The effects of gentamicin on metodurine-induced neuromuscular blockade and its reversal with neostigmine or calcium in the cat / 대한마취과학회지

To determine the neuromuscular effect and its reversals of gentamicin, alone or in combination with metocurine, pharmacodynamic studies were done using a common peroneal nerve- anterior tibialis muscle preparation in 24 adult cats weighing 2.5-4.0 kg. The median effective dose of gentamicin obtained by cumulative dose-response study was 21.6+/-4.83 mg/kg. Under the pretreatment of gentamicin, the onset and duration of metocurine was 1.32+/-0.91 min and 28.8+/-10.95 min, respectively. There was no significant difference in the recovery indicies for its reversal between neostigmine and calcium. Each values of recovery indices were 1.85+/-0.65 and 2.05+/-1.00 min with neostigmine and calcium, respectively. These results suggested that gentamicin by itself had neuromuscular blocking effect. With the pretreatrnent of gentamicin, the onset of metocurine was shortened to one third and its duration was prolonged as much as seven times. Additionally, metocurine induced neuromuscular block with pretreatment of gentamicin was reversed completely.

The Neuromuscular Blocking Actions of Metocurine and its Reversal in Cats with Acute Renal Failure / 대한마취과학회지

Acute renal failure was induced to investigate it effects on the neuromuscular blocking actions and reversals of metocurine in 14 adult cats, either sex, weighing 2.5-4.5 kg. Ligation of both renal pedicles in 6 cats (Group II) and its sham operations in 8 cats (Group I) were done under the pentobarbital anesthesia. Neuromuscular monitoring was done using a common peroneal nerve-tibialis anterior muscle preparation. The mean blood pressures, acid-base status and serum electrolytes at the time of injection of metocurine or neostigmine were not significantly different between two groups. The heart rates at the administration of neostigmine were significantly decreased probably due to the decreased body temperatures in group I. The onset time of metocurine with 3 X ED95 in acute renal failure was simiiar to that in normal renal function. However, the duration of metocurine with 3 X ED95 in acute renal failure was significantly longer that that in normal renal function. The effeets of neostigmine administered at 15%-spontaneous twitch recovery for the recovery indices and antagonism effects were not significantly different between two groups. In conclusion, acute renal failure prolongs the duration of metocurine, but not interfere its onset. Additionally, there is no effect on the reversal actions of neostigmine if administered at the spontaneous recovery of twitch height more than 15%.

The Effects of Metocurine Iodine and Vecuronium Bromide on Intraocular Pressure with the Priming Principle / 대한마취과학회지

We measured the intraocular pressure changes in forty female patients (aged from 20 to 50) without a history of ocular or cardiovascular disease who were classified physical status 1 and 2, and scheduled for elective surgery. They were divided into 4 groups. Group l (n=10); metocurime 0.03 mg/kg as a priming dose and metocurine 0.27 mg/ kg as a intubating dose. Group 2 (n= 10); vecuronium 0.008 mg/kg as a priming dose and vecuronium 0.072 mg as a intubating dose. Group 3 (n=10); vecuronium 0.008mg/kg as a priming dose and metocurine 0.27 mg/kg as a intubating dose. Group 4 (n=10); metocurine 0.03mg/kg as a priming dose and vecuronium 0.072 mg/kg as a intubating dose. In this study, metocurine and vecuronium were used with the priming principle. We also measured changes in blood pressure, pulse rate and T1% of Train of four stimulation and evaluated the discomfort after the administration of the priming dose and the difficulties of intubation. The results were as follows, 1) Compared with the control value, there was no increse in intraocular pressure following intubation in all four groups and intraocular pressure of 2 and 4 minutes following intubation decreased significantly in all four groups. The greatest decrease was seen in group 3, but it was not significant when compared to the other three groups. 2) While a transient increase in blood pressure was seen in all four groups, the lowest increase was seen in group 3 as compared to the control value. Blood pressure 4 minutes following intubation decreased significantly in grop 3. 3) A significant decrease in the T1% of the Train of four stimuli at one minute after administration of the intubating dose was seen in group 3 compared to the other three groups. 4) Group 3 showed the lowest number of difficult intubation. In conclusion, the combination of vecuronium and metoeurine with the priming principle provide optimal conditions for smooth and rapid intubation with no elevation of intraocular pressure, blood pressure and heart rate changes for ocular surgery.

Comparative Hemodynamic Effects of ED95 Dose of Metocurine and Tubocurarine / 대한마취과학회지

On account of its histamine releasing and ganglionic blocking properties tubocurarine is known to have significant hemodynamic effects. Methylation of the compound produces metocurine and should decrease both histamine release and ganglionic blockade. The hemodynamic effects of these two compounds were compared in 40 patients anesthetized with halothane, nitrous oxide, oxygen. These 40 patients were divided into two groups by administering tubocurarine or metocurine. Group I: When patients had no responses to surgical stimuli after induction, mean arterial blood pressure, pulse rate, pulse pressure were measured 1, 3, 5 min before administration of tubocurarine as control value. After administration of tubocurarine 0.51 mg/kg (ED), mean arterial blood pressure, pulse rate, pulse pressure were measured every minute for twenty minutes as experimental value. (n= 20) Group IL Metocurine 0,2S mg/kg (ED) was administered in the same way as the group I. (n=20) Result: Tubocurarine produced a decreaaed mean arterial blood pressure 22.9%, pulae pressure 16%, and an increaaed pulee rate 14.3%, 2 min after administration of drug(p<0.05). Also mean arterial blood pressure decreased for whole 20 min, pulse pressure for 7 min, and pulse rate increased for 4 min, significantly. But metocurine produced no significant hemodynamic effects. These data suggest that the hemodynamic margin of safety of metocurine is much grater than tubocurarine.

Effect of Metocurine Iodide on Neuromuscular Blockade and Hemodynamics / 대한마취과학회지

Among nondepolarizing neuromuscular blocking agents, d-tubocurarine may cause blood pressure reduction due to ganglionic blockade and histamine release, while pancuronium and gallamine are associated with vagal blockade and heart rate acceleration. Metocurine, as a trimethylated derivative of d-tubocurarine synthesized by King in 1935, is known to have relatively long duration of action and produces little change in cardiovascular system. Despite its relative lack of cardiovascular effects, the accumulation of data with regard to human neuromus- cular pharmacology and the clinical use has been scant. One hundred and nine adult patients of either sex were anesthetized with thiopental sodium and 50% nitrous oxide with 1.5-2.5% enflurane. For evaluation of neuromuscular blocking effect of metocurine, train-of-four stimulation (2.0 Hz for 2 seconds) was applied at the wrist along the ulnar nerve distribution and the response was measured via ABM Datex. Systolic, diastolic blood pressure and heart rate were recorded continuously after administration of metocurine, d-tubocurarine or pancuronium. All data were analized by ANOVA, Scheffe test. The results are follows : 1) The mean onset times of metocurine 0.1, 0.2, 0.3 mg/kg groups were 119.5+/-40.0, 120.9+/-61.1, 84.8+/-61,1 seconds and the mean durations were 75.1+/-37.6, 104.9+/-42.1, 131.0+/-42.5 minutes respectively. 2) Single-bolus dose of metocurine 0.1, 0.2, and 0.3 mg/kg did not cause significant cardiovascular changes from the control values, but d-tubocurarine 0.3 mg/kg decreased mean systolic blood pressure significantly from 116.6+/-15.7 to 99.0+/-10.9 mmHg 2 minutes after injection. 3) Systolic blood pressures of metocurine 0.2 mg/kg (107.2+/-11.7 mmHg) and d-tubocurarine 0.3 mg/ kg (100.4+/-12.9 mmHg) were significantly different from that of pancuronivm 0.06 mg/kg (127.8+/-16. 0 mmHg) after 1 minute, and 2 minutes after injection, systolic blood pressure of metocurine 0.2 mg/ kg (110.2+/-14.3 mmHg) and d-tubocurarine 0.3 mg/kg (99.0+/-10.9 mmHg) were different from that of pancuronium 0.06 mg/kg (125.3+13.1 mmHg). Five minutes after injection, systolic pressure of d- tubocurarine 0.3mg/kg group (101.110.2mmHg) was significantly different from that of pancur-onium 0.06 mg/kg group (118.7+/-11.0 mmHg). 4) Diastolic blood pressure of d-tubocurarine 0.3 mg/kg (63.4+/-12.9 mmHg) was significantly differ- ent from that of pancuronium 0.06mg/kg (84.2+/-13.3mmHg) after 1 minute, and 2 minutes after injection, diastolic blood pressure or d-tubocurarine 0.3 mg/kg (65.4+/-11.3 mmHg) was different from that of pancuronium 0.06mg/kg (83.1+/-11.6mmHg). There was no significant difference among the groups with respect to heart rate. In summary, metocurine has relatively rapid onset and long duration of action, and used in a dose sufficient to provide surgical relaxation, it produces little change in cardiovascular system in contrast to d-tubocurarine or pancuronium. 1t is therefore suggested that metocurine may be recommended as a muscle relaxant for patients having cardiovascular disease.

The Hemodynamic Effects of Metocurine during Enflurane Anesthesia / 대한마취과학회지

This study was undertaken to determine the hemodynamic effects of metocurine in 40 adult patients (ASA class I-II) scheduled for elective operation. Anesthesia was induced with thiopental sodium 3-5 mg/kg IV and maintained with enflurane at a constant inspired concentration of 1.5-2.5 vo1%. After 30-minutes of hemodynamic stabilization and when operative stimulus was judged to be unchanged, each patient was randomly assigned to one of following three groups. Group I: Bolus injection of metocurine(0. 28 mg/kg, ED95) within 5 seconds. Group II: Slow injection of metocurine(0.28mg/kg, ED95) within 3 minutes. Group III: Metocurine injection as group I with prophylactic use of H(1)-H(2)-receptor blocker(Cimetidine 300 mg PO, 1 hour before induction and chlorpheniramine 1. 0 mg/kg IV, 10 min. before metocurine injection). There were no significant changes in mean arterial pressure and heart rate throughout the study (p< 0.05), but only one case of group I revealed the evidence of systemic histamine release. Group II and Group III showed no evidence of systemic histamine release. Therefore, we felt that metocurine might be used safely with slow injection or prophylactic use of H(1) and H(2) receptor blocker with rapid bolus injection for any surgical operation, including cardiovascular operations.