Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands; Department of Anaesthesiology, Academic Medical Centre, Amsterdam, Netherlands.
Department of Anaesthesiology, Academic Medical Centre, Amsterdam, Netherlands.
Lancet Gastroenterol Hepatol. 2016 Oct;1(2):105-113. doi: 10.1016/S2468-1253(16)30012-7. Epub 2016 Jul 7.
Epidural analgesia is the international standard for pain treatment in abdominal surgery. Although some studies have advocated continuous wound infiltration with local anaesthetics, robust evidence is lacking, especially on patient-reported outcome measures. We aimed to determine the effectiveness of continuous wound infiltration in hepato-pancreato-biliary surgery.
In this randomised controlled, open label, non-inferiority trial (POP-UP), we enrolled adult patients undergoing hepato-pancreato-biliary surgery by subcostal or midline laparotomy in two Dutch hospitals. Patients were centrally randomised (1:1) to receive either pain treatment with continuous wound infiltration using bupivacaine plus patient-controlled analgesia with morphine or to receive (patient-controlled) epidural analgesia with bupivacaine and sufentanil. All patients were treated within an enhanced recovery setting. Randomisation was stratified by centre and type of incision. The primary outcome was the mean Overall Benefit of Analgesic Score (OBAS) from day 1-5, a validated composite endpoint of pain scores, opioid side-effects, and patient satisfaction (range 0 [best] to 28 [worst]). Analysis was per-protocol. The non-inferiority limit of the mean difference was + 3·0. This trial is registered with the Netherlands Trial Registry, number NTR4948.
Between Jan 20, 2015, and Sept 16, 2015, we randomly assigned 105 eligible patients: 53 to receive continuous wound infiltration and 52 to receive epidural analgesia. One patient in the continuous wound infiltration group discontinued treatment, as did five in the epidural analgesia group; of these five patients, preoperative placement failed in three (these patients were treated with continuous wound infiltration instead), one patient refused an epidural, and data for the primary endpoint was lost for one. Thus, 55 patients were included in the continuous wound infiltration group and 47 in the epidural analgesia group for the per-protocol analyses. Mean OBAS was 3·8 (SD 2·4) in the continuous wound infiltration group versus 4·4 (2·2) in the epidural group (mean difference -0·62, 95% CI -1·54 to 0·30). Because the upper bound of the one-sided 95% CI did not exceed +3·0, non-inferiority was shown. Four (7%) patients in the continuous wound infiltration group and five (11%) of those in the epidural group had an adverse event. One patient in the continuous wound infiltration group had a serious adverse event (temporary hypotension and arrhythmia after bolus injection); no serious adverse events were noted in the epidural group.
These data suggest that continuous wound infiltration is non-inferior to epidural analgesia in hepato-pancreato-biliary surgery within an enhanced recovery setting. Further large-scale trials are required to make a definitive assessment of non-inferiority.
Academic Medical Centre, Amsterdam, Netherlands.
硬膜外镇痛是腹部手术疼痛治疗的国际标准。尽管一些研究主张连续使用局部麻醉剂进行伤口浸润，但缺乏强有力的证据，特别是在患者报告的结果测量方面。我们旨在确定连续伤口浸润在肝胆胰手术中的效果。
在这项随机对照、开放标签、非劣效性试验（POP-UP）中，我们招募了在荷兰的两家医院接受经肋缘下或中线剖腹手术的成年肝胆胰手术患者。患者在中央以 1:1 的比例随机分配（1:1）接受布比卡因加吗啡患者自控镇痛的连续伤口浸润疼痛治疗或接受布比卡因和舒芬太尼的（患者自控）硬膜外镇痛。所有患者均在强化康复环境中接受治疗。随机化按中心和切口类型分层。主要结局是从第 1-5 天的平均整体镇痛评分（OBAS），这是疼痛评分、阿片类药物副作用和患者满意度的综合终点（范围 0 [最佳] 至 28 [最差]）。分析按方案进行。平均差异的非劣效性界限为+3.0。本试验在荷兰试验注册处注册，编号为 NTR4948。
2015 年 1 月 20 日至 2015 年 9 月 16 日期间，我们随机分配了 105 名符合条件的患者：53 名接受连续伤口浸润，52 名接受硬膜外镇痛。连续伤口浸润组有 1 名患者停止治疗，硬膜外镇痛组有 5 名患者停止治疗；这 5 名患者中，3 名患者术前放置失败（这些患者接受连续伤口浸润治疗），1 名患者拒绝硬膜外，1 名患者主要结局数据丢失。因此，55 名患者纳入连续伤口浸润组，47 名患者纳入硬膜外镇痛组进行方案分析。连续伤口浸润组的平均 OBAS 为 3.8（SD 2.4），硬膜外组为 4.4（2.2）（平均差异-0.62，95%CI-1.54 至 0.30）。由于单侧 95%CI 的上限不超过+3.0，因此显示非劣效性。连续伤口浸润组有 4 名（7%）患者和硬膜外组有 5 名（11%）患者发生不良事件。连续伤口浸润组有 1 名患者发生严重不良事件（推注后短暂低血压和心律失常）；硬膜外组未发生严重不良事件。
这些数据表明，在强化康复环境下，连续伤口浸润在肝胆胰手术中不劣于硬膜外镇痛。需要进一步的大规模试验来对非劣效性进行明确评估。
阿姆斯特丹学术医学中心，荷兰。
