High-volume hemofiltration in adult burn patients with septic shock and acute kidney injury: a multicenter randomized controlled trial.

BACKGROUND: Sepsis and septic shock occur commonly in severe burns. Acute kidney injury (AKI) is also common and often results as a consequence of sepsis. Mortality is unacceptably high in burn patients who develop AKI requiring renal replacement therapy and is presumed to be even higher when combined with septic shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood purification technique would be beneficial in this population. METHODS: We conducted a multicenter, prospective, randomized, controlled clinical trial to evaluate the impact of HVHF on the hemodynamic profile of burn patients with septic shock and AKI involving seven burn centers in the United States. Subjects randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while control subjects were managed in standard fashion in accordance with local practices. RESULTS: During a 4-year period, a total of nine subjects were enrolled for the intervention during the ramp-in phase and 28 subjects were randomized, 14 each into the control and HVHF arms respectively. The study was terminated due to slow enrollment. Ramp-in subjects were included along with those randomized in the final analysis. Our primary endpoint, the vasopressor dependency index, decreased significantly at 48 hours compared to baseline in the HVHF group (p = 0.007) while it remained no different in the control arm. At 14 days, the multiple organ dysfunction syndrome score decreased significantly in the HVHF group when compared to the day of treatment initiation (p = 0.02). No changes in inflammatory markers were detected during the 48-hour intervention period. No significant difference in survival was detected. No differences in adverse events were noted between the groups. CONCLUSIONS: HVHF was effective in reversing shock and improving organ function in burn patients with septic shock and AKI, and appears safe. Whether reversal of shock in these patients can improve survival is yet to be determined. TRIAL REGISTRATION: Clinicaltrials.gov NCT01213914 . Registered 30 September 2010.

Epidemiology and outcomes of pediatric burns over 35 years at Parkland Hospital.

BACKGROUND: Since opening its doors in 1962, the Parkland Burn Center has played an important role in improving the care of burned children through basic and clinical research while also sponsoring community prevention programs. The aim of our study was to retrospectively analyze the characteristics and outcomes of pediatric burns at a single institution over 35 years. STUDY DESIGN: The institutional burn database, which contains data from January 1974 until August 2010, was retrospectively reviewed. Patients older than 18 years of age were excluded. Patient age, cause of burn, total body surface area (TBSA), depth of burn, and patient outcomes were collected. Demographics were compared with regional census data. RESULTS: Over 35 years, 5748 pediatric patients were admitted with a thermal injury. Males comprised roughly two-thirds (66.2%) of admissions. Although the annual admission rate has risen, the incidence of pediatric burn admissions, particularly among Hispanic and African American children has declined. The most common causes of admission were scald (42%), flame (29%), and contact burns (10%). Both the median length of hospitalization and burn size have decreased over time (r(2)=0.75 and 0.62, respectively). Mortality was significantly correlated with inhalation injury, size of burn, and history of abuse. It was negatively correlated with year of admission. CONCLUSIONS: Over 35 years in North Texas, the median burn size and incidence of pediatric burn admissions has decreased. Concomitantly, length of stay and mortality have also decreased.

A prospective, randomised study of a novel transforming methacrylate dressing compared with a silver-containing sodium carboxymethylcellulose dressing on partial-thickness skin graft donor sites in burn patients.

This prospective, randomised study compares a new transforming methacrylate dressing (TMD) with a silver-containing carboxymethylcellulose dressing (CMC-Ag) after application to split-thickness skin graft (STSG) donor sites. This was an unblinded, non-inferiority, between-patient, comparison study that involved patients admitted to a single-centre burn unit who required two skin graft donor sites. Each patient's donor sites were covered immediately after surgery: one donor site with TMD and the other with CMC-Ag. The donor sites were evaluated until healing or until 24 days post-application, whichever came first. Study endpoints were time to healing, daily pain scores, number of dressing changes, patient comfort and physicians' and patients' willingness to use the dressings in the future. Nineteen patients had both the dressings applied. No statistically significant difference was noted in time to healing between the two dressings (14·2 days using TMD compared with 13·2 days using CMC-Ag). When pain scores were compared, TMD resulted in statistically significantly less pain at three different time periods (2-5 days, 6-10 days and 11-15 days; P < 0·001 at all time periods). Patients also reported greater comfort with TMD (P < 0·001). Users rated TMD as being less easy to use because of the time and technique required for application. Reductions in pain and increased patient comfort with the use of the TMD dressing, compared with CMC-Ag, were seen as clinical benefits as these are the major issues in donor site management.

Obesity and outcomes following burns in the pediatric population.

PURPOSE: While obesity is associated with increased mortality and decreased functional outcomes in adult burn patients, the ramifications of larger than average body size in the pediatric burn population are less well understood. The present study examines whether obesity was associated with poor outcomes following pediatric burn injuries. METHODS: Thermal injury data for patients ≤ 18 years of age admitted to a Level III burn center over ten years (n=536) was analyzed. Obesity was defined as ≥ 95 th percentile of weight for height according to the WHO growth charts (<2 years of age) or BMI for age according to the CDC growth charts (2-18 years of age). Outcomes were compared between thermally injured obese (n=154) and non-obese (n=382) children. All data was collected in accordance with IRB regulations. RESULTS: Obese and non-obese thermally-injured children did not differ in TBSA, percentage of full thickness burn, or overall mortality. However, these groups were significantly different with respect to age (obese=7.16 ± 0.46 years, non-obese=9.38 ± 0.32 years, p<0.001) and days requiring mechanical ventilation (obese=4.89 ± 1.3 days, non-obese=2.67 ± 0.49 days, p<0.05). For thermally injured children admitted to the BICU without inhalation injury (n=175); the obese (n=46) and non-obese (n=129) did not differ significantly with respect to age, TBSA, percentage of full thickness burn or other outcome measures. However, significant differences between these groups were noted for ICU LOS (obese=18.59 ± 5.18 days, non-obese=9.51 ± 1.82 days, p<0.05) and number of days requiring mechanical ventilation (obese=11.65 ± 3.91 days, non-obese=3.92 ± 0.85 days, p<0.05). CONCLUSION: These data show thermally-injured obese pediatric patients required longer and more intensive medical support in the form of BICU care and respiratory intervention. Counter to findings in adult populations, differences in mortality were not observed. Collectively, these findings suggest obesity as a risk factor for increased morbidity in the pediatric burn population.

A TREM-1 Polymorphism A/T within the Exon 2 Is Associated with Pneumonia in Burn-Injured Patients.

Background. The triggering receptor expressed in myeloid cells (TREM-1) is a key mediator in the activation of the local inflammatory response during lung infections. We aimed to evaluate the effect of a functionally relevant TREM-1 single nucleotide polymorphism within the exon 2 (A→T) on the development of pneumonia in burn patients. Objective. To determine whether a single nucleotide polymorphism (SNP) within the exon 2 (A→T) in the TREM-1 gene is associated with ventilator-associated pneumonia (VAP) in burn-injured patients. Methods. 540 patients with ≥10% total body surface area (TBSA) burn injuries or inhalation injury were prospectively enrolled. The influence of a polymorphism (A→T) in exon 2 of the TREM-1 gene was evaluated for association with increased risk of pneumonia by logistic regression analysis. Measurements and Main Results. 209 patients met criteria for VAP. Multivariate regression analysis showed that, after adjustment for potential confounders, we found that carriage of the TREM-1 T allele is associated with more than a 3-fold increased risk of VAP (OR 6.3, 95% CI 4-9). Conclusions. A TREM-1 single nucleotide polymorphism within the exon 2 (A→T) is associated with the development of pneumonia in burn patients.

Association of mitochondrial allele 4216C with increased risk for sepsis-related organ dysfunction and shock after burn injury.

Impaired mitochondrial activity has been linked to increased risk for clinical complications after injury. Furthermore, variant mitochondrial alleles have been identified and are thought to result in decreased mitochondrial activity. These include a nonsynonymous mitochondrial polymorphism (T4216C) in the nicotinamide adenine dinucleotide dehydrogenase 1 gene (ND1), encoding a key member of complex I within the electron transport chain, which is found almost exclusively among Caucasians. We hypothesized that burn patients carrying ND1 4216C are less able to generate the cellular energy necessary for an effective immune response and are at increased risk for infectious complications. The association between 4216C and outcome after burn injury was evaluated in a cohort of 175 Caucasian patients admitted to the Parkland Hospital with burns covering greater than or equal to 15% of their total body surface area or greater than or equal to 5% full-thickness burns under an institutional review board-approved protocol. To remove confounding unrelated to burn injury, individuals were excluded if they presented with significant non-burn-related trauma (Injury Severity Score > or =16), traumatic or anoxic brain injury, spinal cord injury, were HIV/AIDS positive, had active malignancy, or survived less than 48 h postadmission. Within this cohort of patients, carriage of the 4216C allele was significantly associated by unadjusted analysis with increased risk for sepsis-related organ dysfunction or septic shock (P = 0.011). After adjustment for full-thickness burn size, inhalation injury, age, and sex, carriage of the 4216C allele was associated with complicated sepsis (adjusted odds ratio = 3.7; 95% confidence interval, 1.5-9.1; P = 0.005), relative to carriers of the T allele.

Epistatic interactions are critical to gene-association studies: PAI-1 and risk for mortality after burn injury.

Replication of statistically significant associations between single nucleotide polymorphisms (SNPs) and disease phenotypes has been problematic. One reason for conflicting observations may be failure to consider confounding factors, including gene-gene (epistatic) interactions. Our experience with the insertion/deletion polymorphism at -688 in the promoter region of plasminogen activator inhibitor (PAI-1) seems to support this contention and may foreshadow problems for genome-wide association scans, which tend to use unadjusted analytical methodologies. One hundred forty-nine patients with > or =15% total body surface area (TBSA) burns, without significant nonburn-related trauma (injury severity score < or =16), traumatic or anoxic brain injury or spinal cord injury who survived >48 hours postadmission were enrolled under a protocol approved by the UT Southwestern and Parkland Hospital IRBs. Clinical data were collected prospectively and candidate polymorphisms in PAI-1 (-688), toll-like receptor 4 (+896), CD14 (-159), tumor necrosis factor-alpha (-308), and interleukin-6 (-174) were genotyped. The PAI-1 SNP was significantly associated (P-value for trend = 0.036) with risk for death when evaluated in isolation by unadjusted analysis. However, after adjustment for potential confounders using multiple logistic regression, only age, full-thickness burn size, and CD14 genotype (as previously reported) were associated with increased mortality. Genetic association analyses should be adjusted for interactions between multiple SNPs, injury or disease characteristics, and demographic variables. Increasingly sophisticated analytical methods will be required as gene-mapping studies transition from a candidate-gene based approach to genome-wide association scans.

Self-esteem measurement before and after summer burn camp in pediatric burn patients.

Pediatric burn injury results in significant mortality and morbidity, from which some children will experience prolonged psychological and social difficulty. As early as 1967, it was noted that participation in a group was important in the resolution of problems caused by severe disability and stressful experiences. Since 1982, there have been summer burn camps for children and adolescent burn survivors. The primary focus of camp is to have "fun" at the various daily activities. The principal goal, however, is psychosocial readjustment. Fifty-three burn survivors attended the 1-week duration annual summer camp. Campers were invited to complete a Rosenberg Self-Esteem Scale on the first day of summer burn camp and shortly after the camp ended. Younger children were assisted with the survey tool by their parents. Of the 53 campers, 45 completed both pre- and postcamp surveys. The age of the campers ranged from 6 to 18 years (mean, 12.8 years). Burn size ranged from 1% to 90% TBSA (mean, 30.4% TBSA). The interval from date of injury to camp attendance was 2 months to 15.5 years. Nine campers had never attended burn camp before this year. Twenty- nine percent of the campers had an increase in self-esteem score. Fifty-eight percent had no change, and 13% demonstrated a decrease. The burn camp experience though an enriching summer activity, did not necessarily increase self-esteem in the majority of campers as measured by the survey tool employed.

Effects of oxandrolone on outcome measures in the severely burned: a multicenter prospective randomized double-blind trial.

Severe burns induce pathophysiologic problems, among them catabolism of lean mass, leading to protracted hospitalization and prolonged recovery. Oxandrolone is an anabolic agent shown to decrease lean mass catabolism and improve wound healing in the severely burned patients. We enrolled 81 adult subjects with burns 20% to 60% TBSA in a multicenter trial testing the effects of oxandrolone on length of hospital stay. Subjects were randomized between oxandrolone 10 mg every 12 hours or placebo. The study was stopped halfway through projected enrollment because of a significant difference between groups found on planned interim analysis. We found that length of stay was shorter in the oxandrolone group (31.6 +/- 3.1 days) than placebo (43.3 +/- 5.3 days; P < .05). This difference strengthened when deaths were excluded and hospital stay was indexed to burn size (1.24 +/- 0.15 days/% TBSA burned vs 0.87 +/- 0.05 days/% TBSA burned, P < .05). We conclude that treatment using oxandrolone should be considered for use in the severely burned while hepatic transaminases are monitored.

Electrical injuries: a 20-year review.

Electrical injuries continue to present problems with devastating complications and long-term socioeconomic impact. The purpose of this study is to review one institution's experience with electrical injuries. From 1982 to 2002, there were 700 electric injury admissions. A computerized burn registry was used for data collection and analysis. Of these injuries, 263 were high voltage (> or =1000 V), 143 were low voltage (<1000 V), 277 were electric arc flash burns, and 17 were lightning injuries. Mortality was highest in the lightning strikes (17.6%) compared with the high voltage (5.3%) and low voltage (2.8%) injuries, and mortality was least in electric arc injuries without passage of current through the patient (1.1%). Complications were most common in the high-voltage group. Mean length of stay was longest in this group (18.9 +/- 1.4 days), and the patients in this group also required the most operations (3 +/- 0.2). Work-related activity was responsible for the majority of these high-voltage injuries, with the most common occupations being linemen and electricians. These patients tended to be younger men in the prime of their working lives. Electrical injuries continue to make up an important subgroup of patients admitted to burn centers. High-voltage injuries in particular have far reaching social and economic impact largely because of the patient population at greatest risk, that is, younger men at the height of their earning potential. Injury prevention, although appropriate, remains difficult in this group because of occupation-related risk.