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 Effect of Lidocaine on the Onset Time of Atracurium / 대한마취과학회지

BACKGROUND: Local anesthetics for attenuating sympathetic response have been shown to interact with neuromuscular blockers. Most local anesthetics decrease neuromuscular transmission and potentiate neuromuscular blocks of muscle relaxants. The purpose of this study was to examine the effectiveness of lidocaine on the onset time of atracurium and to compare it with that of uccinylcholine. METHODS: Fifty four patients, ASA physical status I or II, were induced with thiopental (4.0 mg/kg) and maintained with O2 -Enflurane (2.5 vol%). After controlled respiration for 3 minutes, muscle relaxants were given. They were randomly divided into three groups: Atracurium (0.5 mg/kg) was administered intravenously for 1 minute in Group A (n = 18), additional lidocaine (1.0 mg/kg) was given intravenously 1 minute prior to the administration of atracurium in Group L (n = 18), and succinylcholine (1.0 mg/kg) was given in Group S (n = 18). Neuromuscular blockade was assessed by train-of-four (TOF) at the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve (2 Hz, 0.2 msec) every 12 seconds. Endotracheal intubation was performed and intubatin g conditions were evaluated according to the standard scoring method after measuring the onset time (from the end of giving muscle relaxants to the 90 % suppression of the first twitch). RESULTS: The onset time of Group L (116.7 13.2 sec) was shorter than that of Group A (154.2 16.1 sec) (P <0.05), but was not as fast as that of Group S (42.5 5.8 sec) (P <0.05). Intubating conditions were good or excellent in all groups. CONCLUSIONS: Additional lidocaine (1.0 mg/kg) for attenuating sympathetic response can accelerate the onset of atracurium in rapid tracheal intubation.

Analysis of Intradermal Test for Anesthetic Drugs / 대한마취과학회지

BACKGROUND: Intradermal test is a useful diagnostic method for acute anaphylactoid or anaphylactic reactions induced by anesthetic drugs. We analyzed the responses of intradermal test for anesthetic drugs in patients who did not show anaphylactoid or anaphylactic reactions. METHODS: The authors performed intradermal test for anesthetic drugs (thiopental, midazolam, fentanyl, atracurium and vecuronium) in 224 adult patients one hour before induction of anesthesia. The responses were interpreted as measuring the size of wheal and flare. We also did history taking for past allergic history. RESULTS: There were no patient that showed positive reaction. The rate of false positive reaction for atracurium (12.5%) was significantly higher than other anesthetic drugs (p<0.05). And the rate of false positive reaction for atracurium in patients under the age of 40 (20%) was significantly higher than those above the age of 40 (3.8%) (p<0.05). But the difference of the rate of false positive reaction for atracurium between male (8%) and female (15.3%) was not significant statistically. The differences of the rates of false positive reaction for anesthetic drugs between past allergic history group and no past allergic history group were not statistically significant. CONCLUSIONS: In intradermal test for anesthetic drugs, the rate of false positive reaction for atracurium was significantly higher than thiopental, vecuronium, fentanyl and midazolam. Especially, it was significantly higher in patients under the age of 40. So in performing intradermal test to search for causative anesthetic drug, we have to consider the high rate of false positive reaction for atracurium.

Effects of Atracurium in the Patients with Myasthenia Gravis Undergoing Thymectomy / 대한마취과학회지

BACKGROUND: Myasthenia gravis is an autoimmune neuromuscular disorder that shows increased sensitivity to nondepolarizing muscle relaxants. Atracurium is eliminated by Hofmann elimination and ester hydrolysis. We studied the onset and duration of atracurium in patients with myasthenia gravis. METHODS: Ten patients undergoing thymectomy for myasthenia gravis and ten patients of ASA Class I-II without liver, kidney and neuromuscular disease for orthopedic surgical procedures were assigned. Anesthesia was induced with thiopental (4~5 mg/kg) and maintained with inhalation of N2O:O2 (1:1) and enflurane (1.0~2.0 vol%). Atracurium (0.5 mg/kg) was given as a muscle relaxant and then intubation was performed after twitch response was depressed more than 80%. Neuromuscular relaxation was assessed by TOF (T1) at the adductor pollicis with supramaximal stimulation of ulnar nerve at 2 Hz every 12 seconds. The onset and the duration of 5, 25, 50, 75% recovery time of T1 and the recovery index were recorded. RESULTS: Onset of block was shortened and recovery time of 5, 25, 50, 75% and recovery index were prolonged in patients with myasthenia gravis. Conlusions: In patients with myasthenia gravis, atracurium induced rapid onset time and prolonged recovery time of 5, 25, 50, 75% and recovery index.

Action Duration of Atracurium and Vecuronium in Patients with Renal Failure / 대한마취과학회지

BACKGROUND: Atracurium is eliminated by Hofmann elimination and ester hydrolysis, with minimal renal and hepatic excretion. It's action duration is not affected by renal function. Although metabolism of vecuronium is less dependent on the renal function than other steroid type neuromuscular blockers, the action duration of vecuronium is prolonged in renal failure. The purpose of this study is to compare the differences of the action duration of atracurium and vecuronium in patients with renal failure. METHODS: Forty patients with normal renal function and 40 patients with chronic renal failure were assigned to one of four groups: atracurium-normal (n=20, AC group), atracurium-renal failure (n=20, AK group), vecuronium-normal (n=20, VC group), vecuronium-renal failure (n=20, VK group). Anesthesia was induced with thiopental and maintained with the inhalation of nitrous oxide (50%) and isoflurane (0.5~1.5 vol%). Atracurium (0.5 mg/kg) or vecuronium (0.1 mg/kg) was given and endotracheal intubation was performed after twitch response was depressed more than 80%. Neuromuscular blockade was assessed by train-of-four at the adductor pollicis with supramaximal stimulation of ulnar nerve of 2 Hz every 12 sec. The onset time, duration of 5, 25, 50, 75% recovery time and recovery index were checked. RESULTS: Onset of block was not significantly different among four gorups. Recovery time of 5, 25, 50, 75% and recovery index were longer in the both renal failure groups. Action durations in renal failure were not significantly different between AK and VK groups. CONCLUSION: It is concluded that action duration of atracurium and vecuronium are affected by renal function. We would better monitor muscle relaxation and titrate dose of muscle relaxant.

Action Duration of Atracurium in the Elderly Patients / 대한마취과학회지

BACKGROUND: The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of the pharmacokinetic and pharmacodynamic reasons. Atracurium is eliminated by nonorgan dependent pathway, Hofmann elimination and ester hydrolysis. So there are some arguments for age-related differences. The purpose of this study was to compare the differences of the onset and duration of atracurium in young and elderly. METHODS: Eighteen young adults (21-54 yr) and 18 elderly (>65 yr) patients anesthetized with nitrous oxide and enflurane. Atracurium (0.5 mg/kg) was given and then intubation was performed after T1 response was blocked more than 80%. Neuromuscular relaxation was measured by the first twitch of train-of-four (T1) response at the adductor pollicis after supramaximal stimulation of ulnar nerve at 2Hz every 12 sec. The onset (disappearance of T1) and duration of 5, 25, 50, 75% recovery time of T1 and recovery index (time for 25-75% recovery of T1) were recorded. RESULTS: Onset of block was not significantly different between the young and elderly. Recovery time of 5, 25, 50, 75% and recovery index were not prolonged in elderly compared with young adults. CONCLUSIONS: There were no significant differences between young and elderly adults in onest time, recovery time of 5, 25, 50, 75% and recovery index when atracurium is used in a single bolus dose. The results suggest that atracurium in elderly patients has similar onset and action duration compared with younger patients.

Clinical Evaluation of Atracurium for Endotracheal Intubation / 대한마취과학회지

The usefulness of nondepolarizing muscle relaxants for intubation is limited by a relatively slow onset of neuromuscular block compared to that achived with succinylcholine. But, authors have reported that larger doses of nondepolarizing muscle relaxants produce a more rapid onset of maximal neuromuscular block and conditions conductive to endotracheal intubation and recent reports support the use of the "priming principle in the clinical practice of anesthesiology. This phenomenon may apply to all nondepolarizing relaxants: it is reported to facilitated neuromuscular blockade and tracheal intubation when used with atracurium, vecurouium, alcuronium or pancuronium. In this study, administering a small subclinical dose of atracurium (75ug/kg) Smin. prior to the remainder of an intubating doae of atracurium (250ug/kg) had no different on grade of block for intubation compared to single IV bolus of atracurium (500ug/kg).

Clinical Evaluation of Atracurium for Endotracheal Intubation / 대한마취과학회지

The usefulness of nondepolarizing muscle relaxants for intubation is limited by a relatively slow onset of neuromuscular block compared to that achived with succinylcholine. But, authors have reported that larger doses of nondepolarizing muscle relaxants produce a more rapid onset of maximal neuromuscular block and conditions conductive to endotracheal intubation and recent reports support the use of the "priming principle in the clinical practice of anesthesiology. This phenomenon may apply to all nondepolarizing relaxants: it is reported to facilitated neuromuscular blockade and tracheal intubation when used with atracurium, vecurouium, alcuronium or pancuronium. In this study, administering a small subclinical dose of atracurium (75ug/kg) Smin. prior to the remainder of an intubating doae of atracurium (250ug/kg) had no different on grade of block for intubation compared to single IV bolus of atracurium (500ug/kg).