ABSTRACT
INTRODUCTION: Low-dose pancuronium is known to affect serum cholinesterase activity (BChE); however, the dose-response effect of clinical doses of pancuronium on BChE has not been investigated. METHODS: Thirteen ASA I-II patients scheduled for elective surgery requiring muscle relaxation were enrolled in this study. All patients had normal BChE before surgery. Incremental doses of pancuronium (10, 20, 50, and 100 microg/kg) were injected in accordance with surgical needs every 45 min. BChE was measured 3 min after injection by an automatic colorimetric method. RESULTS: BChE decreased significantly in all except one patient in comparison to the baseline (P < 0.05). However all values remained within normal clinical range. A dose of 100 microg/kg yielded significant decrease in comparison to 10 microg/kg but not to other dosages. Linear regression was not significant for the dose-response relationship (P = 0.05). CONCLUSION: After clinical incremental doses of pancuronium, BChE remained within clinical range.
Subject(s)
Butyrylcholinesterase/blood , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Adult , Aged , Dose-Response Relationship, Drug , Female , Humans , Male , Middle AgedABSTRACT
At the end of abdominal surgery deep neuromuscular blockade is required for peritoneal closure. Ideally injecting an intermediate acting drug like atracurium after a long acting drug such as pancuronium should deepen the neuromuscular block without the fear of an inadequate reversal at the completion of surgery. Thirty patients ASA I or II status, without known allergy to myorelaxant and without neuromuscular, hepatic or renal failure were included in this study. Anesthesia was induced and maintained with propofol, fentanyl, and N20. Normal core temperature was maintained by active warming of the upper part of the body. Blood electrolytes and the acid-base status were within the normal range. The accelerographic responses to Train-Of-Four supramaximal stimulation (TOF) of the ulnar nerve was monitored at the thumb. After obtaining a stable response with the accelerograph, the patients randomly received pancuronium (0.10 mg.kg-1, group I, n = 10 and group II, n = 10) or atracurium (0.50 mg.kg-1, group III, n = 10). An additional dose of atracurium (0.16 mg.kg-1, group I and III) or pancuronium (0.03 mg.kg-1, group II) was injected when the first response of TOF stimulation (T1) reached 25% of its initial value. Then the time to obtain a 25% twitch height of T1 (T25), the recovery index (RI 25-75), the delay to obtain 4 responses to TOF and an adequate recovery [TOF ratio of 0.70 (TOF70)] were monitored. Injection of 60% ED95 of atracurium after pancuronium resulted in a similar recovery of neuromuscular function as after 45% ED95 of pancuronium as shown by the same recovery of T25 (66.5 +/- 4.2 min versus 71.4 +/- 7.8 min, group I versus group II, p > 0.05) and TOF70 (131.6 +/- 15.7 min versus 144.0 +/- 17.5, group I versus II, p > 0.05). Nevertheless the RI 25-75 of group I was of intermediate duration between those of group II and III. Electrolytes and acid-base status were similar between groups at the beginning of surgery. Thus this study shows a synergistic effect of the combination of atracurium after pancuronium occurring in non hypothermic patients anesthetized without halogenated agents. Because the duration of action of the drug administered first governs the duration of action of the subsequent neuromuscular myorelaxant, the neuromuscular function should be closely monitored at the end of surgery if neuromuscular drugs are used in combination.
Subject(s)
Anesthetics, Intravenous/administration & dosage , Atracurium/pharmacology , Fentanyl/administration & dosage , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Propofol/administration & dosage , Anesthetics, Inhalation/administration & dosage , Drug Synergism , Evoked Potentials/drug effects , Female , Humans , Male , Middle Aged , Neuromuscular Junction/drug effects , Nitrous Oxide/administration & dosage , Ulnar Nerve/physiologyABSTRACT
INTRODUCTION: Potentiation of mivacurium by low-dose pancuronium is mostly due to an inhibition of plasma butyryl cholinesterase (BchE) resulting in a decreased rate of hydrolysis of mivacurium. Nevertheless, an interaction at the receptor site could not be ruled out. By changing the order of the muscle relaxant injections, we may lessen the pharmacokinetic interaction and assess the impact at the acetylcholine receptor level. METHODS: Twenty patients scheduled for general anesthesia with propofol and fentanyl, and isoflurane were randomized into two groups receiving, mivacurium 100 microg kg-1 followed by pancuronium 15 microg kg-1 (group 1) or pancuronium 15 microg kg-1 followed by mivacurium 100 microg kg-1 (group 2). BchE before and after injection of each relaxant was measured. Neuromuscular block was assessed with a force transducer at the adductor pollicis measuring the elicited twitch to ulnar nerve stimulation. RESULTS: The neuromuscular block was greater when pancuronium was administered before mivacurium (100% versus 96+/-3%; P<0.05). Times to recovery of the elicited twitch response to 25% and 75% of control value were increased by 100% (P<0.05). After pancuronium, decreases in BchE of 11% and 14% in groups 1 and 2 were observed, respectively. CONCLUSION: Interaction between mivacurium and low dose pancuronium is significant only when mivacurium is injected after pancuronium.