Inhalation injuries are found in 10% to 20% of burn patients and increase overall morbidity and mortality. Other factors associated with an increased mortality of these patients include the burn surface area, advanced age, and a low PaO2/FiO2 ratio.[6,7] However, a significant airway injury may exist even in the absence of cutaneous burns.
Among the culprits for lung injury secondary to inhalation are insults from thermal energy or chemical irritants. Heat or thermal injury is usually restricted to supraglottic structures, as the larger area of distribution nullifies the high degree of heat other than in cases of steam jet injury. Heat injury results in massive swelling of the upper airway, resulting in airway compromise.[9,10] Chemical injury to the lower airway occurs as a result of toxins generated from the burning of substances such as rubber, plastics, cotton, and laminated furniture. These toxins cause damage to epithelial and capillary endothelial cells of the airway, resulting in the destruction of mucociliary transport and surfactant loss. Moreover, the leakage of plasma into the airway causes intra-airway coagulation and fibrin deposition. The cellular debris, mucin, and fibrin mixture develops into airway casts, resulting in a perfusion-ventilation mismatch and an increase in dead space.
A devastating complication in burn patients is systemic toxicity from the products of combustion, including carbon monoxide and cyanide. Carbon monoxide is an odorless and colorless gas and is one of the most prevalent etiologies for early morbidity in burn-injured patients. Incremental increases in systemic concentrations of carboxyhemoglobins are associated with a spectrum of clinical presentations. Levels of 10% to 30% are associated with headaches, levels of 30% to 40% cause fatigue, nausea, and impaired cognition, and levels of 40% to 60% can result in combativeness, hallucinations, shock, and unconsciousness. Levels higher than 60% cause respiratory and cardiac depression and are fatal in more than half of patients. Hydrogen cyanide is produced during the combustion of numerous household materials. It inhibits the cytochrome oxidase system and can also act synergistically with carbon monoxide to prolong tissue hypoxia, induce refractory acidosis, and decrease cerebral oxygen consumption.[10,11]
The diagnosis of compromised airways involves primarily a high index of suspicion together with clinical evaluation and direct visualization of the airways. A detailed history pertaining to the type and duration of exposure, the quality of inhaled irritants (house fire or industrial), and unconsciousness should be obtained. Physical examination should focus on the presence of facial injuries, stridor, hoarseness, singed nasal hairs, soot in the naso-oropharynx, carbonaceous material in the sputum, or respiratory distress. Bronchoscopy can confirm an inhalational injury and show mucosal edema, erythema, erosions, necrosis, and the presence of soot or carbonaceous material in the airway.[9–11]
It is often difficult to predict the severity and extent of airway involvement. Proximal injuries observed by bronchoscopy typically exceed those of the peripheral pulmonary parenchyma, and thus, bronchoscopic grading schemes inconsistently predict the severity of the condition.[9,10,12] The measurement of bronchial wall thickness by chest computed tomography is a promising technique for evaluating the severity of the injury and determining the clinical course.
The management of smoke-induced acute lung injury is mainly supportive and depends on the presenting condition. Endotracheal intubation is warranted if airway patency is threatened. However, the security of the ETT should be closely monitored, because upper airway edema makes reintubation difficult. In addition, a larger ETT is recommended in anticipation of the increased amount of secretions and debris. An immediate tracheostomy is rarely required, but early tracheostomy requires less sedation, results in higher airway security, and has been shown to provide better patient comfort and ventilation. Prophylactic antibiotics and empirical glucocorticoids are typically not recommended.[9,10]
Various adjunct therapies have been used to decrease the formation of fibrin casts, thus limiting airway obstruction and improving oxygenation. Although therapies such as inhaled tissue plasminogen activator, danaparoid, activated protein C, antithrombin, and tissue factor pathway inhibitor have only been researched in animal models and with variable success, the combination of nebulized heparin and NAC has shown efficacy in animal and human studies.[2,8] Nebulized heparin inhibits fibrin clot formation and NAC promotes mucolysis and provides antioxidant and anti-inflammatory properties. The use of nebulized heparin and NAC gained popularity after a study by Desai et al.  showed decreased mortality, reintubation rate, and incidence of pneumonia in children with inhalation injuries treated with low doses of heparin (5000 IU) and 3 mL of a 20% solution of aerosolized NAC. The dose of nebulized heparin was 10,000 IU in our patient. A therapy consisting of alternating treatment with nebulized heparin, NAC, and albuterol in adult patients with smoke inhalation injuries decreased the mortality and improved the LIS in 1 retrospective study  and reduced the duration of mechanical ventilation in another. However, another retrospective study by Holt et al  showed no significant difference in mortality, duration of mechanical ventilation, length of stay, or incidence of pneumonia in patients treated with inhaled heparin and NAC.
Retrospective studies showing beneficial effects of nebulized heparin and NAC used either a high-dose (10,000 IU)  or low-dose (5000 IU) [1,15] nebulized heparin regimen. However, a recent prospective randomized study comparing different doses of nebulized heparin in 29 patients with smoke inhalation concluded that the higher dose of 10,000 IU decreased the LIS and duration of mechanical ventilation compared with that in patients treated with a lower dose of 5000 IU. A retrospective analysis with historical controls by Yip et al  showed the safety of nebulized heparin and NAC, which is consistent with the results of the prospective study mentioned previously.
The case we report here highlights several aspects of the challenging management of patients with inhalation injury. The most important aspects involve the early recognition of airway compromise; anticipation of a difficult airway, especially in a patient with obesity; close monitoring of the position of the ETT; and medication and ventilator management. The decision to perform a tracheotomy should be made on an individual basis. On the basis of our experience with this patient, we postulate that a regimen of nebulized heparin and NAC may be safe and beneficial in patients with mild-to-severe inhalation injuries. This regimen should be initiated as soon as possible. Lung protective techniques should be used for patients on mechanical ventilation.
Writing – original draft and literature review: Umair Ashraf, Bharat Bajantri, and Gabriella Roa-Gomez.
Writing – review & editing: Amanda Cantin, Sindhaghatta Venkatram, Gilda Diaz-Fuentes
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. Juschten J, Tuinman PR, Juffermans NP, et al. Nebulized anticoagulants in lung injury in critically ill patients: an updated systematic review of preclinical and clinical studies. Ann Transl Med 2017;5:444.
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. Miller AC, Elamin EM, Suffredini AF. Inhaled anticoagulation regimens for the treatment of smoke inhalation-associated acute lung injury: a systematic review. Crit Care Med 2014;42:413–9.
. Sheridan RL. Fire-related inhalation injury. N Engl J Med 2016;375:464–9.
. Dries DJ, Endorf FW. Inhalation injury: epidemiology, pathology, treatment strategies. Scand J Trauma Resusc Emerg Med 2013;21:31.
. Palmieri TL, Gamelli RL. Jeschke MG, Kamolz L-P, Sjöberg F, Wolf SE. Diagnosis and management of inhalation injury. Handbook of Burns: Acute Burn Care Volume 1. Vienna: Springer Vienna; 2012. 163–72.
. Spano S, Hanna S, Li Z, et al. Does bronchoscopic evaluation of inhalation injury severity predict outcome? J Burn Care Res 2016;37:1.
. Yamamura H, Morioka T, Hagawa N, et al. Computed tomographic assessment of airflow obstruction in smoke inhalation injury: relationship with the development of pneumonia and injury severity. Burns 2015;41:1428–34.
. Miller AC, Rivero A, Ziad S, et al. Influence of nebulized unfractionated heparin and N-acetylcysteine
in acute lung injury after smoke inhalation injury. J Burn Care Res 2009;30:249–56.
. McGinn KA, Weigartz K, Lintner A, et al. Nebulized heparin
and albuterol reduces duration of mechanical ventilation in patients with inhalation injury. J Pharm Pract 2017;0897190017747143s.
. Holt J, Saffle JR, Morris SE, et al. Use of inhaled heparin/N-acetylcystine in inhalation injury: does it help? J Burn Care Res 2008;29:192–5.
. Yip LY, Lim YF, Chan HN. Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital Burns Centre. Burns 2011;37:1154–60.
Keywords:Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
carbon monoxide poisoning; N-acetylcysteine; nebulized heparin; smoke inhalational injury