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The use of neuromuscular blocking drugs in general anaesthesia is an important risk factor for PPCs. The incomplete reversal of this neuromuscular blockade at the end of surgery leads to residual weakness of respiratory muscles and predisposes to aspiration of pharyngeal contents, hypoventilation, and thus to PPCs such as atelectasis and pneumonia. Two reversal drugs for neuromuscular blocking agents are available: neostigmine and sugammadex. Compared with neostigmine, sugammadex use results in more rapid reversal of neuromuscular blockade, and small clinical efficacy studies have suggested an associated lower incidence of PPCs. The comparative clinical effectiveness of the two drugs in reducing length of hospital stay or mortality is uncertain. Moreover, a potential safety concern with sugammadex is the relatively high incidence of life-threatening allergic reactions in countries where this drug has been widely used over the last decade.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>SINFONIA is a pragmatic, randomised, open-label, parallel group, superiority trial with an internal pilot which aims to compare the clinical and cost effectiveness of the two available drugs for reversal of neuromuscular blockade, sugammadex and neostigmine, in patients aged 50\u00a0years or older undergoing major abdominal or non-cardiac thoracic surgery. The trial will randomise 2500 patients from approximately 40 centres in the UK. The primary outcome will be days alive and out of hospital\u00a0at 30 days (DAH-30), with key secondary outcomes of PPC incidence, quality of life, and mortality up to 180\u00a0days. An embedded observational study will investigate the rate of allergic sensitisation following exposure to sugammadex.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Discussion<\/jats:title>\n            <jats:p>The SINFONIA trial addresses an important question for anaesthetists and for patients undergoing major abdominal and thoracic surgery. The choice of reversal agent for neuromuscular blockade between sugammadex and neostigmine is currently largely a matter of anaesthetist preference. A growing body of evidence suggests that sugammadex may reduce the incidence of post-operative pulmonary complications relative to neostigmine. This pragmatic clinical effectiveness trial will provide robust evidence as to the effects of the two drugs on patient-centred outcomes such as DAH-30, as well as on cost effectiveness and the incidence of allergic sensitisation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>The trial was registered on the ISRCTN database (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.isrctn.com\" ext-link-type=\"uri\">https:\/\/www.isrctn.com<\/jats:ext-link>) prior to opening to recruitment (registration no 15109717).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13063-025-08987-4","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:19:40Z","timestamp":1756372780000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sugammadex or Neostigmine for prevention of post-operative pulmonary complications after major abdominal or thoracic surgery: study protocol for the SINFONIA (Sugammadex for preventioN oF pOst-operative pulmonary complIcAtions) randomised controlled superiority trial"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9562-5462","authenticated-orcid":false,"given":"Jonathan A.","family":"Silversides","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Savic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Hiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Booth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Dorey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Smithson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Frempong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramani","family":"Moonesinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara M.","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Creagh-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Kandiyali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Pearse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the SINFONIA investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"McNeill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Padfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalbir","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"8987_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/bja\/aex137","volume":"119","author":"TEF Abbott","year":"2017","unstructured":"Abbott TEF, Fowler AJ, Dobbs TD, Harrison EM, Gillies MA, Pearse RM. 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It will also comply with all applicable UK legislation and the Standard Operating Procedures (SOPs) of the University of Warwick and the Sponsor (Belfast Health and Social Care Trust). Approvals for the trial were granted by the East Midlands Nottingham 2 Research Ethics Committee (22\/EM\/0231) on 12th January 2023, and by the Medicines and Healthcare Regulatory Authority (CTA 32485\/0041\/001\u20130001) on 20th Dec 2022. Before enrolling participants into the trial, each trial site must ensure that the local conduct of the trial has the agreement of the relevant NHS Trust Research & Development (R&D) department. Written, informed consent to participate will be obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"RP is chair of the commissioning committee of the NIHR Health Technology Assessment programme. No other authors report competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"319"}}