Synthesizing Evidence on Adverse Events of Perioperative Clonidine: An Umbrella Review

Abstract

Background: Clonidine, a potent α2-adrenoceptor agonist, is used in anesthesia for its sedative and analgesic properties, but its administration requires careful monitoring due to potential risks of hypotension and bradycardia. As there are increasing number of trials on clonidine, this study aimed to synthesize a conclusion on unwanted consequences of clonidine use in the perioperative period. Materials and Methods: This umbrella review synthesizes evidence on adverse events associated with perioperative prescription of clonidine, following the PRIOR guidelines using three prominent databases of Scopus, PubMed, and Web of Science with a strategic combination of keywords. Studies included were systematic reviews, meta-analyses, and network meta-analyses published in English; studies reviewing prescribing systematic clonidine perioperative; and reporting adverse events. Primary outcomes were cardiovascular events, respiratory, neurological, and gastrointestinal complications. Data were extracted systematically by two independent reviewers and analyzed using random effects models in Stata. Pooled odds ratios and mean differences were calculated, with heterogeneity assessed using the I² statistic. Results: Our umbrella review of 8 systematic review studies including 223 studies from 1980 till now; all of which included only randomized controlled trials (RCTs). The bradycardia analysis, comprising four studies, shows a significant increased risk of bradycardia compared to control (OR: 1.653, 95% CI: 1.013 to 2.700) with some heterogeneity (P=0.0609). Hypotension meta-analysis (four studies) reveals a substantial increased risk (exp(theta): 3.281, 95% CI: 1.696 to 6.347), albeit with moderate heterogeneity (I^2=62.37%, P=0.0355). Heart rate reduction (two studies) and MAP reduction (two studies) meta-analyses indicate significant effects of clonidine, with substantial heterogeneity. Conclusion: Our comprehensive umbrella review highlights significant associations between perioperative clonidine and complications such as bradycardia and hypotension, suggesting the need for careful consideration and further investigation in clinical practice.