V. Fodale, L. B. Santamaria
Jul 1, 2003
Citations
0
Influential Citations
15
Citations
Journal
Acta Anaesthesiologica Scandinavica
Abstract
Sir, Tassonyi et al. (1) report that in their study carried out in patients who had undergone intracranial aneurysm clipping, high laudanosine concentrations were detected in the cerebrospinal fluid (CSF) up to 8h after administration of the atracurium. Tassonyi et al. (1) conclude that laudanosine is found regularly in the CSF of patients undergoing neurosurgery several hours after the end of surgery, with the clinical relevance that in the early postoperative period these patients may be at increased risk of neuroexcitation manifestations or even seizures. Tassonyi et al. (1) come to this conclusion despite reporting that the sensitivity of surgical patients to laudanosine is not known, and that seizures occur in animals at laudanosine plasma concentrations approximately 100—1000-fold higher than in their study. Laudanosine is ametabolite of the neuromuscular-blocking drugs atracurium and cisatracurium. This potentially toxic metabolite has caused concern since the release of atracurium. In particular, the problems concerning possible excitement and seizure activity in the central nervous system (CNS) have aroused great interest and stimulated research in the last few years (2). But the CNS effects of laudanosine may not be limited to eliciting seizures. Tassonyi et al. (1) have summarized that at concentrations comparable to those measured in their neurosurgical patients, laudanosine is able to activate a4b2 nAch subtype receptors, ubiquitarily present in the CNS and involved in chemical signaling in the brain. Several studies indicate that a4b2 nAch subtype receptor activation elicits neuroprotective effects (3, 4). As a consequence, laudanosine at clinical concentrations reported in CSF after administration of atracurium could elicit neuroprotective effects. This hypothesis is further supported by interesting observations summarized by Fodale and Santamaria (2) in a recent review article on laudanosine. Laudanosine, in concentrations seen clinically in blood, and approaching those measured in cerebrospinal fluid after administration of atracurium, displayed an interaction at the dand k-opioid receptors (5). Activation of neuronal d-opioid receptors (6, 7) and k-opioid receptors (8, 9) showed neuroprotective action against hypoxia and ischemia. The clinical implication of this hypothesis is that in patients who undergo neurosurgery, a long-acting laudanosine-mediated neuroprotective action may be elicited when atracurium (and cisatracurium) is administrated as part of the anesthesia.