January 2024 - Burn Trauma
January 2024
EAST Monthly Literature Review
"Keeping You Up-to-Date with Current Literature"
Brought to you by the EAST Manuscript and Literature Review Committee
This issue was prepared by EAST Burn Surgery Committee Members Victoria Miles, MD, Lauren Nosanov, MD and Shawn Tejiram, MD.
Thank you to Haemonetics for supporting the EAST Monthly Literature Review.
In This Issue: Burn Trauma
Article 1 reviewed by Victoria Miles, MD and Lauren Nosanov, MD
A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries. Heyland DK, Wibbenmeyer L, Pollack J, et al. N Engl J Med. 2022 Sep 15;387(11):1001-1010.
Article 2 reviewed by Victoria Miles, MD and Lauren Nosanov, MD
Burn Resuscitation Practices in North America: Results of the Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT). Greenhalgh DG, Cartotto R, Taylor SL, et al. Ann Surg. 2023 Mar 1; 277(3):512-519.
Article 3 reviewed by Shawn Tejiram, MD
Modified Frailty Index is an Independent Predictor of Death in the Burn Population: A Secondary Analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) Study. Sen S, Romanowski KS, Andre JA, Greenhalgh DG, Palmieri TL. J Burn Care Res. 2023 Mar 2;44(2):257-261.
Article 4 reviewed by Shawn Tejiram, MD
Inhalation Injury Severity Score on Admission Predicts Overall Survival in Burn Patients. Flinn AN, Bohan PM, Rauschendorfer C, Le TD, Rizzo JA. J Burn Care Res. 2023 Nov 2;44(6):1273-1277.
Article 1
A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries. Heyland DK, Wibbenmeyer L, Pollack J, et al. N Engl J Med. 2022 Sep 15;387(11):1001-1010.
Optimizing nutrition in a state of significant inflammation and catabolism is critical to improving burn patient outcomes. Conflicting studies have been published evaluating the efficacy of enteral glutamine supplementation in reducing burn morbidity and mortality. This randomized controlled trial was conducted worldwide including patients with second- and third-degree burns treated in the United States, Canada, Europe, Latin America, and Asia. Adult patients were eligible for inclusion if they sustained burns affecting ?10% to ?20% total body surface area (depending on age). Excluded patients included those who had not provided consent within 72 hours of admission, were expected to not survive the burn injury, or had a contraindication to receiving enteral nutrition. Glutamine powder was administered to enrolled patients every four hours until seven days from the last skin graft procedure, discharge, or 3 months stay was reached in the burn facility. Dosage was dependent on body weight. Placebo patients received non-isonitrogenous placebo. Originally, six-month mortality was the primary outcome; time to discharge alive was the secondary outcome. The authors initially planned to enroll 2700 patients to achieve 80% power. However, the sample size was deemed unfeasible at 4 years of study enrollment, and the primary outcome was adjusted to time to discharge alive and the secondary outcome was adjusted to six-month mortality.
From May 2011 to June 2021, 1209 patients were enrolled from 54 burn centers in 14 countries. Nine patients were excluded secondary to death, consent withdrawal, or discharge prior to receiving glutamine/placebo. Therefore, 1200 patients were studied with 596 receiving glutamine and 604 receiving placebo. Protocol adherence was excellent at 91%. The demographics and clinical characteristics were similar between groups. Overall, the authors found no difference in time to discharge alive when the glutamine and placebo groups were compared (40 days – glutamine, 38 days – placebo, p=0.17). Subgroup analyses and covariate adjustment did not alter the results. The authors were able to collect follow-up six-month data for approximately 75% of patients; no difference was noted in 6-month mortality. Additionally, tertiary outcomes including in-hospital mortality, gram negative bacteremia, and length of stay were similar between groups. Importantly, while small increases in urea levels were observed in patients receiving glutamine, there was no impact on rates of acute kidney injury or use of renal replacement therapy, and overall rates of serious adverse events were similar between the two groups. The authors concluded supplemental enteral glutamine does not decrease burn injury mortality or time to discharge alive. While the authors acknowledge that the primary weakness of the study is the low accrual requiring alteration of the sample size and primary outcome, the study is notably larger and more robust than preceding similar efforts. It remains to be seen if the findings of RE-ENERGIZE significantly impact clinical utilization of enteral glutamine supplementation in burn centers.
Article 2
Burn Resuscitation Practices in North America: Results of the Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT). Greenhalgh DG, Cartotto R, Taylor SL, et al. Ann Surg. 2023 Mar 1; 277(3):512-519.
Since the 1947 publication of the Burn Budget Formula and the subsequent introductions of the Evans, Brooke, Modified Brooke, and Parkland formulas, much controversy has revolved around the optimal resuscitative volume and fluid choice for the treatment of acute burn injury. One of the most significant points of contention has been utilization of adjunctive colloid. A large, multicenter trial has long been needed to evaluate the efficacy of albumin. To facilitate this future trial and help tailor its eventual design, the authors hoped to prospectively characterize the use of albumin and crystalloid resuscitation in burn centers of the United States and Canada. (The ongoing follow-up study ABRUPT2 is separately detailed below). The ABRUPT study is a multicenter, non-interventional, prospective observational trial conducted at 21 burn centers across the United States and Canada with the intent to evaluate the use of albumin and crystalloid in the resuscitation of burn patients during the 48 hours post-injury. The authors collected hour-by-hour data including fluid infusion rates, laboratory values, and vital signs. Inclusion criteria included age ≥ 18 years, admission ≤ 12 hours from injury, and acute burn ≥ 20% total body surface area (TBSA). Exclusion criteria included concomitant, significant trauma, surgical burn excision within 48 hours, high voltage electrical injury, comfort care institution or death within 48 hours, or pre-existing severe cardiovascular, hepatic, or renal disease. In addition, patients were excluded if they received other colloids (fresh frozen plasma or hydroxyethyl starch), ascorbic acid, or hypertonic saline. The authors intended to enroll 366 subjects (183/group) to achieve 90% power. The primary outcome was defined as the total fluid resuscitation volume in ml/kg/%TBSA burn at 24 and 48 hours. Secondary outcomes included the in-to-out ratio (ml/kg/%TBSA burn divided by total urine output in ml/kg), albumin proportion (ml albumin divided by total fluid ml), and time to complete resuscitation. Complications including escharotomies, fasciotomies, abdominal compartment syndrome, vasopressor requirement, and acute kidney injury were assessed. Duration of mechanical ventilation, length of stay, and 28-day and in-hospital survival were evaluated.
From April 2017 to June 2020, data from 379 patients meeting inclusion criteria was analyzed. Two-thirds (253 patients) were resuscitated with a combination of albumin and crystalloid, while one-third (126 patients) received crystalloid alone. Body habitsus was similar between groups. Overall, crystalloid was used as the sole resuscitative fluid in patients who were younger, less sick, and had less severe injuries. The albumin group was older (48 vs 42.9 years), sustained a larger (36% vs 24.7%) and deeper (15% vs 0% full thickness) %TBSA burn, and presented with inhalation injury more frequently (17.4% vs 3.2%). Accordingly, there was higher morbidity and mortality in the albumin group, including increased rates of fasciotomy, abdominal compartment syndrome, and renal failure, as well as longer durations of mechanical ventilation and length of stay. Both 28-day and in-hospital survival rates were worse in the albumin group. Albumin utilization was, however, noted to improve in-to-out ratios. The authors caution that the ABRUPT study is not meant to “solve the ‘crystalloid versus colloid’ question”, but rather to shed light on current practices. When crystalloid resuscitation is excessive, there is a tendency to add albumin to crystalloid, and this is often followed by a precipitous drop in fluid requirements and an improvement in the I/O ratio. Findings were in support of continuing to utilize the Parkland Formula target of 4 ml/kg/%TBSA for the first 24 hours with a goal urine output of 0.5-1.0 ml/kg/hr. The authors acknowledge that the study is inherently limited by its observational design, but conclude that the findings were significant enough to justify moving forward with a prospective, randomized, multicenter trial.
Ongoing Research
The Acute Burn ResUscitation Prospective Multicenter Trial 2 (ABRUPT2). Greenhalgh DG, Cartotto R.
The ABRUPT study laid the foundation for ABRUPT2 (The Acute Burn ResUscitation Multicenter Prospective Trial – 2) trial, a multi-center prospective randomized controlled trial which is actively enrolling. The study aims to compare the use of Lactated Ringers (LR) plus 5% albumin versus LR alone in the resuscitation of acute burn shock in adults with major burns. Eligible patients include adults (age 18 years and older) with total body surface area (TBSA) involvement of ? 25% with full thickness component ? 20% admitted to a burn center ? 12 hours post-injury with a plan for formal IV fluid resuscitation. Exclusion criteria include receipt of any colloid prior to enrollment, surgery that alters fluid resuscitation within 48 hours, concurrent traumatic injury, use of resuscitation adjuncts such as hypertonic saline or Vitamin C, and several pre-injury comorbidities. Results of the ABRUPT study were used to power ABRUPT2, with a goal enrollment of 400 patients. Investigators hypothesize that adjunctive albumin infusion initiated within 12 hours of injury will reduce fluid requirements and improve outcomes when compared to LR only resuscitation in the first 48 hours after injury. Randomization is based on intent to treat, and block randomization takes into account age, burn size, and the presence of smoke inhalation injury. The primary outcome of interest is total volume of fluid (ml/kg/% TBSA) at 24 and 48 hours after admission, while secondary outcomes include urinary output, in-to-out ratio, multiple measures of organ failure and over/under-resuscitation, crossover, and mortality. The study is ongoing and is anticipated to take approximately three years to accrue goal enrollment. The findings are likely to have a significant impact on burn resuscitation practices broadly.
Article 3
Modified Frailty Index is an Independent Predictor of Death in the Burn Population: A Secondary Analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) Study. Sen S, Romanowski KS, Andre JA, Greenhalgh DG, Palmieri TL. J Burn Care Res. 2023 Mar 2;44(2):257-261.
Severe burn injury produces significant stress on an individual and their response to this stress can determine survival and recovery. Age and severity of burn injury has traditionally been used to determine likelihood of survival following a burn injury. Further literature indicate that frailty may better reflect the capacity to survive and recover from a severe burn injury. Despite this, work examining the impact of frailty on recovery following burn injury is limited. The authors of this work sought to examine the predictive probability of mortality following burn injury using the 11 item and 5 item Modified Frailty Index. The authors utilized an established dataset from the Transfusion Requirement in Burn Care Evaluation Study (TRIBE). The TRIBE trial was originally a multicenter, randomized controlled study of allogenic blood transfusion in adult burn patients, specifically examining transfusion practices using a liberal goal (hemoglobin less than 10 g/dL) versus a restrictive goal (hemoglobin less than 7 g/dL). This resulted in a total of 347 patients included for study. Patients were retrospectively scored using the Modified Frailty Index-11, a frailty index developed from data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) and is modeled after the 70 item Canada Study of Health and Aging Frailty Index (CSHA-FI). The Modified Frailty Index 5 (MFI-5) was developed in 2015 when the NSQIP database collected only 5 of the factors of the MFI-11, but has a strong correlation to MFI-11 in predicting outcomes. Factors collected in both the MFI-11 and MFI-5 including functional status, presence of diabetes, respiratory problems, presence of cardiovascular disease, and, specific to MFI-11, neurocognitive issues.
Of the 347 patients included for analysis, the mean age of patients was 43 ± 17 years and 79% of the patients were male. The mean total TBSA (second and third degree burn injury) was 38 ± 18% and mean third degree TBSA was 20 (5–32.5)%. Twenty-three percent (80) patients suffered an inhalation injury. Forty-three patients died (25%) during admission and these patients were older (55 ± 18 years vs 41 ± 15 years), comprised of higher proportion of women (33% vs 17%) and suffered a more severe burn injury (TBSA: 48 ± 22% vs 35 ± 15%) compared to patients who survived to discharge. Patients who died suffered from more third degree burn injury [TBSA: 35 (19–51.5)% vs 18 (4–30)%] and inhalation injury (40% vs 19%) compared to survivors. Patients who died also had higher frailty scores for both MFI-5 [1 (0–2) vs 0] and MFI-11 [1 (0–2) vs 0] as well as higher APACHE scores (26 ± 8 vs 17 ± 7). The authors then grouped patients based on MFI-5 and MFI-11 scores of >1 to determine if a higher MFI-5 and MFI-11 score was significantly associated with death during admission. Thirty-seven (11%) patients had an MFI-5 score >1 (MFI-5 >1). These patients were significantly older (65 ± 12 vs 40 ± 15 years) than patients with an MFI-5 score of ≤1. More patients in the MFI-5 >1 group died during admission (42% vs 11%). For the MFI-11>1 group, 13% (43 patients) had an MFI-11 >1. The MFI-11 >1 group was also older (65 ± 12 vs 40 ± 15 years) compared to patients with an MFI-11 score ≤ 1. A significantly higher proportion of patients with an MFI-11 >1 died (41% vs 11%). Multivariate logistic analysis was performed to determine independent predictors for death during admission. Adjusted for age and total TBSA, MFI-11 scores [OR 1.83 (1.18–2.8)], and MFI-5 scores [1.86 (1.11–3.11)] were both independently associated with an increased risk of death during admission. MFI-11 score >1 was also independently associated with death during admission [OR 2.91 (1.1–7.7)], however MFI-5 score >1 was not independently associated with death [OR 2.6 (0.95–7)]. The authors note from their findings that both MFI-11 and MFI-5 were associated with increased risk of death following severe burn injury. They also note that scoring systems already exist to determine survivability in burn injury, such as the “Baux score” and “modified Baux score”, however these scoring systems do not account for an individual’s physiology and response to injury like frailty does. The authors conclude that frailty assessments can be powerful prognosticator tools in the assessment of patients following severe burn injury and in this particular study, MFI was used to highlight vulnerable burn injured patients. Despite this, no evidence based clinical interventions to mitigate or improve outcomes on frail burn patients exist. It is suggested that a mixed approach including “pre-habilitation” and aggressive ongoing physical therapy are likely best to optimize outcomes.
Article 4
Inhalation Injury Severity Score on Admission Predicts Overall Survival in Burn Patients. Flinn AN, Bohan PM, Rauschendorfer C, Le TD, Rizzo JA. J Burn Care Res. 2023 Nov 2;44(6):1273-1277.
Inhalation injury can cause direct thermal injury, or injury via the products of combustion. This generates both a localized and systemic inflammatory response characterized by mucosal sloughing, bronchial edema, bronchiole occlusion, deterioration of gas exchange, ARDS, and even mortality. As a result, acute determination of inhalation injury is paramount. Indirect findings such as hoarseness and singed facial hair may suggest inhalation injury but remain unreliable. Bronchoscopy remains the gold standard for diagnosis of inhalation injury and provides the basis of various injury scoring systems. Three scoring systems, the abbreviated injury score (AIS), inhalation injury severity score (I-ISS), and the bronchoscopic mucosal score (MS) each use an ordinal scale that allow for stratification of injury severity using bronchoscopic findings. The authors of this work sought to compare these three scoring systems and hypothesized strong correlation of scores between each scoring system and that higher scores correlate with worse clinical outcomes. Intubated patients admitted to a burn intensive care unit that underwent bronchoscopic evaluation within 24 hours of suspected inhalation injury were included for study. Variables collected included patient, injury, and treatment related variables such as TBSA involvement, injury severity score assessments, lab work, ventilator settings, and bronchoscopy images for assessment. Bronchoscopic images were de-identified and assessed by two blinded investigators using the AIS, I-ISS, and MS scoring systems to assess severity grade. The primary outcome assessed was in-hospital mortality. Secondary outcomes included development of pneumonia, ARDS, total ventilator days, ICU length of stay, and overall length of stay.
Of the patients included for study, 99 had a complete data set for final analysis. The majority of patients were male (63.6%) with a mean age of 48 (±18.7) years. The median %TBSA and ISS scores were 19.5% (9.0%–39.0%) and 25 (13–34), respectively. The median AIS, I-ISS, and MS scores were each 2 (representing moderate injury; IQR 1–3). Nearly half of patients (48.5%) developed pneumonia, 27.3% developed ARDS, and 23.2% died while hospitalized. Patients who died had a greater injury burden (median ISS 34.0 vs 19.5, P <.001) and %TBSA (median 51.0% vs 15.3%, P < .001). Median admission I-ISS scores were higher among patients who died compared to those who survived (2 [IQR 2–3] vs 2 [IQR 1–2], P = .03). There were no statistically significant differences between rates of pneumonia between survivors and nonsurvivors, (34.8% vs 52.6%, P = .13, and 26.3% vs 30.4%, P = .70, respectively). On univariate regression analysis, %TBSA, ISS, GCS, AIS, and I-ISS were all associated with survival, with more severe injuries (higher %TBSA, higher ISS, lower GCS, and higher AIS and I-ISS) associated with increased risk of mortality (all P < .05). None of the three scoring systems was associated with the development of either pneumonia or ARDS (all P > .05). After controlling for %TBSA, ISS, and GCS on multivariable regression, only I-ISS was independently associated with survival (OR 3.63, 95% CI 1.40–9.40; P = .008). The authors concluded that I-ISS was independently associated with overall survival and no scoring systems were predictive of pulmonary morbidities. The authors posit that correlation among scoring systems is likely due to overlap of categories assessed. The authors further note that current inhalation injury scoring systems may be limited in their ability to predict outcomes due to each grade being weighted equally during comparison. Based on prior literature, they suggest that broader “low-grade” and “high-grade” categorization may reveal more significant and meaningful findings and outcomes. Utilization of broader categorization may require agreement, generalizability, and consistency across literature to assess outcomes of interest in this context.
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