BACKGROUND: The neurological wake-up test (NWT) is used to monitor the level of consciousness in patients with traumatic brain injury (TBI). However, it requires interruption of sedation and may elicit a stress response. We evaluated the effects of the NWT using cerebral microdialysis (MD), brain tissue oxygenation (PbtiO2), jugular venous oxygen saturation (SjvO2), and/or arterial-venous difference (AVD) for glucose, lactate, and oxygen in patients with severe TBI.METHODS: Seventeen intubated TBI patients (age 16-74 years) were sedated using continuous propofol infusion. All patients received intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in addition to MD, PbtiO2 and/or SjvO2. Up to 10 days post-injury, ICP, CPP, PbtiO2 (51 NWTs), MD (49 NWTs), and/or SjvO2 (18 NWTs) levels during propofol sedation (baseline) and NWT were compared. MD was evaluated at a flow rate of 1.0 μL/min (28 NWTs) or the routine 0.3 μL/min rate (21 NWTs).RESULTS: The NWT increased ICP and CPP levels (p < 0.05). Compared to baseline, interstitial levels of glucose, lactate, pyruvate, glutamate, glycerol, and the lactate/pyruvate ratio were unaltered by the NWT. Pathological SjvO2 (<50 % or >71 %; n = 2 NWTs) and PbtiO2 (<10 mmHg; n = 3 NWTs) values were rare at baseline and did not change following NWT. Finally, the NWT did not alter the AVD of glucose, lactate, or oxygen.CONCLUSIONS: The NWT-induced stress response resulted in increased ICP and CPP levels although it did not negatively alter focal neurochemistry or cerebral oxygenation in TBI patients.