CHICAGO – Combination therapy with oxandrolone and propranolol can attenuate burn-induced growth arrest and increase growth rate in severely burned children, according to findings from a prospective, randomized clinical trial.
Of 612 children with burns over at least 30% of their total body surface area (average of more than 50%), 103 were randomized to receive treatment with both oxandrolone and propranolol, 67 received oxandrolone alone, 194 received propranolol alone, and 248 served as controls. After a minimum of 1 year of treatment, the average growth rate was 5.9 cm in the control group and 7.6 cm in the group receiving combination therapy, Dr. David N. Herndon of the University of Texas Medical Branch at Galveston reported at the annual meeting of the American Surgical Association.
“The rate of growth with combination therapy was significantly greater than with either of the individual drugs alone,” Dr. Herndon said.
Further, the period of growth arrest was significantly shorter – by 84 days – among those in the combination-treatment group, compared with those in the control group.
Study subjects were children treated at Shriners Hospitals for Children – Galveston from 1997 to 2015. Boys aged 6 months to 14 years and girls aged 6 months to 12 years were included to eliminate the variable onset of postpubescent growth delay. About two-thirds in each group were boys, and the ages in the patient groups were similar. Mortality was low and was similar across the groups, as was hospital length of stay.
Dr. Herndon and his colleagues controlled for heterogeneous burn distribution between the groups in the course of their analyses, as well as age.
In children with severe, extensive burn injury, the hypercatabolic response is mediated by increased production of catecholamines and corticosteroids, coupled with decreased production of testosterone. This contributes to growth arrest and to decreased strength for up to 2 years after burn injury, he explained. Children with burns over 50% of their total body surface routinely survive acute hospitalization but, at 3 months post injury, are thin, have difficulty walking, and require occupational and physical therapy to help them perform even the simplest activities of daily living.
At 1 year, a raised inflammatory mass covers their wounds, they experience itching, and they have, in large part, stunted growth; there is severe loss of lean body mass and strength, and fracture risk is increased, Dr. Herndon said.
In previous work, he and his colleagues showed that administration of propranolol at an average dose of 4 mg/kg per day for 1 year decreased cardiac work and resting energy expenditure while increasing peripheral lean mass. Further, they found that the testosterone analog oxandrolone, given at 0.1 mg/kg twice per day for 1 year, improved lean body mass accretion and bone mineral content.
The current study was conducted to test the effects of administering both agents in combination.
“The combined use of oxandrolone and propranolol in severely burned children confers an additional benefit on growth over either treatment alone,” Dr. Herndon said, adding that the additive effects of combination therapy may be due to the effects of oxandrolone on bone growth and the anti-inflammatory effects of propranolol.
“The additional benefits point out mechanistic changes that may be eventful in the treatment of hypermetabolism generally and in inflammatory states,” he concluded.
Dr. Herndon reported having no disclosures.