title: Elevated plasma alpha 1-acid glycoprotein levels: lack of connection to resistance to vecuronium blockade induced by anticonvulsant therapy.
abstract: This study was designed to investigate the relationships among anticonvulsant therapy, plasma alpha 1-acid glycoprotein (AAG) levels, and resistance to vecuronium blockade. Thirty-one patients scheduled for routine neurosurgery were included in the study. The patients were treated (TG; n = 20) with phenytoin (n = 15) and/or carbamazepine (n = 4) and/or phenobarbital (n = 3) for > or = 6 days or were left untreated (UG; n = 11, control group). TG patients were further assigned to one of two subgroups according to the plasma anticonvulsant level measured the day before surgery and found to be within (TGW, n = 10) or below (TGB, n = 10) the therapeutic range. Finally, the 31 patients were divided into two more groups according to their plasma AAG levels: higher than (HAAG, n = 17) or within (NAAG, n = 14) the normal range (25-94 mg dl-1). Anesthesia was induced and maintained with propofol and sufentanil. Muscle relaxation was obtained with vecuronium 0.1 mg kg-1. A train-of-four (TOF) stimulation mode at 2 Hz was applied to the ulnar nerve every 15 s, and neuromuscular transmission was assessed using a TOF-Guard accelograph monitor. Plasma AAG concentrations (means +/- SEM) were 103.7 +/- 7.6 mg dl-1 in TG, 80.7 +/- 6.7 mg dl-1 in UG, 95.9 +/- 13.2 mg dl-1 in TGW, 111.6 +/- 7.6 mg dl-1 in TGB. 114.9 +/- 7.4 mg dl-1 in HAAG, and 71.4 +/- 3.8 mg dl-1 in NAAG groups. The differences in plasma AAG concentrations between UG and TG and between HAAG and NAAG groups were statistically significant. No significant relationship was found between plasma AAG levels and phenytoin concentrations (r = -0.26). The time (mean +/- SEM) to recovery of T1 to 25% of control was significantly shorter in TG (28.2 +/- 1.4 min) than in UG (42.2 +/- 3.1 min) but did not differ significantly according to the plasma anticonvulsant level (27.3 +/- 2.0 min in TGW; 29.1 +/- 1.9 min in TGB) and the plasma AAG level 31.7 +/- 1.9 min in HAAG; 35.3 +/- 3.3 min in NAAG). The time for the TOF ratio to recover to 25% yielded similar profiles and statistical significance levels: TG, 32.9 +/- 2.2 min; UG, 51.2 +/- 4.0 min; TGW, 35.0 +/- 3.9 min; TGB, 30.7 +/- 1.8 min; HAAG, 38.1 +/- 3.1 min; NAAG, 42.0 +/- 4.1 min. We conclude that anticonvulsant therapy induces an increase in plasma AAG independently of the plasma anticonvulsant level. However, duration and recovery of vecuronium blockade do not differ according to plasma AAG levels. Consequently, elevated AAG does not contribute to the resistance to vecuronium blockade induced by anticonvulsants.
authors.affiliation: University Department of Anesthesia and Intensive Care Medicine, CHR de la Citadelle, Liege, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Hans
authors.forename: J F
authors.initials: JF
authors.lastname: Brichant
authors.forename: F
authors.initials: F
authors.lastname: Pieron
authors.forename: P
authors.initials: P
authors.lastname: Pieyns
authors.forename: J D
authors.initials: JD
authors.lastname: Born
authors.forename: M
authors.initials: M
authors.lastname: Lamy
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D001285:Atropine / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D002220:Carbamazepine / Q000097:blood / Q000627:therapeutic use; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage*; D009493:Neurosurgery; D009961:Orosomucoid / Q000032:analysis* / Q000378:metabolism; D010634:Phenobarbital / Q000097:blood / Q000627:therapeutic use; D010672:Phenytoin / Q000097:blood / Q000627:therapeutic use; D014673:Vecuronium Bromide / Q000008:administration & dosage*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; D006993:Hypnotics and Sedatives; D003473:Neuromuscular Nondepolarizing Agents; D009961:Orosomucoid; D006919:Hydroxyzine; D002220:Carbamazepine; D010672:Phenytoin; D001285:Atropine; D014673:Vecuronium Bromide; D010634:Phenobarbital; D000525:Alprazolam