Merker M, Kranke P, Morin A M, Rüsch D, Eberhart L H J
Klinik für Anästhesie und Intensivtherapie, Philipps-Universität Marburg, Deutschland.
Anaesthesist. 2011 May;60(5):432-40, 442-5. doi: 10.1007/s00101-010-1825-4. Epub 2010 Dec 12.
The aim of the present study was to conduct a meta-analysis of the results from randomized controlled trials investigating the relative efficacy of droperidol versus metoclopramide for the prevention of postoperative nausea and vomiting (PONV).
A systematic literature search for randomized controlled trials comparing droperidol and metoclopramide for the prevention of PONV was performed according to the PRISMA recommendations. The incidence of PONV within the early (0-6 h) and cumulative postoperative periods (0-48 h) was collated and the pooled relative risk (RR) with the corresponding 95% confidence interval (CI) was calculated. Results from a subgroup analysis are presented excluding the data of a Japanese group (Fujii et al.) which are given in parentheses.
A total of 41 (30) trials with a total number of 3,491 (2,721) patients were included and of these 12 (8) trials with 1,403 (1,083) patients reported data of the early period and 32 (21) studies with 2,656 (1,836) patients comprised data of the cumulative period. A total of 1,797 (1,309) patients were treated with droperidol (0.25-5 mg) and 1,694 (1,412) with metoclopramide (5-50 mg). In the early period the risk for PONV after metoclopramide was 35% (95%-CI: 17-57%) higher than after prophylaxis with droperidol (without Fujii data: 46%; 23-73%). During the cumulative period the risk for PONV after metoclopramide was increased by 20% (95%-CI: 7-37%) compared to droperidol (without Fujii data: 25%; 4-50%). Due to heterogenous dosing of both drugs subgroup analyses with distinct dose intervals were performed with increments of 0.75 mg for droperidol and 7 mg for metoclopramide. Droperidol was superior in 17 (12) out of 19 (14) subgroup analyses. Comparing recommended doses of droperidol (0.75-1.5 mg) with low doses of metoclopramide (7-14 mg) and medium metoclopramide doses (14-21 mg) PONV was increased by 12% (95%-CI: -11% to 42%) and 32% (95%-CI: 4%-66%), respectively when metoclopramide instead of droperidol was used. When higher doses of metoclopramide (>20 mg) were used the superiority of droperidol was less pronounced and did not reach statistical significance due to the limited numbers of trials included in this analysis (3 studies, 662 patients). The risk for PONV after high-dose metoclopramide was increased by 13% (95%-CI: -21% to +61%) for the early period and by 19% (95%-CI: -11% to +57%) for the cumulative observation period.
For the prevention of postoperative nausea and vomiting droperidol is significantly superior to metoclopramide doses below 20 mg. There was no obvious positive dose response with respect to increasing doses of metoclopramide. There was also a trend towards higher efficacy of droperidol compared to higher doses of metoclopramide (≥20 mg). However, there were not enough comparative studies to show a statistically significant result in this subgroup analysis. These data support the notion that droperidol in low doses may represent the more effective D(2)-antagonist for a pharmacological armamentarium to cope with PONV.
本研究旨在对随机对照试验的结果进行荟萃分析,以调查氟哌利多与甲氧氯普胺预防术后恶心和呕吐(PONV)的相对疗效。
根据PRISMA建议,对比较氟哌利多和甲氧氯普胺预防PONV的随机对照试验进行系统文献检索。整理术后早期(0 - 6小时)和累积期(0 - 48小时)内PONV的发生率,并计算合并相对风险(RR)及相应的95%置信区间(CI)。给出了排除日本组(藤井等人)数据后的亚组分析结果(括号内为该组数据)。
共纳入41项(30项)试验,患者总数为3491例(2721例),其中12项(8项)试验共1403例(1083例)患者报告了早期数据,32项(21项)研究共2656例(1836例)患者纳入了累积期数据。共有1797例(1309例)患者接受氟哌利多(0.25 - 5mg)治疗,1694例(1412例)患者接受甲氧氯普胺(5 - 50mg)治疗。在早期,甲氧氯普胺治疗后PONV的风险比氟哌利多预防后高35%(95%CI:17 - 57%)(排除藤井数据:46%;23 - 73%)。在累积期内,与氟哌利多相比,甲氧氯普胺治疗后PONV的风险增加了20%(95%CI:7 - 37%)(排除藤井数据:25%;4 - 50%)。由于两种药物的给药剂量存在异质性,因此进行了不同剂量间隔的亚组分析,氟哌利多剂量递增0.75mg步长,甲氧氯普胺剂量递增7mg步长。在19项(14项)亚组分析中有17项(12项)显示氟哌利多更优。将氟哌利多的推荐剂量(0.75 - 1.5mg)与低剂量甲氧氯普胺(7 - 14mg)和中等剂量甲氧氯普胺(14 - 21mg)进行比较,当使用甲氧氯普胺而非氟哌利多时,PONV分别增加了12%(95%CI: - 11%至42%)和32%(95%CI:4% - 66%)。当使用更高剂量的甲氧氯普胺(>20mg)时,氟哌利多的优势不太明显,由于该分析纳入的试验数量有限(3项研究,662例患者),未达到统计学意义。高剂量甲氧氯普胺治疗后,早期PONV风险增加13%(95%CI: - 21%至 + 61%),累积观察期内增加19%(95%CI: - 11%至 + 57%)。
对于预防术后恶心和呕吐,氟哌利多明显优于20mg以下剂量的甲氧氯普胺。甲氧氯普胺剂量增加时未观察到明显的正向剂量反应。与更高剂量的甲氧氯普胺(≥20mg)相比,氟哌利多也有疗效更高的趋势。然而,该亚组分析中没有足够的比较研究来显示统计学上的显著结果。这些数据支持了低剂量氟哌利多可能是应对PONV更有效的D(2)拮抗剂这一观点。