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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Effect of clonidine on the cutaneous silent period during spinal anesthesia
Sandra Graf Zupcic, Miroslav Zupcic, Viktor Duzel, Tatjana Šimurina, Milan Milošević, Silvio Basic, Vladimira Vuletic, Leonardo Kapural
Sandra Graf Zupcic, Vladimira Vuletic, Clinic of Neurology, Clinical Hospital Centre Rijeka, Rijeka 51000, Croatia
Miroslav Zupcic, Tatjana Šimurina, Silvio Basic, Faculty of Medicine, J. J. Strossmayer University, Osijek 31000, Croatia
Miroslav Zupcic, Clinic of Anesthesiology and Intensive Care Medicine, Clinical Hospital Centre Rijeka, Rijeka 51000, Croatia
Miroslav Zupcic, Vladimira Vuletic, Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
Viktor Duzel, Department of Anaesthesia, Barking, Havering and Redbridge University Hospitals NHS Trust, London RM7 0AG, United Kingdom
Tatjana Šimurina, Department of Health Studies University of Zadar, Zadar 23000, Croatia
Tatjana Šimurina, Department of Anesthesiology and Intensive Care Medicine, General Hospital Zadar, Zadar 23000, Croatia
Milan Milošević, University of Zagreb, School of Medicine, Andrija Stampar School of Public Health WHO Collaborative Centre for Occupational Health, Zagreb 10000, Croatia
Silvio Basic, Department of Neurology, Clinical Hospital Dubrava, Zagreb 10000, Croatia
Leonardo Kapural, Center for Clinical Research, Winston Salem, NC 27103, United States
Author contributions: Graf Zupcic S design of the work, acquisition, analysis and interpretation of data, drafting the work and revising it critically for important intellectual content; Zupcic M contributed through acquisition of data, study design, drafting the manuscript and revising it critically for important intellectual content; Duzel V and Šimurina T contributed through study design, revising it critically, data analysis, interpretation of the results, drafting and prepared the manuscript; Milošević M contributed through conception and design of the study, drafting the manuscript, data analysis and interpretation of the results; Basic S and Vuletic V contributed through data acquisition, interpretation of the results, conception of the study and drafting the manuscript; Kapural L contributed through data interpretation, conception of the study and drafting the manuscript; all co-authors critically reviewed the manuscript and gave their final approval of the version of the manuscript to be published.
Institutional review board statement: This trial was performed in accordance with the 1964 Helsinki declaration and its later amendments. Full approval for the trial was obtained by the local ethics committee of Clinical Hospital Dubrava (registration code 2391-1/15).
Clinical trial registration statement: This study is registered at https://clinicaltrials.gov/ct2/show/NCT03121261. The registration identification number is NTC03121261.
Informed consent statement: All patients provided written informed consent.
Conflict-of-interest statement: No conflicts-of-interest, financial or otherwise, are declared by the author(s).
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Miroslav Zupcic, MD, PhD, Assistant Professor, Clinic of Anesthesiology and Intensive Care Medicine, Clinical Hospital Centre Rijeka, Kresimirova Ulica 42, Rijeka 51000, Croatia. miro_zupcic@yahoo.com
Telephone: +38-55-1407400 Fax: +38-55-1218407
Received: September 10, 2018
Peer-review started: September 10, 2018
First decision: October 11, 2018
Revised: October 17, 2018
Accepted: November 7, 2018
Article in press: November 7, 2018
Published online: December 26, 2018
Processing time: 106 Days and 11.9 Hours
ARTICLE HIGHLIGHTS
Research background
The silent cutaneous period (CSP) is an oligosynaptic spinal inhibitory reflex, largely mediated through small diameter Aδ-fibers. The CSP begins after a noxious stimulus of a cutaneous sensory nerve during a voluntary muscle contraction and is evidenced by a transient lapse of electromyographic (EMG) activity. This is a non-invasive method that requires standard EMG equipment to research changes in Aδ-fibers and can further elucidate the organization of the spinal inhibitory circuit as an integral part of this reflex.
Research motivation
The duration of CSP and its latency are altered in polyneuropathy and various diseases of the central nervous system, such as those that lead to damage of the corticospinal and spinothalamic pathways as well as extrapyramidal disorders. This suggests a possible supraspinal influence on the CSP. Clonidine, a selective partial agonist of alpha-2 receptors, when added to levobupivacaine and administered intrathecally, enhances the effect of the local anesthetic, prolongs the sensory and motor block during SAB, and prolongs the duration of postoperative analgesia. Until now, no other studies have measured the effect of intrathecally-administered clonidine on the CSP.
Research objectives
The research objective of this investigation was to examine the effect of clonidine on the CSP during SAB for inguinal herniorrhaphy.
Research methods
A total of 67 adult patients were included in this randomized, prospective, single-center, double-blind trial. They had no neurological disorders and were scheduled for inguinal hernia repair surgery. The patients were randomized into two groups with regard to the intrathecally-administered solution: either levobupivacaine with clonidine or levobupivacaine alone (34 patients in the levobupivacaine-clonidine (LC) group and 33 patients in the levobupivacaine (L) group). CSP and its latency were measured four times: prior to the SAB, after motor block regression to Bromage scale level 0, with sensory blockade still present, and both 6 and 24 h after SAB.
Research results
The LC group had significantly lower CSP duration (P = 0.007) and higher CSP latency (P < 0.001) values at the timepoint when the Bromage scale was 0 and after 6 h (P < 0.001). Comparing preoperative and postoperative values of CSP duration, there was a statistically significant difference at time points Bromage 0 in the L group (P < 0.001), the LC group (P = 0.007) and after 6 h in the LC group (P < 0.001). When comparing the preoperative and postoperative values of CSP latency, there was a statistically significant difference at timepoints when the Bromage scale was 0 in both groups and after 6 h in the LC group (P < 0.001).
Research conclusions
Intrathecal administration of clonidine as an adjuvant to levobupivacaine for SAB, in comparison with lavobupivacaine alone, results in a shorter duration of CSP and prolongation of CSP latency. Accordingly, we can conclude that during SAB regression, a small dose of intrathecally-administered clonidine ameliorates the inhibitory tonus and accelerates conduction in the oligosynaptic spinal circuit.
Research perspectives
CSP is an oligosynaptic spinal inhibitory reflex. Little is known about the factors that influence the functions of its spinal inhibitory circuits, which should be the subject of further investigations.
