GLP-1 Receptor Agonist Withholding Interval and Residual Gastric Contents Before Anaesthesia: A Systematic Review and Meta-analysis

Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may delay gastric emptying, and pooled binary evidence suggests a nearly six-fold increase in residual gastric contents (RGC) despite fasting (odds ratio (OR) 5.96, 95% confidence interval (CI) 3.96–8.98; 18 studies; 165,522 individuals; 3,831 cases) without a demonstrable increase in pulmonary aspiration (OR 1.04, 95% CI 0.87–1.25; 9 studies; 304,060 individuals; 481 cases). The optimal withholding interval for weekly agents appears to be based on consensus rather than interval-stratified evidence. Methods: A systematic review and dose-interval–response meta-analysis of randomised trials and observational studies reporting RGC or pulmonary aspiration in adults undertaking fasting while receiving GLP-1 RAs was conducted. Random-effects models pooled odds ratios for RGC, pulmonary aspiration, and dose withholding. For RGC, log-odds ratios were regressed on the number of days since the last dose using restricted cubic splines, calibrated against published interval anchors, and translated into number-needed-to-hold values per 10,000 procedures at 3, 5, 7, 10, and 14 days. The certainty of evidence was rated with GRADE, with dose–response as a pre-specified upgrading domain. Results: Exposure was associated with increased odds of RGC (OR 5.96, 95% CI 3.96–8.98; 18 studies) and the endoscopic sub-pool (OR 6.30, 95% CI 5.30–7.49; 12 studies). No analysis demonstrated an association with pulmonary aspiration (OR 1.04, 95% CI 0.87–1.25; OR 1.26, 95% CI 0.86–1.87; adjusted OR 1.07, 95% CI 0.85–1.34; RR 0.98, 95% CI 0.73–1.31). Withholding at least one dose appeared to reduce RGC odds (OR 0.51, 95% CI 0.33–0.81; 5 studies; 1,706 individuals; 208 events). Modelled RGC odds appeared to decline steeply from day 3 (OR 34.4, 95% CI 8.7–136.8) to day 7 (OR 3.3, 95% CI 0.4–30.3) and plateaued at days 10–14 (OR 2.27, 95% CI 0.92–5.59). Withholding for 7 days at a baseline of 24% was estimated to prevent 4,617 RGC events per 10,000 procedures (number needed to hold [NNH] ≈ 2). Conclusions: RGC risk appears to decline substantially across the first week after the last dose and then plateau at a non-zero residual level. For weekly agents, a one-week hold may capture most of the attainable risk reduction; however, withholding alone may be necessary but insufficient. The certainty of evidence is low–moderate for the interval-modelled RGC estimate; interval-stratified aspiration evidence appears to be absent. A prospective registry of aspiration as an interval-stratified endpoint and randomised comparisons of hold durations may be warranted.

Keywords: glucagon-like peptide-1 receptor agonists; residual gastric content; pulmonary aspiration; perioperative fasting; drug withholding; dose-interval-response meta-analysis