Inhalation injury can present as a wide spectrum of symptoms, varying in severity from mild cough to rapid airway compromise causing death. The key to effective treatment is anticipation and early recognition of the myriad of consequences of inhalation exposure. Many of the treatment modalities are supportive, but there are specific therapies for certain complications such as carbon monoxide poisoning.[26]Summerhill EM, Hoyle GW, Jordt SE, et al; ATS Terrorism and Inhalational Disasters Section of the Environmental, Occupational, and Population Health Assembly. An official American Thoracic Society Workshop report: chemical inhalational disasters. Biology of lung injury, development of novel therapeutics, and medical preparedness. Ann Am Thorac Soc. 2017 Jun;14(6):1060-72.
http://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201704-297WS
http://www.ncbi.nlm.nih.gov/pubmed/28418689?tool=bestpractice.com
For less severely ill patients, therapy may only involve brief observation and counselling about recurrent exposure avoidance. Others, however, may require supportive critical care services such as intubation, mechanical ventilation, hyperbaric oxygen therapy, intravenous resuscitation, and haemodynamic support.
Upper airway management
Careful evaluation of the patient's ability to maintain a patent airway should be performed as part of the initial assessment and therapy. An airway should be immediately secured with an endotracheal tube (ETT) if the patient has diminished mental status with poor airway reflexes or history and examination is suggestive of injury with threatened patency. Patients with inhalation injury often have difficult airways to secure, and preparations for a surgical airway should be made in anticipation of ETT placement failure. Care should be taken to secure the ETT to prevent unintended extubation. No evidence exists to support early tracheostomy in burn patients once they have been intubated.[27]ISBI Practice Guidelines Committee, Steering Subcommittee, Advisory Subcommittee. ISBI practice guidelines for burn care. Burns. 2016 Aug;42(5):953-1021.
https://www.sciencedirect.com/science/article/pii/S0305417916301449?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/27542292?tool=bestpractice.com
If the initial assessment does not lead to intubation, reassessment should occur frequently.
Patients presenting with only inhalation exposure or mild clinical disease should be closely observed and monitored during treatment for evolution or worsening of symptoms, which may be delayed for up to 1 day.[1]Rabinowitz, PM, Siegel MD. Acute inhalational injury. Clin Chest Med. 2002 Dec;23(4):707-15.
http://www.ncbi.nlm.nih.gov/pubmed/12512160?tool=bestpractice.com
Cellular asphyxiants
Carbon monoxide (CO) poisoning
Should be treated to prevent the associated persistent and delayed neurological sequelae.[28]Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med. 2009 Mar 19;360(12):1217-25.
http://www.ncbi.nlm.nih.gov/pubmed/19297574?tool=bestpractice.com
All patients should receive high-flow supplemental oxygen to decrease hypoxia and facilitate removal of CO. Current guidelines recommend using high flow oxyen therapy for at least 6 hours, or longer if symptoms persist.[27]ISBI Practice Guidelines Committee, Steering Subcommittee, Advisory Subcommittee. ISBI practice guidelines for burn care. Burns. 2016 Aug;42(5):953-1021.
https://www.sciencedirect.com/science/article/pii/S0305417916301449?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/27542292?tool=bestpractice.com
The use of hyperbaric oxygen has been considered controversial by some.[28]Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med. 2009 Mar 19;360(12):1217-25.
http://www.ncbi.nlm.nih.gov/pubmed/19297574?tool=bestpractice.com
[29]Buckley NA, Juurlink DN, Isbister G, et al. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD002041.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002041.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/21491385?tool=bestpractice.com
While some have recommended its use for pregnant patients or patients with severe disease (coma, seizure, cardiovascular disease, acidosis), the data specific to certain subgroups are unclear.[28]Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med. 2009 Mar 19;360(12):1217-25.
http://www.ncbi.nlm.nih.gov/pubmed/19297574?tool=bestpractice.com
One clinical trial found evidence to suggest that hyperbaric oxygen reduces cognitive sequelae both acutely and at 12 months.[30]Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002 Oct 3;347(14):1057-67.
http://www.nejm.org/doi/full/10.1056/NEJMoa013121#t=article
http://www.ncbi.nlm.nih.gov/pubmed/12362006?tool=bestpractice.com
One retrospective study found that (after adjusting for age, sex, and underlying comorbidities) patients with carbon monoxide poisoning who were treated with hyperbaric oxygen therapy had a lower mortality rate compared with patients who did not receive hyperbaric oxygen.[31]Huang CC, Ho CH, Chen YC, et al. Hyperbaric oxygen therapy is associated with lower short- and long-term mortality in patients with carbon monoxide poisoning. Chest. 2017 Apr 17 [Epub ahead of print].
http://journal.chestnet.org/article/S0012-3692(17)30723-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/28427969?tool=bestpractice.com
The reduction in mortality risk was greatest among patients aged younger than 20 years and those with acute respiratory failure.[31]Huang CC, Ho CH, Chen YC, et al. Hyperbaric oxygen therapy is associated with lower short- and long-term mortality in patients with carbon monoxide poisoning. Chest. 2017 Apr 17 [Epub ahead of print].
http://journal.chestnet.org/article/S0012-3692(17)30723-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/28427969?tool=bestpractice.com
Because of this data, a 2023 Delphi panel deemed hyperbaric oxygen therapy to be of uncertain benefit in patients for whom a hyperbaric chamber is available onsite.[32]Milton-Jones H, Soussi S, Davies R, et al. An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury. Crit Care. 2023 Nov 27;27(1):459.
https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04718-w
http://www.ncbi.nlm.nih.gov/pubmed/38012797?tool=bestpractice.com
This panel recommended against hyperbaric oxygen if it required transfer away from a burn centre.
Cyanide toxicity
While cyanide toxicity is often cited, its true role in inhalation injury is unclear and its treatment is controversial.[21]Barillo DJ. Diagnosis and treatment of cyanide toxicity. J Burn Care Res. 2009 Jan-Feb;30(1):148-52.
http://www.ncbi.nlm.nih.gov/pubmed/19060738?tool=bestpractice.com
If cyanide toxicity is suspected in a patient with inhalation injury, the recommended therapy is the direct cyanide binder hydroxocobalamin with or without sodium thiosulfate.[27]ISBI Practice Guidelines Committee, Steering Subcommittee, Advisory Subcommittee. ISBI practice guidelines for burn care. Burns. 2016 Aug;42(5):953-1021.
https://www.sciencedirect.com/science/article/pii/S0305417916301449?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/27542292?tool=bestpractice.com
[32]Milton-Jones H, Soussi S, Davies R, et al. An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury. Crit Care. 2023 Nov 27;27(1):459.
https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04718-w
http://www.ncbi.nlm.nih.gov/pubmed/38012797?tool=bestpractice.com
[33]Anseeuw K, Delvau N, Burillo-Putze G, et al. Cyanide poisoning by fire smoke inhalation: a European expert consensus. Eur J Emerg Med. 2013 Feb;20(1):2-9.
https://journals.lww.com/euro-emergencymed/fulltext/2013/02000/cyanide_poisoning_by_fire_smoke_inhalation__a.2.aspx
http://www.ncbi.nlm.nih.gov/pubmed/22828651?tool=bestpractice.com
Recommendations regarding the use of sodium thiosulfate as an adjunctive treatment for cyanide toxicity vary across guidelines. A 2013 European expert consensus recommends hydroxocobalamin as the first-line treatment, with sodium thiosulfate as a second-line option.[33]Anseeuw K, Delvau N, Burillo-Putze G, et al. Cyanide poisoning by fire smoke inhalation: a European expert consensus. Eur J Emerg Med. 2013 Feb;20(1):2-9.
https://journals.lww.com/euro-emergencymed/fulltext/2013/02000/cyanide_poisoning_by_fire_smoke_inhalation__a.2.aspx
http://www.ncbi.nlm.nih.gov/pubmed/22828651?tool=bestpractice.com
In contrast, a 2023 international Delphi panel deemed sodium thiosulfate therapy to be of uncertain benefit.[32]Milton-Jones H, Soussi S, Davies R, et al. An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury. Crit Care. 2023 Nov 27;27(1):459.
https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04718-w
http://www.ncbi.nlm.nih.gov/pubmed/38012797?tool=bestpractice.com
The 2016 International Society for Burn Injury practice guidelines for burn care recommend hydroxocobalamin but do not address sodium thiosulfate.[27]ISBI Practice Guidelines Committee, Steering Subcommittee, Advisory Subcommittee. ISBI practice guidelines for burn care. Burns. 2016 Aug;42(5):953-1021.
https://www.sciencedirect.com/science/article/pii/S0305417916301449?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/27542292?tool=bestpractice.com
Blood cyanide levels of higher than 2.6 to 3.0 mg/L are considered fatal.[34]Yeoh MJ, Braitberg G. Carbon monoxide and cyanide poisoning in fire related deaths in Victoria, Australia. J Toxicol Clin Toxicol. 2004;42(6):855-63.
http://www.ncbi.nlm.nih.gov/pubmed/15533025?tool=bestpractice.com
The commonly available 'antidote kit' of sodium nitrite and sodium thiosulfate (known as Nithiodote® in the US) should be used very cautiously because nitrates induce methaemoglobin (which binds systemic cyanide). Methaemoglobin, in the presence of significant carboxyhaemoglobin, contributes to critically lowering oxygen delivering capacity. Nitrates are, therefore, contraindicated in the presence of significant carboxyhaemoglobinaemia.
Lower airway injury
Airway cellular injury leading to oedema, sloughing, and bronchoconstriction causes obstruction in patients with inhalation injury. This lower airway injury is treated largely with supportive care. Patients should be clinically monitored for evidence of respiratory muscle fatigue and ventilatory failure. While high levels of inhaled oxygen (hyperoxaemia) may be used therapeutically for carbon monoxide poisoning, once excluded or resolved hyperoxaemia is no longer recommended, and the patient may be supported with a standard fraction of inspired oxygen sufficient to maintain adequate haemoglobin saturation.[35]Kallet RH, Branson RD. Should oxygen therapy be tightly regulated to minimize hyperoxia in critically ill patients? Respir Care. 2016 Jun;61(6):801-17.
http://rc.rcjournal.com/content/61/6/801.full
http://www.ncbi.nlm.nih.gov/pubmed/27235315?tool=bestpractice.com
Inhaled beta-agonist bronchodilators (e.g., nebulised salbutamol [albuterol]) should be used as needed for bronchoconstriction, and evidence suggests that they may also benefit the patient via anti-inflammatory properties.[36]Palmieri TL. Use of beta-agonists in inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):156-9.
http://www.ncbi.nlm.nih.gov/pubmed/19060734?tool=bestpractice.com
The role of other therapies, such as heparin, tocopherols, and corticosteroids, is under active investigation.[37]Enkhbaatar P, Herndon DN, Traber DL. Use of nebulized heparin in the treatment of smoke inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):159-62.
http://www.ncbi.nlm.nih.gov/pubmed/19180699?tool=bestpractice.com
[38]Traber DL, Traber MG, Enkhbaatar P, et al. Tocopherol as treatment for lung injury associated with burn and smoke inhalation. J Burn Care Res. 2009 Jan-Feb;30(1):164-5.
http://www.ncbi.nlm.nih.gov/pubmed/19060745?tool=bestpractice.com
[39]Greenhalgh DG. Steroids in the treatment of smoke inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):165-9.
http://www.ncbi.nlm.nih.gov/pubmed/19060744?tool=bestpractice.com
Airway clearance should be facilitated by humidification of delivered oxygen and aggressive pulmonary toilet.
Parenchymal lung disease
Patients with lung parenchymal injury (which may progress to acute respiratory distress syndrome [ARDS]) should be treated supportively with oxygen and positive pressure ventilation as the clinical situation warrants. It is reasonable to utilise volume-cycled ventilation with low tidal volume ventilation (4-6 cc/kg of ideal body weight) and avoidance of high plateau pressures (>30 cm H₂O), which has proved beneficial in non-selected ARDS.[40]The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8.
http://www.nejm.org/doi/full/10.1056/NEJM200005043421801#t=article
http://www.ncbi.nlm.nih.gov/pubmed/10793162?tool=bestpractice.com
Alternatively, pressure-cycled ventilation may be used to achieve similar physiological goals. High-frequency oscillatory ventilation was associated with accelerated improvements in pulmonary function in one small randomised controlled trial.[41]Allam NM, Badawy MM. Does high-frequency chest wall oscillation have an impact on improving pulmonary function in patients with smoke inhalation injury? J Burn Care Res. 2021 Mar 4;42(2):300-4.
http://www.ncbi.nlm.nih.gov/pubmed/32860696?tool=bestpractice.com
While several therapeutic modalities (e.g., vitamin C, heparin, beta-agonists, corticosteroids, antithrombin-III) are under investigation, none have been proved effective in large clinical trials.[37]Enkhbaatar P, Herndon DN, Traber DL. Use of nebulized heparin in the treatment of smoke inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):159-62.
http://www.ncbi.nlm.nih.gov/pubmed/19180699?tool=bestpractice.com
[38]Traber DL, Traber MG, Enkhbaatar P, et al. Tocopherol as treatment for lung injury associated with burn and smoke inhalation. J Burn Care Res. 2009 Jan-Feb;30(1):164-5.
http://www.ncbi.nlm.nih.gov/pubmed/19060745?tool=bestpractice.com
[39]Greenhalgh DG. Steroids in the treatment of smoke inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):165-9.
http://www.ncbi.nlm.nih.gov/pubmed/19060744?tool=bestpractice.com
[42]Wolf SE. Vitamin C and smoke inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):184-6.
http://www.ncbi.nlm.nih.gov/pubmed/19060764?tool=bestpractice.com
[43]Latenser, BA. Use of antithrombin III in inhalation injury. J Burn Care Res. 2009 Jan-Feb;30(1):186-8.
http://www.ncbi.nlm.nih.gov/pubmed/19060754?tool=bestpractice.com
[44]Asmussen S, Maybauer DM, Fraser JF, et al. Extracorporeal membrane oxygenation in burn and smoke inhalation injury. Burns. 2013 May;39(3):429-35.
http://www.ncbi.nlm.nih.gov/pubmed/23062623?tool=bestpractice.com
Other considerations
Comorbid conditions or injuries should be evaluated and treated in patients with inhalation injury. Therapies for individual conditions are often at odds (such as aggressive volume infusion for cutaneous burns and the conservative fluid approach for ARDS), and clinicians must carefully develop a treatment strategy unique to the individual patient. Pain and anxiety are common in these patients and should be treated. Analgesia is often indicated to relieve the discomfort of an endotracheal tube, tissue oedema, coincident trauma, and cutaneous burns. Opioid drugs have the additional benefit of relieving dyspnoea.[45]ISBI Practice Guidelines Committee, Advisory Subcommittee, Steering Subcommittee. ISBI practice guidelines for burn care, part 2. Burns. 2018 Nov;44(7):1617-706.
https://www.doi.org/10.1016/j.burns.2018.09.012
http://www.ncbi.nlm.nih.gov/pubmed/30343831?tool=bestpractice.com
Patients not ventilated through an endotracheal tube should be monitored closely, as respiratory suppression can occur. Continuous intravenous morphine or fentanyl provide excellent analgesia for invasive mechanical ventilation. Sedation and anxiolysis are also indicated for patients receiving invasive mechanical ventilation. Propofol and dexmedetomidine are commonly used agents. In March 2022, the European Medicines Agency (EMA) issued a warning about an increased risk of mortality with dexmedetomidine treatment in critically ill patients aged ≤65 years compared with alternative sedatives. This recommendation follows results from an open-label, randomised trial, comparing dexmedetomidine with usual care (propofol, midazolam, or other sedatives) in critically ill adult patients undergoing mechanical ventilation. The study showed no difference in overall 90-day mortality between treatments. However, dexmedetomidine was associated with an increased risk of mortality in patients ≤65 years old, compared with alternative sedatives.[46]Shehabi Y, Howe BD, Bellomo R, et al. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019 Jun 27;380(26):2506-17.
https://www.doi.org/10.1056/NEJMoa1904710
http://www.ncbi.nlm.nih.gov/pubmed/31112380?tool=bestpractice.com
The EMA advises clinicians to weigh these findings against the expected clinical benefit of dexmedetomidine in this age group.[47]European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 7-10 March 2022. March 2022 [internet publication].
https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-7-10-march-2022
Critically ill patients with burns and inhalation injury are at high risk for complications; preventative measures, including hand hygiene, head-of-bed elevation, catheter care, and deep vein thrombosis prophylaxis, are essential.
Similar to other cases of severe refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) may be considered in inhalation injury patients whose condition is refractory to maximal measures. One 2023 systematic review and meta-analysis of 15 retrospective studies including 318 patients on ECMO in the setting of inhalation injury found a pooled percentage of successful decannulation of 65%, but with an ECMO complication prevalence of 67%.[48]Heng X, Cai P, Yuan Z, et al. Efficacy and safety of extracorporeal membrane oxygenation for burn patients: a comprehensive systematic review and meta-analysis. Burns Trauma. 2023;11:tkac056.
https://academic.oup.com/burnstrauma/article/doi/10.1093/burnst/tkac056/7066360
http://www.ncbi.nlm.nih.gov/pubmed/36873286?tool=bestpractice.com
Bleeding and infection were the most common complications.