Publication information

Bibliographic entry:

Johnston AJ, Steiner LA, O'Connell M, Chatfield DA, Gupta AK, Menon DK (2004) “Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients.” Intensive Care Med 30(1):45-50

Abstract:

To explore the pharmacokinetics and pharmacodynamics of dopamine and norepinephrine.

Prospective, controlled, trial.

Neurosciences critical care unit.

Eight patients with a head injury, requiring dopamine or norepinephrine infusions to support cerebral perfusion pressure (CPP).

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 concentrations

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 (r2=0.431), and systemic vascular resistance index (r2=0.605), with a breakpoint (at which cardiac index reduced and SVRI increased) at a dopamine plasma level of approximately 50 nM/l (corresponding to an infusion rate of approximately 15 microg.kg(-1).min(-1)).

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.

Online links:Available online from Springer
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Publication type:Randomized Controlled Trial
Publication status:In print, Electronically published
Publication date:2004 Jan
Electronic publication date:2003 Oct 29
Languages:English
DOI:10.1007/s00134-003-2032-4
ISSN:0342-4642
ESSN:1432-1238
Record status:PubMed - indexed for MEDLINE