The effects of midazolam reversal by RO 15-1788 on cerebral perfusion pressure in patients with severe head injury

Abstract

In patients with severe head injury, midazolam is a convenient agent for sedation during mechanical ventilation, although its sedative effect can be prolonged. We investigated the effects of acute midazolam reversal by RO 15-1788 (RO), a benzodiazepine antagonist, on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and on recovery in 18 studies performed on 15 patients with severe head injury (Glasgow coma score less than 8). ICP increased significantly from 16.3 mmHg +/- 2 (mean +/- SEM) to 24.1 mmHg +/- 4.2 (p less than 0.02) and to 25.2 mmHg +/- 4 (p less than 0.01), 5 and 10 min respectively after RO administration. Analysis of the results showed 2 patterns of response in ICP. In patients with good control of ICP before RO administration, there was no change in ICP and CPP, whereas in patients with abnormal ICP, RO injection induced severe increase in ICP and concomitant decrease in CPP. Arousal after midazolam reversal was obvious in 5 patients who were quickly extubated. Midazolam reversal by RO should not be attempted in patients with severe head injury and unstable ICP.