BACKGROUND:Different opioids have different delays (hysteresis) between their concentrations in blood and their cerebral effects. Possible mechanisms include differences in their rate of penetration into the brain and differences in their distribution volume in the brain. There have been few in vivo studies of the cerebral kinetics of opioids to differentiate these mechanisms.

METHODS:The cerebral kinetics of meperidine and alfentanil were examined using conscious sheep that were fitted with long-term monitoring equipment to measure relative changes in cerebral blood flow and opioid concentration gradients across the brain through frequent sampling of arterial and sagittal sinus blood. The data were compared using hybrid physiologic modeling with membrane-limited (consistent with mechanism 1) and flow-limited (consistent with mechanism 2) models of cerebral kinetics.

RESULTS:Alfentanil had a variable effect on relative cerebral blood flow, whereas meperidine induced a transient increase. The arteriovenous concentration gradients were small after alfentanil but large after meperidine. The flow-limited model gave acceptable descriptions of observed sagittal sinus concentrations for alfentanil and meperidine, whereas the membrane-limited model collapsed to a flow-limited model. The half-lives of equilibrium between blood and brain were 6.3 and 0.8 min for meperidine and alfentanil, respectively:

CONCLUSIONS:The rate of penetration of both opioids into the brain was rapid and not rate-limiting. Large differences in the cerebral distribution volume of meperidine and alfentanil accounted for the respective delays in their peak brain concentration relative to blood.

译文

背景 : 不同的阿片类药物在血液中的浓度与大脑作用之间具有不同的延迟 (滞后)。可能的机制包括它们渗透到大脑的速率的差异以及它们在大脑中的分布体积的差异。关于阿片类药物的脑动力学的体内研究很少,可以区分这些机制。
方法 : 使用配备了长期监测设备的有意识的绵羊检查了哌替啶和阿芬太尼的脑动力学,以通过频繁采样动脉和矢状窦血来测量整个大脑中脑血流量和阿片类药物浓度梯度的相对变化。使用混合生理模型与脑动力学的膜受限模型 (与机制1一致) 和流量受限模型 (与机制2一致) 进行数据比较。
结果 : 阿芬太尼对相对脑血流量有不同的影响,而哌替啶诱导了短暂的增加。阿芬太尼后动静脉浓度梯度较小,而哌替啶后动静脉浓度梯度较大。限流模型对观察到的阿芬太尼和哌替啶的矢状窦浓度给出了可接受的描述,而膜限流模型崩溃为限流模型。对于哌替啶和阿芬太尼,血液和大脑之间的平衡半衰期分别为6.3和0.8分钟:
结论 : 两种阿片类药物进入大脑的速率是快速的,而不是限速。哌替啶和阿芬太尼的脑分布体积差异很大,导致其峰值脑浓度相对于血液的延迟。

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