Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients

Objective To explore the pharmacokinetics and pharmacodynamics of dopamine and norepinephrine.Design Prospective, controlled, trial.Setting Neurosciences critical care unit.Patients Eight patients with a head injury, requiring dopamine or norepinephrine infusions to support cerebral perfusion pressure (CPP).Intervention Patients received in randomised order, either dopamine or norepinephrine to achieve and maintain a CPP of 70 mmHg, and then, following a 30-min period of stable haemodynamics, a CPP of 90 mmHg. Data were then acquired using the second agent. Haemodynamic measurements were made during each period and a blood sample was obtained at the end of each study period for analysis of plasma catecholamine concentrationsMeasurements and results Plasma levels of norepinephrine and dopamine were significantly related to infusion rates but did not have a simple linear relationship to haemodynamic parameters. However, there was a significant quadratic relationship between the infusion rate of dopamine and cardiac index (r ²=0.431), and systemic vascular resistance index (r ²=0.605), with a breakpoint (at which cardiac index reduced and SVRI increased) at a dopamine plasma level of ~ 50 nM/l (corresponding to an infusion rate of ~ 15 g·kg^-1·min^-1).Conclusions Norepinephrine and dopamine have predictable pharmacokinetics; however, those of dopamine do not fit a simple first-order kinetic model. The pharmacodynamic effects of dopamine and norepinephrine show much inter-individual variability and unpredictability. Plasma levels of dopamine appear to relate to variations in adrenergic receptor effects with break points that reflect expectations from infusion-rate related pharmacodynamics.