Sedative and hemodynamic effects of clonidine in mechanically ventilated adult patients: a population pharmacodynamic study

Sedative and hemodynamic effects of clonidine in mechanically ventilated adult patients: a population pharmacodynamic study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 4 October 2025 V1 Latest version Share on Sedative and hemodynamic effects of clonidine in mechanically ventilated adult patients: a population pharmacodynamic study Authors : Michael Cloesmeijer 0000-0002-2810-1570 , Huub van den Oever 0000-0001-6621-8940 [email protected] , Marieke Zeeman , P Nassikovker , C Bles , Fred (A.) L. van Steveninck , Arthur R. de Meijer , Arriette Kruisdijk-Gerritsen , Ron Mathot , and Maurits Arbouw Authors Info & Affiliations https://doi.org/10.22541/au.175958121.16015162/v1 173 views 112 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Purpose The aim of this study was to characterize the the effects of clonidine on sedation, heart rate (HR) and mean arterial blood pressure (MAP) in critically ill, mechanically ventilated adult patients, using population pharmacodynamic modelling. Methods Thirty-two patients received continuous intravenous clonidine, added to standard sedation, at 0, 600, 1200 or 1800 μg/day. Sedation, HR, and MAP were modelled as a function of predicted clonidine concentrations using NONMEM. Model performance was assessed by goodness-of-fit plots, bootstrapping, and visual predictive checks. Results The sedation model included 773 Richmond Agitation-Sedation scale (RASS) assessments with corresponding predicted clonidine concentrations. The probability of deep sedation (RASS ≤-4) was described by a logistic regression model with an intercept of 2.23 (relative standard error (RSE) 25%), slope of -0.383 (RSE 17%), and covariate effects of midazolam (-2.48, RSE 7%) and propofol (-1.54, RSE 13%). The hemodynamic models included 783 paired HR and MAP measurements. HR was best described by a linear model with a baseline of 90.6 bpm (RSE 2%) and slope of -3.30 bpm per µg/L (RSE 10%). MAP was also modelled linearly, with a baseline of 76.9 mmHg (RSE 2%), and slope of -0.887 mmHg per µg/L (RSE 42%). Including inter-individual variability on baseline values significantly improved both models. Conclusion In mechanically ventilated ICU patients, clonidine was associated with a dose-dependent increase in the probability of deep sedation, and with linear, dose-dependent reductions in HR and MAP. Supplementary Material File (caption figure 1.docx) Download 15.20 KB File (caption figure 2.docx) Download 13.77 KB File (caption figure 3.docx) Download 12.30 KB File (caption figure 4.docx) Download 12.30 KB File (caption figure 5.docx) Download 12.38 KB File (manuscript_population pharmacodynamics of clonidine_v4.docx) Download 81.87 KB File (table 1_population pharmacodynamics of clonidine_v4.docx) Download 14.39 KB File (table 2_population pharmacodynamics of clonidine_v3.docx) Download 16.01 KB File (table 3_population pharmacodynamics of clonidine_v3.docx) Download 13.85 KB Information & Authors Information Version history V1 Version 1 04 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Michael Cloesmeijer 0000-0002-2810-1570 Amsterdam Universitair Medische Centra View all articles by this author Huub van den Oever 0000-0001-6621-8940 [email protected] Deventer Ziekenhuis View all articles by this author Marieke Zeeman Saxenburgh Groep View all articles by this author P Nassikovker Deventer Ziekenhuis View all articles by this author C Bles Deventer Ziekenhuis View all articles by this author Fred (A.) L. van Steveninck Deventer Ziekenhuis View all articles by this author Arthur R. de Meijer Deventer Ziekenhuis View all articles by this author Arriette Kruisdijk-Gerritsen Deventer Ziekenhuis View all articles by this author Ron Mathot Amsterdam Universitair Medische Centra View all articles by this author Maurits Arbouw Deventer Ziekenhuis View all articles by this author Metrics & Citations Metrics Article Usage 173 views 112 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Michael Cloesmeijer, Huub van den Oever, Marieke Zeeman, et al. Sedative and hemodynamic effects of clonidine in mechanically ventilated adult patients: a population pharmacodynamic study. Authorea . 04 October 2025. DOI: https://doi.org/10.22541/au.175958121.16015162/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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