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Clonidine Does Not Reduce Pain or Opioid Consumption After Noncardiac Surgery

Turan, Alparslan MD; Babazade, Rovnat MD; Kurz, Andrea MD; Devereaux, Phillip J. MD, PhD; Zimmerman, Nicole M. MS; Hutcherson, Matthew T. BS; Naylor, Amanda J. BA; Ali Sakr Esa, Wael MD; Parlow, Joel MD, FRCPC; Gilron, Ian MD; Honar, Hooman MD; Salmasi, Vafi MD; Sessler, Daniel I. MD

doi: 10.1213/ANE.0000000000001356
Regional Anesthesia and Acute Pain Medicine: Original Clinical Research Report

BACKGROUND: Clonidine is an α2-adrenoceptor agonist, which has analgesic properties. However, the analgesic efficacy of perioperative clonidine remains unclear. We, therefore, tested the hypothesis that clonidine reduces both pain scores and cumulative opioid consumption during the initial 72 hours after noncardiac surgery.

METHODS: Six hundred twenty-four patients undergoing elective noncardiac surgery under general and spinal anesthesia were included in this substudy of the PeriOperative ISchemia Evaluation-2 trial. Patients were randomly assigned to 0.2 mg oral clonidine or placebo 2 to 4 hours before surgery, followed by 0.2 mg/d transdermal clonidine patch or placebo patch, which was maintained until 72 hours after surgery. Postoperative pain scores and opioid consumption were assessed for 72 hours after surgery.

RESULTS: Clonidine had no effect on opioid consumption compared with placebo, with an estimated ratio of means of 0.98 (95% confidence interval, 0.70–1.38); P = 0.92. Median (Q1, Q3) opioid consumption was 63 (30, 154) mg morphine equivalents in the clonidine group, which was similar to 60 (30, 128) mg morphine equivalents in the placebo group. Furthermore, there was no significant effect on pain scores, with an estimated difference in means of 0.12 (95% confidence interval, −0.02 to 0.26); 11-point scale; P = 0.10. Mean pain scores per patient were 3.6 ± 1.8 for clonidine patients and 3.6 ± 1.8 for placebo patients.

CONCLUSIONS: Clonidine does not reduce opioid consumption or pain scores in patients recovering from noncardiac surgery.

From the *Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio; Department of General Anesthesiology, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio; Departments of Cardiology and Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; §Departments of Outcomes Research and Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio; Department of Anesthesiology, Queen’s University and Kingston Hospitals, Kingston, Ontario, Canada; Departments of Anesthesiology and Biomedical and Molecular Sciences, Queen’s University, Kingston General Hospital, Kingston, Ontario, Canada; and #Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio.

Rovnat Babazade, MD, is currently affiliated with Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas.

Accepted for publication March 17, 2016.

Funding: Supported by the Canadian Institutes of Health Research.

The authors declare no conflicts of interest.

Reprints will be available from the authors.

Address correspondence to Alparslan Turan, MD, Department of Outcomes Research, Cleveland Clinic, 9500 Euclid Ave, P-77, Cleveland, OH 44195. Address e-mail to

© 2016 International Anesthesia Research Society