Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial

Gabriel Hundeshagen; Elisabeth Blears; Viktoria Mertin; Andrew G Day; Alen Palackic; Christian Tapking; Valentin Haug; Ulrich Kneser; Björn Bliesener; Adriana C Panayi; Ariel Aballay; Francois Depret; Christian Stoppe; Daren K Heyland

doi:10.1093/burnst/tkad063

Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial

Burns Trauma. 2024 Apr 21:12:tkad063. doi: 10.1093/burnst/tkad063. eCollection 2024.

Authors

Affiliations

¹ Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Str. 13, 67071 Ludwigshafen, Germany.
² Department of Plastic Surgery, Bayview Medical Center, Johns Hopkins University, 4940 Eastern Ave, Baltimore 21224, MD, USA.
³ Kingston General Health Research Institute, Kingston Health Sciences Centre, 76 Stuart Street, Kingston, Ontario, K7L 2V7, Canada.
⁴ Department of Anaesthesiology, Intensive Care Medicine and Burn center, Saint-Louis Hospital, 1 avenue Claude-Vellefaux, 75010, Asistance Publique Hôpitaux de Paris, Paris Cité University, France.
⁵ Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Schwanenweg 21, 24105 Kiel, Germany.
⁶ University Hospital, Würzburg, Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Oberdürrbacher Str. 6, 97080 Würzburg, Germany.
⁷ Departments of Cardiac Anesthesiology & Intensive Care Medicine, Charité Berlin, Augustenburger Platz 1 | 13353, Berlin, Germany.
⁸ Department of Critical Care Medicine, Queen's University, 76 Stuart Street, Kingston, K7L 2V7 Ontario, Canada.

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.

Keywords: Beta blocker; Burns; Critical illness; Hypermetabolism; Oxandrolone.