Pharmacodynamic and Pharmacokinetic Study on the Neuromuscular Blocking Action of Rapacuronium: a Comparison with Other Muscle Relaxants / 대한마취과학회지

BACKGROUND: We evaluated the pharmacodynamic and pharmacokinetic properties of rapacuronium, a new non-depolarizing muscle relaxant. METHODS: The EC50 and EC95 values of rapacuronium, vecuronium, and rocuronium were determined on rat hemidiaphragm, and reversal effects were determined using edrophonium or pyridostigmine. In 57 healthy adults, neuromuscular transmission was monitored at the adductor pollicis. Patients received a single dose of succinylcholine (1.0 mg/kg), rapacuronium (1.5 mg/kg), rocuronium (0.6 mg/kg), or mivacurium (0.16 mg/kg). Onset time, clinical duration, recovery index (RI), total duration (TD), train of four (TOF) ratio at over 95% recovery of control first twitch height, cardiovascular effect, and intubation scores were measured. RESULTS: By in vitro study, the EC50 and EC95 of rapacuronium were 4 to 10 fold larger than those of vecuronium and rocuronium, and by clinical study, the onset time of rapacuronium was similar to those of succinylcholine. The clinical duration of rapacuronium was not different from those of succinylcholine and mivacurium. RI and TD of rapacuronium (9.6 +/- 3.5 min and 30.9 +/- 10.7 min) were longer than those of succinylcholine (3.5 +/- 1.1 min and 18.1 +/- 4.4 min) and mivacurium (6.5 +/- 0.9 min and 23.0 +/- 4.4 min) for spontaneous recovery, but not different during reversal by pyridostigmine (5.0microgram/kg). The TOF ratio was increased after pyridostigmine than during spontaneous recovery. Intubation conditions of rapacuronium were similar to those of succinylcholine. Heart rates were significantly increased (15% of control) within 2 min, but not mean arterial pressure after rapacuronium was administration. CONCLUSIONS: Rapacuronium can be considered a valid alternative to succinylcholine and had no observed cardiovascular effect.

The Effect of Pretreatment with Lidocaine for the Withdrawal Movement Associated with the Injection of Rocuronium in Children / 대한마취과학회지

BACKGROUND: The purpose of this study was two fold; first, to determine the incidence and type of withdrawal movement associated with IV injection of rocuronium in pediatric patients; and second, to determine whether pretreatment with IV lidocaine affects the incidence of movement associated with rocuronium administration in pediatric patients. METHODS: Forty-two pediatric patients were randomly assigned to two groups. After general anesthesia was induced with thiopental sodium 5 mg/kg and manual occlusion of venous inflow was performed, one group of patients received 0.1 ml/kg 1% lidocaine IV. A second group received 0.1 ml/kg of normal saline as a placebo control. Venous inflow occlusion was held for 5 seconds, and immediately followed by the injection of rocuronium 0.6 mg/kg IV. The patient's response to rocuronium injection was graded using a 5-point scale. RESULTS: We observed that the incidence of movement was 100% in the placebo group and was significantly decreased to 28.8% in the group pretreated with lidocaine (P<0.001). CONCLUSIONS: Withdrawal movement on injection of rocuronium in pediatric patients can be decreased or prevented by pretreatment with IV lidocaine.

Interaction between Mivacurium and Nitroglycerin / 대한마취과학회지

BACKGROUND: The neuromuscular blocking effects of a nondepolarizing neuromuscular blocker (NDNM) during a nitroglycerin (NTG) infusion were significantly potentiated and prolonged. NTG reduced the requirement of a NDNM in surgical patients. We investigated the influence of a NTG single bolus injection on a mivacurium nuromuscular blockade. METHODS: We studied 36 adult surgical patients, ASA physical status I or II, between 15 and 53 years old. Neuromuscular monitoring was measured by TOF-GUARD (Biometer Co., Denmark). Anesthesia was induced by thiopental sodium 3-5 mg/kg and fentanyl 3 microgram/kg, and maintained with 3 L/min N2O, 2 L/min O2 and 1 vol.% isoflurane. Patients were randomly assigned to 3 groups: 1) Control group (mivacurium 0.16 mg/kg), 2) N100 group (mivacurium 0.16 mg/kg, NTG 100 microgram), 3) N200 group (mivacurium 0.16 mg/kg, NTG 200 microgram). We measured the train-of-four (TOF) response from the beginning of recovery to the complete regaining of muscle twitch. RESULTS: NTG produced a prolongation of the neuromuscular blocking effect by mivacurium. T1 (contro group: 12.1 +/- 0.5, N100 group: 15.8 +/- 0.4 and N200 group: 11.6 +/- 0.4 min), T25 (16.4 +/- 0.4, 20.5 +/- 0.5 and 14.9 +/- 1.0 min), T75 (22.5 +/- 0.9, 29.4 +/- 0.7 and 20.1 +/- 1.0 min), T95 (27.3 +/- 0.6, 39.6 +/- 0.7 and 24.6 +/- 1.5 min) and the recovery index (6.1 +/- 0.6, 9.0 +/- 0.4 and 5.3 +/- 0.7 min) were significantly prolonged in the N100 and N200 groups (P < 0.05). CONCLUSION: These results suggest that a NTG bolus injection prolonged the neuromuscular blocking effect of mivacurium, dose relatively.

Neuromuscular Blocking Properties of Dantrolene at the Neuromuscular Junction and Its Recovery with Various Antagonists / 대한마취과학회지

BACKGROUND: Dantrolene produces skeletal muscle relaxation by a direct action on excitation-contraction coupling, presumably by decreasing the amount of calcium released from the sarcoplasmic reticulum. The mechanism underlying this action is extrajunctional. The aim of this study was to evaluate the pharmacodynamic properties of dantrolene at the neuromuscular junction and the reversal effects of substances as possible dantrolene antagonists in vitro. METHODS: The effects of evoked twitch tension response have been studied on the isolated phrenic nerve hemidiaphragm muscle strips of the rat, using a single twitch (0.1 Hz) and the train of four (TOF; 2 Hz for 2s) stimulation. The maximum effect (E(max)) and TOF ratio at each point of twitch depression after cumulative doses of dantrolene were measured mechanomyographically. The EC(50) and EC(95) of dantrolene were calculated using an inhibitory sigmoid E(max) model. The reversal effect to E(max) after administration of 10 mM of dantrolene was determined by various doses of neostigmine, pyridostigmine or 4-aminopyridine respectively. RESULTS: The E(max) was 76.14% of the initial twitch tension, but the residual twitch tension was remained until five times (10 mM) of the dose for the E(max) was administered. TOF stimulation to the residual twitch tension did not demonstrate any fade. The EC(50) and EC(95) of dantrolene were 0.379 and 3.177 mM respectively. Neostigmine and pyridostigmine produced a transient but incomplete recovery of twitch tension, which rapidly fell to the level of the twitch response before the drugs were given. However, 4-aminopyridine produced a dose-dependent recovery of the twitch response. The addition of neostigmine (0.5 mg/ml) or pyridostigmine (2.5 mg/ml) did not decrease the EC(50) and EC(95) of 4-aminopyridine in reversing the effect of dantrolene. CONCLUSIONS: These RESULTS have demonstrated the evidence that dantrolene did not completely depress the twitch tension, leaving if at nearly 25%, and accompanying TOF response without fade, and that anticholinesterases were ineffective in antagonizing its blockade. However, 4-aminopyridine was effective and may not be related to the propensity for pre- and postjunctional cholinergic receptor blockade at the neuromuscular junction.

Administration of Atracurium in a Patient Recovering from Organophosphate Poisoning / 대한마취과학회지

A 67-year-old woman accidentally ingested insecticide 3 months ago and received ventilator care for 1 month. Thereafter, she developed tracheal stenosis combined with a tracheal-esophageal fistula, and she was scheduled to receive a tracheal resection anastomosis. We anesthetized her with atracurium under the monitoring of an accelerograph and she did not represent any prolonged respiratory paralysis postoperatively. We administered atracurium 10 mg twice initially and then gave additional 5 mg boluses when the TOF ratio became greater than 0.5. The total dose of administered atracurium was 40 mg and total duration of anesthesia was 360 minutes. We did not extubate her in the operating room in spite of complete recovery from atracurium to preoperative status because her lung condition was not very good preoperatively and severe necK flexion was done for the anastomosis. In the intensive care unit, the patient's condition progressively deteriorated with the development of adult respiratory distress syndrome and acute renal failure. Despite vigorous organ specific support, she discharged hopelessly 24 days after the operation.

Effects of Mivacurium in the Strips of Rat Thoracic Aortic Rings / 대한마취과학회지

BACKGROUND: The hypotensive effects of muscle relaxants has traditionally been associated with a ganglion block and histamine release. However, it was exhibited that the ability of certain analogues of the steroidal muscle relaxant directly caused relaxation of isolated vascular smooth muscles. The ability of mivacurium to elicit a direct relaxant effect on vascular smooth muscle has been studied using isolated rat thoracic aortic rings contracted with phenylephrine (PE). METHODS: Each ring of the thoracic aorta was suspended on wire supports in a 20 ml tissue bath under 2 gm of resting tension. All tissues were bathed in a Tris Tyrode solution at 37oC and 100% oxygen was supplied. RESULTS: Mivacurium 3 X 10 5 M and 10 3 M inhibited PE induced contractions of the aortic rings significantly (P < 0.05) and shifted the cumulative concentration-effect curves of PE to the right. The maximum contractile response from 81.9% to 55.0% (with PE 10 6 M) was the same as that seen with mivacurium 10 3 M pretreatment. Relaxation of aortic ring with mivacurium 10 3 M was not reversed with L-NAME pretreatment. Methylene blue reversed the relaxation of the aortic rings with mivacurium 10 3 M and shifted the cumulative concentration-effect curve of PE to the left. Indomethacine enhanced the relaxation of the aortic rings with mivacurium 10 3 M and shifted this curve to the right. Mivacurium 10 3 M inhibited the influx of extracellular Ca2+. CONCLUSIONS: The results suggest that the relaxation effects of mivacurium is related with the endothelium and at least, in part, cyclooxygenase inhibition and guanylate cyclase activation are related with this relaxation effect. Also, mivacurium inhibited extracelluar calcium influx.

Rocuronium and Lidocaine Pretreatment for Prevention of Biochemical Changes, Fasciculations and Myalgia following Succinylcholine Administration / 대한마취과학회지

BACKGROUND: The purpose of this study was to assess the changes in serum potassium and creatine kinase concentrations and the incidence of fasciculations and myalgia when rocuronium and lidocaine were used in combination and separately as pretreatment before succinylcholine. METHODS: We studied 60 patients undergoing a minor elective surgery, in a prospective double blinded method. Three groups each with 20 patients were pretreated before a 1.5 mg/kg succinylcholine administration with 0.05 mg/kg rocuronium three min before (group R), 1.5 mg/kg lidocaine 30 sec before (group L), or both rocuronium and lidocaine (group RL). Serum potassium and creatine kinase were respectively measured 5 min after succinylcholine administration and 24 h after the operation. Fasciculations and myalgia on postoperative day 1 and day 2 were evaluated. RESULTS: The increase in creatine kinase and incidence of myalgia on postoperative day 1 was less in the RL group than in the R group and L group. The incidence of fasciculations was higher in the L group than in the R group and RL group. There was no increase in serum potassium in any group. CONCLUSIONS: The combined use of rocuronium and lidocaine was more effective in reducing creatine kinase and postoperative myalgia than when they were used separately. However, the fasciculations were only reduced by the use of rocuronium.

Evaluation of Presynaptic Action of Depolarizing Neuromuscular Blocking Agents with Single Twitch Response in Vitro / 대한마취과학회지

BACKGROUND: This study was performed to evaluate the presynaptic effects of depolarizing neuromuscular blocking drugs by using slow and fast frequencies of indirect stimulation on partial twitch depression in vitro. METHODS: A rat phrenic nerve hemidiaphragm was dissected and was mounted in an organ bath containing an oxygenated Krebs solution. The phrenic nerve was stimulated supramaximally and the twitch response (0.1 Hz) was stabilized for at least 30 minutes. T200/T1 ratio (twitch height of the 200th stimuli divided by that of the first stimuli) at frequencies of 0.2, 0.5, 1.0, and 2.0 Hz using a drug concentration which provided approximately 20% twitch depression at 0.1 Hz was calculated. To compare T200/T1 ratios with TOF ratios, a 2.0 Hz TOF response was measured immediately after the 200th stimuli at either frequency of stimulation. RESULTS: T200/T1 ratios produced by succinylcholine (SCC) and decamethonium (C10) were located between alpha-bungarotoxin (ABX) and hexamethonium (C6), however, significant differences among the four drugs were found at 2.0 Hz. The propensity for a decrease in T200/T1 ratios at 2.0 Hz might differ from this study: C6 > C10 > SCC > ABX. T200/T1 ratios at 2.0 Hz were not different from TOF ratios. CONCLUSIONS: It is concluded that small doses of C10 have a greater presynaptic activity than that of SCC, when the observed effects in this study were compared with the result of ABX acting predominantly at postsynaptic receptors and C6 acting predominantly at presynaptic receptors.

Effect of Duration of Lower Motor Neuron Injury on Mivacurium-induced Muscluar Relaxation in Rabbits / 대한마취과학회지

BACKGROUND: The purpose of this study was to investigate whether the effects of mivacurium on muscular relaxation were similar by the duration of more than 2 weeks after the injury of lower motor neurons in rabbits. METHODS: The animals were divided into five groups. The control group was without lower motor neuron injury. In the experimental groups, the lower motor neuron injury was made by denervating with 75 - 80% lesion on the common peroneal nerve to the right anterior tibialis muscle. The experimental groups were subdivided as 1, 2, 3 and 4 week groups (referred to ad the 1 wk, 2, 3 and 4 wks group) according to the durations of the denervation of common peroneal nerve, respectively. The dose-response relationship of mivacurium on the muscle twitches induced by TOF (train of four) stimulation (supramaximal stimulus of 0.2 ms duration, square-wave pulses, 2 Hz rate, repeated every 10 seconds) was studied by calculating ED50 and ED95 in the anterior tibialis muscles and compared between all groups. After recording the muscle twitches, microscopic findings were observed. RESULTS: The effective dose for 95% twitch depression (ED95) of mivacurium at 1week after denervation was significantly higher than that of the control group (P <0.05), but the ED95 of 2, 3 and 4wks groups were not significantly different from that of the control group. However, the ED95 of 3 and 4wks group were inclined to be lower than that of the control and significantly lower than 1wk group (P < 0.05). There was no significant difference in the effective dose for 50% twitch depression (ED50) of mivacurium in all groups. The size of the anterior tibialis muscle was significantly decreased at 4weeks after the lower motor neuron injury (P <0.05), but the number of its sarcoplasmic nuclei was increased, according to the duration after the denervation. CONCLUSIONS: Our results therefore suggest that neuromuscular response of denervated anterior tibial muscle was resistant to intravenous mivacurium in early periods of 1 or 2 weeks but sensitive 4 weeks after the lower motor neuron injury.

The Effect of 4-Aminopyridine with Anticholinesterases on MgSO4-Rocuronium-Induced Neuromuscular Blockade in Vitro / 대한마취과학회지

BACKGROUND: The aim of this study was to evaluate the effect of 4-aminopyridine (4-AP) combined with anticholiesterase (antiChE) in antagonizing MgSO4-rocuronium-induced neuromuscualr blockade using a rat hemidiaphragm. METHODS: A hemidiaphragm with phrenic nerve was dissected and was mounted in a bath containing oxygenated Krebs solution. The phrenic nerve was stimulated supramaximally and the twitch response (0.1 Hz) was stabilized for at least 30 minutes. After maximal twitch inhibition by IC95 (concentration of 95% twitch inhibition) of rocuronium and MgSO4 20 mg was achieved, antagonistic effects of 1.6, 16 microgram/ml of edrophonium, 0.1, 1.0 microgram/ml of neostigmine, 0.5, 5.0 microgram/ml of pyridostigmine, and 0.8 microgram/ml of 4-AP combined with each of the above mentioned antiChEs were investigated. RESULTS: Whereas antiChE alone at low concentration partially recovered only the twitch response, 4-AP combined with antiChE recovered both the twitch and train-of-four responses significantly. CONCLUSIONS: 4-AP enhances antagonism of a magnesium-rocuronium induced neuromuscular blockade by edrophonium, neostigmine or pyridostigmine in vitro.

Does Perioperative Monitoring of the Train-of-Four Response Influence the Frequency of Postoperative Residual Curarization in Propofol Anesthesia? / 대한마취과학회지

BACKGROUND: Sometimes hypoxemia occurs in the postoperative recovery room because of postoperative residual curarization (PORC). Some reports show that postoperative residual curarization is common. PORC occurs after the use of the long-acting muscle relaxants. It has been recommended to use intermediate-acting muscle relaxants and a TOF monitor to decrease PORC. The purpose of this study was to examine whether the use of the TOF monitor during propofol anesthesia affects the incidence of postoperative residual curarization. METHODS: 38 ASA I or II patients were divided randomly into two groups of 19 each. They received propofol-fentanyl-nitrous oxide for anesthesia. Pancuronium (80 100 microgram/kg) was used to facilitate tracheal intubation and additional doses were used to maintain surgical relaxation. The requirement for incremental doses of pancuronium and adequacy of recovery following reversal were assessed, either with (control group:n = 19) or without (experimental group:n = 19) TOF monitoring. Fifteen minutes after the arrival at the recovery room, neuromuscular function was assessed clinically and by using TOF. RESULTS: There were no statistical differences in body weight, age, or duration of operation between the two groups. There was no statistical difference in the total dose of pancuronium and total dose of pancuronium relative to body weight and duration of operation. There were statistical differences in TOF ratio in the recovery room (0.73 vs. 0.86). The incidence of PORC was 47% in the control group and 5% in the experimental group. CONCLUSIONS: Though the monitoring of TOF did not effect the dose of muscle relaxant, it may have reduced the incidence of PORC. However, the PORC had no clinical significance because the mean TOF ratio in the two groups was over 0.7 and there were no clinical signs of residual muscle weakness.

Appropriateness of Administering Rapid Tracheal Intubation with Rocuronium Using the Timing Principle / 대한마취과학회지

BACKGROUND: The "timing principle" utilises a single bolus of nondepolarizing neuromuscular blocking drug followed by an induction drug at the onset of clinical weakness. The purpose of this study was to compare the intubating conditions after succinylcholine or rocuronium and after rocuronium using the timing principle. METHODS: Forty patients were randomly allocated into four groups. Patients in group I received rocuronium 0.6 mg/kg using the timing principle. At the onset of clinical weakness, anesthesia was induced with the thiopental 4-5 mg/kg. Patients in group II, III, and IV received rocuronium 0.6, 0.9 mg/kg, and succinylcholine 1.5 mg/kg respectively using the usual technique. The trachea were intubated 60 s after thiopental induction. Accelerographic response to train-of-four (TOF) stimulation of the ulnar nerve was used for neuromuscular monitoring. Intubating conditions were assessed according to a grading scale. RESULTS: The twitch depression immediately before tracheal intubation in group I, II, III, and IV were 14.5, 28.2, 11.1, and 6.8%, respectively. The TOF count showed no significant differences between groups. The duration of action in group III (45.3 +/- 12.1 min) was significantly prolonged compared to that in group I (31.2 +/- 6.4 min). Intubation conditions were either good or exellent in all patients except one in group II. In group I, three patients recalled shortness of breath or general weakness. CONCLUSIONS: It is concluded that the use of rocuronium 2 X ED95 using the timing principle did not provide additional benefits compared to rocuronium 3 X ED95 using the usual technique except in duration.

The Effect of Mivacurium on Onset and Recovery According to the Durations of Lower Motor Neuron Injury / 대한마취과학회지

BACKGROUND: The purpose of this study was to investigate whether the effects of mivacurium on onset and recovery were affected by the duration of more than 2 weeks after injury of the lower motor neuron in rabbits. METHODS: The animals were divided into five groups. The control group was without lower motor neuron injury. In the experimental groups, the lower motor neuron injury was made by denervating with a 75 - 80% lesion on the common peroneal nerve to the right anterior tibialis muscle. The experimental groups were subdivided as 1, 2, 3 and 4 week groups (named group 1 wk, 2, 3 and 4 wks) according to the duration of the denervation of the common peroneal nerve. The response relationship of mivacurium on the muscle twitches induced by TOF (train of four) stimulation (supramaximal stimulus of 0.2 ms duration, square-wave pulses, 2 Hz rate and 10 mA, repeated every 10 seconds) was studied in the anterior tibialis muscles and compared between all groups. Neuromuscular responses (onset, recovery time to T1(1), T1(25), T1(75), T1(95) and recovery index) of muscle twitches to intravenous mivacurium (0.18 mg/kg) were studied. After recording the muscle twitches, macroscopic findings were observed. RESULTS: The recovery time, T1(1) of group 4 wks was significantly longer than those of group 1, 2 and 3 wks (P < 0.05), but not different from the control group. The recovery time, T1(25), T1(75) and T1(95) of group 4 wks was significantly longer than those of all other groups (P < 0.05), but the onset times of all groups were not significantly different. The recovery index of group 4 wks was significantly higher than that of the control group (P < 0.05), but those of groups 1, 2 and 3 wks were not significantly different from that of the control group. The mass of the anterior tibialis muscle was significantly decreased at 4 weeks after the lower motor neuron injury (P < 0.05). CONCLUSIONS: Our results therefore suggest that the neuromuscular response to intravenous mivacurium on recovery in rabbits becomes prolonged according to the durations of the denervation and represents sensitivity at 4 weeks after the lower motor neuron injury.

Effects of Pseudocholinesterase and/or Neostigmine, Pyridostigmine, Edrophonium and Galanthamine for Reversal of Mivacurium- or Succinylcholine-induced Paralysis in Vitro / 대한마취과학회지

BACKGROUND: The hydrolysis of mivacurium and succinylcholine is impaired in the presence of defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium- or succinylcholine-induced paralysis. In this study, the role of exogenous bovine pseudocholinesterases (BpChE) and/or neostigmine, pyridostigmine, edrophonium or galanthamine in the reversal of mivacurium- or succinylcholine-induced paralysis, were investigated with the rat phrenic nerve-diaphragm preparation. METHODS: Ninety five Sprague-Dawley rats (200 g, male) were divided into 14 groups (n = 10). The phrenic nerve-diaphragm preparation mounted in a bath containing oxygenated Krebs' solution. Twitch response from diaphragmatic muscle evoked by phrenic nerve stimulation were measured. After stabilization of the twitch responses, mivacurium (0.1 microgram/mlml) or succinylcholine (0.1 microgram/ml) was administered incrementally in the preparation to obtain more than 95% twitch inhibition. BpChE (0.1, 1.0 u/ml), and/or neostigmine (0.1, 1.0 microgram/ml), pyridostigmine (0.5, 5 microgram/ml), edrophonium (0.01, 0.1 microgram/ml) or galanthamine (0.1, 1.0 microgram/ml) were added for the reversal of mivacurium- and/or succinylcholine-induced block in each group and the twitch responses (0.1 Hz) were monitored for 60 min. The effect of BpChE (0.1 u/ml), in combination with each of the above four anticholinesterases at lower concentrations also were examined. Twitch heights more than 75% was considered an adequatereversal. RESULTS: BpChE 0.1 and 1.0 u/ml were effective in reversal of mivacurium-induced paralysis. When anticholinestrases were added, there was no effective improvement of twitch height at the end of 60 minutes. In succinylcholine-induced paralysis, BpChE was effective for reversal, but when anticholinesterases were added, BpChE potency was inhibited. CONCLUSIONS: BpChE will reverse mivacurium-induced block more effectively than anticholinesterase. BpChE is effective in reversing succinylcholine block. The addition of anticholinesterases inhibits the activity of pseudocholinesterase.

Neuromuscular Blocking and Vagolytic Effects of Atracurium, Cisatracurium, and Mivacurium in the Anesthetized Cat / 대한마취과학회지

BACKGROUND: Atracurium is a benzylisoquinolium nondepolarizing neuromuscular blocking drug. It releases histamine upon the rapid administration of more than 2 x ED95. Cisatracurium is about three to four times more potent than atracurium, less likely to release histamine, and has weaker cardiovascular or autonomic effects. Mivacurium releases histamine to about the same degree as atracurium at the same dose. This study was undertaken to reevaluate the experimental model for the evaluation of effects on the autonomic nervous system, and to determine the neuromuscular blocking profiles and the vagolytic effects of atracurium, cisatracurium and mivacurium in cats. METHODS: Cats, either sex, anesthetized with pentobarbital, were used. Neuromuscular blocking effects were assessed using the effects on the anterior tibialis muscle twitch evoked with supramaximal stimuli (0.2 ms-duration, 0.1 Hz). Inhibition of the parasympathetic nervous system was assessed in response to bradycardia to vagal nerve stimulation with ten-second trains of square-waves (0.5 ms-duration, 20 Hz). The dose-response curves for both neuromuscular blocking and vagolytic actions were determined for each animal. The dose-response curves were constructed in cumulative fashion. The response for vagal stimuli was measured two minute after each dosing. Vagal ID50 (The doses that produced 50% inhibition of the response to vagus nerve stimulation) were determined. RESULTS: NMB ED95 and NMB ED50, respectively, were 102.0 +/- 28.3 and 143.7 +/- 40.5 microgram/kg for atracurium, 81.4 +/- 13.3 and 110.7 +/- 18.8 microgram/kg for cisatracurium, and 56.8 +/- 17.4 and 74.2 +/- 25.0 microgram/kg for mivacurium. Vagal ID50 was 2,654 +/- 1,651 microgram/kg for atracurium, 655 +/- 389 microgram/kg for cisatracurium, and 606 +/- 182 microgram/kg for mivacurium. The vagal ID50/NMB ED95 and vagal ID50/NMB ED50 were 18.5 and 26.0 for atracurium, 5.9 and 8.1 for cisatracurium, and 8.2 and 10.7 for mivacurium. CONCLUSIONS: Atracurium has a wider margin of safety only for vagal stimulation as compared with cisatracurium and mivacurium. However, we couldn't exclude that either sympathetic stimulation or histamine release might contribute to heart rate.

The Effects of Succinylcholine on the Neuromuscular Block of Mivacurium / 대한마취과학회지

BACKGROUND: We studied the interaction between Succinylcholine (SCh) and mivacurium when mivacurium was administered during early and late recovery from SCh block was investigated. METHODS: Eighty patients undergoing elective surgery under general anesthesia were studied. General anesthesia was induced and maintained with propofol under TCI control. Neuromuscular function was measured in response to TOF stimulation of the ulnar nerve using an electromyographic method. The patients were allocated randomly to the following four groups; group 1 (n = 20): a bolus intravenous injection of 0.08 mg/kg mivacurium; group 2 (n = 20): intravenous injection of 0.08 mg/kg mivacurium after 2 minutes of 1 mg/kg SCh injection; group 3 (n = 20): intravenous injection of 0.08 mg/kg mivacurium after 25% recovery of initial twitch height from twitch height depression induced by 1 mg/kg SCh; group 4 (n = 20): intravenous injection of 0.08 mg/kg mivacurium after 75% recovery of initial twitch height from twitch height depression induced by 1 mg/kg SCh. The onset and duration of neuromuscular blockade, recovery rate and TOF ratio at T75% were measured. RESULTS: The onset of block in groups 3 and 4 were slower than in group 1 (5.2 +/- 0.7 and 2.3 +/- 0.6 vs 2.5 +/- 0.4 min P < 0.05). The clinical duration in groups 2 and 3 were longer than in groups 1 and 4 (12.5 +/- 2.1 min and 11.3 +/- 1.7 min vs 17.0 +/- 3.0 min and 18.5 +/- 2.6 min, p < 0.05). There was no difference in recovery index all groups. The TOF ratio of groups 2, 3 and 4 were smaller than for group 1 (38.2 +/- 5.3, 32.3 +/- 5.6 and 31.5 +/- 4.2 vs 56.0 +/- 7.3, P < 0.05). CONCLUSIONS: The Previous 1 mg/kg SCh injection was affected the time course of action of mivacurium 0.08 mg/kg-induced neuromuscular block.

Effect of Additional Lidocaine on the Onset Time of Vecuronium / 대한마취과학회지

BACKGROUND: Local anesthetics have been shown to interact with neuromuscular blockers. Most local anesthetics decrease neuromuscular transmission and potentiate neuromuscular block from muscle relaxants. The purpose of this study was to examine the effectiveness of lidocaine on the onset time of vecuronium and to compare that with other method such as simply increasing the dose of vecuronium. METHODS: Sixty patients of ASA physical status I or II were induced with thiopental (4-5 mg/kg) and maintained with O2-enflurane (2.5 vol%). They were randomly divided into four groups: Vecuronium (0.1 mg/kg) was administered intravenously in Group C (n = 15), additional lidocaine (1 mg/kg) was given intravenously 1 min prior to administration of vecuronium in Group L (n = 15), increased vecuronium (0.15 mg/kg) was given in Group V (n = 15) and succinylcholine was given in Group S (n = 15), respectively. Neuromuscular blockade was assessed by train-of-four (TOF) at the adductor pollicis muscle with supramaximal stimulation of ulnar nerve (2 Hz, 0.2 ms) every 12 sec. Endotracheal intubation was performed and intubating conditions were evaluated according to the standard scoring method after measuring the onset time (from the end of giving each muscle relaxants to the 90% suppression of the first twitch). RESULTS: The onset time of Group L (122.0+/-11.0 sec) and that of Group V (98.0+/-16.9 sec) were shorter than that of Group C (135.2+/-16.0 sec) (P<0.05), but these were not shorter than that of Group S (42.0+/-6.2 sec). There was no statistical difference between Group L and Group V. Intubating conditions were good or excellent in all groups. CONCLUSIONS: Additional lidocaine for attenuating sympathetic response could accelerate the onset of vecuronium. But the onset time of this method was not shorter than that of simply increasing the dose of vecuroium nor that of succinylcholine.

Prader-Willi Syndrome: A case report / 대한마취과학회지

In 1956, Prader and Willi first described a clinical syndrome that included severe neonatal hypotonia, hyperphagia, obesity, diabetes, hypogonadism, cryptorchidism, dental caries and mental deficiency. We have anesthetized a male patient who had Prader-Willi syndrome. He suffered for both pyoknee. General anesthesia was performed using N2O-O2-isoflurane. During induction and maintenance of anesthesia, we focused on the airway management, hypotonia, abnormal glucose metabolism, protection of aspiration and cardiovascular stabilization. Emergence of anesthesia was unremarkable. But he was expired from sepsis on the fourth postoperative day.

Anesthetic Management with Mivacurium in the Myasthenic Patients: Two cases / 대한마취과학회지

We have used mivacurium in two myasthenic patients, a generalized myasthenia gravis (MG) patient presenting for thymectomy and a Lambert-Eaton myasthenic (LEM) patient for mediastinoscopic lymph node biopsy. Both of them received nitrous oxide/oxygen (1:1)-narcotic-enflurane anesthesia with mivacurium as a muscle relaxant and the neuromuscular blocking effect of mivacurium was monitored continuously through the operation as well as before the induction of anesthesia. The dose of mivacurium for MG patient was 5.5 mg and LEM patient was 12 mg, because MG patient showed more severe clinical symptoms. The response to train-of-four (TOF) ulnar nerve stimulation was recorded using accelography. The onset times to maximal block in MG and LEM patients were 30 and 120 sec, respectively after injection and the recovery times to 25% from maximal block were 117 and 76 min, respectively. Mivacrium would be safe and appropriate for use in myasthenic patients, with relatively small dose under the neuromuscular monitoring.

The Effects of Vecuronium and Pancuronium on the Tension of the Isolated Rat Tracheal Smooth Muscle / 대한마취과학회지

BACKGROUND: Non-depolarizing muscle relaxants have their muscle relaxing effect by competing with acetylcholine (ACh) at the nicotinic receptor level. What are the effects of such muscle relaxants on the tracheal smooth muscle? This present study was set up to address the question as to how vecuronium and pancuronium influence the tracheal smooth muscle. METHODS: Sixty male Sprague-Dawley rat tracheal smooth muscles were isolated at optimal length for isometric force. The preparations were set up in an organ bath containing Tyrode's solution. And isometric force displacement transducer and physiograph were used to record the change in force. After the equilibration period the preparations were contracted with ACh 10(-5) M and carbachol 3x10(-7)M seperately. The preparations were washed with fresh tyrode's solution and allowed to return passively to resting tone. Then the cumulartive effect of ACh (from 3 10(-7) M through 10(-5) M) and carbachol (CCh, from 10(-8) M through 3 10(-6) M) were produced before and after pretreating the preparation with vecuronium (10(-5) M and 10(-6) M) and pancuronium (10(-5) M and 10(-6) M) respectively. Also, we studied the changes of contraction produced by neostigmine before and after pretreatment with vecuronium (10(-5) M and 3 10(-5) M) and pancuronium (3 10(-6) M and 3 10(-5) M). RESULTS: Vecuronium shifted the ACh dose-response curve of the tracheal contraction to the left (p0.05). CONCLUSIONS: Vecuronium inhibits the ACh hydrolyzing enzyme, especially acetylcholinesterase. Therefore it potentiates ACh contraction in the tracheal smooth muscle, but not the CCh contraction, while pancuronium has a different effect in comparison with vecuronium. That is, at a low concentration it reveals an antagonistic effect on the muscarinic M2 receptor and at a higher concentration it has an antagonistic effect on the muscarinic M3 receptor in the tracheal smooth muscle.