Effect of preoperative administration of systemic alpha-2 agonists on postoperative pain: a systematic review and meta-analysis

BACKGROUND: Alpha-2 agonists have sedative, analgesic, and opioid-sparing effects. Moreover, intraoperative or postoperative systemic administration of alpha-2 adrenergic agonists is known to reduce postoperative pain and opioid consumption. This meta-analysis investigated whether preoperative administration of alpha-2 agonists can affect postoperative pain and opioid consumption. METHODS: We searched the MEDLINE, EMBASE, Cochrane Library (CENTRAL), KoreaMed, and KMbase databases through March 2019 to identify relevant randomized controlled trials (RCTs) on the effect of preoperative systemic administration of alpha-2 agonists on postoperative pain and opioid consumption. We conducted a meta-analysis according to the Cochrane Collaboration guidelines. Standardized mean differences (SMDs) of postoperative pain intensity or dose of opioid consumption in the alpha-2 agonist group were extracted and combined using a random-effect model and were compared to those of the control group. RESULTS: Eleven RCTs involving 748 participants were included in this meta-analysis. Preoperative administration of systemic alpha-2 agonists significantly reduced cumulative opioid consumption up to 6 h (SMD, –0.52; 95% confidence interval [–0.90 to –0.14]) and 24 h (SMD, –0.68 [–1.27 to –0.09]) after surgery. Moreover, preoperative administration of alpha-2 agonists significantly reduced postoperative pain intensity at 6 h (SMD, –0.50 [–0.78 to –0.21]) and 24 h (SMD, –0.44 [–0.86 to –0.03]). CONCLUSIONS: In this meta-analysis, high degree of heterogeneity limits the preoperative administration of alpha-2 agonists in reducing postoperative opioid consumption and pain intensity. Future powered large RCTs are required to increase the certainty of evidence on the effect in reducing postoperative opioid consumption and pain intensity.