title: Prolonged duration of succinylcholine in patients receiving anticonvulsants: evidence for mild up-regulation of acetylcholine receptors?
abstract: Succinylcholine (SCh) normally causes a small increase in serum potassium concentration, but certain conditions may predispose to severe hyperkalaemia. This is due to "up-regulation" of skeletal muscle acetylcholine receptors (AChR), which also results in resistance to non-depolarizing muscle relaxants (NDMR). Anticonvulsant therapy causes NDMR resistance because of sub-clinical blockade, and diminished release, of acetylcholine. We studied nine patients chronically receiving anticonvulsants (phenytoin and/or carbamazepine) and nine control patients. Anaesthesia was induced typically with thiopentone or propofol; isoflurane and N2O were used for maintenance. The ulnar nerve was supramaximally stimulated and mechanical twitch height was measured with a force transducer at the adductor pollicis, before and after SCh 1 mg.kg-1, until return to baseline height. Plasma potassium concentration was measured before and at three, five, and ten minutes following SCh. Mean maximum potassium rise was 0.2 mEq.L-1 in each group. The time for return to baseline twitch height was 14.3 +/- 2.3 min (mean +/- SD) in the anticonvulsant group and 10.0 +/- 1.6 min in the control group, P = 0.001. The recovery index (time for 25% to 75% recovery) was 2.6 +/- 0.9 min in the anticonvulsant group and 1.4 +/- 0.3 min in the control group, P < 0.01. The normal potassium response coupled with prolonged duration suggests a hypersensitivity to SCh that is consistent with an anticonvulsant-induced mild up-regulation of AChR.
authors.affiliation: Department of Anesthesiology, University of California, Davis 95616.
authors.forename: A T
authors.initials: AT
authors.lastname: Melton
authors.forename: J F
authors.initials: JF
authors.lastname: Antognini
authors.forename: G A
authors.initials: GA
authors.lastname: Gronert
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D000328:Adult; D000771:Anesthesia, Intravenous; D002220:Carbamazepine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D011930:Reaction Time / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D013390:Succinylcholine / Q000494:pharmacology*; D013997:Time Factors; D014459:Ulnar Nerve / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D011950:Receptors, Cholinergic; D002220:Carbamazepine; D010672:Phenytoin; D013390:Succinylcholine; D000109:Acetylcholine; D011188:Potassium