Abstract
Background: Serotonin 5-HT3 receptor antagonists such as ondansetron have been investigated to attenuate opioid withdrawal signs in studies.
Objective: Therefore, we designed a randomized double-blinded placebo-controlled trial to evaluate this effect on opioid-addicted patients who were admitted to the orthopedic department for surgery due to bone fractures. Methods: Male adults who were addicted to opioids, aged 18 to 79 years were enrolled (n=96) and randomized into intravenous doses (4 & 8 mg) of ondansetron (n=32) and placebo (n=32). The vital signs, withdrawal symptoms and the frequency requirement of fentanyl were recorded during anesthesia, and opioid (pethidine) analgesic was received during the recovery period. Outcome parameters were analyzed for reduction of withdrawal symptoms in addicted adults. Results: We indicated that ondansetron demonstrated significant differences with few vital outcomes including systolic blood pressure (SBP) 20 (SBP3) and 50 min (SBP4) after injection of ondansetron during the period of surgery. Ondansetron could also significantly reduce the frequency requirement of fentanyl at 20 min (dose 3) in general anesthesia. Furthermore, requirement for further administration of opioid analgesic drugs such as pethidine was significantly reduced in the ondansetron groups. Objective opioid withdrawal scale (OOWS) results indicated that few clinical parameters including tremor, hot and cold flushes and anxiety were significantly attenuated in addicted patients who received ondansetron. Conclusion: This study demonstrated supporting evidence for the beneficial treatment of ondansetron for the control of withdrawal symptoms and pain in addicted patients, and more clinical studies are suggested in this regard.Keywords: Serotonin receptors, anesthesiology, antiemetic drugs, abuse, pain, dislocations.
Graphical Abstract
[1]
Leppert W, Krajnik M, Wordliczek J. Delivery systems of opioid analgesics for pain relief: A review. Curr Pharm Des 2013; 19(41): 7271-93.
[http://dx.doi.org/10.2174/138161281941131219130127] [PMID: 23489205]
[http://dx.doi.org/10.2174/138161281941131219130127] [PMID: 23489205]
[2]
Saini S, Bhatnagar S. Cancer pain management in developing countries. Indian J Palliat Care 2016; 22(4): 373-7.
[http://dx.doi.org/10.4103/0973-1075.191742] [PMID: 27803557]
[http://dx.doi.org/10.4103/0973-1075.191742] [PMID: 27803557]
[3]
Podolsky AT, Sandweiss A, Hu J, et al. Novel fentanyl-based dual μ/δ-opioid agonists for the treatment of acute and chronic pain. Life Sci 2013; 93(25-26): 1010-6.
[http://dx.doi.org/10.1016/j.lfs.2013.09.016] [PMID: 24084045]
[http://dx.doi.org/10.1016/j.lfs.2013.09.016] [PMID: 24084045]
[4]
Becker DE, Phero JC. Drug therapy in dental practice: Nonopioid and opioid analgesics. Anesth Prog 2005; 52(4): 140-9.
[http://dx.doi.org/10.2344/0003-3006(2005)52[140:DTD]2.0.CO;2] [PMID: 16596914]
[http://dx.doi.org/10.2344/0003-3006(2005)52[140:DTD]2.0.CO;2] [PMID: 16596914]
[5]
Roychoudhury M, Kulkarni SK. Prevention of morphine discontinuation phenomenon in mice by ondansetron, a selective 5-HT3 antagonist. Methods Find Exp Clin Pharmacol 1996; 18(10): 677-83.
[PMID: 9121224]
[PMID: 9121224]
[6]
Pinelli A, Trivulzio S, Tomasoni L. Effects of ondansetron administration 1 Zofran is the trade name for ondansetron (injectable solution) manufactured by Glaxo Sp A, Verona, Italy. 1 on opioid withdrawal syndrome observed in rats. Eur J Pharmacol 1997; 340: 111-9.
[http://dx.doi.org/10.1016/S0014-2999(97)01349-6] [PMID: 9537805]
[http://dx.doi.org/10.1016/S0014-2999(97)01349-6] [PMID: 9537805]
[7]
Kidd LR, Milner QJ. Paracetamol and unwanted 5-hydroxytryptamine interactions. Anaesthesia 2015; 70(6): 757-8.
[http://dx.doi.org/10.1111/anae.13112] [PMID: 25959188]
[http://dx.doi.org/10.1111/anae.13112] [PMID: 25959188]
[8]
Hui SC, Sevilla EL, Ogle CW. 5-HT3 antagonists reduce morphine self-administration in rats. Br J Pharmacol 1993; 110(4): 1341-6.
[http://dx.doi.org/10.1111/j.1476-5381.1993.tb13966.x] [PMID: 8306073]
[http://dx.doi.org/10.1111/j.1476-5381.1993.tb13966.x] [PMID: 8306073]
[9]
Papadopoulos G, Pouangare M, Papathanakos G, Arnaoutoglou E, Petrou A, Tzimas P. The effect of ondansetron on postoperative delirium and cognitive function in aged orthopedic patients. Minerva Anestesiol 2014; 80(4): 444-51.
[PMID: 24193238]
[PMID: 24193238]
[10]
Badeaux J, Bonanno L, Au H. Effectiveness of ondansetron as an adjunct to lidocaine intravenous regional anesthesia on tourniquet pain and postoperative pain in patients undergoing elective hand surgery: A systematic review protocol. JBI Database Syst Rev Implement Reports 2015; 13(1): 27-38.
[http://dx.doi.org/10.11124/jbisrir-2015-1768] [PMID: 26447005]
[http://dx.doi.org/10.11124/jbisrir-2015-1768] [PMID: 26447005]
[11]
Salimi A, Safari F, Mohajerani SA, Hashemian M, Kolahi AA, Mottaghi K. Long-term relapse of ultra-rapid opioid detoxification. J Addict Dis 2014; 33(1): 33-40.
[http://dx.doi.org/10.1080/10550887.2014.882727] [PMID: 24471478]
[http://dx.doi.org/10.1080/10550887.2014.882727] [PMID: 24471478]
[12]
Roelants F, Lavand’homme P. Clonidine versus sufentanil as an adjuvant to ropivacaine in patient-controlled epidural labour analgesia: A randomised double-blind trial. Eur J Anaesthesiol 2015; 32(11): 805-11.
[http://dx.doi.org/10.1097/EJA.0000000000000347] [PMID: 26426577]
[http://dx.doi.org/10.1097/EJA.0000000000000347] [PMID: 26426577]
[13]
Savant K, Khandeparker RV, Berwal V, Khandeparker PV, Jain H. Comparison of ondansetron and granisetron for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia: A prospective, randomised, and double blind study. J Korean Assoc Oral Maxillofac Surg 2016; 42(2): 84-9.
[http://dx.doi.org/10.5125/jkaoms.2016.42.2.84] [PMID: 27162748]
[http://dx.doi.org/10.5125/jkaoms.2016.42.2.84] [PMID: 27162748]
[14]
Parathoduvil AA, Sisupalan A, Rema PL. Comparison of antiemetic effectiveness of palonosetron versus ondansetron in patients on cancer chemotherapy: A prospective observational study in South Indians. J Clin Diagn Res 2017; 11(5): FC10-4.
[http://dx.doi.org/10.7860/JCDR/2017/25129.9818] [PMID: 28658796]
[http://dx.doi.org/10.7860/JCDR/2017/25129.9818] [PMID: 28658796]
[15]
Owczuk R, Wenski W, Polak-Krzeminska A, et al. Ondansetron given intravenously attenuates arterial blood pressure drop due to spinal anesthesia: A double-blind, placebo-controlled study. Reg Anesth Pain Med 2008; 33(4): 332-9.
[PMID: 18675744]
[PMID: 18675744]
[16]
Sumalatha GB, Dodawad RR, Pandarpurkar S, Jajee PR. A comparative study of attenuation of propofol-induced pain by lignocaine, ondansetron, and ramosetron. Indian J Anaesth 2016; 60(1): 25-9.
[http://dx.doi.org/10.4103/0019-5049.174810] [PMID: 26962251]
[http://dx.doi.org/10.4103/0019-5049.174810] [PMID: 26962251]
[17]
Wakim JH. Alleviating symptoms of withdrawal from an opioid. Pain Ther 2012; 1(1): 4.
[http://dx.doi.org/10.1007/s40122-012-0004-5] [PMID: 25134933]
[http://dx.doi.org/10.1007/s40122-012-0004-5] [PMID: 25134933]
[18]
Chu LF, Sun J, Clemenson A, et al. Ondansetron does not reduce withdrawal in patients with physical dependence on chronic opioid therapy. J Addict Med 2017; 11(5): 342-9.
[http://dx.doi.org/10.1097/ADM.0000000000000321] [PMID: 28514235]
[http://dx.doi.org/10.1097/ADM.0000000000000321] [PMID: 28514235]
24
1