Epidural anaesthesia with levobupivacaine and ropivacaine : effects of
age on the pharmacokinetics, neural blockade and haemodynamics
Simon, M.J.G.
Citation
Simon, M. J. G. (2006, May 11). Epidural anaesthesia with levobupivacaine and ropivacaine
: effects of age on the pharmacokinetics, neural blockade and haemodynamics. Retrieved
from https://hdl.handle.net/1887/4384
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Corrected Publisher’s Version
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Licence agreement concerning inclusion of doctoral thesis in the
Institutional Repository of the University of Leiden
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Epidural Anaesthesia with
Levobupivacaine and Ropivacaine:
Effects of Age on the Pharmacokinetics,
Neural blockade and Haemodynamics
PROEFSCHRIFT
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van de Rector Magnificus Dr. D.D. Breimer,
hoogleraar in de faculteit der Wiskunde en Natuurwetenschappen en die der Geneeskunde, volgens besluit van het College voor Promoties
te verdedigen op donderdag 11 mei 2006 te klokke 16.15 uur
door
Mischa Johan Gerardus Simon geboren te Haarlem
Promotiecommissie:
Promotor: Prof. Dr. Ir. A.G.L. Burm † Prof. Dr. J.W. van Kleef
Co-promotor: Dr. B.Th. Veering Referent: Prof. Dr. M. Danhof
Overige leden: Prof. J. Sjövall, Karolinska Institutet, Stockholm, Sweden Prof. Dr. R.G.J. Westendorp
The studies, described in Chapter 7-9 were supported financially and study medications (levobupivacaine and deuterium-labelled levobupivacaine) were provided by Celltech Chiroscience Ltd., Cambridge, United Kingdom. Plasma concentrations of (deuterium-labelled) levobupivacaine were determined by Inveresk Research International Ltd., Tranent, Scotland, UK.
The studies, described in Chapter 10-11 were supported financially by AstraZeneca, Zoetermeer, The Netherlands. Study medications (ropivacaine and deuterium-labelled ropivacaine) were provided and plasma concentrations of (deuterium-labelled) ropivacaine were determined by AstraZeneca, Södertälje, Sweden.
Copyright: Mischa J.G. Simon, Leiden, The Netherlands.
Except chapter 7 and 8 (copyright 2004, European Journal of Anaesthesiology, Cambridge University Press), chapter 9 (copyright 2004, British Journal of Anaesthesia, Oxford University Press) and chapter 10 and 11 (copyright 2002/2006, Anesthesia & Analgesia, Lippincott Williams & Wilkins).
Permission for reprinting material has been obtained from:
Lippincott Williams & Wilkins (Fig. 1.1-1.2, Fig 2.2, Table 2.1, Fig. 3.2, Fig. 3.3, Fig. 3.5, Fig. 4.1-4.2, Fig 5.3, Fig 5.7-5.9), Excerpta Medica, Inc. (Fig. 5.1), Elsevier (Fig. 1.3-1.4, Fig. 3.6, Table 3.1) and Blackwell publishing Ltd. (Fig 3.4, Fig. 5.5-5.6, Table 5.1-5.2).
Cover: The old and young man on the beach, Plettenberg Bay, South Africa 2005; design by Mischa Simon & Wouter Simon
Printed by PrintPartners Ipskamp, Enschede, the Netherlands
ISBN-10: 90-9020629-9 ISBN-13: 978-90-9020629-5
ʊ CONTENTS ʊ
Section I Introduction
1 Anatomy and physiology of the epidural and subarachnoid space 9 2 Local anaesthetics and epidural anaesthesia: mechanisms, sites of
action and pharmacokinetics
19
3 Chirality and local anaesthetics 33 4 Circulation and epidural anaesthesia 55 5 Age-related factors and effects in relation to epidural anaesthesia 61 6 Aims and design of the studies 79
Section II Clinical effects & pharmacokinetics
7 Comparison of the pharmacokinetics of levobupivacaine and a stable isotope-labelled analogue in healthy male volunteers
85
8 The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients
99
9 Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine 0.75% after epidural administration
115
10 Effect of age on the systemic absorption and systemic disposition of ropivacaine 1.0% after epidural administration
133
Section III Haemodynamic effects
11 The effects of age on neural blockade and haemodynamic changes after epidural anesthesia with ropivacaine 1.0%
149
12 Cardiovascular parameter and liver blood flow after infusion of a colloid solution and epidural administration of ropivacaine 0.75%. The influence of age and level of analgesia.
161
Section IV Modelling
13 Population pharmacokinetic/pharmacodynamic modelling of epidural anesthesia
181
Section V Summary
14 Conclusions & perspectives 197 15 Summary in Dutch / Nederlandse samenvatting 211
Acknowledgements 223
Curriculum Vitae 225
