Application of Dexmedetomidine as an Opioid Substitute in Opioid-Free Anesthesia: A Systematic Review and Meta-analysis

Pain Physician. 2023 Oct;26(6):E635-E649.


Background: Opioid-based general anesthesia was previously used to alleviate perioperative pain; however, several complications associated with using anesthesia have raised several concerns. Various studies have investigated the application prospect of using opioid-free general anesthesia, such as dexmedetomidine, as an opioid substitute.

Objectives: We performed a systematic review and meta-analysis to explore and highlight the safety and effectiveness of dexmedetomidine as an opioid substitute for opioid-free anesthesia.

Study design: A systematic review and meta-analysis.

Setting: We screened for suitable clinical trials from electronic databases, including "PubMed," "Cochrane Library," "EMBASE," and "Web of Science." Eligible trials were included in this meta-analysis.

Methods: The quality of the screened randomized controlled trials (RCTs) was determined using the risk of bias assessment criteria by the Cochrane Collaboration tool. We used the "Review Manager 5.3" and "Stata 10.0" software to perform the meta-analysis. We evaluated the quality of evidence using the "Grading of Recommendations Assessment, Development, and Evaluation" approach.

Results: For the analysis, we included 32 RCTs encompassing 2,509 patients. In the opioid-free group, the 2-hour postoperative pain score of patients (mean difference = -0.53, 95% CI: -1.00, -0.07; P = 0.02, I2=78%) was significantly lower compared to those in the opioid-based group. In addition, several patients required rescue analgesia (risk ratio = 0.70, 95% CI: 0.58, 0.84, P < 0.05, I2 = 71%) and opioids postsurgery. However, the duration of extubation and postanesthesia care unit, as well as the incidences of bradycardia, were high in patients receiving dexmedetomidine as opioid-free general anesthesia.

Limitations: Subgroup analysis for different anesthesia-maintaining drugs had not been conducted. The heterogeneity did not reduce after subgroup analysis. Different doses of dexmedetomidine had not been evaluated.

Conclusions: These findings indicate that opioid-free general anesthesia based on dexmedetomidine could be effective; however, prolonged extubation time and cardiovascular complications are a few risks associated with dexmedetomidine.

Keywords: dexmedetomidine; meta-analysis; Opioid-free anesthesia.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Analgesia*
  • Analgesics, Opioid / therapeutic use
  • Anesthesia, General / adverse effects
  • Dexmedetomidine* / therapeutic use
  • Humans
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / etiology


  • Dexmedetomidine
  • Analgesics, Opioid