Critical Vector · Trial Snapshot

SNaPP: Sugammadex vs Neostigmine

Lancet Respiratory Medicine, published online June 9, 2026. Reviewed against the primary trial and its companion commentary.

1.The Question

Sugammadex and neostigmine both reverse aminosteroid neuromuscular blockade (rocuronium, vecuronium) at the end of surgery. Sugammadex reverses it more completely and faster: a systematic review found complete recovery in 2.2 minutes versus 12.0 minutes for neostigmine, and residual block in 4.8% of patients versus 16.0%.

What was never nailed down by a large, definitive trial: does that better reversal actually translate into fewer postoperative pulmonary complications, the thing that matters to the patient? SNaPP was built to answer exactly that.

2.Trial Design

DesignInternational, multicentre, phase 4, patient- and assessor-blinded RCT
PopulationAge 40+, abdominal or thoracic surgery under general anesthesia lasting 2+ hours, anticipated hospital stay of 1+ night
N3,500 enrolled (July 2023 to July 2025), 1:1 randomization
Groups1,746 sugammadex vs 1,754 neostigmine
Primary outcomeComposite of new postoperative pulmonary complication or death, up to hospital discharge or postoperative day 7
FundingAustralian Medical Research Future Fund; Hong Kong Health and Medical Research Fund

3.Headline Result

19.0%
Sugammadex
21.5%
Neostigmine
RR 0.88
P = .049

Postoperative pulmonary complications or death occurred in 331 of 1,743 patients (19.0%) on sugammadex versus 377 of 1,752 (21.5%) on neostigmine. Risk ratio 0.88 (95% CI 0.77 to 1.00), P=.049. Absolute risk difference: 2.1 percentage points.

P=.049 is a significant result, but only just. This crossed the line by a hair, not by a wide margin.

4.What Actually Drove the Number

The trial authors' own conclusion is carefully worded: sugammadex reduced the composite outcome, but the risk reduction was small, and atelectasis of uncertain clinical significance was the single most common complication in that composite.

That matters because atelectasis picked up on routine postoperative imaging, without clinical consequence, is a soft endpoint. It inflates a composite outcome without necessarily meaning fewer patients got pneumonia, needed reintubation, or died.

The trial's own authors still concluded sugammadex "can be considered as a first-line drug" for reversal, so this isn't a null result. It's a real but modest result, and the modesty is the headline as much as the direction.

5.A Word of Caution

The Lancet paired SNaPP with an invited commentary from Fernandez-Bustamante and colleagues, titled, plainly, "a word of caution." The gist: a borderline P value driven substantially by a soft imaging endpoint is not the same evidentiary weight as a clear reduction in pneumonia, reintubation, or death.

This lands in a context that predates SNaPP: sugammadex is considerably more expensive than neostigmine, and carries a meaningfully higher anaphylaxis risk. Those two facts don't disappear because SNaPP found a small benefit. They just now have to be weighed against a small benefit rather than an unproven one.

6.Prior Evidence, for Contrast

Before SNaPP, the observational literature was a mixed bag, and some of it suggested a much larger effect than SNaPP ultimately found.

SourceFinding
STRONGER cohort (n=45,712)Adjusted OR 0.70 (0.63-0.77) favoring sugammadex
Large retrospective cohort (n=83,250)No difference, adjusted OR 1.01 (0.94-1.08)
Prospective cohort (n=8,795)No difference at 28 days, adjusted OR 1.03 (0.85-1.25)
RCT systematic review (13 trials, 1,307 patients)OR 0.67 (0.47-0.96) favoring sugammadex
2023 meta-analysis (mixed observational + RCT)Pneumonia RR 0.65, atelectasis RR 0.64, reintubation RR 0.62, all favoring sugammadex

The pattern across this literature: bigger, more rigorous studies tend to shrink the effect. SNaPP, the largest and most rigorous of all of them, found the smallest effect, right at the edge of significance.

7.Bottom Line & Sources

Clinical takeaway: sugammadex modestly outperforms neostigmine for postoperative pulmonary complications or death in this population, but the margin is thin and leans heavily on a soft imaging endpoint. It's a reasonable first-line choice where cost and anaphylaxis risk are acceptable, not a mandate that neostigmine is dangerous or that using it reflects cost-cutting at the expense of safety.