The dose-response relationship of acetazolamide on the cerebral blood flow in normal subjects

Acetazolamide (AA) is used to determine the cerebral vasoreactivity (CVR). To investigate whether the usually applied standard dose of 1 g intravenously will guarantee stable test conditions, the dose-response relationship of AA on cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) in normal subjects was determined.

In 59 healthy volunteers, rCBF was measured with a (133)Xenon inhalation device, and CBFV of the middle cerebral artery (MCA) by transcranial Doppler sonography. The first CBF measurement was taken at rest, the second 15 min after application of AA at a dosage of 5, 10, 13, 15 and 18 mg/kg of body weight, respectively. The CBFV (n = 52) of the middle cerebral artery on the side of the better temporal window was taken 25 min after application of AA 13 mg/kg. In order to determine the side effects of AA, statements of an additional 172 patients were included.

A significant dosage dependence of AA on the CBF (fast flow and initial slope index) exists between 5 and 18 mg/kg intravenously. After AA 13 mg/kg, the fast flow increases from 70.8 +/- 10.8 to 110.1 +/- 13.5 ml/100 g/min, the initial slope index from 46.5 +/- 5.4 to 62.8 +/- 5.8, and the CBFV from 51.5 +/- 8.5 to 85.4 +/- 14.2 cm/s. The CVR of CBF and CBFV ascertained that way shows an age dependence equivalent to the situation at rest. Severity and frequency of side effects are dosage-dependent, significantly in part, but reversible without exception.

For the determination of CVR of CBF with AA, a dosage related to body weight is required. The usually applied standard dose of 1 g intravenously is not sufficient for standardized test conditions. For evaluation of the results obtained, the apparent age dependence of CVR must be taken into account. Because of the severity of side effects occurring at a higher dose, an AA dosage of 13 mg/kg intravenously is recommended.