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Safety of clonidine used for long-term sedation in paediatric intensive care: A systematic review

Eberl, S; Ahne, G; Toni, I; Standing, J; Neubert, A; (2020) Safety of clonidine used for long-term sedation in paediatric intensive care: A systematic review. British Journal of Clinical Pharmacology 10.1111/bcp.14552. (In press). Green open access

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Abstract

Aim: Although not approved, the α-adrenoceptor agonist clonidine is considered an option for long-term sedation protocols in paediatric intensive care. We reviewed adverse effects of clonidine occurring in this indication. Methods: Relevant literature was systematically identified from PubMed and Embase. We included interventional and observational studies on paediatric patients admitted to intensive care units and systemically long-term sedated with clonidinecontaining regimes. In duplicates, we conducted standardised and independent fulltext assessment and extraction of safety data. Results: Data from 11 studies with 909 patients were analysed. The studies were heterogeneous regarding patient characteristics (age groups, comorbidity, or comedication) and sedation regimes (dosage, route, duration, or concomitant sedatives). Just four randomised controlled trials (RCTs) and one observational study had comparison groups, using placebo or midazolam. For safety outcomes, our validity evaluation showed low risk of bias only in three studies. All studies focused on haemodynamic problems, particularly bradycardia and hypotension. Observed incidences or subsequent interventions never caused concerns. However, only two RCTs allowed meaningful comparisons with control groups. Odds ratios showed no significant difference between the groups, but small sample sizes (50 and 125 patients) must be considered; pooled analyses were not reasonable. Conclusion: All evaluated studies concluded that the use of clonidine in paediatric intensive care units is safe. However, a valid characterisation of the safety profile remains challenging due to limited, biased and heterogeneous data and missing investigation of long-term effects. This evaluation demonstrates the lack of data, which prevents reliable conclusions on the safety of clonidine for long-term sedation in critically ill children. For an evidence-based use, further studies are needed.

Type: Article
Title: Safety of clonidine used for long-term sedation in paediatric intensive care: A systematic review
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bcp.14552
Publisher version: https://doi.org/10.1111/bcp.14552
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: clonidine, critical care, paediatrics, sedation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10118685
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