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PubMed2001

Different patterns of mast cell activation by muscle relaxants in human skin.

BACKGROUND: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. RESULTS: For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. CONCLUSIONS: Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.

Adult↗
PubMedDate not supplied

[Myasthenia gravis: thymectomy. Muscle relaxation with atracurium besilate].

We have carried out a prospective study on the use of the muscle relaxant, atracurium besilate, in 10 patients with myasthenia gravis, seven had type IIB and three had type IIA, who were scheduled for thymectomy, using ED95 0.20 mg/kg, and ten non myasthenic patients undergoing cholecystectomy using ED95 0.50 mg/kg. After monitoring neuromuscular transmission, the time for establishing maximum blockade (EMB), clinical efficacy time (CET), recovery index (RI) and total duration time (TDT) were measured and evaluated comparatively. Results showed that in myasthenics patients, EMB was faster, CET an TDT were more prolonged and RI was higher than in non myasthenic patients. We conclude that atracurium at doses of 0.20 mg/kg is currently the non depolarizing muscle relaxant of choice in myasthenic patients because of the excellent muscle relaxation allowing extubation in the operating room without reverting muscle blockade and not needing ventilatory support during postoperative period.

Adult↗
PubMed1992

Effect of inspiratory muscle fatigue on inspiratory muscle relaxation rates in healthy subjects.

Simple methods to diagnose inspiratory muscle fatigue in the clinical setting would be of considerable benefit. Inspiratory muscle relaxation rates are known to slow following induction of fatigue. Inspiratory muscle relaxation rates have been measured following a short sharp inspiratory effort against an occluded airway (sniffmouth) or through the unoccluded nostrils (sniffnostrils). Relaxation rates in the absence of fatigue are faster when sniffs are performed through the unoccluded nostrils. While both methods have been shown to be capable of detecting inspiratory muscle fatigue, there may be quantitative or qualitative differences between the two techniques in their ability to detect fatigue similar to the differences observed in the fresh state. Accordingly, we measured relaxation rates with the two sniff techniques in five healthy naive male subjects before and after induction of fatigue. Inspiratory muscle fatigue was induced by threshold loading at 80 percent of Pesmax until the subjects were unable to generate the target pressure. For those trials in which sniffnostrils were performed, the maximum relaxation rate from the esophageal pressure curve (MRRes) was significantly decreased following induction of fatigue in nine of ten trials, while the exponential time constant (taues) was significantly increased in all ten trials. In contrast, for those trials in which sniffmouth were performed, the MRRes was significantly decreased following induction of fatigue in only six of ten trials. Similarly, taues was significantly increased following induction of fatigue in only six of ten trials. In addition, the magnitude of change in the MRR or tau following induction of fatigue was quantitatively greater with sniffnostrils compared with sniffmouth. Similar findings were obtained when relaxation rates were measured from the diaphragmatic pressure tracing. In conclusion, changes in relaxation rate following induction of fatigue were quantitatively greater and more consistently observed when sniffs were performed through the unoccluded nostrils rather than against an occluded airway.

Adult↗
PubMed1992

A national survey on the practice patterns of anesthesiologist intensivists in the use of muscle relaxants.

OBJECTIVE: To determine the practice patterns of anesthesiologist intensivists (with the special certificate of competence in critical care medicine from the American Board of Anesthesiology) in the use of neuromuscular blocking drugs, in the ICU setting. DESIGN: A survey. PARTICIPANTS: All anesthesiologists with the special certificate of competence in critical care (n = 374) were selected for this study. Of the 339 who could be contacted and who were still actively practicing, 185 (55%) completed the survey. RESULTS: In the ICU setting, anesthesiologist intensivists most commonly used vecuronium (52%) administered by bolus injection, bolus injection followed by infusion, or by continuous infusion. The most frequent indication for muscle relaxation was facilitation of mechanical ventilation (89%). Neuromuscular blockade was most commonly monitored clinically (55%), with only 34% of respondents using a peripheral nerve stimulator. All respondents indicated the concomitant use of sedatives or narcotics with muscle relaxants. CONCLUSIONS: This study was created to address the dearth of information regarding actual usage of muscle relaxants in the ICU setting. The survey population was chosen as one with great familiarity in the use of muscle relaxants. The 55% response rate was significantly greater than the expected response rate for a single mailing survey. In the ICU setting, neuromuscular blocking drugs are most frequently used to facilitate mechanical ventilation. The prevalence of vecuronium use is of interest in light of recent case reports of prolonged neuromuscular blockade after long-term vecuronium administration. The low frequency of peripheral nerve stimulator monitoring during muscle relaxation may contribute, in part, to the problem of prolonged blockade after drug withdrawal. Muscle relaxants are not used in the absence of sedation and/or analgesia by this practitioner population.

Anesthesiology↗
PubMed2000

Requirements for muscle relaxants during radical retropubic prostatectomy.

BACKGROUND: The need for the routine use of muscle relaxants to provide an adequate surgical field for intraabdominal surgery has not been established. This study tested the hypothesis that vecuronium decreases the frequency of unacceptable operating conditions for patients undergoing radical retropubic prostatectomy who are anesthetized with isoflurane and fentanyl. METHODS: After obtaining informed consent, patients in this blinded, placebo-controlled study were randomized to receive either an infusion of vecuronium or saline (placebo) beginning 5 min after fascial incision during the maintenance of anesthesia with at least 1 minimum alveolar concentration end-tidal isoflurane and fentanyl infusion. The surgical field was graded from 1 (excellent) to 4 (unacceptable) by the surgeons at 15-min intervals. If a grade 4 rating occurred (defined as a treatment failure), the patient received rescue vecuronium. RESULTS: A total of 120 patients are included in this report (59 in the vecuronium group and 61 in the placebo group). The frequency of treatment failure in the placebo group was 17 of 61 (27.9%) versus 1 of 59 (1.7%) in the control group who received vecuronium (P < 0.001). Thirty-eight patients (62.3%) in the placebo group and 52 patients (88.1%) in the vecuronium group had surgical field ratings of < or = 2 (good to excellent) at each time assessed throughout the procedure. CONCLUSION: The study hypothesis was confirmed. However, an isoflurane-fentanyl anesthetic alone produced a good to excellent surgical field in approximately two thirds of patients undergoing radical retropubic prostatectomy without the use of muscle relaxants. Thus, the routine use of muscle relaxants in adequately anesthetized patients undergoing this procedure may not be indicated.

Aged↗
PubMed1994

Nitric oxide is involved in muscle relaxation but not in changes in short-circuit current in rat ileum.

L-Arginine (L-Arg)-nitric oxide (NO) pathways in rat ileum were studied in an Ussing chamber modified so that a strain gauge transducer could be attached longitudinally on the serosal side of the intestine. Ileal segments from 22 rats were mounted as flat sheets and voltage clamped at zero transmural potential (PD). Changes in short-circuit current (delta ISC) in the absence of carbachol and longitudinal muscle relaxations in the presence of carbachol in response to transmural field stimulation (TMS; 5-s trains of impulses, 0.4-ms impulse duration, 1-10 Hz) were recorded during a control period, in the presence of N omega-nitro-L-arginine (L-NNA; 10(-4) M), and in the presence of L-Arg after treatment with L-NNA. In the control period, the delta ISC and muscle relaxation were frequency dependent with maximal responses generated at a frequency of 10 Hz. Tetrodotoxin (5 x 10(-6) M) blocked muscle relaxation and decreased delta ISC by 94% during TMS at 10 Hz. L-NNA blocked the muscle relaxation induced by TMS but failed to alter delta ISC. Muscle relaxation to TMS was restored dose dependently by L-Arg. In segments from another group of eight rats, saturated NO solutions relaxed the muscle but failed to change ISC either in the presence or absence of carbachol. These results support a role for NO as a neurotransmitter mediating relaxation of ileal smooth muscle but not mediating changes in epithelial ISC.

Animals↗
PubMedDate not supplied

The use of the "progressive muscle relaxation" technique for pain relief in gynecology and obstetrics.

Pain is one of the most frequent symptoms observed in patients and various treatments are proposed for its relief, including relaxation techniques. With the purpose of testing the effect of a specific intervention (progressive muscle relaxation) in a determined situation (pain), this study aimed at verifying the level of pain in post-surgery patients prior to and after the application of the Progressive Muscle Relaxation technique. The subjects, 61 patients, had been submitted to abdominal surgical interventions, of which 52.5% had a gynecological nature and 47.5% obstetrical. Our data showed statistically significant alterations in life parameters as well as muscular alterations after the application of the Progressive Muscle Relaxation technique. It was concluded that the use of the Progressive Muscle Relaxation Technique enabled the subjects to determine that their pain levels decreased.

Adolescent↗
PubMed1993

A versatile, computer-controlled, closed-loop system for continuous infusion of muscle relaxants.

A computer-controlled, closed-loop system for continuous infusion of muscle relaxants that allows the operator to choose either atracurium besylate or vecuronium bromide to provide any desired target level of neuromuscular blockade is described. This new system offers certain advantages over computer-controlled systems described previously for continuous infusion of muscle relaxants--that is, the option to choose either of two muscle relaxants to be infused and the inclusion of monitors to provide feedback about the dosage needed to produce a target level of neuromuscular blockade. The clinical performance of this system was tested in 36 patients who were 18 to 65 years old, were classified in American Society of Anesthesiologists physical status 1 or 2, and were undergoing elective orthopedic, abdominal, or thoracic procedures. In all patients, the control algorithm rapidly induced the target level of neuromuscular blockade and maintained that level of blockade at steady state with minimal oscillation. We conclude that the automatic feedback control system described can induce and precisely maintain any predetermined target level of neuromuscular blockade.

Adolescent↗
PubMed1984

Physiologic responses of clients with essential hypertension to progressive muscle relaxation training.

The effects of progressive muscle relaxation on blood pressure of hypertensive clients were examined. After collection of baseline data, 22 clients received group relaxation training followed by individual monitoring sessions over a 6-week period. The 22 persons in the control group did not receive relaxation training. The group instructed in relaxation had a lower mean systolic blood pressure than the nontrained group at 4-month follow-up. While the relaxation-trained group showed a significant decrease in diastolic pressure from baseline to follow-up, the difference between trained and non-trained groups at follow-up was not significant. Relaxation, taught initially in group with individual follow-up visits, resulted in continued practice of relaxation and subsequent lowering of blood pressure in subjects with essential, uncomplicated hypertension.

Adult↗
PubMed1997

The impact of choice of muscle relaxant on postoperative recovery time: a retrospective study.

UNLABELLED: To test the hypothesis that the use of long-acting muscle relaxants is associated with prolonged postoperative recovery when compared with the use of shorter-acting relaxants, we undertook a retrospective study of 270 patients with induced paralysis recovering from general anesthesia. We calculated the mean recovery time associated with each muscle relaxant used. Regression analyses were performed to control for potential confounding of the results by length and type of surgery, as well as age and sex. Taking these into account, the adjusted difference in mean recovery time between patients receiving short- and intermediate-acting relaxants (mivacurium, atracurium, and vecuronium) versus those receiving long-acting relaxants (d-tubocurarine, pancuronium, and pancuronium and d-tubocurarine combination) was 30 min (95% confidence interval [CI] 8-53). The adjusted difference in mean recovery time between patients receiving vecuronium and those receiving pancuronium (i.e., the single most frequently used drug in each category) was 33 min (95% CI 1-66). Shortened recovery time accounted for an estimated average $37.95 decrease in recovery room charge per patient when vecuronium was used instead of pancuronium, versus a $22.84 increase in drug cost. Our data and analyses support the hypothesis that the use of long-acting muscle relaxants is associated with prolonged recovery after surgery and provide preliminary evidence that restricting the use of the more expensive, shorter-acting muscle relaxants may represent a false economy. IMPLICATIONS: In this retrospective study, the use of old-fashioned, inexpensive, long-acting paralyzing drugs was found to be associated with prolonged postoperative recovery. This has implications when deciding whether, as an economic measure, to restrict the use of the more expensive, shorter-acting paralyzing drugs, because prolonged recovery also has a price.

Adolescent↗
PubMed1999

Intracellular EDTA mimics parvalbumin in the promotion of skeletal muscle relaxation.

Parvalbumin (PA) is an intracellular Ca2+-binding protein found in some muscle and nerves. Its ability to bind Ca2+ and facilitate skeletal muscle relaxation is limited by its Mg2+ off-rate. EDTA serves as an "artificial" PA in that it exhibited similar rate constants for Mg2+ (3 s-1) and Ca2+ (0.7 s-1) dissociation at 10 degrees C. When introduced into frog skeletal muscle, EDTA increased the relaxation rate by approximately 2.7-fold, and with increasing tetanus duration, EDTA lost its ability to contribute to relaxation (and Ca2+ sequestration) at its Mg2+ off-rate. Intracellular EDTA recovered its ability to contribute to muscle relaxation and Ca2+ sequestration at its Ca2+ off-rate. Like PA, EDTA's contribution to muscle relaxation and Ca2+ sequestration was more clearly observed when the SR Ca-ATPase was inhibited. Introduction of EDTA into rat soleus muscle, which has low [PA], increased the relaxation rate in a manner that was analogous to the way in which PA facilitates relaxation of frog skeletal muscle. Thus intracellular EDTA serves as an effective mimic of PA, and its use should aid in our understanding of PA's function in muscle and nerve.

Animals↗
PubMed1993

Time course of action and endotracheal intubating conditions of Org 9487, a new short-acting steroidal muscle relaxant; a comparison with succinylcholine.

In a randomized study, we evaluated lag time (time from the end of injection of muscle relaxant until the first depression of the train-of-four response [TOF]), onset time (time from the end of injection of muscle relaxant until the maximum depression of the first twitch of the TOF [T1]), neuromuscular block, and endotracheal intubating conditions at 1 min after 1 mg/kg succinylcholine (n = 15) and 1.5 mg/kg Org 9487 (n = 30). Two minutes after administration of Org 9487, 15 of the 30 patients received neostigmine for reversal. Recovery of neuromuscular block after succinylcholine, Org 9487 without and Org 9487 with neostigmine were compared using the time until T1 was 90% for the succinylcholine group, and the time until TOF was 70% for the Org 9487 groups. Neuromuscular transmission was monitored mechanomyographically. Onset time was similar (67 [20] and 83 [38] s for succinylcholine and Org 9487, respectively) and endotracheal intubating conditions were also similar after both muscle relaxants. Times until clinically sufficient recovery of neuromuscular block induced by succinylcholine (time until T1 = 90%: 10.6 [3.3] min) and Org 9487 with neostigmine (time until TOF = 70%: 11.6 [1.4] min) were not different. In contrast, in the Org 9487 without neostigmine group, more time was required until complete recovery (24.1 [6.2] min) (P < 0.05). In conclusion, ORg 9487 is a muscle relaxant suitable for endotracheal intubation and short-lasting interventions.

Adult↗
PubMed1976

A comparison of skeletal, cardiac, and smooth muscle actions of dantrolene sodium--a skeletal muscle relaxant.

Dantroline sodium, a skeletal muscle relaxant, has been proposed to inhibit the relase of Ca++ from the sarcoplasmic reticulum. Such a mechanism suggests that other muscle contractile systems operating with the same Ca++ denominator should also be affected by the drug. In the present studies dantrolene sodium effects on smooth, cardiac and skeletal muscle have been evaluated with in situ and in vitro techniques. In anesthetized dogs in situ skeletal muscle contractions were inhibitied in a dose-dependent manner, but cardiac muscle contractions were not. Effects on intestinal smooth muscle responses were highly variable and of short duration. In vitro, ED50 values were developed with dantrolene sodium (0.15-120 mg/l) in DMSO for each tissue. Skeletal muscle was the most sensitive (ED50 = 4.1 mg/l), cardiac muscle contractions were not inhibited by the drug and intestinal smooth muscle (ED50 = 59.0 mg/l) was approximately 1/14 as sensitive as skeletal muscle. It is concluded that skeletal muscle is uniquely sensitive to dantrolene sodium. A hypothesis for this specific action is offered.

Animals↗
PubMedDate not supplied

Respiratory depressant and skeletal muscle relaxant effects of low-dose pancuronium bromide in spontaneously breathing, isoflurane-anesthetized dogs.

OBJECTIVE: To assess and compare the respiratory depressant and skeletal muscle relaxant effects of two low doses of a nondepolarizing neuromuscular blocker, pancuronium bromide. To determine if a "low dose" of pancuronium bromide can produce selective skeletal muscle relaxation in extraocular muscles sufficient to perform intraocular surgery while sparing or minimizing depression of muscles of ventilation. STUDY DESIGN: Blinded, randomized crossover, placebo controlled study. ANIMALS: Six healthy, adult mongrel dogs weighing 20.8 +/- 1.9 kg. METHODS: Spontaneously breathing, isoflurane-anesthetized dogs received 0.02 mg/kg pancuronium bromide, intravenously (i.v.), (high dose [HD]), 0.01 mg/kg pancuronium bromide, i.v., (low dose [LD]), or saline placebo i.v. in a blinded, randomized crossover study. Indices of patient ventilation including tidal volume (Vt), respiratory rate (RR), and minute ventilation (VE) were recorded throughout the study period. Serial arterial blood gas analyses were performed at timed intervals. Neuromuscular blockade of skeletal muscle was assessed at timed intervals with train-of-four stimulus/response ratios. Eye position scores, based on the degree of ocular rotation from a neutral gaze axis, were assigned by an ophthalmologist who was blinded to the treatment given. RESULTS: VT and VE in HD dogs decreased by 82% from baseline after administration of pancuronium bromide. Similarly, Vt and VE in LD dogs decreased 40% and 55%, respectively. Decreased ventilation in HD dogs corresponded with significant (P< .05) neuromuscular blockade, as indicated by train-of-four ratio less than 75% between 0 and 60 minutes. Eye position scores in HD and LD dogs were suitable for intraocular surgery between 0 and 60 minutes. Eye position scores in five of six control dogs were unsuitable for intraocular surgery at any time period. CONCLUSIONS: LD dogs experienced only transient, mild to moderate respiratory depression compared with HD dogs, which experienced prolonged, moderate to severe respiratory depression. Both LD and HD dogs acquired and maintained eye position scores suitable for intraocular surgery between 0 to 60 minutes. A "low dose" of pancuronium bromide, which would provide adequate extraocular muscle relaxation while minimizing ventilatory depression, was not identified. CLINICAL RELEVANCE: All patients receiving any dose of neuromuscular blocking agents should be closely monitored and receive ventilatory assistance as needed.

Anesthesia, Inhalation↗
PubMed2006

Oscillatory cortical activity related to voluntary muscle relaxation: influence of normal aging.

OBJECTIVE: In this study we aimed to investigate if there are age-related differences in cortical oscillatory activity induced by self-paced muscular pure relaxation in comparison with muscle contraction as reference movement. METHODS: Event-related (de)synchronization (ERD/ERS) have been recorded related to voluntary muscle contraction and relaxation in 10 young and 10 elderly right-handed healthy subjects. The muscle relaxation task consisted in a voluntary relaxation of maintained wrist extension without any overt, associated muscle contraction. The muscle contraction task corresponded to a self-initiated brief wrist extension. RESULTS: In elderly subjects compared to young ones, mu and beta ERD preceding muscular relaxation was more widespread, beginning significantly earlier over contralateral frontocentral and parietocentral regions (p<0.05) as well as over ipsilateral regions (p<0.05). The beta synchronization was significantly attenuated (p<0.05). CONCLUSIONS: These results suggest an alteration of inhibitory motor systems and an altered post-movement somesthetic inputs processing with normal aging. These alterations were accompanied by compensatory mechanisms. SIGNIFICANCE: These age-related alterations during different phases of muscle relaxation could participate to explain global sensorimotor slowing observed with normal aging.

Adult↗
PubMedDate not supplied

Ocular interlimbic distance. A new method of monitoring muscle relaxation during anaesthesia.

Measurement of the ocular interlimbic distance (OILD) with a vernier caliper has proved a useful method of studying the reduction in muscle tone caused by general anaesthetic agents and non-depolarising muscle relaxants. The depolarising muscle relaxant, suxamethonium, has a special effect on the extraocular muscles which can be exploited to monitor the incremental use of this drug and to assist in the management of suxamethonium-apnoea in patients with atypical pseudocholinesterase.

Adult↗
PubMed1988

Muscle relaxation with succinylcholine or vecuronium does not alter the rate of CSF production or resistance to reabsorption of CSF in dogs.

The open ventriculocisternal perfusion method was used to determine the rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) in halothane-anesthetized dogs with and without succinylcholine (n = 6) and with and without vecuronium (n = 6). Both Vf and Ra during the use of either muscle relaxant were not different than Vf and Ra when no muscle relaxant was used. Succinylcholine caused muscle fasciculations and raised CSF pressure transiently (increase of 5.5 +/- 1.0 cm H2O [mean +/- SD]), while vecuronium did not. When muscle relaxants were not used, it became difficult to distinguish the effects of cardiovascular and respiratory activity on the CSF pressure waveform, and the coefficient of variability for determination of cisternal outflow rates was increased, making Ra values less reliable. It is concluded that continuous infusion of succinylcholine or vecuronium do not affect Vf or Ra. When Vf and Ra are determined by the method of ventriculocisternal perfusion, immobilization of respiratory muscles improves both the reliability of Ra values and the usefulness of the CSF pressure waveform. If a muscle relaxant is used, either succinylcholine or vecuronium would be suitable for such studies.

Animals↗
PubMed2002

Isobolographic analysis of non-depolarising muscle relaxant interactions at their receptor site.

Administration of certain combinations of non-depolarising muscle relaxants produces greater than expected neuromuscular blockade. Synergistic effects may be explained by drug interactions with the postsynaptic muscle nicotinic acetylcholine receptor. To investigate this hypothesis, the adult mouse muscle nicotinic acetylcholine receptor (alpha(2)beta delta epsilon) was heterologously expressed in Xenopus laevis oocytes and activated by the application of acetylcholine (10 microM). The effects of five individually applied muscle relaxants and six combinations of structurally similar and dissimilar compounds were studied. Drug combinations containing equipotent concentrations of two agents were tested and dose-response curves were determined. All compounds tested alone and in combination produced rapid and readily reversible, concentration-dependent inhibition. Isobolographic and fractional analyses indicated additive interactions for all six tested combinations. These findings suggest that synergistic neuromuscular blocking effects, observed for the administration of certain combinations of muscle relaxants, do not result from purely postsynaptic binding events at the muscle nicotinic acetylcholine receptor, but rather from differential actions on pre- and postsynaptic sites.

Acetylcholine↗