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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 (2Hz 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 μg kg−1 for the pipecuronium, vecuronium and pipecuronium-vecuronium combination groups, respectively. Isobolo graphic 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. (Br. J. Anaesth. 1993; 71: 556–560)

Study Objective : To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by Pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Design : Prospective, randomized, placebo-controlled study. Setting : Inpatient gynecologic and gastroenterologic service at a university Medical center. Patients : Three groups of 20 ASA physical status 1 and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Interventions : Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 μg/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of Pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million I U, or a placebo. Measurements and Main Results : The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-witch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t -test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. Conclusions : When this type of antibiotic is used during anesthesia with pipecuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

The dose-response relation of pipecuronium, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine have been investigated in patients under sevofluraney N2O Anesthesia using a neuromuscular transmission analyzer (Accelograph®, Biometer, Denmark). After an initial dose of pipecuronium (0.04 mg·kg−1, i.v., the maximum block rate, onset time, the time from administration until 25% recovery and 50% recovery of control twitch height of the first response to train-of-four nerve stimulation and the interval time of administration of maintenance dose (0.005 mg·kg−1, i.v.) were 93.7±7.68%, 5.0±1.84, 55.4 ±23.92,73.0±29.44 and 38.7±15.50 minutes, respectively. The average intubation score (excellent; 0, good; 1 fair; 2, poor; 3) was 0.63±0.56 at the level of 95.88±5.06% block. Neostigmine (1.5 mg) promptly reversed the residual neuromuscular blockade induced by pipecuronium (reversal time: 10.1±2.98 minutes). No side effects attributable to pipecuronium was seen in this study.

Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the established agents atracurium besilate and vecuronium bromide. Pipecuronium and Org 9426 are steroidal compounds, the latter being a monoquaternary agent, whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium compounds. Pipecuronium and doxacurium have a relatively slow onset and a long duration of action. Pipecuronium produces maximum block in 3 to 6 min when given in a dose of 45 to 80 micrograms/kg, and a duration of clinical relaxation of between 40 and 110 min. Doxacurium is more potent, but is the least rapid and the longest acting relaxant currently available. When administered in doses of 37 to 80 micrograms/kg, it produces maximum block within 3.5 to 10 min, with a duration of clinical relaxation of 77 to 164 min. The advantage of both pipecuronium and doxacurium is their cardiovascular stability. Both agents are primarily eliminated via the kidneys and both have now been licensed for use in the US. Mivacurium is a muscle relaxant with a short duration of action. When administered in doses of 0.1 to 0.25 mg/kg it produces maximum block in 2 to 4 min, but the duration of clinical relaxation is less than 20 min. Higher doses which could induce a faster neuromuscular block are unfortunately associated with some histamine liberation. The drug is metabolised by plasma cholinesterase. Mivacurium has also been licensed for use in the US. Org 9426 is an agent with a rapid onset but an intermediate duration of action. A dose of 0.5 to 0.6 mg/kg induces maximum block in about 1.5 min and has a duration of clinical relaxation of about 30 min. The rapid onset of effect could be useful for early intubation as an alternative to suxamethonium chloride. However, much more clinical experience is needed with this agent, particularly with regard to duration of action of larger doses and occurrence of side effects. The drug is mainly eliminated via the liver.

In this study, combined neuromuscular blocking effects of ORG9426 with other non-depolarizing neuromuscular blocking agents were investigated. About 20% steady state neuromuscular block was established by a continuous infusion of one of 6 neuromuscular blocking agents (ORG9426, vecuronium, pancuronium, pipecuronium, d-tubocurarine and metocurine). Then 1/7 of the ED50 of ORG9426 or one of other neuromuscular blocking agents was administered in a single injection, and the increase in the neuromuscular block was observed. The combined neuromuscular blocking effect of ORG9426 and d-tubocurarine or ORG9426 and metocurine was significantly (P < 0.05) greater than that of each corresponding control (the combination of same neuromuscular blocking agent). The effect of d-tubocurarine was also potentiated by vecuronium, pancuronium and pipecuronium. These potentiations were not observed between ORG9426 and pancuronium, pipecuronium or vecuronium. Possible mechanisms of these synergistic interactions were discussed.

We have investigated the effects of adenosine i.v. on neuromuscular block induced by rocuronium, vecuronium and pipecuronium in an in vivo guinea-pig sciatic nerve-tibialis anterior preparation. The ED50 of each neuromuscular blocker was determined from cumulative log dose-response regression lines (n = 14). In separate experiments, adenosine 0.1 mg kg-1 min-1 or the same volume of 0.9% NaCl was given i.v. via a constant infusion and the ED50 of each neuromuscular blocking agent was then administered (n = 24). Adenosine 0.1 mg kg-1 min-1 increased significantly maximal block induced by the ED50 of these neuromuscular blockers (55-72%, 49-73% and 60-96%, respectively, for rocuronium, vecuronium and pipecuronium; P0.05). Time to maximal block after rocuronium was significantly prolonged by adenosine (1.4-2.1 min; P0.05) and time to maximal block after vecuronium and pipecuronium was unchanged by adenosine. Time to maximal recovery of twitch tension after administration of the ED50 of all neuromuscular blocking agents was prolonged significantly by adenosine (4.5-10.7 min, 8.2-15.8 min and 47.0-128.7 min, respectively, for rocuronium, vecuronium and pipecuronium; P0.05). We conclude that continuous infusion of adenosine 0.1 mg kg-1 min-1 potentiated the effects of neuromuscular blocking agents in this in vivo guinea-pig preparation.

Background and objective Porcine anaesthesia remains a great problem for cardiac surgery research and especially with cardiopulmonary bypass procedures. This study was designed to develop a suitable anaesthesia model in which miniature pigs could be induced smoothly and be maintained stably during and after a cardiopulmonary bypass procedure. Methods Thirty-one miniature pigs were randomly divided into two groups and induced using ketamine and pentobarbital (K-P group, n = 15) or pentobarbital (P group, n = 16) alone, respectively. Animals in group K-P were induced with intramuscular injections of ketamine 5 mg kg -1 and pentobarbital 20 mg kg -1 body weight, and those in group P were induced with pentobarbital 30 mg kg -1 alone. After intubation and intravenous catheterization, group K-P was maintained by continuous infusion of ketamine and pentobarbital, and pentobarbital was withdrawn after cardiopulmonary bypass started. Group P received a continuous infusion of pentobarbital throughout the operation. In addition, both groups were injected hourly with midazolam and pipecuronium bolus to achieve optimal surgical conditions. Results All of the group K-P animals survived for 24 h postoperatively. Five of the group P animals died from anaesthesia-related respiratory and cardiac arrest: three after induction and two after extubation. The animals in group K-P had more stable haemodynamics and arterial blood gas indices than animals in group P. Furthermore, the percentage of animals achieving satisfactory anaesthetic effects was significantly higher in group K-P than in group P. Conclusion Combination anaesthesia with low-dose ketamine and pentobarbital demonstrated superior haemodynamic and respiratory indices in comparison with pentobarbital. The combination regimen can achieve both hypnosis and analgesia effects with stable circulatory parameters.

The pharmacodynamics and -kinetics of pipecuronium were studied in 12 patients, six of whom received 100-mu-g kg-1 for laryngectomy (Group L), and six who underwent choledochotomy after insertion of the T-drain and were given 50-mu-g kg-1 (Group C). Onset time and clinical duration were 2.3 and 109 min and 2.8 and 39 min in Groups L and C, respectively. All patients could be sufficiently reversed with neostigmine. Terminal half-lives were 101.5 min (Group L) and 179 min (Group C) in a three-exponent decay; the distribution volumes at steady state 0.339 1 kg-1 (Group L) and 0.506 1 kg-1 (Group C); the plasma clearance 3.4 ml kg-1 min-1 (Group L) and 2.5 ml kg-1 min-1 (Group C). Within 24 h, 38.6% and 37% were excreted unchanged in the urine and 4.4% and 1% as 3-desacetyl pipecuronium in Groups L and C, respectively. Within 24 h only 2% was excreted into the bile in Group C. Distribution volume and terminal half-life in Group C were positively correlated with pre-operative serum aminotransferase levels (P

This study was designed to investigate the effect of divided administration of edrophonium on the course of neuromuscular recovery from a pipecuronium neuromuscular blockade. During thiopentone-nitrous oxide-halothane anaesthesia 48 patients were given pipecuronium 70 micrograms.kg-1. Patients were randomly assigned to one of four groups (n = 12 in each) to receive either edrophonium 1 mg.kg-1 (Groups I and II) or edrophonium 0.75 mg.kg-1 (Groups III and IV). In Groups I and III (single-dose groups), edrophonium was administered as a single bolus dose. In Groups II and IV (divided-dose groups) edrophonium was administered as an initial dose of 0.25 mg.kg-1 followed three minutes later by either 0.75 or 0.50 mg.kg-1 respectively. Reversal was attempted at 20% spontaneous recovery of twitch height. Administration of edrophonium in divided doses (Groups II and IV) accelerated the reversal of the pipecuronium neuromuscular blockade. At ten minutes post-reversal, train-of-four (TOF) ratio recovery reached 0.75 or more in 12 (100%) and in ten (83%) patients in Groups II and IV respectively. Similarly, times to attain a TOF of 0.75 (SEM) were shorter in the divided-dose groups than in the single-dose groups (P less than 0.05), being 354.5 (38.7) and 398.3 (49.1) sec in Groups II and IV vs 705.4 (66.6) and 651.2 (54.3) sec in Groups I and III respectively. Time was counted from the first administration of edrophonium. It is concluded that administration of edrophonium in divided doses produced a faster reversal of residual pipecuronium-induced neuromuscular blockade than single bolus administration. Also, administration in divided doses reduced the requirements of edrophonium needed for reversal of pipecuronium neuromuscular blockade.

A new technique involving the use of [125I]labeled rose bengal for the quantification of pipecuronium bromide (a muscle relaxant drug) is presented. This technique, which is based on the ability of rose bengal to react with pipecuronium and then form a complex which can be extracted into an organic solvent, involves two steps : the purification and labeling of rose bengal with 125I, and the quantification of pipecuronium. The specific activity of the compound (106 μCi/mg) allows for the quantification of pipecuronium in biological samples at concentrations as low as 5 ng/ml.

Study Objective : To determine the incubating conditions following the administration of pipecuronium bromide in doses of two (0.07 mg/kg) or three (0.1 mg/kg) times ED 95 (average dose that gives 95% block of the first twitch). Design : To compare intubating conditions at 1 tl2 and 21/2 minutes in 41 patients receiving balanced anesthesia. Setting : Surgical patients at Thomas Jefferson University Hospital. Patients : Forty-one patients undergoing surgical procedure who received general anesthesia. Interventions : After obtaining a stable baseline of train-of f our (TOF), 41 patients r randomly received either 0.07 mg/kg or 0.1 mg/kg of pipecuronium as a single intravenous (IV) bolus dose, and the trachea was intubated either at 112 or 212 minutes. minutes. Measurements and Main Results : Intubating conditions at 212 minutes appeared significantly better than those at 12 minutes, regardless of the pipecuronium dose. The mean time for TI (first twitch of TOF) to reach 50% and 90% suppression was 1.36 ± 0.51 minutes and 2.29 ± 0.8 minutes, respectively, for the 0.07 mg/kg dose and 1.07 ± 0.27 minutes and 1.72 ± 0.45 minutes, respectively, for the 0.1 mglkg dose. This did not make a significant difference in intubating conditions at either time. The time to 25% recovery of TI was 68.2 ± 22 minutes for the 0.07 mg/kg dose and 121.5 ± 49 minutes for the 0.1 mg/kg dose. In patients who had spontaneous recovery of T1 to between 10% and 25% of control, administration of neostigmine or edrophonium resulted in identical recovery in 10 minutes. However, in patients with less than 10% spontaneous recovery of T1, neostigmine appeared to be superior to edrophonium. Conclusion : Pipecuronium has a relatively rapid onset. The trachea could be intubated successfully in 112 minutes with a dose of either 0.07 mg/kg or 0.1 mg/kg. If the clinical situation requires perfect relaxation with no movement or bucking, we recommend waiting at least 212 minutes.

Neostigmine 0.06 mg · kg−1 or edrophonium 1 mg · kg−1 were administered to two groups of 15 patients each for antagonism of pipecuronium-induced neuromuscular block at 20% spontaneous recovery of the first twitch (T1) of the train-of-four (TOF) stimulation. The mean onset of action (± SEM) of edrophonium (18.1 ± 2.4 sec) was significantly more rapid (P < 0.01) than that of neostigmine (47.6 ± 4 sec), as were the times taken to attain a TOF ratio of 0.25 and 0.5. Nevertheless, the reversal time (time taken from the end of injection of the antagonist until TOF ratio value had reached 0.75) was significantly shorter (P < 0.01) in the neostigmine than in the edrophonium group (499.3 ± 62 vs 767 ± 52 sec respectively). The TOF ratio ten minutes after reversal was greater in the neostigmine group than in the edrophonium group (P < 0.01), 0.78 ± 0.02 vs 0.68 ± 0.02 min respectively. At that time, 33% (5 out of 15) and 80% (12 out of 15) patients failed to be reversed adequately (TOF ratio of 0.75) after neostigmine 0.06 mg · kg−1 and edrophonium 1 mg · kg−1, respectively. Administration of one additional dose (one-third of the initial dose) of the same antagonist resulted in adequate antagonism in the remaining five patients in the neostigmine group and in nine patients in the edrophonium group. Two such doses were required in the remaining three patients in the latter group. The mean total dose of neostigmine and edrophonium employed in this study was 0.067 ± 0.002 and 1.3 ± 0.05 mg · kg−1, respectively. Under the conditions of this study, edrophonium in a dose of 1 mg · kg−1 did not consistently antagonize residual neuromuscular blockade induced by pipecuronium at 20% recovery of T1.

The usefulness of the joint application of HPLC and NMR spectroscopy in drug impurity profiling is demonstrated by the following examples: (1) identification of Z and E isomers of 17α-ethynyl-4-oestrene-3β,17-diol-3- acetate-17-(3′-acetoxy-2′-butenoate) in ethynodiol diacetate; (2) identification of the p -tolyl analogue as the impurity of enalapril maleate; (3) identification and quantification of 2′-dehydro-pipecuronium bromide in pipecuronium bromide. The possibilities of utilizing NMR spectroscopy for the identification and quantification of the impurities with and without their isolation are discussed.

Severe tetanus is characterised by muscle spasms and autonomic dysfunction. We recently reported the results of a randomised placebo controlled trial of magnesium sulphate infusions for the treatment of severe tetanus which showed magnesium was associated with improved muscle spasm and cardiovascular control. We hypothesised that magnesium controlled autonomic dysfunction by reducing catecholamine release and thus urinary excretion. Urinary adrenaline and noradrenaline concentrations were measured during the first 24 h of therapy in 180 adults with severe tetanus randomised to treatment with magnesium (n = 92) or placebo (n = 88). Magnesium therapy was associated with lower urinary adrenaline excretion and higher urinary noradrenaline excretion. High urinary adrenaline concentrations were associated with documented autonomic dysfunction. Patients given magnesium had significantly less autonomic dysfunction, required less cardiovascular stabilising drugs, and had lower urinary concentrations of adrenaline. These findings suggest adrenaline is important in the pathophysiology of severe tetanus and magnesium controls autonomic dysfunction by reducing adrenaline release.

A sensitive and selective HPLC method with coulometric electrode array detection for the determination of pipecuronium bromide and its four impurities has been developed. The coulometric electrode array detection at increasing potentials from +300 to +900mV of the porous graphite electrode versus the palladium reference electrode was used. The limit of detection and quantitation for pipecuronium bromide was 8 and 25ngml(-1), respectively. This elaborate method for the simultaneous analysis of pipecuronium bromide and its impurities proved to be fast, precise, accurate, sensitive, and could be applied to analysis in substances and in pharmaceutical preparations.

Pipecuronium is a non-depolarizing neuromuscular blocker with similar properties to pancuronium, but without cardiovascular effects. Neuromuscular effects, conditions of tracheal intubation, and hemodynamic repercussions of two different doses of pipecuronium were evaluated.Patients were divided into two groups according to the dose of pipecuronium: Group I (0.04 mg x kg(-1)) and Group II (0.05 mg x kg(-1)). Intramuscular midazolam (0.1 mg x kg(-1)) was administered 30 minutes before the surgery. Propofol (2.5 mg x kg(-1)), preceded by fentanyl (5 microg x kg(-1)) and pipecuronium (0.04 and 0.05 mg x kg(-1) for Groups I and II, respectively), was administered for anesthetic induction. Patients were ventilated with 100% oxygen via a face mask until a 75% reduction in the amplitude of the response to an isolated stimulus (1 Hz) is achieved, at which time laryngoscopy and intubation were carried out. Anesthetic maintenance was achieved with isoflurane (0.5 to 1%) with a mixture of 50% O2 and N2O. Mechanical ventilation was used to maintain P(ET)CO2 between 32 and 36 mmHg. The pharmacodynamics of pipecuronium was evaluated by acceleromyography.Mean times and standard deviation for the onset of action, clinical duration (T1(25%)), and recovery index (T1(25-75%)) were: Group I (122.10 +/- 4.18 sec, 49.63 +/- 9.54 min, and 48.21 +/- 6.72 min), and Group II (95.78 +/- 8.91 sec, 64.84 +/- 13.13 min, and 48.52 +/- 4.95 min). Onset of action, clinical duration, and conditions of tracheal intubation were significantly different for both groups.Pipecuronium at a dose of 0.05 mg x kg(-1) can be used in prolonged procedures in which cardiovascular changes should be avoided.

Pipecuronium bromide (Arduan) is a bisquaternary, steroid-type neuromuscular blocking agent in clinical use in Eastern Europe. Before its introduction into clinical practice in the USA, in the first phase of this study the neuromuscular potency of pipecuronium was determined under "balanced" and enflurance anaesthesia by the cumulative log dose-response method in 30 patients each. In the second phase the intubation and onset times, clinical duration of the first and repeated doses, spontaneous recovery index, reversibility of its residual neuromuscular effect by an anticholinesterase and its effect on heart rate and blood pressure was compared with the same variables observed in patients, anaesthetized with identical techniques but who had received vecuronium or pancuronium. The neuromuscular potency of pipecuronium was greater under enflurane (ED95 = 23.6 +/- 1.1 micrograms.kg-1 (mean +/- SEM)] than under balanced (ED95 = 35.1 +/- 17 micrograms.kg-1) anaesthesia. Pipecuronium was more potent than vecuronium under both balanced (ED95 = 45.8 micrograms.kg-1) and enflurane anaesthesia (ED95 = 27.4 micrograms.kg-1). Following the administration of 2 x ED95 doses there were no clinically significant differences in the intubation or onset times of pipecuronium, vecuronium and pancuronium. Under balanced anaesthesia the clinical duration of 2 x ED95 dose of pipecuronium (110.5 +/- 0.3 min) or pancuronium (115.8 +/- 8.1 min) were similar and about three times longer than that of vecuronium (36.3 +/- 2.1 min). The recovery indices of pipecuronium (44.5 +/- 8.2 min) and pancuronium (41.3 +/- 4.2 min) were also similar and about three times longer than that of vecuronium (14.3 +/- 1.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)

The haemodynamic effects of 200 micrograms.kg-1 pipecuronium and pancuronium were compared under etomidate/piritramide anaesthesia in 20 patients scheduled for elective coronary artery surgery. Following the completion of the haemodynamic measurements (ten minutes), anaesthesia was maintained by etomidate/sufentanil infusion. The mean changes in cardiac output were approximately -19 and -2 per cent and in heart rate -1 and +26 per cent for pipecuronium and pancuronium respectively. Plasma and urine concentrations of pipecuronium were also measured and the pharmacokinetic variables obtained indicated rapid initial decrease in plasma concentration (t1/2 = 7.6 minutes) followed by a longer terminal phase (t1/2 = 161 minutes). The central compartment volume was 102 +/- 24 ml.kg-1 and plasma clearance was 1.8 +/- 0.4 ml.kg-1 min-1. Approximately 56 per cent of the dose was recovered from the urine within 24 hours of administration and about 25 per cent of this was the metabolite, 3-desacetyl pipecuronium. High-dose pipecuronium administration under the anaesthetic regimen employed did not produce deleterious haemodynamic effects. The pharmacokinetic variables after bolus injection of pipecuronium did not deviate from those reported under normothermic conditions.

To determine in infants and children the neuromuscular effect of pipecuronium during alfentanil-N2O/O2 anesthesia, the authors studied 32 ASA Physical Status 1 and 2 pediatric patients undergoing minor elective surgery, divided into three groups according to their age: group 1 included 12 infants, 1.9 +/- 0.2 months old (mean +/- SE; range, 20 days to 3 months), weighing 5.2 +/- 0.3 kg; group 2, 10 infants, 6.1 +/- 0.9 months old (range, 3-11 months), 6.9 +/- 0.4 kg; and group 3, 10 children 5.6 +/- 0.9 yr old (range, 2-9 yr), 19.6 +/- 2.2 kg. Neuromuscular blockade at the ulnar nerve-adductor pollicis muscle was measured by electromyography. Incremental iv doses of pipecuronium were given (one 20 micrograms/kg first dose, followed by 10 micrograms/kg increments) to reach a 95 +/- 2% twitch depression (ED95). In children ED50 and ED95 of pipecuronium were 45.0 +/- 5.8 micrograms/kg (mean +/- SE) and 70.5 +/- 9.3 micrograms/kg, respectively. In 3- to 12-month-old infants ED50 and ED95 were 25.8 +/- 1.5 micrograms/kg and 48.7 +/- 3.5 micrograms/kg, respectively, and both significantly (P less than 0.05) less than those in children. In 0- to 3-month-old infants ED50 and ED95 were 23.7 +/- 1.7 micrograms/kg and 46.5 +/- 2.9 micrograms/kg, respectively, and also significantly (P less than 0.05) less than those measured in children. Time from maximal initial neuromuscular blockade to 75% recovery was 64.5 +/- 8.8 min in children and significantly shorter (P less than 0.05) in the two infant groups (0- to 3-month-old: 38.7 +/- 5.7 min, 3- to 12-month-old: 43.8 +/- 5.3 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular blocking drugs can induce intraoperative bronchospasm. We characterized the magnitude and the temporal profile of the constriction in normal or in hyperresponsive airways after injections of neuromuscular blocking drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s apneic period in naïve and rabbits sensitized to allergens by ovalbumin. Fifteen s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium was administered in random order. Zrs was then also recorded during the administration of increasing doses of exogenous histamine. To monitor the changes in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time windows, and the airway resistance (Raw) was determined by model fitting. The increases in Raw were significantly larger in the sensitized rabbits than in the naïve animals. The largest increases in Raw and the maximum rate of change in Raw were obtained for succinylcholine (146% +/- 29% and 0.80 +/- 0.12 cm H2O/L, respectively) and mivacurium (80% +/- 25% and 0.71 +/- 0.13 cm H2O/L) and the smallest were obtained for pipecuronium (40% +/- 12% and 0.41 +/- 0.04 cm H2O/L). Allergic sensitization leads to severe and rapidly developing bronchospasm after administrations of mivacurium or succinylcholine. These deleterious side effects should be considered when succinylcholine or mivacurium is administered in the presence of bronchial hyperreactivity.

JUSTIFICATIVA E OBJETIVOS: Uma das mais importantes propriedades dos bloqueadores neuromusculares é o rápido início de ação, possibilitando intubação traqueal precoce. A administração de pequena dose de bloqueador não-despolarizante antes da dose plena é sabidamente redutora da latência da maioria dos bloqueadores neuromusculares utilizados. O brometo de pipecurônio é um agente aminoesteróide de longa duração com grande estabilidade cardiovascular, porém, com início de ação tardio. O objetivo desse estudo foi avaliar o efeito do priming do pipecurônio em pacientes adultos submetidos a cirurgias eletivas sob anestesia geral. MÉTODO: Foram estudados 33 pacientes adultos de ambos os sexos, com idade entre 20 e 65 anos, estado físico ASA I ou II, submetidos a cirurgias eletivas sob anestesia geral. Foram excluídos do estudo pacientes com insuficiência renal ou hepática, neuromiopatia, uso concomitante de drogas que influenciem a sua farmacocinética ou pacientes com histórico familiar de hipertermia maligna. Foram divididos em dois grupos: Grupo 1 onde foi utilizado o priming com 0,01 mg.kg-1 e três minutos depois completada a dose de 0,08 mg.kg-1 e o Grupo 2, sem dose priming (Grupo Controle). O relaxamento neuromuscular foi controlado pela aceleromiografia (Aparelho TOF-Guard) e no momento em que T1 < 10% era realizada a laringoscopia. A análise estatística foi feita pelos testes T para amostras independentes e a normalidade pelo Shapiro Wilks. RESULTADOS: Os grupos foram homogêneos e observou-se que o tempo para T1 < 10% no Grupo 1 foi de 161,4 ± 13,7 segundos e no Grupo 2 foi 217,8 ± 23,4 segundos, com p < 0,001, havendo diferença estatística significativa entre os grupos. CONCLUSÕES: Os resultados do estudo mostraram diferença estatística significativa entre os grupos com e sem priming, indicando que o pipecurônio também tem latência reduzida, assim como os demais bloqueadores neuromusculares conhecidos. BACKGROUND AND OBJECTIVES: One of the most important neuromuscular blockers property is short onset, allowing early tracheal intubation. Low nondepolarizing blocker dose before the full dose is known to decrease the onset of most neuromuscular blockers. Pipecuronium bromide is a long-lasting aminosteroid with major cardiovascular stability, however, with late onset. This study aimed at evaluating pipecuronium priming effect in adult patients submitted to elective surgeries under general anesthesia. METHODS: Participated in this study 33 adult patients of both genders, aged 20 to 65 years, physical status ASA I or II, to be submitted to elective surgeries under general anesthesia. Exclusion criteria were patients with kidney or liver failure, neuromuscular diseases, in concurrent use of drugs influencing pipecuronium pharmacokinetics, and patients with family history of malignant hyperthermia. Patients were divided in 2 groups: Group 1 = priming with 0.01 mg.kg-1 and 3 minutes later the remaining 0.07 mg.kg-1 (total 0.08 mg.kg-1); Group 2 = no priming dose (group control). Neuromuscular relaxation was controlled by acceleromyography (TOF-Guard device) and laryngoscopy was accomplished when T1 < 10%. T test for independent samples was used for statistical analysis and Shapiro Wilks was used to test normality. RESULTS: Groups were homogeneous. Time for T1 < 10% was 161.4 ± 13.7 seconds for Group 1 and 217.8 ± 23.4 seconds for Group 2, with p < 0.001 and statistically significant differences between groups. CONCLUSIONS: Our results have shown statistically significant differences between groups with and without priming, indicating that pipecuronium also has its onset decreased, similarly to other known neuromuscular blockers. JUSTIFICATIVA Y OBJETIVOS: Una de las más importantes propiedades de los bloqueadores neuromusculares es el rápido inicio de acción, posibilitando intubación orotraqueal precoz. La administración de pequeña dosis del bloqueador no despolarizante antes de la dosis completa es consabidamente reductora de la latencia de la mayoría de los bloqueadores neuromusculares utilizados. El bromuro de pipecuronio es un agente aminoesteroide de larga duración con grande estabilidad cardiovascular, sin embargo, con inicio de acción tardía. El objetivo de ese estudio es evaluar el efecto del priming del pipecuronio en pacientes adultos sometidos a cirugías electivas bajo anestesia general. MÉTODO: Fueron estudiados 32 pacientes adultos de ambos sexos, con edad entre 20 y 65 años, estado físico ASA I ó II, a ser sometidos a cirugías electivas bajo anestesia general. Fueron excluidos del estudio pacientes con insuficiencia renal o hepática, neuromiopatia, uso concomitante de drogas que influencien la farmacocinética de la droga o pacientes con histórico familiar de hipertermia maligna. Fueron divididos en dos grupos: Grupo 1 donde fue utilizada el priming con 0,01 mg.kg-1 3 minutos después de completada la dosis de 0,08 mg.kg-1 y el Grupo 2, sin dosis priming (Grupo Control). El relajamiento neuromuscular fue controlado por la aceleromiografía (Aparato TOF-Guard) y en el momento en que T1 < 10% era realizada la laringoscopia. El análisis estadístico fue hecha por la prueba T para muestras independientes y la normalidad testada por el Shapiro Wilks. RESULTADOS: Los grupos fueron homogéneos y se observó que el tiempo para T1 < 10% en el Grupo 1 fue de 161,4 ± 13,7 segundos y en el Grupo 2 fue 217,8 ± 23,4 segundos, con p < 0,001, habiendo diferencia estadísticamente significativa entre los grupos. CONCLUSIONES: Los resultados del estudio mostraron diferencia estadísticamente significativa entre los grupos con y sin priming, indicando que el pipecuronio también tiene latencia reducida, así como también los demás bloqueadores neuromusculares conocidos.

The experience of clinical use of the new Russian myorelaxant of the non-depolarizing action vero-pipecuronium (pipecuronium bromided) manufactured by "Veropharm" is described. Vero-pipecuronium was found to ensure splendid and good conditions for the intubation of the trachea and to maintain reliably myorelaxation. The recommended doses and availability of an antidote (prozerine) provide for a sufficiently controllable myorelaxation. Vero-pipecuronium does not virtually exert any effect on the parameters of hemodynamics and can be successfully used in patients with a high anesthetic risk including heart surgeries. Thus, Russian vero-pipecuronium has now an effective and safe myorelaxant manufactured inside the country, whose parameters are not inferior to those of pipecuronium bromide (arduan) manufactured by "Gedeon Richter", Hungary. Since the described drug is made in Russia, one can hope it will be highly effective both economically and pharmacologically.

A total of 108 patients operated on the abdominal cavity were examined with laparoscopic equipment or via laparotomic assess. The recovery time of neuromuscular conduction was defined for a myorelaxant with organ-depended metabolism (pipecuronium) and, predominantly, nonorgan-depended metabolism (athracurium and cisathracurium) in relation to the type of surgical technique (laparoscopy and laparotomy). It is concluded that carboxyperitoneum prolongs the recovery of neuromuscular conduction for pipecuronium without affecting this parameter in athracurium and cisathracurium. It is more expedient to use these myorelaxants during laparoscopic operations than pipecuronium, a myorelaxant having organ-dependent metabolism.

Summary Fetal movement during intra-uterine fetal therapy makes these procedures technically more dificult and increases the likelihood of trauma to the fetus. Pancuronium or pipecuronium were used in a randomised study to temporarily arrest movement in 16 fetuses undergoing intra-uterine procedures. Under ultrasound guidance, pancuronium or pipecuronium 0.2 mg.kg−1 was injected into the fetal gluteal region. Fetal movements ceased within 4.6 ± 2.3 min in the pancuronium group and 4.5 ± 2.8 min in the pipecuronium group and returned by 115±26 min in the pancuronium group and 121 ± 3 2 min in the pipecuronium group. No adverse effects of the relaxant were observed in the mothers. There bvas no evidence of soft tissue, nerve or muscle damage at the fetal injection site after delivery. Both muscle relaxants provided a safer method for diagnostic and therapeutic procedures. However, four cases in the pancuronium group (50%) developed a fetal tachycardia, and two cases in the same group showed loss of beat-to-beat variability. Pipecuronium appeared to be more suitable for intra-uterine procedures.

Interaction of the steroidal neuromuscular blocking drugs pancuronium, pipecuronium, rocuronium and vecuronium with cardiac muscarinic receptors in rat hearts was investigated in vitro by a tritiated N-methyl hyoscine binding assay. We showed an interaction with cardiac muscarinic receptors with a rank order of potency pancuronium > vecuronium > pipecuronium > rocuronium and demonstrated complex binding characteristics for pancuronium, vecuronium and rocuronium, with "Hill coefficient" of less than unity. We conclude that the haemodynamic differences seen during the use of these neuromuscular blocking drugs may be a result of their interactions with cardiac M2 muscarinic receptors.

Investigation of new neuromuscular blocking agents was started 30 years ago in Richter Ltd. This paper presents the results obtained by Richter's scientists. 2 compounds out of 100 bisquaternary ammonio steroid having androstane skeleton were selected for further pharmacological study. One of these agents, pipecuronium bromide (Arduan) elicited long-lasting block of neuromuscular transmission without cardiovascular side effects in both animal experiments and clinical studies. Arduan is a powerful competitive antagonist of acetylcholine, since it can bind pre- and postsynaptic (N1) receptors of the transmitters. It has no remarkable cumulative effect. Neostigmine rapidly and completely antagonized the neuromuscular blockade caused by pipecuronium. Arduan was introduced into clinical practice. The second compound, RGH-4201 (Duador) evoked a neuromuscular block of short duration. It showed slight atropin-like cardio-vagolytic effect in animal experiments. In the clinical studies, however, the cardiovascular side effects were found to be too strong. Therefore, it was not introduced in clinical practice.

We have examined the prolongation of a maintenance dose of vecuronium after an intubating dose of pipecuronium in 45 patients who received either pipecuronium 70 μg kg-1 or vecuronium 200 μg kg-1 i.v. for tracheal intubation, followed by either pipecuronium 10 μg kg-1 or vecuronium 15 μg kg-1 for maintenance of neuromuscular block. The duration of the vecuronium maintenance dose was greater after pipecuronium (40 (so 12) min) than after vecuronium (29 (9) min) (P = 0.02). The duration of pipecuronium after pipecuronium (49 (15) min) was similar to that of vecuronium after pipecuronium. We conclude that the duration of action of vecuronium is prolonged by prior administration of pipecuronium. (Br. J. Anaesth. 1993; 70: 446–448)

The dose-response relationship and the variability of the time variables in pipercuronium neuromuscular blockade were studied in 29 patients (ASA physical status 3) during halothane anaesthesia. The ED95 (twitch tension) was determined in 9 patients using the cumulative dose response technique. Another 20 patients received the resulting ED95 as a single bolus. The mean ED95 was 35 micrograms.kg-1 (95% confidence interval: 29-41 micrograms.kg-1). Following bolus injection of 1.ED95, an 80-100% twitch depression was achieved within 4.6 +/- 1.3 min (mean +/- s.d.). The duration from end of injection of pipecuronium to 25% twitch recovery, the time from 25% to 75% twitch recovery, and the time from 25% twitch recovery to the train-of-four ratio (TOF) returning to 0.7 was 35 +/- 14, 37 +/- 26, and 63 +/- 27 min, respectively. The time from end of injection to TOF = 0.7 varied within a 2-h range (54-160 min). Thus, the time variables in pipecuronium neuromuscular blockade were as poorly predictable as those reported in the literature on pancuronium, alcuronium and doxacurium.

Carboxyperitoneum and traditional forced ventilation of the lungs have a negative impact on external respiration function during laparoscopic operations, leading to impairment of the ventilation device, pressure rise in airways, and decrease in oxygen diffusion and carbon dioxide release. This leads to accumulation of carbon dioxide in the blood and tissue with a trend to development of acidosis of mixed origin. Cardiovascular changes during laparoscopic cholecystectomy manifest by hypertension and tachicardia in the presence of increased central venous pressure and total peripheral vascular resistance, decreased stroke and cardiac indexes, decreased right-ventricular diastolic function, increased pressure in the pulmonary artery, and deceleration of venous bloodflow in the inferior and superior venae cavae. The most rational variant of forced ventilation of the lungs in laparoscopic cholecystectomy is high-frequency injection ventilation, which appreciably attenuates the negative effect of carboxyperitoneum on central hemodynamics, gas exchange, and external respiration function. The optimal variant of total anesthesia in laparoscopic cholecystectmy is endotracheal combined narcosis with diprivane and fentanide. The key factor in the choice of forced ventilation protocols is the maintenance of adequate gas exchange in the lungs in the presence of the lowest possible mean pressure in the airways.

Choice of induction agent is the decisive factor in utilization of a laryngeal mask (LM) under spontaneous respiration, as insufficient relaxation and unwanted laryngopharyngeal reflexes deteriorate the efficiency of LM functioning during operation and anesthesia. 132 anesthesias with LM were performed, 86 of these for laparoscopic cholecystectomies (LCE) (group 1) and 42 for saphenectomies (group 2). Control group consisted of 60 patients anesthetized for LCE by means of an endotracheal tube (ETT). Combined induction intravenous anesthesia with ketamine, barbiturates, and diprivan was used in group 1 and controls. In group 2 induction anesthesia was based on ketamine and diprivan. Group 1 and control group were matched for demographic characteristics and concomitant diseases. All groups were divided into subgroups, depending on anesthesia. In all groups pipecuronium bromide (0.06 mg/kg) was administered before insertion of EET or LM after injection of induction agents. In total myoplegia, installation of LM was simple, involving no untoward laryngo-pharyngeal reflexes. LM was correctly installed from the first attempt in 98.7% cases. In combined intravenous ketamine-based anesthesia, pressor reaction to LM installation consisted in an increase of heart rate by 5.6% (1K group--control), by 10.2% in 2K group (fractionated ketamine (1.5-2 mg/kg) + diazepam (0.1 mg/kg) and fentanyl (2.6 micrograms/kg); after barbiturates heart rate increased by 6.7% in 1B group (control), after diprivan it did not increase in 1D group (control), while the mean arterial pressure in 2D group (fractionated diprivan (1 mg/kg) + ketamine (25-50 mg), diazepam (0.08 mg/kg) and fentanyl (2.6 micrograms/kg) increased by 10% and heart rate by 6.6%. Reaction to tracheal intubation was pronounced in all types of induction anesthesia. No regurgitation or aspiration was observed in any case. Hence, use of total myoplegia in installation of LM allows the use of various modern anesthetics in optimal doses and notably simplifies the utilization of LM.

A comparative study was performed of general balanced anesthesia on the basis of neuroleptic analgesia (NLA) and inhalation low- and minimal-flow anesthesia with isoflurane in anesthesiological management of extensive operations on the liver. A total of 75 anesthesias were conducted. Because of low hepatotoxicity, absence of its metabolites' pharmacological activity, fast elimination from the body unchanged, isoflurane is effective in long and traumatic operations on the liver. Low-flow isoflurane significantly lowers pharmacological load with opiates, myorelaxants which is essential in patients with hepatic diseases. This leads to more rapid recovery of adequate spontaneous respiration and activation of the patient in low risk of postoperative iatrogenic complications.

Potential for assessing liver function during liver transplantation surgery by monitoring muscle paralysis from nondepolarizing neuromuscular blockers that are hepatically cleared is critically assessed. Rocuronium is strongly favored as a promising pharmacodynamic probe for predicting allograft liver function because it is predominantly eliminated via the liver and its putative metabolites are not active. Prolongation of recovery from rocuronium paralysis is closely correlated with allograft liver function postoperatively. Vecuronium, pancuronium, and perhaps pipecuronium may also prove to be useful probes, but the two former blockers have active metabolites. Further prospective studies are necessary with more precise measurement of neuromuscular function to confirm the predictive value of this method. Alterations in neuromuscular blocker plasma concentrations that are correlated with changes in liver function and either the dose required or the intensity or duration of paralysis needs to be demonstrated for this technique to be clinically useful.

A prospective, randomised, single blind study was conducted to evaluate and compare the intracranial pressure (ICP) and cardiovascular effects of pipecuronium (PPC) and pancuronium (PNC) in 20 patients undergoing supratentorial surgery. Patients were randomly divided into two groups. Patients in Group I (n = 10) received pancuronium (0.1 mg kg(-1)) and in Group II (n = 10) pipecuronium (0.07 mg kg(-1)) for intubation. Intracranial pressure (ICP), heart rate (HR), systolic, diastolic and mean arterial pressures (SAP, DAP, MAP), central venous pressure (CVP), nasopharyngeal temperature and arterial blood gases (ABG) were monitored at the following time periods: before induction (0 minutes); 3 minutes after thiopentone and muscle relaxant; immediately after intubation; and 4, 6, 8, 10, 20 and 30 minutes following intubation. The rise in intracranial pressure at intubation was significantly greater in group I (21.10+/-3.97 torr, 122.59%) when compared to group II patients (1.80+/-0.70 torr, 10.04%) (p0.0 1). Cardiovascular parameters also showed a significantly greater degree of rise in group I when compared to group II patients. Heart rate increased by 29+/-6.32 beats min(-1) (33.52%) and systolic arterial pressure by 11.60+/-7.37 torr (9.47%) in group I. These parameters did not change significantly in group II. No significant alterations were observed in the other measured parameters in either of the two groups.

Neuro-muscular transmission was studied in 100 children operated on for retroperitoneal and mediastinal tumors using the TOF-Guard accelograph. The device was instrumental in cutting down intubation time, monitoring neuro-muscular transmission system (NMTS), predicting the point of transmission recovery and making extubation possible. NMTS monitoring established such advantages of continuous myorelaxant infusion as lower rate of drug administration and lower total dose; the latter is important to avoid drug cumulation. Due to TOF-Guard application 25-30 and 20% of such myorelaxant drugs as arduan and mivacron was saved, respectively; infusion technique required no decurarization medication. There is quite a potential of variation of myorelaxant administration at different stages of surgery and anesthesia.

Summary The onset time and tendency to cumulation of pipecuronium and high-dose vecuronium were compared during nitrous oxide anaesthesia supplemented with a propofol infusion. Pipecuronium 0.06 mg·kg−1 had a similar duration of action to vecuronium 0.2 mg·kg−1 (49 vs 43). Patients who received vecuronium had a shorter onset time of neuromuscular blockade (p < 0.01). Neither pipecuronium nor vecuronium showed marked cumulation.

Rectal temperature, temperature of the brown adipose tissue, and the heart rate were studied in the rabbit foetus under intact and reduced utero-placenta blood flow in the end of the intrauterine development. With the reduced utero-placenta blood flow, bradycardia and a drop in the brown fat metabolism due, probably, to an insufficient development and functional immaturity of this tissue, were revealed.

Background Patients on chronic anticonvulsant drugs are relatively resistant to certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium, pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and atracurium. This study investigated the influence of chronic carbamazepine therapy on the neuromuscular block induced by the new muscle relaxant rocuronium. Methods Twenty-two otherwise healthy individuals scheduled for neurosurgical operations were studied: 11 of them were on chronic treatment with carbamazepine; the others served as control subjects. The median duration of carbamazepine therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam, anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was given for intubation. The ulnar nerve was stimulated, and the evoked electromyogram recorded using a Datex NMT monitor. Results Based on the response to the first of four stimuli, neither the lag time nor the onset-time differed between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and 75% of the baseline response and the recovery index (RI, 25%-75%) were significantly shorter in patients on chronic carbamazepine therapy. Conclusions The authors conclude that the duration of the rocuronium-induced neuromuscular block is significantly shortened by preceding chronic carbamazepine therapy.

Cardiovascular effects of four commonly used non-depolarising muscle relaxants and their ability to increase histamine plasma concentrations were studied in patients scheduled for coronary artery bypass grafting.40 patients were included in the study after informed consent. After premedication with Flunitrazepam (2 mg p.o.) on the evening before and 1 hour prior to surgery anaesthesia was induced with Flunitrazepam (4-6 micrograms kg-1). Fentanyl (3 micrograms kg-1) und Etomidate (150 micrograms kg-1) and the patients were ventilated via face mask with 50% N2O in oxygen. Patients were randomly allocated to one of four groups, and, 15 min after induction of anaesthesia, received equipotent doses of either Pancuronium (0.09 mg kg-1, n = 10). Pipecuronium (0.08 mg kg-1, n = 10), Atracurium (0.6 mg kg-1, n = 10), or Vecuronium (0.1 mg kg-1, n = 10) injected over 20 seconds via a central venous catheter. Cardiovascular variables were determined in the awake patient, 15 min after induction of anaesthesia and following administration of the respective muscle relaxant. In addition, plasma histamine concentrations were assessed before and after relaxation. Evoked muscular response to TOF simulation of the ulnar nerve (plethysmo-mechanogram) was continuously recorded to determine the onset of neuromuscular blockade.Heart rate, mean arterial pressure and cardiac index significantly decreased in all patients following induction of anaesthesia while systemic vascular resistance remained unchanged. Only Pancuronium caused a significant increase in heart rate (53 +/- 11 to 61 +/- 15 min-1) whereas cardiac index and mean arterial pressure did not change significantly. No other neuromuscular blocking agent caused any changes in the cardiovascular variables measured and histamine plasma concentrations remained within the reference range in all of the four groups with no differences detectable between groups.All investigated neuromuscular blocking agents exhibited marked cardiovascular stability which permits their use, being based exclusively on pharmacodynamic and pharmakokinetic considerations even in patients with coronary heart disease. If an increase in heart rate appears beneficial Pancuronium may be advantageous.

Effects of nondepolarizing myorelaxants pancuronium, arduan, and tracrium were studied during surgery in 347 children with thermal injuries aged from several months to 15 years. Nondepolarizing myorelaxants are drugs of choice for providing myoplegia in children operated on for thermal injuries. The optimal initial dose of these agents in children with burns is 30-50% higher than the recommended dose and depends on the size of the lesion. For controllable myoplegia, the doses of subsequent injections are to be 1.-5-2 times lowered in comparison with the initial dose. The effects of pancuronium and arduan depend on the hepatorenal function. Tracrium ensures sufficient controllable myorelaxation in children with burns even in cases with hepatorenal dysfunction.

This study was aimed at assessing the airtightness of the airways during the use of a laryngeal mask (LM) under conditions of myoplegia and traditional forced ventilation of the lungs (FVL) with carboperitoneum (CP) during laparoscopic cholecystectomy (LCE). A total of 146 anesthesias for LCE were carried out using LM (n = 86) or endotracheal tube (ETT) (n = 60). The groups did not differ by the demographic characteristics or concomitant diseases. After premedication and induction of anesthesia it was maintained with N2O:O2--2/1 (Fi O2 = 0.3), fractionated administration of fentanyl (0.1-0.2 mg), and pipecuronium bromide (0.06 mg/kg). A gastric tube was inserted. Two variants of FVL were used: 1) permanent minute respiration volume (MRV) was maintained and 2) MRV was increased in order to maintain the Et CO2 at a constant level. The amount of gastric contents was measured and its pH assessed. Regurgitation and aspiration was assessed (in 33 patients) using methylene blue in gelatin capsules administered orally 10 min before anesthesia. Gas exchange was monitored by the Datex Capnomac-Ultima and by check-ups of acid base balance in the arterial capillary blood, hemodynamics was monitored by noninvasive Criticon Dynamap monitor. Manual FVL with inhalation P no more than 10 cm H2O completely prevented the entry of gas narcotic mixture into the stomach. Application of LM under conditions of total myoplegia and FVL with inhalation P of 23-25 cm H2O provided a satisfactory airtightness of the LM-airways contact without audible (appreciable) leaking of gas narcotic mixture. Leakage of gas narcotic mixture during LM application under total myoplegia and carboperitoneum (with CO2 pressure in the abdominal cavity 12 cm Hg) is no more than 6%, which indicates that LM is a reliable air guide providing good airtightness of the LM-airways contact even under conditions of increased abdominal pressure. No cases of regurgitation and aspiration were observed.

Purpose: To compare the pharmacodynamic behaviour of vecuronium with that of ORG 9487, we measured the time-course of action of equipotent doses of ORG 9487 and vecuronium and investigated their mutual interaction when given in succession. Methods: Sixty ASA I-II patients were anaesthetized with thiopentone, fentanyl, halothane and nitrous oxide and assigned randomly to four groups. Each patient received an initial dose (ID) of either vecuronium (V) or OPG 9487 (O) followed by maintenance doses (MDn) of either V or O (ID/MD: O/O, V/O, O/V and V/V. The time course of action was measured mechanomyographically, determining the duration until 25% recovery of the single twitch (DUR25). Results: The onset time of an ID of ORG 9487 was shorter than that of an ID of vecuronium (96 vs 203 sec, P

The effect of various non-depolarizing neuromuscular blocking agents (gallamine, pancuronium, vecuronium, d-tubocurarine, metocurine, atracurium and pipecuronium) on [3H] acetylcholine release in the response to field electrical stimulation was investigated in vitro in preparations of the guinea pig right atrium. In this preparation, atropine enhanced and oxotremorine, a muscarinic agonist, reduced the release of [3H] acetylcholine. Atropine reversed the inhibitory effect of oxotremorine in a concentration dependent manner, indicating that there is negative feedback modulation of acetylcholine release from the vagal nerve. While pancuronium, gallamine and atracurium enhanced the release of [3H] acetylcholine, d-tubocurarine, metocurine, vecuronium and pipecuronium did not affect it. Pancuronium and gallamine also reduced the inhibitory effect of oxotremorine and the Kd value of pancuronium for muscarinic receptors located on cholinergic nerve terminals was 2.31 μM. These findings indicate that pancuronium and gallamine enhanced the release of acetylcholine from the atrial parasympathetic nerve, probably by inhibiting presynaptic muscarinic receptors.

Presence of endocrine disorders, malfunction of liver and kidneys requests special approach application concerning general anaesthetic use in patients with the hormone producing insulinomas. There were 44 patients examined, in whom tumor was removed. Sodium hydroxybutyrate application while introducing anaesthesia promoted the haemodynamics stabilization. Arduan dosage ought to be reduced because of it possible cumulation in blood due to hepatorenal disorders existing in this patients. The dominance of the blood glucagon at the end of operation and the glucagon-insulin coefficient shift causes the tachycardia and the shock index increase. The proposed direct binasal stimulation of respiration after the anaesthesia conduction promoted rapid muscle tone and respiratory movements restoration in patients.

A general relation between the rate of onset and rate of recovery from non-depolarizing blockade has been demonstrated, with recovery consistently about ten times slower than onset. This observation has led to the suggestion that non-depolarizing agents share a common mechanism of action. Rocuronium, a recently introduced steroidal non-depolarizing agent, is claimed to have a very rapid onset but an intermediate duration and appears to test this hypothesis. To investigate this paradox we have calculated the rates of onset and recovery of rocuronium using the isolated human forearm and compared them with those of pipecuronium. The mean ratio of recovery time/onset time for rocuronium was 31.3, which is significantly greater than that for pipecuronium, 11.6 (P < 0.01). Whilst pipecuronium conforms to the same general relation between onset and offset described previously for other non-depolarizing agents, rocuronium appears to have a disproportionately rapid rate of onset for its rate of recovery. This suggests that onset, recovery, or both onset and recovery, from rocuronium blockade occur in a different manner to that of other non-depolarizing agents.