AUTHOR INFORMATION

Section 1 of 11

Authored by Keith A Lafferty, MD, Adjunct Assistant Professor of Emergency Medicine, Temple University; Consulting Staff, Department of Emergency Medicine, Cape Coral Hospital

Keith A Lafferty, MD, is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, and Pennsylvania Medical Society

Edited by Daniel J Dire, MD, FACEP, FAAP, FAAEM, Clinical Associate Professor, Department of Emergency Medicine, University of Texas-Houston; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; James S Walker, DO, Program Coordinator, Associate Professor, Department of Emergency Medicine, University of Oklahoma Health Sciences Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author's Email:	Keith A Lafferty, MD
Editor's Email:	Daniel J Dire, MD, FACEP, FAAP, FAAEM

eMedicine Journal, May 17 2005, VOLUME 6, Number 5

INTRODUCTION

Section 2 of 11

Background: Smoke inhalation (SI) was described as early as the first century AD, when Pliny reported the execution of prisoners by exposure to the smoke of greenwood fires.

Many victims of fire accidents have both SI and thermal injury. Inhalation injury from smoke and the noxious products of combustion in fires may account for as many as 75% of fire-related deaths in the US, many of which are preventable. Even though the excellence of care rendered at today's burn centers has greatly reduced the mortality from surface burns, the mortality from pulmonary injury has been increasing. Diagnosis of inhalation injury is not always straightforward, sensitive screening tests are lacking, and symptoms may be delayed until 24-36 hours after injury.

Pathophysiology: The 3 primary mechanisms that lead to injury in SI are thermal damage, asphyxiation, and pulmonary irritation.

Thermal damage

Thermal damage usually is limited to the oropharyngeal area. This is due to the poor conductivity of air and the high amount of dissipation that occurs in the upper airways. Animal experiments have shown that if air at 142°C is inhaled, then by the time it reaches the carina it will have cooled to 38°C. Steam, volatile gases, explosive gases, and the aspiration of hot liquids provide some exceptions, as moist air has a much greater heat-carrying capacity than dry air.

Asphyxiation

Tissue hypoxia can occur secondary to several mechanisms. Combustion utilizes oxygen, which in a closed space may be consumed, significantly decreasing the ambient concentration of oxygen to as low as 10-13%. The decrease in fraction of inspired oxygen (FIO₂) leads to hypoxia, despite adequate circulation and oxygen-carrying capacity.

Carbon monoxide (CO) causes tissue hypoxia by decreasing the oxygen-carrying capacity of the blood. Hemoglobin binds CO with an affinity more than 200 times greater than the affinity for oxygen. Even though this tissue hypoxia is the primary insult, other mechanisms attribute to its pathophysiology.

CO also causes a left shift in the oxyhemoglobin saturation dissociation curve. CO has been shown to bind to the cytochrome oxidase chain in vitro. Finally, via binding to myocardial myoglobin, CO decreases myocardial contractility.

Combustion of plastics, polyurethane, wool, silk, nylon, nitriles, rubber, and paper products can lead to the production of cyanide (CN) gas. CN also takes the form of solid crystals bound to sodium and potassium salts. It is also found abound in foods such as cassava and in apple, pear, apricot, and peach seeds. Hydrogen CN is a colorless gas with a bitter almond odor to the 40% of the population who are able to detect it. It is 20 times more toxic than CO and can cause immediate respiratory arrest.

Consider CN toxicity in all patients with SI who have CNS or cardiovascular findings. CN is a chemical asphyxiant that interferes with cellular metabolism by binding to the ferric ion on cytochrome a₃, subsequently halting cellular respiration. As a consequence of the cessation of the electron transport system, anaerobic metabolism ensues, with corresponding high lactate acidosis and decreased oxygen consumption.

Methemoglobinemia occurs in fire due to heat denaturation of hemoglobin, oxides produced in fire, and methemoglobin-forming materials such as nitrites. Occurrence of methemoglobinemia is a rarer phenomenon than CN and CO toxicity. The pathophysiologic consequences of methemoglobin formation are a decrease in the oxygen-carrying capacity of the blood and a shift of the oxyhemoglobin dissociation curve to the left, similar to carboxyhemoglobin (HbCO).

Pulmonary irritation

Irritants can cause direct tissue injury, acute bronchospasm, and activation of the body's inflammatory response system. Activated leukocytes and/or humoral mediators, such as prostanoids and leukotrienes, produce oxygen radicals and proteolytic enzymes. Supporting the importance of the inflammatory response to the mechanism of tissue destruction, some studies have shown that the administration of the cyclooxygenase inhibitor, ibuprofen, was found to reduce the lung lymph flow in animals with SI. The direct injury is a consequence of the size of the particle, its solubility in water, and its acid-base status. Ammonia produces alkaline injury, while sulfur dioxide and chlorine gas lead to acid injuries. Other chemicals act via different mechanisms; for instance, acrolein causes free radical formation and protein denaturation.

The location of injury depends on the solubility of the substance in water. High-solubility substances such as acrolein, sulfur dioxide, ammonia, and hydrogen chloride cause injury to the upper airway. Substances with intermediate solubility, such as chlorine and isocyanates, cause upper and lower respiratory tract injury. Phosgene and oxides of nitrogen have low water solubility and cause diffuse parenchymal injury.

Frequency:

• In the US: Burns and fires are the third leading cause of accidental death in all age groups. They comprise the second leading cause of death in the home for all ages and the leading cause of death in the home for children and young adults. In 1998, approximately 381,500 residential fires occurred in the US, resulting in 3,250 nonfirefighter deaths, 17,175 injuries, and nearly $4.4 billion in property loss. These figures do not include the estimated 90% of fires not reported to fire departments. More than half of all fatal residential fires started between the hours of 11 pm and 7 am.

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

• Internationally: The US has one of the highest fire fatality rates in the developed world, accounting for 2.3 deaths per 100,000 population. In fact, fire death rates in the US and Canada are twice as high as in Western Europe and Japan.

Mortality/Morbidity: Mortality is related to associated cutaneous burns.

• In patients with a burn and no associated SI or respiratory failure, the mortality rate is less than 2%. In patients with SI alone and no burn or respiratory failure, the mortality rate is 7%.

• For patients with a burn and SI, the mortality rate increases to 29%, suggesting that the burn wounds themselves put an additional stress on the compromised lung.
  

• A retrospective chart analysis has recently shown that children with CO poisoning alone compared to those with combined SI and CO toxicity had an increase in mortality rate from 0% to 22.6%.

• In rats and sheep models, cutaneous burns result in systemic complement activation with pulmonary sequestration of activated neutrophils, which in turn release toxic metabolites, further injuring the lung.

Race: One study in New Jersey reports on the demographics of fire fatalities and notes that victims who perished did not parallel the ethnic census of the time.

• Whites accounted for 53% of fatalities and comprised 49% on the census.

• African Americans accounted for 38% of fatalities and 13% of the census.

Sex: The male-to-female ratio is about 3:2.

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

A comprehensive study in Dallas looked at all house fires from 1991-1997. Many of the findings parallel those of the New Jersey study.

• Relative risk of injury was 1.8 for men, 1.4 for boys, 2.8 for blacks, and 2.6 for elderly persons.

• In addition, among the injured, the proportion of injuries that were fatal was higher in persons older than 65 years (53%) and in those younger than 10 years (67%) compared with those aged 10-64 years (30%).

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

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

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

• The cause of the house fires were arson (25.5%), electrical wiring/equipment (16.6%), heating equipment (15.8%), cooking (11.4%), smoking (5.5%), children playing with fire (4.5%), and unknown/other (20.6%).

• The rate of fire-related injury in houses in Dallas without a functioning smoke detector was 8.7 times that of homes with a functioning smoke detectors. Houses that are most likely to have fires were least likely to have functioning smoke detectors.

• As a result of this study, a program in Dallas now provides and installs smoke detectors in census tracts with the highest rates of injuries and deaths related to house fires.

CLINICAL

Section 3 of 11

History:

• Fires in closed spaces increase the risk of SI significantly.

• Particular materials in fires may contain dangerous asphyxiants.

• Polyurethane, wool, and silk increase the patient's risk of CN toxicity.

• Conditions at the scene may yield critical information, such as loss of consciousness or deaths in the same environment.

• Estimate the time that the victim may have been trapped in the fire as well as the transport time to the hospital in order to extrapolate the maximal HbCO level from the measured level.

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

Physical: Inhalation injury can range from an immediate threat to a patient's airway and respiratory status to only minor mucosal irritation. Follow a trauma management protocol.

• Primary survey

• First, assess the airway. Maintain cervical immobilization in any patient who is obtunded, has distracting injuries, has been involved in a significant mechanism of injury, has bony tenderness, or complains of neck symptoms.

• Assess breathing by respiratory rate, chest wall motion, and auscultation of air movement.

• Assess circulation by level of consciousness, pulse rate, blood pressure, capillary refill, and by symmetry and strength of pulses.

• A brief neurological evaluation should include a determination of the Glasgow Coma Scale, pupil size and reactivity, and any focal findings.

• Remove all clothes to expose traumatic injuries/burns and to prevent ongoing thermal injury from smoldering clothes. Evaluate patient's back and perform a log roll if appropriate.

• Respiratory

• Identification of impending respiratory failure is paramount.

• As burns to the upper airway and SI set off the inflammatory cascade with its associated vasodilation and capillary leak, treat any sign or symptom of airway compromise aggressively and early before inevitable rapid progression to upper airway obstruction ensues.

• Hoarseness, change in voice, complaints of throat pain, and odynophagia indicate an upper airway injury that may be severe.

• Carbonaceous sputum should be regarded as a marker of exposure.

• Tachypnea may be present.

• Wheezing, rales and rhonchi, and use of accessory respiratory muscles may be noted.

• Patients with facial burns should be carefully evaluated for SI.

• One study has shown a 59% incidence of respiratory injury with burns involving the nose, lips, brows, and neck area compared with a 22% incidence in patients with either peripheral or no facial burns.

• Patients with facial burns showed an increased mortality and more of a need for ventilatory support.

• Large cutaneous burns indicate an inability to escape flame and a risk for SI injury.

• The secondary survey continues in a complete head-to-toe examination as in any other trauma evaluation.

Causes:

• Based on a very recent study looking at the characteristics of survivors and casualties of fire fatalities, specific risk factors seem to elevate the rate of mortality.

• Age is an important predictor, with elderly persons (>64 y) and young persons ( <10 y) being the most likely to die as a result of a fire.

• Persons having a physical or cognitive disability have a higher mortality rate than matched controls, as do persons under the influence of alcohol or other drugs. For these vulnerable populations, if a nonvulnerable potential rescuer was present, the fatality rate dropped from 49% to 39%.

• The absence of a functioning smoke detector increases the risk of death in a fire by about 60%.

DIFFERENTIALS

Section 4 of 11

Anaphylaxis
Angioedema
Anxiety
Asthma
Chronic Obstructive Pulmonary Disease and Emphysema
Congestive Heart Failure and Pulmonary Edema
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Viral
Pneumothorax, Iatrogenic, Spontaneous and Pneumomediastinum
Pneumothorax, Tension and Traumatic
Pulmonary Embolism
Respiratory Distress Syndrome, Adult

WORKUP

Section 5 of 11

Lab Studies:

• Electrolyte testing can identify an anion gap acidosis.

• Elevated lactate levels may be a source of metabolic acidosis secondary to CN, methemoglobinemia, CO, or hypoxia. Lactate levels higher than 10 mmol/L are a sensitive indicator of CN levels higher than 1 mg/mg; therefore, they should be treated.

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

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

• The pulse oximeter can be misleading in the setting of CO exposure or methemoglobinemia because it uses only 2 wavelengths of light (the red and the infrared spectrum), which detect oxygenated and deoxygenated hemoglobin (Hb) only and not any other form of Hb. Cooximeters transmit 4 wavelengths of light through a blood sample and are capable of detecting methemoglobin and Hb-CO (in addition to Hb and oxyhemoglobin [HbO₂]).

• Be aware that, on routine blood gas analysis, the percent saturation of Hb is calculated from the alveolar-arterial difference in partial pressure of oxygen (PaO₂), which can give a falsely elevated saturation. The difference between saturations obtained by cooximetry and calculated figures is known as the saturation gap and is an indicator that a dyshemoglobinemia is present.

• Finally, light reflection in methemoglobinemia is similar to that in reduced Hb, and a depressed saturation may be shown on pulse oximetry, but the decrease does not accurately reflect the level of methemoglobinemia. In fact, as levels reach 30% or higher, the pulse oximeter does not go below 85%.

• A recent study has shown that acute exposure to smoke results in a transient increase of Clara cell protein (CC16). This small protein molecule is made and secreted by the Clara cells, which reside in the terminal and respiratory bronchioles. Further studies are needed, but this may be an early and sensitive indicator of acute airway injury caused by SI.

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

Imaging Studies:

• Chest radiography

• Obtain chest x-ray films (CXRs) in patients with a history of significant exposure or pulmonary symptoms.

• Most x-ray film findings are normal after SI; initial CXR is only 8% sensitive for SI.

• Findings may include atelectasis, pulmonary edema, and acute respiratory distress syndrome (ARDS).

• Insensitivity of the CXR and lack of reliability of clinical signs of inhalation injury may necessitate use of other diagnostic techniques.

• Xenon ventilation-perfusion scan

• As even bronchoscopic examination may fail to detect injury caused by inhalation of fine particulate aerosol material that may reach terminal bronchioles, consider xenon ventilation-perfusion scans in any patient suspected of having an inhalation injury even if bronchoscopic examination has been negative. This is because bronchoscopy does not evaluate the lower airways and, although 90% of particles measuring 5-10 microns in diameter impact in the upper airways, those measuring 0.5-3 microns reach the terminal bronchioles. In fact, particles this size may escape some filtration devices worn by firefighters.

• Unequal lung field radiation density and/or retention of the radiolabeled gas in the lung field for longer than 90 seconds constitutes a positive scan.

• Although the accuracy is reported as 87%, xenon ventilation-perfusion scan lacks specificity in patients with preexisting pulmonary disease.

• This test may be more appropriate for use in a burn unit or intensive care unit rather than the ED.

• Single-photon emission computed tomography

• In patients with severe CO toxicity, the most common neuropathologic finding on single-photon emission computed tomography (SPECT) in acute and delayed CO encephalopathy is ischemia and necrosis of the basal ganglion.

• This finding is highly specific for CO insult unlike focal cortical hypoperfusion, which is nonspecific.

• Besides this increase in specificity, SPECT is also more sensitive than CT in detecting CO brain injury.

Other Tests:

• Perform electrocardiogram (ECG) in any patient presenting with SI. Potential for decreased oxygen delivery from asphyxiation, dyshemoglobinemia, and cessation of electron transport system can result in myocardial ischemia.

• Pulmonary function test results are abnormal soon after inhalation injuries.

• In atelectasis, consolidation, and ARDS, vital capacity, pulmonary compliance, and functional residual capacity are reduced.

• In patients with bronchospasm, forced expiratory volume in 1 second (FEV₁), peak flow, and midexpiratory flow rates are reduced.

• Diagnostic accuracy is 91%.

Procedures:

• Bronchoscopy can be diagnostic as well as therapeutic, particularly when lobar atelectasis is present.

• This procedure examines the airways from the oropharynx to the lobar bronchi.

• Although it may be performed in the ED, the burn unit may be a more appropriate setting, especially in patients who are intubated.

• Erythema, charring, deposition of soot, edema, and/or mucosal ulceration may be present.

• Impending airway obstruction may be inferred and intubation may be facilitated by this technique.

• Diagnostic accuracy is reported to be 86%.

• A recent study found a 96% correlation between bronchoscopic findings and the triad of closed-space smoke exposure, HbCO levels of 10% or greater, and carbonaceous sputum.

• Another study reports that serial bronchoscopy was twice as sensitive for diagnosing inhalation injury as clinical findings alone.

TREATMENT

Section 6 of 11

Prehospital Care:

• Deliver high-flow oxygen by mask.

• If respiratory failure is present, the patient should have assisted ventilation and/or endotracheal intubation.

• Perform cricothyrotomy if airway obstruction is present or impending and an airway cannot be secured orally.

• Secure IV access, but do not delay transport of patient to the hospital in any way.

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

Emergency Department Care:

• Presently, no specific treatment exists to ameliorate the tissue damage and reduce the vulnerability to infection induced by SI. Once the CO toxicity, CN toxicity, and methemoglobinemia have been corrected, subsequent treatment is predominantly supportive.

• High-flow humidified oxygen is critical to reverse or prevent hypoxia and assist displacement of CO from Hb.

• The most urgent concern in patients relates to the patency of the upper airway and adequacy of ventilation.
  • About 50% of patients with an inhalation injury require endotracheal intubation. The proportion of patients requiring this procedure is higher for those who also have a burn injury: 62% with a burn versus 12% without a thermal injury.

  • It is of vital importance that the magnitude of the swelling in the areas of the face and mandible be closely scrutinized when making decisions about the need for an artificial airway. Threshold for intubation should be lower than in other patients due to rapid development of airway edema. Delays create the possibility that critical airway compromise may be unrecognized or develop quickly, making endotracheal intubation technically impossible.

• If systemic paralysis is necessary, succinylcholine can be used safely in the immediate postburn phase and up to several days out. Inflate tube cuff to minimal levels, even allowing a small leak, in order to prevent iatrogenic tracheal damage in patients with an already compromised tracheal mucosa.

• Studies have shown that positive pressure ventilation with positive end-expiratory pressure (PEEP) initiated immediately after the inhalation injury significantly increases short-term survival and is associated with decreased tracheobronchial cast formation. The mechanism by which PEEP works may be from "splinting" the alveoli and preventing bronchial cast formation and protein-rich fluid from entrapping the airway.

• Other recent studies have shown that high-frequency ventilation also decreases mortality and the incidence of pneumonia and barotrauma. This modality generates pulsatile flow at up to 600 cycles per minute, which entrains the humidified gas by effect on molecular diffusion. Clearance of airway secretions may improve, and continued patency of the lower airways may be allowed. While not as commonly used in the ED, many burn centers consider this standard therapy.

• Administer IV fluids to assure euvolia and adequate perfusion. Use formulas (eg, Parkland) to calculate fluid resuscitation if severe burns are present.

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

  • A recent study has shown that the half-life in the clinical setting, as opposed to an experimental laboratory setting, is approximately 75 minutes breathing 100% oxygen via a nonrebreather face mask or endotracheal tube. This same study also points out that the half-life, while very much dependent upon the PaO₂, is not dependent upon gender, age, history of loss of consciousness, concurrent tobacco smoking, degree of initial metabolic acidosis or initial CO level.

  • CO is not only responsible for most prehospital deaths in SI, it is the leading cause of injury/death due to poisons in general worldwide.

• The main reason for use of HBO therapy is to prevent delayed neurological sequelae.
  • Literature suggests that hypoxic encephalopathy secondary to CO poisoning results from a reperfusion injury in which the products of lipid peroxidation and free radical formation contribute to morbidity and mortality. In addition, improvement in mitochondrial oxidative metabolism, impairment of adherence of neutrophils to cerebral vasculature (decreases inflammation), and preservation of adenosine triphosphate activity was shown with HBO therapy. This partially explains why HbCO levels are poor indicators of the severity of intoxication and why patients with significant toxicity may have low levels. In fact, at the time of the initial HBO treatment, patients enrolled in most studies have normal or near-normal COHb levels.

  • In a recent landmark study, Weaver has recently shown in a prospective, double blind manner that in patients with symptomatic acute CO poisoning, 3 HBO treatments, in comparison to normobaric oxygen therapy, decrease the incidence of cognitive sequelae by 46% at 6 weeks. Furthermore, a benefit continued to be seen at 12-month follow-up. Essentially, for every 6 patients treated with HBO, one case of delayed neurologic sequelae could be avoided. The study had to be stopped before its completion because of the evidence.

  • Neurologic abnormalities and a history of loss of consciousness are the primary clinical features used to define severe CO toxicity. HBO use is indicated in any of these patients as well as those with a base excess lower than -2 mmol/L, a CO level greater than 25% (or >15% in pregnancy), signs of cerebellar dysfunction, cardiovascular dysfunction, pulmonary edema, and in the extremes of age.

• Management of CN toxicity involves creation of an alternate binding site for CN to compete with cytochrome oxidase and also to provide substrate necessary to convert CN to a nontoxic metabolite.
  • The CN antidote kit contains amyl and sodium nitrite to create a methemoglobin level of 3% and 20-30%, respectively, which, in turn, has a higher affinity for CN than for cytochrome a₃. Also included is sodium thiosulfate, which provides substrate for the enzyme rhodanese, which combines thiosulfate and CN to form a nontoxic compound, thiocyanate, which is excreted renally.

  • Induction of methemoglobinemia is theoretically dangerous in the setting of HbCO, and the clinician should consider withholding the nitrite portion of the kit. In one prospective study in which the CN antidote kit was administered to patients requiring intubation, all but one patient, who died of anoxic encephalopathy on the sixth day, had good recovery. This paper, although a small series, may indicate the ability to give the CN antidote kit in its entirely without obvious adverse sequelae. Authors also noted that methemoglobin levels peaked at 50 minutes, by which time the CO level should already be falling in patients treated with HBO. Sodium thiosulfate remains the definitive treatment. A definite statement on the use of nitrites in SI currently cannot be made.

• Methemoglobinemia in SI is relatively rare and rarely requires treatment with methylene blue. This antidote is reduced by the nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase enzyme and in return reduces methemoglobin to normal hemoglobin. Indications for treatment are a change in mental status, acidosis, ECG changes, and ischemic chest pain. Levels lower than 30% may not require treatment, depending on the patient's cardiorespiratory reserve.

• A small subset of patients manifests bronchospasm and may benefit from the use of bronchodilators, although this is not well documented. This is especially true of patients with underlying COPD or asthma.

• Although the pathophysiology of SI involves irritants setting off the inflammatory response, no benefit has been shown with corticosteroid therapy. In fact, many studies report an increased rate of pulmonary infection.

• Inhalation injuries clearly predispose the airways to infection after several days because of cellular injury, reduction of mucociliary clearance, and poor macrophage function. Despite this, prophylaxis with parenteral antibiotics has not shown any benefit. Acute bacterial colonization and invasion peaks at 2-3 days after SI injury. Consider cultures and possible treatment at this time.

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

• Since oxidants are released during the inflammatory cascade and are potentiated via the release of free iron stores, studies have shown that aerosolized deferoxamine, an effective iron chelator, may prevent the injury process. More studies are needed before this modality is used. Also, oxidant injury eventually leads to cast formation of cellular debris in the airways, thus contributing to pulmonary failure. A recent pediatric study has shown that aerosolized heparin/N-acetylcysteine decreases the incidence of atelectasis, reintubation rates, and overall mortality.

Consultations: Obtain trauma surgery consultation in patients with significant exposure.

MEDICATION

Section 7 of 11

Oxygen is the primary medication used in the treatment of SI. Bronchodilators may be of benefit in patients displaying signs of bronchospasm. After this, specific antidotes of methylene blue for methemoglobinemia and thiosulfate/sodium nitrite for CN poisoning are indicated. Certain patients with CO toxicity may require hyperbaric therapy.

Drug Category: Bronchodilators -- These agents act to decrease the muscle tone in the small and large pulmonary airways.

Drug Name	Albuterol (Proventil, Ventolin) -- Beta-agonist useful in treatment of bronchospasm that is refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors and has little effect on cardiac muscle contractility. Airway resistance is decreased, and ventilation is improved.
Adult Dose	0.5 mL (2.5 mg) of the 0.5% inhalation solution diluted in 1-2.5 mL of normal saline q4-6h; may use higher frequency for intensive care patients 2.5-5 mg diluted in 2-5 cc sterile saline or water via nebulizer
Pediatric Dose	<5 years: 0.25-0.5 mL (1.25-2.5 mg) of the 0.5% inhalation solution diluted in 1-2.5 mL of normal saline q4-6h in equally divided doses via nebulizer >5 years: Administer via nebulizer as in adults
Contraindications	Documented hypersensitivity
Interactions	Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders

Drug Category: Antidotes -- Converts a portion of circulating hemoglobin to methemoglobin.

Drug Name	Amyl nitrite (Isoamyl nitrite) -- In the presence of nitrites, hemoglobin is converted to methemoglobin, which has a higher binding affinity for CN than does the cytochrome oxidase complex. As a result, electron transport and cellular respiration are able to continue, producing a methemoglobin level of 5%. This medication is given until an IV line is established and sodium nitrite can be administered.
Adult Dose	Break the ampuls in a gauze sponge for patient to inhale 30 s of each min; if patient is intubated, hold gauze between the oxygen source and the endotracheal tube
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe anemia, closed-angle glaucoma, head trauma, postural hypertension and hypotension, cerebral hemorrhage
Interactions	Coadministration with alcohol may cause severe hypotension and cardiovascular collapse; with calcium channel blockers, may produce symptomatic orthostatic hypotension; aspirin may increase nitrate serum concentrations
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in coronary artery disease and low systolic blood pressure

Drug Name	Sodium nitrite -- In the presence of nitrites, hemoglobin is converted to methemoglobin that has a higher binding affinity for CN than does the cytochrome oxidase complex. As a result, the electron transport and cellular respiration are able to continue, producing a methemoglobin level of 20-30%
Adult Dose	10 mL of a 3% solution IV over 2-4 min
Pediatric Dose	0.3 mL/kg of a 3% solution IV over 2-4 min
Contraindications	Documented hypersensitivity; severe anemia, closed-angle glaucoma, head trauma, postural hypertension and hypotension, cerebral hemorrhage
Interactions	Severe hypotension and cardiovascular collapse may occur when administered concurrently with alcohol; aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in coronary artery disease, and low systolic blood pressure

Drug Category: Sulfur compounds -- Provide a sulfur moiety to rhodanese, allowing the production of thiocyanate, which subsequently is excreted by the kidneys.

Drug Name	Sodium thiosulfate -- After formation of methemoglobin and production of cyanomethemoglobin, thiosulfate acts as a sulfur donor to the endogenous enzyme rhodanese. This enzyme removes CN from the cyanomethemoglobin complex and forms thiocyanate, which is excreted renally. CN also is removed directly from cytochrome oxidase and is converted to thiocyanate in the presence of thiosulfate via the enzyme rhodanese.
Adult Dose	12.5 g IV over 10 min, either alone or in combination with other CN antidotes
Pediatric Dose	7 g/m2; not to exceed 12.5 g/dose
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Rapid IV infusion may cause transient hypotension and ECG changes

Drug Category: Reducing agents -- Used in order to convert methemoglobin to oxyhemoglobin.

Drug Name	Methylene blue -- Tetramethyl thionine chloride moiety that is reduced (it is an electron acceptor) in the presence of NADPH and methemoglobin reductase to leukomethylene blue. Leukomethylene blue then becomes available to reduce methemoglobin to oxyhemoglobin. May be ineffective in treating patients with G-6-PD deficiency because, in the hexose monophosphate shunt, G-6-PD is essential for the generation of NADPH. Without NADPH, methylene blue cannot act as a reducing agent in the transformation of methemoglobin to oxyhemoglobin.
Adult Dose	1-2 mg/kg IV over 5 min; peak effect occurs in 30 min; may be repeated at this time prn
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; renal insufficiency
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Can cause profound anemia in patients with G-6-PD deficiency; do not inject into CNS

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• Patients with SI should be monitored for 4-6 hours in the ED. While there is no definite criteria for admission, the following patients should be strongly considered for hospitalization:

• History of closed-space exposure for longer than 10 minutes

• Carbonaceous sputum production

• Arterial PO₂ less than 60 mm Hg

• Metabolic acidosis

• HbCO levels above 15%

• Arteriovenous oxygen difference (on 100% oxygen) greater than 100 mm Hg

• Bronchospasm

• Odynophagia

• Central facial burns

Further Outpatient Care:

• Although the literature is lacking regarding definite discharge criteria, patients whom otherwise do not meet admission criteria may be sent home after an observation period of 6 hours providing the following criteria are met:

• Normal vital signs

• Normal physical examination

• Short smoke exposure

Transfer:

• Treat patients with isolated SI appropriately in any modern intensive care unit. However, transport patients with significant cutaneous burns (who otherwise meet criteria for transfer to a burn center) when stable.

• Modern burn care has decreased the mortality rate in patients with thermal burns. A large retrospective chart review from 1972-1996 has shown that increasing burn size, older age, inhalation injury, and female sex increase the risk of death, while operative intervention and upper limb burns decrease the risk of death.

Deterrence/Prevention:

• A recent study shows that smoke detectors reduce the risk of death by about 60% in all subgroups of people.

• This is in contrast to past data that suggest that these early warning devices may not be effective in populations that have difficulty responding to an alarm in a timely manner, such as children, older adults, persons with disabilities, or those impaired by alcohol or other drugs.

• These new data clearly exemplify the point that all homes should have a working smoke detector in every room.

• Although smoke detectors have been widely adopted by the public, and 93% of US households have one in place, it is estimated that 30-45% of these are not operational, usually due to nonreplacement or removal of batteries.

• DiGuiseppi et al have shown that just merely giving out free smoke alarms in a deprived, multiethnic, urban community did not reduce injuries related to fire. This was because few alarms had been installed or properly maintained.

Complications:

• While the mortality rate for isolated SI injury is lower than 10%, the addition of a cutaneous burn could almost quadruple this mortality rate.

• Subglottic stenosis

• Bronchiectasis

• Pulmonary edema (4-9%)

• Pneumonia (3-23%)

• Atelectasis (1-5%)

• After the 1987 California forest fire disaster, local EDs saw a dramatic rise in asthmatic patients.

• Another study of firefighters showed certain subgroups to have an exaggerated decline in postexposure FEV₁ that was not predicted by age, smoking history, intensity of exposure, or the use of self-contained breathing apparatus.

• Some of these patients, who had no family history of reactive airway disease, went on to need long-term beta-agonist therapy.

• The many case series in the literature clarify that reactive airway disease, in a small sample of patients with SI, is a real potential sequela.

Patient Education:

• For excellent patient education resources, visit eMedicine's Lung and Airway Center, Procedures Center, and Poisoning Center. Also, see eMedicine's patient education articles Smoke Inhalation, Bronchoscopy, and Carbon Monoxide Poisoning.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• As SI can lead to serious morbidity and mortality, make every effort to diagnose and treat this condition. Avoid the following potential errors in treating SI:

• Beware that patients may appear asymptomatic on arrival but may develop significant signs and symptoms as long as 36 hours after exposure, especially in fires that produce small particles with low water solubility.

• Avoid relying on the HbCO level obtained in the ED. This level does not correlate with tissue hypoxia or long-term neurological sequelae. Ideally, an HbCO level at the scene would be most valuable.

• Be aware of pertinent historical risk factors in treating patients with potential SI injury. These include closed-space fires, carbonaceous sputum, elevated CO levels, and central facial burns.

• While the mortality rate of isolated SI injury is lower than 10%, the coexistence of a burn injury may almost quadruple this mortality rate.

• A significant amount of patients may present with a paucity of upper airway signs or symptoms but still may have serious subglottic injury. The threshold for performing diagnostic bronchoscopy should be low.

TEST QUESTIONS

Section 10 of 11

CME Question 1: A firefighter is brought to the ED after fighting a house fire. Which of the following is the least likely to be a risk factor for significant smoke inhalation exposure?

A: Elevated serum carbon monoxide level
B: Central facial burns
C: Peripheral facial burns
D: Closed-space exposure
E: Carbonaceous sputum production

The correct answer is C: Peripheral facial burns are not associated with significant smoke inhalation injury, while the other choices are. A recent study found a 96% correlation between significant smoke inhalation and the triad of closed-space smoke exposure, carboxyhemoglobin levels of 10% or higher, and carbonaceous sputum.

CME Question 2: Which of the following does not cause a dyshemoglobinemia or an oxygen saturation gap?

A: Methemoglobin
B: Cyanide
C: Carbon monoxide
D: Sulfhemoglobin
E: None of the above

The correct answer is B: Cyanide binds to cytochrome oxidase, not to hemoglobin. The other choices all bind to hemoglobin, and in doing so, displace oxygen. This effect does not distort the partial pressure of oxygen (PO₂). Therefore, the blood gas, which gives an extrapolated oxygen saturation value based on the PO₂, is reported as normal. However, the true oxygen saturation, directly measured with a cooximeter, is low. The difference between the two is the oxygen saturation gap and is proportionate to the toxin. Methemoglobinemia is less common in smoke inhalation injury than carbon monoxide or cyanide toxicity.

Pearl Question 1 (T/F): The most common cause of mortality in fire victims is burns.

The correct answer is False: The most common cause of mortality in fire victims is carbon monoxide toxicity from smoke inhalation.

Pearl Question 2 (T/F): Ventilatory support has been proven beneficial in victims of significant smoke inhalation.

The correct answer is True: Recent studies have shown that high-frequency ventilation decreases mortality and the incidence of pneumonia and barotrauma. This modality generates pulsatile flow at up to 600 cycles per minute, which entrains the humidified gas by effect on molecular diffusion. There may be better clearance of airway secretions, and continued patency of the lower airways may be allowed. While not as commonly used in the ED, many burn centers consider this standard therapy.

Pearl Question 3 (T/F): Of the many possible diagnostic modalities in patients with smoke inhalation injury, pulmonary function tests are the most sensitive for the detection of smoke inhalation.

The correct answer is True: Pulmonary function tests are reported to be 91% sensitive for the detection of smoke inhalation, though the specificity is low.

Pearl Question 4 (T/F): The initial chest x-ray for the detection of smoke inhalation is very sensitive.

The correct answer is False: The initial chest x-ray is only about 8% sensitive for smoke inhalation.

BIBLIOGRAPHY

Section 11 of 11

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