Therapeutics The Journal of Clinical Pharmacology 2016, 56(7) 827–834 C  2015, The American College of Clinical Pharmacology DOI: 10.1002/jcph.666 Comparison of Dexmedetomidine and Clonidine as Adjuvants to Local Anesthetics for Intrathecal Anesthesia: A Meta-Analysis of Randomized Controlled Trials Changsheng Zhang, MD 1 * , Changtian Li, MD 2 * , Massimiliano Pirrone, MD 3 , Li Sun, MD, PhD 4 , and Weidong Mi, MD, PhD 1 Abstract The authors performed a meta-analysis to compare the characteristics of clonidine and dexmedetomidine as adjuvants to local anesthetic in intravertebral anesthesia. Four investigators independently searched electronic databases for randomized trials comparing the characteristics of clonidine vs dexmedetomidine as adjuvants to local anesthetic on adults. The endpoints were onset of analgesia, sensory and motor block, and duration of analgesia. A random-effects model was used to perform quantitative analysis. Seven studies comprising 354 subjects were included in this meta-analysis. The onset of sensory block was signiicantly 40 seconds shorter when dexmedetomidine was added as an adjuvant in the intrathecal injection. The duration of stable sensory block, duration of overall sensory block, and the time before the need for analgesic requirements were signiicantly extended, 10.8 minutes, 22.3 minutes, and 38.6 minutes, respectively, when dexmedetomidine was used as an adjuvant to local anesthetics (bupivacaine or ropivacaine). No signiicant differences were detected in the motor block characteristics and the time to achieve peak sensory level between dexmedetomidine and clonidine as adjuvants to local anesthetics. Compared to clonidine, the addition of dexmedetomidine as an adjuvant to local anesthetics is associated with earlier,prolonged sensory block characteristics and later need for analgesic requirements. Keywords clonidine, dexmedetomidine, local anesthetic, intrathecal anesthesia Spinal, epidural, or combined spinal-epidural anes- thesia are the most popular and reliable techniques for abdominal and lower limb surgery. Prolongation of intraoperative and postoperative intrathecal anesthesia and analgesia has been achieved by the addition of various adjuvants, such as opioids, 1 epinephrine, 2 magnesium sulfate, 3 and α 2 -adrenergic agonists. 4 α 2 -Adrenergic agonists have been demonstrated to have sedative, analgesic, perioperative sympatholytic, anesthetic-sparing, and hemodynamic-stabilizing properties. The α 2 agonists are one of the most extensively studied classes of adjuvants. At present the major α 2 -adrenergic agonists used in perioperative care are clonidine and dexmedetomi- dine. Clonidine is the irst clinically used α 2 -adrenergic agonist. The role of α 2 -adrenergic agonists in anes- thesia was irst established by observations made in patients during anesthesia who were prescribed cloni- dine therapy. 5 Clonidine shares similar analgesic path- ways to local anesthetics and has also been shown to interact synergistically with local anesthetics. 6 Dexmedetomidine is a newly developed and highly selective α 2 -adrenergic agonist with an afinity 8 times greater than clonidine and much less α 1 effect. It shows a high ratio of speciicity for the α 2 receptor (α 2 /α 1 1600 : 1) compared with clonidine (α 2 /α 1 200 : 1), resulting in a higher hypnotic and analgesic effects. 7 Studies comparing the effects of clonidine to the effects of dexmedetomidine administered as adjuvants to local anesthetics (bupivacaine or ropivacaine) during in- trathecal anesthesia have resulted in disputable indings. It is still unclear which of the 2 drugs is superior when used as an adjuvant to bupivacaine or ropivacaine. 1 Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing, China 2 Department of Ultrasound, Chinese PLA General Hospital, Beijing, China 3 Department of Anesthesia, Critical Care and Pain Medicine, Mas- sachusetts General Hospital, Boston, MA, USA 4 Department of Anesthesiology, Beijing Military Region General Hospi- tal, Beijing, China Submitted for publication 15 July 2015; accepted 20 October 2015. Corresponding Author: Weidong Mi, MD, PhD, Professor of Anesthesia, Chinese PLA Medical School, Anesthesiologist in Chief, Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing, P. R. China 100853 Email: plamzk@126.com ∗ These authors contributed equally to this work.