[en] 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.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Hans, Pol ; Université de Liège - ULiège > Département des sciences cliniques > Anesthésie et réanimation
Brichant, Jean-François ; Université de Liège - ULiège > Département des sciences cliniques > Anesthésie et réanimation
Pieron, F.
Rigo, Paulette ; Université de Liège - ULiège > Services généraux (Faculté de philosophie et lettres) > Relations académiques et scientifiques (Philo et lettres)
Born, J. D.
Lamy, Maurice ; Université de Liège - ULiège > Département des sciences cliniques > Anesthésie et réanimation
Language :
English
Title :
Elevated Plasma Alpha 1-Acid Glycoprotein Levels: Lack of Connection to Resistance to Vecuronium Blockade Induced by Anticonvulsant Therapy
Publication date :
January 1997
Journal title :
Journal of Neurosurgical Anesthesiology
ISSN :
0898-4921
eISSN :
1537-1921
Publisher :
Lippincott Williams & Wilkins, United States - Maryland
Messick JM, Maass L, Faust RJ, Cucchiara RF. Duration of pancuronium blockade in patients taking anticonvulsant medication. Anesth Annlg 1982;61:203-4.
Ornstein E, Matteo RS, Silverberg PA, Schwartz AE, Young WL, Diaz J. Chronic phenytoin therapy and nondepolarizing muscular blockade. Anesthesiology 1985;63: A331.
Ornstein E, Matteo RS, Schwartz AE, Silverberg PA, Young WL, Diaz J. The effect of phenytoin on the magnitude and duration of neuromuscular block following atracurium or vecuronium. Anesthesiology 1987;67:191-6.
Tempelhoff R, Modica PA, Jellish WS, Spitznragel EL. Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants. Anesth Analg 1990;71:665-9.
Platt PR, Thackray NM. Phenytoin-induced resistance to vecuronium. Anaesth Intens Care 1993;21:185-91.
Martyn JAJ, White SA, Gronert GA, Jaffe RS, Ward JM. Up-and-down regulation of skeletal muscle acetylcholine receptors: effects on neuromuscular blockers. Anesthesiology 1992;76:822-43.
Garcia E, Calvo R, Rodiguez-Sasian M, Jimenez I, Troconiz F, Suarez E. Resistance to atracurium in rats with experimental inflammation: role of protein binding. Acta Anaesthesiol Scand 1995;39:1019-23.
Kim CS, Arnold FJ, Itani MS, Martyn JAJ. Decreased sensitivity to metocurine during long-term phenytoin therapy may be attributable to protein binding and acetylcholine receptor changes. Anesthesiology 1992;77:500-6.
Hans P, Ledoux D, Bonhomme V, Brichant JF. Effect of plasma anticonvulsant level on pipecuronium induced neuromuscular blockade: preliminary results. J Neurosurg Anesthesiol 1995;7:254-8.
Abramson FP, Lutz MP. The effects of phenytoin dosage on the induction of α1-acid glycoprotein and antipyrine clearance in the dog. Eur J Drug Metab Pharmacokinet 1986;11: 135-43.
Duvaldestin P, Henzel D. Binding of tubocurarine, fazadinium, pancuronium and ORG NC45 serum proteins in normal man and in patients with cirrhosis. Br J Anaesth 1982;54: 513-6.
Foldes FF, Deery A. Protein binding of atracurium and other short-acting neuromuscular blocking agents and their interaction with human cholinesterases. Br J Anaesth 1983;55: 31S-4S.
Yanez P, Martyn JAJ. Prolonged d-tubocurarine infusion and/or immobilization cause upregulation of acetylcholine receptors and hyperkalemia to succinylcholine in rats. Anesthesiology 1996;84:384-91.