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Background: Infections are the most frequent complication and cause of mortality in burn patients. We describe the epidemiology and outcomes of infections among deployed U.S. military personnel with burns., Methods: Military personnel who sustained a burn injury in Iraq or Afghanistan (2009-2014) and were admitted to the Burn Center at U.S. Army Institute of Surgical Research at Brooke Army Medical Center were included in the analysis., Results: The study population included 144 patients who were primarily young (median 24 years) males (99 %) with combat-related burns (62 %) sustained via a blast (57 %), resulting in a median total body surface area burned (TBSA) of 6 % (IQR 3-14 %). Twenty-six (18 %) patients developed infections, with pneumonia being the predominant initial infection (= 16), followed by skin and soft-tissue infections (SSTI, = 6), bloodstream infections (BSI, = 3), and intra-abdominal infections (IAI, = 1). Initial infections were diagnosed at a median of 4 days (IQR 3-5) post-injury for pneumonia, 7 days (IQR 4-12) for SSTIs, 7 days (IQR 6-7) for BSI, and 17 days for IAI. Patients with infections were more severely injured with greater TBSA (median 31 % vs 5 %), more inhalation injury (38 % vs 12 %), and longer time to definitive surgical management (median of 34 days vs 9) compared to those who did not develop infections (p < 0.001). Among patients with inhalation injury, a higher proportion developed pneumonia (42 %) compared to those without inhalation injury (5 %; p < 0.001). Five patients developed an invasive fungal infection. Gram-negative bacilli were most frequently recovered, with 32 % of Gram-negative isolates being multidrug-resistant. Four patients died, of whom all had ≥ 4 infections., Conclusions: Military personnel with burn injuries who developed infections were more severely injured with greater TBSA and inhalation injury. Improved understanding of risk factors for burn-related infections in combat casualties is critical for effective management., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose. All authors approved the final version for submission., (Published by Elsevier Ltd.)

Introduction: The association between military service history and long-term outcomes after burn injury is unknown. This study uses data from the Burn Model System National Database to compare outcomes of individuals with and without self-reported military service history., Methods: Outcome measures were assessed at 12 months after injury including the Veterans Rand-12 Item Health Survey/Short Form-12, Satisfaction With Life Scale, Patient Reported Outcomes Measure Information System 29, 4-D Itch scale, Post Traumatic Stress Disorder Check List - Civilian Version, self-reported Post Traumatic Stress Disorder, and employment status. This study included 675 people with burns of whom 108 reported a history of military service., Results: The military service history group was more likely to be older, and male. Those with military service were most likely to be on Medicare insurance and those without military service history were most likely to be on Private Insurance/HMP/PPO. No significant differences were found between those with and without military service history in the outcome measures., Conclusions: Further research should examine differences in outcomes between civilians and those with military service history, including elements of resilience and post traumatic growth., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2023 Elsevier Ltd and ISBI. All rights reserved.)

Background: Frostbite is an insidious disease that normally affects people of cold climates. Winter Storm Uri, which occurred from February 12-20, 2021, created unique metrological conditions for Texas. It caused prolonged sub-freezing temperatures and led to rolling blackouts, affecting 2.8 million Texans including 300,000 people in San Antonio. We report 13 frostbite patients admitted to one burn center during this event., Objective: We aimed to determine the at-risk population for frostbite, to categorize their injury severity, and to describe their treatment. A secondary aim was to describe the rehabilitation management of these patients., Methods: This is a single-center retrospective study. Each patient's injuries were assessed by a topographical grading system. Comparisons were made among those who were admitted to the intensive care unit (ICU), admitted to the progressive care unit (PCU), and treated as outpatients., Results: Thirteen patients were identified. Ten (76.9 %) considered themselves homeless, and 9 (69.2 %) were directly exposed to the elements. The median delay between time of injury and presentation to a medical facility was 3 days (IQR 1-6). Only 3 patients presented to a medical facility within 24 h. Six (46 %) sustained grade 2 injuries, 2 (15 %) sustained grade 3 injuries, and 5 (38%) sustained grade 4 injuries. Only one patient met criteria to receive tissue plasminogen activator (tPA), which was discontinued due to hematochezia. Patients admitted to the ICU, when compared to patients admitted to the ward, had a longer length of stay (median 73 days v. 12 days, p = 0.0215), and required more amputations at below-the-knee or higher levels (3 v. 0, p-value 0.0442)., Conclusion: In a region unaccustomed and perhaps unprepared to deal with winter storms, the population is particularly vulnerable to frostbite. Lack of awareness of frostbite injuries likely led to the delay in the presentation of patients, which prevented the timely use of tPA. Increasing public awareness may increase readiness., Competing Interests: Conflicts of interests No authors have any conflicts to disclose., (Published by Elsevier Ltd.)

Background: Enterally based resuscitation for major burn injuries has been suggested as a simple, operationally superior, and effective resuscitation strategy for use in austere contexts. However, key information to support its implementation is lacking, including palatability and acceptability of widely available rehydration drinks., Methods: We performed a single-blinded, cross-sectional survey of 60 healthy children (5-14 years), adults (15-54 years) and older adults (≥55 years) to determine palatability and overall acceptability of five oral rehydration solutions (ORS) and a positive control drink (Sprite Zero®) in Ghana. Quantitative data were described and differences between our control drink and the others across age groups were visually examined with Likert plots. Qualitative responses were analyzed using a content analysis framework., Results: Twenty participants in each age group completed the study. Participants were as young as 5 years and as old as 84 years. Nearly two thirds of the sample identified as male (n = 38, 63% of all participants). The positive control was reported to taste 'good or 'very good' by the majority of participants (89%) followed by lemon-flavored ORS (78%) and orange-flavored ORS (78%). Conversely, homemade and low-osmolarity ORS were reported to taste 'good' or 'very good' by only 20% and 15% of participants, respectively. There were no major taste differences across the age groups. However, children more frequently reported positively (i.e., tastes 'good' or 'very good') about flavored and sweet drinks than did adults and older adults. When faced with the hypothetical situation of being critically injured and needing resuscitation, participants tended to be more agreeable to consuming all the drinks, even low-osmolarity and homemade ORS., Conclusions: These findings can be used to support the development of protocols that may be more acceptable among patients undergoing enterally based resuscitation, thus improving the effectiveness of the treatment. Specifically, enterally based resuscitation should likely include citrus-flavored ORS when available, given superior palatability and the fact that different flavor additives for patients of different ages do not seem necessary., Competing Interests: Declaration fo Competing Interest The authors have no real or perceived conflicts of interest to report., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Weight loss is difficult to quantify in critically ill burn patients, as the presence of edema can mask changes in dry body weight. We sought to estimate dry body weight using measured weights adjusted for reported extremity edema. We evaluated patients with at least 20% total body surface area (TBSA) burns admitted to our intensive care unit over a 3½-year period. Body weights were collected for this analysis from admission to the time of a recorded dry weight after wound healing. Extremity edema was collected at the time of each weight measurement and was categorized into three groups: (1) no edema, (2) 1 + pitting edema, (3) 2 + or 3 + pitting edema. Logistic regression yielded the following formula for estimating dry weight (in kg): 0.66 x measured body weight + 25 - (3 for 1 + pitting edema or 4 for 2 + or 3 + pitting edema of either upper extremity) - (4 for any pitting edema to either lower extremity) (p < 0.01, R 2 = 0.81). These results may allow us to better estimate dry body weight changes in our edematous patients with severe burns. Nutrition goals can be adjusted earlier, when appropriate, based on these estimated dry body weight changes., Competing Interests: Declarations of interest None., (Published by Elsevier Ltd.)

Introduction: Burns are an important cause of battlefield injury, accounting for 5-20% of the combat injury burden. To date, no report has examined the full range of burns, from mild to severe, resulting from post-9/11 conflicts. The present study leverages the Expeditionary Medical Encounter Database (EMED), a Navy-maintained health database describing all service member medical encounters occurring during deployment, to capture, quantify and characterize burn-injured service members and the injuries they sustained while deployed in support of post-9/11 operations., Methods: The EMED was queried for all surviving service members with at least one burn injury, identified using injury-specific Abbreviated Injury Scale codes. Demographic and additional injury information were also obtained from the EMED., Results: From 2001 through 2018, 2507 deployed service members sustained 5551 burns. Blasts accounted for 82% of injuries, largely attributed to the use of improvised explosive devices. Concurrent injury was common, with 30% sustaining a traumatic brain injury and 10% sustaining inhalation injury. Most burns were small, with 92% involving< 20% TBSA; 85% of burns involved< 10% TBSA. The head and the hands were the most commonly affected areas, accounting for 48% of all burns, with 80% of service members sustaining at least one burn to these areas., Conclusion: The majority of burns tend to be small in size, with the head and hands most commonly affected. As these areas are often left uncovered by the uniform, prevention measures, particularly improvement in and increased usage of personal protective gear, may help reduce these injuries and their consequences., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Objective: This analysis includes pooled safety data from 2 clinical trials (NCT01437852; NCT03005106) that evaluated the safety and efficacy of StrataGraft in patients with deep partial-thickness (DPT) burns., Methods: The study enrolled 101 adult patients with thermal burns covering 3-49% of total body surface area. Patients were followed for up to 1 year. The pooled safety events included: adverse events (AEs), adverse reactions (ARs), serious AEs (SAEs), discontinuation, and deaths; immunological responses (reactivity to panel reactive antibodies [PRA] and human leukocyte antigen [HLA] class 1 alleles); and persistence of allogeneic DNA from StrataGraft., Results: Eighty-seven (86.1%) patients experienced 397 AEs. Thirty patients (29.7%) experienced ARs; 16 patients (15.8%) experienced SAEs. The most frequent AEs were pruritus (n = 31; 30.7%), and blister, hypertension, and hypertrophic scar (n = 11 each; 10.9%); the most common AR was pruritus (n = 13; 12.9%). One patient discontinued the study; 2 patients experienced SAEs (unrelated to StrataGraft) leading to death. PRA and HLA allele reactivity was ≤ 25% at Month 3, with no persistent allogeneic DNA from StrataGraft., Conclusions: StrataGraft was well tolerated by patients, with a safety profile similar to autograft. StrataGraft may offer a safe alternative to autograft for DPT burns., Competing Interests: Conflicts of interest JHH has equity ownership in Abbott Labs, AbbVie, Imbed Biosciences, and Change Healthcare. JHH is a consultant to Avita Medical and Stratatech and Mallinckrodt Pharmaceuticals plc, Hampton, NJ. LCC, LDF, and BTK have nothing to disclose. JEC has equity positions in PermeaDerm, Inc, and is a consultant for Avita Medical. Research support from Avita Medical, SpectralMD, and Keranetics. KF has been involved in clinical studies for the American Burn Association, Atox-Bio, BARDA, Baxter, Polynovo Biomaterials, Mallinckrodt Pharmaceuticals, Integra LifeSciences, MediWound, MiMedx, Skingenix, Propanolol, Avita Medical, The Canadian Institutes of Health, and Stratatech, all outside the submitted work. HDH, RR, JMS, and RW are employees and shareholders of Mallinckrodt Pharmaceuticals. ALFG is a consultant to Mallinckrodt Pharmaceuticals and Stratatech, a Mallinckrodt company., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The purpose of this study was to examine risk factors for mortality in burned patients with inhalation injury (II). We further sought to compare a cohort of burned military service members to civilian patients with II., Methods: We identified patients treated at our burn center over a 10-year period. Demographics, injury characteristics, and outcomes were compared between patients with and without II. Logistic regression analysis was performed to determine the impact of patient characteristics and II grade on mortality., Results: 3791 patients treated at our burn center met study inclusion criteria. 424 (11.2%) patients were diagnosed with II [II(+)]. Age, % total body surface area (TBSA) burned, % full thickness burned, intensive care unit (ICU) days, hospital days, and mortality were all greater in II(+) patients. Separating the II(+) patients into military and civilian groups, there was a higher incidence of grade 4 II and higher mortality for grades 2-4 II in military patients. Analyses demonstrated that military service was associated with increased mortality in II(+) patients. The bronchoscopic grade of II did not have an association with mortality in this population., Conclusions: II(+) patients were older, had larger burns, needed more ICU and hospital days, and had higher mortality rates. Among II(+) patients, military affiliation was associated with more severe II and increased mortality. Establishment of an objective grading system for II that is associated with mortality is a meaningful future research endeavor., (Published by Elsevier Ltd.)

Animal-assisted interventions have been implemented in both inpatient and outpatient settings and have demonstrated positive outcomes on patients and hospital staff. Animal-assisted interventions have not been previously reported in any burn center. A therapy dog program was established at our burn center with the intent of improving duration and quality of rehabilitation sessions and physical therapy. Satisfaction surveys were distributed to patients and staff. After one year, 14 patient surveys and 23 staff surveys were collected. Implementation of this program was feasible and patients worked with the therapy dogs in all environments of the burn center: outpatient, ward, and ICU. Most patients reported improved pain and anxiety after working with the therapy dogs. All patients reported that they would like more sessions with the therapy dogs. All staff members were satisfied or very satisfied with their therapy dog visit and all enjoyed having the therapy dogs present. Most reported an improved mood after seeing the therapy dogs and wanted that additional therapy dog visits. One year after the implementation of the therapy dog program, we have demonstrated feasibility, acceptability, and desirability of this type of program at our burn center. Given the paramount importance of rehabilitation in the recovery of burn patients, further investigation into therapy should be performed and longer term outcomes assessed., (Published by Elsevier Ltd.)

Background: Determining the amount of analgesics required will help burn centers improve their ability to plan for a burn mass casualty incident (BMCI). We sought to quantify the amount of analgesics needed in an inpatient burn population. We hoped that assessing the analgesic use in daily burn care practice will potentially help estimate opioid needs in a burn mass casualty incident (BMCI)., Methods: We included patients with burns covering equal to or less than 30% total body surface area (TBSA), admitted from spring 2013 to spring 2015. Patient records were reviewed for analgesics and adjuncts, pain scores, age and TBSA. The doses of the different opioids administered were converted into morphine equivalent doses (MED)., Results: We enrolled 141 acute burn survivors with a mean TBSA of 8.2±0.6%. The lowest daily average MED per person was 24.6±2.0mg MED, recorded on the day of injury. The daily average MED per person increased until it peaked at 52.5±5.6mg MED at day 8 post-burn. Then, it declined to 24.6±3.4mg MED by day 14. Bivariate regression analysis of average MED by TBSA showed a significant positive correlation (p<0.001). The analysis of average MED by age showed a significant negative correlation (p<0001)., Conclusion: Our study quantified opioid requirements in an inpatient burn population and identified TBSA (positively) and age (negatively) as significant predictors., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Background: We investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as adjunctive treatments for acute respiratory distress syndrome (ARDS) due to inhalation injury and burns. We hypothesized that these interventions decrease histological end-organ damage., Methods: Anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, then critical care for 72h. The following groups were studied: CTR (no injury, n = 4), ICTR (injured untreated, n = 10), Allo (injured treated with allogenic MSC, n = 10), Auto (injured treated with autologous MSC, n = 10), Hemo (injured and treated with the Hemolung low flow ECLS system, n = 9), and Nova (injured and treated with the NovaLung low flow ECLS system, n = 8). Histology scores from lung, kidneys, liver, and jejunum were calculated. Data are presented as means±SEM., Results: Survival at 72h was 100% in CTR; 40% in ICTR; 50% in Allo; 90% in Auto; 33% in Hemo; 63% in Nova. ARDS developed in 0/10 CTR; 10/10 ICTR; 8/9 Hemo; 5/8 Nova; 9/10 Allo; 6/10 Auto. Diffuse alveolar damage (DAD) was present in all injured groups. MSC groups had significantly lower DAD scores than ICTR animals (Allo 26.6 ± 3.4 and Auto 18.9 ± 1.5 vs. ICTR 46.8 ± 2.1, p < 0.001). MSC groups also had lower DAD scores than ECLS animals (Allo vs. Nova, p < 0.05, Allo vs. Hemo p < 0.001, Auto vs. Nova p < 0.001, Auto vs. Hemo, p < 0.001). Kidney injury ICTR (p < 0.05) and Hemo (p < 0.01) were higher than in CTR. By logistic regression, a PaO 2 -to-FiO 2 ratio (PFR) < 300 was a function of the DAD score: logit (PFR < 300) = 0.84 + 0.072*DAD Score, odds ratio 1.074 (1.007, 1.147, p < 0.05) with a ROC AUC of 0.76, p < 0.001., Conclusion: Treatment with Auto MSC followed by Allo and then Nova were most effective in mitigating ARDS and MOF severity in this model. Further studies will elucidate the role of combination therapies of MSC and ECLS as comprehensive treatments for ARDS and MOF., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Background: The prevalence of acute respiratory distress syndrome (ARDS) in mechanically ventilated burn patients is 33%, with mortality varying from 11-46% depending on ARDS severity. Despite the new Berlin definition for ARDS, prompt bedside diagnosis is lacking. We developed and tested a bedside technique of fiberoptic-bronchoscopy-based optical coherence tomography (OCT) measurement of airway mucosal thickness (MT) for diagnosis of ARDS following smoke inhalation injury (SII) and burns., Methods: 16 female Yorkshire pigs received SII and 40% thermal burns. OCT MT and PaO 2 -to-FiO 2 ratio (PFR) measurements were taken at baseline, after injury, and at 24, 48, and 72h after injury., Results: Injury led to thickening of MT which was sustained in animals that developed ARDS. Significant correlations were found between MT, PFR, peak inspiratory pressure (PIP), and total infused fluid volume., Conclusions: OCT is a useful tool to quantify MT changes in the airway following SII and burns. OCT may be effective as a diagnostic tool in the early stages of SII-induced ARDS and should be tested in humans., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Healing of burn wounds is necessary for survival; however tracking progression or healing of burns is an inexact science. Recently, the relationship of mortality and wound healing has been documented with a software termed WoundFlow. The objective of the current study was to confirm various factors that impact burn wound healing, as well as to establish a timeline and rate of successful healing. A retrospective analysis was performed on adults (n=115) with at least 20% TBSA burn that had at least two computer-based wound mappings. The % open wound (%OW) was calculated over time to document healing trajectory until successful healing or death. Only 2% of patients in the group with successful wound healing died. A decrease in the %OW of 0.8 (IQR: 0.7-1.1) was associated with survival. Disparities in wound healing trajectories between survivors and non-survivors were distinguishable by 2weeks post-injury (P<0.05). When %TBSA was stratified by decile, the 40-49% TBSA group had the highest healing rate. Taken together, the data indicate that wound healing trajectory (%OW) varies with injury severity and survival. As such, automated mapping of wound healing trajectory may provide valuable information concerning patient/prognosis, and may recommend early interventions to optimize wound healing., (Published by Elsevier Ltd.)

Objective: The current conflicts in Iraq and Afghanistan resulted in an increased incidence of burn injury in the military population. We sought to compare the characteristics and outcomes of this population to a civilian cohort cared for at the same burn center over the same time-period., Methods: A retrospective review was performed to examine differences in the demographics, etiology, mortality, and functional status over a 12-year period. Descriptive analyses were performed. Logistic regression was used to calculate the likelihood of mortality., Results: A total of 3814 patients were included in this analysis; 1069 were military casualties. When compared to civilians, military patients were younger, had a higher incidence of flame-induced burn injury, mean total body surface area burned (% TBSA), rate of inhalation injury, and lower mortality. Civilian patients presented with a higher Baux score. Although most military patients had a full functional recovery, they had a greater incidence of severe disability. In a univariate model, likelihood of mortality was higher in civilians. No difference in mortality between the two cohorts was found after adjusting for age, inhalation injury, gender, % TBSA and percent full-thickness burn., Conclusions: Military patients exhibited improved survival and functional recovery over their civilian counterparts. However, mortality did not differ between civilian and military patients after controlling for known covariates. Further studies are needed to improve functional outcomes in civilian patients, who may not have the inherent advantages of younger age and healthier physical status found in military patients., (Published by Elsevier Ltd.)

Background: The injury severity score considers burn size and inhalation injury in estimating overall anatomical injury severity. Models that adjust for injury severity score in addition to total burn size and inhalation injury may therefore be double counting the risk from these individual burn characteristics, and obscuring (or overemphasizing) the contribution of risk from each source. The primary aim of this study was to compare differences in the estimated mortality risk of burn trauma using the traditional injury severity score (ISS) calculation and the non-burn injury severity score (NBISS) to examine how separating out the risk attributable to the burn injury versus other trauma changes the interpretation and clinical assessment., Methods: Among U.S. casualties sustaining burns during combat operations in Iraq and Afghanistan from March 2003 to October 2013, we performed a retrospective cohort study. Unadjusted, adjusted, and weighted Cox proportional hazards models were performed to estimate the risk of age, burn injury severity, and non-burn injury severity on mortality. Weighted hazard ratios and adjusted survival curves were performed using non-parametric inverse probability weighting., Results: Our final sample consisted of 902 service members with a mortality proportion of 5.7% (n=51). Adjusting for non-burn trauma with traditional ISS attenuated the risk of percent total body surface area burned (%TBSA) by 20% when modeled continuously [HR (95% CI): 1.27 (1.10-1.32) vs. 1.07 (0.99-1.15]. However, the adjusted model using NBISS only attenuated the associated mortality risk of burn size by 5% [HR (95% CI): 1.22 (1.12-1.34)] and had a similar model fit (AIC: 484.2 vs. 478.6). For the weighted Cox proportional hazards models, the risk from a large burn (%TBSA≥60) was also attenuated when adjusting for ISS [HR (95% CI): 2.80 (1.18-6.64)] compared to the model adjusting for NBISS [HR (95% CI): 5.63 (2.79-11.35)]., Conclusion: Our analysis comparing the use of traditional ISS and NBISS to measure comorbid non-burn trauma resulted in different interpretations for the effect of %TBSA on subsequent mortality. Our results suggest that the association of %TBSA with death can be obscured by the inclusion of traditional ISS. Therefore, we recommend using NBISS when constructing statistical models in this patient population., (Published by Elsevier Ltd.)

Introduction: Recent reports on the use of extracorporeal membrane oxygenation (ECMO) in critically ill burn patients with Acute Respiratory Distress Syndrome (ARDS) recommended against the use of ECMO. The authors cited the high mortality rates associated with the use of ECMO in these patients with no appreciable benefit. Accumulating evidence from referral centers suggests improved survival in patients with ARDS receiving ECMO. We report our recent experience treating patients with severe ARDS with ECMO in a burn intensive care unit., Methods: This is a case series of consecutive patients placed on ECMO at our burn center from the initiation of our program in September 2012 to September 2017. We included only adult patients who had been placed on ECMO with burn injury, TEN, or inhalation injury and severe ARDS., Results: Fourteen patients with burn injury, inhalation injury or TEN were placed on ECMO from the initiation of the ECMO program to September 1st 2017. The average total body surface area burned in the 11 patients with burn injury was 27% (range 0.25-76%). The cause of ARDS in these patients included inhalation injury, airway trauma and bacterial pneumonia. Four patients had an inhalation injury and 1 patient had a grade 3 inhalation injury but no burn injury. In the majority of cases, prone positioning and use of neuromuscular blockade was also used in an attempt to improve oxygenation and patient synchrony with mechanical ventilation. The average time on ECMO was 276h (range 63-539h). Ten of the 14 patients survived to decanulation from ECMO (71%) and eight of 14 patients (57%) survived to hospital discharge., Conclusions: To our knowledge, this is the lowest mortality rate reported to date in burn patients with ARDS place on ECMO. ECMO is a viable therapy that can be utilized successfully as a rescue modality when conventional interventions are unsuccessful., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Inhalation injury commonly accompanies thermal injury, increasing the likelihood of mortality and multiple organ dysfunction (MOD). Large animal models have given important insight into the pathophysiology of this injury; however recapitulating late MOD has remained difficult. The current report describes experiments using a smoke inhalation and burn model, with follow-up of ambulatory swine for 14days with bronchoscopy, CT scanning, and bronchoalveolar lavage fluid (BALF)/blood collection. Clinically, animals cleared airway damage in the first several days after-injury. This was mirrored with erythematous airways on day 2 after-injury, which resolved by the end of the experiment, as did parenchymal damage seen on CT. An initial rise in the protein content of BALF immediately after-injury was followed by a dramatic increase in the concentration of leukocytes. Circulating neutrophils increased while lymphocytes decreased; both correlated with cell counts in BALF. IL8 levels in BALF increased 30-fold and remained elevated throughout the experiment. IL1ra increased circulation immediately after-injury, and afterwards in BALF. Other cytokines (TNFα, IL12) transiently increased in BALF (and decreased in circulation) on day 2. Taken together, these results display a remarkable capability for the lungs to recover in the absence of intubation, with further evidence of the role of cytokines such as IL8 and IL1ra. The possible exacerbating effects of clinical practices such as ventilation and bronchoscopies should be considered., (Published by Elsevier Ltd.)

Introduction: Cutaneous allograft is commonly used in the early coverage of excised burns when autograft is unavailable. However, allograft is also applied in intermediate-extent burns (25-50%), during cases in which it is possible to autograft. In this population, there is a paucity of data on the indications for allograft use. This study explores the indications for allograft usage in moderate size burns., Methods: Under an IRB-approved protocol, patients admitted to our burn unit between March 2003 and December 2010 were identified through a review of the burn registry. Data on allograft use, total burn surface area, operation performed, operative intent, number of operations, intensive care unit length of stay, and overall length of stay were collected and analyzed. Data are presented as means±standard deviations, except where noted., Results: In the study period, 146 patients received allograft during their acute hospitalization. Twenty-five percent of allograft recipients sustained intermediate-extent burns. Patients with intermediate-extent burns received allograft later in their hospitalization than those with large-extent (50-75% TBSA) burns (6.8 days vs. 3.4 days, p=0.01). Allografted patients with intermediate-extent burns underwent more operations (10.8 vs. 6.1, p=0.002) and had longer hospitalizations (78.3 days vs. 40.9 days, p<0.001) than non-allografted patients, when controlled for TBSA. Clinical rationale for placement of allograft in this population included autograft failure, uncertain depth of excision, lack of autograft donor site, and wound complexity. When uncertain depth of excision was the indication, allograft was universally applied onto the face. In half of allografted intermediate-extent burn patients the inability to identify a viable recipient bed was the ultimate reason for allograft use., Conclusions: Unlike large body surface area burns, allograft skin use in intermediate-extent injury occurs later in the hospitalization and is driven by the inability to determine wound bed suitability for autograft application. Allograft application can be utilized to test recipient site viability in cases of autograft failure or uncertain depth of excision., (Published by Elsevier Ltd.)

Introduction: Historically, mucormycosis infections have been associated with high mortality. The purpose of this study was to determine the incidence, associated mortality, and management strategies of mucormycosis in a major burn center., Methods: A retrospective review was performed via obtaining all patients with mucormycosis admitted from January 2003 to November 2009 at our adult burn center was performed obtaining demographic data relevant to fungal burn wound infection or colonization., Results: The incidence of mucormycosis at our facility was 4.9 per 1000 admissions; specifically, 11 military casualties and one civilian were diagnosed with mucormycosis. The median percentage Total Body Surface Area (TBSA) burned, 11 patients, or open wound, one patient, was 60 (IQR, 54.1-80.0), and the incidence of documented inhalation injury was 66.7% (8 of 12). Ten patients had surgical amputations. A median of eight days (IQR, 3.5-74.5) elapsed from diagnosis of mucormycosis until death in the 11 patients who expired. The overall mortality was 92%; however, autopsy attributed mucormycosis mortality was 54.5% (6 of 11) with all six patients having invasive mucormycosis., Conclusion: Aggressive surgical intervention should be undertaken for invasive mucormycosis; additionally, implementation of standardized protocols for patients with large soft tissue injuries may mitigate mucormycosis superimposition., (Published by Elsevier Ltd.)

Purpose: Compare virtual bronchoscopy (VB) to fiberoptic bronchoscopy (FOB) for scoring smoke inhalation injury (SII)., Methods: Swine underwent computerized tomography (CT) with VB and FOB before (0) and 24 and 48 h after SII. VB and FOB images were scored by 5 providers off line., Results: FOB and VB scores increased over time (p<0.001) with FOB scoring higher than VB at 0 (0.30±0.79 vs. 0.03±0.17), 24 h (4.21±1.68 vs. 2.47±1.50), and 48h (4.55±1.83 vs. 1.94±1.29). FOB and VB showed association with PaO2-to-FiO2 ratios (PFR) with areas under receiver operating characteristic curves (ROC): for PFR≤300, VB 0.830, FOB 0.863; for PFR≤200, VB 0.794, FOB 0.825; for PFR≤100, VB 0.747, FOB 0.777 (all p<0.001). FOB showed 80.3% specificity, 77% sensitivity, 88.8% negative-predictive value (NPV), and 62.3% positive-predictive value (PPV) for PFR≤300 and VB showed 67.2% specificity, 85.5% sensitivity, 91.3% NPV, and 53.4% PPV., Conclusions: VB provided similar injury severity scores to FOB, correlated with PFR, and reliably detected airway narrowing. VB performed during admission CT may be a useful screening tool specifically to demonstrate airway narrowing induced by SII., (Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.)

A prolonged and fulminant inflammatory state, with high levels of pro- and anti-inflammatory mediators, is seen after extensive thermal injury. Blood purification techniques including plasma exchange, continuous venovenous hemofiltration, and adsorbing membranes have the potential to modulate this response, thereby improving outcomes. This article describes the scientific rationale behind blood purification in burns and offers a review of literature regarding its potential application in this patient cohort., (Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.)

Objective: Adult burn patients who experience in-hospital cardiac arrest (CA) and undergo cardiopulmonary resuscitation (CPR) represent a unique patient population. We believe that they tend to be younger and have the added burden of the burn injury compared to other populations. Our objective was to determine the incidence, causes and outcomes following cardiac arrest (CA) and cardio-pulmonary resuscitation (CPR) within this population., Methods: We conducted a retrospective review at the US Army Institute of Surgical Research (ISR) burn intensive care unit (BICU). Charts from 1st January 2000 through 31st August 2009 were reviewed for study. Data were collected all on adult burn patients who experienced in-hospital CA and CPR either in the BICU or associated burn operating room. Patients undergoing CPR elsewhere in our burn unit were excluded because we could not validate the time of CA since they are not routinely monitored with real-time rhythm strips. The study population included civilian burn patients from the local catchment area and burn casualties from the conflicts in Iraq and Afghanistan, but patients with do-not-resuscitate (DNR) orders were excluded., Results: We found 57 burn patients who had in-hospital CA and CPR yielding an incidence of one or more in-hospital CA of 34 per 1000 admissions (0.34%). Fourteen of these patients (25%) survived to discharge while 43 (75%) died. The most common initial cardiac rhythm was pulseless electrical activity (50.9%). The most common etiology of CA among burn patients was respiratory failure (49.1%). The most significant variable affecting survival to discharge was duration of CPR (P < 0.01) with no patient surviving more than 7 min of CPR., Conclusions: CPR in burn patients is sometimes effective, and those patients who survive are likely to have good neurological outcomes. However, prolonged CPR times are unlikely to result in return of spontaneous circulation and may be considered futile. Further, those who experience multiple CA are unlikely to survive to discharge., (Published by Elsevier Ltd.)

This study focused on the impact of noise on the reliability of heart-rate variability and complexity (HRV, HRC) to discriminate between different trauma patients and to monitor individual patients. Life-saving interventions (LSIs) were chosen as an endpoint because performance of LSIs is a critical aspect of trauma patient care. Noise was modeled and simulated by modifying original R-R interval (RRI) sequences via decimation, concatenation, and division of RRIs, as well as R-wave detection using the electrocardiogram. Results showed that under increasing simulated noise, entropy and autocorrelation measures can still effectively discriminate between LSI and non-LSI patients and monitor individuals over time., (© 2013 Elsevier Ltd. All rights reserved.)

Background: Resuscitation fluid rates following burn are currently guided by a weight and burn size formulae, then titrated to urine output. Traditionally, 24h resuscitation is reported as volume of resuscitation received without direct consideration for the physiologic response. We propose an input-to-output ratio to describe the course of burn resuscitation and predict eventual outcomes., Methods: We reviewed admissions to a burn center from January 2003 through August 2006. Inclusion criteria were ≥20%TBSA, admission ≤8h after burn, and survived ≥24h. Demographics, input volume and urine output, and clinical outcomes were recorded. A ratio of input volume (cc/kg/%TBSA/h) to urine output (cc/kg/h) was calculated at 24h. The ratio of fluid intake to urine output reflecting an 'expected' response was developed: 4cc/kg/%TBSA/24h (0.166cc/kg/%TBSA/h) divided by 0.5-1.0cc urine/kg/h for an expected range 0.166-0.334. Subjects were classified based upon the ratio: over-responders (<0.166), expected (0.166-0.334), or under-responders (>0.334). Clinical outcomes were compared and concordance of classification to values was calculated at 12h., Results: 102 subjects met inclusion criteria; 29 in the over-responders, 37 in the expected, and 36 in the under-responders. Resuscitation volume was directly proportional to the calculated ratio while urine output was inversely proportional. Group mortality was 21%, 11%, and 44%, respectively, with a significant difference between the expected and under-responders (p<0.002). We found decreased ventilator-free days in the under-responders, and when deaths were excluded, decreased ICU-free days as well (p<0.05). Concordance of paired data gathered at 12h and 24h was 67% for the under-responder group., Conclusions: We describe a novel ratio to classify acute resuscitation after severe burn including the patient's response. Such a classification is associated with eventual outcomes., (Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.)

Background: Fungal wound infection is a leading cause of burn wound infections, and diagnosis is often delayed as it conventionally requires culture and histopathology. Fungal screening assays have sped diagnosis of invasive fungal infections in other populations. Few studies have evaluated the performance of fungal screening assays outside of the hematologic malignancy and hematopoietic stem cell transplant populations., Methods: We performed a three year retrospective analysis of all fungal screening assays in burn patients in the ICU between 2008 and 2011. The primary goal was to evaluate the correlation between the two available fungal screening assays, (1→3)-β-d-glucan (BG) and galactomannan (GM) assay, and fungal wound colonization (FWC) and infection (FWI). We also evaluated previously hypothesized causes of false positives and their associations with false positives in the burn population., Results: We identified 53 patients [median 29% total body surface area burned (TBSA), IQR 17-51] with BG or GM serological tests available, of which 15 had a FWI or FWC. FWC/FWI was associated with higher TBSA (p=0.02). BG and GM correlated with TBSA (BG 0.57, p<0.01; GM 0.35, p=0.02), but neither assay was associated with FWI/FWC or species of fungus involved when FWI/FWC was diagnosed., Conclusions: Positive BG and GM fungal screening assays are not associated with FWI/FWC, or with species of fungus when FWC/FWI is present. BG false positives are common and associated with higher TBSA burns., (Published by Elsevier Ltd.)

Bacterial infections are a common cause of mortality in burn patients and viral infections, notably herpes simplex virus (HSV) and cytomegalovirus (CMV) have also been associated with mortality. This study is a retrospective review of all autopsy reports from patients with severe thermal burns treated at the US Army Institute of Research (USAISR) burn unit over 12 years. The review focused on those patients with death attributed to a bacterial or viral cause by autopsy report. Of 3751 admissions, 228 patients died with 97 undergoing autopsy. Death was attributed to bacteria for 27 patients and to virus for 5 patients. Bacterial pathogens associated with mortality included Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. This association with mortality was independent of % total body surface area burn, % full-thickness burn, inhalation injury, and day of death post-burn. Bloodstream infection was the most common cause of bacteria related death (50%), followed by pneumonia (44%) and wound infection (6%). Time to death following burn was < or =7 days in 30%, < or =14 days in 59% and < or =21 days in 67%. All of the viral infections associated with mortality involved the lower respiratory tract, HSV for 4 and CMV for 1. Four of these 5 patients had evidence of inhalation injury by bronchoscopy, all had facial and neck burns, and 2 had concomitant Staphylococcus pneumonia. Time to death following burn ranged from 14 to 42 days for the 5 patients. Despite advances in care, gram negative bacterial infections and infection with S. aureus remain the most common cause of bacteria related mortality early in the hospital course. Viral infections are also associated with mortality and numbers have remained stable when compared to data from prior years., (Published by Elsevier Ltd.)

Current guidelines outlining the resuscitation of severely burned patients, in the United States, were developed over 30 years ago. Unfortunately, clinical burn resuscitation has not advanced significantly since that time despite ongoing research efforts. Many formulas exist and have been developed with the intention of providing appropriate, more precise fluid resuscitation with decreased morbidity as compared to the current standards, such as the Parkland and modified Brooke formulas. The aim of this review was to outline the evolution of burn resuscitation, while closely analyzing current worldwide guidelines, adjuncts to resuscitation, as well as addressing future goals.

Advancements in burn care therapy have extended survival of seriously burned patients, exposing burn patients to increased risk of infectious complications, notably fungal infections. We performed a 12-year review of autopsied patients with severe burns for the presence of fungal infection at the US Army Institute of Surgical Research Burn Center between February 1991 and November 2003. The primary goal was to identify the relationship between fungal element noted in autopsy and mortality, and to determine contributing factors that increase a patient's susceptibility to fungal infection. A total of 228 deaths (6.1%) resulted from the 3751 admissions of which 97 underwent autopsy. Fungal elements were identified on histopathology in 44% (43 of 97) of autopsied patients with an attributable mortality of 33% (14 of 43). Aspergillus and Candida were the most frequently recovered fungi, but Aspergillus was recovered in 13 of the 14 cases with fungus identified as an attributable cause of death. The most common sites of infections with attributable mortality were wounds (86%) and the pulmonary system (14%). Total body surface area (TBSA) burn and length of stay (survival after burn) were identified as contributing factors for the incidence of fungal element in autopsy on ROC curve analysis. More severely injured patients with greater %TBSA burn injury and full-thickness burns require a longer recovery period resulting in a longer hospital stay. The propensity for fungal infection increases the longer the wound is present. Therefore, the development of products to close the wound more rapidly, improvement in topical antifungal therapy with mold activity for treating wounds, and implementation of appropriate systemic antifungal therapy may improve outcome for severely injured burn victims susceptible to fungal infections.

Lightning is an uncommon but potentially devastating cause of injury in patients presenting to burn centers. These injuries feature unusual symptoms, high mortality, and significant long-term morbidity. This paper will review the epidemiology, physics, clinical presentation, management principles, and prevention of lightning injuries.

Introduction: The occurrence of organ failure following thermal injury, despite restoration of hemodynamic parameters and urine output during resuscitation, has led to efforts to measure end-organ perfusion. The purpose of this 24-h study was to evaluate the utility of gastrointestinal (GI) tonometry during burn shock and resuscitation., Methods: Male swine (n=11, 23.3+/-0.9 kg) were anesthetized with ketamine and propofol. A 70% full thickness burn was caused by immersion in 97 degrees C water for 30 s. Resuscitation with lactated Ringer's, 4 ml/kg/% burn, was begun at hour 6 and titrated to urine output (UO). Arterial blood gases and pulmonary artery catheter data were measured every 6 h. Gastric and ileal regional PCO(2) (PrCO(2)) were measured continuously by air tonometry, and the gastric and ileal intramucosal pH (pHi) and PCO(2) gap (PrCO(2)-PaCO(2)) were calculated every 6 h., Results: Gastric pHi, ileal PrCO(2), ileal pHi, and ileal PCO(2) gap (but not gastric PrCO(2) or PCO(2) gap) all decreased with shock and were restored to baseline levels by resuscitation. Changes in ileal PrCO(2) were of greater magnitude and demonstrated decreased variability than those in gastric PrCO(2)., Conclusions: In this model, ileal tonometry outperformed gastric tonometry during burn shock and resuscitation.

Introduction: In this study we explored direct and indirect measures of autonomic nervous system function, as well as changes in cardiovascular complexity, during hemorrhagic shock (HS)., Methods: HS was induced in anesthetized sheep (n=8) by removing 40 ml/kg of blood in four 10 ml/kg steps over 40 min. Resuscitation was performed with lactated Ringer's and re-infusion of shed blood. Renal sympathetic nerve activity (RSNA) was measured by microneurography. Spectral analysis of heart rate variability (HRV) employed fast-Fourier transformation of the R-to-R interval (RRI) of the EKG. This generated the normalized high-frequency (HFnu) and low-frequency (LFnu) powers of the RRI, and their ratio (LFnu/HFnu, a proposed index of sympatho-vagal balance). Additionally, non-linear methods were applied: RRI complexity was measured by approximate (ApEn) and sample (SampEn) entropy methods; RRI fractal dimension was measured by curve lengths (FDCL). Plasma catecholamines were determined by HPLC., Results: The model caused profound HS; 2/8 animals survived till the end of resuscitation. RSNA increased in 7/8 sheep and, as HS progressed, multiple burst complexes were identified followed by sympathetic withdrawal. Concomitant decreases in HFnu and increases in LFnu/HFnu occurred after 20 ml/kg blood loss. ApEn and FDCL decreased after withdrawal of 40 ml/kg of blood. Catecholamine concentrations increased throughout HS. LFnu/HFnu and RSNA were not linearly correlated., Conclusions: HS led to an increase in RSNA with subsequent withdrawal. LFnu/HFnu increased during HS in association with vagal withdrawal and loss of RRI complexity. RRI complexity may in part reflect vagal modulation of the heart rate. Changes in directly measured tonic sympathetic traffic do not correlate with non-invasive measures of autonomic modulation of the heart.

An increasing number of burn wound infections are now due to fungi. Historically, therapy of fungal burn wound infections (FWI) consisted of debridement, topical antifungals and/or IV amphotericin B, negating the need to categorize disease further than fungal burn wound colonization (FWC) versus FWI. Newer antifungal agents have varying spectrums of activity, increasing the importance of identifying fungi, often to species. The records of patients admitted to our burn center from April 2000 to March 2005 were reviewed for fungi identified by histopathology. Wound specimens with fungi were classified as FWC or FWI and culture results were compared. The 1515 surgical wound tissue specimens were obtained from 2036 patients. Fungi were detected in the histopathology of 68 patients, 19 with FWI (3.8FWI/year); 9 had corresponding growth on culture. Forty nine patients were identified with FWC, 16 with fungi recovered in corresponding cultures. FWI was associated with increased mortality (OR 25.3, CI 3.12-204.8). Correlation between histopathologic and culture identification of fungi was inconsistent. The etiology of FWI was diverse; fungi with known resistance to each of the three major classes of antifungals were isolated, suggesting empirical use of one class may be inadequate to treat FWI. Future burn wound management must seek to identify fungal pathogens to species.

Background: Burns comprise 5% of casualties evacuated from Operations Iraqi and Enduring Freedom (OIF and OEF). Many OIF/OEF burns result from the enemy's detonation of explosives. We reviewed these to evaluate mission impact and provide recommendations for improved combat burn protection. Data were compared to those from the Vietnam War., Methods: All OIF/OEF patients with significant burns are treated at the U.S. Army Institute of Surgical Research (ISR). A review from April 2003 to April 2005 was undertaken. Records were obtained and demographics, burn severity and pattern, and early outcomes recorded., Results: Two hundred and seventy-four OIF/OEF burn patients were treated, 142 (52%) sustained burns in explosions from hostile action. Age was 26+/-7 years (mean+/-S.D.). Mortality was 4%. The annual rate of combat explosion as a cause for burns increased from 18% to 69%, total body surface area burned increased from 15+/-12 to 21+/-23%, injury severity score rose from 8+/-11 to 17+/-18, and frequency of inhalation injury rose from 5% to 26%. Improvised explosive devices caused 55% of casualties, car bombs 16%, rocket-propelled grenades 15% and 14% other. The hands (80% of patients) and the face (77%) were the most frequently burned body areas. Burns were isolated to the hands in 6% of patients and to the face and hands in 15%. An average of 52+/-30% of the surface area of the hands and 45+/-26% of the face was burned. Mean length of stay was 24+/-25 days (median 14). Though 77% of patients were discharged without global disability, only 36% returned to full military duty. A similar pattern of injury and disposition was seen at the Army burn center in Vietnam (1966-1968), but mortality was higher (7.9%)., Conclusion: Burns resulting from combat explosions increased in frequency, size and injury severity. Burns were concentrated on areas not protected by clothing or equipment. These injuries created long hospital stays and frequently prevented soldiers from returning to duty. While wound distribution has not changed, combat burn care has improved, and continued emphasis on military protective equipment for the hands and face is warranted.

Background: Renal cortical blood flow can be quantified by means of power Doppler ultrasound (PDUS) image analysis. We hypothesized that renal cortical perfusion, estimated by PDUS image intensity (PDUSII), would decrease during burn shock and improve during resuscitation in a porcine model., Methods: Eight anesthetized swine sustained a 75% scald injury. Resuscitation began 6h postburn. Renal cortical blood flow was measured directly using fluorescent microspheres (CORFLO), and was estimated noninvasively by PDUSII. PDUSII, CORFLO, and cardiopulmonary data were recorded every 2h., Results: PDUSII decreased significantly from preburn to postburn hour 6, and increased with resuscitation by hour 8. CORFLO correlated well with PDUS image intensity (n=48, r(2)=0.696) but poorly with urine output (n=48, r(2)=0.252)., Conclusion: PDUS in this study was superior to the urine output in assessing renal cortical microvascular blood flow during shock and resuscitation, and may be useful in the care of injured patients.

Unlabelled: Approximately 13% of thermally injured patients fail resuscitation, in that they die during the first 48 h postburn despite full resuscitative efforts. The purpose of this study was to characterize these patients, and to develop a predictor of resuscitation failure., Methods: Records of 3807 thermally injured patients admitted to this burn centre during 1980-1997 were reviewed. Patients were classified as surviving to hospital discharge ("NONFAIL/LIVE"), as surviving resuscitation but dying later ("NONFAIL/DIE"), or as failing resuscitation ("FAIL"). Ordinal logistic regression was used to develop a predictor of membership in each of these three groups., Results: With respect to total burn size, full-thickness burn size, and inhalation injury, the three groups represented a gradation in injury severity from least severe (NONFAIL/LIVE) to most severe (FAIL). The predictive model had an overall accuracy of 91.6%; however, it correctly classified NONFAIL/LIVE patients more often (97.7% accuracy) than it did NONFAIL/DIE patients (57.5%) or FAIL patients (16.1%)., Conclusion: Patients who failed resuscitation were more severely injured than those who survived resuscitation, but was not possible accurately to predict who will fail resuscitation using data available on admission.

Unlabelled: Chemical burn injury meets the criteria of the American Burn Association for treatment at a specialized burn facility. Over a 51-year period, we have treated 276 patients with chemical burn injury including 146 white phosphorus injuries. In this study, we compare incidence, cause and outcome of chemical burn injury over time and review the management of white phosphorus injuries., Methods: Data for the period 1986-2000 was obtained by retrospective chart review. Data for the period 1950-1985 was obtained from previous studies and from retrospective chart review., Results: Chemical burn injury comprised 2.1% of all admissions between 1969 and 1985, and 2.07% between 1986 and 2000. The mean body surface area involved was 19.5% in the first 19 years of the study compared with 8.6% over the last 15 years. Mortality increased from 5.4% between 1950 and 1968 to 13.8% between 1969 and 1985. Mortality from 1986 to 2000 was 0%. Hospital length of stay decreased from a mean of 90 days in the first 19 years of the study to a mean of 15 days in the most recent 15-year period. The chemical responsible for injury was white phosphorus in 146 cases., Conclusions: Over time, the proportion of burn center admissions caused by chemical injury is constant, while the average total burn size, full thickness burn size, length of stay and mortality have decreased. During peacetime, the chemicals responsible are similar to those seen in civilian burn centers. The experience of this center with burns caused by white phosphorus is unique and needs to be maintained for future conflicts.

To elucidate potential dose-dependent mechanisms associated with wood smoke inhalation injury, the present study evaluated antioxidant status and the extent of pulmonary injury in sheep after graded exposure to smoke. Adult, male sheep (n=4-5 per group) were anesthetized and received 0, 5, 10 or 16 units of cooled western pine bark smoke, corresponding to 0, 175, 350 and 560 s, respectively, of smoke dwell time in the airways and lung. Smoke was mixed at a 1:1 ratio with 100% O2 to minimize hypoxia. Plasma and expired breath samples were collected pre-smoke, and 6, 12, 18, 24, 36 and 48 h after smoke exposure. Sheep were euthanatized 48 h after smoke exposure and lung and airway sections were evaluated histologically for injury and biochemically for indices of oxidative stress. Plasma thiobarbituric acid reactive substances (TBARS) were 66 and 69% higher than controls after moderate and severe smoke exposure at 48 h, whereas total antioxidant potential was not statistically different among groups at any time after exposure. Lung TBARS showed a dose-dependent response to smoke inhalation and were approximately 2-, 3- and 4-fold higher, respectively, than controls after exposure to 5, 10 and 16 units of smoke. Lung myeloperoxidase (MPO) activity was also higher in smoke-exposed animals than controls, and MPO activity was markedly elevated (19- and 22-fold higher than controls in right apical and medial lobes) in response to severe smoke exposure. Smoke exposure also induced a dose-dependent injury to tracheobronchial epithelium and lung parenchyma. Taken together these data show that few indices of oxidative stress responded in a dose-dependent manner to graded doses of smoke inhalation, although most of the indices measured in lung were affected by the highest dose of smoke. Additional time course studies are necessary to determine whether these oxidants are a cause or a consequence of the airway and lung injury associated with exposure to wood smoke.