Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury

Abstract

IntroductionThe optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism.MethodsIn twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios.ResultsBrain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu.ConclusionsArterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.

Treating Hyperglycemia in Neurocritical Patients: Benefits and Perils

“…2 Mechanisms of brain injury from hyperglycemia Experimental animal data and human studies provide evidence that even mild hypoglycemia can induce neuroglycopenia and cerebral metabolic distress. Studies of cerebral metabolism using jugular venous measurements (i.e., arteriovenous oxygen and glucose consumption) [59] and cerebral microdialysis (i.e., brain tissue glucose and lactate/pyruvate ratio) [24,26,60] indicate that serum glucose levels below 108 mg/dl (6 mmol/l) are associated with neuroglycopenia and metabolic distress in patients with severe TBI. Although studies using a combination of microdialysis and [ 18 F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (PET) suggest that severe TBI patients may initially develop increased glucose utilization without necessarily shifting toward anaerobic metabolism [38], this state of hyperglycolysis [39] can subsequently predispose patients to develop metabolic crisis if the glucose supply becomes inadequate.…”

Interrelationship between blood and tissue lactate in a general intensive care unit: A subcutaneous adipose tissue microdialysis study on 162 critically ill patients

“…Microdialysis is widely used in neurointensive care [7][8][9][10], having great potential for exploring the pathophysiology of brain injury. Importantly, continuous monitoring of extracellular metabolites provides early warning of impending cerebral hypoxia/ischemia before neurologic deterioration, allowing timely implementation of neuroprotective therapies [11,12].…”

Hypoglycemia in Critically Ill Patients

“…In acute brain injury, the hypoglycemic threshold is lower compared to normal brain and even mild hypoglycemia can induce neuroglycopenia. In patients after traumatic brain injury, arterial glucose levels < 108 mg/dL resulted in decreased brain glucose concentrations with an increased cerebral uptake of glucose (Meierhans et al, 2010). Microdialysis markers of brain metabolic distress were significantly reduced at brain glucose concentrations > 18 mg/dL, reaching the lowest levels at arterial blood glucose levels between 108-162 mg/dL.…”