Effects Of Neuromuscular Blocking Drugs Research Articles

Effects of neuromuscular blocking drugs on viability of human umbilical vein endothelial cells (HUVECs).

ObjectiveThis study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate whether they cause vascular complications due to cell proliferation.MethodsHUVECs were cultivated with 5% CO2 at 37°C in a predefined supplemented medium over 7 days until confluence of cell monolayers. Assays were conducted during the exponential growth phase. Suxamethonium chloride, vecuronium bromide, atracurium besylate, and rocuronium bromide were used at concentrations of 10–5, 10–6, and 10–7 M in proliferation assays in which cells were incubated with these drugs for 24, 48, and 72 hours. All experiments were performed in four replicates.ResultsThe neuromuscular blocking drugs used had comparable effects on the survivability of HUVECs. Overall, no significant difference was observed in the survivability of HUVECs in a dose-dependent manner after exposure to the study drugs. However, some significant differences in the viability of HUVECs were found among the different measurement times.ConclusionsThe findings of the current study support the safety of the studied neuromuscular blocking drugs in clinically relevant concentrations regarding their effects on endothelial cell proliferation.

Relationship between the muscle relaxation effect and body muscle mass measured using bioelectrical impedance analysis: A nonrandomized controlled trial.

ObjectiveThe dose of neuromuscular blocking drugs is commonly based on body weight, but using muscle mass might be more effective. This study investigated the relationship between the effect of neuromuscular blocking drugs and muscle mass measured using bioelectrical impedance analysis.MethodsPatients who were scheduled for elective surgery using a muscle relaxant were screened for inclusion in this study. Under intravenous anaesthesia, 12 mg or 9 mg of rocuronium was administered to males and females, respectively; and the maximal relaxation effect of T1 was measured using a TOF-Watch-SX® acceleromyograph.ResultsThis study enrolled 40 patients; 20 males and 20 females. For both sexes, the maximal relaxation effect of T1 did not correlate with the body weight-based dose of neuromuscular blocking drugs (males, r2 = 0.12; females, r2 = 0.26). Instead, it correlated with the dose based on bioelectrical impedance analysis-measured muscle mass when injected with the same dose of rocuronium (males, r2 = 0.78, female, r2 = 0.82).ConclusionsThis study showed that the muscle relaxation effect of rocuronium was correlated with muscle mass and did not correlate with body weight when using the same dose. Therefore, a muscle mass-based dose of neuromuscular blocking drugs is recommended.

Neuromuscular Blockers and Reversal Agents

Neuromuscular blocking drugs, which include depolarizing and nondepolarizing drugs, are used to facilitate intubation and provide skeletal muscle relaxation during surgery and in the intensive care unit. The agents differ in their mechanism, duration of action, side-effect profile, and metabolism. Succinylcholine is the only depolarizing agent in clinic use and is typically used for emergent control of the airway, rapid sequence intubations, and short surgical procedures. The risk of hyperkalemia in certain clinical conditions and risk of malignant hyperthermia in susceptible individuals limit the use of succinylcholine in specific patient populations. Nondepolarizing agents vary in their duration of action, but all provide muscle relaxation for a longer duration than succinylcholine. Clinical effects of neuromuscular blocking drugs can be assessed with neuromuscular monitoring, although there is significant variability among providers in the regular use of neuromuscular monitoring. Reversal agents are used to restore neuromuscular transmission, as residual neuromuscular blockade after extubation has been associated with multiple adverse events, including hypoxemia, atelectasis, and aspiration. Sugammadex is an encapsulating agent capable of immediately reversing the effects of rocuronium-induced neuromuscular blockade that will likely impact the way many providers administer rocuronium and may decrease the future use of succinylcholine. This review contains 4 figures, 6 tables, and 41 references. Keywords: hyperkalemia, neuromuscular monitoring, neuromuscular transmission, nondepolarizing neuromuscular blocking agents, residual neuromuscular blockade, reversal agents, succinylcholine sugammadex, sugammadex

Reversal of rocuronium induced neuromuscular blockade using sugammadex in a patient with eclampsia treated by magnesium intraoperatively.

Magnesium has been used frequently both as an anticonvulsant for preeclampsia and in the treatment of preterm labor. Magnesium also results in potentiation of the effects of neuromuscular blocking drugs, and attenuates their reversal with anticholinesterase [1]. Prolongation of the duration of the neuromuscular blockade (NMB) increases the risk of residual paralysis. Unlike anticholinesterase, sugammadex binds steroidal muscle relaxants by encapsulation, and it can rapidly and completely antagonize the action of the NMB. Theoretically, magnesium sulfate may reduce the efficacy of sugammadex [2]. We report a successful reversal of NMB with sugammadex in a patient with eclampsia who was treated with magnesium intraoperatively and showed incomplete reversal with anticholinesterase from rocuronium-induced NMB. A 30-year-old multipara (height 167 cm, weight 62 kg) at 27 weeks and 5 days of gestation visited the emergency room (ER) complaining of epigastric soreness, nausea, vomiting, and headache since the previous night. She had no specific medical history. Her blood pressure was 200/124 mmHg, heart rate 86 beats/min, and respiratory rate 24 breaths/min. According to a non-stress test, the fetal heart rate was 150 beats/min. After intravenous administration of hydralazine 5 mg, her blood pressure decreased to 140/100 mmHg. Forty minutes later, a seizure occurred. Diazepam 10 mg was immediately administered intravenously, and just an hour after the patient’s arrival at the ER, an emergency cesarean section was performed under general anesthesia.

Evaluation of the antimicrobial effects of atracurium, rocuronium and mivacurium. Antimicrobial effects of muscle relaxants

Some anaesthetic agents may be contaminated with microorganisms during the process of preparing an infusion. For this reason, it is important to understand the antimicrobial effects of various anaesthetic agents, which have been investigated to some degree in previous studies. However, studies specifically focusing on antibacterial effects of neuromuscular blocking drugs (anaesthetic agents) are very rare. Herein, we analysed the antimicrobial effects of atracurium, rocuronium, and mivacurium, on four different microorganisms. The in vitro antimicrobial activities of atracurium, rocuronium and mivacurium were investigated using the broth microdilution method. The pH of the test solutions was determined using a pH meter. The test microorganisms included Staphylococcus aureus ATCC 29213, Enterococcus fecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. The pH of the test solutions ranged between 7.20 and 7.32. The minimum inhibitory concentrations of atracurium, rocuronium and mivacurium for S. auereus, E. fecalis, E. coli and P. Aeruginosa were all found to be 512 µg/mL. Atracurium, rocuronium and mivacurium inhibit the growth of common intensive care unit pathogens at the same concentration (512 µg.mL–1). Thus, the neuromuscular blocking drugs, atracurium, rocuronium and mivacurium should be administered at a minimum concentration of 512 µg/mL in intensive care units to achieve this antibacterial effect. In our opinion, when used systemically, atracurium, rocuronium and mivacurium do not cause a systemic antibacterial effect. However, their antibacterial effects may be advantageous for inhibiting the spread of bacterial contamination during the preparation of the infusion solutions.

A Randomized, Dose-Response Study of Sugammadex Given for the Reversal of Deep Rocuronium- or Vecuronium-Induced Neuromuscular Blockade Under Sevoflurane Anesthesia

Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium. We designed this randomized, open-label, dose-response trial to explore the dose-response relationship of sugammadex for the reversal of deep neuromuscular blockade induced by rocuronium or vecuronium under propofol-induced and sevoflurane-maintained anesthesia. As a secondary objective, the safety variables of sugammadex were evaluated. After anesthesia induction with propofol, 102 patients aged > or = 20 and < 65 yr were randomized to receive a single bolus dose of rocuronium 0.9 mg/kg (n = 50) or vecuronium 0.1 mg/kg (n = 52), followed by maintenance doses (rocuronium 0.1-0.2 mg/kg or vecuronium 0.02-0.03 mg/kg) as needed. Neuromuscular blockade was monitored using acceleromyography. After the last dose of NMBD, at 1-2 posttetanic counts, a single bolus dose of sugammadex 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg was administered. The primary efficacy variable was time from start of sugammadex administration to recovery of the T(4)/T(1) ratio to 0.9. The per-protocol population consisted of 48 patients in the rocuronium group and 47 in the vecuronium group. A dose-response effect was demonstrated for decreased mean time to recovery of the T(4)/T(1) ratio to 0.9 with increasing sugammadex dose in both NMBD groups (per-protocol population): rocuronium group, 79.8 (SD 33.0) min (sugammadex 0.5 mg/kg) to 1.7 (0.7) min (4.0 mg/kg) and 1.1 (0.3) min (8.0 mg/kg subgroup); vecuronium group, 68.4 (31.9) min (0.5 mg/kg) to 3.3 (3.5) min (4.0 mg/kg), and 1.7 (0.8) min (8.0 mg/kg subgroup). Neuromuscular monitoring showed recurrent neuromuscular blockade in 5 patients, all in the rocuronium group (2 given sugammadex 0.5 mg/kg and 3 given 1.0 mg/kg), but there were no clinical events attributable to recurrent or residual neuromuscular blockade. Sugammadex at doses of > or = 4 mg/kg provides rapid reversal of deep rocuronium- and vecuronium-induced neuromuscular blockade under sevoflurane maintenance anesthesia.

The undesirable effects of neuromuscular blocking drugs

Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking drugs including the definitions, diagnosis and causes of hypersensitivity reactions and postoperative residual curarisation.

Cyclodextrins and the emergence of sugammadex

Residual paralysis, with its subsequent postoperative pulmonary sequelae, is one of the major complications of anaesthesia, and was recognised shortly after the introduction of neuromuscular blocking drugs into routine clinical practice. Although its incidence decreased with the introduction of intermediate duration drugs, and further diminished with routine neuromuscular monitoring and reversal with cholinesterase inhibitors, residual paralysis still remained a problem. In the search for alternatives to stop the effect of neuromuscular blocking drugs and to match their duration of action to clinical need, chelation of the non-depolarising neuromuscular blocking drugs was considered. It was recognised that cyclodextrins could encapsulate steroidal molecules and thereby inactivate the aminosteroidal neuromuscular blocking drugs. In order to improve the binding of rocuronium to the cyclodextrin and to increase the compound's water solubility, the molecule was modified. This led to the development of sugammadex (Org 25969), a modified gamma-cyclodextrin. The modification of the molecule and the initial in vitro studies that led to in vivo and later human studies of this conceptually new drug for anaesthesia are described.

Reversal of Rocuronium-Induced Neuromuscular Block with the Novel Drug Sugammadex Is Equally Effective Under Maintenance Anesthesia with Propofol or Sevoflurane

In this study we investigated whether the novel reversal drug, sugammadex, is equally effective at reversing rocuronium-induced neuromuscular block (NMB) in patients under propofol or sevoflurane maintenance anesthesia. After receiving propofol for induction, patients were randomized to propofol (n = 21) or sevoflurane (n = 21). Rocuronium 0.6 mg/kg was administered for tracheal intubation. NMB was monitored using acceleromyography. At reappearance of the second twitch of the train-of-four ratio, sugammadex 2.0 mg/kg was administered by IV bolus. The primary end-point was time from start of sugammadex administration to recovery of train-of-four ratio to 0.9. Mean recovery time was 1.8 min after both propofol and sevoflurane anesthesia. The 95% confidence interval for the difference in recovery time between the 2 groups (-0.5 to +0.4 min) was well within the predefined equivalence interval (-1 to +1 min), indicating that recovery from NMB was unaffected by maintenance anesthesia. Thirteen patients (propofol n = 4; sevoflurane n = 9) experienced adverse events; these were treatment-related in 4 patients (propofol n = 3; sevoflurane n = 1). There were no treatment-related serious adverse events and no discontinuations or deaths. No residual paralysis occurred. The safety profile of sugammadex was somewhat more favorable under propofol than under sevoflurane anesthesia.

Botox injections and monitoring neuromuscular blockade

Debate has raged for many years about the ideal place to monitor the effects of neuromuscular blocking drugs. Although there exist proponents of restricting the use of nerve stimulators to the ulnar nerve, we suspect that the majority of anaesthetists use the face as their preferred site for monitoring, placing the electrodes on the side of the patient's forehead, at around the level of the ear. We have found another good reason not to rely upon this site for accurate neuromuscular function monitoring. A youthful-looking 35-year-old woman presented for elective laparoscopic surgery. She was classifiable as ASA physical status I and had had no problems with previous anaesthetics. She was taking no medications. Anaesthesia was induced with fentanyl, propofol and rocuronium was given for neuromuscular blockade, and continued in an uncomplicated fashion for a little over an hour. To judge the need for reversal of the rocuronium, electrodes were placed on her forehead as described above. Train-of-four, double-burst and tetanic stimulation patterns were all tried at maximum current output but to no avail: there were no visible or palpable evoked contractions. The electrodes were checked and were found to be fresh and moist; the device was tested on one of the authors' ulnar nerves at the wrist – the contraction of the small muscles of the hand was vigorous and painful. The device was once again used on the patient's forehead; evoked contractions of the upper facial muscles were still absent. In a moment of inspiration, the lead author placed the electrodes over the patient's ulnar nerve at the wrist. A train-of-four stimulus provoked four forceful and fade-free muscle contractions. No neostigmine was given and the patient enjoyed an uncomplicated emergence from anaesthesia. On questioning once awake in the recovery room, the patient admitted to having given herself a self-indulgent and expensive 35th birthday present: a trip to her local plastic surgeon for Botox injections to her face. These had certainly maintained her youthful appearance, although they had aged her anaesthetist slightly over concerns about her neuromuscular function. This case has changed our practice in two ways: we now use the ulnar nerve whenever possible to monitor neuromuscular function, and we routinely ask youthful-looking patients of either sex whether they have had recent Botox injections.

Impact of Hypothermia on the Response to Neuromuscular Blocking Drugs

Muscle strength is reduced during hypothermia, both in the presence and in the absence of neuromuscular blocking drugs. A 2 degrees C reduction in body temperature may double the duration of neuromuscular blockade. Central body and muscle temperatures decline in parallel, as long as peripheral vasoconstriction does not occur. A reduction in muscle strength must be expected at a body temperature less than 36 degrees C (corresponding to a muscle temperature of approximately 35 degrees C). Local cooling of the hand may make adductor pollicis twitch tension monitoring less useful during clinical anesthesia. The efficacy of neostigmine is maintained during mild hypothermia. The use of a nerve stimulator is strongly recommended to monitor the effect of neuromuscular blocking drugs during intraoperative hypothermia.

Antagonism of neuromuscular blockade but not muscle relaxation affects depth of anaesthesia

Conflicting effects of neuromuscular blocking drugs and anticholinesterases on depth of anaesthesia have been reported. Therefore we evaluated the effect of atracurium and neostigmine on bispectral index (BIS) and middle-latency auditory evoked potentials (AAI). We studied 40 patients (ASA I-II) aged 18-69 yr. General anaesthesia consisted of propofol and remifentanil by target-controlled infusion and neuromuscular function was monitored by electromyography. When BIS reached stable values, patients were randomly assigned to one of two groups. Group 1 received atracurium 0.4 mg kg(-1) and, 5 min later, the same volume of NaCl 0.9%; group 2 received saline first and then atracurium. When the first twitch of a train of four reached 10% of control intensity, patients were again randomized: one group (N) received neostigmine 0.04 mg kg(-1) and glycopyrrolate 0.01 mg kg(-1), and the control group (G) received only glycopyrrolate. Injection of atracurium or NaCl 0.9% had no effect on BIS or AAI. After neostigmine-glycopyrrolate, BIS and AAI increased significantly (mean maximal change of BIS 7.1 [SD 7.5], P<0.001; mean maximal change of AAI 9.7 [10.5], P<0.001). When glycopyrrolate was injected alone BIS and AAI also increased (mean maximal change of BIS 2.2 [3.4], P=0.008; mean maximal change of AAI 3.5 [5.7], P=0.012), but this increase was significantly less than in group N (P=0.012 for BIS; P=0.027 for AAI). These data suggest that neostigmine alters the state of propofol-remifentanil anaesthesia and may enhance recovery.

Effects of neuromuscular-blocking drugs in rats in vivo: direct measurements in the diaphragm and tibialis anterior muscle.

Effects of neuromuscular-blocking drugs are often investigated in rodents using both the diaphragm in vitro and the tibialis anterior muscle in vivo. Differences in the properties of these muscles cannot be neglected. We evaluated the neuromuscular effects of drugs on the rat diaphragm in vivo in comparison with the tibialis anterior muscle, directly measuring twitch tension with a force transducer. Respectively using sternotomy and an approach via the gluteal space, transducers were attached to the diaphragm and the tibialis anterior muscle. Phrenic and sciatic nerves were stimulated supramaximally by single square pulses to record isometric contraction of muscles. Pancuronium, vecuronium, or rocuronium was infused continuously at a rate adjusted repeatedly until stable tension was obtained. Effective doses for 50% (ED 50) and 90% (ED 90) depression of tension were calculated, using a cumulative infusion dosing method. Isometric contraction of the diaphragm could be recorded despite movements of the heart and lungs. For all three drugs, both mean ED 50 and ED 90 were more than twice as large for the diaphragm as for the tibialis anterior (P<0.05). In addition, slopes of dose-response curves for the diaphragm were significantly less steep than those of the tibialis anterior for the three drugs. Neuromuscular-blocking effects on the diaphragm can be recorded in vivo. According to direct contractile force measurement, the diaphragm is more resistant to non-depolarizing neuromuscular-blocking drugs than the tibialis anterior muscle.

Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism.

The duration of action for many pharmaceutical agents is dependent on their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact with these enzyme systems may alter drug efficacy and time course. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs. Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and cholinesterase inhibitors in vivo and in vitro. Inhibition of purified human AChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo experiments were carried out using anesthetized rabbits to test whether SGAs affect recovery from mivacurium-induced paralysis. SGAs inhibited human BuChE at concentrations similar to those found in serum of individuals who have eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with neuromuscular blocking drugs and cholinesterase inhibitors produced additive cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12). These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.

Effect of succinylcholine on the neuromuscular junction of hypoglycemic rats

The aim of the present study was to investigate the effect of neuromuscular blocking drugs on the neuromuscular junction in hypoglycemic rats. Three groups of 6 white adult Wistar albino rats were used. Group A consisted of the control animals with normal blood glucose levels ranging between 80-120 mg/dl. Groups B and C consisted of animals which were made hypoglycemic by intravenous injection of insulin at a dose of 1 iU/100 g b.w. In this way, their blood glucose levels were reduced to 50% of the blood glucose levels of the control animals. The test animals (groups B and C) were sacrificed 40 min after the injection of insulin and the preparations of the phrenic nerve-hemidiaphragm were placed into a 100 ml_bath containing Paradelis-Zaimis solution. The bath was aerized with O2/CO2:95/5%, it's temperature was maintained at 37 degrees C and it's pH at 7.2. After the stabilization of the system and the recording of neuromuscular activity, succinylcholine was administered (1.5 x 10(-8) M in groups A and B and 3.0 x 10(-8) M in group C). For the statistical analysis of the results, student's t-test was used. According to our results, there is a statistically significant difference (with p < 0.02 being considered significant) between the n.bl/t% (magnitude of final neuromuscular blockage) values of the animals of groups B and C and those of the animals of group A. We also observed a statistically significant difference (with p < 0.001 being considered significant) between the t (time required for complete blockage in groups A and C or time required for stabilization of blockage in group B) values of the animals of groups B and C and those of the animals of group A. On the other hand, there was a statistically significant difference (p < 0.02 being considered significant) in the n.bl/5'% (magnitude of neuromuscular blockage 5 min after the administration of succinylcholine) values only between the animals of group A and B. Our results indicate that under hypoglycemic conditions, the amount of succinylcholine required for final neuromuscular blockage is two times greater than that needed under normal glucose blood levels. This finding suggests that the integrity of the neuromuscular junction is altered during hypoglycemia.

Prolonged Paralysis After a Test Dose of Mivacurium in a Patient with Atypical Serum Cholinesterase

Prolonged Paralysis After a Test Dose of Mivacurium in a Patient with Atypical Serum Cholinesterase

The kinetics of effect of neuromuscular blocking drugs.

In attempts to derive pharmacokinetic constants from effect data three methods were explored, using non-depolarizing neuromuscular blocking drugs as the paradigm for obtaining effect data. The first method, based on the simple assumption that following two doses, the drug concentrations at times of equal effect during recovery, were equal. Provided that recovery took place in the log-linear drug elimination phase, the elimination rate constant (beta) could be calculated. This method proved rather inaccurate, a second method, again dependent on recovery in the log-linear phase yielded a constant which was the product of beta and the exponent of the Hill equation (s). This method yielded results within 20% of values calculated from plasma drug assays, and it was demonstrated that the time-effect curve could be described from knowledge of this constant. The third method, using non-linear curve fitting technique, derived values for the rate constants of plasma redistribution (alpha) and elimination (beta) as well as for the rate constant of elimination from an effect compartment (keo). If the values were derived from the effect of two doses of a drug, the intensity and duration of effect of a third dose could be predicted with reasonable accuracy. The dose dependent constants of the usual compartmental equations for the plasma concentration of a drug (A and B) could be derived in terms of the EC50. The method can be applied to any drug whose effect can be measured and whose maximal effect can be defined. We believe that the method may be useful in rapidly and inexpensively estimating population kinetic parameters, and in screening drugs.

Central Nervous System Effects of Intrathecal Muscle Relaxants in Rats

When given for a sufficient time and dose intravenously, neuromuscular blocking drugs eventually can enter the cerebrospinal fluid (CSF). To study the potential pharmacologic consequences of neuromuscular blocking drugs in the CSF, a model was developed in the rat by using an intrathecal infusion of these drugs. A cannula was stereotaxically implanted in a lateral cerebral ventricle of anesthetized male Sprague-Dawley rats (250-300 g). Several days later, the effects of an intraventricular infusion (5 microL/min) of atracurium (0.804 mumol/mL), pancuronium (0.172 mumol/mL), and vecuronium (21.978 mumol/mL) were studied in unanesthetized rats. These rats (n = 6 in each group) exhibited dose-dependent hyperexcitability, during drug infusion, with seizures occurring at threshold doses of (mean), 0.12, 0.26, and 0.065 +/- 0.010 and 3.32 mumol/kg of atracurium, pancuronium, and vecuronium, respectively. The neuromuscular ED50 (intravenous dose required to produce a 50% depression of twitch tension) in rats determined by other investigators are 0.408, 0.115, and 0.352 mumol/kg for atracurium, pancuronium, and vecuronium, respectively. Therefore, seizure threshold doses were not related to the potencies of these drugs as neuromuscular blocking drugs. Based on these data, central nervous system effects were studied over the subseizure dose range approximating 1/100, 1/10, and 1/5 of the cumulative dose causing seizures for each drug (n = 5 for each dose). At 1/100 of seizure dose, decreased locomotor activity and piloerection occurred. At 1/10 to 1/5 of seizure dose, agitation, shivering, splayed limbs, and whole body shaking resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic and cardiovascular effects of neuromuscular-blocking drugs

Autonomic and cardiovascular effects of neuromuscular-blocking drugs

Clinical and Electromyographical Evaluation of Neuromuscular Blockade Which Has Been Observed After the Application of Atracurium Besilat and Pancuronium Bromide

During general anesthesia neuromuscular blocking drugs have been applied. After general anesthesia the effects of neuromuscular blocking drugs on neuromuscular junction have been cured. in patients curing from blockade has been determined by EMG. Train-of-four stimulation was used tor the records of EMG. Two different doses of atracurium and one dose of pancuronium have been applied. Our study has been done on 54 patıents. At the end of our study we observed that curing after every two doses of atracurium was faster than pancuronium.