AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

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. In the past, smoke also has been a form of communication and identification. Smokes are not unique to the military but also are produced in industry by explosion, by mechanical generation, or as a by-product of a chemical interaction. Smoke is made of solid particles of varying sizes that are suspended in air. 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.

Although most smokes used for obscuring purposes are not concentrated enough to be hazardous, any smoke can be hazardous to health if the concentration is sufficient or if the exposure is long enough. The smoke itself can be directly toxic, or it may carry, adsorbed to the particulate surface, any of a variety of toxic gaseous substances that interact with mucosa, skin, or any surfaces of the airway. Smokes consist of particles of various sizes, sedimentation rate, and impact rate. Therefore, smoke inhalation has a complex distribution pattern at various levels in the airway.

This article reviews the pathophysiology and toxic effects of lung and airway injury caused by different smokes: the oxides of nitrogen (NOx), zinc oxide (HC), red phosphorus (RP), sulfur trioxide (FS), titanium tetrachloride (FM), standard gas fuel-2 (ie, fog oil [SGF2]), and pyrolysis of Teflon.

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 given without oxygen) asphyxiant, and nitric oxide, which quickly decomposes to nitrogen dioxide in the presence of moisture.

Zinc oxide

HC smoke is a mixture of equal amounts of hexachloroethane, zinc oxide, and approximately 7% grained aluminum or aluminum powder. Upon combustion, the mixture produces zinc chloride, which rapidly absorbs moisture from the air to form a grayish white smoke. More humid air results in thicker smoke. Other chemicals also are released in the combustion process, such as chlorinated hydrocarbons (eg, phosgene), chlorine gas, carbon monoxide, and several other compounds.

HC smoke resulted from the French and US Chemical Warfare Service, which, after World War I, sought an obscurant that was not fraught with as many difficulties as white phosphorus. HC has a sweetish acrid odor, even at moderate concentrations. Although HC can irritate the upper airway mucous membranes, it probably is studied most for its role in fume fever.

Red phosphorus

After World War II, RP smoke was developed as 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 phosphorus 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.

Sulfur trioxide

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. It 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 the army.

Titanium tetrachloride

FM is a colorless–to–pale yellow liquid that has fumes with a strong odor. Once it comes in 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, where a mild epithelial irritation results and usually subsides within 24 hours. When it is mixed with water, it generates a vigorous exothermic reaction that produces both heat and hydrochloric acid, which can work synergistically to produce deep thermal burns.

Oil fog

SGF2 is one 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.

Teflon particles

Teflon (polytetrafluoroethylene [PTFE]) is used widely in a variety of industrial and commercial settings such as lubricants and fabric treatments. Its lubricity, high dielectric constant, and chemical inertness make it a desirable component in military vehicles such as tanks and aircraft. Closed-space fires in such settings have prompted studies of the toxicity of exposure to the by-products created from incinerated organofluorines. Pyrolysis of PTFE produces a particulate smoke, which, if inhaled, produces a constellation of symptoms termed polymer fume fever (PFF).

Pathophysiology

Oxides of nitrogen

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. Milder yet still severe exposures may result in death with production of yellow frothy fluid in the nasal passages, mouth, and trachea and marked pulmonary edema. The symptoms following the inhalation of NOx are mostly due to nitrogen dioxide.

Zinc oxide

HC is probably the most acutely toxic of the military smokes and obscurants. HC's toxicity mainly is attributed to the irritating effects of zinc chloride. Most likely, carbon monoxide, phosgene, hexachloroethane, and other products contribute to the observed respiratory effects. Primary damage largely is confined to the upper respiratory tract, where zinc chloride acts much like a corrosive irritant.

Studies have demonstrated that 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 presence of pulmonary edema, increased airway resistance, and decreased compliance. When these episodic exposures were stopped, the changes were reversible.

Lung injury comes primarily from the zinc chloride product of HC combustion. In a retrospective cohort study of 20 patients, Hsu et al correlated findings on high-resolution CT with pulmonary function tests (PFTs) performed within 3-21 days following acute exposure.¹ CT findings were predominantly diffuse ground-glass opacities in the lung parenchyma. PFTs showed a restrictive functional impairment with significant reduction in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), total lung capacity (TLC), and diffusing capacity of lung for carbon monoxide (D_LCO) without impairment of FEV₁/FVC ratio. Follow up in 1-2 months showed significant improvement with mild-to-moderate exposures. 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.² 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.³ The article states 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 carcinogen.

Metal fume fever is a well-documented acute disease induced by intense inhalation of metal oxides, especially zinc oxide. The exact pathology is not really understood, but the clinical syndrome is well described and has been studied at length. 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.⁴

Hepatotoxicity has also been described in humans exposed to HC/ZnO smokes in enclosed spaces during military training.⁵ 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. 

Red phosphorus

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

Since FS is an intermediate used to produce sulfuric acid upon its reaction with moisture, the resulting toxicity 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

The same pathophysiologic effects that occur with FS smoke occur with FM smoke, since both are associated with the production of corrosive and irritating acids.

Oil fog

Concentrations of oil mists in industrial settings vary over a wide range (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, after chronic exposure, that pulmonary function endpoints such as total lung capacity, vital capacity, residual volume, D_LCO, compliance, and end-expiratory volume were unaffected by oil fog. 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, polymorphonuclear leukocytes [PMNs], macrophages).

Teflon particles

Pyrolysis of Teflon occurs at approximately 450°C. The mixture of particles that is produced contains a substance called perfluoroisobutylene (PFIB), which appears to be the main cause of toxicity in polymer fume fever. 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 cause 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 fume fever follows. More intense exposures also may produce a chemical conjunctivitis. Hemorrhagic inflammation of the lungs also can occur.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

• 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 disease 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 underlying health of the exposed individual.
  • Mild exposure to nitrogen dioxide 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, 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, once the patient is removed from the exposure, complete recovery is expected within 24 hours.
  
  
  
  • In more severe exposures, the clinical response may be described as triphasic.
    • During phase I, an intense respiratory symptom complex may occur. Severe cough, dyspnea, and rapid onset of pulmonary edema suddenly may arise. Physical exertion actually 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. Fiercer exposures can cause acute bronchiolitis with severe cough, dyspnea, and weakness. This typically resolves 3-4 days postexposure.
      
    
    
    • Phase II lasts from 2-5 weeks and is relatively uneventful. A mild residual cough with malaise and perhaps dyspnea may linger, but the chest radiograph (CXR) typically remains clear.
      
    
    
    • In phase III, symptoms may recur 3-6 weeks after the exposure. 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.
  • Many studies have evaluated effects of NOx on individuals with healthy lungs and those with asthma or chronic obstructive bronchitis. Concentrations of 0.5 ppm or less generally have not affected people with preexisting airway disease. 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 in pulmonary function tests and decreased D_LCO 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 of exposure, since respiratory distress can mimic many different disease processes.
  • Fume fever typically presents in a delayed fashion 4-48 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 1-4 days with supportive care.
    
  
  
  • Milder exposures are characterized by sensations of dyspnea without any radiologic, auscultatory, or blood gas abnormalities.
    
  
  
  • A patient with moderate exposure 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 a CXR showing dense infiltrative processes. This usually clears, but significant hypoxia may persist during the time the CXR 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.
    
  
  
  • A severe exposure can be associated with an explosive persistent cough. If a person has come in contact with unoxidized phosphorus, chemical burns to the skin can cause pain and erythema.
    
  
  
  • Most often, the cough and irritating symptoms resolve after the individual is removed from the exposure source.


• Sulfur trioxide: Because FS smoke is so irritating, those exposed do not remain in it for long.
  • 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.
    
  
  
  • A report by Steuven et al of 12 persons exposed to FS for approximately 2 hours elicited complaints such as pleuritic chest pain, chest tightness, vague chest discomfort, cough, an acidic taste in the mouth, and nasal irritation. Everyone was asymptomatic 6 hours postexposure.⁶  


• Titanium tetrachloride: Although several industrial exposures have occurred with FM liquid and smoke, only 1 death has been reported. This was 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 SGF2 or other oil mists may report mild irritation or slight cough, a sensation of shortness of breath, or headache. Those who have underlying pulmonary disease such as asthma or chronic obstructive pulmonary disease (COPD) may have symptoms triggered after exposure to SGF2.
  


• Teflon particles: Clinical complaints of exposed individuals closely mimic influenzalike symptoms.
  • The individual complains of 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 only occurred in animals with severe lung damage.
    
  
  
  • Cases of PFF 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.⁷

Physical

• Oxides of nitrogen: The severity of physical examination findings depends on the severity of exposure.
• • In a mild exposure, an individual may have 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
• • Like other inhalation injuries, physical examination findings 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
• • Conjunctivitis, corneal erosion with uptake of fluorescein, and lacrimation may be present. Erythema of exposed skin surfaces and an inflammatory reaction of mucosal surfaces also may be present. Intense salivation may follow. The individual may have an explosive cough with bloody sputum, dyspnea, hypoxia, rales, or wheezes.
  
  
  • Obviously, 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 is known to exacerbate symptoms of asthma or COPD and significantly worsen pulmonary function test numbers in these patients
  
  


• Titanium tetrachloride: Physical examination findings are expected to be the same as for FS smoke.


• Oil fog: After an intense and prolonged exposure, a patient may have mild dyspnea, basilar rales, or evidence of bronchoconstriction (eg, wheezing, prolonged expiratory phase).


• Teflon particles
• • Physical examination is 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 postexposure.
  
  
  • CXR findings of pulmonary edema worsen for up to 12 hours and then typically clear by 72 hours.
  
  
  • Deaths have been reported with severe pulmonary edema, hypotension, and gram-negative superinfection.

Causes

• 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.
  
  
  • Severe pulmonary reactions have been reported after accidental exposures in unventilated farm silos, welding in confined spaces, detonating nitrogen-based explosives in enclosed spaces (tanks, ships), handling nitric acid, resurfacing ice arenas, using anesthesia, and in missile fuel oxidizer spills. Any person engaged in associated occupations or environments is at risk.


• Zinc oxide: Since this smoke can be distributed by grenades, candles, pots, artillery shells, and special air bombs, any 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. People also can be exposed to phosphorus smoke at phosphorus loading plants.


• Sulfur trioxide: One may become exposed to FS on the job in a chemical or metal plating industry. 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. Since the army does not use FS much anymore, military exposures are less common.


• Titanium tetrachloride: Because FM smoke breaks down so rapidly in the environment, those 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. Industrial settings where oil mists are created may produce similar exposures (eg, metalworking, automobile and textile industries, pressrooms, mining, die and mould lubrication).


• Teflon particles: As mentioned in Background, exposure to these fumes is common in closed-space fires where Teflon is pyrolyzed. Also, polymer fume fever has been observed in those smoking Teflon-contaminated cigarettes.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Any process that presents with pulmonary symptoms or signs
Pneumonia
Congestive heart failure
Pulmonary embolism
COPD exacerbation
Precipitant of noncardiogenic pulmonary edema, myocardial infarction, pleurisy, or tuberculosis
Any toxic inhalation exposure (eg, cyanide, carbon monoxide, other toxic fumes)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• In the workup of inhalation injuries caused by toxic smokes, the primary investigation is toward the pulmonary system. Other tests should be clinically indicated based on history, physical examination, and underlying health problems.


• Arterial blood gas determination aids in the evaluation of the degree of hypoxia and alerts the health care provider to other possible toxins such as carbon monoxide and methemoglobin.


• Carbon dioxide levels also may be monitored, since patients with prior lung disease such as asthma and COPD may be affected more severely and are at greater risk to retain carbon dioxide.


• Perform baseline pulmonary function tests (PFTs) once the patient is stable. This may be difficult in the emergency department, but 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.

• Exposure to HC/ZnO warrants baseline LFTs on initial presentation. These should be followed over the course of hospitalization if exposure is severe enough to warrant admission.

Imaging Studies

• Chest radiography

• Chest radiography can help in evaluating the presence of hyperinflation that may suggest injury of the smaller airways and air trapping. Noncardiogenic pulmonary edema also is a clue to toxic inhalation.


• CXR changes may lag behind clinical changes by hours or days; therefore, if findings are normal, they may be of limited value.


• Individuals with fume fever often are sent home after 4 hours observation and with a clear CXR, only to return after the initial recovery and latent phase with more severe dyspnea and florid noncardiogenic pulmonary edema.


• CXR in a significant HC exposure may not show anything abnormal until 4-6 hours postexposure. CXR findings slowly may improve with supportive care or advance to a long-standing diffuse interstitial fibrosis.


• In phase III of NOx exposure, a noncardiogenic pulmonary edema pattern may be seen on CXR. Pathologic findings may demonstrate classic bronchiolitis fibrosa obliterans, which may mimic miliary tuberculosis on CXR. Fibrotic changes either may clear spontaneously or proceed to severe respiratory failure.

Other Tests

• ECG and serial cardiac enzymes also are important in the setting of chest pain, as clinically indicated, to evaluate underlying cardiac ischemia, which may be precipitated by hypoxia or increased oxygen demand.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Prehospital Care

• Prehospital care is directed toward securing the airway as needed, administering oxygen, and obtaining intravenous (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.
• Although the care is mostly supportive, prompt delivery to the emergency department should be a priority for prehospital care providers.
• As always, the prehospital care providers must do all in their power to remove the patient from ongoing exposure without becoming casualties themselves.

Emergency Department Care

Treatment of inhalation injuries caused from toxic smokes is based on clinical presentation and involves primarily supportive care directed at the cardiopulmonary system.

• Begin treatment by removing the patient from the source of exposure and providing appropriate detoxification.


• Provide intravenous access, cardiac monitoring, and supplemental oxygen in the setting of hypoxia.


• Begin bronchodilators in a patient with bronchoconstriction.


• Subcutaneous epinephrine has been used in HC exposures.


• Steroids remain controversial but have been suggested as having some value in NOx, HC, RP, FS, FM, and PTFE exposures.


• HC exposures may require British anti-Lewisite (BAL) administration and the chelating agent calcium ethylenediaminetetraacetic acid (CaEDTA).


• If the patient was exposed to particulate RP and burns are present, a topical bicarbonate solution to neutralize phosphoric acids may be used. Mechanical removal and debridement of contaminated wounds helps diminish toxicity to elemental phosphorus.


• FS and FM exposures require washing of irritated skin with water and then a sodium bicarbonate solution. Any eye involvement should prompt generous irrigation and examination with fluorescein. Obtain ophthalmology follow-up care. Mydriasis with atropine sulfate has been suggested as potentially helpful.


• Some animal studies suggest that in the setting of PTFE exposure, increasing concentrations of pulmonary oxygen free radical scavengers containing thiol groups may be valuable. N-acetyl cysteine has been found effective.


• 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.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Bronchodilators

These agents are important in the setting of bronchoconstriction and bronchorrhea. Toxic smokes can cause bronchoconstriction, especially if the exposed individual has underlying asthma or COPD.

Drug Category: Anti-inflammatory agents

Although somewhat debated, steroids are believed to be helpful in toxic smoke inhalation, especially in metal fume fever, which is believed to be mediated by an inflammatory cascade of events involving cytokines and histamine release.

Drug Category: Chelating agents

No reports exist as to the efficacy of chelating agents; however, BAL and CaEDTA have been suggested because of their ability to reduce serum zinc levels.

Drug Name	CaEDTA (Disotate, Endrate, Chealamide)
Description	Second drug used in lead toxicity; although mostly used in lead chelation, use has been associated with lowering serum zinc levels; begin therapy 4 h after BAL is given; only administered IV; continuous infusion is recommended. Zinc toxicity may be treated with a combination of BAL and EDTA or with EDTA alone; Llobet et al studied 16 chelating agents as possible antidotes for acute zinc exposure in mice (Llobet, 1988); BAL and CaEDTA remain most commonly used in zinc toxicity; the combination approach has a higher incidence of nausea, vomiting, and elevated liver enzymes.
Adult Dose	Symptomatic encephalopathic adult patient: 1500 mg/m2/d administered as continuous IV infusion
Pediatric Dose	For severe exposure only: 1500 mg/m2/d continuous IV infusion Symptomatic nonencephalopathic patient: 1000 mg/m2/d continuous IV infusion
Contraindications	Documented hypersensitivity; renal failure
Interactions	Enhances hypoglycemic effects of insulin in patients with diabetes
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Because of potential for renal toxicity, patient should be well hydrated; EDTA may worsen CNS toxicity if given prior to BAL therapy; not recommended for patients in renal failure; to prevent hypocalcemia, use only calcium disodium salt of EDTA for chelation in heavy metal toxicity

Drug Category: Adrenergic agonists

In profound bronchoconstriction and wheezing, SC epinephrine has been helpful in stabilizing mast cells and halting or reversing potentially fatal bronchoconstriction.

Drug Category: Mydriatic agents

These agents relax any ciliary muscle spasm that can cause deep aching pain and photophobia.

Drug Category: Alkalinizing agents

These agents are indicated for FS and FM cutaneous exposure.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Outpatient Care

• Although most individuals recover without lasting sequelae, some relapse into an acute pulmonary syndrome or develop chronic changes in pulmonary function. Obtain serial PFTs to evaluate progression or deterioration in lung function.

Deterrence/Prevention

• 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.

Prognosis

• The prognosis for mild-to-moderate exposures of toxic smokes is generally very good, with the usual outcome return to full recovery without sequelae.
• With more severe exposures, lungs may become severely damaged and develop chronic pulmonary fibrosis.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center and Poisoning Center. Also, see eMedicine's patient education articles Chemical Warfare, Personal Protective Equipment, Smoke Inhalation, and Carbon Monoxide Poisoning.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Perhaps the primary medicolegal pitfall in evaluating and treating toxic smoke inhalation and fume fever is overlooking or ignoring the delayed reactions and clinical deterioration associated with many of these exposures. Acute respiratory distress usually responds very well to aggressive initial management. Normal laboratory values and imaging studies, coupled with clinical improvement, usually give the health care provider a false sense of security. The patient then may be discharged from the health care center only to deteriorate as delayed pulmonary edema ensues. Anyone with significant exposure to toxic smokes should be observed for 24-48 hours and imaged with serial CXRs. Difficulty arises in defining a significant exposure, since the clinical response is so varied.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Daniel T Smith, MD, Andrea M DuPont, MD, and Natalie M Cullen, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

1. Hsu HH, Tzao C, Chang WC, Wu CP, Tung HJ, Chen CY. Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high-resolution CT findings, and pulmonary function test results. Chest. Jun 2005;127(6):2064-71. [Medline].
2. Conner MW, Flood WH, Rogers AE, Amdur MO. Lung injury in guinea pigs caused by multiple exposures to ultrafine zinc oxide: changes in pulmonary lavage fluid. J Toxicol Environ Health. 1988;25(1):57-69. [Medline].
3. Marrs TC, Colgrave HF, Edginton JA, Brown RF, Cross NL. The repeated dose toxicity of a zinc oxide/hexachloroethane smoke. Arch Toxicol. 1988;62(2-3):123-32. [Medline].
4. Kuschner WG, D'Alessandro A, Wong H, Blanc PD. Early pulmonary cytokine responses to zinc oxide fume inhalation. Environ Res. Oct 1997;75(1):7-11. [Medline].
5. Loh CH, Chang YW, Liou SH, Chang JH, Chen HI. Case report: hexachloroethane smoke inhalation: a rare cause of severe hepatic injuries. Environ Health Perspect. May 2006;114(5):763-5. [Medline].
6. Stueven HA, Coogan P, Valley V. A hazardous material episode: sulfur trioxide. Vet Hum Toxicol. Feb 1993;35(1):37-8. [Medline].
7. Patel MM, Miller MA, Chomchai S. Polymer fume fever after use of a household product. Am J Emerg Med. Nov 2006;24(7):880-1. [Medline].
8. Ademoyero A, Gan K. Toxicological Profile for Zinc (Update). US Dept of Health & Human Services -- PHS;1994.
9. Akbar-Khanzadeh F. Short-term respiratory function changes in relation to workshift welding fume exposures. Int Arch Occup Environ Health. 1993;64(6):393-7. [Medline].
10. Bylin G. Health risk evaluation of nitrogen oxide. Controlled studies on humans. Scand J Work Environ Health. 1993;19 Suppl 2:37-43. [Medline].
11. Departments of the Army, the Navy, and the Air Force, and Commandant Marine Corps. Smokes. In: Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries. Part 2. Conventional Military Chemical Injuries. 1995;chap 8. [Full Text].
12. do Pico GA. Toxic fume inhalation. In: Pulmonary and Critical Care Medicine. Vol 2. 1993:11-12.
13. Duerksen-Hughes P, Richter P, Ingerman L. Toxicological Profile for White Phosphorus. US Dept of Health & Human Services -- PHS;1997.
14. Gordon T, Chen LC, Fine JM, Schlesinger RB, Su WY, Kimmel TA. Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits. Am Ind Hyg Assoc J. Aug 1992;53(8):503-9. [Medline].
15. Johnston CJ, Finkelstein JN, Gelein R, Baggs R, Oberdörster G. Characterization of the early pulmonary inflammatory response associated with PTFE fume exposure. Toxicol Appl Pharmacol. Sep 1996;140(1):154-63. [Medline].
16. Johnston CJ, Finkelstein JN, Mercer P, Corson N, Gelein R, Oberdörster G. Pulmonary effects induced by ultrafine PTFE particles. Toxicol Appl Pharmacol. Nov 1 2000;168(3):208-15. [Medline].
17. Little JD, Liccione J, Iannucci A. Toxicological Profile for Sulfur Trioxide and Sulfuric Acid. US Dept of Health & Human Services -- PHS. 1998.
18. Llobet JM, Domingo JL, Corbella J. Antidotes for zinc intoxication in mice. Arch Toxicol. 1988;61(4):321-3. [Medline].
19. Murray E, Llados F. Toxicological Profile for Titanium Tetrachloride. US Dept of Health and Human Services -- PHS. 1997.
20. Paulsen SM, Nanney LB, Lynch JB. Titanium tetrachloride: an unusual agent with the potential to create severe burns. J Burn Care Rehabil. Sep-Oct 1998;19(5):377-81. [Medline].
21. Samet JM, Utell MJ. Air pollution. In: Bone RC, ed. Pulmonary and Critical Care Medicine. Vol 2. 1993:7-12.
22. Selgrade MK, Hatch GE, Grose EC, Illing JW, Stead AG, Miller FJ. Pulmonary effects due to short-term exposure to oil fog. J Toxicol Environ Health. 1987;21(1-2):173-85. [Medline].
23. Selgrade MK, Hatch GE, Grose EC, Stead AG, Miller FJ, Graham JA. Pulmonary effects due to subchronic exposure to oil fog. Toxicol Ind Health. Jan 1990;6(1):123-43. [Medline].
24. Urbanetti JS. Toxic inhalational injury. In: Medical Aspects of Chemical and Biological Warfare. 1997;260-267. [Full Text].

Article Last Updated: Jun 7, 2007