Extracorporeal Membrane Oxygenation in a Patient with Severe Inhalation Injury: Multidisciplinary Burn Team Care.

INTRODUCTION: Inhalation injury is a major risk factor for mortality in burn patients via 3 primary mechanisms: airway edema and obstruction, hypoxemic respiratory failure, and pneumonia. Currently, the mainstay of treatment is supportive care to include early intubation, lung-protective or high-frequency-percussive mechanical ventilation, nebulized heparin, and aggressive pulmonary toilet. Despite these treatments, a subset of these patients progress to severe acute respiratory distress syndrome (ARDS) for which rescue options are limited. CASE PRESENTATION: A 31-year-old woman was found down in a house fire. On admission to the burn intensive care unit, she was diagnosed with grade 3 smoke inhalation injury. Cutaneous thermal injury was absent. By hospital day 2, she developed worsening hypoxemia and hypercapnia despite maximal ventilatory support. She was placed on veno-venous extracorporeal membrane oxygenation (ECMO). She received an average of 2.2 hours of direct rehabilitation a day and completed out-of-bed modalities over 90% of total hospital days. After 159 hours, she was decannulated, and by hospital day 18, she was discharged home on supplemental oxygen. CONCLUSION: Current literature regarding ECMO in inhalation injury is limited, but a growing body of evidence suggests that treatment of severe smoke inhalation injury should include ECMO for those who fail conventional therapy.

Examining the association between military service history and outcomes after burn injury.

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.

Intravenous Autologous Bone Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.

Management of multiple frostbite casualties at a burn center: San Antonio, Texas, 12-20 February 2021.

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.

Critical Care of the Burn Patient.

Care of the critically ill burned patient must integrate a multidisciplinary care team composed of burn care specialists. As resuscitative mortality decreases more patients are surviving to experience multisystem organ failure relating to complications of their injuries. Clinicians must be aware of physiologic changes following burn injury and the implicated impacts on management strategy. Promoting wound closure and rehabilitation should be the backdrop for which management decisions are made.

Military Burn Care and Burn Disasters.

Mass-casualty incidents can occur because of natural disasters; industrial accidents; or intentional attacks against civilian, police, or in case of combat, military forces. Depending on scale and type of incident, burn casualties often with a variety of concomitant injuries can be anticipated. The treatment of life-threatening traumatic injuries should take precedent but the stabilization, triage, and follow-on care of these patients will require local, state, and often regional coordination and support.

Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target.

The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, and there is an unmet demand for pharmacologic therapies targeting the underlying pathology of ARDS in patients suffering from the illness. The complement cascade (ComC) plays an integral role in the regulation of both innate and adaptive immune responses. ComC activation can prime an overzealous cytokine storm and tissue/organ damage. The ARDS and acute lung injury (ALI) have an established relationship with early maladaptive ComC activation. In this review, we have collected evidence from the current studies linking ALI/ARDS with ComC dysregulation, focusing on elucidating the new emerging roles of the extracellular (canonical) and intracellular (non-canonical or complosome), ComC (complementome) in ALI/ARDS pathobiology, and highlighting complementome as a vital nexus of the pathobiological connectome for ALI/ARDS via its crosstalking with other systems of the immunome, DAMPome, PAMPome, coagulome, metabolome, and microbiome. We have also discussed the diagnostic/therapeutic potential and future direction of ALI/ARDS care with the ultimate goal of better defining mechanistic subtypes (endotypes and theratypes) through new methodologies in order to facilitate a more precise and effective complement-targeted therapy for treating these comorbidities. This information leads to support for a therapeutic anti-inflammatory strategy by targeting the ComC, where the arsenal of clinical-stage complement-specific drugs is available, especially for patients with ALI/ARDS due to COVID-19.

Immunopathological Alterations after Blast Injury and Hemorrhage in a Swine Model of Prolonged Damage Control Resuscitation.

Trauma-related hemorrhagic shock (HS) remains a leading cause of death among military and civilian trauma patients. We have previously shown that administration of complement and HMGB1 inhibitors attenuate morbidity and mortality 24 h after injury in a rat model of blast injury (BI) and HS. To further validate these results, this study aimed to develop a swine model and evaluate BI+HS-induced pathophysiology. Anesthetized Yucatan minipigs underwent combined BI and volume-controlled hemorrhage. After 30 min of shock, animals received an intravenous bolus of PlasmaLyte A and a continuous PlasmaLyte A infusion. The survival rate was 80% (4/5), and the non-survivor expired 72 min post-BI. Circulating organ-functional biomarkers, inflammatory biomarkers, histopathological evaluation, and CT scans indicated evidence of multiple-organ damage, systemic innate immunological activation, and local tissue inflammation in the injured animals. Interestingly, a rapid and dramatic increase in plasma levels of HMGB1 and C3a and markedly early myocarditis and encephalitis were associated with early death post-BI+HS. This study suggests that this model reflects the immunopathological alterations of polytrauma in humans during shock and prolonged damage control resuscitation. This experimental protocol could be helpful in the assessment of immunological damage control resuscitation approaches during the prolonged care of warfighters.

Adjusting body weight for edema in severely burned patients.

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, R2 = 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.

Immunopathology of terminal complement activation and complement C5 blockade creating a pro-survival and organ-protective phenotype in trauma.

BACKGROUND AND PURPOSE: Traumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo. EXPERIMENTAL APPROACH: Complement activation products and cytokines were analysed in plasma from 54 combat casualties. The correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed. Nomacopan was administered to rats subjected to lethal TH (blast injury and haemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiological parameters, and laboratory profiles. KEY RESULTS: Early TCA was associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with the severity of tissue damage and mortality. The addition of nomacopan to a damage-control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved haemodynamics and metabolism, attenuated tissue and organ damage, and increased survival. CONCLUSION AND IMPLICATIONS: Previous findings of our and other groups revealed that early TCA represents a rational therapeutic target for trauma patients. Nomacopan as a pro-survival and organ-protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities.

The Phenomenon of Community Reintegration for Veterans with Burn Injury: Supportive Communities and Future-Oriented Thinking.

Combat missions in the Middle East have resulted in approximately 52,000 U.S. veterans who have been wounded in action, with 10% of whom suffered burn injuries. More than 90% of the wounded survived, but many were unable to return to military service. The purpose of this study was to investigate the factors that impacted reintegration of veterans with combat burn injuries. Using a mixed-methods approach and analysis, we asked veterans with combat burns "What was your experience reintegrating into the civilian community?" Additionally, we administered the Community Reintegration of Injured Service Members (CRIS) tool to measure the current level of reintegration. Six veterans with combat burn injury identified two major themes: supportive communities and future-oriented thinking. Supportive communities are defined as communities that are veteran-specific, provide long-term burn/injury care, are financially beneficial, and support hobbies, education, and work opportunities. Future-oriented thinking is defined as thinking in which a veteran experiences a turning point in recovery, has a desire to serve others, develops new meaning in life, and experiences posttraumatic growth. In both themes, peer support was a key component. Community reintegration was enhanced by future-oriented thinking and a supportive community, both of which can be buoyed by peer support. These findings are similar to other studies noting the importance of peer support for veterans. Studies of civilians burn survivors describe similar reintegration issues. These two factors may also be applicable to those survivors. Further qualitative inquiry into peer support in the burn community at large may reveal more actionable evidence which could enable burn survivors to meet the long-term goal of community reintegration.

Preferences for oral rehydration drinks among healthy individuals in Ghana: A single-blind, cross-sectional survey to inform implementation of an enterally based resuscitation protocol for burn injury.

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.

Burn injuries in US service members: 2001-2018.

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.

A Retrospective Cohort Study of Burn Casualties Transported by the US Army Burn Flight Team and US Air Force Critical Care Air Transport Teams.

INTRODUCTION: The US Army Burn Center, the only burn center in the Department of Defense provides comprehensive burn care. The Burn Flight Team (BFT) provides specialized burn care during transcontinental evacuation. During Operations Iraqi and Enduring Freedom, burn injuries accounted for approximately 5% of all injuries in military personnel. To augment BFT capacity, US Air Force Critical Care Air Transport Teams (CCATTs) mobilized to transport burn patients. The purpose of this study was to describe critically ill, burn injured patients transported to the US Army Burn Center by BFT or CCATT, to compare and contrast characteristics, evacuation procedures, in-flight treatments, patient injuries/illnesses, and outcomes between the two groups. MATERIALS AND METHODS: We conducted a retrospective cohort study of CCATT and BFT patients, admitted to the burn ICU between January 1, 2001 and September 30, 2018. Patients with total body surface area burned (TBSA) >30% were evacuated by BFT, while CCATT evacuated patients with ≤ 30% TBSA. RESULTS: Ninety-seven patients met inclusion criteria for this study. Of these, 40 (41%) were transported by the BFT and 57 (59%) were transported by CCATTs. Compared with patients transported by CCATTs, patients transferred by the BFT had higher median TBSA and full-thickness burn size, higher prevalence of chest, back and groin burns, and higher prevalence of inhalation injury. BFT patients had increased hospital days (62 vs. 37; P = .08), ICU days (29 vs. 12; P = .003) and ventilator days (14 vs. 6; P < .001). TBSA was the only variable significantly associated with ARDS (aOR = 1.04; 95% CI: 1.01, 1.08; P = 0.04), renal failure (aOR = 1.07; 95% CI: 1.03, 1.11; P = .002), and mortality (aOR = 1.08; 95% CI: 1.03, 1.13; P = .001). CONCLUSIONS: Evacuation by the BFT was associated with increased ICU and ventilator days, increased mortality, and a greater risk for developing renal failure. The severity of injury/TBSA likely accounted for most of these differences.

Analysis of the Utility of CO2 and Pulse-Dye Lasers Together and Separately in the Treatment of Hypertrophic Burn Scars.

INTRODUCTION: Hypertrophic burn scars (HTBSs) remain a significant source of morbidity. Contemporary treatment has evolved to use CO2 lasers and/or pulse-dye lasers (PDLs) to reduce scar thickness (ST) and erythema. This study seeks to compare treatment efficacy with CO2 or PDL individually and in combination. METHODS: Patients undergoing laser treatments for HTBSs were enrolled. Three 3 × 3 cm squares of HTBSs were randomized to receive treatment with CO2 laser, PDL or CO2 + PDL. Patients underwent 3 treatments, 4 to 6 weeks apart and were followed up over 3 to 6 months. Scar assessments occurred at each visit before treatment and consisted of photographs, ultrasound, colorimetry, and the Patient and Observer Scar Assessment Score. RESULTS: Twenty-five patients were enrolled. Twenty completed 2 treatments (80%) and 11 completed all 3 treatments (44%). Median initial ST was 0.3 cm. Median time since injury was 8 months. Hypertrophic burn scars treated with CO2 or PDL showed a significant decrease in Patient and Observer Scar Assessment Scale score from visit 1 to 3 (P = 0.01 and 0.01, respectively). When separated by ST, thick scars (≥0.3 cm) showed a significant decrease in thickness between visit 1 and 2 using all laser modalities (CO2 + PDL, P = 0.01; CO2, P = 0.02; PDL, P = 0.03). Thin scars (<0.3 cm) showed a reduction in thickness by visit 3 after CO2 + PDL or PDL alone (P = 0.01 and 0.04, respectively). Separating scars by age, younger scars (<9 months) showed a significant reduction in thickness between visit 1 and 2 for CO2 treatment (P = 0.04), and between visit 2 and 3 for CO2 + PDL treatment (P = 0.04). Hypertrophic burn scars treated with PDL did not demonstrate a significant reduction in thickness until visit 3 (P = 0.002). Older scars (≥9 months) showed a significant reduction in thickness between visit 1 and 2 only after CO2 + PDL (P = 0.01). CONCLUSIONS: Hypertrophic burn scars of varying ages, etiologies, and thicknesses were examined in this study with greater degree of early reduction seen in thicker scars using all laser modalities of CO2, PDL or in combination. However, there was no clinically meaningful benefit found with combination as compared with individual treatment. These data support the use of laser to improve HTBS but does not support one modality or combination of modalities over another.

Pooled safety analysis of STRATA2011 and STRATA2016 clinical trials evaluating the use of StrataGraft® in patients with deep partial-thickness thermal burns.

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.