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.

Effects of Dexamethasone on Neuromuscular Transmission in a Phrenic Nerve-Hemidiaphragm Preparation in the Rat / 대한마취과학회지

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.

Effects of Ondansetron on the Neuromuscular Block of Vecuronium, Rocuronium or Atracurium in a Rat Phrenic Nerve-Hemidiaphragm Preparation / 대한마취과학회지

BACKGROUND: Ondansetron, a 5-HT3 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 (1microgram/ml). We also measured the effects of ondansetron. The EC50's and EC90'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 EC50 and EC90 of ondansetron were 14.7microgram/ml and 33.4microgram/ml, respectively. Pretreated ondansetron (1microgram/ml) significantly reduced the EC50's and EC90's of vecuronium, rocuronium and atracurium (P<0.05). CONCLUSIONS: Ondansetron itself may have neuromuscular blocking properties, and it significantly enhances the neuromuscular blocks induced by vecuronium, rocuronium or atracurium.

Effects of Lidocaine, Verapamil and Their Mixture on Neuromuscular Blockade / 대한마취과학회지

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. TOFratios were unchanged after lidocaine, verapamil or lidocaine-verapamil administration compared at the 100% twitch height recovery. RI indices were not significant between groups in reversal recovery or in spontaneous recovery. Mean arterial pressure was reduced significantly until 20 min after a lidocaine-verapamil mixture administration, pulse rates were increased at 2 min only after a lidocaine- verapamil mixture administration. CONCLUSIONS: Twitch height and TOF ratios were not affected by clinical doses of lidocaine, verapamil or a lidocaine-verapamil mixture. However, mean arterial pressure and pulse rates were changed significantly by a lidocaine-verapamil mixture.

Neuromuscular Blocking Properties of alpha-Bungarotoxin, Decamethonium and Lidocaine in the Rat Phrenic Nerve-Hemidiaphragm Preparation / 대한마취과학회지

BACKGROUND: alpha-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 alpha-bungarotoxin, decamethonium or lidocaine were measured mechanomyographically. The EC50 and EC95 of alpha-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 alpha-bungarotoxin, decamethonium or lidocaine were determined. RESULTS: The EC50 and EC95 of alpha-bungarotoxin, decamethonium or lidocaine were 0.179 and 0.320 microgram/ml, 17.07 and 26.84 microgram/ml or 76.80 and 105.70 microgram/ml. TOF fade was produced by alpha-bungarotoxin or decamethonium but not by lidocaine. Neostigmine or pyridostigmine did not reverse the partial neuromuscular block induced by alpha-bungarotoxin, decamethonium or lidocaine. However, 4-AP produced a dose-dependent recovery of the twitch response (P < 0.05). CONCLUSIONS: alpha-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 alpha-bungarotoxin, decamethonium or lidocaine, whereas neostigmine or pyridostigmine did not.

Neuromuscular Blocking Properties of beta-Bungarotoxin, Hexamethonium and Verapamil in the Rat Phrenic Nerve-Hemidiaphragm Preparation / 대한마취과학회지

BACKGROUND: beta-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 beta-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 beta-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 beta- bungarotoxin, hexamethonium or verapamil was determined. RESULTS: The EC50 and EC95 of beta-bungarotoxin, hexamethonium and verapamil were 0.0695 and 0.1160 microgram/ml, 1267.0 and 2033.5 microgram/ml and 29.45 and 37.99 microgram/ml respectively. TOF fade was marked with hexamethonium or verapamil but small with beta-bungarotoxin. Neostigmine or pyridostigmine did not reverse the partial neuromuscular block induced by beta-bungarotoxin, hexamethonium or verapamil. However, 4-AP produced a dose-dependent recovery of the twitch response (P < 0.05). CONCLUSIONS: beta-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 partialneuromuscular block induced by beta-bungarotoxin, hexamethonium and verapamil, whereas, neostigmine and pyridostigmine did not.

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.

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.

Relaxant Effects of Thiopental, Ketamine, and Propofol on Isolated Rat Tracheal smooth Muscle / 대한마취과학회지

BACKGROUND: Intravenous anesthetics may modify airway responsiveness. The author investigated the relaxant effect of thiopental, ketamine, and propofol on isolated rat tracheal smooth muscles. METHODS: The trachea of the rat was dissected and cut into 3-mm rings. The rings were mounted in a water-jacked organ bath filled with Krebs solution aerated with 95% O2 and 5% CO2 at 37degreesC. Thiopental, ketamine, and propofol were given randomly to each ring preconstricted with EC50 of acetylcholine from 10(-6) to 10(-3) M. The relaxation response was the tension during anesthetic equilibration, expressed as a percentage of the tension from EC50 of acetylcholine. RESULTS: Thiopental and propofol (10(-5) to 10(-3) M) relaxed acetylcholine-induced contractions in a dose dependent manner (P < 0.05). Ketamine in doses of 10(-5) and 10(-4) M constricted acetylcholine-induced contractions by 3.2% and 16.5% respectively (P < 0.05). But ketamine in a dose of 10(-3) relaxed acetylcholine-induced contractions by 76.4% (P < 0.05). The relaxation of tracheal smooth muscles was greatest in thiopental, and was least in ketamine (P < 0.05). CONCLUSIONS: All three intravenous anesthetics have an excellent relaxation of tracheal smooth muscles in rats, except in doses of 10(-5) and 10(-4) M of ketamine.

Studies of Interaction between Hexamethonium and Lidocaine, alpha-Bungarotoxin or Decamethonium in Vitro / 대한마취과학회지

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, alpha-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, alpha-bungarotoxin or decamethonium given were measured. The EC50 and EC95 of hexamethonium, lidocaine, alpha-bungarotoxin and decamethonium were calculated using an inhibitory sigmoid Emax model. In the experiment of each combination of two drugs, three points of the isobole for hexamethonium-lidocaine, hexamethonium-alpha-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% confidence 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 < 0.05 respectively), that to the right was found at all EC50 ratios of a hexamethonium-alpha-bungarotoxin and hexamethonium-decamethonium (P < 0.05 respectively). The magnitude of TOF fade depended upon the mixed ratios for their EC50. CONCLUSIONS: The interaction was found to be synergistic in the combination of hexamethonium- lidocaine, and antagonistic in the combination of hexamethonium-alpha-bungarotoxin and hexamethonium- decamethonium.

Lidocaine and Verapamil Enhances Neuromuscular Block Induced by Rocuronium / 대한마취과학회지

BACKGROUND: Lidocaine or verapamil are used as an antiarrhythmic agent or agent blunting the cardiovascular changes induced by intubation or extubation during anesthesia. After recovery from general anesthesia with muscle relaxants, most patients remained in a residual paralytic state, hence it might develop easily recurarization by factors that affect neuromuscular transmission. Lidocaine and verapamil are well known as agents to potentiate the neuromuscular block. We investigated the effects of lidocaine or verapamil on neuromuscular transmission in vitro. METHODS: Square wave, 0.2 ms duration at a frequency of 0.1 Hz supramaximal or train of four stimuli was applied and the twitch height response was recorded mechanomyographically on rat phrenic nerve hemidiaphragm preparations. Dose responses of rocuronium, lidocaine, verapamil, rocuronium pretreated with lidocaine or verapamil, lidocaine pretreated with rocuronium, and verapamil pretreated with rocuronium were observed by cumulative method, and effective doses (Lag dose, ED50 and ED95) between a pretreated and nonpretreated agent were compared statistically. TOF ratios were observed at 80, 70, 40 and 30% of the control twitch height value during the observation of dose responses. RESULTS: Lag dose, ED50 and ED95 of rocuronium were reduced significantly after pretreatment of lidocaine, verapamil or their mixture, and the dose response of lidocaine, verapamil or their mixture were also reduced significantly by rocuronium pretreatment. TOF ratios at the point of each twitch height decreased significantly after pretreatment. CONCLUSIONS: Lidocaine or verapamil itself did not affect the neuromuscular transmission but might have potentiated the neuromuscular blocking effect induced by rocuronium. However, in excessive doses, these agents produced neuromuscular blockade. Consequently, in the residual neuromuscular block induced by rocuronium, lidocaine or verapamil may enhance recurarization.

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.

Comparative Study of Pharmacokinetics in the Onset and Offset of Mivacurium and Other Muscle Relaxants / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate mivacurium in the pharmacokinetics of onset and offset. METHODS: In 127 adult patients of ASA physical status I or II without any factors involving the neuromuscular function under general anesthesia, onset time (lag and manifest time) and clinical duration were measured after bolus or divided doses of ED95 x 2 of succinylcholine (SCC), rocuronium (ROC), atracurium (ATR), mivacurium (MIV), pancuronium (PAN) or vecuronium (VEC). Recovery time was defined as the recovery index and total duration measured after subsequent ED95 of MIV at 25% recovery of control twitch height from neuromuscular block induced by ED95 x 2 of ATR, MIV, PAN or VEC. Plasma cholinesterase (PChE) levels were measured following PAN or ATR. RESULTS: Onset time was faster with SCC and ROC, the low potency drugs, than with ATR, MIV, PAN or VEC, the high potent drugs. Manifest time was shorter in low potency drugs but longer in high potency drugs than lag time after bolus or divided doses of muscle relaxants given. Divided doses of various drugs induced a shortened onset time, but the patterns of relationship between lag and manifest time associated with drug potency did not alter. The recovery times with administered MIV were slowest after PAN pretreatment, and fastest after MIV pretreatment. PChE levels decreased significantly from 3 min to over 180 min after PAN administeration but not ATR. CONCLUSIONS: The onset time of MIV was not improved due to high drug potency as other nondepolarizing neuromuscular blockers. However, in spite of high potency, the recovery time of MIV was faster than other drugs. This results may be depend upon PChE activity rather than drug potency. Additionally, the prolonged recovery of MIV was not only under the influence of low PChE activity but also other some factors such as: the first relaxants administered before MIV dominated the neuromuscular block so that the duration of MIV given subsequently changed to resemble that of the first. The longer elimination half-life of the underlying relaxant prolonged the effects of subsequentshorter acting MIV. Structural similarities or dis-similarities between the interacting MIV and other drugs may have effects more potent in dis-similarity than in similarity.

The Correlation between Perception and Nociception Thresholds by Selected Current Stimuli in Adults / 대한마취과학회지

BACKGROUND: This study was designed to investigate the correlation between pain and non-pain sensation of the cutaneous nociceptors in healthy adults use 250 Hz and 5 Hz evoking neuroselective sinusoidal current to A delta and C-fiber separately. METHODS: Fifty healthy adult volunteers who have no history of neurological illness were examined. Twenty-five of them were male, and twenty-five were female. Their ages ranged from 20 to 46 years, with a mean equal to 29.5 years old. The thresholds for both current perception and nociceptive perception were measured bilaterally in volar aspect of wrist using a Neurometer CPT/C (Quantitative Sensory Nerve Testing Device). The manual mode for current perception threshold and the staircase method for nociceptive current perception threshold was performed individually. RESULTS: The mean values of the threshold for perception evoked by 250 Hz were 0.30 mA in left and 0.31 mA in right, 0.17 mA in left and 0.14 mA in right at 5 Hz respectively. The mean values of the nociception threshold were 0.52 mA in both site at 250 Hz and from 0.35 mA to 0.32 mA at 5 Hz (Table 1). There were no differences between left and right wrist (Fig. 1). Also a significant positive correlation between current perception and nociception thresholds was found (p<0.05) (Fig. 2, 3). There appeared to be different between genders in perception threshold evoked by 250 Hz and nociception threshold evoked by 5 Hz in left (p<0.05) (Table 2). CONCLUSIONS: There exists a meaningful correlation between both sensations of non-pain and pain perception thresholds obtained from all subjects. The measurement of the current perception threshold is considered to be a unique and valuable resource in evaluation of patient with neurologic condition, as well as in serial evaluation of patient to assess the outcome of therapeutic intervention.

The Effect of sium on the Onset Time of Rocuronium-Induced Neuromuscular Blockade in the Isolated Rat Phrenic Nerve-Hemidiaphragm / 대한마취과학회지

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 x EC95, 1.5 x EC95, 2 x 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 x EC95 rocuronium was significantly shortened, but in the case of over 1.5 x 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.

The Effects of Esmolol on Neuromuscular Action of Succinylcholine or Mivacurium / 대한마취과학회지

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.

The Effect of Frequency of Stimulation on Partial Twitch Depression in a Rat Phrenic Nerve Hemidiaphragm Preparation / 대한마취과학회지

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 alpha-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 alpha-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 >alpha-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 alpha-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.

The Neuromuscular Effects of Succinylcholine, Mivacurium and Vecuronium Corresponding to the Blood Flow Occlusion of Time in the Isolated Forearm / 대한마취과학회지

BACKGREOUND: The magnitude of neuromuscular blockade is related to plasma concentration of muscle relaxants. This study was designed to compare the maximal depression of twitch height by blood flow occlusion using a tourniquet at various time interval after intravenous administration of muscle relaxants. METHOD: We studied 127 healthy male adult patients who underwent elective surgery under the general anesthesia with propofol infusion and 50% nitrous oxide. The single supramaximal twitch stimulation applied to the ulnar nerve at the wrist at 1 Hz. The twitch response of adductor pollicis muscles were measured by a 2 kg Load Cell strain gauge with a thumb piece modification and recorded by a Gould TA 240 recorder. After occlusion of blood flow by the tourniquet in the upper arm, in which the neuromuscular monitoring was applied on the wrist, we administered the equipotent dose (ED95) of succinylcholine (S group), mivacurium (M group), and vecuronium (V group) intravenously on the contralateral arm respectively. We measured the maximal depression (%) of twitch height after the releasing tourniquet at 30, 60, 90, 120, 150, and 240 second intervals after the injection of each drug. RESULTS: The depression of twitch height was not found from 90 seconds of tourniquet time in the M group, and 120 seconds of tourniquet time in the S group. However, in the V group, the depression of twitch height was maintained to 240 seconds of tourniquet time. CONCLUSIONS: It is suggested that the plasma concentration of mivacurium declined faster than that of succinylcholine, and that of vecuronium decreased slowest among the groups after intravenous administration of equipotent dose (ED95).

Train-of-Four Fade Related to Potency during Recovery from Neuromuscular Block in Isolated Forearm / 대한마취과학회지

BACKGREOUND: The speed of action of nondepolarizing muscle relaxants might be correlated with the drug potency and the receptor-plasma concentration gradient. However, because of dissociation constants (KDs) being masked by plasma concentration following systemic administration, we investigated the degrees C of train-of-four (TOF) fade at various stages of the measured first twitch height of TOF (T1) during recovery related to potency of various muscle relaxants using isolated forearm technique. METHODS: Thirty two volunteers of the conscious healthy adults who were not receiving any medication which might have influence neuromuscular transmission were involved in this study. The electrodes were applied over the ulnar nerve at the wrist and supramaximal transcutaneous single twitch stimulation (0.1 Hz) delivered by a peripheral nerve stimulator (Innervator, Fisher & Paykel, New Zealand) using a 0.2 ms square wave pulses was applied. The twitch response of the thumb adductor was measured mechanomyographically using a 2 kg Load Cell strain gauge (Model No. 505H, RS Components Ltd., UK) with a thumb piece modification. Following a 5 min. period of stabilization, forearm pneumatic tourniquet was inflated to 300 mmHg in order to occlude the systemic circulation. The equipotent dose (ED95 0.1) of various muscle relaxants diluted in 20 ml of saline was injected into a vein on the dorsal hand respectively: rocuronium 30 microgram/kg, atracurium 25 microgram/kg, mivacurium 8 microgram/kg and vecuronium 4 microgram/kg. Eight volunteers received each dose. The forearm tourniquet was released at 3 min after drugs given. The neuromuscular block was allowed to recovery spontaneously, and at 25, 50, 75 and 100% recovery of control twitch height, TOF stimulation (2 Hz for 2 s) was administered in order to compare TOF ratios between musle relaxants. RESULTS: In the aminosteroid compounds, the TOF ratios of rocuronium were greater than those of vecuronium at all of the assessment points during recovery. In the benzylisoquinolium compounds, the TOF ratios of atracurium were greater than those of mivacurium at 25 and 50% recovery of control twitch height. CONCLUSION: The degree of TOF fade during recovery is related to drug potency at presynaptic receptors separated from the effects of plasma drug concentration.

Influence of Decamethonium on the Neuromuscular Blocking Action of d-Tubocurarine in the Rat Phrenic Nerve Hemidiaphragm Preparation / 대한마취과학회지

BACKGROUND: To elucidate the mechanism of interaction between depolarizing and nondepolarizing muscle relaxants, train-of-four (TOF) fade during onset of neuromuscular blockade of d-tubocurarine (dTC) with or without decamethonium (C10) was evaluated in a rat phrenic nerve hemidiaphragm preparation. METHODS: Phrenic nerve hemidiaphragm preparations from 250~300 g Sprague Dawley rats (n=20) were suspended in a Krebs solution bubbled with 5% CO2 in O2 at 32oC. Phrenic nerves were stimulated with supramaximal stimuli of 0.2 ms duration at 0.15 Hz single twitch and 2 Hz TOF by a Grass S88 stimulator and the contractions of the hemidiaphragm were detected by a Grass FT03 force transducer then recorded. Estimation of ED50 for the dose response data were performed by a linear regression. The statistical significance of the results was determined by Wilcoxon Rank Sum test. p<0.05 was considered significant. RESULTS: Mean ED50 values of dTC and C10 calculated from the dose response relations were 7.76 microgram/ml and 0.65 microgram/ml respectively. Compared to adminstration of 2xED50 of dTC alone, TOF ratios at 75% and 50% of twitch height were markedly decreased by combination of ED50 of C10 and ED50 of dTC with statistic significance (67 +/- 1.9% vs. 46 +/- 3.1% and 36 +/- 2.5% vs. 7 +/- 2.5%). Conclusion: If fade in response to TOF stimulation represents a prejunctional effect, the results from this study suggests that the presynaptic action of C10 has some role in the mechanism of the interaction between dTC and C10 in the rat.