111 New Observations in Cerebral Glucose Metabolism Following Traumatic Brain Injury: The Mystery of the Missing Glucose 246 Studies in 74 Patients and Comparison to Normal Controls.

INTRODUCTION: Previous studies have demonstrated a profound dysfunction of cerebral metabolism following traumatic brain injury (TBI). Despite overall depression of cerebral metabolism, the cerebral metabolic rate (CMR) of oxygen is depressed out of proportion to the mildly reduced CMRglucose. This mismatch has raised the question, where does the missing glucose go if it is not metabolized oxidatively? We have previously demonstrated that an increased proportion of glucose is shunted through the pentose phosphate pathway prompting us to further investigate the total percentage of glucose metabolized by alternative pathways (the "missing glucose") in an attempt to understand the full milieu of altered or dysfunctional metabolism in the injured brain.

METHODS: To determine CMR for oxygen, glucose, and lactate by a modified Kety-Schmidt method, daily arterial and jugular venous blood samples and cerebral blood flow measurements were made in 74 moderate and severe TBI patients over the first 6 days postinjury. Data were also collected from 35 healthy subjects. Using molar units, missing glucose utilization was calculated by CMRglucose (missing) = CMRglucose (total) - (CMRO2/6) + (CMRlactate/2) and converted to a percentage as CMRglucose (missing) % = (CMRglucose (missing)/CMRglucose (total)) × 100. Overall trauma-normal differences were compared using a mixed-effects model with random subject effect to account for the repeated measurements in the trauma group.

RESULTS: The average calculated missing glucose (proportion of alternative glucose metabolism, not accounted for by oxidative metabolism or lactate production) was 34.45% in TBI subjects compared with 12.18% in healthy subjects (P = .004). Overall CMRO2 (0.599 vs 1.391; P < .001), CMRglucose (0.193 vs 0.296; P < .001) and metabolic ratio (3.92 vs 4.93; P = .006) were all depressed in TBI subjects.

CONCLUSION: In addition to an overall depression of cerebral metabolism for oxygen and glucose, the percentage of glucose with alternative metabolic fates (missing glucose) was significantly higher in the posttraumatic brain than in the normal brain, almost a 3-fold elevation. Further study is needed to fully identify the alternative metabolic pathways involved.