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 this 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 was recorded electronically every 5 min for five hours after drug administration. A composite Emax model was used to relate mean arterial pressure changes with plasma dexmedetomidine concentration.
Results: Children had a mean age of 2.67 (range 4 days-14 y) 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%) µ.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%) µ.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 of mean arterial blood pressure (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.