Frequency, complications, and mortality of inhalation injury in burn patients: A systematic review and meta-analysis protocol.

INTRODUCTION: Burns are tissue traumas caused by energy transfer and occur with a variable inflammatory response. The consequences of burns represent a public health problem worldwide. Inhalation injury (II) is a severity factor when associated with burn, leading to a worse prognosis. Its treatment is complex and often involves invasive mechanical ventilation (IMV). The primary purpose of this study will be to assess the evidence regarding the frequency and mortality of II in burn patients. The secondary purposes will be to assess the evidence regarding the association between IIs and respiratory complications (pneumonia, airway obstruction, acute respiratory failure, acute respiratory distress syndrome), need for IMV and complications in other organ systems, and highlight factors associated with IIs in burn patients and prognostic factors associated with acute respiratory failure, need for IMV and mortality of II in burn patients. METHODS: This is a systematic literature review and meta-analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). PubMed/MEDLINE, Embase, LILACS/VHL, Scopus, Web of Science, and CINAHL databases will be consulted without language restrictions and publication date. Studies presenting incomplete data and patients under 19 years of age will be excluded. Data will be synthesized through continuous (mean and standard deviation) and dichotomous (relative risk) variables and the total number of participants. The means, sample sizes, standard deviations from the mean, and relative risks will be entered into the Review Manager web analysis software (The Cochrane Collaboration). DISCUSSION: Despite the extensive experience managing IIs in burn patients, they still represent an important cause of morbidity and mortality. Diagnosis and accurate measurement of its damage are complex, and therapies are essentially based on supportive measures. Considering the challenge, their impact, and their potential severity, IIs represent a promising area for research, needing further studies to understand and contribute to its better evolution. The protocol of this review is registered on the International prospective register of systematic reviews platform of the Center for Revisions and Disclosure of the University of York, United Kingdom (https://www.crd.york.ac.uk/prospero), under number RD42022343944.

Pediatric Polytrauma Fire Victim Simulation.

Introduction: Pediatric trauma has long been one of the primary contributors to pediatric mortality. There are multiple cases in the literature involving cyanide (CN) toxicity, carbon monoxide (CO) toxicity, and smoke inhalation with thermal injury, but none in combination with mechanical trauma. Methods: In this 45-minute simulation case, emergency medicine residents and fellows were asked to manage a pediatric patient with multiple life-threatening traumatic and metabolic concerns after being extracted from a van accident with a resulting fire. Providers were expected to identify and manage the patient's airway, burns, hemoperitoneum, and CO and CN toxicities. Results: Forty learners participated in this simulation, the majority of whom had little prior clinical experience managing the concepts highlighted in it. All agreed or strongly agreed that the case was relevant to their work. After participation, learner confidence in the ability to manage each of the learning objectives was high. One hundred percent of learners felt confident or very confident in managing CO toxicity and completing primary and secondary surveys, while 97% were similarly confident in identifying smoke inhalation injury, preparing for a difficult airway, and managing CN toxicity. Discussion: This case was a well-received teaching tool for the management of pediatric trauma and metabolic derangements related to fire injuries. While this specific case represents a rare clinical experience, it is within the scope of expected knowledge for emergency medicine providers and offers the opportunity to practice managing multisystem trauma.

iNOS inhibitor S-methylisothiourea alleviates smoke inhalation-induced acute lung injury by suppressing inflammation and macrophage infiltration.

OBJECTIVE: We investigated the effects of the inducible NO synthase (iNOS) inhibitor, S-methylisothiourea (SMT), in a mouse model of smoke inhalation-induced acute lung injury (ALI) and explored the underlying molecular mechanism. METHODS AND ANALYSIS: A mouse model of smoke inhalation-induced ALI was established. RNA-sequencing (seq) analysis was conducted to identify the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for functional annotation of DEGs. Moreover, an immunofluorescence assay using macrophage marker F4/80 was performed to assess macrophage infiltration. A hypoxia-induced HUVEC model was used to mimic smoke inhalation-induced injury in endothelial cells. Finally, a transwell assay was used to analyze the chemoattractive effects of endothelial cells on macrophages. RESULTS: SMT markedly alleviated the pulmonary pathological symptoms, edema, and inflammatory response in the mouse smoke inhalation-induced ALI model. RNA-seq analysis revealed that SMT may diminish lung injury by regulating the levels of genes associated with inflammatory responses, cell chemokines, and adhesion. In vivo data revealed that the protective effects of SMT against smoke inhalation-induced ALI were partly achieved by inhibiting the production of adhesion molecules and infiltration of macrophages. Furthermore, in vitro data from the hypoxia-induced HUVEC model revealed that SMT reduced macrophage chemotaxis by inhibiting the production of chemokines and adhesion molecules in endothelial cells. CONCLUSION: iNOS inhibitor SMT protects the lungs from smoke inhalation-induced ALI by reducing the production of pro-inflammatory cytokines, adhesion molecules, and chemokines in endothelial cells, thereby inhibiting inflammation and macrophage infiltration.

Pathophysiologic effects of waterpipe (shisha) smoke inhalation on liver morphology and function in mice.

AIMS: The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. MAIN METHODS: Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. KEY FINDINGS: Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinching-off of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, and IL-1ß, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1α along with alterations in the activity of mitochondrial complexes I, II, III and IV. SIGNIFICANCE: Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Evaluation of hydroxocobalamin use for the treatment of suspected cyanide toxicity secondary to smoke inhalation.

Hydroxocobalamin is used for cyanide toxicity after smoke inhalation, but diagnosis is challenging. Retrospective studies have associated hydroxocobalamin with acute kidney injury (AKI). This is a retrospective analysis of patients receiving hydroxocobalamin for suspected cyanide toxicity. The primary outcome was the proportion of patients meeting predefined appropriate use criteria defined as ≥1 of the following: serum lactate ≥8 mmol/L, systolic blood pressure (SBP) <90 mmHg, new-onset seizure, cardiac arrest, or respiratory arrest. Secondary outcomes included incidence of AKI, pneumonia, resolution of initial neurologic symptoms, and in-hospital mortality. Forty-six patients were included; 35 (76%) met the primary outcome. All met appropriate use criteria due to respiratory arrest, 15 (43%) for lactate, 14 (40%) for SBP, 12 (34%) for cardiac arrest. AKI, pneumonia, and resolution of neurologic symptoms occurred in 30%, 21%, and 49% of patients, respectively. In-hospital mortality was higher in patients meeting criteria, 49% vs. 9% (95% CI 0.16, 0.64). When appropriate use criteria were modified to exclude respiratory arrest in a post-hoc analysis, differences were maintained, suggesting respiratory arrest alone is not a critical component to determine hydroxocobalamin administration. Predefined appropriate use criteria identify severely ill smoke inhalation victims and provides hydroxocobalamin treatment guidance.

Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents.

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.

Circulatory HMGB1 is an early predictive and prognostic biomarker of ARDS and mortality in a swine model of polytrauma.

Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in polytrauma patients. Pharmacological treatments of ARDS are lacking, and ARDS patients rely on supportive care. Accurate diagnosis of ARDS is vital for early intervention and improved outcomes but is presently delayed up to days. The use of biomarkers for early identification of ARDS development is a potential solution. Inflammatory mediators high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1), and C3a have been previously proposed as potential biomarkers. For this study, we analyzed these biomarkers in animals undergoing smoke inhalation and 40% total body surface area burns, followed by intensive care for 72 h post-injury (PI) to determine their association with ARDS and mortality. We found that the levels of inflammatory mediators in serum were affected, as well as the degree of HMGB1 and Toll-like receptor 4 (TLR4) signal activation in the lung. The results showed significantly increased HMGB1 expression levels in animals that developed ARDS compared with those that did not. Receiver operating characteristic (ROC) analysis showed that HMGB1 levels at 6 h PI were significantly associated with ARDS development (AUROC=0.77) and mortality (AUROC=0.82). Logistic regression analysis revealed that levels of HMGB1 ≥24.10 ng/ml are associated with a 13-fold higher incidence of ARDS [OR:13.57 (2.76-104.3)], whereas the levels of HMGB1 ≥31.39 ng/ml are associated with a 12-fold increase in mortality [OR: 12.00 (2.36-93.47)]. In addition, we found that mesenchymal stem cell (MSC) therapeutic treatment led to a significant decrease in systemic HMGB1 elevation but failed to block SDC-1 and C3a increases. Immunohistochemistry analyses showed that smoke inhalation and burn injury induced the expression of HMGB1 and TLR4 and stimulated co-localization of HMGB1 and TLR4 in the lung. Interestingly, MSC treatment reduced the presence of HMGB1, TLR4, and the HMGB1-TLR4 co-localization. These results show that serum HMGB1 is a prognostic biomarker for predicting the incidence of ARDS and mortality in swine with smoke inhalation and burn injury. Therapeutically blocking HMGB1 signal activation might be an effective approach for attenuating ARDS development in combat casualties or civilian patients.

Effects of nebulized adipose-derived mesenchymal stem cells on acute lung injury following smoke inhalation in sheep.

INTRODUCTION: Treatment of ARDS caused by smoke inhalation is challenging with no specific therapies available. The aim of this study was to test the efficacy of nebulized adipose-derived mesenchymal stem cells (ASCs) in a well-characterized, clinically relevant ovine model of smoke inhalation injury. MATERIAL AND METHODS: Fourteen female Merino sheep were surgically instrumented 5-7 days prior to study. After induction of acute lung injury (ALI) by cooled cotton smoke insufflation into the lungs (under anesthesia and analgesia), sheep were placed on a mechanical ventilator for 48 hrs and monitored for cardiopulmonary hemodynamics in a conscious state. ASCs were isolated from ovine adipose tissue. Sheep were randomly allocated to two groups after smoke injury: 1) ASCs group (n = 6): 10 million ASCs were nebulized into the airway at 1 hr post-injury; and 2) Control group (n = 8): Nebulized with saline into the airways at 1 hr post-injury. ASCs were labeled with green fluorescent protein (GFP) to trace cells within the lung. ASCs viability was determined in bronchoalveolar lavage fluid (BALF). RESULTS: PaO2/FiO2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO2/PaO2) was significantly lower in the ASCs group at 36 hr (p = 0.003). Pulmonary shunt fraction tended to be lower in the ASCs group as compared to the control group. GFP-labelled ASCs were found on the surface of trachea epithelium 48 hrs after injury. The viability of ASCs in BALF was significantly lower than those exposed to the control vehicle solution. CONCLUSION: Nebulized ASCs moderately improved pulmonary function and delayed the onset of ARDS.

Predictors and Impact of Pneumonia on Adverse Outcomes in Inhalation Injury Patients.

Inhalation injury (II) is the third mortality prognostic factor for burn injury following age and burn size. II can lead to pulmonary complications such as pneumonia and acute respiratory distress syndrome (ARDS); all of which have been hypothesized to increase morbidity and mortality in II. Herein, we aimed to identify variables associated with the risk of developing pneumonia and to determine the impact of pneumonia on selected II outcomes. De-identified data from the Prospective Inhalation Study titled Inhalation Injury Scoring System to Predict Inhalation Injury Severity (ISIS) were used. II was confirmed by fiberoptic bronchoscopy. Demographics, injury, and hospital course information were recorded. P < .05 was considered significant. One hundred subjects were included. On univariate analysis, pneumonia was associated with burn severity, race, and receipt of colloid during the first 24 hours. Patients who developed pneumonia spent more time on a ventilator, had longer hospitalizations (LOS) and were more likely to need a tracheostomy. On multivariate analysis, total number of ventilator days was associated with pneumonia (Odd ratio (OR) = 1.122 [1.048-1.200], P = .001). Both pneumonia and receipt of colloid were predictive of increased ventilator days (OR = 2.545 [1.363-4.753], P < .001 and OR = 2.809 [1.548-5.098], P < .001, respectively). Pneumonia was not an independent predictor of LOS, ARDS, or mortality. Pneumonia remains a high-risk complication associated with two times more ventilator days in II. Future research should focus on prevention of pneumonia and the relationship between colloid fluids and pneumonia and early ventilator liberation in II patients.

Role of virtual reality distraction technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in middle-aged adults - A randomized controlled study.

BACKGROUND: Burns of the chest region constitute a common burn and develops skin contractures around the thorax region. Inhalation of toxic gases and chemical irritants during the fire leads to Acute Respiratory Distress Syndrome (ARDS). Breathing exercises are painful but are needed to help counteract contractures and increase lung capacity. These patients are usually in pain and extremely anxious about chest physiotherapy. Virtual reality distraction is one such technique that is gaining immense popularity when compared to other pain distraction techniques. However, studies examining the efficacy of the virtual reality distraction technique in this population are lacking. OBJECTIVES: To find and compare the effects of the virtual reality distraction technique as a pain alleviation tool for reducing pain during chest physiotherapy in chest burns patients with ARDS in middle-aged adults. METHODS: A randomized controlled study was conducted at the physiotherapy department between 1st Sep 2020 and 30th Dec 2022. The eligible sixty subjects were randomized into two groups: The virtual reality distraction group (n = 30) received virtual reality distraction technique and the control group (n = 30) received progressive relaxation technique before chest physiotherapy as a pain distraction technique. All the participants received chest physiotherapy as a common treatment (treatment as usual). Primary (Visual Analogue Scale - VAS) and secondary (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF), residual volume (RV), functional residual capacity (FRC), total lung capacity (TLC), RV/TLC, and diffusing capacity for carbon monoxide of the lungs (DLCO) outcome measures were measured at baseline, after four weeks, eight weeks and at six months follow up. The effects between the two groups were analyzed using the independent t-test and chi-square test. The intra-group effect was analyzed with a repeated measure ANOVA test. RESULTS: Baseline demographic characters and study variables show homogenous distribution between the groups (p > 0.05). Four weeks following two different training protocols virtual reality distraction group shows more significant changes in pain intensity, FVC, FEV1, FEV1/FVC, PEF, RV, FRC, TLC, RV/TLC, and DLCO (p = 0.001) but not in RV (p = 0.541). The similar improvements were noted in the 8 weeks and 6 months follow up. CONCLUSION: The reports of the study concluded that virtual reality distraction is an effective and useful technique in reducing pain and increasing lung capacity in chest burn patient with ARDS following smoke inhalation in community-dwelling middle-aged adults. In the virtual reality distraction group, the patients reported significantly less pain and clinically meaningful changes in pulmonary functions as compared to the control group (physiotherapy + relaxation).

Introduction: The Multidisciplinary Team Approach to Burn Care.

Since the first burn units were established following World War II, great advances in understanding and treating burn shock, smoke inhalation injury, pneumonia, and invasive burn wound infections, and in achieving early burn-wound closure, have greatly decreased postburn morbidity and mortality. These advances were the result of closely integrated multidisciplinary teams of clinicians and researchers. The team approach to burns is a model for success in the care of any challenging clinical problem.

Extracorporeal Life Support in Adult Burn Care: A Systematic Review.

We sought to review the role of extracorporeal membrane oxygenation (ECMO) for the management of burn and smoke inhalation injury in the adult patient population. Therefore, we conducted a systematic search of the literature according to specific combination of key words to ascertain the effectiveness of this support strategy. A total of 26 articles were filtered out of 269 and considered suitable for this study. The PICOS approach and PRISMA flow chart were followed for the purposes of our review. Although there is growing evidence supporting the role of ECMO as an option for burn injury in the adult patient population, this strategy should be considered if a likely successful outcome is expected.

Endothelial damage occurs early after inhalation injury as measured by increased syndecan-1 levels.

Inhalation injury is a significant cause of morbidity and mortality in the burn patient population. However, the pathogenesis of inhalation injury and its potential involvement in burn shock is not well understood. Preclinical studies have shown endothelial injury, as measured by syndecan-1 (SDC-1) levels, to be involved in the increased vascular permeability seen in shock states. Furthermore, the lung has been identified as a site of significant SDC-1 shedding. Here we aim to characterize the contribution of endotheliopathy caused by inhalation alone in a swine model. When comparing injured animals, the fold change of circulating SDC-1 levels from preinjury was significantly higher at 2, 4, and 6 hours postinjury (P = .0045, P = .0017, and P < .001, respectively). When comparing control animals, the fold change of SDC-1 from preinjury was not significant at any timepoint. When comparing injured animals versus controls, the fold change of SDC-1 injured animals was significantly greater at 2, 4, 6, and 18 hours (P = .004, P = .03, P < .001, and P = .03, respectively). Histological sections showed higher lung injury severity compared to control uninjured lungs (0.56 vs 0.38, P < .001). This novel animal model shows significant increases in SDC-1 levels that provide evidence for the connection between smoke inhalation injury and endothelial injury. Further understanding of the mechanisms underlying inhalation injury and its contribution to shock physiology may aid in development of early, more targeted therapies.

Factors associated with residential fire-related hospitalisations and deaths: A 10-year population-based study.

This study aims to identify residential fire risk factors and their health outcomes in terms of hospital admissions from burns and smoke inhalation together with related readmissions, length of hospital stay (LOS), costs of hospitalisation and mortality within 30 days of the fire incidence. Residential fire-related hospitalisations from 2005 to 2014 in New South Wales, Australia were identified using linked data. Univariate and multivariable Poisson regression analyses were performed to determine factors associated with residential fires on hospital admission and loss of life. During the study period, 1862 individuals were hospitalised due to residential fires. In terms of prolonged LOS, high hospitalisation cost or mortality, fire incidents' that damaged both contents and structures of the property; were ignited by smokers' materials and/or due to mental or physical impairment of the residents had more adverse outcomes. Individuals aged 65 and over with comorbidities and/or acquired severe injuries from the fire incident were at a higher risk of long-term hospitalisation and death. This study provides information to response agencies in communicating fire safety messages and intervention programs to target vulnerable population. In addition, it also supplies indicators on hospital usage and LOS following residential fires to health administrators.

Extracorporeal life support in pediatric burn care: A systematic review.

A systematic review of the role of extracorporeal life support (ECLS) in pediatric patients with burn and smoke inhalation injury was undertaken. A systematic search of the literature according to a specific combination of keywords to ascertain the effectiveness of this treatment strategy was conducted. A total of 14 articles out of 266 were considered suitable for the analysis in pediatric patients. The PICOS approach and PRISMA flow chart were followed for the purpose of this review. Despite the limited number of studies on the subject, ECMO in burn and smoke inhalation injury provides an additional level of support in pediatric patients leading to positive outcomes. V-V ECMO demonstrated the best overall survival of all configurations, with similar outcomes to non-burned patients. Prolonged mechanical ventilation prior to ECMO decreases survival and increases mortality by 12% with each additional day off ECMO. Good outcomes have been described for scald burns, dressing changes, and pre-ECMO cardiac arrest.

Cyanide Poisoning and Lactate in Smoke Inhalation.

House fires can lead to cyanide poisoning and an associated elevated serum lactate level. Because of delays in obtaining serum cyanide levels, clinical symptoms and serum lactate are often used to guide clinical decision making and antidote administration. However, as this case report identifies, lower levels of serum lactate may in fact correlate with higher levels of serum cyanide that could benefit from treatment with an antidote.

A Comprehensive, Retrospective Analysis of Variables for Potential Mortality Impact in Patients With Thermal or Inhalation Injury.

Age, percentage TBSA burned, and the presence of inhalation injury have been used historically in the prediction of mortality in thermally injured patients despite other factors being also associated with mortality. Recent literature has identified novel factors associated with increased length of stay (LOS) and may provide a better prediction model for mortality in burn patients. The study objective was to perform a subset analysis of a multitude of known and novel variables for potential association with mortality. Demographics and injury characteristics along with during stay variables were collected and analyzed. This study is a re-analysis of a retrospective study examining variables associated with increased LOS. Of the 629 patients screened, 396 were included in the analysis. After univariable analysis, 35 variables had significant associations with mortality, including age, house fire, acute kidney injury, heart failure, inhalation injury, and history of diabetes. After multivariable analysis, the best performing model included heart failure, acute kidney injury, admission Glasgow Coma Scale score, and revised Baux score. Quantile analysis of age revealed greater than 60 years was most predictive of mortality. The best multivariable model for patients greater than 60 years old included heart failure, vasopressor use, acute respiratory distress syndrome, and TBSA burned. Considering only variables present on admission, the best multivariable model for patients greater than 60 years old included heart failure, % TBSA burned, and inhalation injury. The addition of variables into current prediction models and databases may be warranted.