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.

The Battle of the Titans-Comparing Resuscitation Between Five Major Burn Centers Using the Burn Navigator.

The goal of burn resuscitation is to provide the optimal amount of fluid necessary to maintain end-organ perfusion and prevent burn shock. The objective of this analysis was to examine how the Burn Navigator (BN), a clinical decision support tool in burn resuscitation, was utilized across five major burn centers in the United States, using an observational trial of 300 adult patients. Subject demographics, burn characteristics, fluid volumes, urine output, and resuscitation-related complications were examined. Two hundred eighty-five patients were eligible for analysis. There was no difference among the centers on mean age (45.5 ± 16.8 years), body mass index (29.2 ± 6.9), median injury severity score (18 [interquartile range: 9-25]), or total body surface area (TBSA) (34 [25.8-47]). Primary crystalloid infusion volumes at 24 h differed significantly in ml/kg/TBSA (range: 3.1 ± 1.2 to 4.5 ± 1.7). Total fluids, including colloid, drip medications, and enteral fluids, differed among centers in both ml/kg (range: 132.5 ± 61.4 to 201.9 ± 109.9) and ml/kg/TBSA (3.5 ± 1.0 to 5.3 ± 2.0) at 24 h. Post-hoc adjustment using pairwise comparisons resulted in a loss of significance between most of the sites. There was a total of 156 resuscitation-related complications in 92 patients. Experienced burn centers using the BN successfully titrated resuscitation to adhere to 24 h goals. With fluid volumes near the Parkland formula prediction and a low prevalence of complications, the device can be utilized effectively in experienced centers. Further study should examine device utility in other facilities and on the battlefield.

Impact of Alcohol and Methamphetamine Use on Burn Resuscitation.

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.

Higher Initial Formula for Resuscitation After Severe Burn Injury Means Higher 24-Hour Volumes.

Initial fluid infusion rates for resuscitation of burn injuries typically use formulas based on patient weight and total body surface area (TBSA) burned. However, the impact of this rate on overall resuscitation volumes and outcomes have not been extensively studied. The purpose of this study was to determine the impact of initial fluid rates on 24-hour volumes and outcomes using the Burn Navigator (BN). The BN database is composed of 300 patients with ≥20% TBSA, >40 kg that were resuscitated utilizing the BN. Four study arms were analyzed based on the initial formula-2 ml/kg/TBSA, 3 ml/kg/TBSA, 4 ml/kg/TBSA or the Rule of Ten. Total fluids infused at 24 hours after admission were compared as well as resuscitation-related outcomes. A total of 296 patients were eligible for analysis. Higher starting rates (4 ml/kg/TBSA) resulted in significantly higher volumes at 24 hours (5.2 ± 2.2 ml/kg/TBSA) than lower rates (2 ml/kg/TBSA resulted in 3.9 ± 1.4 ml/kg/TBSA). No shock was observed in the high resuscitation cohort, whereas the lowest starting rate exhibited a 12% incidence, lower than both the Rule of Ten and 3 ml/kg/TBSA arms. There was no difference in 7-day mortality across groups. Higher initial fluid rates resulted in higher 24-hour fluid volumes. The choice of 2ml/kg/TBSA as initial rate did not result in increased mortality or more complications. An initial rate of 2ml/kg/TBSA is a safe strategy.

Initial Results of the American Burn Association Observational Multicenter Evaluation on the Effectiveness of the Burn Navigator.

The objective of this multicenter observational study was to evaluate resuscitation volumes and outcomes of patients who underwent fluid resuscitation utilizing the Burn Navigator (BN), a resuscitation clinical decision support tool. Two analyses were performed: examination of the first 24 hours of resuscitation and the first 24 hours postburn regardless of when the resuscitation began, to account for patients who presented in a delayed fashion. Patients were classified as having followed the BN (FBN) if all hourly fluid rates were within ±20 ml of BN recommendations for that hour at least 83% of the time; otherwise, they were classified as not having followed BN (NFBN). Analysis of resuscitation volumes for FBN patients in the first 24 hours resulted in average volumes for primary crystalloid and total fluids administered of 4.07 ± 1.76 ml/kg/TBSA (151.48 ± 77.46 ml/kg) and 4.68 ± 2.06 ml/kg/TBSA (175.01 ± 92.22 ml/kg), respectively. Patients who presented in a delayed fashion revealed average volumes for primary and total fluids of 5.28 ± 2.54 ml/kg/TBSA (201.11 ± 106.53 ml/kg) and 6.35 ± 2.95 ml/kg/TBSA (244.08 ± 133.5 ml/kg), respectively. There was a significant decrease in the incidence of burn shock in the FBN group (P < .05). This study shows that the BN provides comparable resuscitation volumes of primary crystalloid fluid to the Parkland formula, recommends total fluid infusion less than the Ivy index, and was associated with a decreased incidence of burn shock. Early initiation of the BN device resulted in lower overall fluid volumes.

Challenges Associated with Managing a Multicenter Clinical Trial in Severe Burns.

Managing multicenter clinical trials (MCTs) is demanding and complex. The Randomized controlled Evaluation of high-volume hemofiltration in adult burn patients with Septic shoCk and acUte kidnEy injury (RESCUE) trial was a prospective, MCT involving the impact of high-volume hemofiltration continuous renal replacement therapy on patients experiencing acute kidney injury and septic shock. Ten clinical burn centers from across the United States were recruited to enroll a target sample size of 120 subjects. This manuscripts reviews some of the obstacles and knowledge gained while coordinating the RESCUE trial. The first subject was enrolled in February 2012, 22 months after initial IRB approval and 29 months from the time the grant was awarded. The RESCUE team consisted of personnel at each site, including the lead site, a data coordination center, data safety monitoring board, steering committees, and the sponsor. Seven clinical sites had enrolled 37 subjects when enrollment stopped in February 2016. Obstacles included changes in institutional review boards, multiple layers of review, staffing changes, creation and amendment of study documents and procedures, and finalization of contracts. Successful completion of a MCT requires a highly functional research team with sufficient patient population, expertise, and research infrastructure. Additionally, realistic timelines must be established with strategies to overcome challenges. Inevitable obstacles should be discussed in the pretrial phase and continuous correspondence must be maintained with all relevant research parties throughout all phases of study.

Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study.

Acute kidney injury (AKI) after severe burns is historically associated with a high mortality. Over the past two decades, various modes of renal replacement therapy (RRT) have been used in this population. The purpose of this multicenter study was to evaluate demographic, treatment, and outcomes data among severe burn patients treated with RRT collectively at various burn centers around the United States. After institutional review board approval, a multicenter observational study was conducted. All adult patients aged 18 or older, admitted with severe burns who were placed on RRT for acute indications but not randomized into a concurrently enrolling interventional trial, were included. Across eight participating burn centers, 171 subjects were enrolled during a 4-year period. Complete data were available in 170 subjects with a mean age of 51 ± 17, percent total body surface area burn of 38 ± 26% and injury severity score of 27 ± 21. Eighty percent of subjects were male and 34% were diagnosed with smoke inhalation injury. The preferred mode of therapy was continuous venovenous hemofiltration at a mean delivered dose of 37 ± 19 (ml/kg/hour) and a treatment duration of 13 ± 24 days. Overall, in hospital, mortality was 50%. Among survivors, 21% required RRT on discharge from the hospital while 9% continued to require RRT 6 months after discharge. This is the first multicenter cohort of burn patients who underwent RRT reported to date. Overall mortality is comparable to other critically ill populations who undergo RRT. Most patients who survive to discharge eventually recover renal function.