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The interaction between two non-depolarizing neuromuscular blocking agents, pancuronium bromide and vecuronium bromide, has been studied at standardized levels of neuromuscular blockade and alternating the sequence of their administration, in 40 surgical patients. The drug administered first appeared invariably to play a dominant role in influencing both the dose requirements and the duration of action of the subsequent neuromuscular blocker. This resulted in reduced dose requirements and significant prolongation of action of vecuronium administered after pancuronium and increased dose requirements and shortening of neuromuscular blocking action of pancuronium given during vecuronium-induced partial neuromuscular blockade. Possible mechanisms of such interaction are discussed.
The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)
The drug vecuronium bromide, a short acting, non-depolarising agent with little side-effects, has brought much promise in the field of muscle relaxants. Fifth healthy patients were induced with injection thiopentone sodium 4 mg/kg and vecuronium bromide, 0.1 mg/kg was given IV. The earliest time at which the largest percentage of patients could be intubated satisfactorily was noted. The intubating conditions were estimated by scoring method. The duration of clinical relaxation was decided from the time of IV injection of vecuronium bromide to the return of muscle power of the non-respiratory muscles requiring repeat dose of the drug. The ideal intubating condition was achieved at 120 seconds and the duration of clinical relaxation ranged from 11-15 minutes.
Vecuronium bromide 1mg was injected intravenously for priming or precurarization in 42 cases. Apparent dyspnea was observed in 2 cases. The doses of vecuronium bromide in these 2 cases, 0.018 and 0.016 mg.kg-1, respectively were the same and less than those in the other 40 cases (0.018 +/- 0.003 mg.kg-1, mean +/- SD). Although respiratory sparing effect of vecuronium bromide is expected, intensive respiratory assist should be taken at the time of priming or precurarization with the drug.
Vecuronium bromide 70 micrograms kg-1 was used to facilitate tracheal intubation and provide neuromuscular blockade in 52 patients undergoing laparoscopic sterilization. Anaesthesia was maintained with 67% nitrous oxide in oxygen. Patients were monitored clinically and by tactile assessment of the evoked response of the adductor pollicis to a supramaximal train-of-four stimulation. Intubating conditions were assessed at 90 s in the first 33 patients, and were poor. They improved significantly in the subsequent 19 patients when intubation was delayed until 150 s (P less than 0.05). Operating conditions were good in all except two patients. Residual neuromuscular blockade was antagonized rapidly at completion of surgery by neostigmine 2.5 mg i.v., which was administered provided there was at least one twitch response. The mean duration of the procedure was 14.3 min (SD 2.5 min). The mean time from injection of neostigmine to satisfactory spontaneous breathing and neuromuscular recovery was 1.6 min (SD 0.7 min).
The disposition of vecuronium bromide has been investigated in six normal cats (group I) and in six cats with ligated renal pedicles (group II). A combined fluorimetric and chromatographic technique was used to determine the concentrations of vecuronium and its metabolites in biological material. After i.v. injection of 0.6 mg kg-1, vecuronium disappeared rapidly from the plasma of the normal cat. Concentrations decreased bi-exponentially with half-lives of 4.6 and 31 min, respectively. The steady state volume of distribution was 0.23 litre kg-1 and the clearance 11 ml min-1 kg-1. Seventy percent of an i.v. dose of vecuronium (or its metabolites) was recovered: 15% in the urine, 40% in the bile and 15% in the liver. Only 3.8% of this consisted of the 3-hydroxy metabolite. There were no significant differences in pharmacokinetic data or in the amounts of vecuronium and its metabolites recovered in cats with ligated renal pedicles. The 15% of vecuronium normally excreted by the kidney was compensated for by increased hepatic and biliary concentration of vecuronium.
The muscle-relaxation reactions of Ca-antagonist (nifedipine) pretreated patients and a control group (5 in each group) were observed after administration of vecuronium bromide using the "priming principle." Twitch depression induced by the "priming dose" of vecuronium bromide (20 micrograms/kg body weight and T4/T1 ratio in the Ca-antagonist-treated patients (35 +/- 13% and 0.42 +/- 0.14%, respectively), was significantly different (P less than 0.01) when compared with the control group (1.2 +/- 2.7% and 0.75 +/- 0.15%). Similarly, the onset time to maximum blockade after the intubating dose of vecuronium bromide (60 micrograms/kg body wt.) was significantly shorter in the nifedipine group (40 +/- 21 s) when compared with the controls (100 +/- 17 s). The duration of the effect observed clinically (until 25% recovery) in the nifedipine group 32.9 +/- 7.3 min versus 25 +/- 8.15 min was enhanced; however, the difference between the treated group and the control group was not significant.
The authors describe a technique of vecuronium bromide perfusion at constant flow used to obtain curarisation during 50 renal transplantations. The muscular effects of the drug were monitored through an electromyographical recorder, so as to adjust the perfusion rate. The dose of vecuronium bromide was 47.7 +/- 0.74 micrograms X kg-1 X h-1 (mean +/- SEM), this being lower than the dose recommended by D'Hollander (60 micrograms X kg-1 X h-1) for patients with normal renal function. Furthermore, no recurarisation was observed. Therefore, vecuronium can be considered as a satisfactory muscle relaxant in patients with renal failure, but neuromuscular monitoring appears to be a most important safety factor.
The neuromuscular blocking effects of vecuronium 10 mg preparation under enflurane anesthesia have been investigated in 22 patients having elective surgeries. The effect on cardiovascular system in man and laboratory examinations were also investigated. The results are as follows; 1. Onset time (time from end of injection until maximal blockade) after the dose of 0.08 or 0.1 mg.kg-1 of vecuronium bromide was about 2.6 minutes and 1.9 minutes, respectively. 2. Clinical duration of action (time from end of injection until 25% recovery of twitch) in the 0.1 mg.kg-1 group (about 50.1 minutes) was significantly longer than that in the 0.08 mg.kg-1 group (about 35.6 minutes). 3. Recovery time (time elapsing between 25 and 75% recovery of twitch) with neostigmine was 5.3 minutes (0.08 mg.kg-1) and 4.2 minutes (0.1 mg.kg-1). 4. Blood pressure was stable before and after the injection of vecuronium and no abnormal change related to the test drug was observed in the laboratory examinations. These data show that the efficacy and safety of the vecuronium 10 mg preparation are the same as those of the 4 mg preparation reported previously. In conclusion, it is considered that vecuronium 10 mg preparation is clinically useful because it is unnecessary to dissolve the drug frequently with injectable water.
We studied the usefulness of the 10 mg presentation of vecuronium bromide (NC45-10) for endotracheal intubation. Subjects were ASA type I-II patients between 20-65 years of age scheduled for various kinds of surgery who consented to participate in this study. After the entrance of patients into the operating room, we set up monitors and intravenously injected a priming dosage of NC45-10, 0.015 mg.kg-1. Next, we administered thiopental 5 mg.kg-1 and injected initial dosage of either 0.065 mg.kg-1 or 0.1 mg.kg-1 of NC45-10 intravenously 5 minutes after the administration of priming dose. One minute later, we attempted endotracheal intubation. We evaluated the muscle relaxation by the reaction to endotracheal intubation and graded it by the score of 0-3. Satisfactory muscle relaxation on endotracheal intubation was obtained in 80% of the patients with no significant difference between the 2 groups of initial dosage. No side effect or cardiovascular action was observed. It is concluded that this preparation is clinically safe and useful.
Ninety patients were included in a study to assess the clinical characteristics of vecuronium bromide used in children. The myorelaxant was administered to all patients using different routes. The use of vecuronium at a dose approximately equal to 1ED95 was characterised by a duration of action sufficient to allow its use in short operations; on the other hand, it also produced a long induction-intubation interval and not optimal conditions in which to perform intubation. Conditions for intubation improved during induction via inhalation and there was a reduced induction-intubation interval compared to intravenous induction using the same dose of vecuronium. A further reduction in intubation time was obtained by increasing the dose from 50 to 150 micrograms/kg-1 together with an increased clinical duration of action. The "priming principle" technique also allowed intubation time to be shortened without variations in the duration of action provided a full dose of vecuronium, 100 micrograms/kg-1, was used. However, this was also associated with a notable incidence of adverse reactions. Of the various combinations examined, the most advantageous association of pre-dose and interval between doses was the association of a pre-dose of 10 micrograms/kg-1 and an interval of 4 min between doses. Lower doses countered the advantages of priming, whereas higher doses resulted in an increased number of adverse reactions without producing notable changes in the intubation time.
The plasma and bile concentrations, the biliary excretion and the neuromuscular blocking effect of vecuronium bromide were studied during surgery in 13 patients who had received 150 micrograms kg-1 i.v. The amount of vecuronium in liver biopsies taken after i.v injection was measured in a separate group of six patients. Vecuronium appeared early in the bile, in concentrations that were 30-50 times greater than those in the plasma. On the basis of the measured amount of vecuronium excreted in the bile, together with the accepted average daily bile flow, it was estimated that more than 40% of vecuronium was excreted in the bile in 24 h. Liver biopsies indicated that the liver may contain more than 50% of the i.v. dose 30 min after injection. The large distribution of vecuronium into the liver may account for the initial rapid decline in vecuronium plasma concentration and its relatively short duration of action. In this study, neuromuscular blockade was prolonged, possibly as a result of interference, by surgical manipulation, with the rapid hepatic uptake of vecuronium.
The effect and plasma concentrations of vecuronium bromide were measured in normal patients after an intravenous dose of 50, 100, or 150 micrograms/kg and in patients with renal failure after 50 or 100 micrograms/kg. Urinary excretion of vecuronium was studied in normal patients after the 150 micrograms/kg dose. Pharmacokinetic parameters of patients with or without renal failure were similar. No metabolites of vecuronium were found in the plasma. Twenty percent of vecuronium was excreted unchanged in the urine; 5% as the 3-hydroxy derivative. No other metabolites of vecuronium were found in the urine. Increasing doses of vecuronium shortened the onset, but prolonged the duration of action and the recovery rate, to a similar extent in patients with or without renal failure. It was concluded that the disposition of vecuronium was best described by a three compartment model. Both the disposition and the effect of vecuronium are only marginally disturbed by renal failure.
Possible interactions between three calcium entry blocking agents (nifedipine, verapamil and bepridil) and the non-depolarizing neuromuscular blocking agent, vecuronium bromide, were investigated in chloralose-anaesthetized cats. In i.v. doses which caused decreases in arterial pressure, the calcium entry blockers did not affect indirectly-elicited twitches of tibialis muscle, but did potentiate the effects of vecuronium. No such potentiation of vecuronium was observed with the vasodilator drug, sodium nitroprusside. Experiments using close-arterial injections of acetylcholine suggested that the probable site of interaction is on the postsynaptic muscle membrane and probably involves blockade of calcium channels in skeletal muscle.
UNLABELLED: Clinical and electromyographic effects of either succinylcholine (Suc) or vecuronium bromide (VEC) were compared during induction and maintenance of neuromuscular blockade for pelvic laparoscopy. METHODS: Forty ASA class I and II patients (pat.) were studied under general anesthesia with thiopental, enflurane, and nitrous oxide. Group VEC-pat. (n = 20) received 0.015 mg/kg body wt. VEC as priming and 5 min later 0.085 mg/kg as intubation doses. Repetitive doses of 0.01 mg/kg were injected to maintain twitch depression (T1%) less than or equal to 15%. Neuromuscular block was reversed with atropine and pyridostigmine (0.01 resp. 0.1 mg/kg). In group Suc-pat. relaxation was induced with 1.5 mg/kg Suc 5 min after pretreatment with 2 mg alcuronium. Relaxation (10% less than or equal to T1% less than or equal to 15%) was prolonged using a Suc infusion. Neuromuscular blockade was assessed electromyographically (Relaxograph, Datex) using train-of-four (TOF) stimulation (2 Hz for 2 s). Intubation conditions were scored according to Fahey et al. RESULTS: Pretreatment with 0.015 mg/kg VEC compared to 2 mg alcuronium led to a more pronounced decline in T1% and TOF-ratio (P less than 0.001). The time interval between injection of the intubation dose and complete relaxation (T1% less than or equal to 5%) was shorter in group Suc- than in VEC-pat. (P less than 0.001). Suc provides better intubation conditions than VEC (P less than 0.05). Recovery from muscle relaxation was faster in Suc- than in VEC-pat. (P less than 0.001). During Suc infusion in 8 patients a phase-II block (TOF ratio less than or equal to 30%) was observed. DISCUSSION: Postoperative problems are often related to an unrecognized after effects of relaxants. Suc infusion leads to a remarkable number of phase-II blocks, whereas VEC can be antagonized promptly.
The interaction of two orally administered Ca-channel blockers, the dihydropyridines nisoldipine and nifedipine, with the non-depolarizing muscle relaxant, vecuronium bromide, was tested in the indirectly stimulated tibialis anterior muscle of anesthetized and ventilated Sprague-Dawley rats. In both the nisoldipine and the nifedipine group, depression of twitch tension and duration of vecuronium-induced neuromuscular blockade was potentiated when compared with a control group. The possible clinical relevance of these findings is discussed.
Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and their metabolites were followed for 2 h after the addition of 1 mg of either drug to the perfusate. In addition, the rate of change of the hepatic content of these two compounds was calculated by serially subtracting the amount of the compound and the metabolites in the bile and in the perfusate from the dose of drug added to the perfusate. It was found that, whereas the concentration of pancuronium in the perfusate declined slowly and monoexponentially, vercuronium concentration in the perfusate declined rapidly in a biexponential manner. No metabolites of either drug were detected in the perfusate. Approximately 40% of the injected dose of vecuronium was excreted in the bile as unchanged vecuronium and another 30% as the 3-hydroxy metabolite. No other metabolites of vecuronium were found in the bile. In total only about 7% of pancuronium (unchanged) was collected in the bile by the end of the experiment. It is concluded that, in comparison to pancuronium, the rat liver takes up large amounts of vecuronium rapidly, half of which is eliminated as unchanged vecuronium and half as the 3-hydroxy derivative. A small amount of vecuronium or its 3-hydroxy metabolite is returned to the perfusate from the liver. Some possible mechanisms underlying these differences are discussed.