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Intensive Care Med. 2004 Jan;30(1):45-50. Epub 2003 Oct 29.

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

Author information

1
University of Cambridge Department of Anaesthetics, Addenbrooke's Hospital, Box 93, Cambridge, CB2 2QQ, United Kingdom. ajj29@cam.ac.uk

Abstract

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 concentrations

MEASUREMENTS 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 (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)).

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.

PMID:
14586494
DOI:
10.1007/s00134-003-2032-4
[Indexed for MEDLINE]

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