Fleischer J E, Milde J H, Moyer T P, Michenfelder J D
Department of Anesthesiology, Mayo Clinic, Mayo Medical School, Rochester, Minnesota.
Anesthesiology. 1988 Feb;68(2):234-42. doi: 10.1097/00000542-198802000-00010.
The effects of a continuous high-dose infusion of midazolam on cerebral function, metabolism, and hemodynamics were studied in nine dogs receiving a spinal anesthetic and breathing 65% nitrogen/35% oxygen. In five dogs, the effects of 65% nitrous oxide (N2O) inspired and the benzodiazepine antagonist Ro 15-1788 were also examined. Midazolam was infused at a rate of 0.66 mg.kg-1.min-1 for 60 min for a total dose of 40 mg.kg-1. Cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) (measured by venous outflow technique) both decreased until a plateau level was reached at approximately 75% of control values (4.0 +/- 0.2 ml.min-1.100 g-1 and 49 +/- 3 ml.min-1.100 g-1, respectively, mean +/- SEM). This occurred after 6-10 mg.kg-1 of midazolam, corresponding to serum midazolam levels between 18.4 +/- 3.8 and 31.2 +/- 3.3 micrograms.ml-1. Serum midazolam levels increased throughout the midazolam infusion, reaching a mean value of 53 +/- 5.5 micrograms.ml-1 by the end of the midazolam infusion. A similar plateau was seen for changes in the electroencephalogram (EEG), which never developed burst suppression. Five dogs inspired 65% nitrous oxide/35% oxygen during minutes 30-45 of the midazolam infusion, rather than 65% nitrogen/35% oxygen. Nitrous oxide had no effect upon CMRO2, but significantly increased CBF when compared to dogs receiving nitrogen. Ro 15-1788, 1.0 mg.kg-1 caused a return of CMRO2 and EEG activity to control levels. CBF and intracranial pressure (ICP) increased markedly, to greater than control levels immediately following Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)
在9只接受脊髓麻醉并吸入65%氮气/35%氧气的犬中，研究了持续大剂量输注咪达唑仑对脑功能、代谢和血流动力学的影响。对其中5只犬，还研究了吸入65%氧化亚氮（N₂O）以及苯二氮䓬拮抗剂Ro 15 - 1788的影响。咪达唑仑以0.66 mg·kg⁻¹·min⁻¹的速率输注60分钟，总剂量为40 mg·kg⁻¹。脑氧代谢率（CMRO₂）和脑血流量（CBF，通过静脉流出技术测量）均下降，直至达到约为对照值75%的平台水平（分别为4.0±0.2 ml·min⁻¹·100 g⁻¹和49±3 ml·min⁻¹·100 g⁻¹，均值±标准误）。这发生在咪达唑仑剂量达到6 - 10 mg·kg⁻¹之后，此时血清咪达唑仑水平在18.4±3.8至31.2±3.3 μg·ml⁻¹之间。在整个咪达唑仑输注过程中，血清咪达唑仑水平持续升高，在输注结束时达到53±5.5 μg·ml⁻¹的均值。脑电图（EEG）变化也出现类似平台期，且从未出现爆发抑制。5只犬在咪达唑仑输注的第30 - 45分钟吸入65%氧化亚氮/35%氧气，而非65%氮气/35%氧气。氧化亚氮对CMRO₂无影响，但与吸入氮气的犬相比，显著增加了CBF。1.0 mg·kg⁻¹的Ro 15 - 1788使CMRO₂和EEG活动恢复到对照水平。在给予Ro 15 - 1788后，CBF和颅内压（ICP）明显升高，立即超过对照水平。（摘要截短至250字）
