The acute effects of propranolol on metabolic dysfunction in severely burned pediatric patients

Severe burn injury is a profound and lasting form of trauma. Owing to advances over the past several decades, burn injury is no longer thought of as a mortal injury. However, significant morbidity still persists in the post-burn recovery period. Much of this morbidity is stimulated by the long-lasting catecholamine surge that develops after injury. This surge develops metabolic dysfunction that is categorized by significantly elevated energy mobilization through increased glucose production and lipolysis. These metabolic changes contribute to the morbidity associated with delayed recovery. Hyperglycemia, increased infections, insulin resistance, delayed wound healing, and organ dysfunction are all associated with metabolic dysfunction after burn injury. One strategy to curb this response is -adrenergic blockade with the non-selective -blocker propranolol. Studies over the last several decades have shown benefit of propranolol use in pediatric burned patients, but much is still unknown about the acute metabolic changes related to propranolol and burn injury. In this study we used stable isotope infusion techniques to analyze acute metabolism in the first few weeks after severe burn injury. Patients were randomized to receive propranolol or placebo and pathways related to lipid and glucose kinetics were analyzed. Propranolol significantly reduced glucose release, glucose clearance, and FFA release during acute recovery. Propranolol also caused a significant increase in hepatic insulin sensitivity, improving central insulin resistance typically observed in severely burned patients. Lastly, we were also to show a significant correlation between changes in glucose kinetics and lipid kinetics. This correlation was reduced following propranolol administration, indicating this link could be mediated through catecholamines. Further studies are warranted to investigate the link between glucose metabolism and fat metabolism. Propranolol remains underutilized for treatment of severe burns in burn centers across the country. Here, we add evidence of the benefit of propranolol use in severely burned pediatric patients.

Name thesis:degree_name

Human Pathophysiology and Translational Medicine (Doctoral)

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Clayton, Robert Patrick

• Burn Injury
• Trauma
• Metabolism
• Pediatric

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/11340

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/11340