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Potential neuroprotective properties of atracurium and cisatracurium in neurosurgical anaesthesia

Hans, P.; Bonhomme, V.

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European Journal of Anaesthesiology: April 2004 - Volume 21 - Issue 4 - p 334-335

A reply


We thank Drs Fodale, Praticò and Santamaria for their interest in our paper and appreciate the opportunity we have to discuss their concerns.

First of all, the main objective of our review was not to systematically disparage the use of muscle relaxants in neurosurgical patients. There is no doubt that those drugs may be useful and are absolutely necessary in specific circumstances. The aim of our paper was to incite the reader to question the routine use of muscle relaxants in neurosurgical patients according to their expected benefits, potential side-effects and real efficacy that can be modified by specific pharmacokinetic and pharmacodynamic alterations.

Regarding measurements of vecuronium in the cerebrospinal fluid (CSF), we acknowledge that this muscle relaxant has not been detected in the CSF of neurosurgical patients up to 8 h after i.v. administration. However there are no reasons to rule out the possibility of a direct effect when muscle relaxants are given for a sufficient dose and time and when the blood-brain barrier is more or less damaged. As mentioned in the review, subarachnoid accidental injections of muscle relaxants have also been reported and excitatory effects of those agents have been demonstrated in animals.

The major concern relates to a potential neuroprotective effect of laudanosine, a metabolite of atracurium and cisatracurium, through activation of δ- and κ-opioid receptors, and of α4β2 nicotinic acetylcholine sub-type receptors at clinically relevant concentrations actually lower than those susceptible to elicit seizures in animals. Activation of δ- and κ-opioid receptors has indeed some neuroprotective effects in animal models of hypoxia and ischaemia. However, laudanosine is not a selective δ- and κ-opioid agonist. Other analgesics commonly used in clinical practice like morphine also have κ-agonist effects but none has been demonstrated to be neuroprotective in human beings. On the other hand, several papers have recently emphasized a role of neuronal nicotinic acetylcholine receptors in learning and memory. Loss or inactivation of those receptors has also been blamed for neurodegenerative disorders and cognitive dysfunction. We basically agree with the rational background of this hypothesis but excessive enthusiasm should be moderated by some considerations. Postoperative cognitive dysfunction is a complex phenomenon the aetiology of which remains still to be clarified but presumably involves several mechanisms and neurotransmitters. Cholinergic agonists and cholinesterase inhibitors have been shown to markedly potentiate the neurotoxic action of N-methyl-D-aspartate antagonists [1,2]. Many anaesthetic agents interfere with gamma amino butyric acid and Glutamate receptors. Some of them have been suggested to be neuroprotective in experimental models but this effect has not been validated in human beings. Finally at this time, there is no proof that a single drug administration could exert long-lasting effects.

Taking all these data together, we believe that there may be a theoretical background for potential neuroprotection by laudanosine in neurosurgical patients but this effect obviously deserves further investigation.

P. Hans

V. Bonhomme

University Department of Anaesthesia and Intensive Care Medicine; CHR de la Citadelle; Liege, Belgium


1. Corso TD, Sesma MA, Tenkova TI, et al. Multifocal brain damage induced by phencyclidine is augmented by pilocarpine. Brain Res 1997; 752: 1-14.
2. Nardi A, Olney JW, Holtzman DM, et al. Comparing PDAPP and WT mice for vulnerability to neuronal injury triggered by excessive activation of excitatory transmitter receptors. Soc Neurosci Abst 2003 (CD-ROM Annual Meeting Abstracts).
© 2004 European Academy of Anaesthesiology