Abstract
Inhalation injuries heighten the morbidity and mortality associated with burn injury. Nebulized heparin and N-acetylcysteine have been proposed as adjunctive treatments for severe inhalation injury. In this study, a total of 100 inhalation injuries were identified over a 4-year period, with 40 patients suffering grade II-III inhalation injuries confirmed via fiberoptic bronchoscopy. 47.5% of patients received the inhalation protocol of nebulized heparin, N-acetylcysteine, and albuterol. Patient demographics and inhalation injury grade were similar between the groups (2 vs 2, P = .20). The utilization of the inhalation protocol did not shorten the number of ventilator days (5 vs 6, P = .76) or show survival benefit (57.9 vs 52.4%, P = .73). An inhalational protocol did not improve outcomes in burn patients suffering abbreviated injury score (AIS) grade II-III inhalation injuries at our institution. Moving forward, large, multicenter, randomized control trials are needed to determine the true efficacy of nebulized heparin and N-acetylcysteine for AIS grade II-III injuries.
Introduction
Inhalational injury significantly alters the clinical course of burn patients. To combat the deleterious effects of inhalational trauma, therapeutic strategies consisting of nebulized medications have been used. In addition to allowing for direct delivery to the bronchoalveolar tree, nebulized heparin, N-acetylcysteine, and albuterol target key aspects of inhalation injury pathophysiology.
To assess whether these benefits translate to improved patient outcomes, numerous clinical studies have evaluated the role of nebulized heparin and N-acetylcysteine in the management of inhalation injury with studies noting fewer days of mechanical ventilation, optimism has grown, and adjunctive therapies for inhalation injury have been adopted at institutions across the country, including our own.1,2 However, given the variable experimental design, inclusion criteria, and outcomes, we sought to perform a study evaluating the efficacy of nebulized therapies at our institution. We hypothesized that adjunctive heparin and N-acetylcysteine would decrease ventilator dependence and in-hospital mortality.
Methods
Following institutional review board approval, cases of suspected inhalation injury were identified from our burn center patient registry from January 2019 to August 2023. Individual cases were reviewed and only those confirmed by fiberoptic bronchoscopy were included. Abbreviated Injury Severity scores were extracted based on review of admission bronchoscopy procedure notes in the electronic medical record. 3 We thought it valuable to look at the outcomes by AIS grade as we supposed there may be certain AIS grades that do or do not benefit from an inhalation protocol. Grade 0 and grade I were excluded as the inhalation protocol is exclusively used for grade II injuries or higher at our center. We excluded grade IV as this grade is quite rare at our center.
At our institution, the protocol consists of 10,000 units of nebulized heparin, 3 mL of 20% nebulized N-acetylcysteine (600 mg), and 3 mL of .083% nebulized albuterol (2.5 mg) all given every 4 h for either 7 days or until extubation. Demographics, injury characteristics, and hospital outcomes were compared between the treatment and control groups. Wilcoxson rank-sum test and Pearson’s chi-square statistic were used for numerical and categorical variables, respectively. For all analyses, P < .05 was considered statistically significant. All statistical analyses were performed with STATA BE-18 (College Station, TX, USA).
Results
Over the study interval, 169 cases of suspected inhalation injury were identified, with 40.8% of cases either lacking bronchoscopic evaluation or with AIS grade 0. Of the remaining 100 patients, 40% suffered from grade II or grade III injury patterns and were included in the final study population. Of these, 47.5% (n = 19) were treated with the inhalation injury protocol, with the remaining 52.5% (n = 21) serving as historical controls.
Demographics and Injury Characteristics by Treatment Group.
The hemodynamic profile upon hospital presentation was similar between groups. In addition to comparable levels of carboxyhemoglobin on arrival (4.7 vs 1.9, P = .28), the AIS inhalational injury grade was similar between the treatment and control group (2 vs 2, P = .20). The net fluid balance at 24 h (2071 vs 3,715, P = .02) and 48 h (2958 vs 11,264, P < .001) post-admission was significantly higher in the historical control group. For patients receiving the inhalation protocol, the median number of doses received was 15 (5-37). We suspect that the median number of doses was low in part due to 14 patients (74%) of the experimental group being extubated or deceased with less than 7 ventilator days.
Complications and Hospital Outcomes by Treatment Group.
Discussion
Despite initial optimism regarding the use of nebulized heparin and N-acetylcysteine, questions remain regarding the utility of these adjunctive therapies in the management of inhalational injury in adults. Although the sample size in this study is small, the sample size in most published studies on the subject is small. On review of the literature, one of the largest studies examining the use of nebulized heparin and N-acetylcysteine in adults was a study by Holt, et al, which had an experimental group of 62 patients. 4 Of note, this study by Holt, et al also showed that there was no difference between treatment of nebulized heparin and N-acetylcysteine in outcomes for adult patients with inhalational burns. 4 Thus, despite the lack of difference in outcomes in our experimental and control groups, we felt it was necessary to share these results in an effort to combat publication bias. We feel that the lack of difference in outcomes in this cohort is important to note to highlight the need for better, more generalizable data to guide clinical management for patients with AIS grade II and III injuries. The authors do not suggest that based on the findings of this study that the use of inhalation protocol should be discontinued without further investigation. Instead, only wish to emphasize the need for a multi-center, randomized control trial assessing the use of nebulized heparin and N-acetylcysteine for grade II and III inhalation injuries.
Conclusion
In conclusion, the results of our study demonstrated no difference in ventilator dependence or in-hospital mortality with the utilization of nebulized heparin, NAC, and albuterol in adult burn patients suffering grade II or grade III inhalational trauma. The authors acknowledge that the small sample size questions the power of this study. However, as inhalation injury can be relatively infrequent at a single institution these results stress the need for a vigorous, multicenter effort to perform a randomized control trial with a much larger cohort size. Only then can we determine the true role for nebulized therapies in the ongoing management of burn-associated grade II and III inhalation injuries.
Footnotes
Acknowledgments
We would like to acknowledge the efforts of Samantha Baker, Sarina Zahir, John Luttrell, Haily Smith, Jodi Wojcik-Marshall, and Michelle Broers in completing this project and for their ongoing commitment to improving the care of burn patients at the University of Louisville.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
