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Although there are multiple analgesia techniques, opioids remain the most widely used drug for pain control. Postoperative Nausea and Vomiting (PONV), sleepiness, respiratory, and gastrointestinal disorder are common complications of postoperative opioid use, which makes the decrease in opioid demand, through combination with non-opioid agents, desirable. Dexmedetomidine (DEX) is an alpha2-adrenergic agonist with sedative and anxiolytic effects. Recently, some studies proved the evidence of its notable opioid-sparing effect. Furthermore DEX, compared to opioids, seems to have the advantage of not inhibiting spontaneous breathing. Aim: This systematic review protocol aims to define the analgesic effect of perioperative DEX infusion and the cumulative opioid consumption of patients undergoing general anesthesia. Methods: The review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and MetaAnalysis Protocols (PRISMAP) statement and the Cochrane recommendations for Systematic Reviews of Interventions. Results: The primary outcomes will be 1) The effect of DEX infusion, on pain control, compared to placebo or other treatments and 2) The opioid-sparing effect of DEX infusion compared to placebo or other treatments. The secondary outcome will be a) Respiratory depression, b) Hypotension requiring fluid infusion and/or amine, c) Bradycardia requiring vasoactive drugs, d) Needing of prolonged hospital stay, e) PONV and gastrointestinal disorders. Conclusion: A sub-analysis is planned for i) The type of surgery performed, ii) Patient’s gender, iii) Patients age. If possible, a metaanalysis (including subanalysis and sensitivity analysis for all assessed outcomes) will be performed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be followed to create a Summary of Findings. The Registration Number for this Systematic Review is CRD42018086687.

Perioperative Dexmedetomidine Infusion, as Opioid-Sparing Strategy, in Patients Undergoing General Anesthesia: A Systematic Review Protocol