposures. Petroleum oil smokes are the least toxic smokes. They seldom produce ill effects even after prolonged or multiple exposures.

Concentrations of oil mists in industrial settings range widely (0.8-50 mg/m3), with most at 3 mg/m3. The particle sizes also vary more than 1-5 µm in median diameter. They typically have a high molecular weight and are saturated hydrocarbons derived from distilled petroleum. Exposures to such smoke are likely to last for many hours in a single day or repeatedly over consecutive days.

Animal studies have demonstrated that chronic exposure to oil fog had no effect on pulmonary function endpoints such as total lung capacity, vital capacity, residual volume, DLCO, compliance, and end-expiratory volume. One exception exists; male rats exposed at 1.5 mg/L had decreased end-expiratory volume. Bronchiolar lavage and histopathology showed changes consistent with a mild inflammatory edema (ie, increased protein content, total cells, PMNs, macrophages).

Teflon particles

Teflon is used widely, for a variety of purposes (eg, as lubricants, insulators, nonstick coatings), in a range of industrial, commercial, and military settings. Closed-space fires in such settings have prompted studies of the toxicity of exposure to the by-products created from incinerated organofluorines. Pyrolysis of Teflon produces a particulate smoke that, if inhaled, produces a constellation of symptoms termed polymer fume fever (PFF).

Pyrolysis of Teflon occurs at approximately 450°C. Among the particles produced by pyrolysis is perfluoroisobutylene (PFIB), which appears to be the main cause of toxicity in PFF. The ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which suggests an oxidative injury. PMNs may regulate the inflammatory process with cytokine and antioxidant expression.

PFIB particles have an extremely rapid toxic effect on pulmonary tissues. Evidence of microscopic perivascular edema is observed within 5 minutes. Less intense exposures are followed by a latent period during which normal physiologic compensatory measures to control developing pulmonary edema ensue. Once these mechanisms are overcome, the time frame of which depends on the degree of exposure, the clinical syndrome of PFF follows.

More intense exposures also may produce a chemical conjunctivitis. Hemorrhagic inflammation of the lungs also can occur.

Etiology

Most often, inhalation injury results from direct damage to exposed epithelial surfaces and causes conjunctivitis, corneal edema, rhinitis, pharyngitis, laryngitis, tracheitis, bronchitis, bronchiolitis, and alveolitis. Systemic absorption of toxins also occurs. Ascertaining if respiratory insufficiency is due to direct pulmonary injury or is the result of the extensive metabolic, hemodynamic, and subsequent infectious complications of surface burns is difficult.

Inhalants are classified as irritants, asphyxiants, or systemic toxins. Irritants cause extensive cell injury within the respiratory tract. Systemic toxins are absorbed through the respiratory tract and go on to damage other organ systems. Toxic gases are liberated during the combustion of various substances, as listed in the table below.

Table. Inhalants[1, 25]



View Table

See Table

Carbon monoxide

Individual cases of CO poisoning can occur under many circumstances (eg, furnace malfunction, motor vehicle exhaust exposure). Multiple cases may occur after large-scale disasters that result in widespread, long-term power outages (eg, major hurricanes), where the residential use of portable gas generators in poorly ventilated areas creates the ideal situation for CO poisoning. In a study evaluating unintentional CO poisoning of Florida state residents from 1999-2007, 89% of all CO poisoning-related deaths were non–fire related.[26]

Oxides of nitrogen

At ground level, NOx are produced during electric or arc welding, combustion of fuels, detonation of nitrate-based explosives, combination of nitrogen-containing products, and decomposition of organic matter. Recently filled farm silos have high nitrogen dioxide levels for approximately 10 days, peaking at 4000 ppm. Significant quantities of nitrogen dioxide also are found in diesel engine exhaust.

Any person in one of the following occupational tasks or environments is at risk for accidental exposure to NOx:

Zinc oxide

Since this smoke can be distributed by grenades, candles, pots, artillery shells, and special air bombs, any military personnel engaged in the use or activity of these tools are at risk for HC exposure. Exposure to zinc oxide also is common among welders and those who are engaged in the smelting of zinc.

Red phosphorus

Phosphorus smokes are used in military formulations for smoke screens, incendiaries, smoke markers, colored flares, and tracer bullets. Workers at phosphorus loading plants also can be exposed to phosphorus smoke.

Sulfur trioxide

Exposure to FS is an occupational hazard in the chemical and metal plating industries. FS exposure also may occur in the production of detergents, soaps, fertilizers, or lead-acid batteries (car batteries), in printing and publishing, or in photography shops. With reduced use of FS by the military, exposure in that setting has become less common.

Titanium tetrachloride

Because FM smoke breaks down so rapidly in the environment, people who work with it in industry seem to be most at risk. Because titanium tetrachloride is extremely irritating and corrosive in both the liquid formulation and the smoke formulation, its use has diminished.

Oil fog

Military personnel can be exposed to fine-particle oil fog when it is used in training or in combat. Similar exposures may occur in industrial settings where oil mists are created, such as the following:

Teflon particles

Exposure to these fumes is common in closed-space fires where Teflon is pyrolyzed. In addition, polymer fume fever has been observed in persons with occupational exposure to Teflon powder whose cigarettes became contaminated with Teflon.[27]

Epidemiology

Estimates for fatal residential building fires reported annually to US fire departments are 1,800 incidents, 2,635 deaths, 725 injuries, and $196 million in property loss. The death rate has decreased in the past 3 decades, from 30 deaths per million population to 11 deaths per million population.[28] Fire death rates in the United States and Canada are twice as high as in Western Europe and Japan.[29] Burns and fires are the third leading cause of nontransport-related accidental death in all age groups in the United States. They comprise the second leading cause of death in the home for all ages and the leading cause of death in the home for children and young adults.[29]

In 2011, an estimated 484,500 structure fires—370,000 of them residential—occurred in the United States. Overall, fires resulted in 3,005 nonfirefighter deaths, 17,500 injuries, and $11.7 billion in property loss.[30] These figures do not include the estimated 90% of fires not reported to fire departments. More than half of all fatal residential fires started between the hours of 11 pm and 7 am.[29]

The incidence of smoke inhalation increases from less than 10% in patients with a mean total body surface area (TBSA) burn size of 5% to more than 80% in patients with a mean TBSA burn size of 85% or more. Smoke inhalation is present in one third of patients treated at burn centers. The magnitude of smoke inhalation is devastating, as the presence of an inhalation injury has a greater effect on mortality than either patient age or surface area burned.

Racial, sexual, and age-related differences in incidence

One study in New Jersey reports on the demographics of fire fatalities and notes that victims who perished did not parallel the ethnic census of the time.[5, 29] Whites accounted for 53% of fatalities and comprised 49% on the census. African Americans accounted for 38% of fatalities and 13% of the census.

The male-to-female ratio in fire fatalities is about 3:2.

The New Jersey study also showed that children and the elderly represented a disproportionate percentage of people injured by fire.[29] People younger than 11 years or older than 70 years constituted 22% of the population but accounted for 40% of all fire fatalities. These statistics closely match national figures.

Small children are especially vulnerable because they are less likely to escape a confined space and they also have a higher minute ventilation, which increases exposure to smoke and other toxins released during pyrolysis. In addition, their relatively smaller airways are more severely affected by airway edema and obstructing material.

Burns in children are 2.5 times more likely to occur by scalding rather than flame exposure. Hence, the percentage of children who experience respiratory symptoms after burns is less than that of adults, who are more often exposed to smoke-producing flames. About 50% of all burn deaths are related to inhalation injuries. Early hypoxemia is a contributor to over 50% of smoke inhalation deaths, with CO intoxication accounting for as much as 80% of the fatalities.

A comprehensive study in Dallas, Texas looked at all house fires from 1991-1997.[31] Many of the findings parallel those of the New Jersey study. Relative risk of injury was 1.8 for men, 1.4 for boys, 2.8 for blacks, and 2.6 for elderly persons. In addition, among the injured, the proportion of injuries that were fatal was higher in persons older than 65 years (53%) and in those younger than 10 years (67%) compared with those aged 10-64 years (30%).

The lowest income tracts had the highest rate of injury. The rate of injury in households with a median income below $20,000 per year was 8 times that of tracts with a median income greater than $80,000 per year. In fact, tracts with extremely low incomes, less than $10,000 per year, had rates of injury 20 times that of the above.

Houses built in the 1950s and 1960s were somewhat more likely to burn than houses built before this time. This may be a case of "selection of the fittest" houses, with those houses most prone to burn having already done so, leaving the most structurally sound ones still standing.

Fires caused by arson occurred predominately in census tracts with lower median incomes. Eighty percent of fires occurred in homes with median incomes of less than $40,000 per year.

Causes of the house fires were as follows:

The rate of fire-related injury in houses in Dallas without a functioning smoke detector was 8.7 times that of homes with functioning smoke detectors. Houses that are most likely to have fires were least likely to have functioning smoke detectors. As a result of this study, a program in Dallas now provides and installs smoke detectors in census tracts with the highest rates of injuries and deaths related to house fires.[31]

Prognosis

Most inhalation injuries are self-limited and resolve within 48-72 hours. The severity of direct pulmonary parenchymal injury depends on the extent of exposure and the type of inhaled toxins produced during combustion. Most patients do not manifest spirometry changes. Rare long-term sequelae include tracheal stenosis, bronchiectasis, interstitial fibrosis, and bronchiolitis obliterans.

The prognosis for mild-to-moderate exposures of toxic smokes is generally very good, with the usual outcome return to full recovery without sequelae. Metal fume fever is self-limited and usually resolves after a short period of observation. Exposure to white smoke (HC) in a military setting can lead to acute lung injury and in severe cases to ARDS. With more severe exposures, lungs may become severely damaged and develop chronic pulmonary fibrosis.

Children with acute pulmonary injury from toxic inhalations generally do well once supported through the initial period of inflammation and damage. Most of the pulmonary damage is self-limited and resolves within 2-3 days. The degree of recovery depends on the extent of the pulmonary parenchymal injury and subsequent hypoxic damage to the organs.

Complications

Complications may include the following:

Bacterial pneumonia often complicates inhalation injury within 4-5 days of presentation. This additional cellular damage can cause significant mortality days to weeks after the initial injury.

Exacerbation of pre-existing respiratory disease (eg, asthma, chronic obstructive pulmonary disease) is a potential sequela.[32] A study of firefighters showed certain subgroups to have an exaggerated decline in postexposure forced expiratory volume in 1 second (FEV1) that was not predicted by age, smoking history, intensity of exposure, or the use of self-contained breathing apparatus.[33] Some of these patients, who had no family history of reactive airway disease, went on to need long-term beta-agonist therapy. Exposures to some smokes, such as isocyanates, can cause asthma in people with no history of the disease.

Airway hyperreactivity generally improves over several months following inhalation injury. However, some authors documented long-term respiratory symptoms such as cough, wheeze, and shortness of breath even after mild inhalation injury. The long-term effects of inhaled toxins on pulmonary function are not yet determined.

Carbon monoxide poisoning

Concurrent CO poisoning and inhalation of other products of combustion can cause hypoxemia, end-organ injury, and morbidity. CO intoxication is a particularly serious consequence of smoke inhalation and may account for as much as 80% of fatalities from inhalation injury.

Most patients who arrive alive to the emergency department make a full recovery. However, up to one third of patients with significant CO exposure develop a secondary syndrome of long-term neurologic or neuropsychiatric dysfunction within 1-3 weeks after exposure. Higher cortical functions seem most severely affected. Whether the use of hyperbaric oxygen (HBO) therapy alters the outcome of delayed-onset neurologic dysfunction from CO poisoning remains controversial.

Mortality

Severe pulmonary injury, edema, and the inability to oxygenate or ventilate can result in death. A study of the characteristics of survivors and casualties of fire fatalities found that the following specific risk factors seem to elevate the rate of mortality[34] :

The combination of cutaneous burn and smoke inhalation results in far higher mortality rates than occur with either injury in isolation. In patients with a burn and no associated smoke inhalation or respiratory failure, the mortality rate is less than 2%. In patients with smoke inhalation alone and no burn or respiratory failure, the mortality rate is 7%. For patients with both a burn and smoke inhalation, the mortality rate increases to 29%, suggesting that the burn wounds themselves put an additional stress on the compromised lung.[35]

In a study by Chou et al of 150 children with CO poisoning who were referred for hyperbaric oxygen therapy, none of the children with CO poisoning alone died, compared with 22.6% of those with the combination of CO poisoning and smoke inhalation. Among children who died, 60% had the following combination of risk factors[36] :

Patient Education

Clinicians should encourage the use of smoke and CO detectors in the home, which can decrease the risk of injury by permitting early escape. Regular checks to ensure that the detectors are functioning should be part of the household routine. In one study, the presence of a functioning smoke detector lowered the risk of death in a residential fire by over 60%.[31]

Programs aimed at educating young children about the dangers of playing with lighters and matches and programs teaching families how to safely escape from burning buildings should be used to further limit the number of children experiencing inhalation and burn injury. Anticipatory guidance during well child visits should include fire safety instructions.

For patient education resources, see the Lung and Airway Center, First Aid and Injuries Center, Procedures Center, and Poisoning Center, as well as Smoke Inhalation and Carbon Monoxide Poisoning.

History

In patients exposed to smoke, details of the exposure—the duration, the amount of smoke inhaled, and the toxins contained in the smoke--can help determine the risk for inhalation injury. Unfortunately, these details are often not known, although some information can often be garnered from rescuers and other observers present at the scene.

Critical information regarding the scene includes the severity of injury to other victims, especially loss of consciousness or death. In addition, exposure to fire in a closed space, prolonged duration of entrapment, evidence of carbonaceous sputum, the requirement for cardiopulmonary resuscitation (CPR) at the scene, the presence of respiratory distress, and obtundation all increase the risk for significant pulmonary disease and hypoxic injury.

Simple carbon soot is not particularly toxic, although it may carry and deposit other toxins directly onto the airway surfaces, thereby increasing exposure. Significant toxicity occurs with the inhalation of asphyxiants, including carbon monoxide (CO), nitrogen, and methane. These asphyxiants cause injury by interrupting the delivery of oxygen to the tissues. Asphyxiants either displace oxygen from the air or interfere with tissue oxygen delivery by blocking the action of hemoglobin or cytochrome oxidase (eg, CO, cyanide [CN]).

CO poisoning must be considered in any person injured in a fire. CO is a major component of smoke produced in most open fires, particularly those involving wood, coal, gasoline, and other organic substances. In addition, significant CO exposure can occur in the absence of open flames, as a result of malfunctioning domestic equipment (eg, poorly ventilated space heaters, cooking gas) or exposure to automobile exhaust fumes either from a suicide attempt or accidentally from poor ventilation.

Hydrogen CN is an asphyxiant that is released during the incomplete combustion of products such as cellulose, nylon, wool, silk, asphalt, polyurethane, and plastics. CN has a characteristic almondlike odor. Hydrogen CN is absorbed rapidly, producing an almost immediate effect if exposure is by inhalation. In contrast, CN salts (eg, potassium, sodium CN, and, particularly, silver and copper CN), which are typically ingested, must be converted to hydrogen CN and are absorbed more slowly.

Damage varies with the chemical activity of the particular inhalants, their size, solubility, and the duration and concentration of exposure. Upper airway injuries tend to be caused by the more irritating, water-soluble, larger particles. Substances of smaller size and lower water solubility cause alveolar and parenchymal injury.

A history of respiratory illnesses, such as asthma or chronic obstructive pulmonary disease (COPD), predisposes patients to respiratory insufficiency.

The extent of illness from smoke inhalation can be notably different between children and adults, despite similar exposures. Children frequently become disoriented at fire scenes and may attempt to hide from flames and smoke, thereby prolonging their exposure to toxic inhalants. In addition, children have greater minute ventilation relative to body size than do adults, further increasing their exposure to toxic inhalants.

Inhalation injuries occur without skin burns or other obvious external injury; hence, a high degree of suspicion must be maintained. A retrospective review of 4,451 children with thermal injuries over 10 years demonstrated that inhalation injury was often not recognized, manifested late, and usually had significant consequences, including parenchymal injury and secondary pneumonia.[37]

Thermal injury is generally confined to the upper airway, because of its vast heat capacitance. Inhalation of steam is a notable exception, in which lower airway and pulmonary parenchymal thermal injury are common. Theoretically, continued combustion of inhaled particulate matter could possibly produce more distal airway injury.

Thermal injury to the mucosa produces burns and edema of the nose, mouth, pharynx, and larynx. The loose tissues of the upper airway swell readily in response to injury. Loss of colloid oncotic pressure can result in obstruction of the airway, particularly in patients receiving fluid resuscitation.

The full extent of airway compromise may not be evident until 12-24 hours after the initial injury. For patients with extensive surface burns, chest wall restriction may occur because of eschar formation, necessitating emergent escharotomy.

Toxic smokes

Different clinical presentations may result from exposure to smoke containing the following toxins:

Oxides of nitrogen

Because of their insolubility in water, NOx tend not to cause immediate upper airway irritation. Unfortunately, this may allow a significant exposure to remain undetected for prolonged periods. As with most toxic inhalations, severity of illness and presentation are related to the concentration of the smoke or fumes, length of time of exposure, manner in which the exposure was delivered, and the health status of the exposed individual.

Mild exposure to NOx results in upper airway and ocular irritation such as itching or burning eyes. Cough, dyspnea, fatigue, chest tightness, throat tightness, nausea, vomiting, vertigo, somnolence, and loss of consciousness also may occur from mild exposure.

At weaker concentrations of NOx, the individual may experience very little discomfort, quickly accommodating to the cough, mild choking, or upper airway irritation. Because of this, symptoms may appear quickly or remain unnoticed for a few hours. Although the symptoms of mild exposure may become quite dramatic, complete recovery is expected within 24 hours, once the patient is removed from the exposure.

In more severe exposures, the clinical response may be described as triphasic. During phase 1, an intense respiratory symptom complex may occur. Severe cough, dyspnea, and pulmonary edema may arise suddenly. Physical exertion may be a precipitating factor, quickening the progression to pulmonary edema. If the patient survives this episode, spontaneous remission occurs within 48-72 hours postexposure.

Phase 2 lasts from 2-5 weeks and is relatively uneventful. A mild residual cough with malaise and perhaps dyspnea may linger, but the chest radiograph typically remains clear.

In phase 3, which occurs 3-6 weeks after the exposure, symptoms may recur. Severe cough, fever, dyspnea, and cyanosis may develop in the setting of rales and increasing carbon dioxide retention.

More acutely severe exposures can result in immediate death from bronchiolar spasm, laryngeal spasm, reflex respiratory arrest, or simple asphyxia. Some exposures can progress from mild upper airway irritation to pulmonary edema in 3-30 hours.

Even in individuals with asthma or chronic obstructive bronchitis, NOx concentrations of 0.5 ppm or less generally have no effect. levels from 0.5-1.5 ppm begin to bother patients with asthma, who notice minor airway irritation. With concentrations greater than 1.5 ppm, people with healthy lungs experience decreases on pulmonary function tests and decreased carbon monoxide diffusing capacity (DLCO), with widening of the alveolar-arterial gradient on arterial blood gas measurement.

Zinc oxide

Individuals exposed to HC smoke may complain of nose, throat, and chest irritation. They may experience cough and some nausea. Individuals with severe exposures may present in severe respiratory distress, and such exposures can be fatal. A thorough social history offers vital clues to exposure, since respiratory distress can mimic many different disease processes (see Etiology).

Patients with fume fever typically present in a delayed fashion 4-8 hours after exposure with a pattern of symptoms including dryness of the throat, coughing, substernal chest pain or tightness, and fever. Other symptoms include hoarseness, sore throat, retching, paroxysmal coughing, rapid pulse, malaise, shortness of breath, and abdominal cramps. Respiratory symptoms generally disappear in 1-2 days with supportive care.

Milder exposures are characterized by sensations of dyspnea without any auscultatory, radiologic, or blood gas abnormalities. A patient with moderate exposure to HC may demonstrate rapid clinical improvement within 6 hours. These patients usually are sent home, only to return in 24-36 hours with rapidly worsening dyspnea and dense infiltrative processes on chest radiography. The radiographic abnormalities usually clear, but significant hypoxia may persist during the time the chest radiograph is abnormal.

Prolonged exposures or exposures to very high doses of HC may result in sudden early collapse and death. This may be due to laryngeal edema or glottal spasm. If severe exposure does not kill the individual immediately, hemorrhagic ulceration of the upper airway may occur, with paroxysmal cough and bloody secretions. Death may occur within hours secondary to an acute tracheobronchitis.

Most individuals with HC inhalation injuries progress to complete recovery. Of exposed individuals, 10-20% develop fibrotic pulmonary changes. Distinguishing between those who will recover and those who will not is difficult, since both groups make an early clinical recovery.

Red phosphorus

Individuals with toxic inhalation usually have a history of exposure to the smoke either on the battlefield or in some other setting where phosphorus smokes are used. Complaints of eye, nose, and throat irritation are common. Severe exposure can be associated with an explosive, persistent cough. Most often, the cough and irritating symptoms resolve after the individual is removed from the exposure source. Contact with unoxidized phosphorus can produce painful, erythematous chemical burns to the skin.

Sulfur trioxide

FS smoke is extremely irritating. Consequently, people escape the smoke as soon as possible, and exposure tends to be brief.

FS-exposed individuals complain of cough; substernal ache or soreness; and a burning sensation in the eyes, nose, mouth, and throat. Blurry vision and photophobia also may be complaints. If inhalant injury is severe enough, explosive cough and shortness of breath may develop. The individual may complain of a prickling sensation of the exposed skin, which could be the prelude to pending chemical dermatitis.

Titanium tetrachloride

Several industrial exposures to FM liquid and smoke have been reported, but only 1 death. This was in a worker who accidentally was splashed over his entire body with liquid FM. He died from complications resulting from inhalation of FM fumes and overwhelming superinfection.

Oil fog

Individuals exposed to Smoke Generator Fog 2 (SGF2) or other oil mists may report mild irritation or slight cough, a sensation of shortness of breath, or headache. In persons with underlying pulmonary disease such as asthma or COPD, exposure to SGF2 may trigger symptoms of their disease.

Teflon particles

Exposure to smoke containing Teflon particles may result in influenzalike illness, with malaise, fever (at times to 104°F), chills, sore throat, sweating, and chest tightness 1-4 hours postexposure. These symptoms usually resolve 24-48 hours after the patient is removed from the source.

More intensely exposed individuals complain of dyspnea on exertion, orthopnea, and later, dyspnea at rest. Cough productive of bloody sputum occasionally is seen. Some animal studies have demonstrated disseminated intravascular coagulation and other organ involvement, but this may be due to global hypoxia, since this occurred only in animals with severe lung damage.

Cases of polymer fume fever from pyrolysis of Teflon have been reported in persons exposed to pyrolyzed hairspray and horse-rug waterproofing spray and in one individual smoking hand-rolled cigarettes after working with dry lubricant.[38]

Physical Examination

In the primary survey, assess patency of the airway, breathing, and circulation. Maintain cervical immobilization in any patient who is obtunded, has distracting injuries, has been involved in a significant mechanism of injury, has bony tenderness, or complains of neck symptoms.

Assess breathing by respiratory rate, chest wall motion, and auscultation of air movement. Assess circulation by level of consciousness, pulse rate, blood pressure, capillary refill, and by symmetry and strength of pulses.

Perform a brief neurological evaluation, including a determination of the Glasgow Coma Scale, pupil size and reactivity, and any focal findings. Remove all clothing to expose traumatic injuries/burns and to prevent ongoing thermal injury from smoldering clothes. Evaluate patient's back and perform a log roll if appropriate.

Identification of signs or symptoms of airway compromise is important to permit early and aggressive treatment before rapid progression to upper airway obstruction and respiratory failure ensues.

The secondary survey continues in a complete head-to-toe examination as in any other trauma evaluation. Burns on the face, soot marks, and singed eyebrows or facial hair are indicative of smoke inhalation. Large cutaneous burns indicate an inability to escape flame and a risk for smoke inhalation injury. However, inhalation injury can occur without evidence of burns.

Recognizing that upper airway swelling may take several hours to develop is imperative. Thus, facial burns, hoarseness, stridor, upper airway injury with mucosal lesions identified upon oral examination or bronchoscopy, and carbonaceous sputum are indications to promptly secure artificial airway access.

Symptoms of lower respiratory tract injury include the following:

Neurologic injury

Signs of neurologic injury may take longer to appear than evidence of respiratory injury. Neurologic injury may result from hypoxia at the time of injury or hypoxia secondary to pulmonary dysfunction. Fear, severe pain, and obtundation from inadequate perfusion may cloud the neurologic examination. Serial examinations assessing the sensorium are extremely helpful in guiding the initial resuscitation and stabilization.

Patients exposed to asphyxiants, including CO and cyanide (CN), present with hypoxic injury and subsequent CNS depression, lethargy, and obtundation. Hypoxia is caused by an asphyxiant and is usually evident upon presentation. Irritability, severe temporal headache, and generalized muscle weakness are also common findings.

Coma following exposure to fire is nearly always indicative of CO poisoning and should be promptly treated with 100% oxygen. Suspect CN toxicity in the patient whose sensorium remains clouded and who does not respond to oxygen therapy.

Cardiovascular injury

Complex cardiovascular changes associated with surface burns may coexist with inhalation injury. Heart rate, capillary refill, warmth of unburned extremities, and blood pressure should be promptly evaluated at presentation and at frequent regular intervals during the initial stabilization.

Pay careful attention to narrowed pulse pressure because this may indicate inadequate volume resuscitation. Hypotension is invariably a late finding of volume loss.

Other injury

Renal tubular acidosis, hepatitis, and bone marrow insufficiency are not uncommon, particularly when hypoxic injury is either severe or prolonged. Organ system dysfunction is also common as a result of the complex hemodynamic and inflammatory reactions associated with significant burns. In the obtunded patient, assume coexistent spine injury.

Carbon monoxide

Altered vital signs in patients with CO toxicity may include tachycardia, hypertension or hypotension, and hypothermia or hyperthermia. Mild tachypnea may be present; rarely, patients with severe intoxication may have marked tachypnea. Noncardiogenic pulmonary edema may be present.

The skin may exhibit pallor; the classic sign of cherry-red skin occurs rarely and is generally a postmortem finding. Findings on ophthalmologic examination may show reveal bright red retinal veins, flame-shaped retinal hemorrhages, and papilledema.

Cyanide

CN stimulates nociceptors, leading to a sensation of burning and dryness in the throat and nose. Therefore, hoarseness, change in voice, complaints of throat pain, and/or odynophagia indicate an upper airway injury that may be severe. Tachypnea may be present. Wheezing, rales and rhonchi, and use of accessory respiratory muscles may be noted.

Low levels of CN increase cardiac output. At higher levels, a wide variety of bradyarrhythmias and tachyarrhythmias occurs. With progressively higher levels of exposure, obtundation, seizures, and apnea occur. In the most severe cases, death occurs immediately from respiratory arrest.

Oxides of nitrogen

The severity of physical examination findings depends on the severity of exposure. Mild exposure may result in injected conjunctivae and normal to mildly erythematous-appearing mucous membranes. After a more severe exposure, signs may range from mild respiratory distress (eg, tachypnea, accessory muscle use) to more severe signs of wheezes and rales, yellow frothy sputum, and yellow staining of the mucous membranes. This may be followed by cyanosis, lethargy, convulsions, coma, and death.

Zinc oxide

As with other inhalation injuries, physical examination findings in zinc oxide exposure depend on the time of exposure, concentration of the gas, method of gas distribution, and underlying general health of the exposed individual. Physical examination findings may range from slight dyspnea and increased work of breathing to severe respiratory distress, convulsions, coma, or death. Hoarseness and cough are common findings. Retching, fever, tachycardia, hypoxia, and cyanosis may be present, as well as pulmonary wheezes and rales.

Red phosphorus

Physical examination findings are those associated with irritation of mucosal surfaces. A cough or chemical burns to exposed skin surfaces from direct contact with unoxidized phosphorus may be present.

Sulfur trioxide and titanium tetrachloride

Physical examination findings vary due to length of exposure, concentration of FS smoke, environment of the exposure, and underlying health of the exposed individual. FS smoke exacerbates symptoms of asthma or COPD and can worsen pulmonary function test results in these patients.

Conjunctivitis, corneal erosion, lacrimation, erythema of exposed skin surfaces, and mucosal inflammation may be present. Intense salivation may follow. The individual may have a cough with bloody sputum, dyspnea, hypoxia, rales, or wheezes.

Teflon particles

Physical examination findings in patients exposed to Teflon fumes similar to that of patients with chemical inhalation injury, but fever often is present as well. Dyspnea, increased work of breathing, and rales are common. Pulmonary edema usually is mild and typically does not require oxygen supplementation.

More intense toxicity and hypoxia may be seen, requiring more invasive methods of oxygenation and ventilation. Pulmonary edema is also worse if the individual exercises after exposure.

Approach Considerations

In the workup of inhalation injuries caused by toxic smoke, the primary investigation focuses on the pulmonary system. Other tests may be clinically indicated based on history, physical examination, and underlying health problems. Initial blood tests should include lactate and CO-oximetry in addition to electrolytes and arterial blood gases. Carbon dioxide levels also may be monitored, since patients with prior lung disease such as asthma and chronic obstructive pulmonary disease may be affected more severely and are at greater risk to retain carbon dioxide.

Studies may include the following:

Pulse Oximetry and CO-oximetry

Pulse oximetry readings can be misleading in the setting of carbon monoxide (CO) exposure or methemoglobinemia because these devices use only 2 wavelengths of light (the red and the infrared spectrum), which detect oxygenated and deoxygenated hemoglobin only and not any other form of hemoglobin. Readings are falsely elevated by CO-bound hemoglobin (carboxyhemoglobin).

In methemoglobinemia, light reflection is similar to that in reduced hemoglobin. Pulse oximetry may show a depressed oxygen saturation, but the decrease does not accurately reflect the level of methemoglobinemia. In fact, as methemoglobin levels reach 30% or higher, the pulse oximetry reading converges on approximately 85%.

CO-oximeters use 4 wavelengths of light and are capable of detecting carboxyhemoglobin and methemoglobin as well as hemoglobin and oxyhemoglobin. Some newer co-oximeters use 5 wavelengths and are also able to measure sulfhemoglobin. The percent of oxyhemoglobin measured by CO-oximetry is an accurate measure of the arterial oxygen saturation. The difference between saturations obtained by CO-oximetry and calculated figures is known as the saturation gap and is an indicator of dyshemoglobinemia.

Arterial Blood Gases

Arterial oxygen tension (partial pressure of arterial oxygen [PaO2]) does not accurately reflect the degree of CO poisoning or cellular hypoxia. The PaO2 level reflects the oxygen dissolved in blood that is not altered by the hemoglobin-bound CO. Because dissolved oxygen makes up only a small fraction of arterial oxygen content, a PaO2 level within the reference range may lead to serious underestimation of the decrement in tissue oxygen delivery and the degree of hypoxia at the cellular level that occurs when CO blocks the delivery of oxygen to the tissues.

With most blood gas machines, the oxygen saturation is calculated on the basis of the PaO2 level. Thus, such a reading does not give an accurate determination of oxygen saturation, which must come from CO-oximetry.

ABG measurements are nonetheless useful to assess the adequacy of pulmonary gas exchange. Although the presence of a PaO2 level that is within the reference range may not exclude significant tissue hypoxia due to the effects of CO, the presence of a low PaO2 (< 60 mm Hg in room air) or hypercarbia (alveolar [arterial] carbon dioxide pressure [PaCO2] level of 55 mm Hg) indicate significant respiratory insufficiency. Metabolic acidosis suggests inadequate oxygen delivery to the tissues.

The difference between the partial pressure of oxygen in the alveolus and that measured on an ABG is the alveolar-arterial (A-a) gradient. This value, usually less than 5-10 mm Hg, may be several hundred mm Hg in the setting of significant pulmonary injury and can be used to assess improvement or deterioration in lung function when measured at a stable fraction of inspired oxygen (FiO2).

The alveolar gas equation can be used to estimate the efficiency of pulmonary oxygen delivery to the arterial circulation in the presence of supplemental oxygen administration. This formula determines the alveolar oxygen pressure.

The formula is as follows: PaO2 = (FiO2)(PB - PH2 O) - (PaCO2/RQ). PB represents barometric pressure, PH2 0 represents the partial pressure of water vapor (47 mm Hg at body temperature, ambient pressure), and RQ represents the respiratory quotient (estimated at 0.8).

Carboxyhemoglobin Level

Carboxyhemoglobin levels in the blood and the corresponding clinical manifestations are as follows[1] :

Blood carboxyhemoglobin levels may underestimate the degree of CO intoxication because of oxygen administered to the patient before arrival to the hospital. Smokers may have baseline levels up to 5-10% and may experience more significant CO poisoning for the same level of exposure as nonsmokers. Finally, correlation between carboxyhemoglobin levels and eventual neurologic outcome is poor.

Lactate and Other Blood Studies

Elevated lactate levels may result from metabolic acidosis secondary to the following:

Lactate levels associated with CN poisoning have been reported as being above 8 mmol/L.[12] The concentration of lactate increases proportionally with the degree of CN poisoning, and lactate levels higher than 10 mmol/L are a sensitive indicator of CN levels higher than 1 mg/mg.[39] Note that in most institutions, CN levels can take hours to days for results; therefore, one must rely on clinical and indirect laboratory data.

Other Blood Studies

Electrolyte testing can identify an anion gap acidosis. In patients who require large-volume fluid resuscitation, measure electrolytes at regular and frequent intervals to monitor for the electrolyte abnormalities that may occur in these patients. Use results to adjust both fluid and electrolyte replacement.

Blood urea nitrogen (BUN) and creatinine levels should be obtained for baseline renal function determination in patients in shock or with rhabdomyolysis. Patients with large cutaneous burns, crush injuries, or prolonged immobilization should have their serum creatine kinase (CK) checked and, if appropriate, urine myoglobin.

Exposure to zinc oxide warrants baseline liver function tests on initial presentation. Liver function should be followed over the course of hospitalization if exposure is severe enough to warrant admission.

Thermal degradation products of various compounds, including phosphorus-based fire retardants, are capable of impairing cholinesterase activity. A prospective study measured serum erythrocyte cholinesterase activity at the scene of residential fires for 49 victims. A significant lower level of cholinesterase activity was noted in these patients as compared to controls. Obviously, further investigation into the clinical significance of this lower enzymatic activity is needed before it can be used clinically.

Lead-containing paint is common in structures built before 1977, and this element can become aerosolized and absorbed directly into the bloodstream from the lungs. While it is true that severe smoke inhalation has been shown to increase serum lead levels more than 2-fold, no evidence suggests that these elevations are clinically relevant.[40]

CBC Count

A baseline CBC count is warranted, as certain types of smoke are associated with a significant drop in hemoglobin and hematocrit beginning at 1 week postexposure.[41] A baseline white blood cell count can also be used for comparison when concerns arise about infection.

Hemoconcentration resulting from fluid losses is common immediately following injury. Adequate restoration of intravascular volume results in a progressive fall in hematocrit. Severe anemia may require blood transfusion, particularly in the presence of significant hypoxia or hemodynamic instability.

Cyanide Levels

Cyanide (CN) levels correlate closely with the level of exposure and toxicity, but these values may not be readily available. Many hospitals send out tests for CN levels, and results may not return for several days to a week. In a setting consistent with potential CN exposure, institute specific empiric therapy while waiting for laboratory confirmation of the diagnosis.

Findings indicative of CN intoxication include the following:

Radiography

Obtain chest radiographs in patients with a history of significant exposure or pulmonary symptoms. The chest film is likely to be normal—initial studies have only 8% sensitivity for smoke inhalation—but it provides a baseline for subsequent comparison in cases of significant injury. Radiographic evidence of pulmonary injury typically does not appear until 24-36 hours after the inhalation.

When present, abnormal findings may include atelectasis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Hyperinflation may suggest injury of the smaller airways and air trapping.

Individuals with fume fever often are sent home after 4 hours of observation and with a clear chest radiograph, only to return after the initial recovery and latent phase with more severe dyspnea and florid noncardiogenic pulmonary edema. The chest film in a patient with significant zinc oxide exposure may not show any abnormality until 4-6 hours post exposure. Radiographic abnormalities in these patients may improve slowly with supportive care or advance to a long-standing diffuse interstitial fibrosis.

In phase III of oxides of nitrogen exposure, a noncardiogenic pulmonary edema pattern may be seen on the chest radiograph. The chest radiograph may also show a pattern similar to military tuberculosis, which corresponds to a pathologic finding of classic bronchiolitis fibrosa obliterans. Fibrotic changes either may clear spontaneously or proceed to severe respiratory failure.

Cervical spine radiography is indicated to investigate neck injury in all unconscious patients and in those with a potential mechanism of injury (eg, a patient who jumped from a window to escape fire or fell down stairs).

Computed Tomography

Chest computed tomography (CT) scans may show ground-glass opacities in a peribronchial distribution and/or patchy peribronchial consolidations. These findings may be present on CT scan as early as a few hours after inhalation injury.[42]

A CT scan of the brain may show signs of cerebral infarction due to hypoxia, ischemia, and hypotension. An interesting and well-reported finding for severe CO toxicity is bilateral globus pallidus low-density lesions. These lesions may not appear until several days after the exposure days. This finding is highly specific for CO insult—unlike focal cortical hypoperfusion, which is nonspecific.

Radionuclide Scintigraphy

Delayed or inhomogeneous clearance of 133Xenon can be used to detect small-airway parenchymal injury. However, this study adds little to the clinical management and is not known to offer any particular therapeutic advantage.[43]

Likewise, increased clearance of aerosolized technetium-99m–labeled diethylenetriaminepentaacetate (99mTcDTPA) is a sensitive indicator of injury to the alveolar capillary membrane. However, its clinical use is not yet established.

Pulmonary Function Testing

Perform baseline pulmonary function tests (PFTs) once the patient is stable. In the ED, serial peak flow readings may be helpful. Later, PFTs allow evaluation and comparison of lung function and reversibility with bronchodilators and potentially steroids. If the patient develops dyspnea on exertion, then perform PFTs with exertion if PFTs at rest cannot explain the symptoms.

Pulmonary function test results become abnormal soon after inhalation injuries. Vital capacity, pulmonary compliance, and functional residual capacity are reduced. In patients with bronchospasm, forced expiratory volume in 1 second (FEV1), peak flow, and midexpiratory flow rates are reduced. Diagnostic accuracy is 91%.

In patients with cutaneous burns, the reduction in vital capacity and FEV1 correlates closely with the extent of surface burns. Full resolution of pulmonary function test result abnormalities may take several months. Some agents, particularly chlorine gas, may result in reactive airways syndrome, with subsequent development of airflow obstruction.

Direct Laryngoscopy and Fiberoptic Bronchoscopy

A significant number of patients may present with a paucity of upper airway signs or symptoms but may still have serious subglottic injury. The threshold for performing diagnostic bronchoscopy should be low. Bronchoscopy can be diagnostic as well as therapeutic, particularly when lobar atelectasis is present.

Bronchoscopy is the criterion standard for diagnosis of smoke inhalation injury.[42] This procedure examines the airways from the oropharynx to the lobar bronchi. Although it may be performed in the ED, the intensive care unit or burn unit may be a more appropriate setting, especially in patients who are intubated.

Erythema, charring, deposition of soot, edema, and/or mucosal ulceration may be present, although severe vasoconstriction from hypovolemia may mask significant injury. Impending airway obstruction may be inferred. Diagnostic accuracy is reported to be 86%. Fiberoptic bronchoscopy can also be used to facilitate endotracheal tube placement, even in the technically difficult airway.

Studies have shown up to a 96% correlation between bronchoscopic findings and the triad of closed-space smoke exposure, carboxyhemoglobin levels of 10% or greater, and carbonaceous sputum. In another study, serial bronchoscopy was twice as sensitive for diagnosing inhalation injury as clinical findings alone. Bronchoscopy is more sensitive and accurate than clinical examination alone in diagnosing inhalation injury and is, therefore, particularly useful in cases in which the decision to perform endotracheal intubation is unclear.

The use of bronchoscopy in patients with inhalation injury complicated by pneumonia is associated with a decreases in the duration of mechanical ventilation, length of intensive care unit stay, and overall hospital cost.[44] Serial bronchoscopy can help remove debris and necrotic cells in cases with aggressive pulmonary toilet or when suctioning and positive pressure ventilation are insufficient.

Bronchoscopy in children requires the use of a bronchoscope with a relatively small diameter, in order to accommodate the narrow pediatric airway. Extremely small diameter fiberoptic bronchoscopes with a suction port (capable of entering an endotracheal tube sized for a small toddler or infant) have only recently become available, and whether these limit the ability to remove heavy particulate matter is unclear.

Approach Considerations

Beware that patients may appear asymptomatic on arrival but may develop significant signs and symptoms as long as 36 hours after exposure, especially in fires, which produce small particles with low water solubility. Be aware of pertinent historical risk factors when treating patients with potential smoke inhalation injury. These include closed-space fires, carbonaceous sputum, elevated carbon monoxide (CO) levels, and central facial burns.

Acute respiratory distress usually responds very well to aggressive initial management. Normal laboratory values and imaging studies, coupled with clinical improvement, can give the health care provider a false sense of security. The patient then may be discharged, only to deteriorate as delayed pulmonary edema ensues. Any patient with significant exposure to toxic smokes should be observed for 24-48 hours and imaged with serial chest radiographs. Difficulty arises in defining a significant exposure, since the clinical response is so varied.

Provide intravenous (IV) access, cardiac monitoring, and supplemental oxygen in the setting of hypoxia. A small subset of patients manifests bronchospasm and may benefit from the use of bronchodilators, although this is not well documented. This is especially true of patients with underlying chronic obstructive pulmonary disease (COPD) or asthma.

Treatment of inhalation injuries caused from toxic smokes is based on clinical presentation and involves primarily supportive care directed at the cardiopulmonary system. In some cases (eg, cyanide [CN] poisoning, methemoglobinemia), specific antidotes are available. Subcutaneous epinephrine has been used in zinc oxide (HC) exposures.

Corticosteroids are attractive for suppressing inflammation and reducing edema, but no direct data support their use in smoke inhalation. Because of the increased risk of pulmonary infection and delayed wound healing, prolonged use of steroids is discouraged. However, consider a brief course of steroids in those patients with otherwise unresponsive severe lower airway obstruction. In addition, patients receiving steroids prior to injury who may experience adrenal insufficiency should receive stress doses of steroids.

In a case series by Huang et al, 25% of patients presented after HC exposure with acute lung injury requiring ventilatory support. All of these patients survived with glucocorticoids, antibiotics and lung-protective ventilatory management. However, there was no control group, so a causal link could not be made between survival and steroid treatment.[3, 45]

Smoke inhalation injuries predispose the airways to infection because of cellular injury, reduction of mucociliary clearance, and poor macrophage function. Acute bacterial colonization and invasion peaks at 2-3 days after smoke inhalation. Prophylactic antibiotics should not be used, as they are not only ineffective but increase the risk of emergence of resistant organisms.

Discerning secondary infection from the effects of inhalation injury can be very difficult because both may produce fever, elevated white blood cell counts, and abnormal radiography findings. Antimicrobial therapy should be reserved for patients with definitive microbiologic evidence of infection that is not responding to aggressive support therapy or when clinical deterioration occurs in the first 72 hours.

The most common organisms in secondary pneumonia after smoke inhalation injury are Staphylococcus aureus and Pseudomonas aeruginosa. Direct parenteral coverage with antibiotics to cover these bacteria if infection is suspected.

Prehospital Care

As always, prehospital care providers must do everything in their power to remove the patient from ongoing exposure without becoming casualties themselves. Although emergency department (ED) care is mostly supportive, prompt delivery to the ED should be a priority.

Secure the airway as needed, deliver high-flow oxygen by mask, and obtain IV access. Cardiac monitoring also is important for any patient with respiratory distress. Beta-agonists such as albuterol may be given as a nebulized treatment to those who demonstrate signs of bronchoconstriction.

If respiratory failure is present, the patient should have assisted ventilation and/or endotracheal intubation. Perform cricothyrotomy if airway obstruction is present or impending and an airway cannot be secured orally.

Obtain a CO level at the scene if possible. In a consecutive case series of 18 patients, cardiac arrest complicating CO toxicity was uniformly fatal, despite administration of hyperbaric oxygen (HBO) therapy after the initial resuscitation. The prognosis of this condition should be considered when making triage decisions for these patients.[40]

Emergency Department Care

Presently, no specific treatment exists to ameliorate the tissue damage and reduce the vulnerability to infection induced by smoke inhalation. Administer 100% oxygen because of the likelihood of carbon monoxide (CO) inhalation in fires. Once CO toxicity, cyanide (CN) toxicity, and methemoglobinemia have been addressed, subsequent treatment is predominantly supportive.

The most urgent concern in patients is the patency of the upper airway and adequacy of ventilation. Check for exposure to heat and thermal injury to the nose, mouth, face, and singed hair. Consider smoke involvement if soot is on the face and in sputum, although smoke inhalation is possible without evidence of soot. The proportion of patients with an inhalation injury who require endotracheal intubation is higher for those who also have a burn injury: 62% with a burn versus 12% without a thermal injury and the incidence of inhalation injury increases with the size of the burn.[2] See the image below.



View Image

Smoke inhalation in pediatric victims. Note the many hallmarks of smoke inhalation complexed with burn injury (ie, facial burns, carbonaceous particle....

It is of vital importance that the magnitude of the swelling in the areas of the face and mandible be closely scrutinized when making decisions about the need for an artificial airway. The threshold for intubation should be lower than in other patients due to the potential of rapid development of airway edema. This is especially true of the pediatric patient. When upper airway injury is suspected, elective intubation should be considered because progression of edema over the next 24-48 hours may make later intubation difficult if not impossible.

If systemic paralysis is necessary for intubation, succinylcholine can be used safely in the immediate post-burn phase and up to several days afterward, although one should be cognizant of the possibility of a rise in serum potassium. Inflate the tube cuff to minimal levels, even allowing a small leak, in order to prevent iatrogenic tracheal damage in patients with an already compromised tracheal mucosa.

Patients whose injury involves cutaneous burns have ongoing circulatory derangements. Fluid loss through burned areas from intense inflammation with vasodilatation and capillary leak or from the subsequent infectious complications necessitates large fluid volume resuscitation. Large-bore IV catheter access may be needed to facilitate fluid resuscitation.

Use formulas (eg, Parkland) to calculate fluid resuscitation if severe burns are present. Even minor errors in estimation of body surface area; burned surface area; and fluid, electrolyte, and protein requirements can produce profound hemodynamic and respiratory compromise. Frequent evaluation of heart rate, perfusion, and blood pressure are needed to determine stability and guide therapy.

In mass casualty scenarios, the use of fiberoptic bronchoscopy may be beneficial to rapidly triage patients to intensive care, ward, or observation status. Mobilization of otolaryngology and/or anesthesia resources may be necessary to accomplish this in a timely fashion.

Hospital Admission Criteria

Patients with smoke inhalation should be monitored for 4-6 hours in the ED. Those who are at low risk for injury and whose vital signs and physical examination findings remain normal can usually be discharged with close follow-up and instructions to return if symptoms develop.

While there are no definite criteria for admission, patients with any of the following should be strongly considered for hospitalization:

For patients with isolated smoke inhalation, treatment in an intensive care unit is appropriate. However, patients with significant cutaneous burns should be transferred to a burn center when stable, if they meet the criteria for transfer.

Carbon Monoxide Poisoning

Assume elevated levels of carboxyhemoglobin in all fire victims. Carbon monoxide (CO) is not only responsible for most prehospital deaths due to smoke inhalation, it is also the leading cause of injury/death from all poisons worldwide.[10]

The half-life of CO is 320 minutes on room air, 90 minutes on 100% oxygen, and 23 minutes in a hyperbaric chamber at 3 atmospheres absolute (ATA). Elimination of CO depends primarily on the law of mass action, so alveolar PO2, rather than alveolar ventilation, is the critical factor in its removal.

Hyperbaric oxygen therapy

In patients with CO poisoning from smoke inhalation, the main reason for use of hyperbaric oxygen (HBO) therapy is to prevent delayed neurological sequelae. Carboxyhemoglobin levels are poor indicators of the severity of intoxication; patients with significant toxicity may have low levels. In fact, at the time of the initial HBO treatment, patients enrolled in most studies have normal or near-normal carboxyhemoglobin levels.

At this time, 6 prospective, randomized controlled trials have compared HBO with normobaric oxygen (NBO) therapy for CO poisoning. Four of these studies show a benefit for CO poisoning; two do not. The data and conclusions drawn from these studies are conflicting and highlight the controversy surrounding the utility of HBO.

In a prospective, double-blind study that compared HBO with NBO in patients with symptomatic acute CO poisoning, Weaver and colleagues found that 3 HBO treatments decreased the incidence of cognitive sequelae by 46% at 6 weeks.[46] Furthermore, a benefit continued to be seen at 12-month follow-up. Essentially, for every 6 patients treated with HBO, one case of delayed neurologic sequelae could be avoided. The evidence of benefit with HBO was so strong that the study was halted before its scheduled completion.

Although there has been much debate regarding the accuracy of neuropsychometric testing, including the fact that patients who are depressed and who have attempted suicide with non-CO means perform as poorly as CO-exposed patients, such testing remains an objective means to evaluate cognitive function.

Neurologic abnormalities and a history of loss of consciousness are the primary clinical features used to define severe CO toxicity and are indications for HBO. In addition, HBO use is indicated in patients with any of the following:

Note that the incidence of delayed neurologic sequelae increases with a more symptomatic initial clinical picture, in older patients, and in those with a prolonged exposure.[10]

The American College of Emergency Physicians Clinical Policies Subcommittee recommended in 2008 continued use of HBO in CO poisoning, especially in children and pregnant women, due to the conflicting results of previous studies.[47]

Cyanide Poisoning

Individuals exposed to cyanide (CN) poisoning may present with a variety of symptoms ranging from headache and altered mental status to hypotension, arrhythmia, and cardiovascular collapse followed by shock. Management of CN toxicity has historically involved the creation of an alternate binding site for CN to compete with cytochrome oxidase and also to provide substrate necessary to convert CN to a nontoxic metabolite.

Although not universally available, hydroxocobalamin (Cyanokit) is the preferred treatment of CN toxicity. In fact, many prehospital personnel use this product before the patient arrives if there is a high index of suspicion. It has been used in France for more than 30 years and was approved by the US Food and Drug Administration (FDA) in 2006.

Hydroxocobalamin is a hemelike molecule with a complexed cobalt atom that binds directly to CN to form cyanocobalamin (vitamin B-12), which is excreted renally. In vitro studies indicate that hydroxocobalamin penetrates cells and can act intracellularly. Adverse effects are chromaturia and reddening of the skin. Empiric administration to patients subsequently confirmed to have CN poisoning has been shown to be associated with 67% survival.

Hydroxocobalamin has a rapid onset of action, is easy to administer, does not interfere with tissue oxygenation, is well tolerated, and is safe for smoke inhalation patients. Additionally, it is not associated with hypotension or the formation of a dyshemoglobinemia (as was found in previous antidote kits) and it improves hemodynamic stability.[5, 48, 49]

The traditional CN antidote kit contains amyl and sodium nitrite to create a methemoglobin level of 3% and 20-30%, respectively, which, in turn, has a higher affinity for CN than for cytochrome a3. Also included is sodium thiosulfate, which provides substrate for the enzyme rhodanese; this combines thiosulfate and CN to form a nontoxic compound, thiocyanate, which is excreted renally.

Induction of methemoglobinemia is theoretically dangerous in a patient with an elevated carboxyhemoglobin level because further reduces oxygen-carrying capacity, so the clinician should consider withholding the nitrite portion of the kit. Another drawback of this treatment is the delayed onset of thiosulfate. Note that there is limited information about the efficacy of sodium thiosulfate for CN poisoning, as there are no clinical trials of sodium thiosulfate available.[12] Finally, this treatment may be more preventative rather than curative.

Though no prospective studies have conclusively demonstrated a decrease in mortality with the use of sodium thiosulfate alone, optimal treatment at this time is the combined use of hydroxocobalamin and thiosulfate. This is due to the fact that sodium thiosulfate has poor intracellular penetration and slow onset.[50] The combination of treatments allows quick extraction of CN without the formation of other dyshemoglombinemias and offers a sulfur-donating drug that maximizes the function of rhodanese.

Methemoglobinemia

Methemoglobinemia in smoke inhalation is relatively rare and rarely requires treatment with methylene blue. This antidote is reduced by the nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase enzyme and, in return, reduces methemoglobin to hemoglobin. Indications for treatment with methylene blue as follows:

Methemoglobin levels lower than 30% may not require treatment, depending on the patient's cardiorespiratory reserve.

Pulmonary Irritants

Since the pathophysiology of smoke inhalation involves irritants setting off the inflammatory response, many recent studies have investigated the benefit of anti-inflammatories and anticoagulants as treatment options for this underlying pathogenesis of injury. Treatment with heparin and pentoxifylline has been shown to improve lung function after smoke inhalation.

Aside from its known effect on thrombin, heparin has been recognized to have a protective effect on microvascular endothelium. Its anionic sulfate groups give the compound the ability to function as a cation exchanger, thereby limiting the endothelial permeability of cationic proteases released by polymorphonuclear leukocytes (PMLs). Pentoxifylline has not only been observed to improve microvascular circulation, but also suggested to play a role in down-regulating the production and release of inflammatory mediators.

Currently, both heparin and pentoxifylline are delivered systemically, but with limited success in penetrating the deep lung areas. However, a feasible delivery alternative allowing deeper penetration and a rapid local onset of action for the acceleration of healing may provide clinical benefits in the future.

A study of inhalable aerosol formulations of heparin and pentoxifylline in particles 5 µm or smaller demonstrated that co-spraying of heparin or pentoxifylline with leucine supplementation over a 24-hour period allowed for deep lung drug deposition and a possible efficient route to improve therapeutic outcomes for smoke inhalation.[7]

In contrast, a systematic review of heparin use in burn injury (topically, subcutaneously, intravenously, or via aerosol) found no strong evidence that heparin can improve clinical outcomes. Oremus and colleagues suggested that poor methodologic quality in studies of heparin may have led to severe bias in reports of its benefit.[51]

Experimental Treatments

Studies on experimental induction of smoke inhalation confirm the presence of an acute surfactant deficiency. Instillation of artificial surfactant shortly after injury was beneficial. Larger studies are needed before instituting such therapy.

Oxidant injury eventually leads to cast formation of cellular debris in the airways, thus contributing to pulmonary failure. A pediatric study has shown that aerosolized heparin/N -acetylcysteine decreases the incidence of atelectasis, reintubation rates, and overall mortality.[52]

Acetylcysteine and L-3,4 dehydroproline and a combined regimen of hydrocortisone and penicillamine have been used to treat ARDS induced by inhalation of smoke from smoke bombs. Positive outcomes were attributed to early treatment with penicillamine.[17] In animal studies, acetylcysteine has also been found effective for PTFE exposure.

In an animal model, whole-body hypothermia has been shown to suppress oxidant bronchoalveolar damage and pulmonary inflammation.[53] Mechanistically, this appears to halt the progression of bronchoalveolar-capillary permeability.

Pulmonary Toilet

As with many respiratory conditions, the use of chest physiotherapy is widely accepted in inhalation injury but remains unproven in controlled trials. The use of percutaneous cupping and postural drainage seem reasonable to clear airways of cellular debris and soot, thereby preventing atelectasis and obstruction. Obviously, care must be taken in attempting this in the presence of significant chest wall burns.

Encourage extubated patients to cough and deep breathe. In patients who are intubated, use gentle suctioning to remove mucus, debris, and sloughed epithelium. Fiberoptic bronchoscopy may be helpful in removing the debris and in facilitating pulmonary toilet.

Mechanical Ventilation

Mechanical ventilation may be necessary in patients with declining lung function, oxygenation levels, and ventilation. Use of positive pressure ventilation with low tidal volumes (3-5 mL/kg) and positive end-expiratory pressure (PEEP) and maintenance of plateau pressures below 30 cm water significantly increases short-term survival and is associated with decreased tracheobronchial cast formation. In fact, this treatment has been shown to increase the intensive care unit (ICU) survival rate from 29% to 62%.

PEEP may assist in opening obstructed closed alveoli and help ventilation in those patients with poor compliance by increasing functional residual capacity. Ideally, PEEP stents alveoli open, preventing the atelectasis and alveolar flooding that can result from surfactant dysfunction, increasing interstitial fluid, and third-spacing.[54]

High-frequency percussive ventilation (HFPV), while not as commonly used in the ED, is considered standard therapy in many burn centers. HFPV generates pulsatile flow at up to 600 cycles per minute, which entrains the humidified gas by its effect on molecular diffusion. It can improve clearance of airway secretions and allow continued patency of the lower airways. In patients with inhalation injury and burns involving less than 40% of total body surface area, HFPV decreases both morbidity and mortality.[54, 55, 56]

Tracheostomy

The timing of tracheostomy continues to be controversial.[57] Certainly, tracheostomy can be lifesaving for patients in whom endotracheal intubation is not possible, because of severe airway edema or burns. With early recognition of upper airway injury, this should be a rare occurrence.

Tracheostomy, especially through burned tissue, has an increased complication rate and risk of sepsis when compared with endotracheal intubation. Thus, most patients can be effectively managed with endotracheal intubation through the mouth or nose. In patients expected to have a long period of convalescence because of severe neurologic or pulmonary injury, however, tracheostomy may be desirable for patient comfort and is easy to maintain.

Diet

Patients should take nothing by mouth until it becomes clear that they will not require tracheal intubation because of significant respiratory or hemodynamic compromise.

Even with extensive burns, most patients can tolerate enteral feedings at the end of the first 24 hours. Begin enteral feedings as soon as possible. As enteral intake increases, decrease intravenous fluids accordingly. Patients may demonstrate marked hypermetabolism. Therefore, providing adequate nutritional support is important.

Prevention

Primary prevention with functioning fire and smoke alarms and family education for fire hazards is critical to help avoid fire injuries. Fire prevention should be viewed as the primary means to avoid inhalation injury

Smoke detectors reduce the risk of death by about 60% in all subgroups of people.[31] This finding stands in contrast to past data that suggested that these early warning devices may not be effective in populations that have difficulty responding to an alarm in a timely manner, such as children, older adults, persons with disabilities, or those impaired by alcohol or other drugs. These new data clearly reinforce the point that all homes should have a working smoke detector in every room.

Although smoke detectors have been widely adopted by the public— 93% of US households have one in place—it is estimated that 30-45% of these devices are not operational, usually because the battery has died or has been removed. DiGuiseppi et al have shown that merely giving out free smoke alarms in a deprived, multiethnic, urban community did not reduce injuries related to fire, because few of the alarms were installed or properly maintained.[58]

In the military setting, the mission-oriented protective posture (MOPP) gear ensemble provides adequate protection against all smokes. In the industrial setting, guidelines have been established for the protection of the worker as well as any person who may come in contact with toxic smokes. Aim preventive efforts at decreasing the concentration of the smoke and the time of exposure and recognizing underlying health problems that may be exacerbated by exposure to toxic smokes.

Medication Summary

The primary treatment of smoke inhalation injury is oxygen. Bronchodilators may be of benefit in patients displaying bronchospasm. In addition, specific antidotes are methylene blue for methemoglobinemia and thiosulfate/sodium nitrite for cyanide (CN) poisoning. Certain patients with carbon monoxide (CO) toxicity may require hyperbaric oxygen therapy (HBO).

Oxygen is used for any suspected significant inhalation injury. Treat with high concentrations of humidified oxygen en route to the hospital.

Use of high oxygen flow rates and a nonrebreathing-type face mask with a tight seal facilitates delivery of high levels of supplemental oxygen, which helps reverse the oxygenation defect created by ventilation-perfusion mismatch. Inhaled oxygen also helps in the displacement of CO from hemoglobin, decreasing the half-life of carboxyhemoglobin from 4-6 hours in room air to 40-60 min in 100% fractional concentration of oxygen in inspired air (FiO2).

HBO therapy also displaces CO from intracellular stores and may improve mitochondrial function. HBO requires special facilities that are not available at all centers, resulting in a delay in treatment while the patient is transported to facility with HBO.

Hyperbaric therapy should be considered in those patients who have high carboxyhemoglobin levels greater than 25%, who are unconsciousness, have other neurologic findings, or have severe metabolic acidosis (ph < 7.1). The benefit of treating patients 12 hours or more after CO exposure remains unproven.

Albuterol (Proventi HFAl, Ventolin HFA, VoSpire ER, ProAir HFA)

Clinical Context:  Albuterol is a beta-agonist that is useful in treatment of bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by acting on beta2-receptors, while having little effect on cardiac muscle contractility. Airway resistance is decreased, and ventilation is improved.

Epinephrine racemic (AsthmaNefrin, S2)

Clinical Context:  Racemic epinephrine alleviates airway edema and reflex bronchospasm. Although it has not been directly studied in smoke inhalation, inhaled racemic epinephrine can theoretically provide relief from both airway edema and reflex bronchospasm in this setting.

Terbutaline

Clinical Context:  Terbutaline is used for severe bronchoconstriction, especially in patients with underlying reactive airways disease. This agent acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.

Epinephrine (Adrenalin, EpiPen, Adrenaclick)

Clinical Context:  Epinephrine is used for severe bronchoconstriction, especially in patients with underlying reactive airways disease. This agent has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. The beta-agonist effects of epinephrine include bronchodilation, chronotropic cardiac activity, and positive inotropic effects.

Class Summary

These agents relieve reversible bronchospasm by relaxing smooth muscles of the bronchi. Increased resistance from airway edema and reflex bronchoconstriction from irritation of airway receptors contribute to airway obstruction.

Bronchodilators are important in the treatment of bronchoconstriction and bronchorrhea. Toxic smokes can cause bronchoconstriction, especially if the exposed individual has underlying asthma or chronic obstructive pulmonary disease (COPD). In patients with profound bronchoconstriction and wheezing, subcutaneous epinephrine has been helpful in stabilizing mast cells and halting or reversing potentially fatal bronchoconstriction.

Sodium thiosulfate

Clinical Context:  After formation of methemoglobin and production of cyanomethemoglobin, thiosulfate acts as a sulfur donor to the endogenous enzyme rhodanese. This enzyme removes CN from the cyanomethemoglobin complex and forms thiocyanate, which is excreted renally. CN also is removed directly from cytochrome oxidase and is converted to thiocyanate in the presence of thiosulfate via the enzyme rhodanese.

Methylene blue (ProvayBlue)

Clinical Context:  Methylene blue is used to convert methemoglobin to oxyhemoglobin. It contains a tetramethyl thionine chloride moiety that is reduced (it is an electron acceptor) in the presence of nicotinamide adenine dinucleotide phosphate–oxidase (NADPH) and methemoglobin reductase to leukomethylene blue. Leukomethylene blue then becomes available to reduce methemoglobin to oxyhemoglobin.

Methylene blue may be ineffective in treating patients with glucose-6-phosphodiesterase (G-6-PD) deficiency because, in the hexose monophosphate shunt, G-6-PD is essential for the generation of NADPH. Without NADPH, methylene blue cannot act as a reducing agent in the transformation of methemoglobin to oxyhemoglobin.

Hydroxocobalamin (Cyanokit)

Clinical Context:  Hydroxocobalamin is a vitamin B-12 precursor that contains a cobalt ion, which has greater affinity for cyanide than does cytochrome oxidase. Binding of cyanide to the cobalt ion results in the formation of cyanocobalamin, which is excreted renally. Hydroxocobalamin has few adverse effects and has the following advantages over other cyanide treatments:

This agent is safe to use in victims of smoke inhalation.[59, 60] Cyanocobalamin is a pigmented compound, and interferes with spectrophotometric tests. Any necessary blood samples should be drawn prior to administration of antidote if possible, because it will not be possible to obtain accurate results for most blood tests afterward.

Amyl nitrite

Clinical Context:  In the presence of nitrites, hemoglobin is converted to methemoglobin, which has a higher binding affinity for CN than does the cytochrome oxidase complex. Administration of amyl nitrite produces a methemoglobin level of 5% and subsequent formation of cyanomethemoglobin, allowing electron transport and cellular respiration to continue. This medication is given until an IV line is established and sodium nitrite can be administered.

Sodium thiosulfate & sodium nitrite (Nithiodote)

Clinical Context:  In the presence of nitrites, hemoglobin is converted to methemoglobin that has a higher binding affinity for CN than does the cytochrome oxidase complex. Administration of sodium nitrite produces a methemoglobin level of 20-30% and subsequent formation of cyanomethemoglobin, allowing electron transport and cellular respiration to continue.

Class Summary

Several CN antidotes exist, which work by different mechanisms of action. Hydroxocobalamin binds to CN to form cyanocobalamin. Amyl nitrite and sodium nitrite convert a portion of circulating hemoglobin to methemoglobin. Sodium thiosulfate allows the production of thiocyanate.

Methylprednisolone (Medrol, Depo-Medrol, Solu-Medrol, A-Methapred)

Clinical Context:  Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear neutrophils (PMNs) and reversing increased capillary permeability.

Dexamethasone (Dexamethasone Intensol)

Clinical Context:  Dexamethasone decreases immune reactions. It provides a local anti-inflammatory effect while minimizing some of the gastrointestinal and other risks associated with systemic medications. Dexamethasone suppresses the migration of polymorphonuclear leukocytes (PMNs) and reduces capillary permeability.

Class Summary

Whether corticosteroids are beneficial in toxic smoke inhalation is a matter of some debate, but many experts consider these agents helpful in this setting. Corticosteroids are considered especially useful in metal fume fever, which is believed to be mediated by an inflammatory cascade of events involving cytokines and histamine release.

Dimercaprol (BAL in Oil)

Clinical Context:  Dimercaprol is the drug of choice for treatment of mercury toxicity; although not formally indicated for zinc toxicity, its use has been suggested in the setting of severe zinc oxide inhalation injury, since it lowers serum zinc levels. It is administered by deep intramuscular injection.

Edetate calcium disodium

Clinical Context:  Although edetate calcium disodium is used mostly in lead chelation, for which it is a second-line agent, treatment with this agent has been associated with lowering of serum zinc levels. Begin therapy 4 h after giving dimercaprol. The IV route is used exclusively, and continuous infusion is recommended.

Class Summary

No reports exist as to the efficacy of chelating agents; however, dimercaprol and edetate calcium disodium (CaEDTA) have been suggested because of their ability to reduce serum zinc levels. Zinc toxicity may be treated with a combination of dimercaprol and CaEDTA or with EDTA alone. Nausea, vomiting, and elevated liver enzymes occur more commonly with combination therapy.

Atropine ophthalmic

Clinical Context:  This agent acts at parasympathetic sites in smooth muscle to block the response to acetylcholine of the sphincter muscle of the iris and the muscle of the ciliary body, causing mydriasis and cycloplegia.

Class Summary

Adjunctive therapy may be useful in patients with eye irritation accompanying smoke inhalation injury. These agents relax ciliary muscle spasm, which can cause deep aching pain and photophobia.

Sodium bicarbonate

Clinical Context:  Rinse affected skin thoroughly before applying sodium bicarbonate solution. Potential exists for exothermic reaction (burns) whenever a base is mixed with an acid; therefore, after titanium chloride or sulfur trioxide exposure, rinse affected skin thoroughly and copiously with water or saline.

Pharmacists at Walter Reed Medical Center recommend using a 5% solution of sodium bicarbonate to rinse over the affected area, followed by rinsing copiously with water or saline. The author believes that copious irrigation alone with water or saline should be sufficient, along with proper wound care, rather than introducing another chemical onto an already irritated area of skin.

Nebulized sodium bicarbonate may be helpful in cases of chlorine gas inhalation. It should not be used for inhalation of other gases.

Class Summary

These agents are indicated for topical treatment of patients who have experienced cutaneous exposure to sulfur trioxide or titanium tetrachloride.

What is smoke inhalation injury?Which physical findings are characteristic of smoke inhalation injury?What are the signs and symptoms of lower respiratory tract injury caused by smoke inhalation?What are the signs and symptoms of asphyxiant exposure due to smoke inhalation?What is included in the workup of smoke inhalation injury?What is the role of carboxyhemoglobin blood levels in the assessment of smoke inhalation injury?How are smoke inhalation injuries treated?When are steroids indicated in the treatment of smoke inhalation injury?When is hospitalization indicated in the treatment of smoke inhalation injury?How is mechanical ventilation administered in the treatment of smoke inhalation?What are the indications for hyperbaric oxygen (HBO) therapy in the treatment of smoke inhalation injury?What are the effects of smoke inhalation?What are the possible chemical exposures of smoke inhalation injury?How are smoke inhalation injuries diagnosed?How are smoke inhalation injuries treated in children?What is the pathophysiology of carbon monoxide asphyxiation from smoke inhalation?What is the pathophysiology of methemoglobinemia from smoke inhalation?What are the mechanisms of smoke inhalation injury?What is the pathophysiology of thermal injury from smoke inhalation?What is the pathophysiology of asphyxiation from smoke inhalation?What are sources of cyanide gas in smoke inhalation?What is the pathophysiology of cyanide asphyxiation from smoke inhalation?What are the possible neurological sequelae of cyanide toxicity from smoke inhalation?What is the pathophysiology of pulmonary irritation from smoke inhalation?What is the pathophysiology of smoke inhalation in the lower lung areas?What is the pathophysiology of smoke inhalation associated with the military or industry?What is the pathophysiology of smoke inhalation caused by oxides of nitrogen?What is the pathophysiology of smoke inhalation caused by zinc oxide?What is the pathophysiology of metal fume fever caused by smoke inhalation?What is the pathophysiology of smoke inhalation caused by red phosphorus?What is the pathophysiology of smoke inhalation caused by sulfur trioxide?What is the pathophysiology of smoke inhalation caused by titanium tetrachloride?What is the pathophysiology of smoke inhalation caused by oil fog?What is the pathophysiology of smoke inhalation caused by Teflon particles?What causes smoke inhalation injury?How does carbon monoxide (CO) cause smoke inhalation injury?How do oxides of nitrogen (NOx) cause smoke inhalation injury?Which factors increase the risk of smoke inhalation injury from oxides of nitrogen (NOx) exposure?How does zinc cause smoke inhalation injury?How does red phosphorus cause smoke inhalation injury?How does sulfur trioxide cause smoke inhalation injury?How does titanium tetrachloride cause smoke inhalation injury?Who is at highest risk of smoke inhalation injury from oil fog exposure?How do Teflon particles cause smoke inhalation injury?What is the prevalence of smoke inhalation injury?What are the racial and sexual predilections of smoke inhalation injuries?Which age groups have the highest prevalence of smoke inhalation injuries?What is the prevalence of smoke inhalation injury from house fires?What is the prognosis of smoke inhalation injury?What are the possible complications of smoke inhalation injury?What is the prognosis of carbon monoxide poisoning relevant from smoke inhalation?What is the mortality of smoke inhalation injury?Which factors increased the mortality risk of smoke inhalation in children?What is included in the patient education about smoke inhalation injury?Which clinical history findings are characteristic of patients affected by smoke inhalation?Which chemical exposures affect the clinical presentation of smoke inhalation?Which clinical history findings are characteristic of smoke inhalation caused by oxides of nitrogen?Which clinical history findings are characteristic of smoke inhalation caused by zinc oxide?Which clinical history findings are characteristic of smoke inhalation caused by red phosphorus?Which clinical history findings are characteristic of smoke inhalation caused by titanium tetrachloride?Which clinical history findings are characteristic of smoke inhalation caused by oil fog?Which clinical history findings are characteristic of smoke inhalation caused by Teflon particles?What is included in the physical exam to evaluate smoke inhalation injury?Which physical findings suggest lower respiratory tract injury following smoke inhalation?Which physical findings suggest neurologic injury following smoke inhalation?Which physical findings suggest cardiovascular injury following smoke inhalation?Which physical findings are characteristic of smoke inhalation?Which physical findings are characteristic of carbon monoxide smoke inhalation?Which physical findings are characteristic of cyanide smoke inhalation?Which physical findings are characteristic of oxides of nitrogen smoke inhalation?Which physical findings are characteristic of zinc oxide smoke inhalation?Which physical findings are characteristic of red phosphorus smoke inhalation?Which physical findings are characteristic of sulfur trioxide and titanium tetrachloride smoke inhalation?Which physical findings are characteristic of Teflon particles smoke inhalation?What are the differential diagnoses for Smoke Inhalation Injury?What is the primary focus of the initial workup of smoke inhalation?What is the role of pulse oximetry and carbon monoxide (CO)-oximetry in the workup of smoke inhalation injury?What is the role of arterial blood gases in the workup of smoke inhalation injury?How do carboxyhemoglobin levels in the blood correspond to the clinical presentation of smoke inhalation injury?What causes elevated lactate levels following smoke inhalation?What is the role of blood studies in the workup of smoke inhalation injury?What is the role of a CBC count in the workup of smoke inhalation injury?How is the level of cyanide (CN) intoxication assessed in the workup of smoke inhalation injury?What is the role of radiography in the workup of smoke inhalation injury?What is the role of CT scans in the workup of smoke inhalation injury?What is the role of radionuclide scintigraphy in the workup of smoke inhalation injury?What is the role of pulmonary function testing (PFT) in the workup of smoke inhalation injury?What is the role of bronchoscopy in the workup of smoke inhalation injury?What are approach considerations in the treatment of smoke inhalation injury?What is included in the prehospital care for smoke inhalation injury?How are smoke inhalation injuries treated in the emergency department (ED)?When is hospitalization indicated for the treatment of smoke inhalation injury?How is carbon monoxide (CO) eliminated during the treatment of smoke inhalation injuries?When is hyperbaric oxygen (HBO) therapy indicated in the treatment of smoke inhalation injury?How is cyanide poisoning treated following smoke inhalation?How is methemoglobinemia treated in smoke inhalation injury?What is the role of heparin and pentoxifylline in the treatment of smoke inhalation injuries?What is the role of artificial surfactant in the treatment of smoke inhalation injury?What is the role of aerosolized heparin/N -acetylcysteine in the treatment of smoke inhalation injury?Which combination therapies have been suggested for the treatment of smoke inhalation injury?What is the role of hypothermia in the treatment of smoke inhalation injury?What is the role of chest physiotherapy in the treatment of smoke inhalation injury?What is the role of mechanical ventilation in the treatment of smoke inhalation injury?What is the role of tracheostomy in the treatment of smoke inhalation injury?Which dietary modifications are used in the treatment of smoke inhalation injury?How are smoke inhalation injuries prevented?Which medications are used in the treatment of smoke inhalation injury?What is the role of humidified oxygen in the treatment of smoke inhalation?What is the role of hyperbaric oxygen (HBO) in the treatment of smoke inhalation?Which medications in the drug class Alkalinizing Agents are used in the treatment of Smoke Inhalation Injury?Which medications in the drug class Cycloplegics/Mydriatics are used in the treatment of Smoke Inhalation Injury?Which medications in the drug class Chelators are used in the treatment of Smoke Inhalation Injury?Which medications in the drug class Corticosteroids are used in the treatment of Smoke Inhalation Injury?Which medications in the drug class Antidotes, Other are used in the treatment of Smoke Inhalation Injury?Which medications in the drug class Beta2 Agonists are used in the treatment of Smoke Inhalation Injury?

Author

Keith A Lafferty, MD, Adjunct Assistant Professor of Emergency Medicine, Temple University School of Medicine; Medical Student Director, Department of Emergency Medicine, Gulf Coast Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia V Martinez, MD, Resident Physician, Department of Emergency Medicine, State University of New York Downstate College of Medicine

Disclosure: Nothing to disclose.

Denise Serebrisky, MD, Associate Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director, Division of Pulmonary Medicine, Lewis M Fraad Department of Pediatrics, Jacobi Medical Center/North Central Bronx Hospital; Director, Jacobi Asthma and Allergy Center for Children, Jacobi Medical Center

Disclosure: Nothing to disclose.

Keisha Bonhomme, MD, Resident Physician, Department of Internal Medicine, St Vincent’s Medical Center

Disclosure: Nothing to disclose.

Rachel Dillinger, Lewis Katz School of Medicine at Temple University

Disclosure: Nothing to disclose.

Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Disclosure: Nothing to disclose.

Chief Editor

Joe Alcock, MD, MS, Associate Professor, Department of Emergency Medicine, University of New Mexico Health Sciences Center

Disclosure: Nothing to disclose.

Acknowledgements

Michael R Bye, MD Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Charles Callahan, DO Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center

Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, and Christian Medical & Dental Society

Disclosure: Nothing to disclose.

Heidi Connolly, MD Associate Professor of Pediatrics and Psychiatry, University of Rochester School of Medicine and Dentistry; Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center

Heidi Connolly, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Robert G Darling, MD, FACEP Adjunct Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director, Center for Disaster and Humanitarian Assistance Medicine

Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Telemedicine Association, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio

Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Harry J Goett, MD Assistant Professor of Emergency Medicine, Department of Emergency Medicine, Temple University Hospital

Harry J Goett, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mark Keim, MD Senior Science Advisor, Office of the Director, National Center for Environmental Health, Centers for Disease Control and Prevention

Mark Keim, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Emily B Nazarian, MD Assistant Professor of Pediatrics, Fellowship Director, Pediatric Critical Care, Golisano Children's Hospital at Strong

Emily B Nazarian, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Girish D Sharma, MD Professor of Pediatrics, Rush Medical College; Senior Attending, Department of Pediatrics, Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush University Medical Center

Girish D Sharma, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Royal College of Physicians of Ireland

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

James Steven Walker, DO, MS Clinical Professor of Surgery, Department of Surgery, University of Oklahoma College of Medicine

James Steven Walker, DO, MS is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Smoke inhalation in pediatric victims. Note the many hallmarks of smoke inhalation complexed with burn injury (ie, facial burns, carbonaceous particles in the nasal cavity, periorbital edema, hair singeing). Early endotracheal tube placement is necessary to secure patency of the upper airways and adequate ventilation.

Smoke inhalation in pediatric victims. Note the many hallmarks of smoke inhalation complexed with burn injury (ie, facial burns, carbonaceous particles in the nasal cavity, periorbital edema, hair singeing). Early endotracheal tube placement is necessary to secure patency of the upper airways and adequate ventilation.

Smoke inhalation in pediatric victims. Note the many hallmarks of smoke inhalation complexed with burn injury (ie, facial burns, carbonaceous particles in the nasal cavity, periorbital edema, hair singeing). Early endotracheal tube placement is necessary to secure patency of the upper airways and adequate ventilation.

Type Inhalant Source Injury/Mechanism
Irritant gasesAmmoniaFertilizer, refrigerant, manufacturing of dyes, plastics, nylonUpper airway epithelial damage
ChlorineBleaching agent, sewage and water disinfectant, cleansing productsLower airway epithelial damage
Sulfur dioxideCombustion of coal, oil, cooking fuel, smeltingUpper airway epithelial damage
Nitrogen dioxideCombustion of diesel, welding, manufacturing of dyes, lacquers, wall paperTerminal airway epithelial damage
Asphyxiants (mitochondrial toxins)Carbon monoxideaCombustion of weeds, coal, gas, heatersCompetes for oxygen sites on hemoglobin, myoglobin, heme-containing intracellular proteins
Hydrogen cyanide (CN)bBurning of polyurethane, nitrocellulose (silk, nylon, wool)Tissue asphyxiation by inhibiting intracellular cytochrome oxidase activity, inhibits ATP production, leads to cellular anoxia
Hydrogen sulfidecSewage treatment facility, volcanic gases, coal mines, natural hot springsSimilar to CN, tissue asphyxiant by inhibition of cytochrome oxidase, leads to disruption of electron transport chain, results in anaerobic metabolism
Systemic toxinsHydrocarbonsInhalant abuse (toluene, benzene, Freon); aerosols; glue; gasoline; nail polish remover; typewriter correction fluid; ingestion of petroleum solvents, kerosene, liquid polishesCNS narcosis, anesthetic stats, diffuse GI symptoms, peripheral neuropathy with weakness, coma, sudden death, chemical pneumonitis, CNS abnormalities, GI irritation, cardiomyopathy, renal toxicity
OrganophosphatesInsecticides, nerve gasesBlocks acetylcholinesterase; cholinergic crisis with increased acetylcholine
Metal fumesMetal oxides of zinc, copper, magnesium, jewelry makingFlulike symptoms, fever, myalgia, weakness
a Major component of smoke.



b Smells like almonds, component of smoke from fires.



c Smells like rotten eggs.