Abstract
Despite low pain scores after minimally invasive gynecologic surgery (MIGS), opioids remain overprescribed in patients undergoing these procedures. In a single-blind randomized trial conducted at a tertiary-care academic center, we assessed whether a multimodal opioid-free exit prescription (OFP) for analgesia would result in noninferior postoperative pain control compared to an opioid-containing prescription in patients undergoing MIGS. Female patients without prior pain conditions undergoing outpatient laparoscopic MIGS were randomized to receive either an OFP or a restrictive opioid prescription (ROP; five tablets hydromorphone 1 mg) alongside multimodal analgesia. The primary outcome was patient-reported pain on postoperative day (POD) 1. Secondary outcomes included patient-reported pain and measures of recovery such as total opioid consumption, participant mobility, opioid-related side effects, return to emergency room or clinic, need for rescue analgesia prescription, overall satisfaction with pain control and overall satisfaction with postoperative care, which were assessed on POD1 and POD7 by a blinded outcome assessor. Of n = 110 patients randomized, n = 103 completed the study (OFP = 49, ROP = 54). No significant difference in mean pain scores on POD1 (3.1 versus 3.5, P = 0.31) or POD7 (1.0 versus 1.5, P = 0.14) were found. Mobility and satisfaction were comparable. ROP patients experienced more nausea and vomiting (14.3% versus 35.2%, P = 0.01). No OFP patients required rescue opioids. Only 27.8% and 11.1% of ROP patients consumed opioids by POD1 and POD7 respectively. Thus, in patients undergoing outpatient MIGS, an OFP resulted in noninferior postoperative pain compared to an ROP, suggesting that opioids may be safely omitted in this clinical context. ClinicalTrials.gov identifier: NCT04837014.
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Data availability
The datasets generated from this study are not publicly available due to privacy. De-identified participant data are available from the corresponding author upon reasonable request within a delay of one month. Data are stored in a secure, controlled-access repository at the McGill University Health Centre Royal Victoria Hospital, Glen Site. Source data are provided with this paper.
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Acknowledgements
A.Z. and J.D. disclose support in the amount of Canadian $10,000 for this project from the Canadian Foundation for Women’s Health (CFWH). C.D.R. discloses support for this work from the Fonds de Recherche du Québec - Santé (FRQS) (Master’s Training Scholarship, BF1 - 353466).
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All listed authors participated in the conduct of this research project. A.Z., J.D., W.L.P.S. and D.B.N. were involved in study conceptualization. A.Z., J.D., W.L.P.S., D.B.N. and J.P.S. were involved in study design and methodology. J.D., C.D.R. and S.K. were involved in data curation. A.Z., C.D.R., L.G., S.K. and F.W.M. were involved in formal analysis. A.Z., J.D. and C.D.R. were involved in writing of the original draft. D.B.N., F.W.M., W.L.P.S., L.G., J.P.S., S.K., A.Z., J.D. and C.D.R. were involved in reviewing and editing. C.D.R. performed project administration and A.Z., C.D.R. and J.D. were involved in funding acquisition.
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Nature Medicine thanks Sean C. Dowdy, Annmarie Vilkins and Peng Wei for their contribution to the peer review of this work. Peer reviewer reports are available. Primary Handling Editor: Ashley Castellanos-Jankiewicz, in collaboration with the Nature Medicine team.
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Extended data
Extended Data Fig. 1 Box plots of pain scores on postoperative day 1 per procedure and study arm.
Box plots of pain scores on postoperative day 1 per procedure in the opioid-free prescription (OFP) arm (A) and the restrictive opioid prescription (ROP) arm (B). The box represents the (interquartile range (IQR), spanning the 25th to 75th percentiles. The horizontal line within each box indicates the median. No significant difference in distribution was found between groups. Sample size: n = 103. Wilcoxon rank-sum nonparametric test was applied, using a two-sided p-value of <0.05 as statistically significant.
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Supplementary Information (download PDF )
Consort checklist, anesthesia protocol, surgical checklist, study protocol and statistical analysis plan.
Source data
Source Data Figs. 1 and 2 and Extended Data Fig. 1 (download XLSX )
Pain scores on postoperative days 1 and 7.
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Zakhari, A., Désilets, J., Della Rocca, C. et al. Eliminating opioid prescriptions from outpatient minimally invasive gynecologic surgery: a randomized trial. Nat Med 32, 746–751 (2026). https://doi.org/10.1038/s41591-025-04096-6
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DOI: https://doi.org/10.1038/s41591-025-04096-6
