Comparison between intravenous and intratecal clonidine for postoperative analgesia of patients submitted to laparoscopic cholecystectomy: randomized clinical trial
Introduction and objectives
Alpha2 adrenergic agonists, such as clonidine, are used as adjuvants during anesthesia due to their analgesic, sedative, and cardiovascular effects. The objective of the present study was to compare the effect of clonidine administered intravenously and intrathecally on the postoperative pain score of patients undergoing laparoscopic cholecystectomy, according to the route of administration and postoperative opioid consumption.
This randomized clinical trial, blind to patients and evaluator, assessed 60 patients, candidates for elective laparoscopic cholecystectomy under standardized general anesthesia techniques. Patients were randomly allocated into three groups (20 in each group): Control Group (CG), Intrathecal Clonidine Group (ITCG) and Intravenous Clonidine Group (IVCG). The primary outcome was the comparison of pain, Blood Pressure (BP) and Heart Rate (HR) scores among groups. The secondary outcome was report of adverse effects such as bradycardia, hypotension and sedation, and the need for rescue medication.
The mean age was 37.2 ± 8.2 years, and the mean body mass was 28.3 ± 3.6 kg.m-2. Regarding HR (p = 0.003) and pain (p = 0.027), patients in ITCG and CG showed a different profile over time, with CG showing higher consumption of morphine as rescue medication (p = 0.005).
The administration of intrathecal and intravenous clonidine in low doses can reduce hemodynamic parameters and decrease postoperative requirement of analgesics. Further studies should investigate the ideal dose and method.
1 V. Minutolo, A. Licciardello, M. Arena, et al. Laparoscopic cholecystectomy in the treatment of acute cholecystitis: comparison of outcomes and costs between early and delayed cholecystectomy Eur Rev Med Pharmacol Sci, 18 (2 Suppl) (2014), pp. 40-46
2 M. Mishra, S.P. Mishra, S.K. Mathur Clonidine versus nitroglycerin infusion in laparoscopic cholecystectomy JSLS., 18 (2014) e2014.00305
3 J. Joris, I. Cigarini, M. Legrand, et al. Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy Br J Anaesth, 69 (1992), pp. 341-345
4 S. Sjövall, M. Kokki, H. Kokki Laparoscopic surgery: a narrative review of pharmacotherapy in pain management Drugs, 75 (2015), pp. 1867-1889
5 H. Yilmaz, O. Arun, S. Apiliogullari, et al. Effect of laparoscopic cholecystectomy techniques on postoperative pain: a prospective randomized study J Korean Surg Soc., 85 (2013), pp. 149-153
6 H. Mirhosseini, M.H. Avazbakhsh, M.H. Amiri, et al. Effect of oral clonidine on shoulder tip pain and hemodynamic response after laparoscopic cholecystectomy: a randomized double-blind study Anesth Pain Med, 7 (2017) e61669-e
7 J. Ortiz, L.C. Chang, D.A. Tolpin, et al. Randomized, controlled trial comparing the effects of anesthesia with propofol, isoflurane, desflurane and sevoflurane on pain after laparoscopic cholecystectomy Braz J Anesthesiol, 64 (2014), pp. 145-151
8 N. Govil, P. Kumar Intraperitoneal levobupivacaine with or without clonidine for pain relief after laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled trial Anesth Essays Res., 11 (2017), pp. 125-128
9 K. Gritsenko, Y. Khelemsky, A.D. Kaye, et al. Multimodal therapy in perioperative analgesia Best Pract Res Clin Anaesthesiol., 28 (2014), pp. 59-79
10 M. De Kock, P. Lavand’homme, H. Waterloos The short-lasting analgesia and long-term antihyperalgesic effect of intrathecal clonidine in patients undergoing colonic surgery Anesth Analg, 101 (2005), pp. 566-572
11 K. Gupta, M. Lakhanpal, P.K. Gupta, et al. Premedication with clonidine versus fentanyl for intraoperative hemodynamic stability and recovery outcome during laparoscopic cholecystectomy under general anesthesia Anesth Essays Res, 7 (2013), pp. 29-33
12 G. Blaudszun, C. Lysakowski, N. Elia, MR. Tramèr Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials Anesthesiology, 116 (2012), pp. 1312-1322
13 N. Anjum, H. Tabish, S. Debdas, et al. Effects of dexmedetomidine and clonidine as propofol adjuvants on intra-operative hemodynamics and recovery profiles in patients undergoing laparoscopic cholecystectomy: A prospective randomized comparative study Avicenna J Med, 5 (2015), pp. 67-73
14 Ministério da Saúde. Resolução nº 466, de 12 de dezembro de 2012. Dispõe sobre as diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Ministério da Saúde. Conselho Nacional de Saúde. [acessado em 20 de março 2019]. Disponível em: https://bvsms.saude.gov.br/bvs/saudelegis/cns/2013/res0466_12_12_2012.html.
15 D.J. Doyle, A. Goyal, P. Bansal, et al. American Society of Anesthesiologist Classification (ASA Class) Disponível em: StatPearls Publishing, Treasure Island (FL), https://pubmed.ncbi.nlm.nih.gov/28722969/ (2019)
16 J.G.S. Fortunato, M.S. Furtado, L.F.A. Hirabae, Oliveira Escalas de dor no paciente crítico: uma revisão integrativa Rev HUPE., 12 (2013), pp. 110-117
17 E.J. Gallagher, P.E. Bijur, C. Latimer, W. Silver Reliability and validity of a visual analog scale for acute abdominal pain in the ED Am J Emerg Med, 20 (2002), pp. 287-290
18 A. Samantaray, M.H. Rao, A. Chandra The effect on post-operative pain of intravenous clonidine given before induction of anaesthesia Indian J Anaesth, 56 (2012), pp. 359-364
19 N. Bharti, S. Dontukurthy, I. Bala, G. Singh Postoperative analgesic effect of intravenous (i.v.) clonidine compared with clonidine administration in wound infiltration for open cholecystectomy Br J Anaesth, 111 (2013), pp. 656-661
20 F. Ahmed, M. Khandelwal, A. Sharma A comparative study of the effect of clonidine, fentanyl, and the combination of both as adjuvant to intrathecal bupivacaine for postoperative analgesia in total abdominal hysterectomy J Anaesthesiol Clin Pharmacol., 33 (2017), pp. 102-106
21 Y. Zhang, X. Zhang, Y. Wang, J. Zhang Effect of clonidine on hemodynamic responses during laparoscopic cholecystectomy: a systematic review and meta-analysis Surg Laparosc Endosc Percutan Tech, 27 (2017), pp. 335-340
22 M. Singh, A. Choudhury, M. Kaur, et al. The comparative evaluation of intravenous with intramuscular clonidine for suppression of hemodynamic changes in laparoscopic cholecystectomy Saudi J Anaesth, 7 (2013), pp. 181-186
23 H. Sahajananda, S. Rao Effects of intravenous clonidine on haemodynamics and on plasma cortisol level during laparoscopic cholecystectomies Indian J Anaesth, 59 (2015), pp. 53-56
24 S.P. Kamble, Y. Bevinaguddaiah, D.C. Nagaraja, et al. Effect of magnesium sulfate and clonidine in attenuating hemodynamic response to pneumoperitoneum in laparoscopic cholecystectomy Anesth Essays Res, 11 (2017), pp. 67-71