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Necessity and Risks of Arterial Blood Sampling in Healthy Volunteer Studies

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Abstract

Arterial blood sampling is necessary when drugs such as the fast-acting opioid analgesic remifentanil exhibit relevant differences between arterial and venous blood concentrations. Arterial cannulation is generally considered to be clinically safe and has thus become a standard procedure in pharmacokinetic–pharmacodynamic assessments. However, rare cases of arterial occlusions have to be considered in risk–benefit assessments of arterial sampling in pharmacokinetic studies, especially when including healthy volunteers. In an actual case, arterial occlusion requiring surgical repair was caused by a factor V Leiden thrombophilia associated genetic variant F5 1691G>A (rs6025) and aggravated by a hypoplastic radial artery. Neither risk factor had been identified prior to enrolment by routine laboratory tests such as the prothrombin time (international normalized ratio), partial thromboplastin time and the clinical Allen’s test of arterial function. Re-assessment of the necessity of arterial sampling showed that none of the potential alternatives, target concentrations of computerized infusions or venous concentrations during non-steady-state and steady-state conditions could provide the arterial concentrations. Relying on venous concentrations may result in erroneous pharmacodynamic parameters. Accurate pharmacokinetic–pharmacodynamic studies relying on precisely measured blood concentrations require serial sampling techniques during both steady-state and non-steady-state conditions. However, as illustrated by the presented case, incidents involving the generally safe procedure of arterial sampling are possible, although rare. To further minimize the risks, screening of subjects for prothrombotic risks and careful assessment of the suitability of the artery should be considered in pharmacokinetic studies requiring arterial cannulation.

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Acknowledgments

The Dr. Robert Pfleger Foundation, Bamberg, Germany (BGO), is acknowledged for study support. The authors declare no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

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Authors and Affiliations

  1. pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, J. W. Goethe-University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Bruno Georg Oertel, Johannes Vermehren, Thomas Tao Huynh, Alexandra Doehring, Nerea Ferreiros, Gerd Geisslinger, Sebastian Harder & Jörn Lötsch

  2. Department of Anesthesia, Intensive Care and Pain Therapy, J. W. Goethe-University Hospital, Frankfurt, Germany

    Michael Zimmermann

  3. Department of Law, J. W. Goethe-University Hospital, Frankfurt, Germany

    Stephan Senzel

  4. Department of Vascular and Endovascular Surgery, J. W. Goethe-University Hospital, Frankfurt, Germany

    Thomas Schmitz-Rixen

  5. Praxis für Angiologie und Hämostaseologie, Frankfurt, Germany

    Matthias Erbe

  6. Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA

    Martin S. Angst

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  1. Bruno Georg Oertel
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  2. Johannes Vermehren
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Oertel, B.G., Vermehren, J., Zimmermann, M. et al. Necessity and Risks of Arterial Blood Sampling in Healthy Volunteer Studies. Clin Pharmacokinet 51, 629–638 (2012). https://doi.org/10.1007/s40262-012-0001-1

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