非甾体抗炎药注射剂用于术后镇痛的疗效与安全性系统评价和Meta分析

Efficacy and safety of injectable non-steroidal anti-inflammatory drugs for postoperative analgesia: a systematic review and Meta-analysis

摘要

目的: 系统评价多种非甾体抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)注射剂用于术后镇痛的有效性和安全性。方法: 计算机检索CNKI、WanFang、VIP、SinoMed、PubMed、Embase、Web of Science及Cochrane Library数据库,并补充检索临床试验注册平台,检索时限均从建库至2025年9月。采用Cochrane偏倚风险评估工具评价纳入研究质量,采用RevMan 5.4和Stata软件进行数据合并。结果: 共纳入58项研究,涉及9种NSAIDs药物。与安慰剂相比,所有NSAIDs均能减少术后24 h阿片类药物用量(P＜0.05),其中苯胺洛芬降幅最显著(合并减少率36.8%,95%CI:32.0%~40.0%),并能降低术后24 h患者自控镇痛的补救需求[RR=0.42,95%CI(0.30, 0.58),P＜0.001]及有效按压次数。在镇痛效果方面,帕瑞昔布和布洛芬可降低术后24 h疼痛评分(均P＜0.001);安全性方面,帕瑞昔布组显著降低了总体不良事件发生风险[RR=0.61,95%CI(0.51, 0.73)]和胃肠道事件发生风险[RR=0.67,95%CI(0.54, 0.85)],苯胺洛芬亦显示出良好的安全性趋势。结论: NSAIDs注射剂可有效降低术后疼痛评分并减少阿片类药物消耗量,帕瑞昔布和苯胺洛芬安全性良好。未来研究应关注特定患者人群的剂量-反应关系和长期安全性。

Abstract

Objective: To systematically evaluate the efficacy and safety of injectable non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative analgesia. Methods: A comprehensive literature search was conducted across databases including CNKI, WanFang, VIP, SinoMed, PubMed, Embase, Web of Science, and the Cochrane Library, supplemented by clinical trial registries, from inception to September 2025. The Cochrane Risk of Bias tool was utilized to assess the methodological quality of the included studies. Data synthesis and Meta-analysis were performed using RevMan 5.4 and Stata software. Results: A total of 58 studies involving nine injectable NSAIDs were included. Compared with placebo, all evaluated NSAIDs significantly reduced cumulative opioid consumption at 24 hours postoperatively (all P＜0.05). Notably, binaprofen exhibited the most substantial opioid-sparing effect (pooled reduction rate: 36.8%, 95% CI: 32.0% to 40.0%). Furthermore, binaprofen significantly decreased the requirement for patient-controlled analgesia (PCA) rescue [RR=0.42, 95%CI(0.30, 0.58), P＜0.001] and the number of effective PCA demands at 24 h. Regarding analgesic efficacy, both parecoxib and ibuprofen significantly lowered pain scores at 24 h postoperatively (both P＜0.001). In terms of safety, parecoxib significantly reduced the risk of overall adverse events [RR=0.61, 95%CI (0.51, 0.73)] and gastrointestinal events [RR=0.67, 95%CI (0.54, 0.85)]. Binaprofen also demonstrated a favorable safety profile. Conclusion: Injectable NSAIDs effectively alleviate postoperative pain and exert a significant opioid-sparing effect, with parecoxib and binaprofen demonstrating favorable safety profiles. Future well-designed studies should focus on the dose-response relationship and long-term safety in specific patient populations.

关键词

非甾体抗炎药 / 注射剂 / 术后镇痛 / 阿片类药物节约效应 / Meta分析

Key words

non-steroidal anti-inflammatory drugs / injections / postoperative analgesia / opioid-sparing effect / Meta-analysis

[1] GAN TJ, HABIB AS, MILLER TE, et al. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey[J]. Curr Med Res Opin, 2014, 30(1): 149-160.
[2] APFELBAUM JL, CHEN C, MEHTA SS, et al. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged[J]. Anesth Analg, 2003, 97(2): 534-540.
[3] COZOWICZ C, BEKERIS J, POERAN J, et al. Multimodal pain management and postoperative outcomes in lumbar spine fusion surgery: a population-based cohort study[J]. Spine, 2020, 45(9): 580-589.
[4] YIU CH, GNJIDIC D, PATANWALA A, et al. Opioid-related adverse drug events in surgical patients: risk factors and association with clinical outcomes[J]. Expert Opin Drug Saf, 2022, 21(9): 1211-1223.
[5] MCCORQUODALE CL, GREENING R, TULLOCH R, et al. Opioid prescribing for acute postoperative pain: an overview of systematic reviews related to two consensus statements relevant at patient, prescriber, system and public health levels[J]. BMC Anesthesiol, 2023, 23(1): 294.
[6] MESÍA R, VIRIZUELA ECHABURU JA, GÓMEZ J, et al. Opioid-induced constipation in oncological patients: new strategies of management[J]. Curr Treat Options Oncol, 2019, 20(12): 91.
[7] WICK EC, GRANT MC, WU CL. Postoperative multimodal analgesia pain management with nonopioid analgesics and techniques: a review[J]. JAMA Surg, 2017, 152(7): 691.
[8] TOCHIE JN, BENGONO BENGONO RS, METOGO JM, et al. The efficacy and safety of an adapted opioid-free anesthesia regimen versus conventional general anesthesia in gynecological surgery for low-resource settings: a randomized pilot study[J]. BMC Anesthesiol, 2022, 22(1): 325.
[9] VANE JR, BOTTING RM. Anti-inflammatory drugs and their mechanism of action[J]. Inflamm Res, 1998, 47(2): 78-87.
[10] KÖHLER O, PETERSEN L, MORS O, et al. Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes[J]. Brain Behav, 2015, 5(8): e00338.
[11] AGRAWAL R, TESTI I, LEE CS, et al. Evolving consensus for immunomodulatory therapy in non-infectious uveitis during the COVID-19 pandemic[J]. Br J Ophthalmol, 2021, 105(5): 639-647.
[12] 国家卫生健康委员会医管中心加速康复外科专家委员会, 浙江省医师协会临床药师专家委员会, 浙江省药学会医院药学专业委员会. 中国加速康复外科围手术期非甾体抗炎药临床应用专家共识[J]. 中华普通外科杂志, 2019, 34(3): 283-288.
[13] STEPHENS J. The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors[J]. Rheumatology, 2003, 42(90003): 40iii-40i52.
[14] GUAN JB, FENG NN, YANG KT, et al. The efficacy and safety of ketorolac for postoperative pain management in lumbar spine surgery: a meta-analysis of randomized controlled trials[J]. Syst Rev, 2024, 13(1): 275.
[15] DOMPER ARNAL MJ, HIJOS-MALLADA G, LANAS A. Gastrointestinal and cardiovascular adverse events associated with NSAIDs[J]. Expert Opin Drug Saf, 2022, 21(3): 373-384.
[16] HUANG YX, LIU FM, LAI JD, et al. The adjuvant treatment role of ω-3 fatty acids by regulating gut microbiota positively in the acne vulgaris[J]. J Dermatol Treat, 2024, 35: 2299107.
[17] PUNTILLO F, GIGLIO M, VARRASSI G. The routes of administration for acute postoperative pain medication[J]. Pain Ther, 2021, 10(2): 909-925.
[18] RECHBERGER T, MACK RJ, MCCALLUM SW, et al. Analgesic efficacy and safety of intravenous meloxicam in subjects with moderate-to-severe pain after open abdominal hysterectomy: a phase 2 randomized clinical trial[J]. Anesth Analg, 2019, 128(6): 1309-1318.
[19] HU SL, LIU X, WAN QH, et al. Bioequivalence of meloxicam nanocrystal injection in healthy Chinese volunteers[J]. Clinical Pharm Drug Dev, 2024, 13(12): 1339-1344.
[20] MA CH, TWOREK KB, KUNG JY, et al. Systemic nonsteroidal anti-inflammatories for analgesia in postoperative critical care patients: a systematic review and meta-analysis of randomized control trials[J]. Crit Care Explor, 2023, 5(7): e0938.
[21] CHOI M, WANG L, CORONEOS CJ, et al. Managing postoperative pain in adult outpatients: a systematic review and meta-analysis comparing codeine with NSAIDs[J]. Can Med Assoc J, 2021, 193(24): E895-E905.
[22] HIGGINS JPT, ALTMAN DG, GOTZSCHE PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials[J]. BMJ, 2011, 343(oct18 2): d5928.
[23] 邓嘉陵, 李军祥, 杨小霖. 氟比洛芬酯和帕瑞昔布钠对腰椎间盘术后疼痛影响[J]. 西部医学, 2015, 27(8): 1187-1189.
[24] NONG LD, SUN Y, TIAN YK, et al. Effects of parecoxib on morphine analgesia after gynecology tumor operation: a randomized trial of parecoxib used in postsurgical pain management[J]. J Surg Res, 2013, 183(2): 821-826.
[25] 安玉明. 结肠癌术后镇痛及肠道不良反应观察[J]. 现代消化及介入诊疗, 2019, 24(12): 1452-1454.
[26] 丁永英. 帕瑞昔布钠对开胸手术患者术后吗啡用量的影响[J]. 中国药师, 2011, 14(8): 1176, 1211.
[27] 张彦, 张秀山, 刘海根. 帕瑞昔布钠在鼻内镜手术术后镇痛的应用[J]. 中国医院药学杂志, 2009, 29(21): 1858-1861.
[28] 林志超, 杨国超, 王文绍. 帕瑞昔布治疗腹部手术后肠系膜牵拉早期疼痛的疗效观察[J]. 北方药学, 2019(12): 106-107.
[29] 张琴, 李卿, 朱磊. 右美托咪定和帕瑞昔布钠预防瑞芬太尼麻醉患者术后痛觉过敏的临床研究[J]. 当代医学, 2019, 25(6): 141-143.
[30] 潘德标, 徐胜前. 帕瑞昔布钠用于腹腔镜胆囊切除术患者术后镇痛效果的观察[J]. 现代实用医学, 2017, 29(9): 1195-1196.
[31] 胡小风. 帕瑞昔布对腹腔镜下Dixon术患者术后疼痛及IL-12、IL-4的影响[D]. 长沙: 中南大学, 2010.
[32] 张颉驰, 马珏, 李红英. 帕瑞昔布不同给药方式对开腹术后镇痛及胃肠功能恢复的影响[J]. 国际医药卫生导报, 2015(15): 2201-2204.
[33] 陈锴. 帕瑞昔布钠对老年患者术后镇痛及细胞免疫的影响[D]. 延安: 延安大学, 2016.
[34] 陈斌, 魏云海, 束龙文. 帕瑞昔布钠用于宫颈癌根治术后镇痛效果的临床研究[J]. 中国性科学, 2015(4): 8-10.
[35] 张爱春, 杨凤兰, 向智勇. 帕瑞昔布钠用于妇科腹腔镜手术患者术后镇痛效果的观察[J]. 浙江创伤外科, 2014, 19(2): 325-327.
[36] 农丽丹, 孙怡, 赵国栋. 帕瑞昔布对妇科肿瘤手术后吗啡静脉镇痛的影响[J]. 临床麻醉学杂志, 2011, 27(4): 349-350.
[37] 孙立新, 丛丽, 时飞, 等. 帕瑞昔布钠复合吗啡对腹部手术患者自控镇痛及呼吸功能的影响[J]. 中国临床药理学与治疗学, 2011, 16(3): 308-312.
[38] 陈康卫, 蓝丽霞. 帕瑞昔布钠用于妇科腹腔镜术后镇痛50例[J]. 中国药业, 2011, 20(9): 61-62.
[39] 吴跃, 裘卫东. 帕瑞昔布钠对胃癌根治术后镇痛与机体应激反应的影响[J]. 医药导报, 2009, 28(12): 1558-1561.
[40] 蒋巧芬, 雷月, 晋维林, 等. 帕瑞昔布钠用于腹腔镜胆囊切除术后镇痛的临床观察[J]. 江苏医药, 2010, 36(10): 1220.
[41] WANG RD, ZHU JY, ZHU Y, et al. Perioperative analgesia with parecoxib sodium improves postoperative pain and immune function in patients undergoing hepatectomy for hepatocellular carcinoma[J]. Evaluation Clinical Practice, 2020, 26(3): 992-1000.
[42] 黄帅豪, 郑秋坚, 王义生, 等. 非甾体类抗炎镇痛药在腰椎后路内固定术后镇痛效果的比较[J]. 实用医学杂志, 2014, 30(20): 3321-3323.
[43] 周小平. 帕瑞昔布钠用于术后镇痛60例临床观察[J]. 武警医学院学报, 2011, 20(7): 563-564.
[44] 武若杰. 帕瑞昔布钠通过下调CXCL8-CXCR1/2改善腹腔镜下直肠癌根治术患者炎症微环境[D]. 蚌埠: 蚌埠医科大学, 2025.
[45] 李俊, 于涛, 李红玉. 帕瑞昔布钠联合自控静脉镇痛在胸外科手术麻醉中的应用[J]. 智慧健康, 2023, 9(22): 62-65.
[46] 贾瑞芳, 左明章. 氟比洛芬酯对中重度术后疼痛患者吗啡用量及效果的影响[J]. 医药导报, 2009, 28(1): 62-64.
[47] 邓志福. 氟比洛芬酯用于腹部手术患者术后镇痛效果观察[J]. 白求恩医学杂志, 2018, 16(6): 547-549.
[48] 卢宜民, 于哲. 氟比洛芬酯超前镇痛对子宫切除术后镇痛的影响[J]. 中国医师进修杂志, 2009, 32(21): 50-52.
[49] 施宏垒, 黄炎. 氟比洛芬酯对不同部位腹腔镜手术术后镇痛作用的分析[J]. 中国现代医生, 2009, 47(23): 103-104, 108.
[50] 宋闯. 氟比洛芬酯对直肠手术病人IL-2和IL-8及术后镇痛的影响[D]. 长春: 吉林大学, 2009.
[51] 邱庆荣, 张世清. 氟比洛芬酯对子宫切除患者术后镇痛的效应[J]. 安徽医学, 2009, 30(8): 939-940.
[52] 齐小冰. 氟比洛芬酯用于阴式子宫切除术后镇痛效果的观察[D]. 沈阳: 中国医科大学, 2009.
[53] 张维清. 氟比洛芬酯注射液对择期子宫次全切手术患者术后镇痛效果的观察[J]. 辽宁中医药大学学报, 2009, 11(7): 124-126.
[54] WANG VC, PRESTON MA, KIBEL AS, et al. A prospective, randomized, double-blind, placebo-controlled trial to evaluate intravenous acetaminophen versus placebo in patients undergoing robotic-assisted laparoscopic prostatectomy[J]. J Pain Palliat Care Pharmacother, 2018, 32(2-3): 82-89.
[55] ARYAIE AH, LALEZARI S, SERGENT WK, et al. Decreased opioid consumption and enhance recovery with the addition of IV Acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study)[J]. Surg Endosc, 2018, 32(8): 3432-3438.
[56] BERNSTEIN J, SPITZER Y, OHAEGBULAM K, et al. The analgesic efficacy of IV acetaminophen for acute postoperative pain in C-section patients: a randomized, double-blind, placebo-controlled study[J]. J Matern Fetal Neonatal Med, 2022, 35(5): 933-940.
[57] MAMOUN NF, LIN PR, ZIMMERMAN NM, et al. Intravenous acetaminophen analgesia after cardiac surgery: a randomized, blinded, controlled superiority trial[J]. J Thorac Cardiovasc Surg, 2016, 152(3): 881-889.e1.
[58] JELACIC S, BOLLAG L, BOWDLE A, et al. Intravenous acetaminophen as an adjunct analgesic in cardiac surgery reduces opioid consumption but not opioid-related adverse effects: a randomized controlled trial[J]. J Cardiothorac Vasc Anesth, 2016, 30(4): 997-1004.
[59] DE OLIVEIRA GS Jr, RODES ME, BIALEK J, et al. Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: a prospective, randomized, double-blinded, placebo controlled, clinical trial[J]. Breast J, 2018, 24(3): 240-244.
[60] RINDOS NB, MANSURIA SM, ECKER AM, et al. Intravenous acetaminophen vs saline in perioperative analgesia with laparoscopic hysterectomy[J]. Am J Obstet Gynecol, 2019, 220(4): 373.e1-373.e8.
[61] TYLER MA, LAM K, ASHOORI F, et al. Analgesic effects of intravenous acetaminophen vs placebo for endoscopic sinus surgery and postoperative pain: a randomized clinical trial[J]. JAMA Otolaryngol Head Neck Surg, 2017, 143(8): 788.
[62] EKINCI M, CIFTCI B, CELIK EC, et al. A randomized, placebo-controlled, double-blind study that evaluates efficacy of intravenous ibuprofen and acetaminophen for postoperative pain treatment following laparoscopic cholecystectomy surgery[J]. J Gastrointest Surg, 2020, 24(4): 780-785.
[63] NAM S, YOO S, PARK SK, et al. Additive effect of asingle intravenous dose ofacetaminophen administered at the end of laparoscopic hysterectomy on postoperative pain control with nefopam and fentanyl-based patient-controlled analgesia: a double-blind, randomized controlled trial[J]. BMC Anesthesiol, 2025, 25(1): 88.
[64] LANGE M, LEE CW, KNISELY T, et al. Efficacy of intravenous acetaminophen in length of stay and postoperative pain control in laparoscopic roux-en-Y gastric bypass surgery patients[J]. Bariatr Surg Pract Patient Care, 2018, 13(3): 103-108.
[65] KROLL PB, MEADOWS L, ROCK A, et al. A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (IV-ibuprofen) in the management of postoperative pain following abdominal hysterectomy[J]. Pain Pract, 2011, 11(1): 23-32.
[66] SOUTHWORTH S, PETERS J, ROCK A, et al. A multicenter, randomized, double-blind, placebo- controlled trial of intravenous ibuprofen 400 and 800 Mg every 6 hours in the management of postoperative pain[J]. Clin Ther, 2009, 31(9): 1922-1935.
[67] GAGO MARTÍNEZ A, ESCONTRELA RODRIGUEZ B, PLANAS ROCA A, et al. Intravenous ibuprofen for treatment of post-operative pain: a multicenter, double blind, placebo-controlled, randomized clinical trial[J]. PLoS One, 2016, 11(5): e0154004.
[68] KOTSOVOLIS G, KARAKOULAS K, GROSOMANIDIS V, et al. Comparison between the combination of gabapentin, ketamine, lornoxicam, and local ropivacaine and each of these drugs alone for pain after laparoscopic cholecystectomy: a randomized trial[J]. Pain Pract, 2015, 15(4): 355-363.
[69] SIVRIKOZ N, KOLTKA K, GURESTI E, et al. Perioperative dexketoprofen or lornoxicam administration for pain management after major orthopedic surgery: a randomized, controlled study[J]. Agri, 2014, 26(1): 23-28.
[70] 孙立新, 侯念果, 艾登斌, 等. 氯诺昔康复合吗啡镇痛对肺切除患者术后呼吸功能的影响[J]. 临床麻醉学杂志, 2010, 26(4): 295-297.
[71] KORKMAZ DILMEN O, TUNALI Y, CAKMAKKAYA OS, et al. Efficacy of intravenous paracetamol, metamizol and lornoxicam on postoperative pain and morphine consumption after lumbar disc surgery[J]. Eur J Anaesthesiol, 2010, 27(5): 428-432.
[72] 郭金伟, 叶健, 杨博文, 等. 酮咯酸氨丁三醇对椎间孔镜术后疼痛的影响[J]. 中国老年保健医学, 2018, 16(6): 59-60, 63.
[73] 彭高伟, 许国兵. 酮咯酸氨丁三醇对宫颈癌手术患者术后吗啡镇痛效果的影响[J]. 海峡药学, 2017, 29(2): 212-213.
[74] 何丹, 杨胜男, 邹爱伟, 等. 酮咯酸氨丁三醇对瘢痕子宫剖宫产术后子宫收缩疼痛的影响[J]. 中国药物与临床, 2021, 21(18): 3109-3111.
[75] SOYALP C, YAYIK AM, ÖKSÜZ E, et al. Efficacy of preemptive intravenous ibuprofen and dexketoprofen on postoperative opioid consumption in laparoscopic cholecystectomy: Randomized controlled study[J]. PLoS One, 2025, 20(9): e0318059.
[76] SHARPE KP, BERKOWITZ R, TYNDALL WA, et al. Safety, tolerability, and effect on opioid use of meloxicam IV following orthopedic surgery[J]. J Pain Res, 2020, 13: 221-229.
[77] BERGESE SD, MELSON TI, CANDIOTTI KA, et al. A phase 3, randomized, placebo-controlled evaluation of the safety of intravenous meloxicam following major surgery[J]. Clinical Pharm Drug Dev, 2019, 8(8): 1062-1072.
[78] 石家庄以岭药业股份有限公司. 苯胺洛芬注射液治疗术后中、重度疼痛的有效性及安全性的多中心、随机、双盲、安慰剂平行对照Ⅲ期临床试验临床研究报告(临床试验登记号: CTR20210721)[R]. 石家庄: 石家庄以岭药业股份有限公司, 2023.
[79] 石家庄以岭药业股份有限公司. 苯胺洛芬注射液治疗妇科术后疼痛的有效性及安全性的多中心、随机、双盲、安慰剂平行对照Ⅲ期临床试验临床研究报告(临床试验登记号: CTR20210949)[R]. 石家庄: 石家庄以岭药业股份有限公司, 2023.
[80] VARRASSI G, PERGOLIZZI JV, DOWLING P, et al. Ibuprofen safety at the golden anniversary: are all NSAIDs the same? a narrative review[J]. Adv Ther, 2020, 37(1): 61-82.