Effects of Flumazenil on Cerebral Blood Flow and Oxygen Consumption After Midazolam Anaesthesia for Craniotomy

Abstract

Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were measured by a modification of the Kety-Schmidt technique using i.v. xenon-133 in 20 patients undergoing craniotomy for supratentorial cerebral tumours. Anaesthesia was induced and maintained with midazolam, fentanyl and nitrous oxide. Pancuronium was given for neuromuscular block. The lungs were ventilated to normocapnia. The first flow measurements were performed approximately 1 h after induction of anaesthesia. At the end of operation the patients were allocated to two groups. Ten patients were given flumazenil 0.01 mg kg-1 and 5 min later the second flow measurement was performed. In the other 10 patients the second flow measurement was performed before the administration of flumazenil. Plasma concentrations of midazolam were measured at the time of each measurement of CBF. There was no difference between the groups in plasma concentration of midazolam, CBF or CMRO2. Flumazenil had no effect on CBF and CMRO2.

Impact of anesthetic agents on cerebrovascular physiology in children

“…In contrast, Knudsen et al. demonstrated that flumazenil had no effect on CBF and CMRO 2 when used for reversal of midazolam anesthesia for craniotomy (144).…”

The Effects of Flumazenil After Midazolam Sedation on Cerebral Blood Flow and Dynamic Cerebral Autoregulation in Healthy Young Males

“…However, the present observation of a further reduction in MCBFV after flumazenil administration was inconsistent with previous studies that reported restoration or no changes in steady-state CBF after flumazenil administration. 3,4 The present results suggest for the first time that, despite complete antagonism of the sedative effects of midazolam, flumazenil administration does not antagonize both the decreases in steady-state CBF and alterations in dynamic cerebral autoregulation induced by midazolam. The present study also attempted to reveal the effects on cerebral circulation of flumazenil alone without midazolam sedation.…”

“…14,15 However, the antagonistic effects on CBF of flumazenil administered after midazolam are controversial. 3,4 As mentioned in the introduction, this discrepancy between previous studies may be explained by the differences in the level of sedation/awareness and/or the sequence of administration of the 2 drugs. Therefore, the present study investigated the changes in steady-state MCBFV after midazolam sedation followed by flumazenil administration, with assessment of sedation/awareness levels.…”

“…However, the antagonistic effects of flumazenil administered after midazolam on CBF are controversial. 3,4 A previous study reported that flumazenil administration following midazolam anesthesia with fentanyl and nitrous oxide did not antagonize reductions in CBF, 4 whereas another report states that simultaneous administration of flumazenil and midazolam antagonized the midazolam-induced reductions in CBF. 3 Several factors, such as the level of awareness, subsequent resedation due to midazolam, influence of other drugs, and/or the sequence of midazolam and flumazenil administrations, could have led to these discrepancies in the changes in CBF.…”

“…3 Several factors, such as the level of awareness, subsequent resedation due to midazolam, influence of other drugs, and/or the sequence of midazolam and flumazenil administrations, could have led to these discrepancies in the changes in CBF. 3,4 Moreover, our previous study showed that midazolam sedation alters dynamic cerebral autoregulation, which reflects responses of CBF to rapid changes in cerebral perfusion pressure. 5 However, it remains unclear whether flumazenil antagonizes the alteration in dynamic cerebral autoregulation induced by midazolam.…”