TREATMENT OF THE HYPERMETABOLIC RESPONSE TO CNS INJURY

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The objective of this research is to improve outcome from a nuerological injury by providing the optimal systemic environment for recovery of the injured brain. Neurological injury causes systemic abnormalities that may have adverse effects on neurological recovery. Hypermetabolism can rapidly result in protein-calorie malnutrition, causing immunoincompetence, multi-organ failure, and delayed healing of the injury. Hyperglycemia, due to the systemic stress response, may worsen the severity of lactic acidosis of the injured brain. The first specific aim of the proposed project is to develop a method of alimenting neurologically injured patients which will satisfy cerebral and systemic protein and energy requirements without producing hyperglycemia. A clinical trial will evaluate the use of triacetin and 1,3-butanediol as nonprotein caloric sources in head injured patients. The effects of the feedings on both cerebral and systemic metabolism will be evaluated. The second specific aim is to determine if these metabolic and physiological therapies will improve mortality after severe head injury. The tird specific aim is to study the relationship of the systemic hypermetabolism to the CNS inflammatory response to neurological injury. These studies will be performed in association with a clinical trial of the anti-inflammatory drugs, chloroquine and colchicine, as described in detail in Project 4.