Hartvig P, Larsson E, Joachimsson P O
Hospital Pharmacy, Akademiska sjukhuset, Uppsala University, Sweden.
J Cardiothorac Vasc Anesth. 1993 Apr;7(2):148-53. doi: 10.1016/1053-0770(93)90207-2.
Constant rate infusions of ketamine supplemented with intermittent doses of midazolam were given postoperatively to 10 children in order to provide analgesia and sedation during mechanical ventilation after cardiac surgery as well as during weaning from the ventilator and during spontaneous breathing. The aims of the study were to determine the pharmacokinetics of ketamine and evaluate the suitability of ketamine as an analgesic and sedative in postoperative pediatric cardiac patients. The children were between one week and 30 months old. Five children were given 1 mg/kg/h of ketamine and five children had 2 mg/kg/h. Blood was sampled during infusion and up to 24 hours after infusion for plasma concentrations of ketamine and the main plasma metabolite, norketamine, which were determined by gas chromatography and were compared to the degree of sedation. The children were arousable when ketamine concentrations were below 1.0 to 1.5 micrograms/mL. Plasma ketamine concentrations at steady state were within a narrow range for each infusion regimen and the calculated pharmacokinetic parameters were similar. Mean plasma clearance of ketamine was 0.94 +/- 0.22 L/kg/h. The elimination half-life was 3.1 +/- 1.6 hours, but in some children late samples indicated an even longer elimination half-life. Norketamine did not reach a steady state, but at the end of the infusion, the mean plasma concentration was higher than that of ketamine. The elimination half-life of norketamine was estimated to be 6.0 +/- 1.8 hours. Both ketamine infusion regimens were supplemented with midazolam and provided similarly acceptable analgesia and sedation during mechanical ventilation and during and after weaning from the ventilator.(ABSTRACT TRUNCATED AT 250 WORDS)
术后给10名儿童持续输注氯胺酮,并间断给予咪达唑仑,以便在心脏手术后机械通气期间、脱机期间及自主呼吸期间提供镇痛和镇静作用。本研究的目的是确定氯胺酮的药代动力学,并评估氯胺酮作为小儿心脏术后镇痛和镇静药物的适用性。这些儿童年龄在1周至30个月之间。5名儿童给予1mg/kg/h的氯胺酮,另外5名儿童给予2mg/kg/h的氯胺酮。在输注期间及输注后长达24小时采集血样,检测血浆中氯胺酮及其主要血浆代谢产物去甲氯胺酮的浓度,采用气相色谱法测定,并与镇静程度进行比较。当氯胺酮浓度低于1.0至1.5微克/毫升时,儿童可被唤醒。每种输注方案的氯胺酮稳态血浆浓度在较窄范围内,计算得到的药代动力学参数相似。氯胺酮的平均血浆清除率为0.94±0.22升/千克/小时。消除半衰期为3.1±1.6小时,但在一些儿童中,后期样本显示消除半衰期更长。去甲氯胺酮未达到稳态,但在输注结束时,其平均血浆浓度高于氯胺酮。去甲氯胺酮的消除半衰期估计为6.0±1.8小时。两种氯胺酮输注方案均补充了咪达唑仑,在机械通气期间以及脱机期间和脱机后均提供了类似的可接受的镇痛和镇静效果。(摘要截短至250字)