Dexmedetomidine hemodynamics in children after cardiac surgery.

Background: Dexmedetomidine has opposing effects on the cardiovascular system. Action in the central nervous system produces sympatholysis and a reduction in blood pressure, while peripherally it causes vasoconstriction leading to an increase in blood pressure. The purpose of our study is to define the concentration–response profile for these hemodynamic effects in children after cardiac surgery. Methods: A simultaneous pharmacokinetic–pharmacodynamic analysis of data from 29 children given a single bolus of dexmedetomidine 1–4 mcg·kg−1 following cardiac surgery was undertaken using mixed effects modeling. There were four dexmedetomidine concentrations available from each patient, and mean arterial blood pressure (MAP) was recorded electronically every 5 min for 5 h after drug administration. A composite Emax model was used to relate mean arterial pressure changes to plasma dexmedetomidine concentration. Results: Children had a mean age of 2.67 years (range 4 days–14 years) and a mean weight of 12.34 (range 3.4–48.4) kg. The peripheral vasopressor effect was directly related to plasma concentration with an Emaxpos of 50.3 (CV 44.50%) mmHg, EC50pos 1.1 (48.27%) μg·l−1 and a Hillpos coefficient of 1.65. The delayed central sympatholytic response was described with an Emaxneg of −12.30 (CV 37.01%) mmHg, EC50neg 0.10 (104.40%) μg·l−1 and a Hillneg coefficient of 2.35. The equilibration half-time ( T1/2keo) was 9.66 (165.23%) min. Conclusions: Dexmedetomidine administered as a single bolus dose following cardiac surgery produces a biphasic effect on MAP. A plasma dexmedetomidine concentration of above 1.0 μg·l−1 was associated with a 20% increase in MAP in this specific cohort. A dosage regimen involving a small bolus dose (0.5 μg·kg−1) followed by a continuous infusion should be used to avoid initial increases in MAP. [ABSTRACT FROM AUTHOR]