The aim of the study was to study a possible pharmacokinetic- pharmacodynamic (PK-PD) relationship for midazolam in pediatric intensive care patients and to determine how adequate sedation could be reached using the COMFORT® scale as sedation scale. Twenty-one pediatric intensive care patients (2 days to 17 years) received a midazolam infusion (0.05-0.4 mg/kg/h, 3.8 hours to 25 days). Sedation levels were determined using the COMFORT scale as well as plasma concentrations of midazolam and metabolites. An evident PK-PD relationship was not found. In 20 of the 21 patients midazolam dosing could be effectively titrated to the desired level of sedation, assessed by the COMFORT scale. Based on our findings that there is no relationship between pharmacokinetic parameters and pharmacodynamic outcome, we recommend that midazolam dosing should be titrated according to the desired clinical effect in combination with a validated assessment instrument, eg, the COMFORT scale.

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Therapeutic Drug Monitoring
Department of Pediatrics

de Wildt, S.N, de Hoog, M, Vinks, A.A, Joosten, K.F.M, van Dijk, M, & van den Anker, J.N. (2005). Pharmacodynamics of midazolam in pediatric intensive care patients. Therapeutic Drug Monitoring, 27(1), 98–102. doi:10.1097/00007691-200502000-00018