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.

[Advances on the application of physical airway clearance techniques in the treatment of inhalation injury].

Although the treatment of patients with burns combined with inhalation injury has achieved great success, from the perspective of epidemiology, inhalation injury is still the most common cause of death in mass burns. Such patients often suffered burns of large total body surface area, which is difficult to treat, with airway management as one of the core links. Physical airway clearance technique (ACT) acts on a patient's respiratory system by physical means, to discharge secretions and foreign bodies in the airway, achieve airway clearance, and improve gas exchange. In addition, the technique can prevent or alleviate many complications, thereby improving the clinical outcome of patients with inhalation injury. This article reviews the application of physical ACT in the field of inhalation injury, and to provide decision-making basis for clinical medical staff to choose physical ACT corresponding to the patient's condition.

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.

Insignificant Difference in Early Post-injury Gene Expression Between Patients with Burns Only and Those with Inhalation Injury: A Bioinformatics Analysis.

Airway obstruction is fatal but common among burn patients in the early period after inhalation injury, during which most tracheotomies are performed within 48 h post-injury. Inflammation is common in laryngoscopy; however, the related gene expression has rarely been studied. In this study, we obtained the data of healthy control and patient samples collected within 8-48 hours post-injury from the Gene Expression Omnibus database and classified them into 10 inhalation-injury patients, 6 burn-only, and 10 healthy controls. Differential gene expression was identified between the patient groups; however, principal component analysis and cluster analysis indicated a similarity between groups. Furthermore, enrichment analysis, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses showed no significant differences in immune regulation and cell adjustment between the patient groups; but differences were shown when comparing either patient group to the healthy control group, including prominent regulation in inflammatory cells, infection, and cell adjustment. Thus, the gene expression in inhalation injury and burn-only patients does not significantly differ in the early period after injury, especially in inflammation, indicating the absence of specific diagnostic markers or anti-inflammatory treatment in inhalation injury patients, with the potential to identify more subtle differences. Further research is warranted.

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.

Protection of laryngeal mucosa and function in laryngeal burns by heat absorption of perilaryngeal tissue.

OBJECTIVE: The laryngeal tissue carries most of the heat during inhalation injury. This study aims to explore the heat transfer process and the severity of injury inside laryngeal tissue by horizontally studying the temperature rise process at various anatomical layers of the larynx and observing the thermal damage in various parts of the upper respiratory tract. METHODS: The 12 healthy adult beagles were randomly divided into four groups, and inhaled room temperature air (control group), dry hot air of 80 °C (group I), 160 °C (group II), and 320 °C (group III) for 20 min, respectively. The temperature changes of the glottic mucosal surface, the inner surface of the thyroid cartilage, the external surface of the thyroid cartilage, and subcutaneous tissue were measured every minute. All animals were immediately sacrificed after injury, and pathological changes in various parts of laryngeal tissue were observed and evaluated under a microscope. RESULTS: After inhaling hot air of 80 °C, 160 °C and 320 °C, the increase of laryngeal temperature in each group was ΔT = 3.57 ± 0.25 °C, 7.83 ± 0.15 °C, 11.93 ± 0.21 °C. The tissue temperature was approximately uniformly distributed, and the difference was not statistically significant. The average laryngeal temperature-time curve showed that the laryngeal tissue temperature in group I and group II showed a trend of "first decrease and then increase", except that the temperature of group III directly increased with time. The prominent pathological changes after thermal burns mainly concluded necrosis of epithelial cells, loss of the mucosal layer, atrophy of submucosal glands, vasodilatation, erythrocytes exudation, and degeneration of chondrocytes. Mild degeneration of cartilage and muscle layers was also observed in mild thermal injury. Pathological scores indicated that the pathological severity of laryngeal burns increased significantly with the increase of temperature, and all layers of laryngeal tissue were seriously damaged by 320 °C hot air. CONCLUSIONS: The high efficiency of tissue heat conduction enabled the larynx to quickly transfer heat to the laryngeal periphery, and the heat-bearing capacity of perilaryngeal tissue has a certain degree of protective effect on laryngeal mucosa and function in mild to moderate inhalation injury. The laryngeal temperature distribution was in accordance with the pathological severity, and the pathological changes of laryngeal burns provided a theoretical basis for the early clinical manifestations and treatment of inhalation injury.

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.

Inhalation Injury: Which Providers Can Assess the Need for Intubation?

Previous studies have suggested that many burn patients undergo unnecessary intubation due to concern for inhalation injury. We hypothesized that burn surgeons would intubate burn patients at a lower rate than non-burn acute care surgeons (ACSs). We performed a retrospective cohort study of all patients admitted to an American Burn Association-verified burn center who presented emergently following burn injury from June 2015 to December 2021. Patients excluded include polytrauma patients, isolated friction burns, and patients intubated prior to hospital arrival. Our primary outcome was intubation rates between burn and non-burn ACSs. 388 patients met inclusion criteria. 240 (62%) patients were evaluated by a burn provider and 148 (38%) were evaluated by a non-burn provider; the groups were well-matched. In total, 73 (19%) of patients underwent intubation. There was no difference in the rate of emergent intubation, diagnosis of inhalation injury on bronchoscopy, time to extubation, or incidence of extubation within 48 hours between burn and non-burn ACSs. We found no difference between burn and non-burn ACSs in the airway evaluation and management of burn patients. Surgical providers with acute care surgery backgrounds and Advanced Trauma Life Support training are well-equipped for initial airway management in burn patients. Further studies should seek to compare other types of provider groups to identify opportunities for intervention and education in preventing unnecessary intubations.

Machine learning approach for predicting inhalation injury in patients with burns.

BACKGROUND: The coronavirus disease pandemic has had a tangible impact on bronchoscopy for burn inpatients due to isolation and triage measures. We utilised the machine-learning approach to identify risk factors for predicting mild and severe inhalation injury and whether patients with burns experienced inhalation injury. We also examined the ability of two dichotomous models to predict clinical outcomes including mortality, pneumonia, and duration of hospitalisation. METHODS: A retrospective 14-year single-centre dataset of 341 intubated patients with burns with suspected inhalation injury was established. The medical data on day one of admission and bronchoscopy-diagnosed inhalation injury grade were compiled using a gradient boosting-based machine-learning algorithm to create two prediction models: model 1, mild vs. severe inhalation injury; and model 2, no inhalation injury vs. inhalation injury. RESULTS: The area under the curve (AUC) for model 1 was 0·883, indicating excellent discrimination. The AUC for model 2 was 0·862, indicating acceptable discrimination. In model 1, the incidence of pneumonia (P < 0·001) and mortality rate (P < 0·001), but not duration of hospitalisation (P = 0·1052), were significantly higher in patients with severe inhalation injury. In model 2, the incidence of pneumonia (P < 0·001), mortality (P < 0·001), and duration of hospitalisation (P = 0·021) were significantly higher in patients with inhalation injury. CONCLUSIONS: We developed the first machine-learning tool for differentiating between mild and severe inhalation injury, and the absence/presence of inhalation injury in patients with burns, which is helpful when bronchoscopy is not available immediately. The dichotomous classification predicted by both models was associated with the clinical outcomes.

Delayed Tracheoesophageal Fistula and Refractory Respiratory Failure Caused by Inhalation Burns and Emergency Venovenous ECMO to Facilitate Its Management: A Case Report.

Acquired tracheoesophageal fistulae are uncommon in burn patients but can occur as a complication of inhalation injury. We report a case of a 30-yr-old male patient presenting after suffering from inhalation and 25% total body surface area burns. On postburns day 14, he developed a massive tracheoesophageal fistula causing refractory acute respiratory failure. Veno-venous extracorporeal membrane (VV ECMO) oxygenation was initiated without systemic anticoagulation via bi-femoral cannulation under transthoracic echocardiography guidance. He underwent successful 5-hr apnoeic ventilation-assisted surgical repair of the fistula via a right posterolateral thoracotomy. ECMO was discontinued after 36 hr, and he was discharged to the ward after 33 d in the intensive care unit. Inhalation burn injury can cause a delayed life-threatening tracheoesophageal fistula. Surgical repair can be successfully performed for this condition. VV- ECMO can be used to facilitate prolonged apnoeic surgery and to manage refractory respiratory failure due to this condition.