Epidural anaesthesia with levobupivacaine and ropivacaine : effects of age on the pharmacokinetics, neural blockade and haemodynamics

Simon, M.J.G. (2006)

Doctoral Thesis

Epidural neural blockade results from processes after the administration of a local anaesthetic in the epidural space until the uptake in neural tissue. The pharmacokinetics, neural blockade and haemodynamics after epidural anaesthesia may be influenced by several factors, with age as the most important one. Using the stable-isotope-method, the pharmacokinetics of the enantiomeric-pure local anaesthetics ropivacaine and levobupivacaine were derived and the influence of age on the pharmacokinetics was investigated. These local anaesthetics showed a bi-phasic absorption pattern. The fraction absorbed during the initial absorption process for levobupivacaine was low. The initial absorption parameters decreased with increasing age for epidurally administered levobupivacaine and ropivacaine.After epidural administration the level of analgesia was higher for levobupivacaine and ropivacaine and motor blockade was increased for ropivacaine in elderly patients. Haemodynamic changes, like the decrease in mean arterial pressure (MAP), were more pronounced in elderly patients after epidural administration of ropivacaine. It was postulated that this decrease is not only the result of the higher level of analgesia in elderly patients, but also from age-related changes in the cardiovascular and autonomic nervous system. Finally, a population pharmacokinetic/ pharmacodynamic model of the lumbar epidural space was developed that was able to demonstrate the importance of age on the spread of the sensory blockade as well as on the speed of onset/offset of blockade.

• Anaesthesiology
• Epidural anaesthesia
• Local anaesthetics
• Levobupivacaine
• Ropivacaine
• Pharmacokinetics
• Neural blockade
• Haemodynamic effects
• Ageing
• Old age

• All authors: Simon, M.J.G.
• Supervisor: Kleef, J.W. van; Burm, A.G.L.
• Co-supervisor: Veering, B.T.
• Qualification: Doctor (dr.)
• Awarding Institution: Department of Anesthesiology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2006-05-11
• ISBN (print): 9789090206295
• Court: LEI Universiteit Leiden
• Sponsorship: 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. Financial support for the printing of this thesis was provided by AstraZeneca BV, Zoetermeer, Mundipharma Pharmaceuticals BV, Amersfoort, Abbott BV, Hoofddorp, GlaxoSmithKline BV, Zeist and Pfizer BV, Capelle a/d IJssel.