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兔体内丙泊酚前体药物磷丙泊酚不同持续时间连续输注后的最低输注速率及恢复时间:与丙泊酚乳剂的比较

Minimum infusion rates and recovery times from different durations of continuous infusion of fospropofol, a prodrug of propofol, in rabbits: a comparison with propofol emulsion.

作者信息

Li Rui, Zhang Wen-sheng, Liu Jin, Tang Min, Yang Ying-ying, Luo Nan-Fu

机构信息

Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Vet Anaesth Analg. 2012 Jul;39(4):373-84. doi: 10.1111/j.1467-2995.2012.00733.x. Epub 2012 May 30.

DOI:10.1111/j.1467-2995.2012.00733.x
PMID:22642486
Abstract

OBJECTIVE

To explore, in rabbits, the minimum infusion rates (MIR) required and recovery time from long duration (≤ 8 hours) continuous infusion of fospropofol disodium, a novel water-soluble prodrug of propofol, and compare it with propofol.

STUDY DESIGN

Prospective, randomized, blinded experimental trial.

ANIMALS

Ninety-six adult laboratory rabbits, mean ± SD weight 2.20 ± 0.15 kg.

METHODS

Stage 1. 16 rabbits were assigned to receive fospropofol disodium or propofol to measure MIR, using an up-and-down method with response to tail-clamping stimulus (TCS). Stage 2. Eighty rabbits were allocated to group F (fospropofol disodium) or group P (propofol), and further subdivided (n = 10 in each subgroup) according to infusion time (2, 4, 6 or 8 hours), to groups F(2h), F(4h), F(6h), F(8h) and P(2h), P(4h), P(6h), P(8h). Fospropofol or propofol were infused, and tail clamping applied to maintain the same depth of anaesthesia until infusion was completed. Times to recover righting reflex (RR), to respond to TCS, and total recovery to different durations of continuous infusion of two anaesthetic drugs were noted. Respiratory and pulse rates and oxygen saturation were analyzed. The plasma concentrations of fospropofol disodium, the active metabolite propofol (propofol(F) ) and propofol emulsion were measured with respect to loss and recovery of RR and TCS.

RESULTS

MIR of fospropofol disodium was 2.0 mg kg(-1) minute(-1) , and MIR of propofol was 0.9 mg kg(-1) minute(-1) . Times in minutes to total recovery from anaesthesia in groups F and P were as follows, F(2h) 15 ± 3; F(4h) 26 ± 4; F(6h) 52 ± 6; F(8h) 84 ± 10; and P(2h) 10 ± 1; P(4h) 19 ± 7; P(6h) 36 ± 7; P(8h) 48 ± 5.

CONCLUSIONS AND CLINICAL RELEVANCE

After continuous intravenous infusion in rabbits (≤ 8 hours), fospropofol disodium and propofol both show an extension of recovery time with increasing infusion time, fospropofol disodium showing a significantly greater prolongation compared to propofol emulsion when infusion time increases to 6 and 8 hours.

摘要

目的

探讨兔持续输注新型水溶性异丙酚前体药物丙泊酚二钠长达8小时所需的最低输注速率(MIR)及其恢复时间,并与丙泊酚进行比较。

研究设计

前瞻性、随机、盲法实验性试验。

动物

96只成年实验兔,平均体重±标准差为2.20±0.15kg。

方法

第一阶段,16只兔被分配接受丙泊酚二钠或丙泊酚,采用上下法并根据夹尾刺激(TCS)反应来测量MIR。第二阶段,80只兔被分为F组(丙泊酚二钠)或P组(丙泊酚),并根据输注时间(2、4、6或8小时)进一步细分(每个亚组n = 10),分为F(2h)、F(4h)、F(6h)、F(8h)组和P(2h)、P(4h)、P(6h)、P(8h)组。输注丙泊酚二钠或丙泊酚,并施加夹尾刺激以维持相同的麻醉深度直至输注完成。记录恢复翻正反射(RR)、对TCS反应以及两种麻醉药物不同持续时间连续输注后的总恢复时间。分析呼吸、脉搏率和血氧饱和度。测量丙泊酚二钠、活性代谢物丙泊酚(丙泊酚(F))和丙泊酚乳剂的血浆浓度,以观察RR和TCS的丧失及恢复情况。

结果

丙泊酚二钠的MIR为2.0mg·kg-1·min-1,丙泊酚的MIR为0.9mg·kg-1·min-1。F组和P组从麻醉中完全恢复的时间(分钟)如下:F(2h) 15±3;F(4h) 26±4;F(6h) 52±6;F(8h) 84±10;P(2h) 10±1;P(4h) 19±7;P(6h) 36±7;P(8h) 48±5。

结论及临床意义

兔连续静脉输注(≤8小时)后,丙泊酚二钠和丙泊酚的恢复时间均随输注时间延长而延长,当输注时间增加至6小时和8小时时,丙泊酚二钠的延长幅度显著大于丙泊酚乳剂。

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