Camann W, Abouleish A, Eisenach J, Hood D, Datta S
Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Reg Anesth Pain Med. 1998 Sep-Oct;23(5):457-62. doi: 10.1016/s1098-7339(98)90027-x.
Combinations of local anesthetics and opioids are frequently used during spinal and epidural analgesia for the relief of labor pain. This combination allows for a dose-sparing effect which may reduce potential side effects or toxicity. The precise nature of the interaction between opioids and local anesthetics in the clinical setting, i.e., additivity versus synergism, has not been established. This trial was designed to utilize a validated technique of analysis of drug interactions, isobolography, to investigate this interaction.
One hundred healthy laboring patients at term receiving a combined spinal and epidural technique were divided into nine groups as follows: intrathecal sufentanil 2, 5, or 10 microg (2 mL volume) and epidural saline (10 mL); epidural bupivacaine 5, 12.5, or 25 mg and intrathecal saline (2 mL volume); or combination of l, 2.5, and 5 microg intrathecal sufentanil plus 2.5, 6.25, or 12.5 mg epidural bupivacaine, using similar volumes, respectively. All drugs were administered in a randomized, double-blind fashion. Pain relief scores were assessed 20 minutes after drug injection, and isobolographic analysis was utilized to determine the nature of the interaction.
The ED50 of intrathecal sufentanil alone was 2.3 microg (95% CI 1.7-3.2), and the ED50 for epidural bupivacaine was 24 mg (95% CI 12-50). The combined sufentanil and bupivacaine fractional dose ED50 (in fractions of the single-dose ED50 values) was found to be approximately one-third and one-tenth of the single drug fractional dose, respectively: sufentanil 0.85 microg (0.36) and bupivacaine 2.2 mg (0.09). The duration of analgesia was nearly equivalent in all sufentanil-alone groups (83, 102, and 99 minutes); a dose-response effect was more apparent in the bupivacaine group (35, 42, and 74 minutes; P = .006) and the combination group (60, 79, 101 minutes; P = .028). Isobolography showed the combination dose to lie well within the area of synergism; however, the 95% confidence limits cross the line of additivity thus a pure additive interaction cannot be excluded.
Markedly reduced doses of these drugs in combination can be used to provide adequate analgesia during labor compared with either single drug alone.
局部麻醉药与阿片类药物联合使用常用于脊髓和硬膜外镇痛以缓解分娩疼痛。这种联合用药具有剂量节省效应，可减少潜在的副作用或毒性。在临床环境中，阿片类药物与局部麻醉药之间相互作用的确切性质，即相加作用与协同作用，尚未明确。本试验旨在利用一种经过验证的药物相互作用分析技术——等效应线图分析法来研究这种相互作用。
100例足月接受联合脊髓和硬膜外技术的健康产妇被分为9组，如下：鞘内注射舒芬太尼2、5或10微克（2毫升容积）加硬膜外注射生理盐水（10毫升）；硬膜外注射布比卡因5、12.5或25毫克加鞘内注射生理盐水（2毫升容积）；或分别使用相似容积，鞘内注射1、2.5和5微克舒芬太尼加硬膜外注射2.5、6.25或12.5毫克布比卡因的联合用药组。所有药物均采用随机、双盲方式给药。在注射药物20分钟后评估疼痛缓解评分，并利用等效应线图分析法确定相互作用的性质。
单独鞘内注射舒芬太尼的半数有效剂量（ED50）为2.3微克（95%可信区间1.7 - 3.2）；硬膜外注射布比卡因的ED50为24毫克（95%可信区间12 - 50）。舒芬太尼和布比卡因联合用药的分数剂量ED50（以单药分数剂量值表示）分别约为单药分数剂量的三分之一和十分之一：舒芬太尼0.85微克（0.36）和布比卡因2.2毫克（0.09）。所有单独使用舒芬太尼组的镇痛持续时间几乎相同（83、102和99分钟）；布比卡因组（35、42和74分钟；P = 0.006）和联合用药组（60、79、101分钟；P = 0.028）的剂量 - 反应效应更明显。等效应线图显示联合用药剂量处于协同作用区域内；然而，95%可信区间跨越相加作用线，因此不能排除纯粹的相加相互作用。
与单独使用单一药物相比，联合使用这些药物时显著降低的剂量可用于分娩期间提供充分的镇痛。
