Sevoflurane multiple Wash In/Wash Out at the end of anesthesia to reduce agitation: a multicenter double-blind randomized controlled trial (OPERA).

BACKGROUND

Postoperative neurocognitive disorders are common and associated with adverse clinical outcomes. Existing preventive interventions are limited; the Wash In/Wash Out technique (or "wave-like awakening") might reduce the risk of postoperative neurocognitive complications. Therefore, this trial evaluated the effect of the Wash In/Wash Out technique on emergence agitation after sevoflurane-based anesthesia.

METHODS

In this multicenter, double-blind, randomized trial, adult patients undergoing elective open abdominal surgery under general anesthesia with sevoflurane were randomly assigned to either an intervention group (wave-like awakening group) or a control group (standard emergence from general anesthesia). In the intervention group, sevoflurane was intermittently discontinued and immediately resumed in three consecutive cycles before awakening. The primary outcome was the incidence of emergence agitation (EA), defined as a Richmond Agitation-Sedation Scale score ≥  +2 during emergence.

RESULTS

Between March 2021 and February 2025, 202 patients were enrolled across three centers. The frequency of the primary endpoint was markedly low at just 1.5%, well below the anticipated rate. We found no difference in the rate of emergence agitation which occurred in 2/101 (2%) of patients in the intervention group and 1/101 (1%) in the control group (relative risk (RR), 2.00; 95% confidence interval (CI), 0.18-21.71; p > 0.999), delirium (5.9% vs. 8.9%; RR, 0.67; 95% CI, 0.25-1.82; p = 0.421), or delayed neurocognitive recovery (7.9% vs. 10.9%; RR, 0.72; 95% CI, 0.30-1.72; p = 0.470). A composite of the three postoperative neurologic complications was 13/101 (13%) vs. 19/101 (19%) (p = 0.25). We found that the median duration of delirium was shorter in the intervention group (1 [1; 1] days) than in the control group (2 [2; 3] days). No adverse event was noted.

CONCLUSIONS

In this multicenter randomized controlled trial, the Wash In/Wash Out strategy was feasible and safe but we cannot exclude clinically relevant benefit or harm on the incidence of emergence agitation due to the low event rates. We found a reduction in delirium duration in adult patients undergoing elective abdominal surgery under sevoflurane anesthesia which should be considered hypothesis generating.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04765488. Registered 15 February 2021.