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At least 19 recordsLinked to original sources
PubMedDate not supplied

The impact of practice guidelines on prescribing patterns of nondepolarizing neuromuscular blocking agents.

Guidelines for selecting nondepolarizing neuromuscular blocking agents (NNMBAs) were developed and implemented by an interdisciplinary team for use in our intensive care units. They suggest pancuronium as the drug of choice if the patient does not have renal insufficiency and is hemodynamically stable. If either of these criteria is not met and hepatic function is normal, vecuronium is recommended. Atracurium is reserved for patients not meeting either criterion. A 12-month retrospective chart review was performed for 24 patients 18 years of age or older who received continuous infusion of an NNMBA beginning 7 months after the guidelines were implemented. Before the guidelines, atracurium, vecuronium, and pancuronium were prescribed for 68% (17), 24% (6), and 8% (2) of patients, respectively. Their use was inappropriate based on organ function and hemodynamic stability in 88% (15), 83% (5), and 0% of patients, respectively. After guideline implementation, atracurium, vecuronium, and pancuronium were prescribed for 33% (8), 21% (5), and 46% (11) of patients, respectively, and use was inappropriate in 38% (3), 60% (3), and 0% of patients, respectively. Overall, the prevalence of inappropriate NNMBA selection decreased from 80% (20) to 25% (6). Further analysis is necessary to determine the associated pharmacoeconomic impact of decreased inappropriate NNMBA prescribing.

Atracurium↗
PubMed1981

An analytical pharmacodynamic model for nondepolarizing neuromuscular blocking agents.

A pharmacodynamic model for nondepolarizing neuromuscular blocking agents (NMBA) is developed and tested with different sets of data (NMBA plasma concentration and time evolution of muscular paralysis). This model takes into account the binding of NMBA to the cholinergic motor endplate receptors and thus permits estimation of the apparent equilibrium constant of the NMBA-receptor exchange. The parameters defining the relationship between relative postsynaptic receptor occupation and muscular paralysis can also be determined. The simulated muscular paralysis time curves, calculated for various modes of NMBA administration (loading injection and multiple injections or continuous infusion) are comparable to those observed clinically. As compared to previous NMBA pharmacodynamic models, the model presented in this study utilizes and describes all the main steps between changes in the plasma NMBA concentration and the observed response: pharmacokinetics, ligand-receptor exchanges, and receptor occupation-effect relationship. This model illustrates a general methodology for the study of pharmacokinetic and pharmacodynamic problems.

Humans↗
PubMed1991

Use of nondepolarizing neuromuscular blocking agents in mechanically ventilated patients.

The pharmacology and history of development of nondepolarizing neuromuscular blocking agents are presented, and the pharmacokinetics and pharmacodynamics of these agents, administration guidelines for mechanically ventilated patients, adverse effects, factors affecting paralysis, and methods for blockade reversal are reviewed. Nondepolarizing neuromuscular blocking agents (tubocurarine, metocurine, pancuronium, vecuronium, and atracurium) are frequently used to induce prolonged pharmacologic paralysis in patients in the intensive-care unit (ICU). These agents are poorly absorbed after oral administration and must be administered by injection, preferably by the i.v. route. Individualized adjustment of the dose is necessary to maintain the desired degree of paralysis. Dosing modifications may be necessary in patients with underlying renal or hepatic diseases and in pediatric and geriatric patients. Patients with thermal burns require larger doses of these drugs than other patients. These agents can cause several important adverse effects, including histamine release, cardiovascular changes, and muscle atrophy. Pathophysiologic variables and drug interactions can affect the degree of paralysis. Generally, patients no longer requiring paralysis in the ICU will be allowed to spontaneously regain muscle function after drug therapy has been discontinued. If the effects of the nondepolarizing neuromuscular blocking agents must be reversed more rapidly, acetylcholinesterase-inhibiting agents such as physostigmine, neostigmine, pyridostigmine, and edrophonium can be used. Nondepolarizing neuromuscular blocking agents can be used to paralyze mechanically ventilated patients, facilitating optimal oxygenation and ventilation.

Aged↗
PubMed1994

Prolonged paralysis due to nondepolarizing neuromuscular blocking agents and corticosteroids.

The long-term use of nondepolarizing neuromuscular blocking agents (ND-NMBA) has recently been implicated as a cause of prolonged muscle weakness, although the site of the lesion and the predisposing factors have been unclear. We report 3 patients (age 37-52 years) with acute respiratory insufficiency who developed prolonged weakness following the discontinuation of ND-NMBAs. Two patients also received intravenous corticosteroids. Renal function was normal but hepatic function was impaired in all patients, and all had acidosis. Electrophysiologic studies revealed low amplitude compound motor action potentials, normal sensory studies, and fibrillations. Repetitive stimulation at 2 Hz showed a decremental response in 2 patients. The serum vecuronium level measured in 1 patient 14 days after the drug had been discontinued was 172 ng/mL. A muscle biopsy in this patient showed loss of thick, myosin filaments. The weakness in these patients is due to pathology at both the neuromuscular junction (most likely due to ND-NMBA) and muscle (most likely due to corticosteroids). Hepatic dysfunction and acidosis are contributing risk factors.

Adrenal Cortex Hormones↗
PubMedDate not supplied

A retrospective analysis of long-term use of nondepolarizing neuromuscular blocking agents in the intensive care unit, and guidelines for drug selection.

Nondepolarizing neuromuscular blocking agents (NNMBAs) are frequently administered to patients in the intensive care unit (ICU). We conducted a retrospective study of patients in intensive care who received infusions (> 48 hrs) of commonly used NNMBAs. The goals were to describe NNMBA use in our ICUs, determine patient characteristics, and assess the cost of the individual drugs. We found that atracurium was prescribed for 68% of study patients; 68% of the patients did not have renal, hepatic, or cardiovascular disease; dosages of NNMBAs varied; a statistically significant increase in dosage requirements over time occurred with atracurium; assessment of neuromuscular blockade was 100% subjective; and 41% and 17% of patients receiving atracurium and vecuronium, respectively, experienced prolonged neuromuscular weakness documented subjectively. As a result of this study, guidelines for agent selection were developed to facilitate cost effective use of NNMBA in our ICUs. Using these guidelines would potentially significantly decrease drug expenditures in this setting.

Adult↗
PubMedDate not supplied

Resistance to nondepolarizing neuromuscular blocking agents.

Several case reports of resistance to short-term administration of nondepolarizing neuromuscular blocking agents (NNMBAs) have been reported in research and surgical settings. Recently, several reports documented resistance to NNMBAs during therapy for prolonged paralysis in critically ill patients. Adverse outcomes associated with NNMBA resistance may include inadequate ventilatory management or suppression of patient movement, and an increased risk of dose-dependent cardiovascular adverse effects. Pharmacoeconomic issues must be considered in that the cost of NNMBA therapy in a resistant patient may be significant. Although the specific etiologies of resistance are not clear, several pharmacodynamic and pharmacokinetic alterations may occur as a consequence of disease state or concomitant drug therapy. Pharmacodynamic changes include altered acetylcholine receptor physiology or sensitivity, inhibition of serum cholinesterase activity, and interaction with plasma constituents. Alterations in distribution volume, protein binding, and clearance may also contribute to resistance in several disease states.

Animals↗
PubMed2000

Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels.

OBJECTIVE: Long-term treatment with nondepolarizing neuromuscular blocking agents and corticosteroids in the intensive care unit is not benign, and an increasing number of patients with acute quadriplegic myopathy have been reported with increased use of these drugs. The purpose of this study was to investigate the mechanisms underlying acute quadriplegic myopathy. DESIGN: Percutaneous muscle biopsy samples were obtained, and electrophysiologic examinations were performed during the acute phase and during recovery in patients with acute quadriplegic myopathy. Regulation of muscle contraction and myofibrillar protein synthesis was studied using cell physiologic techniques, ultrasensitive electrophoresis, in situ hybridization, and histopathologic techniques. SETTING: All patients were seen in the intensive care unit of different university hospitals. PATIENTS: All patients were critically ill with sepsis. They had been given massive doses of corticosteroids in combination with variable doses of neuromuscular blocking agents. All patients developed paralysis of spinal nerve-innervated muscles. On the other hand, cranial nerve-innervated muscle and sensory and cognitive functions were well maintained after discontinuation of treatment with neuromuscular blocking agents. INTERVENTION: Muscle biopsy samples were obtained and electrophysiologic examinations were performed in all patients. MEASUREMENTS AND MAIN RESULTS: The major observations in patients with acute quadriplegic myopathy were, as follows: a) a general decrease in myofibrillar protein content; b) specific but highly variable partial or complete loss of myosin and myosin-associated proteins; c) very low thick-filament/thin-filament protein ratios; d) absence of myosin messenger RNA; and e) a dramatically impaired muscle cell force-generating capacity in the acute phase of acute quadriplegic myopathy. During clinical improvement, normal expression of myosin messenger RNAs, reexpression of thick-filament proteins, and increased specific tension were observed. CONCLUSIONS: Acute quadriplegic myopathy is associated with a specific decrease in thick-filament proteins related to an altered transcription rate. Although the decreased content of thick-filament proteins is important for prolonged muscle weakness, it is not the primary cause of muscle paralysis in the acute stage, during which impaired muscle membrane excitability probably plays a more significant role. Several factors contribute to this condition, but the action of corticosteroids seems to be the predominant one, along with potentiation by neuromuscular blocking agents, immobilization, and probably also concurrent sepsis.

Acute Disease↗
PubMed2004

Anaphylaxis during surgical and interventional procedures.

OBJECTIVE: To describe the current evidence-based knowledge of the causes, diagnostic evaluation, and treatment of patients with anaphylaxis associated with surgical and interventional procedures. DATA SOURCES: Articles published between 1966 and 2003 were identified in MEDLINE using the keywords anaphylactoid, anaphylaxis, anesthetics, antibiotics, cephalosporins, contrast media, colloids, flow cytometry, hypersensitivity, latex, neuromuscular depolarizing agents, neuromuscular nondepolarizing agents, penicillins, radioallergosorbent test, skin test, and vancomycin. Additional studies were identified from article reference lists. STUDY SELECTION: Relevant, peer-reviewed original research articles and reviews. RESULTS: Neuromuscular blocking agents, natural rubber latex, antibiotics, and induction agents are the most common causes of anaphylaxis during surgical and interventional procedures. Colloids, opioids, and radiocontrast media probably account for less than 10% of all reactions. Newer agents implicated in anaphylaxis include isosulphan blue and chlorhexidine. Skin tests are useful for evaluating allergic reactions to anesthetic agents and penicillins and for selecting alternative agents. Skin testing and specific IgE measurements for latex vary in allergen standardization and sensitivity and specificity, respectively. Flow cytometric allergen stimulation tests show promise in differentiating allergic from idiosyncratic ("pseudoallergic") reactions. Drug desensitization has been shown to be useful for penicillin anaphylaxis. Premedication with histamine receptor antagonists and corticosteroids helps prevent or attenuate radiocontrast media reactions. CONCLUSIONS: Anaphylaxis during surgical and interventional procedures may be difficult to evaluate because of the rapid, successive use of multiple drugs or diagnostic agents. Careful analysis of anesthetic records and diagnostic tests for all the putative agents are necessary to ensure a complete evaluation.

Anaphylaxis↗
PubMed2001

Increased sensitivity to depolarization and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms.

BACKGROUND: Newborn neuromuscular junctions are more sensitive to d-tubocurarine than more mature preparations. It is unclear whether the same modifications occur with newer nondepolarizing agents and depolarizing agent succinylcholine. The purpose of this study was to determine the relative sensitivity of newborn neuromuscular junctions to succinylcholine and five nondepolarizing agents. METHODS: The phrenic nerve-hemidiaphragm preparation from 60 rats was used, 30 aged 9-12 days (newborn) and 30 aged 27-33 days (adult). Five rats from each group were exposed to one of six neuromuscular blocking agents (d-tubocurarine, cisatracurium, atracurium, vecuronium, rocuronium, and succinylcholine). Indirectly elicited twitch tension was measured during control conditions in the absence of blocking agent, followed by four concentrations of one of the six agents. Concentration-response curves were constructed and the EC50 (concentration required to produce 50% depression of twitch tension) was obtained. Potency ratios (EC50adult/EC50newborn) were derived for each agent. RESULTS: Newborn preparations were significantly (P < 0.001) more sensitive than their adult counterparts for all six agents tested. For nondepolarizing agents, the potency ratio was in the 6-12 range. The EC50adult/EC50newborn were as follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 microM; cisatracurium, 2.73/0.47 microM; vecuronium, 5.47/0.59 microM; rocuronium, 9.7/0.78 microM; and atracurium, 12.3/1.9 microM. Succinylcholine was three times as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 microM. The ratio for succinylcholine was significantly less than for all nondepolarizing drugs (P < 0.02). CONCLUSION: The newborn neuromuscular junction of the rat shows an increased sensitivity to all neuromuscular blocking agents tested, including succinylcholine. However, the potency ratio was greater for nondepolarizing than depolarizing drugs. The optimal dose of these agents for certain situations such as cesarean section and anesthesia in neonates should be reassessed.

Animals↗
PubMed1997

Masseter muscle rigidity and nondepolarizing neuromuscular blocking agents.

Masseter muscle rigidity has been identified as a possible risk factor for malignant hyperthermia (MH) and is usually noted in children receiving intravenously administered succinylcholine chloride after mask induction with halothane. Nondepolarizing muscle relaxants are considered safe for persons susceptible to MH. In this article, we present a case of clinically recognized jaw rigidity in the absence of succinylcholine after administration of a non-depolarizing muscle relaxant that was reported to the Malignant Hyperthermia Association of the United States hot line. The patient had recurrent jaw rigidity during subsequent anesthesia when a different non-depolarizing muscle relaxant was given. The North American MH Registry was then reviewed for similar cases. Three cases of masseter muscle rigidity in the presence of nondepolarizing muscle relaxants were discovered. Two of the patients were not found to be susceptible to MH; however, the third patient had positive findings on muscle biopsy. These cases do not provide enough information to confirm the ability of nondepolarizing muscle relaxants to cause jaw rigidity in the absence of MH.

Adult↗
PubMed1999

Pharmacology of G-1-64, a new nondepolarizing neuromuscular blocking agent with rapid onset and short duration of action.

BACKGROUND: Chances are slim that a clinically useful ultra-short-acting neuromuscular blocking agent of rapid onset will emerge from the benzylisoquinolinium or the aminosteroid series to which all currently popular relaxants belong. G-1-64 is a promising prototype of a new series of bis-quaternary ammonium salt of bistropinyl diester derivatives we have synthesized and studied in the laboratory. METHODS: Neuromuscular block (NMB) and autonomic and cardiovascular side effects were studied on appropriate preparations of anesthetized rats, rabbits, cats, ferrets, pigs and monkeys. Neuromuscular blocking characteristics, cumulativeness, and pharmacological reversibility were determined. Cardiac vagal block was evaluated by the inhibition of the bradycardic response to stimulation of the vagus in the cat, rat, ferret, and pig. Sympathetic ganglion block was evaluated on the cat's superior cervical ganglion/nictitating membrane preparation. Arterial blood pressure and heart rate were determined in all species. RESULTS: G-1-64 produced nondepolarizing NMB with train-of-four (TOF) and tetanic fades, and reversible with anticholinesterases. Its ED50 ranged between 60 and 800 microg/kg in these species. It showed a significantly faster onset (0.9-2.1 min) and/or shorter duration of action (5-12 min) than either atracurium or mivacurium. It did not show cumulativeness on repeated doses or infusion. A varying degree of cardiac vagal block was present, dependent on the species at doses exceeding the ED80 for NMB. Cardiovascular changes, ganglion block or signs suggesting histamine release were absent. CONCLUSION: With favorable neuromuscular blocking characteristics and modest side effects, G-1-64 and similar derivatives may have clinical potential.

Androstanols↗
PubMed1994

The role of nondepolarizing neuromuscular blocking agents in mechanically ventilated patients.

Prolonged use of the nondepolarizing neuromuscular blocking agents in the critical care setting has greatly increased in the recent past. Accompanying the increased use of these agents are numerous accounts of long-lasting adverse outcomes such as muscular atrophy and neuropathy that can be attributed to pharmacologic paralysis. There has been a financial impact on hospitals as well. Responding to these facts, the medical staff at the Medical College of Georgia Hospital and Clinics recently approved guidelines for the use of nondepolarizing neuromuscular blocking agents in the intensive care setting. These guidelines recommend clinical indications for these agents and dosing ranges reflecting current medical opinion.

Atracurium↗
PubMed1998

Neuromuscular blocking and cardiovascular effects of Org 9487, a new short-acting aminosteroidal blocking agent, in anaesthetized animals and in isolated muscle preparations.

This study was undertaken to investigate the neuromuscular blocking profile and cardiovascular effects of Org 9487, a new aminosteroidal, non-depolarizing, neuromuscular blocking agent structurally related to vecuronium, in anaesthetized animals and in isolated muscle preparations. In in vitro functional assays of neuromuscular blocking activity, Org 9487 was between eight and 15 times less potent than vecuronium. In cats and monkeys the potency of Org 9487 was approximately one-seventh and one-twentieth, respectively, that of vecuronium. In both species, Org 9487 induced rapidly developing (onset times between 1.5 min and 1.9 min) neuromuscular paralysis, which was shorter-lasting than that of vecuronium and similar in time course to suxamethonium. The vagal: neuromuscular blocking dose ratio for Org 9487 was 3 and ganglion block was seen only at approximately 20 times the neuromuscular blocking dose. There was no evidence in the rat that Org 9487, administered at doses up to 3 mg kg-1, inhibited noradrenaline re-uptake. In anaesthetized dogs, Org 9487 (3 x 90% blocking dose) induced only relatively small and transient haemodynamic effects. The administration of clinically relevant doses of neostigmine or pyridostigmine shortened the time-course profile of Org 9487, even when administered during profound neuromuscular block. In animals, Org 9487 is a low potency, nondepolarizing neuromuscular blocking agent with a time course profile similar to that of suxamethonium. Although Org 9487 is less selective than vecuronium for the neuromuscular junction, it is unlikely to produce prohibitive cardiovascular side effects in man.

Adrenergic alpha-Agonists↗
PubMed2006

Onset and duration of mivacurium-induced neuromuscular blockade in children with Charcot-Marie-Tooth disease. A case series with five children.

BACKGROUND: The Charcot-Marie-Tooth (CMT) disorders are a group of hereditary motor and sensory neuropathies characterized clinically by peripheral muscle wasting and weakness. We hypothesized that unknown involvement of the muscle used for monitoring neuromuscular block may account for the conflicting reports about the effect of nondepolarizing neuromuscular agents in these patients. The aim of this study was to compare onset and recovery from mivacurium-induced neuromuscular block on the adductor pollicis and orbicularis oculi muscles. METHODS: We used mivacurium 0.2 mg.kg(-1) in five children (aged 7-12 years) with CMT type I undergoing propofol-fentanyl-oxygen-air anesthesia for orthopedic surgery. Using acceleromyography, neuromuscular transmission was monitored in parallel in the eye and thumb muscles, and onset and duration times were recorded. RESULTS: Following bolus administration of 0.2 mg.kg(-1) of mivacurium the onset time ranged between 135 and 240 s and 75 and 165 s in the eye and in the thumb, respectively. The recovery time varied between 5.3 and 16 min and 6 and 31.3 min in the eye and in the thumb, respectively. CONCLUSIONS: In our small series of patients with CMT the clinical duration of mivacurium-induced neuromuscular block was similar to data known from children without neuromuscular disease.

Anesthesia Recovery Period↗
PubMed2003

Comparative fading responses induced by mivacurium, cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat.

PURPOSE: It has been suggested that the different degrees of fade induced by nondepolarizing neuromuscular blocking agents in repetitive muscular contractions may be due to the varying affinities or binding kinetics of presynaptic nicotinic receptors. We compared the degree of fade induced by mivacurium, cisatracurium, and d-tubocurarine in the cat muscular compound action potential (mCAP). METHODS: In 21 cats, mCAPs of the gastrocnemius muscle were evoked by paired (conditioning and test stimuli) and 2 Hz train-of-four (TOF) sciatic nerve stimulation. The interval between the paired stimuli was changed stepwise from 7 to 1000 ms. The ratios of the amplitude evoked by test stimulus to that evoked by the conditioning stimulus (M2/M1 ratios) and TOF ratios were measured. After baseline variables had been obtained, the cat received either mivacurium (0.08 mg x kg(-1), n = 7), cisatracurium (0.05 mg x kg(-1), n = 7), or d-tubocurarine (0.5 mg x kg(-1), n = 7). A series of M2/M1 ratios and TOF ratios were measured at various levels of partial block during recovery. RESULTS: At 10% of baseline amplitude, all agents significantly depressed the M2/M1 ratios (i.e., fade) at relatively longer intervals of paired stimuli (mivacurium, > or = 100 ms; cisatracurium. > or = 40 ms; and d-tubocurarine, > or = 20 ms), when compared with baseline. The order of activity to produce fade was mivacurium < cisatracurium < d-tubocurarine. A similar result was obtained in TOF ratios measured at various levels of neuromuscular block. CONCLUSION: Our results suggest that mivacurium shows a lesser degree of fade during partial neuromuscular block than cisatracurium and d-tubocurarine.

Action Potentials↗