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Primary outcome was intensity of acute pain (up to 6\u00a0hr postoperatively). Secondary outcomes were cumulative 24\u2010hr morphine consumption, incidence of postoperative nausea and vomiting (PONV), and chronic pain. We used an original three\u2010step approach. First, meta\u2010analyses were performed when data from at least three trials could be combined; secondly, trial sequential analyses were used to separate conclusive from unclear evidence. And thirdly, the quality of evidence was rated with GRADE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy\u2010three trials (5,512 patients) tested loco\u2010regional blocks (paravertebral, pectoralis), local anaesthetic infiltrations, oral gabapentinoids or intravenous administration of glucocorticoids, lidocaine, N\u2010methyl\u2010D\u2010aspartate antagonists or alpha2 agonists. With paravertebral blocks, pectoralis blocks and glucocorticoids, there was conclusive evidence of a clinically relevant reduction in acute pain (visual analogue scale\u00a0&gt;\u00a01.0\u00a0cm). With pectoralis blocks, and gabapentinoids, there was conclusive evidence of a reduction in the cumulative 24\u2010hr morphine consumption (&gt; 30%). With paravertebral blocks and glucocorticoids, there was conclusive evidence of a relative reduction in the incidence of PONV of 70%. For chronic pain, insufficient data were available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mainly with loco\u2010regional blocks, there is conclusive evidence of a reduction in acute pain intensity, morphine consumption and PONV incidence after breast surgery. For rational decision making, data on chronic pain are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This quantitative systematic review compares eight interventions, published across 73 trials, to prevent pain after breast surgery, and grades their degree of efficacy. The most efficient interventions are paravertebral blocks, pectoralis blocks and glucocorticoids, with moderate to low evidence for the blocks. Intravenous lidocaine and alpha2 agonists are efficacious to a lesser extent, but with a higher level of evidence. Data for chronic pain are lacking.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1648","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T16:14:03Z","timestamp":1597940043000},"page":"5-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Preventing pain after breast surgery: A systematic review with meta\u2010analyses and trial\u2010sequential analyses"],"prefix":"10.1002","volume":"25","author":[{"given":"Ariane","family":"Lepot","sequence":"first","affiliation":[{"name":"Division of Anaesthesiology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Elia","sequence":"additional","affiliation":[{"name":"Division of Anaesthesiology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Faculty of Medicine Institute of Global Health University of Geneva Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin Richard","family":"Tram\u00e8r","sequence":"additional","affiliation":[{"name":"Division of Anaesthesiology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benno","family":"Rehberg","sequence":"additional","affiliation":[{"name":"Division of Anaesthesiology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000108"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000436117.52143.bc"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31827d88d8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/2356-9115.184078"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0b013e3181cb406e"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.12.005"},{"issue":"7","key":"e_1_2_9_8_1","first-page":"S149","article-title":"General anesthesia with thoracic paravertebral block for modified radical mastectomy","volume":"93","author":"Arunakul P.","year":"2010","journal-title":"Journal of the Medical Association of Thailand = Chotmaihet Thangphaet"},{"key":"e_1_2_9_9_1","first-page":"145","article-title":"Evaluation of the effect of a preoperative single dose of gabapentin on emergence agitation in patients undergoing breast cancer surgery","volume":"4","author":"Azemati S.","year":"2013","journal-title":"Middle East Journal of Cancer"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-018-4670-9"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/AAP.0000000000000163"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annfar.2008.10.006"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5049.93341"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2008.11.043"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2044.2006.04793.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/aas.12287"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ans.12541"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-018-0770-1"},{"key":"e_1_2_9_19_1","first-page":"2505","article-title":"Intraoperative and postoperative infusion of dexmedetomidine combined with butorphanol for intravenous patient\u2010controlled analgesia after radical mastectomy: A double\u2010blind, randomized clinical trial","volume":"10","author":"Chang J.","year":"2017","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.12442"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ecc.12686"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annfar.2008.10.008"},{"key":"e_1_2_9_23_1","volume-title":"Cancer incidence in five continents","author":"Curado M. 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