Every year, 250,000 NHS patients over 50 undergoing major abdominal or chest surgery risk lung complications because their breathing muscles remain partially paralysed after anaesthesia. The problem is that the standard drug used to reverse this paralysis, neostigmine, has been used since the 1950s and can itself cause muscle weakness. A newer drug, sugammadex, works faster and more completely, but it costs more and has been linked to allergic reactions in Japan. Without solid trial evidence, the NHS has no clear basis to choose one over the other. This trial will randomly assign patients in 40 NHS hospitals to receive either sugammadex or neostigmine at the end of surgery. The key measure is how many days patients spend alive and out of hospital within 30 days—a direct reflection of whether complications kept them in bed longer. If sugammadex proves superior, it could become the standard of care for hundreds of thousands of patients each year, reducing pneumonia, collapsed lungs, and deaths after major surgery. If it does not, the NHS will avoid spending millions on a drug that offers no clear benefit. Either way, the trial will settle a question that currently leaves clinical practice relying on guesswork.
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RESEARCH QUESTION In patients aged >=50 years undergoing major abdominal or thoracic surgery, does the use of sugammadex for reversal of neuromuscular blockade increase the number of Days Alive and out of Hospital within 30 days after surgery (DAH30), compared to neostigmine? BACKGROUND General anaesthesia often involves neuromuscular blocking agents (NMBAs), drugs which temporarily paralyse skeletal muscles, including those involved in airway reflexes and breathing, to facilitate invasive ventilation and surgical access. Incomplete reversal of paralysis is hard to detect. Despite careful monitoring, and administration of a reversal agent at the end of anaesthesia, one in three patients experience residual paralysis which leaves them with weak airway and respiratory muscles, predisposing to post-operative pulmonary complications (PPCs) such as atelectasis and pneumonia. Of more than 1.5 million NHS patients who receive an NMBA each year, the 250,000 patients aged >=50 years undergoing major abdominal and thoracic surgery are at particular risk of PPCs which lead to longer hospital stay and higher mortality, reflected in the patient-centred outcome measure of DAH30. Two NMBA antagonist drugs are available to reverse paralysis. Neostigmine has been used since the 1950s, but can itself cause muscle weakness. A newer drug, sugammadex, reverses NMBAs more rapidly than neostigmine, reducing post-operative residual paralysis. Observational data suggest sugammadex may reduce PPCs by a third compared with neostigmine, but it is only used in a minority of NHS patients because the patient benefit remains unproven, and because of concerns about cost and drug allergy. In Japan, routine sugammadex use has led to a dramatic increase in allergic reactions. We must define the risks and benefits of sugammadex use before we consider this the NMBA reversal drug of choice in the NHS. OBJECTIVES 1. To investigate whether sugammadex is superior to neostigmine for reversal of neuromuscular blockade after major abdominal or thoracic surgery. 2. To investigate the cost effectiveness of sugammadex compared to neostigmine for reversal of neuromuscular blockade after major abdominal or thoracic surgery. METHODS SINFONIA is a pragmatic multi-centre randomised trial with an efficient trial design. Patients aged >=50 years undergoing major thoracic or abdominal surgery in one of 40 participating NHS hospitals will be eligible. Patients will be randomly assigned to sugammadex or neostigmine for NMBA reversal at the end of surgery. The primary outcome is Days Alive and out of Hospital within 30 days after surgery (DAH30). Secondary outcomes are PPCs, mortality, health-related quality of life and cost effectiveness. DELIVERY TIMELINES SINFONIA will run for 54 months from 1st March 2022. Month 0-6: trial setup. Month 7-18: internal pilot. Month 19-42: patient recruitment. Month 43-48: follow-up, data cleaning and analysis. Months 49-54: Analysis and dissemination. IMPACT AND DISSEMINATION SINFONIA will define the standard of care for NMBA reversal for patients having major surgery. Findings will be disseminated to doctors through journal articles and conference presentations, and to patients, policy makers and public through lay summaries, infographics, and a dissemination workshop.
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