• N Disma, B M Goffredo, S Cairoli, G Cirillo, J D Morse, B J Anderson, and TREX (Trial Remifentanil DEXmedetomidine) Italian Investigators.
• Unit for Research and Innovation, Department of Anaesthesia, IRCCS Istituto Giannina Gaslini, Genova, Italy.
• Paediatr Anaesth. 2022 Nov 17; 33 (3): 236242236-42.

IntroductionDexmedetomidine is the sedative agent administered in combination with remifentanil and low dose of sevoflurane in the interventional arm of the ongoing TREX trial (Trial Remifentanil DExmedetomidine). The TREX pilot study (published in Paediatr Anaesth 2019;29:59-67) established infusion rates higher than those initially proposed. This could be attributed to an inappropriate target concentration for sedation or incorrect initial pharmacokinetic parameter estimates.MethodsThe TREX study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicentre, superiority trial comparing neurological outcome after standard sevoflurane anaesthesia with dexmedetomidine/remifentanil and low dose sevoflurane anaesthesia in children aged less than 2 years undergoing anaesthesia of 2 hours or longer. In this report, dexmedetomidine pharmacokinetics were analysed in the interventional arm of the Italian population.ResultsThere were 162 blood samples from 32 infants (22 male and 10 female). The median (IQR) age was 12 (5.2-15.5) months, weight 9.9 (7.3-10.8) kg. Duration of anaesthesia ranged from 2-6 hours. None of the children were born premature (median postnatal age 39 weeks, IQR 38-40 weeks). A 3-compartment PK model that incorporated allometric scaling and a maturation function demonstrated plasma concentration observations from the current Italian arm of the TREX study were consistent with those predicted by a "universal" model using pooled data obtained from neonates to adults.ConclusionsThis current PK analysis from the Italian arm of the TREX study confirms that plasma concentration of dexmedetomidine is predictable using known covariates such as age and size. The initial target concentration (0.6 μg.L-1 ) used to sedate children cared for in the intensive care after cardiac surgery was inadequate for infants in the current TREX study. A target concentration 1 mcg.L-1 , corresponding to a loading dose of 1 mcg.kg-1 followed by an infusion of 1 mcg.kg-1 .hour-1 , provided adequate sedation.This article is protected by copyright. All rights reserved.

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