Pharmacogenetic Predictors of Postoperative Opioid-Related Adverse Events: A Systematic Review

Backgrounds/Aims: This systematic review aimed to assess associations between genotypes and the risk of experiencing postoperative opioid-related adverse drug events (ORADEs). Methods: Following PRISMA guidelines and registered with PROSPERO, we searched MEDLINE, Embase and CENTRAL for studies assessing genetic predictors of ORADEs within 24 h postoperatively. Eligible studies included English-written retrospective and prospective cohort studies as well as randomised trials. Risk of bias was assessed using the QUIPS tool. Data were extracted in duplicate, and relative risks with 95% confidence intervals were calculated. Meta-analyses were conducted when ≥ 2 studies assessed the same genetic predictor and ORADE relationship. Results: Of the 119 523 citations, 27 studies (5279 patients) met inclusion criteria. All included studies ranked high risk of bias. Of the 28 investigated predictors, 17 significantly increased or decreased ORADE risk in individual studies. Of the 31 meta-analyses, only two demonstrated significant associations (p < 0.05; COMT rs4680 AA and nausea, and CYP2D6 IM and hyperhidrosis). Conclusion: While finding two significant associations, we would expect one to two significant associations at random given the 31 meta-analyses. Findings were limited by heterogeneity, few studies and small sample sizes. The current evidence does not suggest that genotypes should have a central place in the risk stratification of the occurrence of postoperative ORADEs.