Response of pial vessel diameter and regional cerebral blood flow to CO2 during midazolam administration in cats.

Midazolam has been demonstrated to preserve the response of cerebral blood flow to CO2. However, the responsiveness of cerebral vessels or microcirculation during midazolam administration related to alteration of cerebral blood flow has not been explored. The purpose of this study was to examine the effects of midazolam on cerebral microcirculation. Nine cats were paralyzed and mechanically ventilated under nitrous oxide/oxygen anaesthesia. Using the closed cranial window technique and laser Doppler flowmetry, diameter of pial vessels and regional cerebral blood flow (rCBF) were examined on the surface of the cerebral cortex which was perfused by the middle cerebral artery. Before midazolam administration, haemodynamic variables, blood gases, rCBF, and diameter of pial vessels were determined as a control under normocapnia, hypocapnia, and hypercapnia conditions. After midazolam administration, given initially at 0.8 mg.kg-1.min-1 for 10 min and subsequently at 0.04 mg.kg-1.min-1 (total dose 10 mg.kg-1), the same variables were again analyzed. With regard to CO2 responsiveness, an 8.85% increase in rCBF was demonstrated for a Paco2 elevation of 1 kPa before midazolam administration, compared with a 7.47% increase after midazolam administration. With regard to the correlation between CO2 response and vessel diameter, arterioles less than 50 microns in diameter were more sensitive than those more than 50 microns in diameter, although there were no significant differences before or after midazolam administration. We conclude that CO2 responsiveness is preserved in terms of rCBF and vessel diameter after high doses of midazolam (10 mg.kg-1) in cats.

Effects of flumazenil during administration of midazolam on pial vessel diameter and regional cerebral blood flow in cats.

We implanted closed cranial windows in ten cats in order to observe the response of pial vessel diameter by microscopy using fluorescein isothiocyanate-labeled dextran and regional cerebral blood flow (rCBF) by laser Doppler flowmetry during administration of midazolam and reversal with flumazenil. Midazolam was given at 0.8 mg.kg-1 x min-1 for 10 min and maintained at 0.04 mg.kg-1 x min-1 for 50 min (total 10 mg.kg-1). The diameter of arterioles and venules and rCBF showed no significant change. During the last 10 min of midazolam administration, flumazenil, given at 0.1 mg.kg-1 x min-1 for 10 min (total 1 mg.kg-1), caused an increase of MAP and rCBF (P < 0.01) at 5 min after infusion and diameter of larger arterioles (> 50 microns) and venules (50-100 microns) were dilated (P < 0.05). These results indicate that midazolam does not affect the diameter of cerebral arterioles and venules; however, the reversal effects of flumazenil against midazolam are transient vasodilation of larger arterioles accompanied by an elevation of MAP, and an increase in CBF.

[Effect on cerebral blood flow of midazolam during modified neurolept-anesthesia].

Midazolam (0.2 mg.kg-1) was administered to ten patients undergoing neurosurgical operation and its influence on CBF was studied under modified NLA. Simultaneously, the plasma concentration of midazolam was measured. Heart rate and mean arterial blood pressure showed no significant changes after injection in comparison with the control. Cerebral blood flow (CBF) decreased for about 15-20% after 5 minutes, 10 minutes and 15 minutes in comparison with the control. However, 30 minutes later, CBF showed a trend to return to the control. This change in CBF is related to the changes of cerebro-vascular resistance. We applied cerebral oxygen extraction fraction (OEF) to evaluate cerebral metabolism. OEF was constant, showing no significant changes. It is concluded that cerebral oxygen consumption (CMRO2) has decreased together with the decrease in CBF. The plasma concentration of midazolam was 250-300 ng.ml-1 or greater after 5 minutes, 10 minutes and 15 minutes. We think that the sedative dose of midazolam can also sufficiently reduce CBF and CMRO2. The results suggest that midazolam is a safe and effective agent to use for anesthesia and provides adequate sedation for patients with intracranial hypertension.

[General anesthesia with sevoflurane and vecuronium for patients with dystrophia myotonica and progressive muscular dystrophy].

A 9 year old male previously diagnosed as progressive muscular dystrophy whose serum CPK5430IU.l-1 was very high received general anesthesia. Before anesthesia, dantrolene sodium 2 mg.kg-1 was given. Anesthesia was induced with thiamylal 100 mg and vecuronium bromide 3 mg. Anesthesia was maintained with sevoflurane (0.5%) in nitrous oxide (66%) and oxygen (33%). The course of anesthesia was uneventful. The operative time was 80 minutes. At the end of the operation, the patient recovered smoothly from anesthesia. A 46 year old female with dystrophia myotonia also received general anesthesia. The patient was diagnosed as having this disease 26 years previously. Preoperatively, the patient was suspected to have cardiac damage. Anesthesia was induced with thiamylal 100 mg, fentanyl 100 micrograms, midazolam 5 mg and vecuronium bromide 4 mg, and maintained with sevoflurane (1.0%) in nitrous oxide (66%) and oxygen (33%). Anesthesia was uneventful, but at the end of the operation, the patient could not breath fully by herself. She was placed on a ventilator and observed carefully. The endotracheal tube was removed 150 minutes after the induction of anesthesia. In these two cases, sevoflurane and vecuronium bromide were used safely.