Schmidt A, Øye I, Akeson J
Department of Anaesthesia and Intensive Care, Lund University, Malmö University Hospital, Malmö, Sweden.
Acta Anaesthesiol Scand. 2005 Nov;49(10):1436-42. doi: 10.1111/j.1399-6576.2005.00838.x.
Little is known about the influence of ketamine and its enantiomers on cerebral haemodynamics, and there are no direct comparison reports. This study was designed to evaluate cerebrovascular responses to bolus injections of racemic, S(+)- and R(-)-ketamine in an established experimental model.
Anaesthesia was induced with propofol in 14 pigs and maintained with fentanyl and vecuronium. The intra-arterial xenon clearance technique was used to calculate the cerebral blood flow (CBF). Eight pigs (part I) were given three consecutive 60-s intravenous (i.v.) bolus injections of 10 mg/kg of racemic ketamine (Ketalar, Pfizer), and cerebral and systemic physiological responses were studied for 30 min after each injection. Following the determination of equipotent doses of the racemate and its enantiomers by recumbency tests, bolus injections of racemic ketamine (10 mg/kg), S-ketamine (5 mg/kg) and R-ketamine (20 mg/kg) were given in randomized sequence to another six pigs (part II) and evaluated at 1, 5, 10, 15, 25 and 40 min.
No statistically significant acute tolerance in the CBF response to racemic ketamine was found in part I of the study. In part II, the decreases in the mean arterial pressure (MAP) and CBF by S-ketamine were significantly smaller than those by racemic and R-ketamine (both P < 0.001). No study drug had any significant effect on the cerebral arteriovenous oxygen content difference (C(av)O(2)) over time, but S-ketamine was associated with lower C(av)O(2) than racemic ketamine (P = 0.008) and R-ketamine (P = 0.016).
Bolus injection of S-ketamine was associated with less cerebral and systemic haemodynamic depression than racemic or R-ketamine in equipotent doses in this experimental model. These findings indicate possible advantages of S-ketamine over racemic ketamine.
关于氯胺酮及其对映体对脑血流动力学的影响知之甚少，且尚无直接比较的报道。本研究旨在评估在一个既定的实验模型中，脑对外消旋氯胺酮、S(+)-氯胺酮和R(-)-氯胺酮单次注射的脑血管反应。
14头猪用丙泊酚诱导麻醉，并用芬太尼和维库溴铵维持。采用动脉内氙清除技术计算脑血流量（CBF）。8头猪（第一部分）连续3次静脉推注10mg/kg外消旋氯胺酮（凯他敏，辉瑞公司），每次注射后研究30分钟的脑和全身生理反应。通过卧倒试验确定外消旋体及其对映体的等效剂量后，将外消旋氯胺酮（10mg/kg）、S-氯胺酮（5mg/kg）和R-氯胺酮（20mg/kg）随机顺序单次注射给另外6头猪（第二部分），并在1、5、10、15、25和40分钟时进行评估。
在研究的第一部分中，未发现外消旋氯胺酮对CBF反应有统计学上显著的急性耐受性。在第二部分中，S-氯胺酮引起的平均动脉压（MAP）和CBF下降明显小于外消旋氯胺酮和R-氯胺酮（均P<0.001）。随着时间的推移，没有研究药物对脑动静脉氧含量差（C(av)O(2)）有任何显著影响，但S-氯胺酮的C(av)O(2)低于外消旋氯胺酮（P=0.008）和R-氯胺酮（P=0.016）。
在该实验模型中，等效剂量下，单次注射S-氯胺酮比外消旋氯胺酮或R-氯胺酮引起的脑和全身血流动力学抑制更小。这些发现表明S-氯胺酮相对于外消旋氯胺酮可能具有优势。
