Comparison of brain tissue oxygen tension to microdialysis-based measures of cerebral ischemia in fatally head-injured humans

This study investigated the relationship between brain tissue oxygen tension (PbtO(2)) and cerebral microdialysate concentrations of several compounds in five patients with refractory intracranial hypertension after severe head injury. The following substances were assayed: lactate and glucose; the excitatory amino acids glutamate and aspartate; and the cations potassium, calcium, and magnesium. Glucose concentrations did not correlate with PbtO(2), but lactate increased as PbtO(2) decreased. The lactate/glucose ratio exhibited a close relationship to PbtO(2), increasing sharply only when oxygen tension reached zero. Although glucose and oxygen eventually reached very low levels and zero, respectively, in these fatally head-injured patients, the terminal decrease in PbtO(2) slightly preceded that of glucose in four of the five patients. This time lag is the cause of the poor correlation between glucose and PbtO(2). Glutamate and aspartate concentrations both demonstrated a close relationship to PbtO(2), with sharp increases not occurring until PbtO(2) was zero. Concentrations of these amino acids exhibited a similar pattern in response to decreasing glucose concentrations. Potassium concentrations began increasing at a PbtO(2) of 35 mm Hg, which is not generally considered indicative of hypoxia. Sharper increases began occurring once PbtO(2) dropped below 15 mm Hg, with a slight rise in the minimum potassium concentrations recorded at these low PbtO(2) values. Calcium and magnesium concentrations did not vary in response to PbtO(2). In summary, the most robust biochemical indicators of cerebral anoxia were elevations in the lactate/glucose ratio and in the concentrations of lactate and of the excitatory amino acids glutamate and aspartate. Furthermore, the fact that glucose concentrations continue to decrease for a short period after oxygen levels reach zero suggests that cells continue to utilize glucose anaerobically for such functions as maintenance of cellular integrity, with collapse of the cell membrane as evidenced by increases of extracellular glutamate and aspartate not occurring until both oxygen and glucose concentrations reach zero.