Neuromuscular Blockers and Reversal Agents

2019 ◽  
Author(s):  
Kristen Flight ◽  
Jennifer J Yang ◽  
Lindsay M Urben ◽  
Michael J Schontz

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

2002 ◽  
Vol 30 (2) ◽  
pp. 123-133 ◽  
Author(s):  
T. A. Torda

Persistent neuromuscular blockade is not uncommon in the recovery room and contributes to postoperative morbidity and possibly mortality. The use of neuromuscular monitoring and intermediate rather than long-acting neuromuscular blocking drugs have been shown to reduce its incidence. Clinically available methods of detecting and quantitating neuromuscular blockade are reviewed. The writer concludes that such monitoring should be routine when neuromuscular blocking drugs are used.


2018 ◽  
Vol 23 (1) ◽  
pp. 48-53
Author(s):  
N'Diris Barry ◽  
Joshua C. Uffman ◽  
Dmitry Tumin ◽  
Joseph D. Tobias

OBJECTIVES Neuromuscular blocking agents (NMBAs) are administered to facilitate endotracheal intubation and provide skeletal muscle relaxation in surgical procedures. Sugammadex (Bridion) recently received approval by the United States Food and Drug Administration for reversal of rocuronium and vecuronium-induced neuromuscular blockade thereby providing an alternative to acetylcholinesterase inhibitors such as neostigmine. This quality improvement analysis sought to investigate the clinical reasons and common clinical perceptions for choosing sugammadex over neostigmine to reverse NMBAs. METHODS One hundred cases were reviewed where sugammadex was used for neuromuscular blockade reversal in the operating room. Cases were identified from electronic medical record reports. Anesthesia providers responsible for administering sugammadex were interviewed to obtain rationales for sugammadex use in the perioperative setting. Responses were reviewed to identify distinct reasons for using sugammadex. Two independent raters ranked the reasons according to prevalence. The study was exempt from Institutional Review Board approval as a quality improvement (QI) project. RESULTS Forty-two anesthesia providers (15 Certified Registered Nurse Anesthetists, 5 anesthesiology trainees, and 22 attending anesthesiologists) were interviewed to identify reasons why sugammadex was administered intraoperatively in 100 surgical cases (69/31 male/female patients, age 9.4 ± 6.5 years). The author identified the top 19 common reasons respondents chose to use sugammadex for each case, and independent raters reviewed the response summaries for those 19 primary reasons sugammadex was used. The most common reasons for choosing sugammadex were: 1) beneficial pharmacokinetics of the agent; 2) sugammadex's perceived superior efficacy over neostigmine; and 3) concerns regarding adverse effects of neostigmine and/or the anticholinergic agent. CONCLUSIONS Sugammadex has recently been introduced for clinical use to reverse NMBAs at our institution. Primary reasons and perceptions for its use over neostigmine included a limited adverse effect profile, a greater sense of control and predictability of patients' response, and a limited incidence of residual neuromuscular blockade.


2018 ◽  
Vol 29 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Nicole Stawicki ◽  
Patty Gessner

Residual neuromuscular blockade is a widespread challenge for providers in the acute care setting that, if left unrecognized or untreated, places patients at higher risk for morbidity and mortality. The condition is estimated to occur in 26% to 88% of patients undergoing general anesthesia. The role of the advanced practice nurse in the acute care setting is to facilitate a safe recovery process by identifying early signs of deterioration and supporting the patient until full muscular strength has returned. This article discusses the prevalence of residual neuromuscular blockade and associated complications and patient risk factors. A review is included of the current uses for neuromuscular blockade, pathophysiology of the neuromuscular junction, pharmacologic characteristics of neuromuscular blocking agents (including drug-drug interactions), monitoring modalities, and effectiveness of reversal agents. Treatment recommendations pertinent to residual neuromuscular blockade are outlined.


2018 ◽  
Vol 129 (5) ◽  
pp. 970-988 ◽  
Author(s):  
John J. Savarese ◽  
Hiroshi Sunaga ◽  
Jeff D. McGilvra ◽  
Matthew R. Belmont ◽  
Matthew T. Murrell ◽  
...  

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.


2021 ◽  
Vol 62 (6) ◽  
Author(s):  
Doan Minh Nhut ◽  
Nguyen Van Chinh

Introduction: In Vietnam, using a muscle accelerator to measure the TOF index to monitor residue neuromuscular blockade has not been performed routinely, extubation is mainly based on subjective clinical assessments. Methods: A cross-sectional study on 96 patients undergoing laparoscopic appendectomy at Nguyen Tri Phuong Hospital, from November 2020 to May 2021. Objectives: The study was conducted with 2 objectives including (1) Determine the progression of TOF index at 7 time points: immediately after arriving in the recovery room, after extubation, 15 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes after extubation; (2) Determination of residual muscle relaxant rate of patients undergoing laparoscopic appendectomy at Nguyen Tri Phuong Hospital. Results: The average TOF ≥ 0,9 index after laparoscopic appendectomy at the time of resuscitation was 88.11%, extubation was 90.53% and at 120 minutes after extubation. is 99.88%. Residual muscle relaxation after surgery when TOF index < 0.9. At the time of resuscitation, the highest residual rate of muscle relaxant accounted for 58.33%, followed by the time of extubation 39.58%, 15 minutes after extubation was 21.88%. Until 120 after extubation, there is no case that has residue neuromuscular blockade. Conclusion: Through the study results, it is necessary to monitor patients undergoing laparoscopic appendectomy with quantitative devices to more accurately assess the clinical index of muscle relaxation.


2000 ◽  
Vol 93 (2) ◽  
pp. 510-519 ◽  
Author(s):  
Daniel S. McGehee ◽  
Matthew D. Krasowski ◽  
Dennis L. Fung ◽  
Barry Wilson ◽  
Gerald A. Gronert ◽  
...  

Background 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. Methods 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. Results 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). Conclusions 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.


2000 ◽  
Vol 93 (5) ◽  
pp. 1194-1197 ◽  
Author(s):  
Hironori Itoh ◽  
Keizo Shibata ◽  
Masahiro Yoshida ◽  
Ken Yamamoto

Background In most publications about myasthenia, monitoring neuromuscular blockade during anesthesia is recommended. In healthy patients, the relation of blockade between muscles has been established, but there is little information about the relation in myasthenic patients. Our objective was to investigate whether the relation between the orbicularis oculi and adductor pollicis muscles is the same in healthy patients and myasthenic patients. Methods After anesthesia was induced with 4-6 mg/kg thiopental and 2 microg/kg fentanyl, followed by 2% sevoflurane and 60% nitrous oxide in oxygen, 10 healthy patients and 10 myasthenic patients received 0. 025 and 0.01 mg/kg vecuronium, respectively. Neuromuscular monitoring was performed with use of accelerometry at the orbicularis oculi and the adductor pollicis muscles by stimulating the temporal branch of the facial nerve and the ulnar nerve. Results The relation of blockade between these two muscles was not the same in healthy patients and myasthenic patients: in healthy patients, the maximum neuromuscular blockade with 0.025 mg/kg vecuronium was less in the orbicularis oculi than in the adductor pollicis (median 72% vs. 91%; P &lt; 0.05); in contrast, in myasthenic patients, the blockade with 0.01 mg/kg vecuronium was greater in the orbicularis oculi than in the adductor pollicis (median 96% vs. 62%; P &lt; 0.05). Conclusion Neuromuscular monitoring at the orbicularis oculi may overestimate blockade in myasthenic patients. Extubation must be performed when the muscle most sensitive to neuromuscular blocking agents is recovered. Therefore, neuromuscular monitoring at the orbicularis oculi is recommended to avoid persistent neuromuscular blockade in patients with myasthenia gravis.


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