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[氟烷、恩氟烷和异氟烷对小儿米库氯铵药效学的影响]

[Effect of halothane, enflurane and isoflurane on the pharmacodynamics of mivacurium in children].

作者信息

Neidhart G, Pabelick C, Kuhn I, Leuwer M, Vettermann J

机构信息

Zentrum der Anästhesiologie und Wiederbelebung des Klinikums, Johann Wolfgang Goethe-Universität Frankfurt am Main.

出版信息

Anasthesiol Intensivmed Notfallmed Schmerzther. 1996 Jun;31(5):293-7. doi: 10.1055/s-2007-995923.

Abstract

INTRODUCTION AND OBJECTIVE

Mivacurium is a new non-depolarising muscle relaxant with a relatively rapid onset and short duration of action. In children, intravenous injection of 0.2 mg/kg produces satisfactory relaxation. Because inhalational anaesthetics have been found to enhance the potency of muscle relaxants we determined if onset or recovery times following mivacurium are influenced by inhalation of halothane (HAL), enflurane (ENF) or isoflurane (ISO).

METHODS

After intramuscular induction, 36 surgical children (2-6 years, ASA I) were randomly assigned to inhale either HAL (n = 12); ENF (n = 12) or ISO (n = 12). The train-of four (TOF) response was determined electromyographically (Relaxograph, Datex) at 20-second time intervals. Following ten minutes of inhalation of either HAL, ENF or ISO (0,8; 1,2; 1,0 vol% respectively) in N2 O/O2 (2:1), 0.2 mg/kg of mivacurium was injected intravenously. Patients were intubated at maximal T1-suppression and the intubating conditions were judged according to a graded score. Upon recovery of T1 = 25%, six patients in each group were antagonised with 30 micrograms/kg of neostigmine and 15 micrograms/kg of atropine; the recovery indices were compared with those from non-antagonised patients. Differences between groups were tested with multifactorial analysis of variance (p < 0.05).

RESULTS

Intubating conditions were graded as "excellent" or "good" in all patients but one who showed moderate breath holding following the tube passage. Onset times of mivacurium were not different between patients receiving HAL: 2.4 min +/- 0.52 (+/ SD); ENF: 2.4 min +/- 0.55 or ISO: 2.6 min +/- 0.68. Time to T1 = 25% was 7.6 min +/- 2.91 (HAL); 7.9 min +/- 1.55 (ENF) and 8.6 min +/- 2.30 (ISO). Recovery indices were not significantly different between groups. Total duration of action in non-antagonised patients was 13.0 min +/- 3.32 (HAL); 14.3 min +/- 4.01 (ENF) and 19.6 min +/- 5.17 (ISO), whereas antagonised duration of action was 13.4 min +/- 5.11 (HAL); 13.3 min +/- 1.97 (ENF) and 15.6 min +/- 4.25 (ISO). The shorter total duration of action in patients receiving neostigmine (average 0.5-2 minutes) was statistically insignificant.

DISCUSSION AND CONCLUSION

Following injection of 0.2 mg/kg of mivacurium, no clinically relevant differences in onset or recovery times were found between children receiving halothane, enflurane or isoflurane. No differences in heart rate or blood pressure were found between groups. Compared to previous investigations with mivacurium, we noted a 30-60% longer mean onset time and a 30% shorter mean spontaneous recovery time. This may be explained by the lower mean age of our patients, which correlates with a relatively higher volume of distribution, resulting in lower plasma concentrations if the dose is calculated per kilogramme body weight. The reduction of the mean recovery time by 2 minutes following neostigmine injection seems to be clinically irrelevant. Similar to adult, a twofold ED95 produces satisfactory surgical muscle relaxation in children receiving mivacurium. Thus, its onset time is comparable to that of vecuronium or atracurium. The shorter duration of action offering a tighter control over relaxation may be of clinical advantage in this age group.

摘要

引言与目的

米库氯铵是一种新型非去极化肌松药,起效相对较快,作用时间较短。在儿童中,静脉注射0.2mg/kg可产生满意的肌松效果。由于已发现吸入麻醉药可增强肌松药的效能,我们测定了吸入氟烷(HAL)、恩氟烷(ENF)或异氟烷(ISO)后米库氯铵的起效或恢复时间是否受到影响。

方法

36例外科手术儿童(2 - 6岁,ASA I级)在肌肉注射诱导后,随机分为三组,分别吸入HAL(n = 12)、ENF(n = 12)或ISO(n = 12)。每隔20秒通过肌电图(Relaxograph,Datex)测定四个成串刺激(TOF)反应。在N₂O/O₂(2:1)中分别吸入HAL、ENF或ISO(浓度分别为0.8%、1.2%、1.0%体积分数)10分钟后,静脉注射0.2mg/kg米库氯铵。当T₁最大程度抑制时进行气管插管,并根据分级评分判断插管条件。当T₁恢复至25%时,每组6例患者用30μg/kg新斯的明和15μg/kg阿托品进行拮抗;将恢复指标与未拮抗患者的指标进行比较。组间差异采用多因素方差分析(p < 0.05)。

结果

除1例患者在插管后出现中度屏气外,所有患者的插管条件均评为“优秀”或“良好”。接受HAL的患者米库氯铵起效时间为2.4分钟±0.52(±标准差);接受ENF的患者为2.4分钟±0.55;接受ISO的患者为2.6分钟±0.68。恢复至T₁ = 25%的时间为7.6分钟±2.91(HAL);7.9分钟±1.55(ENF)和8.6分钟±2.30(ISO)。组间恢复指标无显著差异。未拮抗患者的总作用时间为13.0分钟±3.32(HAL);14.3分钟±4.01(ENF)和19.6分钟±5.17(ISO),而拮抗后的作用时间为13.4分钟±5.11(HAL);13.3分钟±1.97(ENF)和15.6分钟±4.25(ISO)。新斯的明注射后总作用时间缩短约0.5 - 2分钟,差异无统计学意义。

讨论与结论

注射0.2mg/kg米库氯铵后,接受氟烷、恩氟烷或异氟烷的儿童在起效或恢复时间上无临床相关差异。组间心率和血压无差异。与先前米库氯铵的研究相比,我们注意到平均起效时间长30 - 60%且平均自主恢复时间短30%。这可能是由于我们患者的平均年龄较低,这与相对较高的分布容积相关,如果按每千克体重计算剂量,会导致血浆浓度较低。新斯的明注射后平均恢复时间缩短2分钟似乎无临床意义。与成人相似,两倍的ED95可使接受米库氯铵的儿童产生满意的外科肌松效果。因此,其起效时间与维库溴铵或阿曲库铵相当。作用时间较短,能更严格地控制肌松,在该年龄组可能具有临床优势。

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