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Clonidine as an Adjuvant to Intrathecal Local Anesthetics for Surgery: Systematic Review of Randomized Trials
  1. Nadia Elia, M.D.a,
  2. Xavier Culebras, M.D.b,
  3. Christian Mazza, Ph.D.c,
  4. Eduardo Schiffer, M.D.a and
  5. Martin R. Tramèr, M.D., D.Phil.a
  1. aDivision of Anesthesiology, University Hospitals of Geneva, Geneva
  2. bClinique de Genolier, Genolier, University of Geneva, Geneva, Switzerland
  3. cDivision of Mathematics, University of Geneva, Geneva, Switzerland.


Background and Objectives: Clonidine is added to intrathecal local anesthetics to improve intraoperative analgesia and to increase the duration of sensory and motor block. The aim of this systematic review is to quantify beneficial and harmful effects of clonidine when used as an adjuvant to intrathecal local anesthetics for surgery.

Methods: We included data from 22 randomized trials (1,445 patients) testing a large variety of doses of clonidine, added to intrathecal bupivacaine, mepivacaine, prilocaine, or tetracaine.

Results: Clonidine 15 to 150 μg prolonged in a linear, dose-dependent manner, the time to 2 segment regression (range of means, 14 to 75 minutes) and the time to regression to L2 (range of means, 11 to 128 minutes). The time to first analgesic request (median 101 minutes, range 35 to 310) and of motor block (median 47 minutes, range 6 to 131) was prolonged without evidence of dose-responsiveness. Time to achieve complete sensory or motor block, and extent of cephalic spread remained unchanged. There were fewer episodes of intraoperative pain with clonidine (relative risk, 0.24; 95% confidence interval [CI], 0.09-0.64; number needed to treat, 13) but more episodes of arterial hypotension (relative risk, 1.81; 95% CI 1.44-2.28; number needed to harm, 8) without evidence of dose-responsiveness. The risk of bradycardia was unchanged.

Conclusions: This study may serve as a rational basis to help clinicians decide whether or not to combine clonidine with an intrathecal local anesthetic for surgery. The optimal dose of clonidine, however, remains unknown.

  • Surgery
  • Regional anesthesia
  • Analgesia
  • Dose-response
  • Alpha2 adrenoreceptor agonist

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  • Reprint requests: Nadia Elia, M.D., Division of Anesthesiology, University Hospitals of Geneva, 24, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. E-mail: nadia.elia{at}

  • Dr. Elia's salary was provided by the EBCAP foundation ( The project was funded by institutional funds. Part of this work was presented at the annual scientific meeting of the SSAR (Swiss Society of Anesthesia and Reanimation) in Interlaken, Switzerland, November 2-4, 2006.