Reversal of Growth Arrest With the Combined Administration of Oxandrolone and Propranolol in Severely Burned Children

Abstract

Background: The hypercatabolic response in severely burned pediatric patients is associated with increased production of catecholamines and corticosteroids, decreased formation of testosterone, and reduced strength alongside growth arrest for up to 2 years after injury. We have previously shown that, in the pediatric burned population, the administration of the testosterone analog oxandrolone improves lean body mass accretion and bone mineral content and that the administration of the β1-, β2-adrenoceptor antagonist propranolol decreases cardiac work and resting energy expenditure while increasing peripheral lean mass. Here, we determined whether the combined administration of oxandrolone and propranolol has added benefit.

Methods: In this prospective, randomized study of 612 burned children [52% ± 1% of total body surface area burned, ages 0.5-14 years (boys); ages 0.5-12 years (girls)], we compared controls to the individual administration of these drugs, and the combined administration of oxandrolone and propranolol at the same doses, for 1 year after burn. Data were recorded at discharge, 6 months, and 1 and 2 years after injury.

Results: Combined use of oxandrolone and propranolol shortened the period of growth arrest by 84 days (P = 0.0125 vs control) and increased growth rate by 1.7 cm/yr (P = 0.0024 vs control).

Conclusions: Combined administration of oxandrolone and propranolol attenuates burn-induced growth arrest in pediatric burn patients. The present study is registered at clinicaltrials.gov: NCT00675714 and NCT00239668.

Figure 1

Flow Diagram. Out of 6,361 acute pediatric admissions to Shriners Hospitals for Children^®—Galveston between 1997 and 2015, 612 patients were included in our study. Inclusion criteria were based on age (0.5–12 years for male subjects, 0.5–14 years for female subjects at the time of the admission) and burn size (≥30% total body surface area burned).

Figure 2

Years of enrollment for each group.

Figure 3

Difference in duration of growth arrest among groups. Data are shown as mean ± standard error. *p=0.0125 vs. Ctrl.

Figure 4

Difference in growth slope among groups. Data are shown as mean ± standard error. *p=0.0024 vs. Ctrl; ^†p=0.0145 vs. Ox;^‡ p=0.0145 vs. Prop.