Thiopental attenuates energetic impairment but fails to normalize cerebrospinal fluid glutamate in brain-injured patients

Objectives: Brain-injured patients are susceptible to secondary brain damag e related to decreased cerebral perfusion pressure associated with edema fo rmation and increased intracranial pressure (ICP). Whenever conventional th erapy fails to reduce elevated ICP, barbiturate coma represents an addition al intervention that may control ICP. In patients suffering from severe tra umatic brain injury, cerebrospinal fluid levels of glutamate, hypoxanthine, and lactate were measured during barbiturate coma and correlated to electr oencephalographic recordings and ICP. Design: Prospective, descriptive study. Setting: Ten-bed surgical intensive care unit in a university hospital. Patients: Twenty-one patients with severe traumatic brain injury (Glasgow C oma Scale score less than or equal to 9); 11 required barbiturate coma beca use of refractory intracranial hypertension, and 10 were manageable with co ntinuous administration of fentanyl and midazolam. Interventions: Thiopental was administered continuously for increased ICP w ithin the first 24 hrs after trauma and adjusted to the burst-suppression p attern (four to six bursts per minute) on continuous electroencephalographi c monitoring. Measurements and Main Results: Glutamate and hypoxanthine were analyzed usi ng high-performance liquid chromatography, whereas lactate was measured enz ymatically. Patients requiring thiopental presented with significantly high er ICP, glutamate, and hypoxanthine levels than patients receiving fentanyl and midazolam (p < .05). Within the first 24 hrs, thiopental significantly reduced cerebrospinal fluid glutamate and hypoxanthine levels in all patie nts, i.e., the burst-suppression pattern was successfully induced (p < .001 ). Interestingly, in five patients cerebrospinal fluid glutamate increased to initial values again despite unchanged neuronal activity. In these patie nts, ICP, hypoxanthine, and lactate remained significantly elevated compare d with the six patients with steadily decreasing cerebrospinal fluid glutam ate, hypoxanthine, lactate, and ICP values (p < .02). Conclusions: Barbiturate coma does not unequivocally preserve energetic sta bility despite successful suppression of neuronal activity. Despite the use of barbiturate coma in patients with refractory intracranial hypertension, persistent release or impaired uptake of glutamate may be associated with continuous anaerobic metabolism, as shown by increases in cerebrospinal flu id hypoxanthine and lactate levels.