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

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 (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 μg·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.

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Acknowledgements

Dr Andrew Johnston is supported by a grant from Codman. Dr Luzius Steiner is supported by a Myron B. Laver Grant (Department of Anaesthesia, University of Basel, Switzerland) and grants from the Margarete und Walter Lichtenstein-Stiftung (Basel, Switzerland) and the Swiss National Science Foundation. He is recipient of an Overseas Research Student Award (Committee of Vice-Chancellors and Principals of the Universities of the United Kingdom). Work of the department is supported by a grant from the Medical Research Council (Grant No. G 9439390 ID56833).

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Correspondence to Andrew J. Johnston.

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Johnston, A.J., Steiner, L.A., O’Connell, M. et al. Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients. Intensive Care Med 30, 45–50 (2004). https://doi.org/10.1007/s00134-003-2032-4

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Keywords

  • Norepinephrine
  • Dopamine
  • Pharmacokinetics
  • Pharmacodynamics
  • Critical care
  • Intensive care