From the Department of Anesthesia, Perioperative Medicine and Pain Management, Dalhousie University, Nova Scotia Health Authority and Izaak Walton Killam Health Centre, Halifax, Nova Scotia, Canada.
Research Methods Unit, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada.
Anesth Analg. 2020 Jan;130(1):111-125. doi: 10.1213/ANE.0000000000003975.
Fentanyl and morphine are the 2 most commonly added opioids to bupivacaine for spinal anesthesia during cesarean delivery. Numerous clinical trials have assessed efficacy and safety of different doses of fentanyl added to intrathecal bupivacaine for spinal anesthesia, yet its benefit, harm, and optimal dose remain unclear. This study aimed to systematically review the evidence of the efficacy of fentanyl when added to intrathecal bupivacaine alone and when added to bupivacaine with morphine for spinal anesthesia during cesarean delivery.
Key electronic databases (PubMed, Embase, and Cochrane Library) were searched for randomized controlled trials in the cesarean delivery population. The primary outcome was the failure rate of spinal anesthesia, as assessed by the need for either conversion to general anesthesia or intraoperative analgesic supplementation. Two reviewers independently extracted the data using a standardized electronic form. Results are expressed as relative risks or mean differences with 95% CIs.
Seventeen randomized controlled clinical trials (most judged as low or unclear risk of bias) with 1064 participants provided data for the meta-analysis. Fentanyl added to intrathecal bupivacaine alone reduced the need for intraoperative supplemental analgesia (relative risk, 0.18; 95% CI, 0.11-0.27; number needed to treat, 4) and the incidence of nausea/vomiting (relative risk, 0.41; 95% CI, 0.24-0.70; number needed to treat, 6.5), with longer time to first postoperative analgesia request (mean difference, 91 minutes; 95% CI, 69-113). No difference was observed regarding the need for conversion to general anesthesia (relative risk, 0.67; 95% CI, 0.12-3.57), the incidence of hypotension, the onset of sensory block, or the duration of motor block. However, the addition of intrathecal fentanyl was associated with higher incidence of intraoperative pruritus (relative risk, 5.89; 95% CI, 2.07-16.79; number needed to harm, 13.5). The inclusion of fentanyl to intrathecal bupivacaine-morphine compared to intrathecal bupivacaine-morphine alone conferred a similar benefit, with a significantly reduced need for intraoperative supplemental analgesia (relative risk, 0.16; 95% CI, 0.03-0.95; number needed to treat, 9). Analysis using a funnel plot indicated a possibility of publication bias in included studies.
Current evidence suggests a benefit of using fentanyl as both an additive to intrathecal bupivacaine alone and to intrathecal bupivacaine combined with morphine for cesarean delivery under spinal anesthesia. The possibility of publication bias, small sample size, and high risk of bias in some of the included studies warrant treating the results with caution.
芬太尼和吗啡是剖宫产椎管内麻醉时最常添加到布比卡因中的两种阿片类药物。大量临床试验评估了不同剂量芬太尼添加到蛛网膜下腔布比卡因中用于椎管内麻醉的效果和安全性，但它的益处、危害和最佳剂量仍不清楚。本研究旨在系统评价芬太尼单独添加到蛛网膜下腔布比卡因中和与吗啡联合添加到蛛网膜下腔布比卡因中用于剖宫产时的疗效证据。
在剖宫产人群中，检索主要电子数据库（PubMed、Embase 和 Cochrane Library）的随机对照试验。主要结局是椎管内麻醉失败率，评估方法为需要转为全身麻醉或术中镇痛补充。两名评审员使用标准化电子表格独立提取数据。结果以相对风险或均数差值及其 95%置信区间表示。
17 项随机对照临床试验（大多数被判定为低风险或不确定偏倚风险），共 1064 名参与者提供了用于荟萃分析的数据。芬太尼单独添加到蛛网膜下腔布比卡因中减少了术中补充镇痛的需要（相对风险，0.18；95%置信区间，0.11-0.27；需要治疗的人数，4）和恶心/呕吐的发生率（相对风险，0.41；95%置信区间，0.24-0.70；需要治疗的人数，6.5），但首次术后镇痛请求的时间延长（平均差值，91 分钟；95%置信区间，69-113）。两组在需要转为全身麻醉（相对风险，0.67；95%置信区间，0.12-3.57）、低血压发生率、感觉阻滞开始时间或运动阻滞持续时间方面无差异。然而，鞘内芬太尼的添加与术中瘙痒的发生率增加相关（相对风险，5.89；95%置信区间，2.07-16.79；需要治疗的人数，13.5）。与单独鞘内布比卡因-吗啡相比，鞘内布比卡因-吗啡中添加芬太尼具有相似的益处，术中补充镇痛的需要明显减少（相对风险，0.16；95%置信区间，0.03-0.95；需要治疗的人数，9）。漏斗图分析表明，纳入研究中存在发表偏倚的可能性。
目前的证据表明，芬太尼无论是单独添加到蛛网膜下腔布比卡因中，还是添加到蛛网膜下腔布比卡因与吗啡联合使用，对剖宫产椎管内麻醉都有一定的益处。纳入研究中存在发表偏倚的可能性、样本量小和部分研究的高偏倚风险，提示应谨慎对待这些结果。
