Fanning Rebecca A, Campion Deirdre P, Collins Colm B, Keely Simon, Briggs Liam P, O'Connor John J, Carey Michael F
Department of Perioperative Medicine, Coombe Women and Infants University Hospital, Dublin 8, Ireland.
Anesth Analg. 2008 Oct;107(4):1303-7. doi: 10.1213/ane.0b013e3181804245.
Epidural analgesia with levobupivacaine and bupivacaine is a common and effective method of labor pain relief. However, its use is associated with an increased instrumental delivery rate. One of the mechanisms postulated to account for this unwanted effect is the direct effect of local anesthetics on myometrial contractility. We determined the effects of bupivacaine and levobupivacaine on the amplitude and frequency of contractions of human term myometrium.
Uterine specimens were obtained from nonlaboring parturients scheduled for elective lower-segment cesarean delivery at term. Longitudinal muscle strips were prepared and mounted vertically in tissue chambers, and changes in the amplitude (peak force) and the frequency of contractions were recorded. Spontaneous contractions commenced after a period of application of 1 g (9.81 mN) of tension to the myometrial strips. No uterotonic drugs were used. The muscle strips were then exposed to cumulative concentrations of bupivacaine and levobupivacaine and dose-response curves were generated.
Both bupivacaine and levobupivacaine decreased the amplitude of contractions in human myometrium in a concentration-dependent manner, reaching significance at 1x10(-4) M for both bupivacaine and levobupivacaine compared with the internal control amplitude. With both drugs, the decrease in amplitude was accompanied by an increase in the frequency of contractions reaching significance at 3x10(-5) M for both bupivacaine and levobupivacaine compared with the internal control frequency.
The concentrations required for the effects on amplitude are much higher (33 fold) than the clinically relevant plasma concentrations of these drugs after epidural administration, and are unlikely to be significant in the setting of low-dose epidural analgesia in labor.
左旋布比卡因和布比卡因用于硬膜外镇痛是一种常见且有效的分娩镇痛方法。然而,其使用与器械助产率增加有关。推测导致这种不良影响的机制之一是局部麻醉药对子宫肌层收缩力的直接作用。我们测定了布比卡因和左旋布比卡因对足月人子宫肌层收缩幅度和频率的影响。
子宫标本取自足月计划行择期下段剖宫产的未临产产妇。制备纵行肌条并垂直安装于组织浴槽中,记录收缩幅度(峰值力)和频率的变化。在对子宫肌条施加1g(9.81mN)张力一段时间后开始出现自发收缩。未使用宫缩剂。然后将肌条暴露于布比卡因和左旋布比卡因的累积浓度下,并生成剂量-反应曲线。
布比卡因和左旋布比卡因均以浓度依赖性方式降低人子宫肌层的收缩幅度,与自身对照幅度相比,布比卡因和左旋布比卡因在1×10⁻⁴M时均达到显著水平。两种药物在使收缩幅度降低的同时,收缩频率均增加,与自身对照频率相比,布比卡因和左旋布比卡因在3×10⁻⁵M时均达到显著水平。
对收缩幅度产生影响所需的浓度比硬膜外给药后这些药物的临床相关血浆浓度高得多(33倍),在低剂量分娩硬膜外镇痛情况下不太可能具有显著意义。