The dose effect of ephedrine on the onset time of vecuronium

A small dose of ephedrine decreases the onset time of rocuronium and cisatracurium; however, ephedrine might be associated with adverse hemodynamic effects. The appropriate dose of ephedrine has not been determined. We, therefore, studied 120 patients anesthetized with fentanyl 2 microg/kg and propofol 2-2.5 mg/kg who were randomly divided to receive either ephedrine (30, 70, or 110 microg/kg) or saline. During propofol anesthesia, the neuromuscular block was monitored by mechanomyography by using submaximal current of train-of-four stimulation every 10 s. To determine cardiac output, a transcutaneous Doppler probe was placed externally at the suprasternal notch. Tracheal intubation was performed by a blinded investigator at 2 min after vecuronium. Neuromuscular block, intubating conditions, and hemodynamic effects were measured during the induction of anesthesia. Both ephedrine 70 and 110 microg/kg improved intubating conditions at 2 min after vecuronium; however, 110 microg/kg was associated with adverse hemodynamic effects. We conclude that ephedrine 70 microg/kg given before the induction of anesthesia improved intubating conditions at 2 min after vecuronium, probably by increased cardiac output without significant adverse hemodynamic effects. IMPLICATIONS:Ephedrine 70 microg/kg given before the induction of anesthesia improved tracheal intubating conditions at 2 min after vecuronium by increased cardiac output without significant adverse hemodynamic effects.     

Accelerated onset of vecuronium neuromuscular block with pulmonary arterial administration

The purpose of this study was to determine the onset times of vecuronium neuromuscular block administered into either the central circulation or a peripheral vein. One hundred and twenty adult patients with a pulmonary artery (PA) catheter were randomly divided into one of three groups with respect to the routes of vecuronium administration (n = 40 in each group). Anaesthesia was induced with midazolam 2.5 mg iv and fentanyl 10–50 μg · kg^{? 1} iv and maintained with intermittent doses of fentanyl 50 μg iv and nitrous oxide 60–70% in oxygen. After immobilization of the forearm in a splint, the ulnar nerve was stimulated supramaximally every 12 sec. The resulting force of the evoked thumb twitch was recorded (Myograph 2000, Biometer, Denmark). The times from the injection to the first depression of twitch response (latent onset) in patients given vecuronium 0.08 mg · kg^{? 1} into the pulmonary artery, the right atrium, and a peripheral vein on the hand were 58.0 ± 19.5, 71.5 ± 17.1, and 82.4 ± 18.0 sec (mean ± SD), respectively. The latent onset of neuromuscular block occurred sooner in patients given vecuronium into the central vein than when administered into a vein on the hand (P < 0.01). In comparing the patients given vecuronium into the central vein, the onset times to 95% twitch depression (onset) were 152.3 ± 40.7 and 168.2 ± 35.5 sec. The onset of block was found to be faster when vecuronium was administered into the pulmonary artery than into the right atrium (P < 0.01). These findings suggest that the administration of vecuronium into the pulmonary artery is one approach to accelerate neuromuscular blockade in patients with a PA catheter.     

Rapid tracheal intubation with propofol, alfentanil and a standard dose of vecuronium

We studied 60 ASA I patients with Mallampati grade 1 airways to compare emergency intubating conditions with either alfentanil 20 micrograms kg- 1, propofol 2.5 mg kg-1 and vecuronium 0.1 mg kg-1, or with thiopentone 5 mg kg-1 and suxamethonium 1 mg kg-1. Ease of laryngoscopy, vocal cord status and cough response were graded. The trachea of all patients was intubated; 83% of patients in the alfentanil-propofol-vecuronium group and 86% in the thiopentone-suxamethonium group were considered to have satisfactory intubating conditions at 60 s. We conclude that the combination of alfentanil 20 micrograms kg-1, propofol 2.5 mg kg-1 and vecuronium 0.1 mg kg-1 provided adequate conditions for rapid tracheal intubation.      

Duration of action of vecuronium after an intubating dose of rapacuronium, vecuronium, or succinylcholine

Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We investigated the duration of action of a maintenance dose of VEC after intubation with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general anesthesia were randomly allocated to receive a tracheal intubating dose of RAP 1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular function was monitored with electromyography. Recovery of the intubating dose of neuromuscular blocker was allowed to occur spontaneously until the first twitch of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5 x 95% effective dose [ED(95)]) was administered. The onset, duration, and recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/- 13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4 +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50% they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD), respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a maintenance dose of VEC was similar after an intubating dose of RAP or VEC but was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The duration of action of a maintenance dose of vecuronium was longer after an endotracheal intubating dose of rapacuronium compared with succinylcholine.     

A pharmacodynamic analysis of the onset of neuromuscular blockade by nondepolarizing muscle relaxants--the pharmacodynamics of a large dose of vecuronium

From Sheiner's equation on pharmacokinetics and pharmacodynamics, we derived a new equation which described the pharmacodynamics of nondepolarizing muscle relaxants during the onset phase. This equation showed that log (l0/l-1) had a linear relation to log (t) where "t" is the time after the administration of nondepolarizing muscle relaxant and "l" and "l0" are the twitch height at t = t and t = 0 respectively. It also implies that the administration dose (D) is inversely proportional to the onset time (OT), i.e., D.OT = const. We proved that these two relations held well for the actual 7 cases of vecuronium use in man. In conclusion, when vecuronium dose level was within 0.15-0.30 mg.kg-1 i.v., the dose was inversely proportional to the onset time which was defined as the time interval from the end of the administration of vecuronium until the single twitch was depressed under 5% of control value, i.e., Dose (mg.kg-1) x onset-time (sec) not equal to 24. During anesthesia with enflurane as well as during neuroleptanesthesia, a dose of vecuronium 0.3 mg.kg-1 (n = 7) was found to produce a duration of neuromuscular blocking action equal to the mean duration produced by pancuronium 0.1 mg.kg-1.     

Ephedrine fails to accelerate the onset of neuromuscular block by vecuronium

The onset time of neuromuscular blocking drugs is partially determined by circulatory factors, including muscle blood flow and cardiac output. We thus tested the hypothesis that a bolus of ephedrine accelerates the onset of vecuronium neuromuscular block by increasing cardiac output. A prospective, randomized study was conducted in 53 patients scheduled for elective surgery. After the induction of anesthesia, the ulnar nerve was stimulated supramaximally every 10 s, and the evoked twitch response of the adductor pollicis was recorded with accelerometry. Patients were maintained under anesthesia with continuous infusion of propofol for 10 min and then randomly assigned to ephedrine 210 microg/kg (n = 27) or an equivalent volume of saline (n = 26). The test solution was given 1 min before the administration of 0.1 mg/kg of vecuronium. Cardiac output was monitored with impedance cardiography. Ephedrine, but not saline, increased cardiac index (17%; P = 0.003). Nonetheless, the onset of 90% neuromuscular block was virtually identical in the patients given ephedrine (183 +/- 41 s) and saline (181 +/- 47 s). There was no correlation between cardiac index and onset of the blockade. We conclude that the onset of the vecuronium-induced neuromuscular block is primarily determined by factors other than cardiac output. The combination of ephedrine and vecuronium thus cannot be substituted for rapid-acting nondepolarizing muscle relaxants. IMPLICATIONS: Ephedrine increased cardiac index but failed to speed onset of neuromuscular block with vecuronium. We conclude that ephedrine administration does not shorten the onset time of vecuronium.     

Accidental epidural administration of vecuronium

We report a case of accidental epidural injection of vecuronium during cholecystectomy in a 55-year-old man (63 kg, 158 cm). Following 3 ml of lidocaine 1% as an epidural test dose, inadvertent epidural (T7-8) injection of vecuronium 4.25 mg instead of ropivacaine occurred. After immediate removal of the syringe containing vecuronium, 10 ml of ropivacaine 0.375% was injected epidurally. Intubation was performed under propofol infusion using a target-controlled infusion system with intravenous vecuronium 10 mg. There was a 3 min interval between inadvertent epidural and intravenous injection of vecuronium. Anesthesia was maintained with propofol infusion (2.6-3.0 microg x ml(-1)) titrated to maintain bispectral index between 35-55 and buprenorphine 0.16 mg with 40% oxygen in air. T1 response in the train-of-four (TOF) appeared 87 min after epidural vecuronium injection. Ten minutes later, additional vecuronium 0.5mg was required due to bucking. Seven minutes after that, T1 in the TOF reappeared and the operation was finished. Twenty-three minutes after the additional vecuronium, 4 responses in the TOF were obtained. Following reversal with atropine 1.0 mg and neostigmine 2.0 mg, the patient was able to sustain head lift and handgrip, and to protrude the tongue fully awake. The patient was extubated 124 min after epidural vecuronium injection. There was no memory of back pain during epidural vecuronium injection. There was no postoperative respiratory insufficiency or neurological disorder. We suspect the duration of action of epidural vecuronium is approximately twice that of intravenous injection and becomes prolonged with higher doses and advanced age.     

Duration of action of an equipotent dose of vecuronium in infants and in children

During general anaesthesia without any volatile anaesthetic agents, ten infants and ten children received incremental doses of vecuronium to achieve a 95% neuromuscular block. Thereafter, the thenar electromyographic response was allowed to recover spontaneously. Total dose of vecuronium to establish a 95.0 ± 0.5% (mean ± SEM) neuromuscular block was 66% greater for children than for infants (73 ± 4 vs. 44 ± 4 μg·kg^?1, P < 0.0001). However, recovery index and time to complete recovery of the neuromuscular function were 88 and 89% longer, respectively, in infants than in children (P < 0.0001). These results of the effect of an equipotent dose of vecuronium in infants and in children confirm that vecuronium is a long acting neuromuscular blocking agent in infants.     

Duration of action of supplemental doses of vecuronium is related to the duration after the initial dose

Vecuronium was administered in an initial dose of 0.1 0.3mg·kg^–1 and in supplemental doses of 0.03mg·kg^–1 or 0.05mg·kg^–1 in 74 patients (ASA class 1 or 2) scheduled for abdominal surgery. The duration of the neuromuscular blockade provided by vecuronium after both the initial and supplemental doses was determined using the evoked integrated electromyographic device. A statistically significant positive correlation (correlation coefficient: 0.83 0.91) was found between the duration of action of the initial dose and that of the first to fourth supplemental doses.The regression lines of each of the first four supplemental doses to the initial dose were very similar to each other. These results suggest that, since the duration of action of supplemental doses of vecuronium was prolonged in patients showing a long duration of action of the initial dose, it would be wise to avoid blind adherence to a predetermined schedule for supplemental administration. Rather, anesthesiologists should take into account the patients response to the initial dose and then decide the most appropriate timing for supplemental doses. Moreover, since vecuronium shows little cumulative effect even after 4 supplemental administrations in clinical-range doses, it can be concluded that vecuronium can be safely used in a wide dose range.(Otagiri T, Narita M, Nishizawa M, et al.: Duration of action of supplemental doses of vecuronium is related to the duration after the initial dose. J Anesth 6: 138–144, 1992)     

Effect of prior administration of succinylcholine on duration of action of vecuronium during enflurane anaesthesia

The effects of succinylcholine, which was given to facilitate tracheal intubation on the duration of action of subsequently administered vecuronium bromide, were evaluated in 54 adult patients who underwent abdominal surgeries under enflurane anaesthesia. The electromyographic response to train–of–four ulnar nerve stimulation was measured. Twenty–seven patients received 1 mg–kg^-1 of succinylcholine, followed by 0.15 mg kg^-1 of vecuronium when the electromyographic response recovered to 50% of control after succinylcholine–induced neuromuscular blockade. The other 27 patients served as the control group, receiving 0.15 mg kg^-1 of vecuronium without prior administration of succinylcholine. In both groups, administration of supplemental 0.04 mg kg^-1 of vecuronium was repeated whenever the electromyographic response recovered to 25% of control during surgical procedures. The duration of blockade induced by the initial 0.15 mg kg^-1 of vecuronium was 56.5 ± 12.8 (mean ± s.d.) min for the group with succinylcholine, and 58.5 ± 21.5 min for the control group. In both groups, the average duration of four consecutive supplemental doses of vecuronium was approximately 35 min. No significant differences between groups were found in the duration of neuromuscular blockade induced by initial and supplemental doses of vecuronium.     

Antagonism of an intubation dose of vecuronium

To study the problem of rapid antagonization of an intubation dose of vecuronium (0.08 mg/kg), 36 surgical patients undergoing barbiturate/halothane anesthesia were given edrophonium 0.5, 0.75, and 1.0 mg/kg or neostigmine 0.04, 0.06, and 0.08 mg/kg precisely 5 min following injection of the muscle relaxant. T1 twitch (T1/Tc) and train-of-four (TOF) ratios (T4/T1) of the hypothenar muscle were monitored every 20 s with the aid of a commercially available EMG monitor (Datex-Relaxograph). As documented by T1 and T4/T1 follow-up curves (Figs. 1 and 2) and derived parameters of relaxation as well (Dur25, Dur50, Dur75, recovery index, and reversal time; Table 4), both edrophonium and neostigmine resulted in a significantly shorter duration of vecuronium blockade (P less than 0.001). The mean time for recovery of TOF ratio to above 0.7 was between 10.8 +/- 6.0 (neostigmine 0.08 mg/kg) and 21.2 +/- 7.8 (neostigmine 0.06 mg/kg) min (mean +/- SD) following injection of the antagonist as compared to 58 +/- 18.4 min in the control group (P less than 0.001). Recurarization did not occur. Differences between drugs and dose-dependent effects were minimal; edrophonium did not prove superior to neostigmine with the exception of less pronounced muscarinic side effects, hence less bradycardia and a minimum heart rate of 57 +/- 8.2 bpm 20 min after the injection of neostigmine as opposed to 72 +/- 8.2 bpm following edrophonium (P less than 0.05; Fig. 4). As to the restitution of a ventilatory force sufficient to allow spontaneous breathing, no definite conclusions can be made.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the action kinetics of alcuronium and vecuronium by electromyographic monitoring

Twenty-eight ASA I or ASA II adults undergoing microsurgery were anaesthetized according to a standard protocol using droperidol, phenoperidine and thiopentone followed by enflurane. The patients were randomly assigned to two homogeneous groups: the first group (n = 14) received 0.2 mg.kg-1 alcuronium, whereas the second group (n = 14) received 0.08 mg.kg-1 vecuronium. There was no reinjection of either drug and curarization tapered off spontaneously. Neuromuscular monitoring was begun once anaesthesia was stable and after intentional isovolaemic haemodilution. The type of stimulus used was the train-of-four, delivered by a Relaxograph monitor to the ulnar nerve. Muscle response was measured at the hypothenar eminence. The kinetic study considered the time interval required between the injection of the muscle relaxant and the appearance of the minimal value of the twitch (first response of the train-of-four = T1min). The times to recovery of the twitch height to 25, 75 and 100% of the reference value (T1/T0) and of the fourth response of the train-of-four to 25 and 75% of the ratio (T4/T1) were also recorded. Finally, the recovery indexes represented by the times required for T1/T0 and T4/T1 to rise from 25% to 75% respectively were studied. The maximal twitch height inhibition was significantly greater (p less than 0.001) in the vecuronium group (T1min = 0.36 +/- 1.33%) than in the alcuronium group (T1min = 4.36 +/- 5.08%); it occurred significantly more quickly (p less than 0.001) with vecuronium (139 +/- 48 s) than with alcuronium (316 +/- 133 s).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary aspiration of gastric contents after a priming dose of vecuronium

A case is presented of a 16-year-old girl with ectodermal dysplasia for whom dental surgery under general anaesthesia was planned. Following a priming dose of vecuronium, and immediately after injection of sodium thiopentone (5 mg·kg⁻¹) pulmonary aspiration of gastric contents occurred. It is hypothesized that, because of the rapid speed of onset of neuromuscular blocking agents on the laryngeal muscles, that partial laryngeal paralysis was present at the time of induction of anaesthesia and that this was responsible in part for the episode of pulmonary aspiration.     

Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium

High-dose narcotic anesthetic inductions usually avoid circulatory depression better than do other techniques; however, the selection of a narcotic and neuromuscular blocker influences subsequent hemodynamic responses. One hundred-one patients having aortocoronary bypass graft (CABG) surgery were investigated using four combinations of a narcotic and neuromuscular blocker: group FP (fentanyl 50 micrograms/kg, pancuronium 100 micrograms/kg); group FV (fentanyl 50 micrograms/kg, vecuronium 80 micrograms/kg); group SP (sufentanil 10 micrograms/kg, pancuronium 100 micrograms/kg); and group SV (sufentanil 10 micrograms/kg, vecuronium 80 micrograms/kg), each combination being administered over 2 minutes. Hemodynamic functions were then monitored for 10 minutes before tracheal intubation. Significant changes included increases in heart rate in the groups receiving pancuronium and decreases in those receiving vecuronium. In all groups mean arterial pressure initially decreased; systemic vascular resistance index decreased significantly in all groups except SV. Cardiac index decreased significantly only in group SV. Circulatory depression requiring treatment with vasopressor or anticholinergic drugs was more common in patients given vecuronium. Cardiac arrhythmia occurred most often in group SP; only in group FP were there no arrhythmias, ischemic changes, or hemodynamic disturbances requiring intervention. Time to onset of neuromuscular blockade did not differ among the four groups, but transient chest wall rigidity occurred significantly more often with sufentanil than with fentanyl. Overall, the fentanyl/pancuronium combination afforded the greatest hemodynamic stability, whereas the sufentanil/vecuronium combination proved least satisfactory because of bradycardia and hypotension, requiring treatment in 35% of group SV patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protracted action of vecuronium in a patient with chronic renal insufficiency treated by dialysis

Although the pharmacokinetics of vecuronium are altered by the loss of kidney function, they do not differ significantly between patients with normal renal function and patients with renal failure. Therefore, the drug has become a preferred neuromuscular blocking agent in anuric patients. The author observed complete relaxation--verified by nerve stimulation--for more than 3 h following a single dose of 0.09 mg/kg vecuronium in a patient with chronic renal failure. Liver function was normal, and no drugs known to interact with vecuronium were used. The authors conclude that the altered pharmacokinetics of vecuronium in anuric patients might cause clinically significant effects in some patients.     

Possible bronchospasm after administration of vecuronium]

A 62 year-old female developed bronchospasm after intravenous vecuronium administration. Vecuronium is reported to have major advantages over pancuronium due to the lack of significant histamine-releasing activity and cardiovascular side effects. However, macular rash, systemic collapse and bronchospasm have been reported before. The patient received cholecystectomy under general anesthesia. She had a history of urticaria when she had had a intravenous pyelography and showed positive skin test to antibiotic, ceftizoxime. During induction with thiopental plus vecuronium and on addition of vecuronium, bronchospasm was induced within five minutes in each time. Both episodes of bronchospasms were relieved with intravenous aminophylline and methylprednisolone. During the operation arterial blood gas samples were taken twice and showed no abnormal findings. Further blood samples were taken for complement C3, C4, plasma IgE and white blood cell counts. Skin test to vecuronium was also performed. In spite of these data, the mechanism of bronchospasm remained obscure. Careful attention should be paid to the use of vecuronium, especially for the patient who showed allergic response to some drugs.