ABSTRACT
Background: Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods: The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results: More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, p = 0.01). Conclusions: The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.
ABSTRACT
Background: In this systematic review, we summarize the aetiology as well as the current knowledge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment options. Severe burn injuries with >20% total body surface area (TBSA) affected commonly leave the patient requiring several surgical procedures, prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term phase. Particularly in severely burned patients, the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial complications. Methods: A systematic and protocol-based search for suitable publications was conducted following the PRISMA guidelines. Articles were screened and included if deemed eligible. This encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients. Results: Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are, nonetheless, lacking in detail. We describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ systems. Lastly, the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized, as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term well-being. Conclusions: The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury, especially concerning thermoregulation. We offer an outlook on concepts of altered central thermoregulation from non-burn research as potential areas of future research interest and aim to provide an overview of the clinical implications of temperature management in burn patients.