The immunomodulatory effect of sugammadex in vitro and after total hip arthroplasty: A randomised controlled pilot and retrospective cohort study.

Abstract

Background: Postoperative immunosuppression is a well known phenomenon associated with infectious complications. Peri-operative immune dysregulation is likely induced by surgical damage and anaesthetics, but remains far from comprehensively characterised. To address this, the effects of individual drugs on immune function must be explored. Sugammadex, a cyclodextrin that encapsulates rocuronium, also binds other drugs and structures and may influence the inflammatory response.

Objective: Investigate the potential immunomodulatory effect of sugammadex.

Design: An in-vitro experiment, randomised controlled pilot study and retrospective cohort study.

Setting: Tertiary teaching hospital.

Patients: Twelve healthy donors, 20 adults undergoing total hip arthroplasty and 1000 major abdominal surgery patients.

Intervention: In vitro: isolated peripheral blood mononuclear cells were exposed to sugammadex and rocuronium before stimulation with Escherichia coli lipopolysaccharides (LPS).Pilot study: patients undergoing total hip arthroplasty under single shot spinal anaesthesia randomised to sugammadex (8 mg kg-1) or placebo at the end of surgery.

Main outcome measure: In vitro: TNF, IL-1β and IL-6 production capacity.Pilot study: Ex-vivo cytokine production capacity after whole blood stimulation with LPS.Retrospective cohort: sugammadex as a predictor of postoperative infectious complications.

Results: In vitro: rocuronium suppressed TNF and IL-1β production capacity. Higher doses of sugammadex (100 and 1000 μg ml-1; 100 μg ml-1 corresponds to plasma concentration reached upon 8 mg kg-1 sugammadex) restored suppression of TNF and IL-1β.Pilot study: no differences in ex-vivo cytokine production capacity between the sugammadex and placebo group at the end of surgery or on postoperative day 1.Retrospective cohort study: no association between sugammadex and postoperative infectious complications (OR = 1.000, 95% CI 0.998 to 1.002).

Conclusion: Sugammadex preserved cytokine production capacity of TNF and IL-1β in vitro. The clinical pilot study and retrospective cohort study revealed no early postoperative immunomodulatory effects for sugammadex in the clinically used dosing range.

Trial registration: clinicaltrials.gov identifier: NCT05723406 and NCT05244655.