Sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications (SNaPP): an international, randomised, controlled, phase 4 trial
The Lancet Respiratory Medicine, 2026; 0
DOI: 10.1016/S2213-2600(26)00158-X
What's the question?
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Does reversal of neuromuscular blockade with sugammadex reduce the incidence of postoperative pulmonary complications or death compared with neostigmine in adults having major abdominal or thoracic surgery under general anaesthesia?
Background Information
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Postoperative pulmonary complications are among the most common, serious, and costly complications of surgery and anaesthesia.
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Neuromuscular-blocking drugs are used in millions of patients each year; residual neuromuscular blockade is a well-established risk factor for postoperative pulmonary complications.
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Sugammadex is a cyclodextrin reversal agent specific to the aminosteroid drugs rocuronium and vecuronium. Unlike neostigmine, which has a ceiling effect, sugammadex directly encapsulates these drugs, achieving more complete and rapid reversal.
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Prior systematic reviews of small randomised trials suggested a benefit of sugammadex on postoperative pulmonary complications, but no large definitive randomised trial had been completed.
The study
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Pragmatic, international, multicentre, randomised controlled phase 4 trial across 44 hospitals in Australia, Aotearoa New Zealand, and Hong Kong.
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Eligible patients: adults aged 40 years or older having abdominal or thoracic surgery under general anaesthesia lasting at least two hours, with an anticipated hospital stay of at least one postoperative night.
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Patients randomised 1:1 to sugammadex or neostigmine; patients, outcome assessors, and the adjudication committee were masked to treatment allocation.
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Primary outcome: composite of new postoperative pulmonary complications (atelectasis, pneumonia, acute respiratory distress syndrome, or aspiration pneumonitis) or death to hospital discharge or postoperative day 7, using validated StEP-COMPAC definitions.
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3,498 patients included in the intention-to-treat analysis.
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Primary outcome occurred in 19.0% (sugammadex) vs 21.5% (neostigmine); risk ratio 0.88 (95% CI 0.77–1.00; p=0.049).
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Atelectasis was the dominant complication and main driver of the difference: 18.4% vs 21.1% (risk ratio 0.86; p=0.030).
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Rates of pneumonia, acute respiratory distress syndrome, aspiration pneumonitis, postoperative nausea and vomiting, and unplanned ICU admission were similar between groups.
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Sugammadex achieved a train-of-four ratio >0.9 at extubation in 87.4% of monitored patients vs 64.3% with neostigmine, with shorter time from reversal to extubation.
Strengths and Weaknesses
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Strengths: Large sample (n=3,498) with near-complete follow-up (99.8%); pragmatic design across 44 diverse sites in three countries; patients and outcome assessors masked to allocation; pre-specified and published statistical analysis plan; validated standardised outcome definitions.
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Weaknesses: Anaesthesiologists administering the drugs could not be masked; discretion over dosing, timing, and monitoring may have introduced heterogeneity. Differential crossover occurred, with more patients switching from neostigmine to sugammadex than vice versa. Results are limited to adults aged 40 years and older having major abdominal or thoracic surgery. The trial was underpowered to detect uncommon adverse events such as sugammadex anaphylaxis. First Nations peoples were under-represented. No differences were found in ICU admission, days alive at home at 30 days, or quality of life at 3 months, leaving the long-term clinical significance of the atelectasis reduction uncertain.
PHRACC's Conclusions
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Sugammadex significantly reduced the composite incidence of postoperative pulmonary complications or death compared with neostigmine (risk ratio 0.88; p=0.049).
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The benefit was modest: absolute risk reduction 2.1%, number needed to treat 47, driven almost entirely by a reduction in atelectasis of uncertain long-term significance.
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Sugammadex achieved more reliable reversal of neuromuscular blockade and faster tracheal extubation.
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No meaningful differences were found in pneumonia, nausea and vomiting, ICU admission, or health-related quality of life at 3 months.
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Sugammadex can be considered a first-line agent for reversal of aminosteroid-induced neuromuscular blockade in older adults having major abdominal or thoracic surgery.
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