Cerebral Vascular and Metabolic Effects of Fentanyl and Midazolam in Young and Aged Rats

Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO₂) were measured, and electroencephalogram (EEG) was recorded in young (6-month-old) and aged (28-month-old) rats during ventilation with 70% N₂O/30% O₂ and following fentanyl or midazolam administration. Cerebral blood flow (CBF) was measured with radioactive microspheres, and cerebral oxygen consumption (CMRO₂) was calculated from the arterial-sagittal sinus oxygen content difference and CBF measurements. Fentanyl at the highest dose used (200 µg/kg and 400 µg • kg⁻¹ • h⁻¹) depressed the EEG and decreased CBF 49% and CMRO₂ 39% in young rats, whereas in old rats, this fentanyl dose decreased CBF 37% and CMRO₂ 34%, both significantly less than in young rats (P < 0.05). Midazolam at the highest dose used (5.75 mg/kg) also depressed EEG in both age groups, and decreased CBF 51% and CMRO₂ 38% in young rats. This depression was significantly less than the 62% decrease in CBF and 59% decrease in CMRO₂ produced by midazolam in old rats (P < 0.05). These results indicate that aging attenuates the cerebrovascular and cerebral metabolic depression produced by fentanyl, but potentiates the same effects produced by midazolam. The enhanced cerebral metabolic depression produced by midazolam in the aged is similar to that seen with phenobarbital, and suggests a similar action of these drugs at the central GABA-benzodiazepine-barbiturate receptor complex.