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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Clonidine use during dexmedetomidine weaning: A systematic review
Sanu Rajendraprasad, Molly Wheeler, Erin Wieruszewski, Joseph Gottwald, Lindsey A. Wallace, Danielle Gerberi, Patrick M Wieruszewski, Nathan J Smischney
Sanu Rajendraprasad, Department of Pulmonary & Critical Care, Mayo Clinic, Rochester, MN 55905, United States
Molly Wheeler, Erin Wieruszewski, Patrick M Wieruszewski, Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, United States
Joseph Gottwald, Nathan J Smischney, Department of Anesthesiology & Perioperative Medicine, Mayo Clinic, Rochester, MN 55905, United States
Lindsey A. Wallace, Critical Care Medicine Independent Multidisciplinary Program, Mayo Clinic, Rochester, MN 55905, United States
Danielle Gerberi, Mayo Medical Libraries, Mayo Clinic, Rochester, MN 55905, United States
Author contributions: Rajendraprasad S, Wieruszewski P, and Smischney N designed the research; Rajendraprasad S, Wheeler M, and Wieruszewski E performed the research; Gottwald J and Wallace L analyzed the data; Rajendraprasad S, Wheeler M, Gottwald J, Wallace L, Wieruszewski P, and Smischney N drafted the paper; All authors reviewed and edited the manuscript and approved the final version.
Conflict-of-interest statement: All authors declare no conflicts of interest.
PRISMA 2009 Checklist statement: The study followed the PRISMA guidelines. The protocol was a priori registered in the PROSPERO database (No. CRD42022330666).
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 NonCommercial (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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Nathan J Smischney, MD, MS, Associate Professor, Department of Anesthesiology & Perioperative Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, United States. smischney.nathan@mayo.edu
Received: September 13, 2022
Peer-review started: September 13, 2022
First decision: October 21, 2022
Revised: November 15, 2022
Accepted: November 30, 2022
Article in press: November 30, 2022
Published online: January 9, 2023
BACKGROUND
Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation. As clonidine is an enterally available alpha-2A adrenergic agonist, it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes. The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known. The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms.
AIM
To systematically review the practice, dosing schema, and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults.
METHODS
This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults (≥ 18 years). Randomized controlled trials, prospective cohorts, and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included. The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal. Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use, re-initiation of dexmedetomidine, duration of mechanical ventilation, and ICU length of stay.
RESULTS
A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients. All three studies were observational, two being prospective and one retrospective. In all included studies, the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician. Weaning time ranged from 13 to 167 h on average. Enteral clonidine was started in the prospective studies in a similar protocolized method, with 0.3 mg every 6 h. After starting clonidine, patients remained on dexmedetomidine for a median of 1-28 h. Following the termination of dexmedetomidine, two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h, 12h, and 24 h, followed by clonidine discontinuation. For indicators of enteral clonidine withdrawal, the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol. The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation. The re-initiation of dexmedetomidine was not documented in any study. Only 17 (37%) patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies. ICU lengths of stay were similar.
CONCLUSION
Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine. There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.
Core Tip: In this systematic review of enteral clonidine use during dexmedetomidine weaning in critically ill patients, an association of increased withdrawal symptoms and agitation with the use of a clonidine taper and no difference in intensive care unit length of stay with or without clonidine taper was observed. However, varied techniques and a small total sample size restrict utility of the findings.
