Porphyrinogenic effects of atracurium, vecuronium, and pancuronium in a primed rat model.
Steroidal muscle relaxants might theoretically be contraindicated in acute hepatic porphyrias. Atracurium, on the other hand, has been proposed as the muscle relaxant of choice because of its extrahepatic degradation. To further investigate this problem, equipotent doses of atracurium, vecuronium, and pancuronium were determined in male Sprague Dawley rats, using evoked electromyography. After this pilot study, 64 rats were anesthetized, mechanically ventilated, and randomly allocated to eight groups. Animals in groups 1 through 4 received an intraperitoneal injection of arachis-oil 20 h before the experiments. For groups 5 through 8, an experimental porphyria was induced by use of the chemical substance 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC), which was dissolved in arachis-oil and given 20 h prior to the beginning of the study. Rats of groups 1 and 5 served as controls; they received saline and were not given muscle relaxants throughout the experiment. For groups 2 and 6, atracurium was administered at a dosage of 4 mg/kg of body weight, followed by a continuous infusion of 15 mg/kg/h. Animals of groups 3 and 7 received vecuronium at a dosage of 1.5 mg/kg, followed by 7.5 mg/kg/h. For groups 4 and 8, pancuronium was given (0.75 mg/kg and 2.5 mg/kg/h, respectively). At the end of the 3-h study period, the liver was perfused and excised, and urine was obtained. Activity of the hepatic enzyme delta-aminolevulinic acid synthase (ALAS) and urinary concentrations of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) were determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Böhrer
H
H
Department of Anesthesia, University of Heidelberg, Germany.
Schmidt
H
H
Bach
A
A
Martin
E
E
Kohl
B
B
Bolsen
K
K
Goerz
G
G
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D010197:Pancuronium / Q000494:pharmacology*; D011162:Porphobilinogen / Q000652:urine; D011164:Porphyrias / Q000139:chemically induced; D011166:Porphyrins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014673:Vecuronium Bromide / Q000494:pharmacology*
D011166:Porphyrins; D001279:Atracurium; D011162:Porphobilinogen; D014673:Vecuronium Bromide; D000622:Aminolevulinic Acid; D000624:5-Aminolevulinate Synthetase; D010197:Pancuronium