提示: 手机请竖屏浏览!

抗生素和阑尾切除术治疗阑尾炎的随机比较试验
A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis


The CODA Collaborative* 其他 • 2020.11.12
相关阅读
• 抗生素是不劣于阑尾切除术的急性阑尾炎治疗方法 • 阑尾炎非手术疗法是一个可行的选择 • 哪些因素增加了阑尾炎的漏诊概率

单纯抗生素治疗与外科手术在成人急性阑尾炎治疗策略的效果评价

 

潘宏

上海嘉会国际医院普通外科

 

在世界范围内,急性阑尾炎至今仍是普通外科急诊中最常见的疾病,尤其是穿孔性阑尾炎更是具有较高的致死性。将外科手术治疗作为急性阑尾炎的主要治疗手段,已经是现代外科临床教育的标准化内容。阑尾切除术和所有外科手术一样,都有关于手术指征、手术反指征、手术安全与风险评估,以及备选治疗策略的讨论。尽管广谱、高效、安全的抗生素在临床被广泛应用,并对许多外科疾病的手术指征产生了一定影响(如急性重症胰腺炎的外科手术),大样本、高质量的有关急性阑尾炎单纯抗生素治疗与外科手术治疗之间的对照研究并不多见。

查看更多

摘要


背景

有人提出将抗生素疗法作为阑尾炎手术疗法的替代方案。

 

方法

我们在美国25家医疗中心开展了一项实用性、非盲、非劣效性、随机试验,本试验比较了抗生素疗法(10日疗程)和阑尾切除术对阑尾炎的治疗效果。主要结局是利用欧洲五维生活质量量表(EQ-5D)评估的30日健康状态(评分范围为0~1分,评分较高表示健康状态较好;非劣效性界值,0.05分)。次要结局包括截至90日时抗生素组的阑尾切除术,以及并发症;本试验预先设定了亚组分析(根据是否有阑尾粪石定义亚组)。

 

结果

共计1,552例成人患者(414例有阑尾粪石)被随机分组;776例被分配接受抗生素治疗(47%首次治疗未住院),776例接受了阑尾切除术治疗(96%接受了腹腔镜手术)。根据30日EQ-5D评分(平均差异,0.01分;95%置信区间[CI],-0.001~0.03),抗生素不劣于阑尾切除术。在抗生素组中,截至90日时,29%的患者已接受了阑尾切除术,包括41%有阑尾粪石的患者和25%无阑尾粪石的患者。抗生素组的并发症发生率高于阑尾切除术组(每100例参与者中8.1例vs. 3.5例;率比,2.28;95% CI,1.30~3.98);抗生素组较高的发生率可归因于有阑尾粪石的患者(每100例参与者中20.2例vs. 3.6例;率比,5.69;95% CI,2.11~15.38),而非无阑尾粪石的患者(每100例参与者中3.7例vs. 3.5例;率比,1.05;95% CI,0.45~2.43)。在抗生素组和阑尾切除术组中,严重不良事件的发生率分别为每100例参与者中4.0起和3.0起(率比,1.29;95% CI,0.67~2.50)。

 

结论

在治疗阑尾炎方面,根据健康状态的常规指标,抗生素不劣于阑尾切除术。在抗生素组中,截至90日时,每10例参与者中已有近3例接受了阑尾切除术。有阑尾粪石的参与者接受阑尾切除术和出现并发症的风险高于无阑尾粪石的参与者(由以患者为中心的结局研究会[Patient-Centered Outcomes Research Institute]资助,CODA在ClinicalTrials.gov注册号为NCT02800785)。





作者信息

The CODA Collaborative*
The affiliations of the members of the writing committee are as follows: the University of Washington (D.R.F., G.H.D., S.M., A.K.S., E.F., D.C.L., B.A.C., P.J.H., L.G.K.), the Washington State Hospital Association (B.B.), Harborview Medical Center (H.E., J.C.), the Swedish Medical Center (K.A.M.), and the Virginia Mason Medical Center (J.T.Y., A.W.), Seattle, Madigan Army Medical Center, Tacoma (V.S., K.M.), and Providence Regional Medical Center Everett, Everett (C.S.F., S.M.S.) — all in Washington; Beth Israel Deaconess Medical Center (N.I.S., S.R.O.) and Boston University Medical Center (S.E.S., F.T.D.) — both in Boston; Columbia University Medical Center (K.F.), Tisch Hospital, NYU Langone Medical Center (P.A.-C., W.C.), Bellevue Hospital Center, NYU School of Medicine (P.A.-C., W.C.), and Weill Cornell Medical Center (R.J.W., S.C.) — all in New York; Henry Ford Health, Detroit (J.J., J.H.P.), and the University of Michigan, Ann Arbor (H.B.A., P.K.P.); University of Iowa Hospitals and Clinics, Iowa City (B.A.F., D.A.S.); the University of Texas Lyndon B. Johnson Medical Center (M.K.L.) and the University of Texas Health Science Center at Houston (L.S.K.) — both in Houston; the University of Mississippi Medical Center, Jackson (M.E.K.); Maine Medical Center, Portland (B.C., D.W.C.); Ohio State University Medical Center, Columbus (A.R., S.S.); Rush University Medical Center, Chicago (T.P.P.); UCHealth University of Colorado Hospital, Denver (L.F., M.S.); Harbor UCLA Medical Center (D.A.D., A.H.K.), Olive View UCLA Medical Center (G.J.M., D.S., A.K.), and Ronald Reagan UCLA Medical Center (D.A.T.) — all in Los Angeles; and Vanderbilt University Medical Center, Nashville (C.M.T., W.H.S.). Address reprint requests to Dr. Flum at the Surgical Outcomes Research Center, Department of Surgery, University of Washington, Box 356410, Seattle, WA 98195-6410, or at daveflum@uw.edu. *A complete list of members of the CODA Collaborative is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Coldrey E. Treatment of acute appendicitis. Br Med J 1956;2:1458-1461.

2. Eriksson S, Granström L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg 1995;82:166-169.

3. Styrud J, Eriksson S, Nilsson I, et al. Appendectomy versus antibiotic treatment in acute appendicitis: a prospective multicenter randomized controlled trial. World J Surg 2006;30:1033-1037.

4. Turhan AN, Kapan S, Kütükçü E, Yiğitbaş H, Hatipoğlu S, Aygün E. Comparison of operative and non operative management of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2009;15:459-462.

5. Hansson J, Körner U, Khorram-Manesh A, Solberg A, Lundholm K. Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg 2009;96:473-481.

6. Vons C, Barry C, Maitre S, et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet 2011;377:1573-1579.

7. Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA 2015;313:2340-2348.

8. Ehlers AP, Talan DA, Moran GJ, Flum DR, Davidson GH. Evidence for an antibiotics-first strategy for uncomplicated appendicitis in adults: a systematic review and gap analysis. J Am Coll Surg 2016;222:309-314.

9. Sceats LA, Trickey AW, Morris AM, Kin C, Staudenmayer KL. Nonoperative management of uncomplicated appendicitis among privately insured patients. JAMA Surg 2019;154:141-149.

10. American College of Surgeons. COVID-19 guidelines for triage of emergency general surgery patients. March 25, 2020 (https://www.facs.org/covid-19/clinical-guidance/elective-case/emergency-surgery. opens in new tab).

11. Davidson GH, Flum DR, Talan DA, et al. Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment. BMJ Open 2017;7(11):e016117-e016117.

12. Ehlers AP, Davidson GH, Deeney K, Talan DA, Flum DR, Lavallee DC. Methods for incorporating stakeholder engagement into clinical trial design. EGEMS (Wash DC) 2017;5:4-4.

13. Ehlers AP, Davidson GH, Bizzell BJ, et al. Engaging stakeholders in surgical research: the design of a pragmatic clinical trial to study management of acute appendicitis. JAMA Surg 2016;151:580-582.

14. Methodology Committee of the Patient-Centered Outcomes Research Institute (PCORI). Methodological standards and patient-centeredness in comparative effectiveness research: the PCORI perspective. JAMA 2012;307:1636-1640.

15. Flum DR, Alfonso-Cristancho R, Devine EB, et al. Implementation of a “real-world” learning health care system: Washington State’s Comparative Effectiveness Research Translation Network (CERTAIN). Surgery 2014;155:860-866.

16. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt) 2010;11:79-109.

17. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt) 2017;18:1-76.

18. EuroQol Group. EuroQol — a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208.

19. Le QA, Doctor JN, Zoellner LA, Feeny NC. Minimal clinically important differences for the EQ-5D and QWB-SA in post-traumatic stress disorder (PTSD): results from a doubly randomized preference trial (DRPT). Health Qual Life Outcomes 2013;11:59-59.

20. American College of Surgeons, National Surgical Quality Improvement Program. User guide for the 2014 ACS NSQIP participant use data file (PUF). October 2015 (https://www.facs.org/~/media/files/quality%20programs/nsqip/nsqip_puf_userguide_2014.ashx. opens in new tab).

21. Koumarelas K, Theodoropoulos GE, Spyropoulos BG, Bramis K, Manouras A, Zografos G. A prospective longitudinal evaluation and affecting factors of health related quality of life after appendectomy. Int J Surg 2014;12:848-857.

22. Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA 2012;308:2594-2604.

23. Fraser N, Gannon C, Stringer MD. Appendicular colic and the non-inflamed appendix: fact or fiction? Eur J Pediatr Surg 2004;14:21-24.

24. Sakran JV, Mylonas KS, Gryparis A, et al. Operation versus antibiotics — the “appendicitis conundrum” continues: a meta-analysis. J Trauma Acute Care Surg 2017;82:1129-1137.

25. Mahida JB, Lodwick DL, Nacion KM, et al. High failure rate of nonoperative management of acute appendicitis with an appendicolith in children. J Pediatr Surg 2016;51:908-911.

26. Huang L, Yin Y, Yang L, Wang C, Li Y, Zhou Z. Comparison of antibiotic therapy and appendectomy for acute uncomplicated appendicitis in children: a meta-analysis. JAMA Pediatr 2017;171:426-434.

27. Salminen P, Tuominen R, Paajanen H, et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA 2018;320:1259-1265.

28. Drake FT, Florence MG, Johnson MG, et al. Progress in the diagnosis of appendicitis: a report from Washington State’s Surgical Care and Outcomes Assessment Program. Ann Surg 2012;256:589-594.

29. Lee SL, Spence L, Mock K, Wu JX, Yan H, DeUgarte DA. Expanding the inclusion criteria for nonoperative management of uncomplicated appendicitis: outcomes and cost. J Pediatr Surg 2017 October 9 (Epub ahead of print).

30. Talan DA, Saltzman DJ, Mower WR, et al. Antibiotics-first versus surgery for appendicitis: a US pilot randomized controlled trial allowing outpatient antibiotic management. Ann Emerg Med 2017;70(1):1.e9-11.e9.

服务条款 | 隐私政策 | 联系我们