Kate Leslie, Kate Leslie, Jai N Darvall, Matthew T V Chan, Philip J Peyton, Paul S Myles, Tomás B Corcoran, Timothy G Short, Benjamin L Olesnicky, Ashley R Webb, Nancy Devlin, An Tran-Duy, Helen Maxwell-Wright, Cindy Schultz-Ferguson, Phoebe Fitzpatrick, Sofia Sidiropoulos, Sabine Braat, David A Story, Kate Leslie, Kate Leslie, Jai N. Darvall, Matthew T.V. Chan, Philip J. Peyton, Paul S. Myles, Tomás B. Corcoran, Timothy G. Short, Benjamin L. Olesnicky, Ashley R. Webb, Nancy Devlin, An Tran-Duy, Helen Maxwell-Wright, Cindy Schultz-Ferguson, Phoebe Fitzpatrick, Sofia Sidiropoulos, Sabine Braat, David A. Story, Daniel Steinfort, Asha Bonney, Ned Douglas, Matthew Durie, David A. Scott, Christopher Bain, Susan Burney, Emily Karahalios, Sandra Peake, Sophie Zaloumis, Vi Ha, Bhavita Patel, Violet Mukaro, Karen Goulding, Paige Druce, Gillian Ormond, Lachlan F. Miles, Ashleigh Harson, Karen McCrohan, Eric Knauf, Mohammad Mahdi Zamani, Alan Bullingham, Hazel Uy, Libia Machado Munoz, Lyndall Watkins, Mervyn Atkinson, Patrick Sowula, Louise de Prinse, Holly Alford, David Bramley, Anna Truong, Lisa Coward, Natasha Gatt, Stuart Marshall, Ben Moran, Mary Keehan, Andrew Walters, Natasha Pearson, Emerald Stewart, Caitlyn Lovi, Suresh Singaravelu, Tracy Hess, Shravya Karna, Dhiraj Bhatia Dwivedi, Brian Chee, Margaret Quayle, Nicole Forbes-Olivier, Jane Fuller, Julian Marshall, Suhaila Kamrani, Matthew Wang, Jade Radnor, Jacqueline Lake, Darren Lowen, Andrea Ditoro, Russell Hodgson, Fergus Morrison, Julia Dubowitz, Bernhard Riedel, Xantine Garrido, Suejin Shim, David Highton, P Sivalingam, Allison Kearney
BACKGROUND: Sugammadex and neostigmine are used to reverse aminosteroid neuromuscular-blocking drugs at the end of surgery. We aimed to determine whether reversal of neuromuscular blockade with sugammadex reduces the incidence of postoperative pulmonary complications or death compared with neostigmine. METHODS: We conducted a pragmatic, international, multicentre, randomised, controlled, phase 4 trial involving 44 hospitals in Australia, Aotearoa New Zealand, and Hong Kong. Eligible patients were adults (aged ≥40 years) who were having abdominal or thoracic surgery under general anaesthesia and lasting at least 2 h, with an expected postoperative hospital stay of 1 night or longer. Patients were randomly assigned (1:1) to sugammadex or neostigmine, administered intravenously in doses chosen by the attending anaesthesiologist, for reversal of rocuronium-induced or vecuronium-induced neuromuscular blockade at the end of surgery. Randomisation was done via a web-based service, in random permuted blocks of varying sizes of 2 and 4 and stratified by centre. Patients, research staff who were responsible for outcome assessments, and members of the endpoint adjudication committee were masked to group assignment. The primary outcome was postoperative pulmonary complications or death up to hospital discharge (or postoperative day 7 if still in hospital). The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000394640) and is closed to accrual. FINDINGS: Patients were recruited between July 21, 2023, and July 3, 2025; 3498 patients were included in the intention-to-treat population (1745 [49·9%] in the sugammadex group and 1753 [50·1%] in the neostigmine group). Postoperative pulmonary complications or death occurred in 331 (19·0%) of 1743 patients in the sugammadex group and 377 (21·5%) of 1752 patients in the neostigmine group (risk ratio [RR] 0·88 [95% CI 0·77-1·00]; p=0·049). Death occurred in one (0·1%) and two (0·1%) patients (RR 0·50 [95% CI 0·05-5·53]; p >0·99), atelectasis in 320 (18·4%) of 1742 patients and 370 (21·1%) of 1750 patients (0·86 [0·76-0·99]; p=0·030), pneumonia in 37 (2·1%) of 1742 patients and 38 (2·2%) of 1750 patients (0·98 [0·62-1·53]; p=0·92), and pulmonary aspiration in four (0·2%) of 1742 and seven (0·4%) of 1750 patients (0·57 [0·17-1·96]; p=0·38) in the sugammadex and neostigmine groups, respectively. Acute respiratory distress syndrome was not reported. No adverse events were deemed to be treatment related. INTERPRETATION: Sugammadex reduced the incidence of postoperative pulmonary complications or death compared with neostigmine. The risk reduction was small with atelectasis of uncertain clinical significance being the most common complication. Sugammadex can be considered as a first-line drug for reversal of aminosteroid-induced neuromuscular blockade at the end of surgery. FUNDING: Australian Medical Research Future Fund and the Hong Kong Health and Medical Research Fund.