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Background: We evaluated the pharmacodynamic and pharmacokinetic properties of rapacuronium, a new non-depolarizing muscle relaxant. Methods: The and 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 weremeasured. Results: By in vitro study, the and 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 A 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 (5.0/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.

Background: Ondansetron, a receptor antagonist, is widely used for the prevention of postoperative nausea and vomiting. However, the interaction of ondansetron with non-depolarizing muscle relaxants have not been reported until now. Therefore we studied the effects of ondansetron on the neuromuscular block of vecuronium, rocuronium or atracurium in vitro. Methods: A square wave 0.1 Hz supramaximal stimuli was applied to the phrenic nerve-hemidiaphragm preparation of a rat, and the twitch height response was recorded mechanomyographically. We measured cumulative concentration response curves of vecuronium, rocuronium or atracurium alone and after pretreating with ondansetron (1/ml). We also measured the effects of ondansetron. The 's and EC's of these muscle relaxants alone and after pretreatment with ondansetron were calculated using an inhibitory sigmoid Emax model. Results: Ondansetron depressed the twitch height in a dose-dependent manner, and its potency was lower than the muscle relaxants. The and of ondansetron were 14.7/ml and 33.4/ml, respectively. Pretreated ondansetron (1/ml) significantly reduced the EC's and EC's of vecuronium, rocuronium and atracurium (P

Background: MacFarlane and Rosenthal reported a case of acute quadriplegia after nondepolarizing muscular blocking agents in status asthmaticus patient treated with high doses of corticosteroid. Reports regarding the reactions of glucocorticoid treated muscles to neuromuscular blocking agents are sparse and inconsistent. The aims of this study were to examine the degree of muscle atrophy and its effects on sensitivity to neuromuscular blocking agents in relation to the dose and duration of dexamethasone. Methods: Sixty Sprague-Dawley rats were divided into six groups. They were treated daily with dexamethasone 0.4 mg/kg and 4 mg/kg daily for 1 week or 3 weeks. The two control groups were treated with normal saline. The day after treatment, the dose-response curves of vecuronium were measured using a phrenic nerve-hemidiaphragm preparation. To classify muscle fiber, the diaphragm was stained for myofibrillar adenosine triphosphatase after alkaline and acid preincubation, and a morphometric examination was carried out. Results: The diaphragmatic muscle in rats treated with long term, high dose dexamethasone showed significant atrophy. For the short term, low dose dexamethasone group, the ED50 and ED95 of vecuronium decreased 41.5% and 26.8% compared to those of the control group, respectively (P ＜ 0.05). However, the ED50 of vecuronium in the long term, high dose dexamethasone group increased 22.2% compared to that of the control group (P ＜ 0.05). Conclusion: This study suggests that sensitiviy to vecuronium was not modulated by dexamethasone-induced muscle atrophy. Quantitative changes of receptors at the neuromuscular junction or some anoother process might be responsible for this change.

Background: β-Bungarotoxin irreversibly changes the presynaptic membrane, hexamethonium acts on the presynaptic nicotinic receptor, and verapamil blocks the ion channels on the presynaptic membrane. The effect of these drugs on twitch height and train of four (TOF) ratio were investigated, as well as the reversal effects of neostigmine, pyridostigmine or 4-aminopyridine (4-AP) on the partial neuromuscular blockade induced by these drugs. Methods: Square wave, 0.1 Hz supramaximal stimuli or 2 Hz, 0.2 ms train of four stimuli, was applied to the phrenic nerve-hemidiaphragm preparation of the rat, and the twitch height response was recorded mechanomyographically. The cumulative concentration effects and TOF ratios at each point of twitch depression after β-bungarotoxin, hexamethonium or verapamil were measured. TOF ratios were observed at 75, 50 and 25% of the control twitch height value during observation of the concentration effect. The EC50 and EC95 of β-bungarotoxin, hexamethonium or verapamil were calculated using an inhibitory sigmoid Emax model. The reversal effect of some doses of neostigmine, pyridostigmine or 4-aminopyridine to the partial neuromuscular block produced by EC50 of βbungarotoxin, hexamethonium or verapamil was determined. Results: The EC50 and EC95 of β-bungarotoxin, hexamethonium and verapamil were 0.0695 and 0.1160μg/ml, 1267.0 and 2033.5μg/ml and 29.45 and 37.99μg/ml respectively. TOF fade was marked with hexamethonium or verapamil but small with β-bungarotoxin. Neostigmine or pyridostigmine did not reverse the partial neuromuscular block induced by β-bungarotoxin, hexamethonium or verapamil. However, 4-AP produced a dose-dependent recovery of the twitch response (P < 0.05). Conclusions: β-Bungarotoxin, hexamethonium and verapamil produced different degree of TOF fade, and this may be due to different sites of action of these drugs. 4-AP reversed effectively the partial

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 α-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. (Korean J Anesthesiol 2001; 40: 532∼537) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Background: Lidocaine, verapamil or a lidocaine-verapamil mixture was effectively applied for blunting extubation during recovery from anesthesia. However, these drugs can enhance neuromuscular blockade and cardiovascular depression. We investigated the neuromuscular and the cardiovascular effect of lidocaine, verapamil or a lidocaine-verapamil mixture before extubation in the recovery from anesthesia. Methods: We studied ninety nine healthy adult patients (ASA class I or II), excluding the patients with cardiovascular diseases and with factors affecting neuromuscular function. Induction of anesthesia was performed with thiopental sodium 5 mg/kg and fentanyl 0.1 mg, and maintained with O2-N2O (50%)-enflurane (2%). Supramaximal single twitch stimuli (0.1 Hz) were applied to the ulnar nerve and the twitch response of the adductor pollicis was recorded by the Gould TA 240 recorder via a 2 kg Load Cell Strain Gauge modification. After stabilization of the twitch response, mivacurium (0.16 mg/kg) or vecuronium (0.1 mg/kg) was administered intravenously and endotracheal intubation was performed. Twitch heights were spontaneously recovered without a reversal agent from the neuromuscular blockade as a spontaneous group. Pyridostigmine 10 mg and glycopyrrolate 0.2 mg were administered intravenously around the time of 10% recovery of baseline twitch height as a reversal recovery group. At the time of 100% recovery of twitch height, train of four (TOF) stimuli was applied and then lidocaine, verapamil or a lidocaine-verapamil mixture was administered intravenously in both groups. Maximum depression of twitch height and the TOF ratio at this point, recovery index (RI) measured, and mean arterial pressure and pulse rates were measured before and at 2, 5, 10, 20 and 30 min. after the lidocaine-verapamil mixture administration. Results: Twitch heights were depressed slightly after lidocaine, verapamil or a lidocaine-verapamil mixture administration; however, there were no significant differences to compare with the control. TOF

Background: Interactions of neuromuscular blocking agents are antagonistic in a combination of depolarizing and nondepolarizing agents, additive in a combination of relative two compounds or synergistic in a combination of different two nondepolarizing agents. However, the interactions of neuromuscular blocking agents with a different site of action from each other have not been studied clearly. This study was designed to examine the interaction between hexamethonium and lidocaine, α-bungarotoxin or decamethonium with markedly different pre and postsynaptic sites of action. Methods: Square wave, 0.1 Hz supramaximal stimuli or 2 Hz, 0.2 ms train of four (TOF) stimuli, was applied to the rat phrenic nerve-hemidiaphragm preparation, and the twitch height response was recorded mechanomyographically. The cumulative concentration effect and TOF ratio at each point of twitch depression after hexamethonium, lidocaine, α-bungarotoxin or decamethonium given were measured. The EC50 and EC95 of hexamethonium, lidocaine, α-bungarotoxin and decamethonium were calculated using an inhibitory sigmoid E model. In the experiment of each combination of two drugs, three points of the isobole for hexamethonium-lidocaine, hexamethonium-α-bungarotoxin and hexamethonium-decamethonium were established using ratios of 1: 3, 1: 1 and 3: 1 of their EC50. Points on the line of theoretical additivity and 95% canfidence intervals were calculated according to Tallarida et al. TOF ratios were observed at 75, 50 and 25% of the control twitch height value during each combination ratio of their EC50. Results: Significant deviations of points on the isobole from the line of additivity to the left were found at all EC50 ratios of hexamethonium-lidocaine (P

Background: α-Bungarotoxin, decamethonium or lidocaine has a neuromuscular blocking effect. The aim of this study was to evaluate the pharmacodynamic properties of these drugs at the neuromuscular junction and the reversal effects of antagonists in vitro. Methods: The effects of evoked twitch tension response have been studied on the isolated phrenic nerve hemidiaphragm preparation of the rat, using a single twitch (0.1 Hz) and the train of four (TOF; 2 Hz for 2 s) stimulation. The cumulative concentration effect and TOF ratio at each point of twitch depression after α-bungarotoxin, decamethonium or lidocaine were measured mechanomyographically. The EC50 and EC95 of α-bungarotoxin, decamethonium or lidocaine were calculated using an inhibitory sigmoid Emax model. The reversal effects of various doses of neostigmine, pyridostigmine or 4-aminopyridine (4-AP) to the partial neuromuscula r block produced by EC50 of α-bungarotoxin, decamethonium or lidocaine were determined. Results: The EC50 and EC95 of α-bungarotoxin, decamethonium or lidocaine were 0.179 and 0.320μg/ml, 17.07 and 26.84μg/ml or 76.80 and 105.70μg/ml. TOF fade was produced by α-bungarotoxin or decamethonium but not by lidocaine. Neostigmine or pyridostigmine did not reverse the partial neuromuscular block induced by α-bungarotoxin, decamethonium or lidocaine. However, 4-AP produced a dose-dependent recovery of the twitch response (P < 0.05). Conclusions: α-Bungarotoxin, decamethonium or lidocaine produced different degree of TOF fade, and it means that this may be due to different site of action of these drugs. 4-AP reversed effectively the partial neuromuscular block induced by α-bungarotoxin, decamethonium or lidocaine, whereas neostigmine or pyridostigmine did not. (Korean J Anesthesiol 2001; 40: 763∼772) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Background : Magnesium sulfate (MgSO4) is widely used in the treatment of preeclamptic Hyperreflexia. Eclamptic convulsions are almost always prevented by MgSO4 in plasma concentrations of 4 to 7 mEq/L. It is well known that MgSO4 enhances the effect of nondepolarizing neuromuscular blockade. But the onset time of rocuronium is not shortened by MgSO4. Methods : The effect of magnesium on the onset time of rocuronium-induced neuromuscular blockade was investigated in vitro rat phrenic nerve-hemidiaphragm preparation. The phrenic nerve-hemidiaphragm was dissected and suspended in an organ bath containing modified Krebs' solution and produced single twitch responses under 0.2 ms, 0.1 Hz, electrical stimulation. We added rocuronium until the twitch height decreased more than 95% of the initial level and determined a dose in 95% decrease twitch height as an effective concentration (EC95). After the administration of MgSO4, the onset time of neuromuscular blockade by rocuronium 1 × EC95, 1.5 × EC95, 2 × EC95 was compared with the onset time without MgSO4. Results : EC50 and EC95 of rocuronium was 0.178 and 1.10 mg/dl. After administration of MgSO4, the concentration of Mg2 in the organ bath was 4.38 mEq/L. The onset time of the neuromuscular blockade by 1 × EC95 rocuronium was significantly shortened, but in the case of over 1.5 × EC95, it was not influenced by MgSO4. Conclusions : The concentration of Mg2 was within the therapeutic range for inhibition of uterine contraction. The onset time of rocuronium-induced neuromuscular blockade was shortened by magnesium but because a high dose of rocuronium was administered for intubation due to low potency and high plasma concentration, the effect of magnesium on the onset time of rocuronium seems to be masked. Therefore clinically, the onset time of rocuronium-induced neuromuscular blockade was not shortened by MgSO4. (Korean J Anesthesiol 1999; 37: 467∼471)

Background : This study was designed to determine whether presynaptic receptor blockade could be differentiated from postsynaptic receptor blockade by examining the effect of increasing frequencies of indirect stimulation on partial twitch depression in vitro rat phrenic nerve hemidiaphragm preparations. Methods: After isolating rat phrenic nerve hemidiaphragm preparation, T200/T1 ratio (twitch height of the 200th stimuli divided by that of the 1st 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, 2.0 Hz TOF response was measured immediately after 200th stimuli at either frequency of stimulation. Results : Hexamethonium caused a marked decrease in T200/T1 ratio at 0.5∼2.0 Hz of stimulation, whereas α-bungarotoxin caused no change in T200/T1 ratios at up to 2.0 Hz of stimulation. The T200/T1 ratios produced by d-tubocurarine, vecuronium, mivacurium, and rocuronium located intermediate between α-bungarotoxin and hexamethonium, however significant differences among four drugs were found at 2.0 Hz. The propensity for decrease in T200/T1 ratios at 2.0 Hz might differ from this study: hexamethonium ＞d-tubocurarine ＞rocuronium ＞mivacurium = vecuronium ＞α-bungarotoxin. T200/T1 ratios at 2.0 Hz were not different from TOF ratios. Conclusions : When the observed effects in this study were provided with result of α-bungarotoxin acting predominantly at postsynaptic receptors and hexamethonium acting predominantly at presynaptic receptors, the effects of nondepolarizing muscle relaxants at each binding site could be differentiated by examining the T200/T1 ratios at 2.0 Hz. (Korean J Anesthesiol 1998; 35: 831∼838)

Background: Esmolol is rapid hydrolyzed by plasma esterase but may inhibit plasma cholinesterase activity based on its structure. This study was designed to evaluate the interactions between esmolol and succinylcholine or mivacurium which are metabolized by plasma cholinesterase and to determine the inhibitory effect of esmolol on human plasma cholinesterase. Methods: Neuromuscular effects of succinylcholine (1.0 mg/kg) and mivacurium (0.15 mg/kg) with or without esmolol (0.5 mg/kg or 1.0 mg/kg) were compared in 57 adult patients (ASA class I) during O2-N2O-isoflurane anesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the hypothenar muscle resulting from supramaximal train of four stimuli applied to the ulnar nerve. Also plasma cholinesterase activity was measured before and 5, 10 minutes after injection of esmolol. Results: Time from injection to onset of over 95% block, clinical duration from injection to 25% recovery of control twitch, and recovery index defined as from 25% to 75% twitch recovery of succinylcholine or mivacurium were not altered by pretreatment of esmolol. Plasma cholinesterase activity was not decreased after injection of esmolol 0.5 mg/kg, but decreased by 5% after injection of 1.0 mg/kg (p＜0.05). Conclusions: It is unlikely that neuromuscular blocking effects of succinylcholine and mivacurium are prolonged by administration of clinical doses of esmolol (0.5∼1.0 mg/kg) due to inhibition of plasma cholinesterase activity in human. (Korean J Anesthesiol 1998; 35: 908∼913)

The neuromuscular and hem+odynamic effects of mivacurium 0.15 mg/kg and succinylcholine 1 mg/kg were compared in 26 adult patients (ASA I and II) during nitrous oxide-oxygen-propofol-fentanyl anesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the hypothenar muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of over 95% block and duration to 25% recovery of control twitch after injection of mivacurium were significantly longer than for succinylcholine (201 +/- 37.6 vs 54 +/- 5.2 sec and 13.0 +/- 2.2 vs 8.4 +/- 2.1 min; mean +/- SD). Onset of mivacurium with priming technique was shortened (125 +/- 20.7 sec), but was also slower than that of succinylcholine. Although the recovery index during spontaneous recovery was significantly longer for mivacurium than for succinylcholine (6.9 +/- 1.3 vs 5.1 +/- 0.9 min), antagonism with neostigmine at 25% recovery of twitch height sufficiently facilitated the recovery index of mivacurium (4.5 +/- 1.0 min) to a level similar to that of succinylcholine with no statistical difference. The hemodynamic effects of mivacurium were few as compared to those of succinylcholine. In conclusion, mivacurium is considered to have additional advantages for short procedures when succinylcholine is undesirable.

Neurologic deficits following spinal anesthesia are extremely rare since the use of sterile spinal anesthesia kit and the relative small doses of the local anesthetics employed. We have experienced 29 years old healthy female patient developed left S root radiculopathy with dysesthesia and motor weakness of left foot after spinal anesthesia for appendectomy. And the patient recovered spontaneously after 6 months without specific treatment except physical and symptomatic therapy.