Cardiovascular and Neurological Effects of Laudanosine

Abstract

The effects of laudanosine, a metabolite of atracurium, on the behaviour of conscious mice, rats and dogs, and on cardiovascular function in conscious and anaesthetized dogs have been evaluated: EEG studies were performed in anaesthetized dogs. In mice and rats, i.v. bolus doses of laudanosine 10-20 mg kg-1, caused convulsions and hind limb extensions; these effects were prevented by pretreatment with diazepam. After the continuous infusion of laudanosine to conscious dogs, plasma concentrations in the order of 1.2 micrograms ml-1 did not cause behavioural disturbances. In anaesthetized dogs, laudanosine plasma concentrations of more than 6 micrograms ml-1 caused hypotension and bradycardia, laudanosine concentrations greater than 10 micrograms ml-1 induced epileptic EEG spiking and plasma concentrations greater than 17 micrograms ml-1 produced prolonged seizures. There is a wide difference between laudanosine plasma concentrations in patients given atracurium by bolus injection or by short-term infusion for surgical use and those required to induce epileptic activity in dogs. However, during the prolonged infusion of atracurium to patients this difference will be decreased. It is unlikely that the use of atracurium, in patients, would result in plasma concentrations of laudanosine capable of producing neurological or cardiovascular disturbances.

Nitrous Oxide Antagonizes CNS Stimulation by Laudanosine in Mice

“…The introduction of atracurium into clinical practice has thus renewed interest in the CNS actions of laudanosine [8][9][10][11].…”

Living Donor Liver Transplantation for Acute Liver Failure With Fixed Pupils: Are We Fixed?

“…9 In ALF, although the BBB is largely structurally intact, increased pinocytotic activity, endothelial swelling, inflammatory and oxidative stress could lead to disruption of BBB. 10 However, our patient was still receiving muscle relaxant postoperatively when some pupillary response was observed. We had attributed the gradual and sustained change in pupil size and reaction to progressively rising ICP.…”

“…Our dilemma was solved by performing ancillary test of CT head angiography which confirmed the presence of normal cerebral blood flow, 10,11 ruling our brain stem herniation.…”

Recent advances in myorelaxant therapy

“…The only important metabolite is laudanosine (60). Laudanosine lacks significant neuromuscular blocking effects but has been reported to produce central nervous system excitation in high doses in animals (61). However, this is unlikely to become a concern in clinical practice, since plasma concentrations associated with seizure activity have not been documented with atracurium (62,63) or cisatracurium (64).…”