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Anesthesiology Dec 1986The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and...
The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium-neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Atracurium; Edrophonium; Humans; Neostigmine; Neuromuscular Blocking Agents; Pancuronium; Time Factors; Vecuronium Bromide
PubMed: 2878631
DOI: 10.1097/00000542-198612000-00002 -
Anesthesiology Mar 2004The duration of action of vecuronium is reduced in patients receiving phenytoin. In this study, the authors examined, simultaneously, the influence of phenytoin on both...
BACKGROUND
The duration of action of vecuronium is reduced in patients receiving phenytoin. In this study, the authors examined, simultaneously, the influence of phenytoin on both the pharmacokinetics and the pharmacodynamics of vecuronium.
METHODS
This study was approved by the institutional review board of the University of California, San Francisco, and patients gave written informed consent. Twenty-two patients, 11 taking phenytoin and all scheduled to undergo prolonged neurosurgical procedures with general anesthesia, participated in the study. In 12 patients (6 phenytoin, 6 control), vecuronium was infused at 7.5 microg x kg(-1) x min(-1) until the first response (T1) of each train-of-four decreased by 50%; in the remaining 10 patients (5 phenytoin, 5 control), 200 microg/kg vecuronium was infused over 10 min. Arterial blood samples were drawn at intervals over the next 5-7 h. Plasma concentrations of vecuronium and 3-desacetylvecuronium were measured by capillary gas chromatography. Pharmacokinetic and pharmacodynamic modeling was used to characterize the disposition of vecuronium and patient responses to it in the two groups.
RESULTS
Clearance was typically increased by 138% (95% confidence interval, 93-183%) in patients taking phenytoin. The effect of vecuronium was well described using a sigmoid Emax model. The concentration of vecuronium giving 50% twitch depression was increased 124% (45-202%) in patients taking phenytoin.
CONCLUSIONS
Chronic phenytoin therapy reduces the effect of vecuronium by mechanisms that include both increased vecuronium metabolism and reduced sensitivity of the patient to circulating concentrations of vecuronium.
Topics: Adult; Anticonvulsants; Biotransformation; Craniotomy; Drug Interactions; Female; Humans; Male; Middle Aged; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Phenytoin; Supratentorial Neoplasms; Vecuronium Bromide
PubMed: 15108978
DOI: 10.1097/00000542-200403000-00024 -
Anaesthesia Feb 1985
Topics: Aged; Female; Heart Block; Humans; Intraoperative Complications; Neuromuscular Blocking Agents; Pancuronium; Vecuronium Bromide
PubMed: 2858166
DOI: 10.1111/j.1365-2044.1985.tb10728.x -
British Journal of Anaesthesia Apr 1987In 39 healthy patients antagonism, by neostigmine 0.07 mg kg-1 or edrophonium 0.8 mg kg-1, of neuromuscular blockade induced by vecuronium or atracurium, was compared.... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
In 39 healthy patients antagonism, by neostigmine 0.07 mg kg-1 or edrophonium 0.8 mg kg-1, of neuromuscular blockade induced by vecuronium or atracurium, was compared. Reversal was attempted when the height of the single twitch (TH) had recovered spontaneously to 5% of the control value. The evoked responses, initially single twitch, then train-of-four (TOF) were observed until the TOF ratio was 70%. Induced recovery from TH 5% to 25% was shorter following edrophonium than following neostigmine with both vecuronium (P less than 0.05) and atracurium (P less than 0.05). The recovery indices and times until TH was 75% of control and until the TOF ratio was 70% were not different. The time from a TH of 75% to a TOF ratio of 70% was shorter following neostigmine than following edrophonium with both vecuronium (P less than 0.01) and atracurium (P less than 0.01). Edrophonium had a much more variable effect on vecuronium than on atracurium. These results show that although the onset of action of edrophonium was faster than that of neostigmine, this did not lead to a faster clinical recovery, and antagonism by edrophonium may be delayed in a number of patients if vecuronium is the neuromuscular blocker.
Topics: Adult; Atracurium; Edrophonium; Humans; Muscle Contraction; Neostigmine; Time Factors; Vecuronium Bromide
PubMed: 2882769
DOI: 10.1093/bja/59.4.478 -
Anesthesiology Dec 2015The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. (Comparative Study)
Comparative Study
BACKGROUND
The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation.
METHODS
The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine.
RESULTS
In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate.
CONCLUSIONS
Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.
Topics: Androstanols; Animals; Atracurium; Dose-Response Relationship, Drug; Heterocyclic Compounds, 4 or More Rings; Male; Neostigmine; Neuromuscular Nondepolarizing Agents; Rats; Rocuronium; Sugammadex; Sulfonic Acids; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 26418697
DOI: 10.1097/ALN.0000000000000868 -
British Journal of Anaesthesia Oct 1991A possible interaction between betamethasone and vecuronium was examined in 20 rat phrenic nerve-hemidiaphragm preparations. Ten preparations were bathed in a... (Comparative Study)
Comparative Study
A possible interaction between betamethasone and vecuronium was examined in 20 rat phrenic nerve-hemidiaphragm preparations. Ten preparations were bathed in a physiological solution with betamethasone 1 mumol litre-1 added and, after a 30-min period were exposed to vecuronium at concentrations of 4, 6, 8 and 10 mumol litre-1 with vecuronium free washings between each exposure. Ten control experiments were performed also using a betamethasone-free bathing solution. In comparison with control, the betamethasone group had significantly (P = 0.0008) less depression of muscle contraction (twitch) force at all concentrations of vecuronium. The calculated ED50 (50% depression of muscle contraction force) was 5.65 mumol litre-1 for controls and 7.39 mumol litre-1 for betamethasone-pretreated preparations. This study confirms our previous clinical observations that an interaction occurs between vecuronium and betamethasone which is characterized by resistance to neuromuscular block.
Topics: Animals; Betamethasone; Depression, Chemical; Diaphragm; Dose-Response Relationship, Drug; Drug Interactions; Male; Muscle Contraction; Organ Culture Techniques; Phrenic Nerve; Rats; Vecuronium Bromide
PubMed: 1681841
DOI: 10.1093/bja/67.4.447 -
Yonsei Medical Journal Mar 1992The interaction between succinylcholine (SCC) and non-depolarizers, atracurium or vecuronium was investigated in 36 cats of either sex using the sciatic nerve-anterior...
The interaction between succinylcholine (SCC) and non-depolarizers, atracurium or vecuronium was investigated in 36 cats of either sex using the sciatic nerve-anterior tibialis muscle preparation. Additionally, the relation of SCC to pseudocholinesterase activity was examined. The duration of action of vecuronium (6.5 +/- 1.3 to 7.3 +/- 2.2 minutes) in cats pretreated with SCC was greater than those (2.0 +/- 0.6 minutes) in non-pretreated cats. However, SCC had no influence on the duration of atracurium. The serum pseudocholinesterase activity was decreased after the injection of atracurium or neostigmine in contrast to vecuronium. The authors conclude that the prior administration of SCC prolongs the duration of vecuronium but not that of atracurium, and pseudocholinesterase activity is not related to the prolonging effect of SCC.
Topics: Animals; Atracurium; Cats; Female; Male; Succinylcholine; Vecuronium Bromide
PubMed: 1354401
DOI: 10.3349/ymj.1992.33.1.81 -
Anesthesiology Jan 1998Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done...
BACKGROUND
Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done to determine the actions and mechanisms of action of pancuronium on coronary and renal arteries other than those as a sympathomimetic agent.
METHODS
Helical strips of coronary and renal arteries from mongrel dogs were suspended in oxygenated, warmed Ringer-Locke solution, and changes in the isometric tension were recorded. In some strips, transmural electrical stimulation (5 Hz for 40 s) was applied to activate perivascular adrenergic nerves.
RESULTS
Pancuronium (10[-7] to 10[-5] M) caused dose-dependent relaxation in coronary and renal arteries contracted with prostaglandin (PG) F2alpha, whereas no significant response was induced with vecuronium. The relaxation was endothelium independent and abolished by indomethacin or tranylcypromine, a PGI2 synthase inhibitor. Transmural electrical stimulation caused coronary arterial relaxation, which was augmented by pancuronium and vecuronium. Desipramine also increased the response, and additional potentiation of the response was not elicited by pancuronium and vecuronium. In renal arteries, electrical stimulation caused contraction, which was also augmented by pancuronium and vecuronium. With desipramine treatment, these muscle relaxants did not potentiate the response. Endothelium-dependent coronary arterial relaxation caused by bradykinin was not affected by pancuronium.
CONCLUSIONS
Pancuronium-induced relaxations in canine coronary and renal arteries appear to be mediated by PGI2 released from subendothelial tissues. Potentiations by pancuronium and vecuronium of the response to adrenergic nerve stimulation are expected to be due to an inhibition of the norepinephrine uptake but not to facilitated release of the amine.
Topics: Animals; Coronary Vessels; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Endothelium, Vascular; Epoprostenol; Female; Indomethacin; Male; Neuromuscular Nondepolarizing Agents; Pancuronium; Renal Artery; Vasodilation; Vecuronium Bromide
PubMed: 9447869
DOI: 10.1097/00000542-199801000-00024 -
British Journal of Anaesthesia Feb 1989Vecuronium was used as the only neuromuscular blocking agent in 81 paediatric patients (neonates to adolescents) during fentanyl and nitrous oxide anaesthesia. The...
Vecuronium was used as the only neuromuscular blocking agent in 81 paediatric patients (neonates to adolescents) during fentanyl and nitrous oxide anaesthesia. The thenar electromyogram was used to monitor neuromuscular blockade. Neonates and infants had a mean requirement of vecuronium 105 micrograms kg-1 during the first 1 h of anaesthesia, to establish and maintain 90-98% neuromuscular blockade, compared with a mean requirement of 217 micrograms kg-1 for children aged 3-10 yr (P less than 0.05). Vecuronium 100 and 150 micrograms kg-1 maintained neuromuscular blockade greater than 90% for 59 and 110 min, respectively, in neonates and infants, but only for 18 and 38 min in children and for 37 and 68 min in adolescents (P less than 0.05). Vecuronium may be regarded as a long-acting neuromuscular blocking agent in patients aged less than 1 yr.
Topics: Adolescent; Age Factors; Anesthesia, General; Child; Child, Preschool; Humans; Infant; Neuromuscular Junction; Synaptic Transmission; Time Factors; Vecuronium Bromide
PubMed: 2564279
DOI: 10.1093/bja/62.2.184 -
British Journal of Anaesthesia Oct 1993We have studied the neuromuscular effects of pipecuronium, vecuronium and their combination in 130 ASA group I or II patients. Patients were anaesthetized with 0.8%...
We have studied the neuromuscular effects of pipecuronium, vecuronium and their combination in 130 ASA group I or II patients. Patients were anaesthetized with 0.8% halothane and 60% nitrous oxide in oxygen. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 10-s intervals). The dose-response curves were determined by probit analysis. The calculated doses producing 50% depression of the first twitch height were 15.6, 16.9 and 15.0 micrograms kg-1 for the pipecuronium, vecuronium and pipecuronium-vecuronium combination groups, respectively. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined neuromuscular effect of pipecuronium and vecuronium and to define the type of interaction between these drugs. The interaction between pipecuronium and vecuronium was found to be additive.
Topics: Adolescent; Adult; Dose-Response Relationship, Drug; Drug Synergism; Female; Humans; Male; Middle Aged; Muscle Contraction; Neuromuscular Junction; Pipecuronium; Ulnar Nerve; Vecuronium Bromide
PubMed: 7903151
DOI: 10.1093/bja/71.4.556