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Jeschke M.G.,University of Texas Medical Branch | Jeschke M.G.,Ross Tilley Burn Center | Gauglitz G.G.,Ludwig Maximilians University of Munich | Finnerty C.C.,University of Texas Medical Branch | And 3 more authors.
Annals of Surgery | Year: 2014

OBJECTIVE:: To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients. BACKGROUND:: Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival. METHODS:: A total of 230 severely burned children with burns exceeding 30% of the total body surface, requiring at least 1 surgical procedure were enrolled in this prospective cohort study. Demographics, clinical outcomes, and inflammatory and acute-phase responses (serum cytokines, hormones, and proteins) were determined at admission and at 11 time points for up to 180 days postburn. Statistical analysis was performed using a 1-way analysis of variance, the Student t test, χ test, and Mann-Whitney test where appropriate. RESULTS:: Survivors and nonsurvivors exhibited profound differences in critical markers of inflammation and metabolism at each time point. Nonsurvivors had significantly higher serum levels of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, C-reactive protein, glucose, insulin, blood urea nitrogen, creatinine, and bilirubin (P < 0.05). Furthermore, nonsurvivors exhibited a vastly increased hypermetabolic response that was associated with increases in organ dysfunction and sepsis when compared with survivors (P < 0.05). CONCLUSIONS:: Nonsurvivors have different trajectories in inflammatory, metabolic, and acute phase responses allowing differentiation of nonsurvivors from survivors and now possibly allowing novel predictive models to improve and personalize burn outcomes. © 2013 by Lippincott Williams & Wilkins.


Abdullahi A.,University of Toronto | Abdullahi A.,Ross Tilley Burn Center | Abdullahi A.,Sunnybrook Research Institute | Amini-Nik S.,University of Toronto | And 5 more authors.
Cellular and Molecular Life Sciences | Year: 2014

Burn injury is a severe form of trauma affecting more than 2 million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury, to elucidate the pathophysiology, and to explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. © 2014 Springer.


Abdullahi A.,Sunnybrook Research Institute | Jeschke M.G.,Sunnybrook Research Institute | Jeschke M.G.,University of Toronto | Jeschke M.G.,Ross Tilley Burn Center
Nutrition in Clinical Practice | Year: 2014

Thermal injury is a devastating injury that results in a number of pathological alterations in almost every system in the body. Hypermetabolism, muscle wasting, depressed immunity, and impaired wound healing are all clinical features of burns. Failure to address each of these specific pathological alterations can lead to increased mortality. Nutrition supplementation has been recommended as a therapeutic tool to help attenuate the hypermetabolism and devastating catabolism evident following burn. Despite the wide consensus on the need of nutrition supplementation in burn patients, controversy exists with regard to the type and amount of nutrition recommended. Nutrition alone is also not enough in these patients to halt and reverse some of the damage done by the catabolic pathways activated following severe burn injury. This has led to the use of anabolic pharmacologic agents in conjunction with nutrition to help improve patient outcome following burn injury. In this review, we examine the relevant literature on nutrition after burn injury and its contribution to the attenuation of the postburn hypermetabolic response, impaired wound healing, and suppressed immunological responses. We also review the commonly used anabolic agents clinically in the care of burn patients. Finally, we provide nutrition and pharmacological recommendations gained from prospective trials, retrospective analyses, and expert opinions based on our practice at the Ross Tilley Burn Center in Toronto, Canada. © 2014 American Society for Parenteral and Enteral Nutrition.


Stanojcic M.,Sunnybrook Research Institute | Chen P.,Sunnybrook Research Institute | Harrison R.A.,Sunnybrook Research Institute | Wang V.,Sunnybrook Research Institute | And 6 more authors.
Critical Care Medicine | Year: 2014

OBJECTIVES: Severe thermal injury is associated with extreme and prolonged inflammatory and hypermetabolic responses, resulting in significant catabolism that delays recovery or even leads to multiple organ failure and death. Burned patients exhibit many symptoms of stress-induced diabetes, including hyperglycemia, hyperinsulinemia, and hyperlipidemia. Recently, the nucleotide-binding domain, leucine-rich family (NLR), pyrin-containing 3 (NLRP3) inflammasome has received much attention as the sensor of endogenous "danger signals" and mediator of "sterile inflammation" in type II diabetes. Therefore, we investigated whether the NLRP3 inflammasome is activated in the adipose tissue of burned patients, as we hypothesize that, similar to the scenario observed in chronic diabetes, the cytokines produced by the inflammasome mediate insulin resistance and metabolic dysfunction. DESIGN: Prospective cohort study. SETTING: Ross Tilley Burn Centre & Sunnybrook Research Institute. PATIENTS: We enrolled 76 patients with burn sizes ranging from 1% to 70% total body surface area. All severely burned patients exhibited burn-induced insulin resistance and hyperglycemia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined the adipose tissue of control and burned patients and found, via flow cytometry and gene expression studies, increased infiltration of leukocytes -especially macrophages -and evidence of inflammasome priming and activation. Furthermore, we observed increased levels of interleukin-1β in the plasma of burned patients when compared to controls. CONCLUSIONS: In summary, our study is the first to show activation of the inflammasome in burned humans, and our results provide impetus for further investigation of the role of the inflammasome in burn-induced hypermetabolism and, potentially, developing novel therapies targeting this protein complex for the treatment of stress-induced diabetes. © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Li A.L.K.,Ross Tilley Burn Center | Gomez M.,Saint Johns Rehab Hospital | Fish J.S.,Ross Tilley Burn Center
Journal of Burn Care and Research | Year: 2010

The purpose of this study was to evaluate the effectiveness of pain management after electrical injury. A retrospective hospital chart review was conducted among electrically injured patients discharged from the outpatient burn clinic of a rehabilitation hospital (July 1, 1999, to July 31, 2008). Demographic data, numeric pain ratings (NPRs) at initial assessment and discharge, medications, nonpharmacologic modalities, and their effects before admission and after rehabilitation were collected. Pain management effects were compared between high (≥1000 v) and low (<1000 v) voltage, and between electrical contact and electrical flash patients, using Student's t-test and χ, with a P < .05 considered significant. Of 82 electrical patients discharged during the study period, 27 were excluded because of incomplete data, leaving 55 patients who had a mean age ±SD of 40.7 ± 11.3 years, TBSA of 19.2 ± 22.7%, and treatment duration of 16.5 ± 15.7 months. The majority were men (90.9%), most injuries occurred at work (98.2%), mainly caused by low voltage (n = 32, 58.2%), and the rest caused by high voltage (n = 18, 32.7%). Electrical contact was more common (54.5%) than electrical flash (45.5%). Pain was a chief complaint (92.7%), and hands were the most affected (61.8%), followed by head and neck (38.2%), shoulders (38.2%), and back torso (38.2%). Before rehabilitation, the most common medication were opioids (61.8%), relieving pain in 82.4%, followed by acetaminophen (47.3%) alleviating pain in 84.6%. Heat treatment was the most common nonpharmacologic modality (20.0%) relieving pain in 81.8%, followed by massage therapy (14.5%) alleviating pain in 75.0%. During the rehabilitation program, antidepressants were the most common medication (74.5%), relieving pain in 22.0%, followed by nonsteroidal antiinflammatory drugs (61.8%), alleviating pain in 70.6%. Massage therapy was the most common nonpharmacologic modality (60.0%), alleviating pain in 75.8%, and then cognitive behavioral therapy (54.5%), alleviating pain in 40.0%. There were pain improvements in all anatomic locations after rehabilitation except for the back torso, where pain increased 0.7 ± 2.9 points. Opioids were more commonly used in high voltage (P < .05), and cognitive behavioral therapy in low-voltage injuries (P < .05). Opioids were used in both electrical flash and electrical contact injuries. Pain in electrically injured patients remains an important issue and should continue to be addressed in a multimodal way. It is hoped that this study will guide us to design future interventions for pain control after electrical injury. © 2010 by the American Burn Association.


Jeschke M.G.,Ross Tilley Burn Center | Jeschke M.G.,University of Toronto
Journal of Burn Care and Research | Year: 2016

Hypermetabolism is the ubiquitous response to a severe burn injury, which was first described in the nineteenth century. Despite identification of important components of this complex response, hypermetabolism is still not well understood in its entirety. This article describes this incredibly fascinating response and the understanding we have gained over the past 100 years. Additionally, this article describes novel insights and delineates treatment options to modulate postburn hypermetabolism with the goal to improve outcomes of burn patients. Copyright © 2014 by the American Burn Association 1559-047X/2014.


Hall K.L.,Ross Tilley Burn Center | Shahrokhi S.,Ross Tilley Burn Center | Jeschke M.G.,Ross Tilley Burn Center
Nutrients | Year: 2012

Failure to adequately address the increased levels of inflammatory mediators, catecholamines and corticosteroids central to the hypermetabolic response post burn injury can lead to catastrophic results. One of the most important perturbations is provision of adequate and early nutrition. The provision of the right balance of macro and micronutrients, along with additional antioxidants is essential to mitigating the hypermetabolic and hypercatabolic state that results following a burn injury. As it is now widely accepted that enteral feeding is best practice for the burn population research has been more closely examining the individual components of enteral nutrition support. Recently fat to carbohydrate ratios, glutamine and antioxidants have made up the balance of this focus. This paper provides a review of the most recent literature examining each of these components and discusses the practices adopted in the Ross Tilley Burn Centre at Sunnybrook Health Sciences Centre. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


Shiga S.,Ross Tilley Burn Center | Cartotto R.,Ross Tilley Burn Center
Journal of Burn Care and Research | Year: 2010

Acute fluid requirements in toxic epidermal necrolysis (TEN) have neither been quantified nor reported. The purpose of this study was to examine acute fluid administration in TEN patients. A consecutive series of criteria and biopsy-confirmed cases of TEN admitted to our burn centre were selected for retrospective analysis. Charts were reviewed for demographic and resuscitation variables for the first (D0), second (D1), and third (D2) 24-hour periods after burn center admission. Twenty-one TEN cases were available for study, with a mean epidermal detachment of 53 ± 24% TBSA. Mortality was 29%, with all deaths occurring after the study period. Average crystalloid volumes decreased from D0 (2.2 ± 1.5 ml/kg/%TBSA) through D1 (1.6 ± 1.1 ml/kg/%TBSA) and D2 (1.4 ± 1.0 ml/kg/%TBSA), whereas urine output increased from D0 (1.3 ± 0.9 ml/kg/hr) through D1 (1.4 ± 0.9 ml/kg/hr) and D2 (1.8 ± 1.1 ml/kg/hr). Worst base deficit (BD) corrected significantly from D0 to D1 (P = .01) and from D1 to D2 (P = .002). There was no correlation between daily crystalloid volumes and %TBSA detachment. Nonsurvivors had significantly higher severity-of-illness score for TEN and 24-hour mean and worst BDs than survivors, but did not require significantly more crystalloid or display lower urine outputs. Initial provision of approximately 2 ml/kg/%TBSA epidermal detachment to patients with TEN resulted in more than adequate urine output and significant correction of the BD. We emphasize that these data do not represent a resuscitation formula but rather a guideline for initial fluid administration, which should then be titrated to the patient's response. © 2010 by the American Burn Association.


Walia G.,Ross Tilley Burn Center | Jada G.,Ross Tilley Burn Center | Cartotto R.,Ross Tilley Burn Center
Journal of Burn Care and Research | Year: 2011

High-frequency oscillatory ventilation (HFOV) is a mainstay in the ventilatory management of severe acute respiratory distress syndrome in our burn center. Many patients require burn surgery while on HFOV, potentially necessitating the use of HFOV during general anesthesia in the operating room. The purpose of this study was to describe the technique of providing and maintaining intraoperative HFOV. This is a retrospective analysis of the hospital and anesthesia records of all adult burn patients who went to the operating room on HFOV at our regional burn center between October 22, 1999, and April 30, 2009. There were 57 procedures performed on 36 patients who were receiving HFOV for severe acute respiratory distress syndrome available for analysis (age 45 ± 16 years, %TBSA burn 43 ± 14, % full-thickness burn 32 ± 19, and 69% with inhalation injury). Intraoperative HFOV settings were mean airway pressure 33 ± 4 cm H2O, frequency 5 ± 1 Hz, and FiO2 0.7 ± 0.2. There were no significant changes in oxygenation as measured by the PaO2/FiO2 ratio and the oxygenation index, but there was a transient but significant increase in PaCO2 intraoperatively. Existing continuous infusions of midazolam, opioids, and neuromuscular blockers were continued during surgey and were augmented by a variety of parenteral agents, including propofol, fentanyl, and ketamine during surgery. Prone positioning was required in 16 of 57 procedures. Subanalysis of the prone cases showed no significant changes in the PaO 2/FiO2 ratio or oxygenation index but again showed a significant but temporary increase in intraoperative PaCO2. HFOV was aborted for conventional mechanical ventilation in three cases due to respiratory deterioration (2 cases) and hemodynamic instability (1 case). There were no intraoperative deaths. In-hospital mortality was 33%. Intraoperative HFOV was feasible and safe in the overwhelming majority of cases, and aside from an inconsequential period of intraoperative hypercapnia, this was not associated with any hemodynamic instability or compromise in oxygenation. Copyright © 2011 by the American Burn Association.


Cartotto R.,Ross Tilley Burn Center | Zhou A.,Ross Tilley Burn Center
Journal of Burn Care and Research | Year: 2010

Fluid creep was recognized nearly a decade ago. Although many burn centers are now aware of fluid creep, it is not clear whether any reversal of this phenomenon has occurred. The purpose of this study was to examine whether we have made any headway in reversing fluid creep at our facility. This is a retrospective review of the first 48 hours of fluid resuscitation using the Parkland formula among patients with ≥15% TBSA burns admitted to our adult regional burn centre (BC) between January 1, 2000, and May 30, 2008. All values are reported as the mean ± SD. There were 196 consecutive resuscitations available for analysis. Group characteristics were age 46 ± 18 years, burn size 31% ± 15% (range 15-81%), and full-thickness burn size 13% ± 16%, with a 26% incidence of inhalation injury. The delay between injury and BC admission was 4.5 ± 2.6 hours. During this time, a total crystalloid volume of 1.5 ± 1.0 ml/kg/%burn, or nearly 40% of the recommended 24-hour Parkland volume, was administered. Total crystalloids given in the first 24 hours (prior to and within the BC) were 6.3 ± 2.9 ml/kg/%TBSA, with 76% of all resuscitations receiving >4.3 ml/kg/%burn (the upper limit predicted by Baxter). Hourly urine output (UO) in the first 24 hours postburn was 1.2 ± 0.7 ml/kg/h. There were minimal insignificant downward trends in the volume of resuscitation fluids and the mean hourly UO of the 194 cases over the 8-year period of the study. In contrast, use of colloids (5% albumin) and formal measurement of intraabdominal pressures increased during the same time period. Despite awareness of fluid creep, we have not substantially reversed this phenomenon, primarily because of failure to titrate down fluid infusion rates and by accepting higher than recommended UO. Excessive pre-BC fluid also continues to be a contributing factor. © 2010 by the American Burn Association.

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