Growing up with Midazolam in the Neonatal and Pediatric Intensive Care

Eleonora      L. Swart; Pauline      R. Slort; Frans      B. Plotz

Abstract

A variety of developmental changes is of influence on the pharmacokinetics and pharmacodynamics of midazolam in neonatal and pediatric intensive care patients. However, dosing regimens in children are based upon rather empirical extrapolations from the dosing regimens in adults. Based on current available studies it appears that with the rising of age, the pharmacokinetics of intravenously administered midazolam alter, resulting in a shorter half-life due to a higher hepatic clearance in older children as compared to newborn. Also, with the rising of age, the pharmacodynamics of intravenously administered midazolam may alter due to a decrease in density of receptors, possibly leading to a decreased clinical response. These findings implicate opposite effects and it is uncertain which of these effects are predominant. In conclusion, there is a large interindividual variability in the response to midazolam in children, which may be caused by differences in pharmacokinetics and pharmacodynamics. Both are subject to considerable developmental changes. It remains remarkable that high-quality evidence to support the use of midazolam for continuous sedation in the neonatal and pediatric intensive care setting is lacking.

Keywords: Neonatal intensive care unit, pediatric intensive care unit, pharmacodynamics, pharmacokinetics, midazolam, Albumin Binding, NICU, Renal Function