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The Cochrane Database of Systematic... Aug 2017Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources.
OBJECTIVES
The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults.
SEARCH METHODS
We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs.
MAIN RESULTS
We included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.We compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I = 84%; 10 studies, n = 835; GRADE: moderate quality).We compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I = 0%; two studies, n = 114; GRADE: low quality).For our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I= 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I= 0%; 10 studies, n = 959; GRADE: low quality).Application of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis.
AUTHORS' CONCLUSIONS
Review results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).
Topics: Adult; Androstanols; Atracurium; Cholinesterase Inhibitors; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Randomized Controlled Trials as Topic; Rocuronium; Sugammadex; Time Factors; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 28806470
DOI: 10.1002/14651858.CD012763 -
Journal of Anesthesia Apr 2016Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common... (Review)
Review
Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.
Topics: Anaphylaxis; Androstanols; Anesthesia; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine; Sugammadex; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 26646837
DOI: 10.1007/s00540-015-2105-x -
Steroids Dec 2021Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively...
Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the H, C, and N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.
Topics: Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Neuromuscular Blocking Agents; Vecuronium Bromide
PubMed: 34655596
DOI: 10.1016/j.steroids.2021.108928 -
British Journal of Anaesthesia Mar 2024The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium...
The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.
Topics: Humans; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Androstanols; Rocuronium; Vecuronium Bromide; Neuromuscular Blocking Agents
PubMed: 38135525
DOI: 10.1016/j.bja.2023.12.001 -
Contact in Context 2023This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots...
This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.
PubMed: 38187821
DOI: 10.6084/m9.figshare.24846285 -
Anesthesia, Essays and Researches 2016The present study is undertaken to compare the hemodynamic effects using vecuronium versus rocuronium for maintenance in patients undergoing general surgical procedures.
AIMS
The present study is undertaken to compare the hemodynamic effects using vecuronium versus rocuronium for maintenance in patients undergoing general surgical procedures.
SETTINGS AND DESIGN
It is a prospective, randomized, and cohort study.
SUBJECTS AND METHODS
100 patients were randomly divided into two groups. All patients were induced with 5 mg/kg of thiopentone sodium, and intubation conditions were achieved with 1.5 mg/kg of suxamethonium, using a well-lubricated cuffed endotracheal tube of appropriate size. When the patient started to breathe spontaneously, they were administered either 0.6 mg/kg of rocuronium (Group A) or 0.1 mg/kg of vecuronium (Group B). Hemodynamic parameters (heart rate and mean arterial pressure [MAP]) were monitored before administering the drug; at 1, 5, 10, 15, and 20 min after the drug and at the end of the surgery.
STATISTICAL ANALYSIS USED
Data were compiled, analyzed and presented as frequency, proportions, mean, standard deviation, percentages, and t-test using SPSS (version 16). A P < 0.05 was considered as significant.
RESULTS
The heart rate increased significantly at 1-min and 5-min after administration of rocuronium (83.76 ± 10.37 and 86.8 ± 9.98), unlike vecuronium. However, it gradually declined towards normal, and change in heart rate with either drug was not significant beyond 10 min. The MAP decreased significantly at 1-min after administration of rocuronium (96.68 ± 7.57) which later showed a gradual increasing trend when compared to vecuronium which had no statistically significant change at any time.
CONCLUSIONS
For short surgical procedures rocuronium is a good alternative to vecuronium, as the drug is reasonably cardio stable, produces excellent intubation conditions, has a shorter duration of action, and shows minimal cumulative effect.
PubMed: 26957692
DOI: 10.4103/0259-1162.164740 -
Pediatric Emergency Care Jun 2020Sugammadex reverses neuromuscular blockade by the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. In 2015, it was approved in the... (Review)
Review
Sugammadex reverses neuromuscular blockade by the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. In 2015, it was approved in the United States by the Food and Drug Administration for adult use. However, there are ongoing clinical trials investigating its use in the pediatric population. Before approval in adult use in the United States, several adverse effects were noted to occur in patients receiving sugammadex in clinical trials including prolonged QT interval, bradycardia, hypersensitivity reactions, and prolongation of coagulation parameters. Additional investigations further elucidated the risks of these adverse events. Sugammadex is approved for use in children older than 2 years in other countries in Europe and Asia. Investigations suggest that the efficacy, safety, and pharmacokinetic profile is similar in children when compared with adults. Published pediatric data favor the use of sugammadex in children older than 2 years, but there are some data in young children younger than 2 years. Case reports discuss the use of sugammadex in pediatric patients with neuromuscular diseases. Although sugammadex is typically used in the operating room for reversing neuromuscular blockade for surgical procedures, there is a small but important role for sugammadex use in the emergency department. In cases where rapid neurological examination is required after neuromuscular blockage with rocuronium or vecuronium, sugammadex can assist in facilitating a timely comprehensive neurological examination where pharmacologic or surgical management may depend on examination findings such as in the case of cerebral vascular accident, status epilepticus, or traumatic brain injury. Some clinicians have advocated for the use of sugammadex in the cannot intubate, cannot ventilate scenario. However, caution should be exercised in this situation as reversal of paralysis can take up to 22 minutes to occur.
Topics: Child; Diagnostic Techniques, Neurological; Emergency Medicine; Humans; Neuromuscular Blockade; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 32483081
DOI: 10.1097/PEC.0000000000002126