帕瑞昔布预防性镇痛促进月夷十二指肠切除术后患者加速康复的安全性、有效性研究

Effectiveness and safety of preventive analgesia using parecoxib in enhanced recovery after surgery strategy for patients undergoing pancreaticoduodenectomy

目的:评价帕瑞昔布预防性镇痛对开放胰十二指肠切除(pancreaticoduodenectomy,PD)手术患者围术期实施加速康复外科(enhanced recovery after surgery,ERAS)路径的安全性及有效性.方法:前瞻性纳入2017年10月至2019年2月在北京大学第一医院普通外科行开放PD手术且符合入组标准的患者,采用随机数字表法随机分为帕瑞昔布组(P组)和对照组(C组).两组患者均于围术期接受全部ERAS项目,P组患者于手术结束时静脉注射帕瑞昔布40mg,术后每间隔12h静脉注射帕瑞昔布40mg至术后5d,期间根据疼痛情况,可以随时追加阿片类(吗啡、哌替啶等)镇痛药物;C组患者术后除常规应用硬膜外自控镇痛泵(patient controlled epidural analgesia,PCEA)镇痛外,根据患者疼痛情况,按需使用阿片类(吗啡、哌替啶等)镇痛药物.两组患者均以术后不发生重度疼痛作为术后镇痛的目标.记录两组患者术前第1天、手术后当天清醒后、手术后第1~5天的静息视觉模拟评分法(visual analogue scale,VAS)评分;术后阿片类药物的使用次数、术后排气时间、首次离床活动时间、拔除胃管时间、进流质食物时间和术后住院时间;比较两组患者术后并发症发生率、围术期病死率和术后30 d内再入院率.结果:58例患者完成本研究,其中P组28例,C组30例,两组均无围术期死亡发生.两组患者在手术后当天清醒后至第4天的VAS评分显著增高,至第5天基本恢复至术前水平,两组患者术后VAS评分差异无统计学意义,均未出现重度疼痛.与C组相比,P组患者使用阿片类药物次数显著减少[(10.0±0.4)次和(2.8±0.3)次,P<0.001],术后排气时间[(2.6±1.2)d和(3.9±1.6)d,P=0.032]和首次离床活动时间[(2.2±0.4)d和(3.0±1.1)d,P=0.046]明显缩短.两组患者术后拔除胃管时间、进流质食物时间和术后住院时间差异均无统计学意义,术后并发症发生率及再入院率比较两组患者差异无统计学意义.结论:ERAS策略中以帕瑞昔布预防性镇痛至PD术后5d安全可行,能显著减少阿片类药物的用量,促进患者术后胃肠道功能恢复,缩短术后排气和离床活动时间,不增加术后并发症发生风险.

Objective:To investigate the analgesic effect and safety of preventive analgesia using parecoxib in enhanced recovery after surgery(ERAS)strategy for patients undergoing pancreaticoduodenectomy(PD)procedure.Methods:Patients who underwent open PD in our hospital from October 2017 to February 2019 and met the inclusion criteria were enrolled in this prospective study.All the patients were randomly allocated into the parecoxib group(group P)and the control group(group C)using a random number table method.Patients in both groups received all ERAS items during the perioperative period.Patients in group P received 40 mg parecoxib intravenously at the end of the operation,and then every 12h until 5d after surgery.And if necessary,opioids(morphine or pethidine)could be administrated in order to avoid a severe pain.Patients in group G received opioids(morphine or pethidine)as needed to relieve pain after surery.In both groups,the goal of postoperative analgesia was to avoid severe pain.The resting visual analogue scale(VAS)scores of the two groups before surgery,the day of surgery(Do),and l-5d(D4) after surgery were recorded.The doses of opioid drugs,the first time of flatus,off-bed activity,gastric tube removal:oral fluid and food intake,as well as length of postoperative hospital stay,rates of complications,mortality and readmission within 30 d,were compared between the 2 groups.Results:A total of 58 patients were finally included in the study,including 28 cases in group P and 30 in group C.No perioperative death occurred in all these patients.The VAS scores in both of the 2 groups were increased significantly after surgery,until D5 when the pain was relieved to near the level of that before surgery.There was no significant difference in VAS scores between the 2 groups,and no severe pain occurred in all the patients.Compared with group 0,the uses of opioids in group P was significantly reduced[(10.0±0.4)doses vs(2.8±0.3)doses,P<0.001].The first time of flatus[(2.6±1.2)d vs(3.9±1.6)d,P<0.032]and off-bed activity[(2.2±0.4)d vs(3.0±1.1)d,P=0.046]were both significandy shortened in group P.However,there were no significant differences in the time of gastric tube removal,oral fluid and food intake,length of postoperative hospital stay,and the rates of complications,mortality and readmission between the 2 groups.Conclusions:The preventive analgesia using parecoxib until D5 in ERAS strategy for patient undergoing PD is safe and feasible.It can significandy reduce the doses of opioids and promote the recovery of gastrointestinal function after PD,shorten postoperative flatus time and off-bed activity without increasing the risk of postoperative complications.