Table 1.

Key papers studying the role of glucose levels and/or glycemic control parameters after traumatic brain injury and clinical and physiological outcome measures.

References	Title	Type	Aims	Conclusions
Timofeev et al. (14)	Cerebral extracellular chemistry and outcome following traumatic brain injury: A microdialysis study of 223 patients	Observational study	Determine the relationship between the fundamental biochemical markers and neurological outcome in a large cohort of patients with traumatic brain injury	Significant association of higher lactate/pyruvate ratio with increased mortality and unfavorable outcomes after TBI
Hattori et al. (30)	Correlation of regional metabolic rates of glucose with glasgow coma scale after traumatic brain injury	Observational study	Compare the regional cerebral metabolic rate of glucose with the severity of injury and level of consciousness in adults with TBI and healthy controls	Significant difference in glucose metabolism between comatose and non-comatose patients acutely after TBI; the metabolic rate of glucose in these regions significantly correlated with the level of consciousness at the time of PET
Oddo et al. (31)	Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: A microdialysis study	Observational study	Analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury	In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extra-cellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality
Goodman et al. (32)	Extracellular lactate and glucose alterations in the brain after head injury measured by microdialysis	Observational study	Study cerebral glucose and lactate metabolism in 126 head-injured patients using microdialysis	Increased lactate and decreased glucose, indicating accelerated glycolysis, commonly occurred with cerebral ischemia or hypoxia is associated with a poor outcome
Vespa et al. (33)	Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: A microdialysis study	Observational study	Assess whether posttraumatic reductions in extracellular glucose levels are due to ischemia and are associated with poor outcomes	The level of extracellular glucose is typically reduced after traumatic brain injury and total duration of low glucose is associated with poor outcome, but not with ischemia
Vespa et al. (34)	Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury	Observational study	Determine whether intensive glycemic control using insulin results in reduced brain extracellular glucose and glucose metabolic rates after TBI; compare the effects of intensive vs. loose glycemic control on clinical outcome and incidence rate of microdialysis markers of cellular distress	Intensive glycemic control did not reduce global cerebral metabolic rate compared with routine glycemic control; intensive glycemic control resulted in reduced microdialysis glucose concentrations and increased microdialysis markers of brain metabolic distress (LPR and glutamate); no differences found in mortality rate or functional outcome between intensive and loose glycemic control
Meier et al. (35)	Differential temporal profile of lowered blood glucose levels (3.5–6.5 vs. 5–8 mmol/l) in patients with severe traumatic brain injury	Observational study	Assess whether maintaining arterial blood glucose between 3.5 and 6.5 mmol/l, as compared with 5 to 8 mmol/l, significantly decreases mortality and reduces rates of infectious complications in patients with severe TBI	High serum glucose levels in the 1st week after injury and reduced glucose targets thereafter are associated with improved outcomes, including reduced instances of elevated ICP
Rostami (36)	Glucose and the injured brain-monitored in the neurointensive care unit	Review	Review studies reporting on monitoring of cerebral glucose with microdialysis in patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and ischemic stroke	Low cerebral glucose in patients with TBI and SAH provides valuable information on development of secondary ischemia and has been correlated with worse outcome
Rajagopalan et al. (37)	Hierarchical cluster analysis identifies distinct physiological states after acute brain injury	Observational study	Test whether data-driven approaches can identify distinct physiological states from intracranial multimodality monitoring data	Patients with a favorable outcome had a greater proportion of physiologically normal events, whereas patients with an unfavorable outcome had a greater proportion of ischemia and hyperglycolysis
Jalloh et al. (38)	Focally perfused succinate potentiates brain metabolism in head injury patient	Observational study	Investigate whether focal administration of succinate, a tricarboxylic acid cycle intermediate, could improve cerebral metabolism in TBI patients	Infusion of succinate via cerebral microdialysis catheter improved glucose utilization and decreased LPR in acute TBI
Stovell et al. (39)	The effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury	Observational study	Study the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio) and tissue NADH/NAD+ redox state (L/P ratio) using microdialysis in patients with acute major TBI	Succinate improves NADH/NAD+ redox state (decreases L/P ratio) in the traumatized human brain; a significant correlation between percentage decrease in L/P ratio and percentage increase in PCr/ATP suggests that succinate supplementation can increase brain energy metabolism