ORIGINAL ARTICLE The Effect of Methylnaltrexone on the Side Effects of Intrathecal Morphine after Orthopedic Surgery under Spinal Anesthesia Farid Zand, MD; Afshin Amini, MD; Saman Asadi, MD; Arash Farbood, MD Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran & Abstract: Methylnaltrexone is a peripheral opioid recep- tor antagonist that does not cross the blood–brain barrier; so without interference with pain relief, it could reverse the peripheral opioid side effects such as constipation, pruritus, postoperative ileus, and urinary retention. This study has been designed to evaluate the effect of methylnaltrexone on postoperative side effects of intrathecal morphine. In sev- enty-two 18- to 55-year-old patients scheduled for elective orthopedic operations under spinal anesthesia, neuraxial blockade was achieved using 10 mg 0.5% hyperbaric bupivacaine and 0.1 mg preservative-free morphine sulfate. The first group (M) received 12 mg methylnaltrexone, while the second group (P) received normal saline, subcutaneously, immediately after spinal block in a randomized, double-blind fashion. There was a significant decrease in the rate of nausea and vomiting in group M, but there was no significant difference in the rate of pruritus or urinary retention between the two groups. Pain score was significantly lower in group M. Respiratory depression or decreased level of consciousness was not reported in any patient. Subcutaneous administration of methylnaltrexone was not effective in decreasing postoperative urinary retention and pruritus, but lowered the rate of nausea and vomiting and pain score after intrathecal bupivacaine and morphine. & Key Words: methylnaltrexone, intrathecal morphine, uri- nary retention, postoperative nausea and vomiting, PONV, pain score INTRODUCTION Orthopedic surgeries are among the most painful procedures that require special attention to reduce pain postoperatively. Intra-operative anesthesia and postop- erative analgesia can be achieved with spinal anesthesia combining long-acting local anesthetics and opioids. Morphine sulfate is one of the long-acting opioids whose intrathecal administration can result in decreased post- operative pain for about 24 hours 1–3 , making it a reasonable choice to use in combination with bupiva- caine for spinal anesthesia in lower extremity orthopedic surgeries. As morphine is a potent water-soluble opioid, it has some significant side effects such as nausea and vomiting, pruritus, constipation, urinary retention, respiratory depression, and decreased level of conscious- ness. 4,5 Most of the morphine side effects are mediated through peripheral opioid receptors, but analgesia is the result of the effect of morphine sulfate on central nervous system receptors. 6 The main receptors of morphine sulfate are the mu (l1, l2, l3) receptors. These receptors are present dominantly in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas of the brain. Also, there are some l-receptors in the other sites such as spinal nucleus of the fifth cranial nerve. The l1-receptors are responsible for analgesia and physical Address correspondence and reprint requests to: Afshin Amini, MD, Department of Anesthesiology, Shahid Faghihi Hospital, Shiraz 71348- 44119, Iran. E-mail: aamini@sums.ac.ir, afshinaminie@gmail.com. Clinical Trial Registration No.: IRCT; 201204145172N3. Submitted: July 05, 2013; Revision accepted: January 10, 2014 DOI. 10.1111/papr.12185 © 2014 World Institute of Pain, 1530-7085/14/$15.00 Pain Practice, Volume , Issue , 2014 –