Beta-Blockade Reduces Catabolism in Severely Injured Trauma Patients

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DESCRIPTION (provided by applicant): Advances in ICU care allow initial survival of critically injured patients, however survivors often suffer from long term morbidity. Optimizing resistance to infection, wound healing, and return to function remains a challenge. While the genesis of these problems is complex, one proposed underpinning is the postinjury catabolic state. This hypermetabolic period observed in the critically injured patient has considerable costs to the individual, including nitrogen loss, insulin resistance, immune dysfunction and failure of pivotal synthetic pathways. A successful reduction of this period of catabolism may have a powerful impact on long term outcome. Reducing the effects of the postinjury catabolic period has proved difficult. Supplementation of nutritional support with high levels of protein, specific amino acids, or hormones has not been shown to have a substantial impact on net nitrogen loss or functional outcomes in trauma patients. The disappointing results of these efforts may be due to the persistent adrenergic contribution to these metabolic systems. The (-adrenergic system is responsible for mediating many of the effects engendered by inflammation. Many in vitro and animal studies have demonstrated (-adrenergic mediated hyperglycemia, insulin resistance, protein catabolism, leukocyte dysfunction, cytokine production and pro-inflammatory intracellular signaling. A potential therapy in the trauma population is (-blockade, results of which have looked promising in recent controlled burn trials. We propose a randomized controlled trial of propranolol treatment in severely injured trauma patients. Our hypothesis is that propranolol reduces the hypermetabolic response, attenuates the (-adrenergic stimulus to inflammation and reduces morbidity and mortality. We propose to randomize severely injured ICU patients on their third postinjury day. One arm will receive treatment with propranolol; the other will receive current standard of care. Outcome measures will include cytokine levels, resting energy expenditure, fat-free mass, skeletal muscle mass, glucose levels, cortisol levels, insulin requirements, infections, organ failure, ICU morbidity and mortality. Results of this study will elucidate the (-adrenergic contribution to the catabolic problems of the severely injured. This information will provide a platform from which to launch both basic science and clinical research into the (-adrenergic system and its effects on inflammation, catabolism, and functional outcome