{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:02:37Z","timestamp":1780074157901,"version":"3.54.0"},"reference-count":34,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"unspecified","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,5,14]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Postoperative nausea and vomiting (PONV) is a common and distressing complication following surgery, persisting despite advances in prophylactic regimens. Growth differentiation factor-15 (GDF-15) has been identified as a biomarker inversely associated with PONV risk and severity. As metformin is known to elevate circulating GDF-15 levels, we hypothesise that preoperative metformin use may be associated with a lower incidence of PONV. This study aims to evaluate the association between a history of preoperative metformin administration and the occurrence of PONV in adults undergoing general anaesthesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a single-centre, prospective, observational cohort study. We plan to enrol 909 adult patients scheduled for surgery under general anaesthesia with endotracheal intubation from December 2025 to December 2028. Participants will be divided into two groups based on their preoperative metformin exposure: an exposed group (n=303) with a documented history of metformin use and a non-exposed group (n=606) without such history, using a 1:2 ratio. The metformin regimen (choice of agent and daily dosage) will be determined by the attending physician as part of routine clinical care, independent of this study. The primary outcome is the incidence of PONV, defined as the occurrence of any nausea, retching or vomiting, within 120 hours post-surgery. Secondary outcomes include the incidence of PONV in the early (0\u201324\u2009hours) and late (24\u2013120\u2009hours) postoperative phases; the severity of PONV symptoms and the requirement for rescue antiemetic medication during these intervals; the quality of recovery (assessed at 0\u201324, 24\u201348, 48\u201372, 72\u201396 and 96\u2013120\u2009hours); potential PONV risk factors in blood or urine and long-term survival rates at 1, 3 and 5 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study protocol (version 04, dated 23 November 2025) was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (Approval No. 2025ZSLYEC-689) prior to the initiation of participant recruitment. The first participant was enrolled under protocol version 04. A subsequent protocol amendment (version 05, dated 25 December 2025) was approved by the same Ethics Committee. This amendment added a quality of recovery assessment using the 15-item quality of recovery scoring system questionnaire at 30 days postoperatively. This amendment did not alter the primary or secondary outcomes, the sample size calculation, or any other key elements of the study design. The results of this study will be disseminated at scientific conferences and published in international peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial results\" xlink:href=\"NCT07244575\">NCT07244575<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-117537","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:05:22Z","timestamp":1780070722000},"page":"e117537","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Association between preoperative metformin exposure and postoperative nausea and vomiting in 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