For the assessment the effect of succinylcholine (SCh) on pipecuronium, 52 adult patients undergoing elective surgery under general anesthesia were subjected to this study in which the EMG response (twitch height of the hand to TOF stimulation with 2Hz) of ulnar nerve was monitored and recorded with Datex Relaxograph. According to the amount and mode of the drugs administered, the patients were divided into four experimental groups: 1) Group I: a bolus injection of pipecuronium in dose of 0.05 mg/kg. 2) Group II: pipecuronium 0.1 mg/kg, a double dose of group l. 3) Group IU: pipecuronium 0.05 mg/kg given when the depressed twitch height by SCh (1 mg/kg) recovered to 25%6 of initial twitch height. 4) Group IV: mixed injection of SCh (1 mg/kg) and pipecumnium (0.05 mg/kg). The results were as follows ; 1) Mean onset time of pipecuronium was 6.5+/-0.5 minutes in group I and 4.1+/-0.5 minutes in group II, the latter being significantly shorter than group I (p<0.01). In group Ill, it was 2.1+/-0.23 minutes being significantly shorter than group I, II (p<0.001). In group IV it was 1.1+/-0.1 minutes which was more significantly shorter than group I, II, and IU. 2) Mean action duration of pipecuronium was 50.9+/-6.7 minutes in group I and 141.9+/-15.4 minutes in group II, the latter being longer significantly (p<0.001). In group IIl, it was 53.9+/-5.2 minutes which was similar to group I, but it was 69.8+/-6.5 minutes in group IV, being significantly longer than those of group I and III (p<0.05). 3) Mean potency of pipecuronium expressed by the percentage change of initial twitch height was 7.6+/-1.9% in group I, but it was significantly decreased to 4.2+/-0.9% in group II (p<0.05). In group III, it was 0.2+/-0.1% being sinificantly decreased than group I, II (p<0.001). In group IV, it was 0.0+0.0% being more significantly decreased than other groups (p<0.001). 4) Presence of pipecuronium in group IV did not affect on the intensity of fasciculation induced by SCh. These results indicate that succinylcholine may potentiate the pipecuronium based on the findings that succinylcholine increased the potency and lengthened the duration of action of pipecuronium.
Adult ; Anesthesia, General ; Fasciculation ; Hand ; Humans ; Pipecuronium* ; Succinylcholine* ; Ulnar Nerve

The effects and interactions of pipecuronium and atracurium with diltiazem and verapalmil on the electrically-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat phrenic-hemidiaphragm preparation. Pipecuronium (3X10(-7) -4X10(-6)) and atracurium (10(-6) -3X10(-5) M) decreased the electrically-evoked twitch response, train-of-four and tetanus ratio in a dose-related fashion and the pipecuronium was more potent than atracurium. The inhibitory effects of pipecuronium and atracurium were potentiated by pretreatment of 5 uM diltiazem and verapamil, Ca++-channel blokers, in which the concentration of diltiazem or verapamil has no obvious effect on the twitch response itself. Futhermore, it is noteworthy that the inhibitory effects of pipecuronium and atraeurium were markedly potentiated by 150 uM hemicholinium pretreatment. On the basis of these findings, the results of present study suggests that the muscle relaxation by pipecuronium and atracurium is mediated by pre- and post-junctional receptor blockade, and that diltiazem or verapamil intensifies neuromuscular blockade produced by these musele relaxants. The potentiating effect of diltiazem or verapamil may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.
Acetylcholine ; Animals ; Atracurium ; Calcium ; Diltiazem* ; Hemicholinium 3 ; Muscle Relaxation ; Neuromuscular Blockade* ; Pipecuronium ; Rats ; Tetanus ; Verapamil*

The neuromuscular blocking effect of pipecuronium was evaluated in 35 patients under N2O-O2-isoflurane anesthesia with visual and/or tactile counts for the twitch of the adductor pollicis muscle in response to train-of-tour(TOF) stimulation of the ulnar nerve at the wrist. Group I, II and III were classified according to the initial dose of pipecuronium of 50, 80 and 100ug/kg, respectively. The additional dose, 30 ug/kg, was given in all three groups when the first twitch of TOF(T) reappeared. The onset time in Group I, II and III was 361.4+/-98.6, 218.7+/- 80.8 and 239.0+/-73.7 seconds, respectively. The onset time in Group I was significantly slower(p<0.005) than those in the other groups. All three doses of pipecuronium provided good to exceUent intubating condition in about 4 to 6 minutes after the administration of the initial dose. The time interval from the disappearance of T1 to the reappearance of T1 was 39.0+/-20.8 min in Group I, which was significantly longer(p<0.05) in Group II(67.7+/-26.4 min) or III(63.8+/-20.8 min). The cumulative effect of pipecuronium was evaluated by comparing the mean time intervals of an additional dose to the succeeding ones. The intervals between additional doses were independent of the size or duration of the initial dose. There were no significant differences in the intervals between additional doses. Heart rates, rhythms and mean arterial blood pressures were not significantly changed in any groups following the administration of pipecuronium In conclusion, pipecuronium bromide can be recommended as a long-acting neuromuscular blocking agent with an absence or minimum of cumulative and cardiovascular effects for patients in whom a long operation is scheduled and the cardiovascular stability is required.
Anesthesia ; Arterial Pressure ; Heart Rate ; Humans ; Neuromuscular Blockade ; Pipecuronium* ; Ulnar Nerve ; Wrist

There is an evidence that onset time and potency of the non-depolarizing neuromuscular blocking agents are related. However the relationship between onset time and the recovery has not been investigated yet. In this experiment, the onset times of six neuromuscular blocking agents have been compared with their recovery times. The neuromuscular transmission of mivacurium 0.15 mg/kg, atracurium 0.4 mg/kg, vecuronium 0.08 mg/kg, pipecuronium 0.08 mg/kg, pancuronium 0.1 mg/kg and succinylcholine 1 mg/kg were studied in 58 adult healthy patient (ASA I and II) during O2-N2O-isoflurane anesthesia using train-of-four stimulation with Relaxograph. It has been demonstrated that there is a close relationship between onset time and recovery in depolarizing neuromuscular blocking agent but not in non-depolarizing agents. Consequently, it is proposed that the relationships between the onset time and the recovery may hardly expected in clinical practice following systemic administration of non-depolarizing neuromuscular blocking agents.
Adult ; Anesthesia ; Atracurium ; Humans ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents ; Pancuronium ; Pipecuronium ; Succinylcholine ; Vecuronium Bromide

BACKGROUND: Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of metocurine, atracurium, doxacurium, and pipecuronium. This study examine neuromuscu-lar blocking effect and recovery of mivacurium in isolated rat phrenic-hemidiaphragm with two-weeks phenytoin pretreatment. METHOD: After the administration of 14 days of phenytoin 40 mg/kg, administered intraperitoneally twice daily (n=10), ED90, antagonism of neostigmine and 4-aminopyridine on the electrically evoked twitch response and train-of-four (TOF) stimulation were compared to control groups in isolated rat phrenic-hemidiaphragm preparation. RESULTS: ED90 was significantly greater in the phenytoin group than in the control group (319 +/- 39.5 g vs. 209.5 +/- 52.2 g, respectively). After the administration of neostigmine 0.75 M, the recovery of the single twitch and TOF ratio were significantly lesser in the phenytoin group than in the control group (single twitch; 19.6 +/- 6.6% vs. 69.2 +/- 9.4%, TOF ratio; 0.258 +/- 0.149 vs. 0.543 +/- 0.1, respectively). After the administration of 4-aminopyridine 40uM, the recovery of the single twitch and TOF ratio were no significant differrence between the phenytoin group and the control group (twitch; 118.1 +/- 25.3% vs. 122.6 +/- 24.8%, TOF ratio; 0.937 +/- 0.051 vs. 0.949 +/- 0.067, respectively). CONCLUSION: Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of mivacurium.
4-Aminopyridine ; Animals ; Atracurium ; Drug Interactions ; Neostigmine ; Neuromuscular Blockade* ; Phenytoin* ; Pipecuronium ; Rats*

BACKGROUND: Magnesium sulfate (MgSO4) is widely utilized in the treatment of preeclamptic hyperreflexia. It is well known that magnesium enhances nondepolarizing neuromuscular blockade. Eclamptic convulsions are almost always prevented by magnesium in plasma concentrations of 4 to 7 mEq/L. METHODS: The effects of various concentration of magnesium on the potency and reversibility of pipecuronium were investigated in vitro rat phrenic nerve-hemidiaphragm. The phrenic nerve-hemidiaphragm was dissected and suspended in organ bath containing modified Krebs' solution. Forty samples were divided into 4 groups (n=10 in each group). Group I was studied at the physiologic magnesium concentration(2.4 mEq/L, control group). Group II, III, IV were studied at the concentration of 4, 5.5, and 7 mEq/L, respectively. In each group, we added pipecuronium until twitch height decreased more than 90% of initial level. To compare the recovery, we added neostigmine and calcium, and then, measured TOF ratio. RESULTS: The amounts of added pipecuronium were 73.8+/-15.2 microgram (mean+/-S.D.) in Group I, 38.1+/-5.0 microgram in Group II, 33.0+/-4.1 microgram in Group III and 16.1+/-1.7 microgram in Group IV. The amounts of pipecuronium in Group II, III, IV were significantly less than Group I. After the addition of neostigmine, the values of TOF ratio were under 0.6 in all groups. But after the addition of calcium, all groups were recovered with TOF ratio over 0.85 except Group I. CONCLUSIONS: This study indicated that the increased magnesium concentration potentiated pipecuronium-induced neuromuscular blockade and at higher level, it was more apparent. Neostigmine was not significantly effective to reverse the pipecuronium-induced neuromuscular blockade potentiated with magnesium. But calcium was significantly effective.
Animals ; Baths ; Calcium ; Magnesium Sulfate ; Magnesium* ; Neostigmine ; Neuromuscular Blockade* ; Pipecuronium ; Plasma ; Rats* ; Reflex, Abnormal ; Seizures

The effects and interactions of metabolic and respiratory acid-base changes on electrically-evoked twitch response, train-of-four and tetanic stimulation with pipecuronium (Pip), vecuronium (Vec) and atracurium (Tra) were studied in the isolated rat hemi-diaphragm preparation. pip (3X10(-7) - 4X10(-6) M), Vec (3X10(-6) - 15X10(-6) M) and Tra (10(-6) - 3X10(-5) M) decreased the electrically-evoked (phrenic nerve stimulation, 0.1 Hz, 0.2 ms, 10 V) twitch response in a dose related fashion and Pip was more potent than Vec and Tra. In the alkali state (pH 7.6 or high HCO3 ), the decrements of twitch response, train-of-four and tetanus ratio induced by Pip (1.5uM) were potentiated, but the effects of Vec or Tra were markedly intensified by acid midium (pH 7.2 or low HCO3 ). And also, decreasing pH by increasing PCO2 or by decreasing HCO3 intensified the effects of Vec and Tra, whereas it reversed by Pip. Conversely, increasing pH by decreasing PCO2 or by increasing HCO3 antagonized the effects of Vec and Tra, whereas it potentiated the Pip effect. On the basis of these finding, the result of the present study suggest that neither PCO2 nor HCO3 has a specific action, but that changes in pH may be responsible for the results. In addition, the differences of the above results by each drugs may not be due to the number of quaternary ammonium of the agents. And also, indicate that the effective site of the influence of the acid-base change upon the neuromuscular blocking effects might be prejunctional nerve terminal.
Alkalies ; Ammonium Compounds ; Animals ; Atracurium ; Hydrogen-Ion Concentration ; Neuromuscular Blockade ; Pipecuronium ; Rats* ; Tetanus ; Vecuronium Bromide

BACKGROUND: Pipecuronium bromide is a long-acting steroidal neuromuscular blocking drug. This study was designed to evaluate the neuromuscular-blocking action and the cardiovascular effects of pipecuronium in patients under O2-N2 O-enflurane anesthesia, by comparing with those of pancuronium and vecuronium. METHODS: Fifty-one adult patients (ASA class 1 or 2) were randomly received pipecuronium 0.1 mg/kg (n=17), pancuronium 0.12 mg/kg (n=17), or vecuronium 0.1 mg/kg (n=l7) as a single intravenous bolus dose. Anesthesia was induced with thiopental 5 mg/kg, followed by one of the muscle relaxants. Patients were then given O2 (2 L/min) - N2O(2 L/min)-enflurane(1.8 vol%) by face mask. Trachea was intubated, and anesthesia was maintained with O2 (2 L/min)- N2O(2 L/min)-enflurane(1-2.5 vol%) during whole study period. Neuromuscular blocking effect was assessed by response of the adductor pollicis muscle in 2Hz train-of-four(TOF) stimulation of ulnar nerve every 20 seconds. The times from administration of initial dose to loss and reappearance of four twitches to TOF were measured. Systolic and diastolic blood pressure(SAP,DAP) and heart rate(HR) were noninvasively measured. RESULTS: The onset times of pipecuronium, pancuronium, and vecuronium were 278+/-99, 268+/-67, and 208+/-56 seconds, respectively. The duration of action of pipecuronium, pancuronium, and vecuronium were 148+/-99, 145+/-35, and 52+/-12 minutes, respectively. SAP and DAP with pancuronium were significantly greater than those with pipecuronium or vecuronium I minute after the administration. No significant difference in SAP and DAP was found until 5 minutes after the administration among the agents. HR was increased significantly until 20 minutes after the administration of pancuronium. CONCLUSION: Pipecuronium is a long-acting drug suitable for longer operations in which cardiovascular stability is required.
Adult ; Anesthesia ; Blood Pressure ; Heart ; Humans ; Masks ; Neuromuscular Blockade* ; Pancuronium* ; Pipecuronium* ; Thiopental ; Trachea ; Ulnar Nerve ; Vecuronium Bromide*

BACKGROUND: It has been shown that L-type calcium channel blockers increase the muscle relaxation effects of non-depolarizing neuromuscular blocking agents whereas the potentiated neuromuscular blocking effects by L-type calcium channel blocker are resistant to reversal by neostigmine. The aims of this study were 1) to see whether the pretreatment of L-type calcium channel blocker, such as verapamil, aggravates the pipecuronium-induced muscle relaxation, 2) if so, to see whether these effects are reversed by anticholinesterase, such as neostigmine and edrophonium or potassium channel blocker, such as 4-aminopyridine. METHODS: The rat-phrenic nerve-hemidiaphragms (n=60) were prepared. Twenty microgram of pipecuronium was administered to all organ bath. All samples were divided into two groups according to the administration of 10uM of verapamil i.e. verapamil pretreated, non-pretreated group. The amounts of administered pipecuronium were gradually increased by 4ug until the force of twitch decreased to 10% of control value in both groups. Each group was subdivided into three groups according to the administration of 0.75 M of neostigmine, 12.4 uM of edrophonium or 40uM of 4-aminopyridine. RESULTS: The dose of pipecuronium required for the decrease of contractile force to 10% of control value was less in verapamil pretreated group than in non-pretreated group. And, the decrease of contractile force in both groups was more effectively reversed by 4-aminopyridine than neostigmine and edrophonium. CONCLUSIONS: Verapamil potentiates the pipecuronium-induced neuromuscular blockade and 4-aminopyridine is more effective to reverse verapamil pretreated, pipecuronium induced neuromuscular blockade.
4-Aminopyridine* ; Baths ; Calcium Channels, L-Type ; Edrophonium* ; Muscle Relaxation ; Neostigmine* ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents ; Pipecuronium* ; Potassium Channels ; Verapamil*

BACKGROUND: Studies in animals suggest that pipecuronium dose not induce hemodynamic chan-ges related to histamine release or to an effect on the autonomic nervous system. Therefore the effects of bolus administration of large doses of pipecuronium, up to 0.20 mg/kg, on the intubation condition, onset and duration of neuromuscular blockade, heart rate and blood pressure were studied during fentanyl- nitrous oxide anesthesia. METHOD: Forty adults were randomly assigned to receive a bolus injection of either 0.05, 0.10, 0.15, 0.20 mg/kg of pipecuronium. Neuromuscular blockade was measured using mechanomyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve. Four subgroups of 10 patients received pipecuronium doses of 0.05, 0.10, 0.15 and 0.20 mg/kg, respectively, as an intubating dose. RESULTS: The times of onset and clinical duration (mean sem) after each dose were as follows: 0.05 mg/kg, 2.98 0.42 and 41.5 2.42 min; 0.10 mg/kg, 1.54 0.06 and 82.9 7.48 min; 0.15 mg/kg, 1.41 0.14 and 124.8 13.1 min; 0.20 mg/kg, 1.12 0.05 and 187.1 12.8 min. The intubation condition, time of onset and duration after doses of 0.05 mg/kg were significantly different from values after the higer doses. The duration was increased with dose-increments. No dose-related changes in heart rate or blood pressure were observed. CONCLUSION: The authors conclude that dose of 0.10 mg/kg and over has good intubation condition clinically and large bolus dose of pipecuronium can be safely used with a significantly prolonged duration of action without hemodynamic change.
Adult* ; Anesthesia ; Animals ; Autonomic Nervous System ; Blood Pressure ; Heart Rate ; Hemodynamics ; Histamine Release ; Humans ; Intubation ; Intubation, Intratracheal* ; Neuromuscular Blockade ; Nitrous Oxide ; Pipecuronium* ; Ulnar Nerve