Intracranial volume-pressure relationship following flumazenil in anesthetized dogs

A series of infusions of mock cerebrospinal fluid (CSF) was used to determine intracranial volume-pressure relationships in 12 anesthetized dogs. Measures of intracranial volume-pressure relationships included (a) CSF pressure prior to volume infusion (Po), (b) peak CSF pressure (Pp) caused by volume injection, (c) intracranial compliance [C, calculated as the ratio of change of intracranial volume (DeltaLV) to change of CSF pressure (DeltaLP)], (d) the volume pressure response (VPR, a measure of elastance, calculated as the ratio of DeltaLP to DeltaLV), (e) the pressure-volume index (PVI, calculated as the ratio of DeltaLV to log Pp/Po), and (f) estimated intracranial compliance (Ce, calculated from PVI as 0.4343PVI/Po). Measurements were made before giving flumazenil and after flumazenil doses of 0.0025 and 0.16 mg/kg in dogs receiving midazolam and in dogs not receiving midazolam (controls). The midazolam and control groups were examined both when CSF pressure was normal and when CSF pressure was increased to approximately 35 cm H2O. In dogs receiving midazolam at normal CSF pressure, 0.16 mg/kg of flumazenil (but not 0.0025 mg/kg) increased Po (by 4 +/- 2 cm H2O) and PVI, decreased Ce, and did not significantly changes C or VPR. Neither does of flumazenil caused consistent changes in dogs receiving midazolam when CSF pressure was increased prior to giving flumazenil, or in dogs not receiving midazolam. It is concluded that, in the presence of a benzodiazepine effect, large does of flumazenil increase CSF pressure from preflumazenil values and may be interpreted as worsening the intracranial volume-pressure relationship when the relationship is assessed by measures strongly affected by Po (PVI and Ce) but not when the relationship is assessed by indices that are relatively independent of Po (C and VPR).