Emerg Med Clin N Am 21 (2003) 533557

Acute inhalation injury

Ken Miller, MD, PhDa,*, Andrew Chang, MDb
Orange County Fire Authority, EMS Section, 145 South Water Street, Orange, CA 92866-2123, USA b University of CaliforniaIrvine Medical Center, Department of Emergency Medicine, Route 128, 101 The City Drive South, Orange, CA 92868, USA
a

In industrialized countries, inhalational exposures to various toxicants are commonplace. Although the cases of inhalational anthrax in late 2001 have caused renewed concern about chemical agents and bioterrorism in general, most acute toxic inhalations come from nonterrorist sources, such as from industries, home, and recreational sources. Unfortunately, the varied presentations result in a nonspecic clinical syndrome and make diagnosis somewhat dicult. A detailed history becomes even more important in such a patient and may help make a dierence in the often chaotic setting of the emergency department (ED). Fortunately, symptomatic and supportive therapy is usually all that is needed, although in selected cases the administration of the proper antidote is critical to patient survival.

Classication schemes Numerous classication schemes have been developed as a way to organize the enormous numbers of possible inhaled toxicants. Most reviews of acute toxic inhalations are based on the agents mechanism of toxicity, such as whether it is a pulmonary irritant or systemic toxicant [1,2]. For this review, the authors have chosen to organize the toxicants based on the location or source of the exposure, because this is often how patients (especially multi-casualty patients) actually present to the ED. The general locations or sources that the authors use are occupational/industry, home/ community, and war/chemical weapons (Box 1).

* Corresponding author. Orange County Fire Authority, EMS Section, 145 South Water Street, Orange, CA 92866-2123. E-mail address: kenmiller@ocfa.org (K. Miller). 0733-8627/03/$ - see front matter 2003, Elsevier Inc. All rights reserved. doi:10.1016/S0733-8627(03)00011-7

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Box 1. Categorization by source of exposure Industry/occupation Home/community War/chemical weapons

Although the authors approach this broad topic based on the source of exposure, it is worthwhile to review the basic pathogenesis of inhalational injuries. Such injuries in general occur either through localized pulmonary damage or by systemic absorption after inhalation. Those that cause localized pulmonary damage can be subdivided further into irritant gases and those that cause pulmonary sensitization (Box 2). Those that cause systemic toxicity can be subdivided into simple and chemical asphyxiants, organophosphates, hydrocarbons, and metal fumes (Box 3). As can be seen in Box 2, there can be signicant overlap, as many toxicants can t in multiple categories. Treatment is usually symptomatic with the exception of organophosphates and certain chemical asphyxiants, such as cyanide and carbon monoxide.

Box 2. Pulmonary inhalational toxicants Irritant gases Ammonia Chlorine Formaldehyde Nitrogen dioxide Phosgene Hydrogen uoride Acrolein Ozone Antigens/sensitizers Ammonia Chlorine Formaldehyde Nitrogen dioxide Toluene Vinyl plastics Animal and plant proteins Bacteria Fungi

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Box 3. Systemic inhalational toxicants Asphyxiants Carbon monoxide Hydrogen cyanide Hydrogen sulde Carbon dioxide Methane Helium Organophosphates Nerve gases Sarin (GB) Tabun (GA) Soman (GD) Venon X Insecticides Hydrocarbons Freon Benzene Toluene Vinyl chloride Tricholoroethylene Tricholoroethane Metal fumes Beryllium Cadmium Mercury Nickel Zinc Chromium

Mechanisms of acute inhalation injury Relevant respiratory anatomy Several elements of respiratory anatomy contribute to protection of the airways and lungs from inhaled toxicants and particulates. In the upper airway, particulates in the 510-lm range are trapped through air turbulence on the mucosal surface of the nasal turbinates. In the conducting airways, ciliated and mucus-secreting epithelium constitutes the mucociliary escalator, which moves inhaled particles up proximally. Within the trachea and bronchi, this mucociliary escalator can move inhaled particles up the airway at approximately 14 cm per hour.

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In the more distal airways, alveolar macrophages phagocytose inhaled particulates. These macrophages are able to move around the alveolar unit by way of the air space, lymphatics, and pulmonary capillaries. Lysosomes containing acid hydrolases destroy particulates; however, the interactions of macrophages with inhaled particulates also can trigger inammatory and immunologic reactions within the lung. Lymphatic clearance is another, albeit less important mechanism, of removing inhaled particulates.

Relevant respiratory physiology and physicochemical principles The lung parenchyma is capable of xenobiotic metabolism of some compounds such as polycyclic aromatic hydrocarbons, but overall it is a minor contributor of toxicant biotransformation and clearance compared with renal and hepatic clearance. In the case of paraquat, lung biotransformation to reactive oxidative paraquat intermediates contributes to the pulmonary parenchymal injury of that compound. Inhaled toxicants can be in the form of gases, vapors, particulates, or aerosols (droplets of liquid or ne particulates suspended in a gas). Gases, vapors, or liquids can be adsorbed onto the surface of particulates and carried into the airways. Three fundamental parameters determine the extent of inhaled toxicant exposure: water solubility of the toxicant, duration of exposure, and minute ventilation. Water solubility plays a signicant role in determining the location of gas or vapor inhalation injury. Compounds that are more water-soluble aect the upper airways as they dissolve and concentrate in the aqueous phase of mucus. At high concentrations or with prolonged exposure, however, watersoluble compounds may cause lower airway injury also. Compounds that are less water-soluble aect the lower airways, resulting in damage to the alveoli and epithelium of the respiratory bronchioles. Damage to pulmonary capillary endothelial cells and alveolar macrophages can contribute to later superimposed bacterial infection and chemical pneumonitis. Characteristics of particulates that contribute to toxicity include particle size, density, and shape. The principle contributor to airway penetration is particle size. Particles with an aerodynamic diameter greater than 10 lm are ltered in the nasopharynx or deposited on the larynx. Particles 310 lm in size are deposited in the conducting airways, whereas particulates 0.53 lm in size are deposited in distal airways and alveoli. Particulates less than 0.5 lm in size (submicron particles) behave like a gas and may be exhaled with exhaled air. Water-soluble particulates can be absorbed across the respiratory bronchiolar or alveolar epithelium into the blood. Insoluble particulates are eliminated by expectoration, swallowing, lymphatics, or phagocytosis and subsequent lysis. Phagocytosed particulates leading to lysis of alveolar macrophages can result in pulmonary brosis, granuloma, or emphysema.

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Clinical anatomic and physiologic correlates The eects of inhalation exposure to toxicants can be thought of as follows: simple asphyxiants, tissue asphyxiants, nonrespiratory systemic toxicants with pulmonary absorption, and direct airway cellular injury. Simple asphyxiants, such as nitrogen, helium, hydrogen, methane, propane, and natural gas, displace atmospheric oxygen but are otherwise essentially physiologically inert. Occupational safety limits established by the Occupational Safety and Health Administration (OSHA) [3] require atmospheric oxygen concentrations in conned spaces to be between 19.5% and 23.5%. Hypoxic atmospheres less than 19.5% can impair function and judgment and can lead to accident and injury. Atmospheres less than 16% oxygen below 3,000 feet altitude are considered immediately dangerous to life and health (IDLH). As altitude increases and atmospheric pressure decreases, this hypoxic atmospheric IDLH increases. Hyperoxic atmospheres greater than 23.5% in conned spaces increase the risk for re. Tissue asphyxiants, such as carbon monoxide, hydrogen cyanide, hydrogen sulde, and azides, inhibit mitochondrial electron transport and oxygen use. Tissue asphyxiants and their participation in the syndrome of acute inhalation injury are discussed in the section on smoke inhalation. Many chemicals exert systemic toxic eects when absorbed by way of the pulmonary circulation but cause no direct acute airway or lung injury. Examples include halogenated aliphatic hydrocarbons, benzene and other aromatic compounds, gas or aerosol forms of the tissue asphyxiants, and many solvents. The discussion of inhalation toxicology here focuses on those toxicants causing acute lung injury. Direct airway cellular injury results from epithelial cell injury and death and from airway edema. The consequences of epithelial cell injury include reduction of mucociliary clearance of inhaled particulates, leak between intercellular junctions, and sloughing of dead epithelium leading to airway obstruction. Airway edema results from epithelial junction leak and from cytokines and mediators released in response to cellular injury. These mediators contribute to inammation, edema, and airway smooth muscle contraction. The nasopharynx and larynx manifest these cellular injuries earliest because they are exposed to the highest concentrations of inhaled toxicants. Clinical manifestations include hoarseness, stridor, and laryngeal edema. Mucosal ulceration, hemorrhage, and edema, however, may be delayed up to several hours postexposure. Tracheobronchitis together with paralyzed cilia and impaired mucus clearance can follow prolonged exposure to particulates containing adsorbed toxicants [4]. There is a gradual but progressive airway response to direct cellular injury. Within a few hours postexposure there is extensive but mild mucosal edema, no ulceration, and deceptively minimal clinical symptoms. Over the next 848 hours there is progressive airway edema, mucopurulent membrane production, and bronchorrhea. Within

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4872 hours there is mucosal slough and evolution of a membranous tracheobronchitis [5]. Bronchoconstriction, peribronchial edema, and bronchial mucosal slough all can contribute to the development of atelectasis. In the distal airways and alveoli, epithelial and endothelial injury result in permeability-induced edema. This can manifest anywhere from mild interstitial edema to pulmonary insuciency. Alveolar ooding can occur at normal pulmonary capillary hydrostatic pressure or may be retrograde from more proximal airway bronchorrhea. As in other forms of the acute respiratory distress syndrome (ARDS), this results in decreased lung compliance, increased alveolar-arterial oxygen gradient, and increased pulmonary vascular resistance. Pulmonary edema may be immediate in pulmonary high-concentration toxicant exposure or may be delayed 2448 hours postexposure. There may be dierences in etiology, treatment, and outcome between the syndrome of ARDS caused by a systemic inammatory response (extrapulmonary ARDS) and that caused by acute lung injury (primary pulmonary ARDS) [6]. Finally, excessive physiologic responses may be part of the acute inhalation injury syndrome. Cough, mucous secretion, and bronchoconstriction are all normal responses to inhaled irritants. An incapacitating cough may accompany pre-existing airway hyperresponsiveness. Chronic mucus hypersecretion can follow continued exposure to irritants (industrial bronchitis). Breath holding and laryngospasm may occur in conscious victims attempting an escape from a hazardous atmosphere.

Clinical assessment and treatment of acute inhalation injury Clinical assessment Symptoms of acute inhalation injury can be delayed in onset. The clinical setting of facial burns, inamed nares, sputum production, and wheezing in victims of res or explosions in enclosed spaces, or altered mental status at the scene aecting the ability to escape, can all be conditions preceding the onset of symptoms of acute inhalation injury. Cough is likely the rst symptom. Occasionally cough may reect cough-variant asthma or irritant-associated vocal cord dysfunction caused by direct vocal cord inammation [7]. Tissue asphyxiants may cause dizziness, headache, chest pain, nausea, and vomiting. The most acute clinical problem might be rapidly evolving upper airway obstruction caused by thermal or chemical burns to the face, nares, or oropharynx. An unpredictable fraction of these patients go on to life-threatening obstruction. If resources and consultative services allow clinical observation in an intensive care unit with serial beroptic laryngoscopy and bronchoscopy, the need for tracheal intubation may be minimized. Such serial examinations, however, can be uncomfortable in patients with upper airway inammation. When these resources are not available, early preemptive tracheal intubation is the best choice.

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Spirometry gives a good general picture of airow dynamics. The forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC) decreases in obstructive lung disease. Peak expiratory ow rate (PEFR) can be measured in a patient during symptomatic and asymptomatic periods and may reect early airway obstruction [8]. Normal spirometry does not exclude signicant lung disease and can be dicult to apply in critically ill patients or may be unavailable in a timely fashion in the ED. The most available diagnostic tests in the ED are arterial blood gases (ABGs) and chest radiography. ABGs can provide information on oxygenation (PaO2 and SaO2), ventilation (PaCO2), acid-base status (pH), and alveolar gas exchange (PA-aO2), but still can be normal in the immediate postexposure period. Arterial oxyhemoglobin saturation (SaO2) should be measured by cooximetry rather than by infrared-visible dual wavelength pulse oximetry, because pulse oximetry cannot distinguish carboxyhemoglobin or methemoglobin from oxyhemoglobin. Chest radiography is readily available but it is nonspecic (many pathologies produce similar radiographic changes), correlates poorly with clinical manifestations of interstitial lung disease, and may be normal in the immediate postexposure period. Common radiographic ndings in acute inhalation injury are diuse interstitial, alveolar, or mixed inltrates, segmental consolidation, or hyperination. Noncontrast spiral chest computed tomography also can be used to further characterize interstitial lung abnormalities [9]. Fiberoptic laryngoscopy and bronchoscopy, when available, allows the visualization of erythema, edema, ulceration, and hemorrhage from the level of the posterior pharynx to four to ve generations of bronchi. Fiberoptic inspection can provide early information on airway injury severity, and when done serially can assess the success of therapy. Treatment Out-of-hospital management Dyspnea, tachypnea, hypoxia by pulse oximetry, altered mental status, and suspected carbon monoxide toxicity in the clinical setting of acute inhalation injury are all indications for oxygen administration by nonrebreather mask (FIO2 approximately 0.9 at 15 L/min). If stridor or other physical evidence of upper airway edema is present, preemptive intubation may prevent precipitous airway obstruction from progressive airway edema that otherwise would make delayed laryngoscopy dicult or impossible. Adjunctive airway devices such as the esophageal-tracheal Combitube (ETC) or laryngeal mask airway (LMA) may facilitate ventilation when bag-valve-mask ventilation is dicult because of oropharyngeal edema. It is important to keep in mind that the LMA does not protect the airway from aspiration and neither the ETC nor LMA can protect the airway from evolving laryngeal edema. In addition, a nonintubating LMA cannot support positive pressure ventilation greater than peak airway pressures of 2030 cm H2O. The inherently smaller diameter

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of the pediatric airway predisposes it to obstruction. There is a disproportionate increase in airway resistance and decrease in cross-sectional area for equivalent degrees of edema in pediatric and adult airways. Airway suction also may be necessary to clear reactive secretions. Aerosolized bronchodilators should be used for bronchoconstriction. If necessary, aerosolized beta-agonists can be administered by way of a nebulizer in series with bag-valveassisted ventilation using a mask, endotracheal tube, or airway adjunct. Burn center, trauma center, and hyperbaric facility triage decisions are guided by local standards of practice and out-of-hospital treatment guidelines. The decision to use hyperbaric oxygen is discussed in the section on smoke inhalation. In physiologically unstable patients, early transport is desirable after adequate airway management and necessary spinal immobilization have been completed. Intravenous access and electrocardiographic monitoring can be established en route to the receiving hospital. If thermal or chemical cutaneous burns accompany the acute inhalation injury, narcotic analgesia should be considered. If the patient is unable to provide a history of the inhalation exposure incident, observations at the scene can be helpful in determining future therapy, observation periods, and likely prognosis. If an explosion or re resulting in patient entrapment or altered mental status was associated with the inhalation injury, this may reect a greater duration of inhalation exposure and the potential for delayed onset symptoms. If hazardous materials response teams have conducted reconnaissance, atmospheric monitoring, or eld environmental testing, these data and any actual or presumptive identication of the toxicant involved can assist in clinical decision making later. Emergency department management Although more options are available in the ED to assess and manage the airway, management as a whole continues from the fundamental principles begun during the out-of-hospital phase of patient care. When equipment and consultative resources are available, beroptic laryngoscopy can help determine the extent of upper airway injury and the need for preemptive tracheal intubation. If airway edema is already a problem, the beroptic laryngoscope, exible intubation guides, specialized laryngoscope blades (eg, the Bainton pharyngeal blade), intubating laryngeal masks, retrograde intubation, transtracheal jet ventilation, and cricothyroidotomy are all options to assist or achieve tracheal intubation. Bronchodilators can be administered by aerosol inhalation in the spontaneously breathing patient or during assisted ventilation; however, corticosteroids should be avoided. Studies have been conicting, but evidence of reduced lung bacterial clearance and increased incidence of bacterial pneumonia as a late complication of inhalation injury outweighs any potential anti-inammatory eects [10,11].

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Diagnostic studies that can help characterize the severity of the inhalation injury include chest radiography, arterial blood gases (ABGs) with cooximetry, serial peak expiratory ow rates (PEFR), and bedside spirometry when available. It is important to keep in mind that these studies may be normal in the immediate postexposure period. Aside from serial vital sign measurements, other studies that may assist in clinical decision making are 12-lead electrocardiography to identify cardiac ischemia or infarction and blood and urine toxicology studies to identify coexisting toxicity that may have contributed to the cause of the inhalation injury and complicate its course. Pulse oximetry can be deceiving in the presence of a toxic hemoglobinopathy, so cooximetry should be used to determine oxyhemoglobin saturation. Persistent hypoxia despite tracheal intubation, supplemental oxygen administration, bronchodilators, and suction of airway secretions may reect early pulmonary parenchymal injury requiring mechanical ventilation with positive end-expiratory pressure (PEEP). Fluid management in a patient with a combination of cutaneous burns and inhalation injury can be a complex balance between replacing burn uid losses without excessive interstitial lung water accumulation because of the pulmonary capillary leak of inhalation injury. Achieving this balance requires monitoring of uid intake and output and pulmonary artery catheter hemodynamic parameters. Less severely injured patients present challenges also. When physical examination reveals a reasonably well appearing patient, the history of exposure may be the critical determining factor in the duration of subsequent observation. Serial ABGs, chest radiography, PEFR, airway and lung examination, and bedside spirometry where available help detect the evolution of delayedonset distal airway and pulmonary parenchymal injury. History or suspicion of inhalation injury should lead to an observation period of at least 24 hours.

Home and community Smoke inhalation The single most likely cause of acute inhalation injury in emergency medicine practice is smoke inhalation from residential or commercial structure res. In addition, smoke inhalation emergencies can present as multi-casualty incidents. Smoke inhalation is the leading cause of death from structure res, particularly from re in multistory structures. Smoke inhalation also adds to mortality from cutaneous thermal burns. Mortality rates from smoke inhalation are approximately 5%8% [6]. Mortality rates for combined major burn injury and inhalation injury, however, exceed that of either injury alone [6]. Early deaths are usually caused by airway compromise or metabolic poisoning. Smoke inhalation represents a combination of direct pulmonary injury and systemic and metabolic toxicities.

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There are three time-related but highly variable phases of acute smoke inhalation. The early resuscitation phase is within 36 hours postexposure and is characterized by acute pulmonary insuciency [12]. The following discussion focuses on this phase, as it is the time the patient is managed in the emergency department. The postresuscitation phase is approximately 25 days postinjury and is characterized by mucosal necrosis and slough, viscous secretions, and distal airway obstruction with atelectasis, pulmonary interstitial edema, and bronchopneumonia. The inammatoryinfection phase is approximately 5 days and beyond in the postinjury period and continues until there is lung healing and burn wound closure. This phase is characterized by nosocomial bronchopneumonia, hypermetabolic-induced respiratory fatigue, and acute respiratory distress syndrome. Pathophysiologically, smoke inhalation injury can be thought of as having two principle components: direct smoke lung injury and systemic smoke inhalation syndrome. Smoke lung injury The composition of smoke is variable and dicult to predict for toxicologic assessment of the individual patient. Smoke toxicity depends on the fuels that are burning, the completeness of combustion, and the generated heat intensity. In addition, even within the same structure, smoke composition can vary in time during the burning and extinguishment process and location within the structure. Filtered smoke in rooms removed from the seat of the re can contain metabolic toxicants, as can smoke from relatively smokeless combustion (eg, internal combustion engine exhaust). In these cases, metabolic eects can exceed pulmonary eects. Clinical consequences of smoke exposure depend on chemical composition, particulate size, exposure time, and minute ventilation. Surrogate markers for these parameters include historical exposure time, neurologic status, and carboxyhemoglobin. Neurologic status interpretation is frequently complicated by coexisting head injury and drug or alcohol ingestion. Unless the patient is exposed to steam, direct heat injury to the airway is limited to supraglottic structures because of the heat dissipating properties of the upper airway [13]. Steam has approximately 4,000 times the heat carrying capacity of hot air, so at any given temperature steam has more heat to give up than an equal volume of dry air [14]. The consequence can be rapidly fatal obstructive glottic edema, thermal tracheitis, and hemorrhagic edema of the bronchial mucosa. Gas phase constituents of smoke include carbon monoxide, hydrogen cyanide, acid and aldehyde gases, and oxidants [15]. These components are mucosal irritants and can lead to bronchorrhea, bronchoconstriction, and airway edema. Smoke also contains particulates, the size of which are determined by the nature of the fuel that is burning. Particle size in the 35-lm range seems to predominate in structure res, within the range

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allowing more distal airway penetration and retention. These particulates can adhere to the mucosa and perpetuate local tissue injury by keeping adsorbed toxicants in contact with the mucosa. Particulate clearance from the airways is inhibited by the local airway injury. Lung pathophysiologic response to smoke inhalation depends on several factors. The preinjury health status of the patient and reactive airway disease or chronic lung changes contributes to smoke inhalation injury severity. Direct mucosal injury compromises the mucociliary escalator and particulate, mucus, and bacterial clearance. Increase in bronchial blood vessel permeability contributes to submucosal edema and the increased bronchial blood ow can lead to vascular engorgement-related mass eect and airway lumen narrowing. Tissue destruction and secondary inammatory response results in mucosal slough and increases mucus production. Although alveolar ooding is observed in the early postinjury period, it is more likely caused by retrograde ooding from proximal airway edema rather than alveolar capillary leak that usually occurs after the initial 2436 hours.

Systemic smoke inhalation injury Early systemic changes include a decrease in cardiac lling pressure and cardiac index. These eects may be caused by myocardial tissue anoxia from the mitochondrial toxicity of carbon monoxide or hydrogen cyanide. They also may be caused by decreased blood volume from capillary leak and uid and protein loss into lung and systemic tissue. The inammatory eects causing capillary leak are complimentary following cutaneous burns and inhalation injury. Cutaneous burns increase the degree of pulmonary capillary leak, and inhalation injury increases the rate of burn edema formation. Early uid resuscitation is necessary to maintain adequate perfusion. Later systemic eects of inhalation injury include inammation within the airways and lung parenchyma by postinjury day 2 or 3. Nosocomial pneumonia and the presence of cutaneous burns can exacerbate a systemic inammatory hyperdynamic state with increased tissue oxygen demand and blood ow maldistribution. Facial and neck burns result in cross contamination, colonization, and infection of the airways and lung. Resuscitation phase: the rst 36 hours Frequently the diagnosis and treatment of this phase establishes the subsequent course of the smoke inhalation syndrome. Early diagnosis may be largely based on clinical suspicion. A history of disorientation or unconsciousness at the scene can reect the results of smoke inhalation or indicate prolonged smoke exposure. Respiratory symptoms may be delayed in onset, but carbonaceous sputum, singed nasal or facial hair, facial burn, cough, or wheezing can indicate the presence of smoke inhalation syndrome. Initial ABGs may be normal. There may be a metabolic acidosis caused by carbon

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monoxide toxicity and a decrease in measured SaO2. The PaO2/FIO2 ratio may have some bearing on prognosis [16]. A value greater than 300 has been associated with survival after initial resuscitation. The initial chest radiograph also is frequently normal. The early injury is to the airways rather than the lung parenchyma. Peribronchial cung and perivascular haziness may be early but nonspecic radiographic signs. Atelectasis, increasing lung water, and focal inltrates evolve over the rst few days. Entrapment or unresponsiveness within a structure re can expose the victim to a toxic and hypoxic atmosphere. Hypoxia alone should result in reversible neurologic dysfunction unless prolonged. Tissue asphyxiants released during combustion include carbon monoxide and hydrogen cyanide. Carbon monoxide is rapidly transported across the alveolar membrane and binds to hemoglobin. Measured arterial hemoglobin saturation (SaO2) by co-oximetry is decreased below that expected for the PaO2. Pulse oximetry (SpO2) is unreliable because of similar light absorption by carboxyhemoglobin and oxyhemoglobin so that SpO2 overestimates SaO2. Carboxyhemoglobin (HbCO) saturation can be directly measured by co-oximetry and may be lower by the time of emergency department evaluation as compared with the scene because of out-of-hospital oxygen administration. Carboxyhemoglobin shifts the oxyhemoglobin dissociation curve to the left, thereby impairing the unloading of oxygen at the tissue level. With prolonged exposure, carbon monoxide saturates cells and binds to cytochrome oxidase, which then uncouples mitochondrial oxidative phosphorylation and reduces ATP production. This results in a metabolic acidosis. Unlike cyanide poisoning, mild to moderate carbon monoxide poisoning is common. Patients often present with vague symptoms such as headache, nausea, vomiting, dizziness, and confusion. With sucient duration of exposure, subtle neuropsychiatric symptoms may persist. Carbon monoxide is displaced from hemoglobin by the administration of supplemental oxygen. The half-life of carboxyhemoglobin is aected by several factors [17]. Carbon monoxide accumulation in tissue and intrapulmonary shunting prolongs elimination. An increased minute ventilation and to some extent a reduced cardiac output, allowing more time for alveolar gas mass transfer, increases elimination. The half-life of carboxyhemoglobin (HbCO) with the patient breathing clean air is 46 hours. Breathing 90% 100% oxygen at 1 atmosphere absolute pressure (1 ATA) reduces the HbCO half-life to 6090 minutes. Breathing 100% oxygen at 3 ATA (common hyperbaric treatment pressures are 2.43.0 ATA) reduces the HbCO half-life to 2030 minutes. Hyperbaric oxygen (HBO) is more eective at removing carbon monoxide from mitochondrial cytochromes. Clinical outcome studies of HBO treatment in carbon monoxide toxicity have been conicting [18], and objective clinical markers for patient selection for treatment are lacking. HbCO levels alone do not correlate well with clinical outcomes, especially neuropsychiatric symptoms, so treatment decisions are based on mortality and morbidity risk factors. Current recommendations for the use of HBO are

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HbCO [ 25%30%, neurologic compromise, metabolic acidosis, or electrocardiographic evidence of myocardial ischemia, infarction, or dysrhythmias [19]. Other considerations for treatment include HbCO [ 10% in pregnancy (because of greater fetal hemoglobin anity for CO), HbCO[15% in patients with known ischemic heart disease or failure of clinical improvement within 4 hours of treatment with 100% normobaric oxygen delivered by way of a good tting nonrebreather mask [45]. Hydrogen cyanide and aerosolized or particulate-adsorbed cyanide salts are absorbed across the alveolar membrane. Hydrogen cyanide is a combustion and pyrolysis product of natural and synthetic materials. The contribution of cyanide toxicity in acute smoke inhalation syndrome is debated [20]. Cyanide-related fatalities are rare and tend to be associated with high HbCO levels. In addition, the use of the methemoglobin-producing components of the cyanide antidote kit would further compromise oxygen transport. Cyanide binds to mitochondrial cytochromes, leading to impaired mitochondrial ATP production and tissue ATP depletion. Cyanide does not bind to reduced hemoglobin (Fe2+) but does bind to oxidized hemoglobin (Fe3+), forming cyanomethemoglobin. Because the central nervous system and myocardium are the most sensitive to tissue hypoxia and ATP depletion, coma, seizure, reduced cardiac output, and metabolic acidosis can all occur. Mixed venous oxygen content (CvO2) approaches the arterial oxygen content (CaO2) because oxygen extraction from tissue is impaired. Pulse oximetry reects the oxyhemoglobin saturation in cyanide toxicity in the absence of HbCO and if methemoglobinemia has not been induced as part of the therapy. Cyanide is detoxied in tissue, especially the liver, by sulfur transferase (rhodanese) to thiocyanate that is then excreted by the kidney. This process regenerates methemoglobin from the cyanomethemoglobin. Unlike carbon monoxide, mild acute cyanide toxicity is not commonly seen because of the marked toxicity of cyanide. Also, unlike carbon monoxide, there is no practical, timely, clinical cyanide test. When cyanide is measured, abnormal levels are considered greater than 0.1 mg/L [21]. A surrogate marker of cyanide toxicity is blood lactate level greater than 10 mmol/L that is refractory to restoration of adequate ventilation, oxygenation, and perfusion. Restoring cardiopulmonary function and tissue (especially liver) perfusion increases the sulfur transferase clearance of cyanide. The USA cyanide antidote kit relies on two pharmacologic principles. Nitrites are administered by inhalation (amyl nitrite) or intravenous infusion (sodium nitrite) to induce approximately 8% methemoglobin to facilitate transport of cyanide as cyanomethemoglobin from the mitochondrial cytochromes to hepatocytes. The substrate sulfur is then supplied by way of the intravenous administration of sodium thiosulfate for the conversion of cyanide to thiocyanate by sulfur transferase. When oxygen transport is already compromised, as in carboxyhemoglobinemia, the sodium thiosulfate can be administered alone. Hyperbaric oxygen has been tried in cyanide toxicity but has not been proven eective. An alternative therapeutic strategy is the administration of intravenous hydroxycobalamin.

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In the presence of cyanide, hydroxycobalamin is converted to cyanocobalamin (vitamin B12). Although attractive as an alternative to methemoglobinemia and thiosulfate, FDA-approved formulations of hydroxycobalamin for the treatment of pernicious anemia are far too dilute to permit the administration of the 4-g intravenous dose necessary for cyanide toxicity without excessive volume infusion. The suggested approach to suspected cyanide toxicity in the setting of smoke inhalation with metabolic acidosis (especially lactic acidosis with lactate levels [ 10 mmol/L) refractory to uid resuscitation and oxygen (after reassessment of uid status, ventilation, and associated injuries) is the intravenous administration of 12.5 g of sodium thiosulfate. Another component of the early resuscitation of the smoke inhalation victim is upper airway obstruction from tissue edema. Inhalation of heated gases greater than approximately 150 C (300 F) results in facial, oropharyngeal, and supraglottic thermal burns [13]. The immediate eects on the upper airway are edema, which is progressive over the next 1218 hours, erythema, and ulceration. Cutaneous burns magnify the injury to the airway in proportion to burn depth and body surface area aected because of uid resuscitation volume and inammatory mediators. Steam has a much greater heat-carrying capacity than air (approximately 4000 times the heat capacity) [7]. Consequently, inhalation of steam transfers heat more eciently to the upper airway structures, resulting in rapidly fatal obstructive glottic edema, thermal tracheitis and bronchial mucosal destruction, and hemorrhagic alveolar edema. Stridor, dyspnea, and increased work of breathing reect critical airway narrowing. Upper airway noise reects airow turbulence preceding obstruction. Airway noise from profuse thick mucosal secretions may be dicult to distinguish from obstruction. By the time symptoms of airway edema develop, extensive anatomic distortion is present. If tracheal intubation is not necessary initially, serial beroptic laryngoscopy and bronchoscopy can be used to assess the evolution of airway mucosal injury and track edema of the rst 18 24 hours. The need for tracheal intubation is determined by the need to maintain airway patency, protect against pulmonary aspiration, provide pulmonary toilet to decrease mucous plugging and risk for infection, and to provide positive pressure ventilation. Intubation impairs the cough mechanism and can increase the risk for nosocomial pulmonary infection. Heat, however, is a lesser contributor to airway injury from smoke inhalation than is chemical injury to the upper and lower airways. Combustion and pyrolysis gases like acetaldehyde, formaldehyde, acrolein, ammonia, hydrogen chloride, sulfur dioxide, and hydrogen uoride can cause upper or lower airway injury with airway closure and atelectasis resulting in impaired gas exchange. Alveolar edema is not a component of the early stage of smoke inhalation. Early alveolar ooding may be caused by retrograde bronchorrhea. The extent of this chemical airway injury may not be evident for 2448 hours. Early symptoms include bronchospasm and bronchorrhea. Intense

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early bronchorrhea can be mistaken for fulminant pulmonary edema. Soot in airway secretions indicates smoke exposure but is not a necessary nding to predict the occurrence or consequence of airway and pulmonary injury. There can be decreased lung compliance, an increased work of breathing, impaired clearance of secretions, and increased minute ventilation. ABGs may reect ventilation/perfusion mismatch and an increased alveolararterial oxygen gradient. Several approaches can be taken for airway maintenance and pulmonary support. Prophylactic continuous positive airway pressure (CPAP) may prevent the deterioration of oxygenation and intrapulmonary shunting. Positive end-expiratory pressure (PEEP) maintains small airway patency and adequate functional residual capacity. PEEP helps hold edematous airways open until the edema resolves. Larger diameter orotracheal tubes are preferred over smaller diameter tubes to allow for the more ecient clearance and suction of thick airway secretions and to facilitate beroptic bronchoscopy. In addition orotracheal intubation may be preferred over nasotracheal intubation in part because of tracheal tube size limitations but also because prolonged placement of nasotracheal tubes contribute to the development of sinusitis. Humidied oxygen administration assists with the clearance of secretions and may improve oxygen delivery. Head-of-bed elevation of approximately 20 30 also can assist with secretion clearance when not otherwise contraindicated. Aerosolized bronchodilators can help reverse bronchospasm in the immediate and early postinjury period, but wheezing beyond 1824 hours postinjury is more likely caused by increased airway resistance from edema. Adding PEEP rather than bronchodilators may correct an increasing alveolararterial oxygen gradient in the later postinjury period. Prophylactic antibiotics are not indicated because they select out the more resistant organisms. Antibiotic use should be based instead on serial sputum cultures. Corticosteroids given in the presence of a cutaneous burn increases mortality. Experimental interventions include antioxidants, exogenous surfactant, and high-frequency ventilation [6]. Common pitfalls in the initial management of smoke inhalation are: using initial PaO2 to predict adequacy of oxygenation, placing small diameter nasotracheal tubes, intubating without applying PEEP, and restricting uids in concomitant inhalation and burn injury. Cleaning products Certain household cleaning products possess properties that can cause acute inhalation injury when used improperly, when used without adequate ventilation, or when mixed. Hypochlorite, an oxidizer, is a component of bleaching cleaners and disinfectants. Household bleach contains hypochlorite at concentrations less than 6%. Mixing hypochlorite bleach or cleaners with other incompatible products can generate irritant gases resulting in cough and dyspnea. Mixing hypochlorite solutions with acids like

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hydrochloric acid, sulfuric acid, or phosphoric acid generates chlorine. Mixing hypochlorite solutions with ammonium hydroxide-containing cleaners generates chloramine. Both chlorine and chloramine are irritant gases. Methylene chloride is a component of paint remover, paint thinner, and other solvent mixtures. Halogenated hydrocarbon solvents such as methylene chloride and tetrachloroethylene (used as a dry cleaning solvent) can cause dose-related central nervous system depression. Some are carcinogenic or hepatotoxic. Pulmonary absorption is the principle source of systemic toxicity. The absorbed dose depends on the blood/air partition coecient, duration of exposure, atmospheric concentration, and minute ventilation. Symptoms following absorption include dizziness, headache, ataxia, progressive abdominal pain, coma, and apnea. Dysrhythmias have been attributed to myocardial catecholamine sensitization. Pulmonary injury does not follow halogenated hydrocarbon inhalation unless other pulmonary irritants such as phosgene or hydrogen chloride are also present. Complications of halogenated hydrocarbon inhalation include aspiration pneumonia, chemical hepatitis, and hypoxic encephalopathy. Methylene chloride has the additional property of being metabolized to carbon monoxide, similar to the methylene bridges of bilirubin. Carboxyhemoglobinemia may further contribute to cardiac ischemia and infarction. HbCO levels may increase gradually and not decline as quickly with oxygen administration as expected following carbon monoxide inhalation. Oxygen therapy and particularly hyperbaric oxygen have not been studied in carboxyhemoglobinemia following methylene chloride inhalation. Using the same rationale as in treating carbon monoxide poisoning from other sources, however, morbidity and mortality risk factors or HbCO [ 25% 30% are reasonable criteria for considering HBO therapy. CO production can continue despite eorts at enhancing its elimination. Clinical and cellular CO eects following methylene chloride inhalation are the same as in inhaled CO exposure. Residual central nervous system eects may reect the solvent, hypoxia or, less likely, CO. Automobile airbags Thousands of airbag deployments occur annually with only some reports of physical or metabolic injury. Airbag deployment occurs when an accelerometer detects extremely rapid deceleration, in the case of front driver side and passenger side airbags, or direct impact, as in side-impact and headprotective airbags. The electrical signal then either detonates material generating a gas or releases a compressed gas to inate the airbag. In front driver side and passenger side airbags, sodium azide and an oxidizer are detonated to generate nitrogen. Typical ignition materials are boron and potassium nitrate with nitrocellulose sometimes added as an ignition enhancer. Filters then partially cool the nitrogen and remove particulates to protect the airbag from excessive heat. Deation of the airbag is

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passive with release of the nitrogen from ventilation ports behind the airbag. Although sodium azide can cause methemoglobinemia and uncouple oxidative phosphorylation, the disks or pellets are located within a containment housing and pose virtually no hazard to the vehicle occupants. Detonation of the sodium azide, oxidizer, and accelerants generates gas, principally nitrogen. Some combustion gases and particulates are released into the passenger compartment as carbon dioxide, hydrogen, and small amounts of carbon monoxide. In studies measuring these combustion gases, passenger compartment atmospheric concentrations were well below occupational limits for short-term exposure. Respirable particulates are generated that can include low concentrations of sodium hydroxide. The principle visible particulates generated following airbag deployment are talc that is present on the surface of the airbag to protect it and ensure smooth, symmetric deployment. Occasionally occupants and rescue personnel experience eye and nose irritation and the trace of sodium hydroxide can cause chemical keratitis. Rarely these gases and particulates may exacerbate bronchospasm in victims with pre-existing reactive airway disease. The vented nitrogen has caused supercial thermal burns to the dorsum of the hand or forearm. Mild to moderate eye, orbital, or maxillofacial injuries have been reported following driver side airbag deployment and cervical spine injuries have occurred in small adults and children following front passenger side airbag deployment. Airbags deploy at a velocity of 50200 mph, with the greater velocity on the front passenger side to compensate for the greater distance the airbag must travel to reach the passenger. Inhalation injuries tend to be rare and mild.

Occupation and industry Exposure to toxic inhalations can occur in almost any occupation (Box 4). For purposes of this review, the authors discuss a select group of industries. The reader is referred to the textbook by Sullivan and Krieger for a more thorough discussion of toxic exposures that can occur in many other industries [22]. Regardless of the industry or occupation, however, any case of syncope in an industry in which gases or vapors are present needs a thorough workplace investigation by health professionals [22].

Semiconductor manufacturing Thousands of chemicals may be used to make a computer chip. In addition, some gases that are used are so toxic that they have separate gas lines with remote storage. Surprisingly, only a small group of workers directly handle the chips, but they can require signicant attention because they are exposed to many chemical hazards. Dichlorosilane, trichlorosilane, and silicon tetrachloride are gases used extensively in the semiconductor industry. All three compounds yield

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Box 4. Occupations and industries Semiconductor manufacturing Plastic manufacturing Tire and rubber manufacturing Aerospace industry Biotechnology Dental health care Mining and smelting Pulp and paper industry Hazardous-waste disposal and waste treatment Shipbuilding and ship repairing Health care industry Construction industry Fireghters Agricultural industry

hydrochloric acid and other silicon-containing compounds on exposure to water, water vapor, or moist mucous membranes [23,24]. In one urban accident, workers were exposed after a spill of silicon tetrachloride. Most developed mild eye and upper respiratory irritation. Chest radiographs and pulmonary function studies did not reveal any abnormalities attributable to the spill [25]. Arsine is extremely toxic and at high enough concentrations can be instantly lethal. Systemic eects include hypoxemia and hemolysis leading to severe anemia. Renal failure also occurs from direct nephrotoxicity or from hemoglobinuria. Although exchange transfusion is recommended for severe hemolysis, most therapy is directed at general support and possibly dialysis. Although there have been no reported deaths from arsine in the semiconductor industry, multiple deaths have occurred in other industries. Fortunately, semiconductor manufacturers are nding substitutes for arsine. Phosphine is a direct severe pulmonary irritant at high concentrations and can lead to death by way of pulmonary edema. Patients often present with nonspecic complaints of nausea, vomiting, cough, chest tightness, and headache. Diborane is another pulmonary irritant and can present with cough, dyspnea, wheezing, and chest tightness. In animals, it has been shown to cause pulmonary edema [26]. Inert gases such as argon and nitrogen are used extensively in the semiconductor industry. Although considered safe, there have been cases of syncope from asphyxiation caused by leaks in the system. Although most ED physicians are familiar with the management of hydrouoric acid injuries to the skin and eyes, inhalational exposure also

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can occur. There is some evidence to suggest a benecial use of nebulized calcium gluconate (2.5%3.0%) [27]. Both pulmonary and systemic eects can occur. Plastic manufacturing Plastics are ubiquitous in our society. During production, many plastics are heated and release various degradation products to which workers can be exposed. The composition of the mixture of gases and vapors that evolves is complex and depends on the chemical constituents and temperature. Lower temperatures (300 400 F, 150 200 C) result in incomplete combustion, thus producing larger, more complex molecules. Higher temperatures ([ 1600 F, [ 870 C) produce low molecular-weight gases after complete combustion [22]. Common polymers include polyethylene, polyvinyl chloride, polystyrene, uoropolymers, polyurethane, and phenolic polymers. Respiratory and systemic irritants are generated as breakdown products. Examples of degradation products include carbon monoxide, cyanide, ammonia, vinyl chloride, phosgene, and nitrogen dioxide. These and other combustion products may be released during a re and may present a health hazard to reghters and the public. Mining Mining, which is the process of removing mineral resources from the earth, has one of the highest mortality rates among all occupations. Although most deaths are associated with traumatic injuries [28], signicant morbidity can occur through toxic inhalations of various mine gases and dusts. Prolonged exposure to mine dusts can cause various pneumoconioses, such as silicosis, asbestosis, coal-workers pneumoconiosis, and other brotic lung diseases. These entities, however, are usually chronic in nature and usually do not present acutely to the ED. The average time before detection of silicosis is approximately 20 years [29]. Various respiratory irritants and asphyxiants can be encountered, including carbon dioxide, carbon monoxide, hydrogen sulde, methane, nitrogen oxides, and sulfur dioxide. Many of these mine gases are produced as a byproduct of the mining process itself, such as from blasting operations. Agriculture Farm workers are exposed to a variety of chemicals, fertilizers, pesticides, and fumigants. Not surprisingly, farmers have a higher incidence of respiratory disease when compared with nonfarmers [30]. Organic dust toxic syndrome and acute hypersensitivity pneumonitis occur 412 hours after exposure to concentrated organic dust or antigens, respectively. There is some evidence that systemic steroid therapy is of benet in acute hypersensitivity pneumonitis. Farmers lung, which is a hypersensitivity pneumonitis, caused

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by inhalation of material from moldy hay containing actinomyces bacteria [31], may resemble a viral syndrome clinically. Fatigue, fever, malaise, and a nonproductive cough are the major symptoms. Chest radiograph may show bilateral reticular interstitial patterns. The diagnosis often is made when the patient presents with identical symptoms after being re-exposed to moldy hay or grain. Construction Construction workers are exposed to numerous agents that are hazardous to the respiratory system. In terms of acute inhalation injuries, painters may be exposed to acetone, amyl acetate, methyl ethyl ketone, and n-butyl lactate, which are used as components or solvents in paints, varnishes, or lacquers [32]. Cement workers also may be exposed to amyl acetate and methyl ethyl ketone, both of which are components of cement. Welders can be exposed to ammonium chloride and boron triuoride when soldering. Metal fume fever, which presents as upper respiratory tract irritation, metallic taste, nausea, and fever, also can occur during welding operations [33].

Chemical and biologic weapons Unlike most occupational inhalational exposures, chemical warfare agents often need specic immediate treatment in addition to the usual supportive care. Suspicion for such agents are obviously higher in times of war, criminal acts, or acts of terrorism. Anthrax There are three principal types of anthrax: cutaneous, gastrointestinal, and inhalational. Inhalational anthrax historically results from occupational exposure to contaminated animal hides. Until the fall of 2001, the incidence of inhalational anthrax in the United States had averaged less than one case per year for the past 20 years [34]. The deadliness of anthrax when manufactured as a biologic weapon was revealed in 1979 when at least 68 people died of inhalational anthrax in Sverdlovsk following the accidental release of weapons-grade anthrax spores by a research facility. This anthrax was manufactured to a size of 15 lm, and cases in humans occurred as far away as 4 km from the site of the facility, with cases in animals occurring as far away as 50 km. Iraq admitted producing and deploying weaponized anthrax in missiles during the Gulf War [35]. In addition, in late 2001, of the 12 cases of anthrax that were reported, six were of the inhalational variety and three of these patients died. Bacillus anthracis is a large, gram-positive, aerobic, spore-forming bacillus that measures approximately 1.01.5 lm by 3.010.0 lm. Endospores that are inhaled become deposited in the alveolar spaces where they are

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engulfed by macrophages and transported to mediastinal and peribronchial lymph nodes. They then germinate and become a vegetative form that causes toxemia and massive septicemia. The median lethal inhalational dose for humans, extrapolated from primate data, has been estimated to be 2,500 to 55,000 spores [36]. Inhalational anthrax classically presents as a biphasic illness [37]. After an incubation phase of 16 days, patients develop a nonspecic illness characterized by mild fever, malaise, myalgia, nonproductive cough, and some chest or abdominal pain. Within 23 days, the second phase starts abruptly and is characterized by acute dyspnea, diaphoresis, cyanosis, and persistent fever. Half of the patients may be obtunded by complicating anthrax meningitis. After the start of the second stage, shock, hypothermia, and death can occur within 2436 hours. It may be dicult to dierentiate inhalational anthrax from other more common viral illnesses such as inuenza. Some possible clues that might lead one to consider anthrax include abnormalities on chest radiograph or helical chest computed tomography (widened mediastinum, eusions, and mediastinal adenopathy), abdominal pain concurrent with the chest symptoms, and the lack of features such as nasal congestion and rhinorrhea [34]. Anthrax is not spread from person to person. Presumptive diagnosis can be made by way of growth on sheeps bloodagar cultures or by way of direct Grams stain smear of blood, cerebrospinal uid, or skin lesion showing encapsulated, broad, gram-positive bacilli [38]. Conrmatory tests, however, must be performed at specialized laboratories. Treatment of clinically evident inhalational anthrax should start with intravenous ciprooxacin or doxycycline. Although there have been no controlled studies supporting a multiple drug approach, the CDC recommends adding another agent predicted to be eective, such as rifampin, vancomycin, imipenem, chloramphenicol, penicillin, ampicillin, clindamycin, and clarithromycin [39]. Chemoprophylaxis of asymptomatic persons is only recommended after public health or law-enforcement authorities have ascertained that there is an evident risk for exposure to a source conrmed to be anthrax. Nerve agents In 1995, terrorists left a plastic bag of Sarin on an underground train in Tokyo. They then allegedly pierced the bag with umbrella tips. The resultant vapor caused 12 deaths and 3,796 injuries [40]. Nerve gases are organophosphate compounds that are especially toxic. Common agents include Sarin, Tabun, Soman, and VX. VX (O-ethyl-S-[2(diisoproprylamine)ethyl]methylphosphoeithioate) has greater potency but lower volatility than other nerve agents [41]. They act by inhibiting acetylcholinesterase, resulting in a cholinergic crisis. At room temperature they are liquids but produce a vapor capable of penetrating respiratory epithelium, cornea, and skin. Patients thus present with respiratory and visual symptoms,

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such as dimming of vision and miosis. Diaphoresis and fasciculation of muscle groups also may occur after skin absorption. In patients with systemic poisoning, immediate treatment with atropine needs to be started and continued until the patient demonstrates signs of atropinization, specically reduction in airway secretions and bronchorrhea [41]. In addition, oximes such as pralidoxime should be given to reactivate the inhibited acetylcholinesterase at nicotinic sites. Mustard gas Sulfur mustard is a blister agent that has been used in various wars to incapacitate large numbers of soldiers. At room temperature it is an oily liquid but becomes aerosolized when dispersed by spraying or by explosive blast from a shell or bomb. The vapor can penetrate ordinary clothing. Fortunately the mortality rate is low (3% during World War I) [42]. Sulfur mustard is a vesicant alkylating agent whose most important eect is inhibition of cellular glycolysis. There is a characteristic latent period of approximately 412 hours before the onset of symptoms. Although the main eects are partial thickness burns, those with inhalational injuries develop tracheobronchitis with symptoms such as chest pressure, cough, sore throat, and hoarseness [43]. Sinusitis, sinus pain, increasing cough, and tachypnea develop as symptoms progress. Bronchospasm and bronchiolar obstruction by sloughed epithelium and secretions also can occur. In severe inhalational exposures, hemorrhagic pulmonary edema, secondary pneumonia, and respiratory failure can occur after just 2448 hours. Myelosuppression can contribute to later secondary pulmonary infections. Phosgene Phosgene is a gas that smells like moldy hay. Severe pulmonary edema can develop several hours after being inhaled because phosgene causes an increase in capillary permeability [43]. Riot control agents Riot control agents are used to cause the temporary incapacitation of individuals by way of intense irritation of mucous membranes and skin. They usually result in intense reex lacrimation, although some cause vomiting and others cause uncontrolled sneezing and coughing. Exposure can occur by way of inhalational, dermal, and oral routes. Although they have low toxicity, they are not entirely without risk. Two of the most common riot control agents include chlorobenzylidene malononitrile (CS) and oleoresin capsicum (OC). CS has essentially replaced CN (chloroacetophenone). The U.S. military considers CN obsolete, although it is still common in police agency mixtures and survives as the principal component in a liquid mixture under the trade name Mace [44].

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CS is now the most widely used tear gas in riot control situations [44]. OC, also known as pepper spray, is available over the counter for personal protection. Although most compounds act primarily on the eye, they also can aect the pulmonary system. CS is a white crystalline powder with a pungent pepper-like odor that is immediately detectable. It is used extensively in tear gas. Irritation of the respiratory tract is associated with sneezing and coughing, increased tracheobronchial secretions, and tightness of the chest [44]. The lethal eects of CS by inhalation are caused by lung damage that can lead to asphyxia and circulatory failure. Rarely respiratory tract injury may be complicated by secondary pneumonia. OC is a mixture of compounds obtained by extracting dried, ripe fruit of Cheyenne peppers. Capsaicin is the principal constituent and is the major pungent component in many peppers. It elicits respiratory-related responses such as nasal irritation, bronchoconstriction, shortness of breath, severe coughing, and sneezing. Although generally considered safe, serious eects on the respiratory system including bronchospasm, pulmonary edema, and respiratory arrest have occurred.

Summary The lungs can be an ecient means for the absorption of inhaled toxicants, resulting in airway and pulmonary injury or systemic toxicity. Although a few specic antidotes exist for inhaled toxicants, the syndrome of acute inhalation injury and clinical therapeutics are linked by common pathways of pathophysiology. Understanding the mechanisms of inhalation injury and occupation- or situation-specic toxicants can simplify the decision-making process for the out-of-hospital emergency responder and the emergency physician when confronted with a patient and the myriad of potential inhaled toxicants.

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