用于程序镇静的氯胺酮丙泊酚给药模拟。

Ketofol dosing simulations for procedural sedation.

作者信息

Coulter Finn L S, Hannam Jacqueline A, Anderson Brian J

机构信息

From the *Emergency Department, Auckland City Hospital; and †Department of Anaesthesiology, University of Auckland, Auckland, New Zealand.

出版信息

Pediatr Emerg Care. 2014 Sep;30(9):621-30. doi: 10.1097/PEC.0000000000000222.

DOI:10.1097/PEC.0000000000000222

PMID:25162687

Abstract

BACKGROUND

Propofol mixed with racemic ketamine (or "ketofol") is popular for short procedural sedation and analgesia, yet the optimal combination is unknown. We aimed to determine a ketofol dosing regimen for short procedural sedation and analgesia of 5- to 20-minute duration in healthy patients (2-20 y).

METHODS

Pharmacokinetic-pharmacodynamic parameters were used to simulate drug concentration and effect profiles over time for different ketamine-to-propofol ratios (1:1-1:10). The target effect was a Children's Hospital of Wisconsin Sedation Scale score of less than 2. Combined effects were additive, with a propofol EC50 of 1.54 μg/mL (concentration required to produce hypnosis in 50% of patients), a ketamine EC50 of 0.44 μg/mL, and a slope of 5.3. Emergence threshold concentrations for propofol were 2.0 μg/mL in children and 1.8 μg/mL in adults as well as 0.5 μg/mL for ketamine (children and adults). The EC50 for propofol antiemesis was 0.343 μg/mL.

RESULTS

A ketamine-to-propofol ratio of 1:3 was the best combination for intermittent dosing, achieving a rapid onset of a Children's Hospital of Wisconsin Sedation Scale score of less than 2 within 1 minute and a time to emergence of 9 to 19 minutes in all ages after a 10-minute sedation. The optimal ketofol dosing in children (2-11 y) was 0.1 mL/kg initially followed by 0.05 mL/kg at 2 minutes and then 0.025 mL/kg for the subsequent doses. The adults (12-20 y) received 0.05 mL/kg of ketofol initially followed by 0.025 mL/kg for the subsequent doses. These regimens maintain a propofol antiemesis for 30 to 40 minutes after the last dose.

CONCLUSIONS

We suggest an optimal ratio of racemic ketamine to propofol of 1:3 for boluses during short procedures (5-20 minutes). A short ketofol infusion, ratio 1:4, is a suitable alternative to intermittent boluses. Ratios greater than 1:3 result in delayed recovery after 20 minutes.

摘要

背景

丙泊酚与消旋氯胺酮混合（即“氯胺酚”）常用于短期操作的镇静和镇痛，但最佳组合尚不清楚。我们旨在确定一种氯胺酚给药方案，用于健康患者（2至20岁）5至20分钟的短期操作镇静和镇痛。

方法

利用药代动力学-药效学参数模拟不同氯胺酮与丙泊酚比例（1:1至1:10）下药物浓度和效应随时间的变化情况。目标效应是威斯康星儿童医院镇静量表评分低于2分。联合效应具有相加性，丙泊酚的半数有效浓度（EC50）为1.54μg/mL（使50%患者产生催眠作用所需的浓度），氯胺酮的EC50为0.44μg/mL，斜率为5.3。丙泊酚的苏醒阈值浓度在儿童中为2.0μg/mL，在成人中为1.8μg/mL，氯胺酮的苏醒阈值浓度为0.5μg/mL（儿童和成人）。丙泊酚止吐的EC50为0.343μg/mL。

结果

氯胺酮与丙泊酚比例为1:3是间歇性给药的最佳组合，在1分钟内迅速使威斯康星儿童医院镇静量表评分低于2分，在10分钟镇静后，各年龄段的苏醒时间为9至19分钟。儿童（2至11岁）氯胺酚的最佳给药方案为初始剂量0.1 mL/kg，然后在2分钟时给予0.05 mL/kg，随后的剂量为0.025 mL/kg。成人（12至20岁）初始给予0.05 mL/kg氯胺酚，随后剂量为0.025 mL/kg。这些方案在最后一剂后可维持丙泊酚止吐作用30至40分钟。