Kissin I, Brown P T, Bradley E L
Department of Anesthesiology, University of Alabama, Birmingham 35294.
Life Sci. 1993;52(8):PL55-60. doi: 10.1016/0024-3205(93)90241-t.
Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continuous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 micrograms.kg-1.h-1) was given together with midazolam (3 mg.kg-1.h-1), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 micrograms.kg-1.h-1) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg.kg-1) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 micrograms.kg-1) with or without midazolam (3 mg.kg-1) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.
在大鼠中通过持续输注或推注给药的方式研究了阿芬太尼与咪达唑仑的镇痛相互作用。通过测量对有害压力的运动反应阈值来确定镇痛效果。持续恒速输注阿芬太尼表明，在最初的峰值之后，由于急性耐受性的发展，镇痛作用显著下降。当阿芬太尼（250微克·千克⁻¹·小时⁻¹）与咪达唑仑（3毫克·千克⁻¹·小时⁻¹）同时给药时，阿芬太尼镇痛作用的下降得到缓解。在以恒速（250微克·千克⁻¹·小时⁻¹）输注阿芬太尼4小时后，急性耐受性已经形成，推注咪达唑仑（3毫克·千克⁻¹）增强了阿芬太尼诱导的麻醉作用。同时，当阿芬太尼以推注方式给药（30微克·千克⁻¹），无论是否同时推注咪达唑仑（3毫克·千克⁻¹），均未观察到表明咪达唑仑增强阿芬太尼镇痛作用的变化。结果表明，咪达唑仑可减轻对阿芬太尼镇痛作用急性耐受性的发展。
