Medscape General Medicine 1(3), 1999. © 1999 Medscape

Abstract

Introduction

Injury in smoke inhalation should be viewed as the result of three separate insults: exposure to heat (thermal injury), exposure to asphyxiants (asphyxiation), and pulmonary irritation (toxin-induced lung injury).

Carbon Monoxide Toxicity

Carbon monoxide causes a reversible displacement of oxygen on the hemoglobin molecule, forming carboxyhemoglobin (COHb). The reduced oxygen affinity of COHb results in impaired oxygen delivery to tissues. Additionally, utilization of oxygen by the peripheral tissues is compromised when COHb interacts with mitochondrial cytochrome oxidase aa₃ complex.^[8] Furthermore, myocardial oxygen utilization is markedly reduced by the binding of CO to cardiac myoglobin.^[9] The symptoms of CO toxicity depend on the duration of exposure and resultant serum levels. The spectrum of symptoms therefore varies from headache and confusion to coma and death (see Table I). Below the lethal level of 60%, CO level does not predict which patients will develop respiratory failure or die.^[10,11]

Carbon monoxide is eliminated from the blood by the law of mass action, as oxygen is exchanged for CO on the hemoglobin molecule. Therefore, the therapy for CO toxicity is simply oxygen (support of ventilation). Breathing room air, a patient will eliminate CO in 250 minutes.^[12] When placed on 100% oxygen, the half-life of CO is reduced to 40 to 60 minutes.^[13] The half-life is reduced to 30 minutes when the patient is placed in a 100% oxygen environment pressurized to 3 atmospheres. Hyperbaric oxygen (HBO) has a limited therapeutic role in the patient with CO toxicity combined with either an inhalation injury or a thermal injury. The obvious drawback in such cases is the inability to have full access to a patient with cardiopulmonary instability. Hyperbaric oxygen therapy is more useful in those patients who have CO toxicity without concomitant smoke inhalation or thermal injury. No prospective randomized trials have been performed to establish the role of HBO in preventing long-term neurologic sequelae.

Cyanide Toxicity

Cyanide gas (HCN) is the other common cellular asphyxiant that can cause early death following smoke inhalation. Hydrogen cyanide is produced from the burning of plastics or polyurethane. Cyanide gas inhibits the final step of oxidative phosphorylation by binding the cytochrome aa₃ complex and halting mitochondrial aerobic metabolism. This results in lactic acidosis and cellular asphyxia, despite adequate arterial blood oxygen content. Symptoms of CN toxicity include altered levels of consciousness, dizziness, headache, tachycardia, and tachypnea. The lethal serum level of CN is 1.0mg/L to 3.0mg/L, as determined by the Conway diffusion assay.^[14] This assay, however, is not available at most institutions; therefore, CN levels are not available to guide therapy. Cyanide toxicity should be suspected when the patient presents with CO levels in excess of 15%, severe anion gap metabolic acidosis, and a high venous oxygen saturation.Cyanide gas and CO may act synergistically to cause death, even when either toxin, taken individually, is present at sublethal levels.^[15] Cyanide is detoxified by hepatic rhodanase which requires sulfate as a substrate. The resulting thiocyanate is inactive and subsequently excreted in the urine. This reaction is slow and limited by the availability of sulfate.

A commercially available cyanide antidote kit is used to treat cases of suspected cyanide toxicity(This kit consists of sodium thiosulfate, amyl nitrite, and a sodium nitrite solution). The goal of the CN antidote test is to induce the formation of methemoglobin with the administration of nitrites (amyl nitrite and sodium nitrite). The resultant methemoglobin molecule then competes with the mitochondrial cytochrome oxidase for the hydrogen cyanide. Methemoglobin binds with hydrogen cyanide to form cyanomethemoglobin. Cyanomethemoglobin slowly dissociates, releasing free cyanide, but the release of free cyanide occurs at a rate such that the hepatic enzyme, rhodanase, does not become "overwhelmed," with free cyanide accumulating. The antidote kit provides additional rhodanase. Thiosulfate is administered to provide the required sulfate and enhance the rate of the detoxifying reaction. Caution needs to be exercised to prevent the methemoglobin levels from exceeding 40%.^[16]

With methemoglobinemia, the iron moiety of the hemoglobin molecule is in the ferric state and unable to bind oxygen. This may further depress the arterial oxygen content for patients in whom the normal hemoglobin may be bound to CO. Methemoglobin levels must be monitored closely by obtaining a blood gas for cooximetry.

Mechanism

Chemicals suspended in the smoke will react with components of the cell membrane. These interactions produce oxygen radicals which disrupt the cell membranes, damaging pulmonary endothelium and resulting in increased microvascular permeability.^[18-20] Furthermore, compounds such as ammonia, hydrogen chloride, and sulfur dioxide adhere to mucous membranes and form corrosive acids and alkalies. The result is death of mucosal cells, ulceration, and further edema.^[21]

Pathogenesis

The first pathologic event to occur in toxin-induced lung injury is direct mucosal injury with associated loss of ciliary activity. This results in an impaired ability to clear mucus and particulate matter. Airway closure with atelectasis or air-trapping are responsible for impaired gas exchange in the early phase of the injury. Ineffective mucociliary transport combined with cellular debris produces a profound bronchorrhea. Alveolar flooding occurs due to the retrograde flow of bronchorrhea. Edema to the alveolus (ie, pulmonary edema) is not responsible for the impaired gas exchange.

Subsequently, there is a marked increase in pulmonary blood flow and vascular permeability. These two derangements result in submucosal edema and narrowing of the airway.^[22] The third phase of the injury is tissue destruction and necrosis, which results in the sloughing of mucosa of both the large and small airways as well as a marked increase in mucus production. Bronchial edema combines with the bronchorrhea to cause partial or complete obstruction of the conducting airways, with further atelectasis, air-trapping, and ventilation-perfusion mismatching.

Any patient with a history of smoke exposure in a closed space should be considered to have an inhalation injury until proven otherwise. Burns to the face and the finding of soot in the sputum certainly are evidence that the patient was exposed to smoke, but their absence should not be used to exclude the diagnosis. Maintaining a high index of suspicion is important because symptoms and signs are frequently absent on initial evaluation. The true extent of this injury may not manifest for 24 to 72 hours following exposure. During this "calm before the storm," early symptoms may appear to be resolving; however, the peak period of mucosal sloughing has not yet occurred. The magnitude of the injury should not be underestimated based on this initial presentation.

Toxin-induced irritation of the bronchial mucosa results in an intense bronchorrhea which may falsely appear to the uninitiated as fulminant pulmonary edema. Investigators have attempted to reduce the oxidative damage caused by inhaled toxins. Withholding resuscitation fluids does not protect the lung or lessen the respiratory injury. On the contrary, underresuscitation aggravates pulmonary dysfunction by reducing pulmonary blood flow and increasing neutrophil-induced oxidative damage.^[23]

Clinical Course and Work-up

Bronchospasm is usually the first symptom to appear, and in most cases presents 18 to 24 hours following the inhalation event. This bronchospasm responds well to bronchodilator therapy. The use of racemic epinephrine will reduce bronchospasm as well as abrogate the edema of the trachea and bronchial mucosa. Bronchospasm and mucosal edema decrease pulmonary compliance and increase work of breathing. Desai and colleagues^[24] have shown that children treated with aerosolized heparin and acetylcysteine have fewer ventilator days, reduced rates of pneumonia, and a lower mortality rate. A declining or low PaO₂/FiO₂ ratio (ie, <300) should prompt early intubation and bronchoscopy. Early chest radiographs almost always underestimate the extent of the injury because the initial injury is to the airway and not the lung parenchyma, and several days are required to develop radiographically-detectable changes.^[25] When pathologic changes do appear on chest radiographs, it is important to recognize that the changes are due to retrograde alveolar flooding and not hydrostatic pulmonary edema.

Pulmonary function tests are not uniformly helpful in the diagnosis of smoke inhalation injury. Pulmonary function tests require the cooperation of the patient and are effort-dependent. Patients are frequently unable to comply due to concomitant thermal or traumatic injuries, the influence of narcotics, or alcohol. When dealing with a large number of patients from a mass-casualty incident, pulmonary function tests allow for the rapid evaluation and triaging of ambulatory patients. By comparing the measured FEV₁/FVCratio to the predicted, the clinician can gauge the severity of injury.

¹³³Xenon ventilation perfusion scanning involves the identification of retained radiolabeled gas in segmental areas of airway obstruction secondary to inhalation. This study is not often utilized due to the necessity of transporting a potentially critically ill patient out of the intensive care unit, the duration of the test, and the logistics of mobilizing technicians at odd hours.

Issues in Management

A decision must be made early as to whether the patient requires endotracheal intubation. Because the most urgent concern in patients relates to the patency of the upper airway and adequacy of ventilation, whenever there is doubt, it is safer to intubate.^[26,27] Generally, the largest endotracheal tube possible should be used because these patients will develop copious amounts of thick secretions, and a larger-diameter tube will allow more effective suctioning and bronchoscopy. A small-diameter tube is more likely to plug, and reintubation may become technically impossible once facial and mucosal edema develop. Following intubation, visualization of the upper and lower airways with fiberoptic bronchoscopy can certainly secure the diagnosis and determine the extent of the inhalation injury. However, because initial evaluation often poorly correlates with the subsequent clinical course and long-term sequelae, bronchoscopy findings cannot be used to prognosticate.

Endotracheal intubation should not be delayed until stridor or upper airway sounds develop: these are late findings, and intubation at this point may be difficult or even impossible.^[28,27] If upper airway edema results in a critical airway obstruction, a single attempt at orotracheal or nasotracheal intubation should be made. If this attempt fails, further efforts using muscle relaxants should not be made, because they will likely cause total loss of the airway, inability to ventilate by face mask, and loss of valuable time for management. Cricothyroidotomy should then be performed. The conversion from orotracheal or nasotracheal intubation to a tracheostomy in the first several days may more readily allow for removal of secretions and greatly facilitate the pulmonary management of these patients. The tracheostomy should not be placed through burned tissue. If the anterior neck is burned, the neck should be excised and grafted, and tracheostomy can proceed several days later through the newly grafted skin.^[29]

Procedures

The early application of positive end-expiratory pressure (PEEP) has been reported to decrease mortality after smoke inhalation.^[26] The initiation of PEEP should occur early in the course and perhaps even prior to the development of abnormal gas exchange because the prevention of airway closure is much simpler than recruitment following collapse.

High-frequency percussive ventilation (HFPV) (VDR-4, Percussionare Corporation, Sandpoint, ID) reduces morbidity and mortality in inhalation injuries.^[30,31] This unique method allows uniform ventilation of a very heterogeneous lung parenchyma by utilizing a series of low-volume, rapid-sequenced, partially cumulative breaths. The subtidal volumes are delivered in a stacked fashion until a pre-set pressure limit is reached, at which time the delivery is interrupted. After interruption, the airway pressure returns to baseline, and this allows for a convective exchange to occur similar to conventional ventilation. The exhaled convective breath is well-mixed in comparison to conventional volume or pressure-limited breaths. Because airway pressure is incrementally increased, there is equilibration between preferential and nonpreferential airways. By avoiding preferential airway ventilation, the risk of barotrauma is greatly reduced.

Use of HFPV in inhalation injuries is associated with a significantly reduced rate of pneumonia and a marked reduction in mortality.^[30] This method of ventilation should be used prophylactically in patients who have sustained an inhalation injury.^[32] An additional advantage of HFPV in burn patients is its ability to mobilize secretions and cellular debris, thereby reducing plugging, air trapping, and atelectasis.^[33,34] The HFPV also achieves similar oxygenation at lower FiO₂ than conventional modes of ventilation.^[35,36] In patients with adult respiratory distress syndrome (ARDS), HFPV has been shown to reduce the pulmonary shunt fraction (Qs/Qt) using lower peak inspiratory pressure, PEEP, and mean airway pressure.^[37,38]

Despite advances in critical care and ventilatory management, the care of the patient with inhalation injury remains mostly supportive. Appropriate fluid resuscitation combined with aggressive pulmonary care and early burn excision may reduce the mortality rate from the accepted 30% to 70%.

Editorial Comment

The assessment of airway and pulmonary damage due to smoke inhalation can be very difficult. In cases where burns are also more generalized, or even localized to just the face and/or upper body, the fact that the respiratory system is involved is often missed or not even considered.

Inhalation or injury to the respiratory tract comes in three broad forms, as detailed by Guy and Peck in this issue. The clinical history is vital and all efforts should be made to speak to witnesses at the scene of the incident; any knowledge of the contents of an involved building, ie, factory, warehouse, domestic dwelling, should be communicated. Information on chemicals stored at the scene for example, could be invaluable in guiding management.

Thermal injury is difficult to assess. Even if there are obvious facial burns, it is hard to determine how far the respiratory tree has been penetrated by high-temperature air. Generally, fires with a high flame content mainly cause facial burning and the associated dry heat will not penetrate far down the respiratory tract. Air cools rapidly once inhaled, even from excessive temperatures. However, all patients with obvious thermal burns to the face should be admitted and observed for potential inhalation injury. Dense smoke, particularly in a confined space, is likely to cause high mortality among those who are exposed. However, most subjects exposed to smoke do not inhale it. Often the rescuers inhale more than the victims. If the smoke is mixed with burning gases from substances such as varnish, paints, or polyurethane, then the risk of cyanide gas and other toxic products of combustion increases. Other hazardous products include acrolein, carbon monoxide, hydrogen chloride, hydrogen cyanide, oxides of nitrogen, sulfur dioxide, and particulates. Again, it is the firefighter or rescue worker who may experience a greater, or at least a chronic, exposure to these hazardous substances.

In this article by Guy and Peck, the acute care of smoke inhalation is thoroughly reviewed -- although as they emphasize, the decision regarding when to intubate is difficult. Spirometry or peak expiratory flow rate may be useful in assessing upper airway patency, but if the lips and mouth are burned, such pulmonary function testing may be too painful to adequately perform. Our practice is to bronchoscope early using an intubating fiberscope to assess the vocal cords for the presence of soot (ie, evidence of inhalation) and edema. Edematous cords are an indication for early intubation.

What of the long-term consequences of smoke inhalation to the lung?

Although acute reductions in forced expiratory volume in one second (FEV₁) have been recorded in firefighters immediately after a fire,^[1,2] evidence for long-term damage is less well-documented. This may be because those firefighters who develop respiratory problems retire or transfer to other duties. No evidence of long-term functional impairment was found in 27 patients convalescing from burns,^[3] whereas other studies have reported airflow obstruction immediately after smoke inhalation,^[4,5] with general resolution during the subsequent periods of observation.^[5] There are case reports of persistent structural and functional abnormalities of the respiratory tract after thermal injuries and smoke inhalation, including stenosis of the trachea^[6] and bronchial tree,^[7] bronchiectasis,^[6,7] obliterative bronchiolitis,^[7] and small airways disease unresponsive to corticosteroids.^[8]

Results of a 2-year follow-up of lung function changes in individuals who survived the London Underground fire at Kings Cross Station in 1987 were reported. This was a high-intensity fire that involved inhalation of smoke and cyanide and was associated with a high mortality. Fourteen survivors were studied, and at 6 months, 9 had persistent symptoms of hoarseness, cough, and shortness of breath.^[9] Evidence of small airways obstruction was found in 11 of the survivors and persisted in 7 at 2 years. An 8-year follow-up of transfer factor in Seattle firefighters showed a trend for single-breath diffusing capacity of carbon monoxide to decline faster than predicted, although the sensitivity of the methodology might be a factor.^[10]

Nevertheless, the risk of long-term damage to the airways should be evaluated, especially in victims with obvious abnormal lung function at the time of the inhalation accident.

Stephen G. Spiro, MD, FRCP
Department of Medicine
University College London
St. Pancras Hospital
London, UK

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