Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial.

INTRODUCTION Post-operative agitation (PA) is a common problem (20-70%) in children anaesthetised with sevoflur-ane. Clonidine is widely used off-label in children for several indications, including PA, but the current level of evidence is limited. Our aim is to investigate the impact of prophylactic intravenous (IV) clonidine administered at the end of surgery on the incidence and degree of PA. Furthermore, the pharmacokinetic profile of IV clonidine in children is not well established and our aim is to obtain pharmacokinetic data relating hereto. METHODS This is a multicentre, randomised and blinded clinical trial in which we will be enrolling 380 children aged 1-5 years who are planned for anaesthesia with sevoflurane and fentanyl. Inclusion is based on computer-generated randomisation (1:1) and stratified by age and site. The study drug is administered IV approximately 20 min. before the expected completion of surgery (intervention: clonidine 3 µg per kg; placebo: equal quantity of saline). CONCLUSION The primary outcome is PA measured on the Watcha scale. The secondary outcomes include post-operative pain relief and adverse effects, including a 30-day follow-up. In total, 40 children will be allocated to drug assay sampling, enabling a compartmental pharmacokinetic analysis. FUNDING Funded by the participating departments and by two unrestricted scientific grants from the Danish Society of Anaesthesia and Intensive. TRIAL REGISTRATION This study was approved by the Danish Health and Medicines Authority (EudraCT number 2014-001466-10), the Ethics Committee of the Capital Region of Denmark (H-2-2014-072) and registered with Clinicaltrials.gov (NCT02361476).