We evaluated bedside cerebral on-line microdialysis for early detection of cerebral hypoxia in patients with traumatic brain injury. 24 severely head injured patients (Glasgow Coma Score < or = 8) were studied. Patients underwent continuous brain tissue PO2 (PtiO2) monitoring using the LICOX (GMS mbH, Germany) microcatheter device. The catheter was placed into the non-lesioned frontal white matter within 32.2 (7-48) hrs post injury. The microdialysis catheter (CMA 100, Sweden) was placed close to the PtiO2 probe via a 2- or 3-way skull screw, connected to a pump and perfused with Ringer solution (0.3 microliter/min). The microdialysis samples were collected hourly and analyzed at the bedside for glucose, lactate, lactate-pyruvate-ratio and glutamate (CMA 600, Sweden). We identified 252 episodes of impending hypoxia (PtiO2 < 15 mm Hg; 11,810 minutes) and 38 episodes of cerebral hypoxia (PtiO2 < 10 mm Hg; 1996 minutes). Before cerebral hypoxia, glucose decreased significantly. Glutamate was unchanged when no hypoxia or impending hypoxia occurred but increased 3-4 fold before a hypoxic episode appeared. We conclude that early metabolic detection of cerebral hypoxia before a critical decrease in brain tissue PtiO2 is seen and possibly allows earlier changes in treatment (e.g. reduction of hyperventilation therapy).