Clonidine for Tourniquet-related Pain in Children

Summary

This study is designed as a randomized, placebo-controlled, double-blinded, clinical trial with two parallel groups. This study investigates the association between a single dose of the drug, Clonidine, and the total amount of opioid administered under and 24 hours after surgery in children undergoing orthopedic limb surgery with the use of tourniquet. The investigators hypothesize that administration of clonidine to children undergoing limb surgery with the use of inflatable tourniquets would reduce post-procedural pain. This study is a pilot to obtain an effect size. Based on this the investigators will calculate a sample size for the main trial enabling us to reach a power of 0.8 with a significans level of 0.05.

Timeline

Start

2021-03-01

Primary completion

2021-12-20

Completion

2022-01-01

Publications

• Background Budic I, Pavlovic D, Kitic D, Kocic G, Cvetkovic T, Simic D, Jevtovic-Stoimenov T. Tourniquet-induced ischemia-reperfusion injuries during extremity surgery at children's age: impact of anesthetic chemical structure. Redox Rep. 2013;18(1):20-6. doi: 10.1179/1351000212Y.0000000037.
• Background Kumar K, Railton C, Tawfic Q. Tourniquet application during anesthesia: "What we need to know?". J Anaesthesiol Clin Pharmacol. 2016 Oct-Dec;32(4):424-430. doi: 10.4103/0970-9185.168174.
• Background Kruse H, Christensen KP, Moller AM, Gogenur I. Tourniquet use during ankle surgery leads to increased postoperative opioid use. J Clin Anesth. 2015 Aug;27(5):380-4. doi: 10.1016/j.jclinane.2015.03.034. Epub 2015 May 12.
• Background Rudkin AK, Rudkin GE, Dracopoulos GC. Acceptability of ankle tourniquet use in midfoot and forefoot surgery: audit of 1000 cases. Foot Ankle Int. 2004 Nov;25(11):788-94. doi: 10.1177/107110070402501106.
• Background Budic I, Pavlovic D, Kocic G, Cvetkovic T, Simic D, Basic J, Zivanovic D. Biomarkers of oxidative stress and endothelial dysfunction after tourniquet release in children. Physiol Res. 2011;60(Suppl 1):S137-45. doi: 10.33549/physiolres.932170. Epub 2011 Jul 19.
• Background Estebe JP, Davies JM, Richebe P. The pneumatic tourniquet: mechanical, ischaemia-reperfusion and systemic effects. Eur J Anaesthesiol. 2011 Jun;28(6):404-11. doi: 10.1097/EJA.0b013e328346d5a9.
• Background Gourdin M, Dubois P, Mullier F, Chatelain B, Dogne JM, Marchandise B, Jamart J, De Kock M. The effect of clonidine, an alpha-2 adrenergic receptor agonist, on inflammatory response and postischemic endothelium function during early reperfusion in healthy volunteers. J Cardiovasc Pharmacol. 2012 Dec;60(6):553-60. doi: 10.1097/FJC.0b013e31827303fa.
• Background Jellinge ME, Petersen RH. [Clonidine can reduce opioid medication during post-operative pain]. Ugeskr Laeger. 2015 Nov 30;177(49):V05150415. Danish.
• Background Isaac L. Clonidine in the central nervous system: site and mechanism of hypotensive action. J Cardiovasc Pharmacol. 1980;2 Suppl 1:S5-19.
• Background Ydemann M, Nielsen BN, Wetterslev J, Henneberg S, Lauritsen T, Steen N, Edstrom B, Afshari A. Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial. Dan Med J. 2016 Jun;63(6):A5234.
• Background Lambert P, Cyna AM, Knight N, Middleton P. Clonidine premedication for postoperative analgesia in children. Cochrane Database Syst Rev. 2014 Jan 28;2014(1):CD009633. doi: 10.1002/14651858.CD009633.pub2.
• Background Boric K, Dosenovic S, Jelicic Kadic A, Batinic M, Cavar M, Urlic M, Markovina N, Puljak L. Interventions for postoperative pain in children: An overview of systematic reviews. Paediatr Anaesth. 2017 Sep;27(9):893-904. doi: 10.1111/pan.13203. Epub 2017 Jul 14.
• Background Wang W, Huang P, Gao W, Cao F, Yi M, Chen L, Guo X. Efficacy and Acceptability of Different Auxiliary Drugs in Pediatric Sevoflurane Anesthesia: A Network Meta-analysis of Mixed Treatment Comparisons. Sci Rep. 2016 Nov 10;6:36553. doi: 10.1038/srep36553.
• Background Moore AD, Anghelescu DL. Emergence Delirium in Pediatric Anesthesia. Paediatr Drugs. 2017 Feb;19(1):11-20. doi: 10.1007/s40272-016-0201-5.
• Background Afshari A. Clonidine in pediatric anesthesia: the new panacea or a drug still looking for an indication? Curr Opin Anaesthesiol. 2019 Jun;32(3):327-333. doi: 10.1097/ACO.0000000000000724.
• Background Ydemann M, Nielsen BN, Henneberg S, Jakobsen JC, Wetterslev J, Lauritsen T, Steen N, Edstrom B, Afshari A; PREVENT AGITATION Research Group. Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018 Jan;2(1):15-24. doi: 10.1016/S2352-4642(17)30127-X. Epub 2017 Nov 2.
• Background Khetani JD, Madadi P, Sommer DD, Reddy D, Sistonen J, Ross CJ, Carleton BC, Hayden MR, Koren G. Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study. Paediatr Drugs. 2012 Dec 1;14(6):411-5. doi: 10.2165/11633570-000000000-00000.
• Background Kelly LE, Sommer DD, Ramakrishna J, Hoffbauer S, Arbab-Tafti S, Reid D, Maclean J, Koren G. Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial. Pediatrics. 2015 Feb;135(2):307-13. doi: 10.1542/peds.2014-1906.
• Background Jay MA, Thomas BM, Nandi R, Howard RF. Higher risk of opioid-induced respiratory depression in children with neurodevelopmental disability: a retrospective cohort study of 12 904 patients. Br J Anaesth. 2017 Feb;118(2):239-246. doi: 10.1093/bja/aew403.
• Background Oderda GM, Senagore AJ, Morland K, Iqbal SU, Kugel M, Liu S, Habib AS. Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden. J Pain Palliat Care Pharmacother. 2019 Sep-Dec;33(3-4):82-97. doi: 10.1080/15360288.2019.1668902. Epub 2019 Oct 14.
• Background Berghmans JM, Poley MJ, van der Ende J, Weber F, Van de Velde M, Adriaenssens P, Himpe D, Verhulst FC, Utens E. A Visual Analog Scale to assess anxiety in children during anesthesia induction (VAS-I): Results supporting its validity in a sample of day care surgery patients. Paediatr Anaesth. 2017 Sep;27(9):955-961. doi: 10.1111/pan.13206. Epub 2017 Jul 14.
• Background Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR. The revised FLACC observational pain tool: improved reliability and validity for pain assessment in children with cognitive impairment. Paediatr Anaesth. 2006 Mar;16(3):258-65. doi: 10.1111/j.1460-9592.2005.01773.x.
• Background Pedersen LK, Rahbek O, Nikolajsen L, Moller-Madsen B. The revised FLACC score: Reliability and validation for pain assessment in children with cerebral palsy. Scand J Pain. 2015 Oct 1;9(1):57-61. doi: 10.1016/j.sjpain.2015.06.007.

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