Effects Of Neuromuscular Blocking Agents Research Articles

Neuromuscular Blocking Agents and Cancer: A Narrative Review

Objective. Neuromuscular blocking agents (NMBAs) are part of the three elements of general anaesthesia (sedation, analgesia, and muscle relaxation), which can relax muscles and facilitate intubation and surgery. It has been reported that cancer cells are prone to invasion or metastasis during surgery, but various anaesthetics are currently used in cancer resection, particularly NMBA, and the effects on cancer cell behavior are poorly understood. Guidelines for the correct application of NMBA in cancer surgery have not been reported; therefore, the aim of this paper is to explore the relationship between NMBA and cancer. Methods. Two investigators independently searched PubMed, Embase, the Cochrane Library, Web of Science, and CBM for articles of NMBA and cancer. Results. The available evidence suggests that cisatracurium may be more appropriate for use in anaesthesia for cancer surgery, while rocuronium deserves further attention, particularly for breast and gastric cancer surgery, and vecuronium is suitable for breast cancer and non-small-cell lung cancer, while it is used with caution in gastric cancer. Also, the relationship between NMBA (mivacurium, succinylcholine, gantacurium, and decamethonium bromide) and cancer is unclear and deserves further study. Conclusion. The effect of different NMBAs on cancer cells varies, and the effect of some NMBAs on cancer cells is unclear, and most of the current findings are only from in vitro studies, which need to be validated by further clinical studies in the future to better guide the clinical application of NMBAs.

Neuromuscular blocking agents for acute respiratory distress syndrome: an updated meta-analysis of randomized controlled trials

BackgroundsThe aim of this study is investigating the benefits and harms of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS).MethodsWe comprehensively searched PubMed, EMBASE, and Cochrane library for randomized controlled trials comparing NMBAs to any other comparator. We pooled data using relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals. We assessed the quality of included studies using the Cochrane tool and levels of evidence using the GRADE method.ResultsFinally, six RCTs (n = 1557 patients) were eligible for analysis. The results showed NMBAs use was not associated with reduced 28 days mortality (RR 0.78; 95% CI, 0.58 to 1.06; P = 0.11), 90 days mortality (RR, 0.92; 95% CI, 0.81 to 1.04; P = 0.16), and intensive care unit (ICU) mortality (RR, 0.90; 95% CI, 0.79 to 1.03; P = 0.13) in patients with ARDS. However, 21–28 days mortality was slightly lower in patients received NMBAs (RR 0.73; 95% CI, 0.54 to 0.99; P = 0.04; I2 = 53%). Besides, NMBAs use could improve the PaO2/FiO2 ratio at 48 and 72 h, decrease plateau pressure and PEEP at 72 h. Additionally, NMBAs had no significant effects on days free of ventilation at day 28 (WMD, 0.55; 95% CI, − 0.46 to 1.57; P = 0.29), days not in ICU at day 28 (WMD, 0.12; 95% CI, − 0.85 to 1.08; P = 0.82), ICU-acquired weakness (RR, 1.23; 95% CI, 0.99 to 1.93; P = 0.06). Finally, NMBAs use was associated with a lower risk of barotrauma (RR, 0.55; 95% CI, 0.35 to 0.85; P = 0.007).ConclusionIn patients with respiratory distress syndrome, NMBAs may be beneficial in reverse refractory hypoxemia and may be associated with reduced short-term mortality and incidence of barotrauma. However, there is no significant effects of NMBAs on mid-term and long-term mortality, and further studies are required.

Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen.

The appropriate level of sedation in patients with an open abdomen following damage control laparotomy (DCL) is debated. Chemical paralysis with neuromuscular blocking agents (NMBAs) has been used to decrease time to abdominal closure. We sought to evaluate the effect of NMBA use on sedation requirements in patients with an open abdomen and to determine the effect of sedation on patient outcomes. A retrospective cohort study was conducted at an American College of Surgeons' verified level 1 trauma center. Adult trauma patients who underwent DCL between 2009 and 2015 were included. Patients with an intensive care unit length of stay of less than 48hours and those who died before abdominal closure were excluded. The NMBA+ group received continuous NMBA within 24hours of DCL; the NMBA- group did not. The primary outcome was cumulative sedation dose during the 7days following DCL. Secondary outcomes included Richmond Agitation-Sedation Scale (RASS) score, mechanical ventilation-free days, and delirium-coma-free days. Delirium-coma-free days were analyzed with linear regression. A total of 222 patients were included (NMBA+ 125; NMBA- 97). Demographics were similar between groups including age, Injury Severity Score, and mechanism of injury. The median time to closure in the overall cohort was 2days (interquartile range [IQR] 1-2days). Propofol and fentanyl were the primary sedatives used. The NMBA+ group received higher cumulative doses of propofol (NMBA+ 5405mg, IQR 3103-10,573mg; NMBA- 3601mg, IQR 1605-6887mg; p=0.007), but not of fentanyl. Time to abdominal closure, but not NMBA use, was associated with a higher cumulative propofol dose on multivariate analysis. The NMBA+ group had significantly lower RASS scores on the first 3days following DCL. Mechanical ventilation-free days (NMBA+ 20days vs NMBA- 18days, p=0.960) and delirium-coma-free days (NMBA+ 18days vs NMBA- 18days, p=0.610) were similar between the groups. On linear regression, cumulative propofol dose was associated with fewer delirium-coma-free days (β-coefficient -0.007, 95% confidence interval -0.015 to -0.003). In trauma patients managed with DCL, higher cumulative sedative doses were administered in patients who received adjunctive NMBA, although NMBA therapy was not associated with a higher cumulative propofol dose on multivariate analysis. Consideration must be given to the potential effect of sedation on delirium and awakening following DCL.

Recovery of muscle function after deep neuromuscular block by means of diaphragm ultrasonography and adductor\xa0of pollicis acceleromyography with comparison of neostigmine vs. sugammadex as reversal drugs: study protocol for a randomized controlled trial

BackgroundThe extensive use of neuromuscular blocking agents (NMBAs) during surgical procedures still leads to potential residual paralyzing effects in the postoperative period. Indeed, neuromuscular monitoring in an intra-operative setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle block, but their short half-life may lead to residual curarization in the ward, especially when intermediate or long-acting NMBAs have been administered. Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been shown to give full and rapid recovery of muscle strength, thus minimizing the occurrence of residual curarization. Acceleromyography of the adductor pollicis is the gold standard for detecting residual curarization, but it cannot be carried out on conscious patients. Ultrasonography of diaphragm thickness may reveal residual effects of NMBAs in conscious patients.Methods/designThis prospective, double-blind, single-center randomized controlled study will enroll patients (of American Society of Anesthesiologists physical status I–II, aged 18–80 years) who will be scheduled to undergo deep neuromuscular block with rocuronium for ear, nose, or throat surgery. The study’s primary objective will be to compare the effects of neostigmine and sugammadex on postoperative residual curarization using two different tools: diaphragm ultrasonography and acceleromyography of the adductor pollicis. Patients will be extubated when the train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate the thickening fraction, which is the difference between the end expiratory thickness and the end inspiratory thickness, normalized to the end expiratory thickness. Ultrasonography will be performed before the initiation of general anesthesia, before extubation, and 10 and 30 min after discharging patients from the operating room. The secondary objective will be to compare the incidence of postoperative complications due to residual neuromuscular block between patients who receive neostigmine and those who receive sugammadex.DiscussionPostoperative residual curarization is a topic of paramount importance, because its occurrence can cause complications and increase the length of stay in hospital and the related costs. Diaphragm ultrasound assessment may become a bedside integrative tool in the neuromuscular monitoring field to detect concealed residual curarization in surgical patients who have received paralyzing agents.Trial registrationEudraCT, 2013-004787-62. Registered on 18 June 2014, as “Evaluation of muscle function recovery after deep neuromuscular blockade by acceleromyography of the adductor pollicis or diaphragmatic echography: comparison between sugammadex and neostigmine.”ClinicalTrials.gov,NCT02698969. Registered on 15 February 2016, as “Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs.”

The Effects of Neuromuscular Blocking Agents in Soft Tissue Balancing During Primary Total Knee Arthroplasty

We present a case of elective total knee arthroplasty where the surgical procedure was affected by the neuromuscular blocking agent administered at induction of general anaesthesia. Recognition of this effect was vital to avoid additional bone resection at the soft tissue balancing stage of the procedure.

Succinylcholine Improves Tidal Volumes During Facemask Ventilation

To determine the effects of neuromuscular blocking agents on facemask ventilation, researchers allocated 31 consecutive healthy patients with normal

The Role of Neuromuscular Blockers in Early ARDS

The use of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) remains controversial. However, NMBAs are used in 25% to 45% of ALI/ARDS patients for a mean period of 1±2 days, especially in severe ARDS. Hypoxemia and facilitation of mechanical ventilation are the main indications of NMBAs. Three randomized, controlled trials showed that the systematic early use of NMBAs is associated with a sustained improvement in oxygenation in ARDS patients. The most recent trial reported a decrease in 90-day in-hospital mortality rate when severe ARDS patients received a short course of muscle relaxants. The use of NMBAs in the early phase of ARDS could reinforce the beneficial effects of a lung-protective ventilation strategy. However, the role of prolonged NMBA administration in intensive care unit–acquired paresis in ARDS patients remains largely questioned. This review analyzes the recent findings in the literature concerning the effects of NMBAs on gas exchange and patient outcomes, and their potential adverse effects in ARDS.

Can sugammadex encapsulation eliminate the antigenic activity of aminosteroidal neuromuscular blocking agent?

To the Editor: Anaphylaxis is one of the most serious adverse events caused by neuromuscular blocking agents (NMBAs) [1]. In the epidemiological surveys conducted in Europe, it was found that NMBAs are responsible for approximately 50–70% of the anaphylactic reactions that occur during anesthesia [1, 2]. The quaternary ammonium (QA) ions, which are essential for the neuromuscular-blocking effects of NMBAs, have been suggested to be the allergenic epitope of NMBAs [1]. Therefore, all NMBAs may cause anaphylaxis, and allergic cross-reactivity between NMBAs has been reported [1, 2]. Sugammadex can bind to aminosteroidal NMBAs (e.g., rocuronium and vecuronium) via chemical encapsulation and cause reversal of the neuromuscular blockade. Recently, McDonnell et al. [3] reported a case in which rapid improvement of rocuronium-induced anaphylaxis was observed after sugammadex administration. Although this case indicates that sugammadex may be a novel therapeutic agent for NMBA-induced anaphylaxis, the underlying mechanism(s) of its therapeutic effects remains unknown. The lack of a suitable animal model makes it difficult to study the effects of sugammadex therapy. However, one possible mechanism is that the QA epitopes on NMBA molecules are eliminated from circulation by sugammadex encapsulation [4]. To confirm this hypothesis, we conducted an in vitro experiment using specific reagent strips as QA indicator (Merkoquant 117920; Merck KGaA, Germany) to observe whether NMBA QA epitopes were encapsulated by sugammadex. QA compounds react with the indicator, resulting in a change in color of the test strips from yellow to green. These test strips showed positive results (green) for all tested NMBAs such as rocuronium, vecuronium, and succinylcholine, but showed a negative result (yellow) for sugammadex alone (Fig. 1). However, the QA reaction of rocuronium (50 lg/ml) and vecuronium (50 lg/ml) was diminished when they were premixed with sugammadex (C200 lg/ml; response ratio 4:1). On the other hand, even the highest test concentration (400 lg/ml) of sugammadex had no effect on QA response of succinylcholine (50 lg/ml) (Fig. 1). As sugammadex has no binding affinity for succinylcholine, we assume that the interaction of sugammadex with the QA epitopes of aminosteroidal NMBAs is associated with the formation of chemical encapsulation. Our results suggest that a high dose of sugammadex can rapidly hide the QA epitopes on the surface of circulating aminosteroidal NMBAs. This may subsequently prevent QA epitopes of NMBAs binding to immunoglobulin E, thus interrupting the anaphylactic reaction and prevent mediator release. In consistent with our findings, Leysen et al. [5] reported that sugammadex prevented in vitro basophil activation induced by rocuronium in three patients with established rocuronium allergy. However, QA epitopes are reported to be the most important, but not only, allergenic determinant of NMBAs [1, 2]. Furthermore, Leysen et al. [5] demonstrated that sugammadex failed to halt ongoing rocuronium-induced basophil activation. Therefore, it still remains unknown whether sugammadex T. Kawano (&) M. Yokoyama Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan e-mail: takashika@kochi-u.ac.jp

Electromyographic Study of Differential Sensitivity to Succinylcholine of the Diaphragm, Laryngeal and Somatic Muscles: A Swine Model

Neuromuscular blocking agents (NMBAs) might diminish the electromyography signal of the vocalis muscles during intraoperative neuromonitoring of the recurrent laryngeal nerve. The aim of this study was to compare differential sensitivity of different muscles to succinylcholine in a swine model, and to realize the influence of NMBAs on neuromonitoring. Six male Duroc-Landrace piglets were anesthetized with thiamylal and underwent tracheal intubation without the use of an NMBA. The left recurrent laryngeal nerve, the spinal accessory nerve, the right phrenic nerve and the brachial plexus were stimulated. Evoked potentials (electromyography signal) of four muscle groups were elicited from needle electrodes before and after intravenous succinylcholine bolus (1.0 mg/kg). Recorded muscles included the vocalis muscles, trapezius muscle, diaphragm and triceps brachii muscles. The onset time and 80% recovery of control response were recorded and analyzed. The testing was repeated after 30 minutes. The onset time of neuromuscular blocking for the vocalis muscles, trapezius muscle, diaphragm and triceps brachii muscle was 36.3 ± 6.3 seconds, 38.8 ± 14.9 seconds, 52.5 ± 9.7 seconds and 45.0 ± 8.2 seconds during the first test; and 49.3 ± 10.8 seconds, 40.0 ± 12.2 seconds, 47.5 ± 11.9 seconds and 41.3 ± 10.1 seconds during the second test. The 80% recovery of the control response for each muscle was 18.3 ± 2.7 minutes, 16.5±6.9 minutes, 8.1±2.5 minutes and 14.8±2.9 minutes during the first test; and 21.5±3.8 minutes, 12.5 ± 4.3 minutes, 10.5 ± 3.1 minutes and 16.4 ± 4.2 minutes during the second test. The sensitivity of the muscles to succinylcholine, ranked in order, was: the vocalis muscles, the triceps brachii muscle, the trapezius muscle and the diaphragm. We demonstrated a useful and reliable animal model to investigate the effects of NMBAs on intraoperative neuromonitoring. Extrapolation of these data to humans should be done with caution.

Control of perioperative muscle strength during ambulatory surgery

This review describes strategies to control perioperative muscle strength in patients undergoing ambulatory surgery. Although it is impossible to improve muscle relaxation (defined as absence of electrical activity) of intact resting muscle by hypnotics, analgesia is required to prevent pain-evoked muscular contractions during surgery. Regional anesthesia, as well as hypnotics and opioids, promotes intraoperative muscle relaxation. Neuromuscular blocking agents (NMBAs) induce dose-dependent muscle relaxation, but their effects vary widely between individuals, and postoperative residual curarization (PORC) exposes patients to additional risk. Low doses of NMBAs should, therefore, be used, effects be monitored quantitatively by acceleromyography, and residual neuromuscular block be reversed. Acetylcholinesterase inhibitor reversal can cause respiratory side effects, so the lowest efficacious dose should be used: as little as 0.015-0.025 mg kg(-1) of neostigmine is required at a train-of-four count of four with minimal fade. Sugammadex encapsulates steroidal NMBAs. Sugammadex reversal is a viable approach to rapidly antagonize deep levels of neuromuscular block. Optimal muscle relaxation for ambulatory surgery results from a judicious combination of regional anesthesia, opioids, and low doses of NMBAs. The effects of NMBAs should be monitored quantitatively by acceleromyography and reversed appropriately.

Differential Effects of Neuromuscular Blocking Agents on Suxamethonium-Induced Fasciculations and Myalgia

OSULLIVAN, E. P.; WILLIAMS, N. E.; CALVEY, T. N.; Roizen, Michael F. M.D. Author Information

Effects of neuromuscular blocking agents and acetylcholinesterase inhibitors on the response of pectoral fin muscle of the sculpin (Enophrys bison) to indirect stimulation.

The neuromuscular junction of the buffalo sculpin (Enophrys bison) was characterized in situ by examining the effects of various neuromuscular blocking agents and acetylcholinesterase inhibitors (ACHE-I) on pectoral muscle response to indirect stimulation. The injection of either d-tubocurarine (350 micrograms/kg) or alpha-bungarotoxin (alpha-Butx) (1 mg/kg) resulted in a flaccid paralysis. The depolarizing agents, succinylcholine (11 micrograms/kg) and decamethonium (42 micrograms/kg), produced a spontaneous contraction. The administration of the ACHE-I, diisopropyl fluorophosphate (DFP), and eserine resulted in responses which were contrary to those expected based on similar experiments using mammalian skeletal muscle. Twitch potentiation did not occur and the ability to maintain a tetanic response was not abolished even after the administration of clearly lethal concentrations of ACHE-I.

Pre-and Postjunctional Effects of Neuromuscular Blocking Agents and Their Antagonists

Pre-and Postjunctional Effects of Neuromuscular Blocking Agents and Their Antagonists

The Inhibitory Effect of Neuromuscular Blocking Agents and Their Antagonists on Human Cholinesterases

The Inhibitory Effect of Neuromuscular Blocking Agents and Their Antagonists on Human Cholinesterases

EFFECT OF CURARE ON CORTICAL RESPONSES EVOKED BY AFFERENT STIMULATION

ArticlesEFFECT OF CURARE ON CORTICAL RESPONSES EVOKED BY AFFERENT STIMULATIONMortimer Ostow, and Francisco GarciaMortimer Ostow, and Francisco GarciaPublished Online:01 Jul 1949https://doi.org/10.1152/jn.1949.12.4.225MoreSectionsPDF (668 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByCerebroprotective drugs shorten the hypoxia-induced onset of electrical silence in unanesthetized ratsPharmacological Research, Vol. 42, No. 3On the Effect of Neuromuscular Blocking Agents on the Central Nervous SystemReferencesPossible role of hyperventilation in the CNS effects attributed to tubocurarineElectroencephalography and Clinical Neurophysiology, Vol. 19, No. 5Central Action of Intravenous CurareNature, Vol. 207, No. 4994Central effects of five muscle relaxantsCanadian Anaesthetists’ Society Journal, Vol. 8, No. 4The effects of curare on cortical activityElectroencephalography and Clinical Neurophysiology, Vol. 13, No. 1The Electrographic Activity of the Cooled Human Frontal Lobe and its Response to HypotensionJournal of Neurosurgery, Vol. 17, No. 5Observations on evoked dendritic potentials of human cortexElectroencephalography and Clinical Neurophysiology, Vol. 9, No. 3EXPERIMENTAL ANALYSIS OF THE INHIBITORY ACTION OF LYSERGIC ACID DIETHYLAMIDE ON CORTICAL DENDRITIC ACTIVITYAnnals of the New York Academy of Sciences, Vol. 66, No. 3Elektrobiologie des StoffwechselsThe Mechanisms of Discharge of the Electric Organs in Relation to General and Comparative ElectrophysiologyProgress in Biophysics and Biophysical Chemistry, Vol. 7Action of natural and synthetic curares on the cortical activity of the rabbitElectroencephalography and Clinical Neurophysiology, Vol. 5, No. 2Vergleichende Untersuchung der muskelerschlaffenden MittelLiteraturRECENT ADVANCES IN THE PHARMACOLOGY OF CURAREAnnals of the New York Academy of Sciences, Vol. 54, No. 3SOME ASPECTS OF THE RELATIONSHIP BETWEEN CHEMICAL CONSTITUTION AND CURARE-LIKE ACTIVITYAnnals of the New York Academy of Sciences, Vol. 54, No. 3The Effect of d-Tubocurarine on the Mono- and Polysynaptic Relfex of the Spinal Cord Including a Comparison with the Effect of Strychnine.Acta Physiologica Scandinavica, Vol. 21, No. 1 More from this issue > Volume 12Issue 4July 1949Pages 225-229 https://doi.org/10.1152/jn.1949.12.4.225PubMed18134216History Published online 1 July 1949 Published in print 1 July 1949 Metrics