Cerebrospinal fluid concentrations of atracurium, laudanosine and vecuronium following clinical subarachnoid hemorrhage.
BACKGROUND
Neuromuscular blocking agents may exert central nervous system effects when they reach the brain. This study assessed the concentrations and the time course of passage of vecuronium, atracurium, and its metabolite laudanosine in the cerebrospinal fluid (CSF) of patients undergoing intracranial aneurysm clipping.


METHODS
Twenty-five patients with subarachnoid hemorrhage were randomly allocated to receive an intravenous infusion of vecuronium (n=13) or atracurium (n=12). Arterial blood and lumbar CSF were sampled before and 1, 2, 3, 4 and 8 h after the start of the relaxant infusion. The samples were analyzed by liquid chromatography-electrospray ionization mass spectrometry (vecuronium) and high-pressure liquid chromatography (atracurium and laudanosine).


RESULTS
The data of 20 patients (10 in both groups) were analyzed. In 11 CSF samples from five patients atracurium was detected in concentrations from 10 to 50 ng/ml. Laudanosine was retrieved in all CSF samples at 1, 2, 3, 4 and 8 h; the highest CSF concentration of laudanosine occurred at 3 h [38 (18-63) ng/ml: median (range)]. Vecuronium was not found in any CSF sample.


CONCLUSIONS
Significant concentrations of atracurium and laudanosine but not of vecuronium were detected in the CSF of patients during and immediately after intracranial aneurysm surgery.
Tassonyi
E
E
Department of Anesthesia, Pharmacology and Surgical Intensive Care, University Hospitals and University Medical Center (CMU), Geneva, Switzerland.
Fathi
M
M
Hughes
G J
GJ
Chiodini
F
F
Bertrand
D
D
Muller
D
D
Fuchs-Buder
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001279:Atracurium / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D002491:Central Nervous System Agents / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000601:surgery*; D007546:Isoquinolines / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D013997:Time Factors; D014673:Vecuronium Bromide / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*
D002491:Central Nervous System Agents; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D014673:Vecuronium Bromide; C001522:laudanosine