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Journal of Clinical Anesthesia Jun 2017Sugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been... (Comparative Study)
Comparative Study Meta-Analysis Review
STUDY OBJECTIVE
Sugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been established, data are conflicting as to whether it accelerates discharge to the surgical ward compared with neostigmine, which is traditionally used for reversing NMB. The object of this systematic review and meta-analysis was to review the research comparing sugammadex and neostigmine in the context of patient discharge after general anesthesia.
DESIGN
Systematic review and meta-analysis.
SETTING
University medical hospital.
PATIENTS
Five-hundred eighteen patients from six studies were included.
METHODS
A comprehensive search was conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library electronic databases to identify randomized controlled trials written in English. Two reviewers independently selected the studies, extracted data regarding postoperative discharge, and assessed the trials' methodological quality and evidence level. Postoperative discharge time was determined from the operating room (OR) to the postanesthesia care unit (PACU) and from the PACU to the surgical ward. This study was conducted using PRISMA methodology.
MEASUREMENTS
Time to discharge after NMB reversal with sugammadex or neostigmine.
MAIN RESULTS
Compared with neostigmine, sugammadex was associated with a significantly faster discharge from the OR to the PACU (mean difference [MD]=22.14min, 95% CI (14.62, 29.67), P<0.0001, I=0%) and from the PACU to the surgical ward (MD=16.95min, 95% CI (0.23, 33.67), P=0.0469, I=98.4%). Similarly, discharge-readiness was shorter for sugammadex than for neostigmine from the OR to the PACU (MD=5.58min, 95% CI (3.03, 8.14), P≤0.0001, I=0%). However, discharge-readiness was similar in both groups for patients moving from the PACU to the surgical ward (MD=-1.10min, 95% CI (-5.69, 3.50), P=0.6394, I=25.3%).
CONCLUSIONS
Results from this meta-analysis suggest that sugammadex accelerates postoperative discharge of patients after general anesthesia compared with neostigmine.
Topics: Androstanols; Anesthesia, General; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Randomized Controlled Trials as Topic; Rocuronium; Sugammadex; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 28494905
DOI: 10.1016/j.jclinane.2017.03.004 -
The Journal of Allergy and Clinical... Feb 2023Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely...
BACKGROUND
Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely among reports.
OBJECTIVE
To determine maximal ST nonirritant concentrations (NICs) of NMBAs (cisatracurium, rocuronium, succinylcholine, and vecuronium), NMBA-reversal agents (neostigmine and sugammadex), and S-R-Cx in NMBA-tolerant and NMBA-naïve participants.
METHODS
A single-center, prospective study between October 2019 and November 2021 of adult participants with or without a planned surgical procedure. The reference standard was tolerance of medication tested during a procedure (NMBA-tolerant group) before ST. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 5-7 increasing concentrations of 1 or more medications. All medications were reconstituted according to package insert instructions and diluted with 0.9% saline. A concentration was considered irritant when more than 5% of participants had a positive test per ST positivity criteria (wheal ≥3 mm than initial wheal and associated erythema of the same size or greater than wheal). We also compared our results with current guidelines.
RESULTS
A total of 187 participants (78% NMBA-tolerant) underwent 7812 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT NICs (mg/mL): cisatracurium (0.02), rocuronium (0.05), succinylcholine (0.8), vecuronium (0.01), neostigmine (0.2), sugammadex (50), and S-R-Cx (sugammadex 7.14 + rocuronium 2).
CONCLUSION
Our results suggest that SPT may be performed with undiluted stock concentrations. We confirm maximal IDT NICs for cisatracurium and rocuronium. We also propose that currently recommended maximal IDT NICs of succinylcholine, neostigmine, sugammadex, and S-R-Cx could be increased, whereas the maximal IDT NIC of vecuronium could be decreased compared with current guidelines and prior reports.
Topics: Adult; Humans; Sugammadex; Rocuronium; Vecuronium Bromide; Neuromuscular Nondepolarizing Agents; Neostigmine; gamma-Cyclodextrins; Succinylcholine; Prospective Studies; Androstanols; Neuromuscular Blockade; Neuromuscular Blocking Agents
PubMed: 36108924
DOI: 10.1016/j.jaip.2022.08.049 -
Critical Care Explorations Jan 2020We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry...
OBJECTIVES
We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia.
DESIGN
We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children's Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions.
SETTING
PICU of a quaternary, free-standing children's hospital.
PATIENTS
Children admitted to the hospital who received vecuronium and/or esmolol infusion.
MEASUREMENTS AND MAIN RESULTS
Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel-blood gas) sodium within 12 hours of the vecuronium administration ( < 0.0018). Esmolol showed a similar trend ( = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions.
CONCLUSIONS
Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.
PubMed: 32166293
DOI: 10.1097/CCE.0000000000000073 -
Expert Opinion on Drug Metabolism &... Sep 2016Sugammadex is the first clinical representative of a class of drugs called steroidal muscle relaxant encapsulators. Due to its 1:1 binding of rocuronium or vecuronium,... (Review)
Review
INTRODUCTION
Sugammadex is the first clinical representative of a class of drugs called steroidal muscle relaxant encapsulators. Due to its 1:1 binding of rocuronium or vecuronium, sugammadex can reverse any depth of neuromuscular block and has therefore revolutionized the way anesthetists think about drug reversal.
AREAS COVERED
This review gives an overview of the clinical pharmacology and efficacy of sugammadex in healthy patients as well as in patients with pre-existing diseases.
EXPERT OPINION
After approval in Europe in 2008 and Asia in 2010, sugammadex has recently been approved in the USA and Canada. This will open the field for further research especially for the use in special patient populations and specific diseases. Due to its pharmacodynamic profile, sugammadex in combination with rocuronium might have the potential to displace succinylcholine as the gold standard muscle relaxant for rapid sequence inductions. The use of rocuronium or vecuronium with the potential to reverse its action with sugammadex seems to be safe in patients with impaired neuromuscular transmission, i.e. (neuro)muscular diseases including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence towards an economic advantage of using sugammadex, justifying the relatively high costs for an anesthesia-related drug, is missing.
Topics: Androstanols; Animals; Humans; Neuromuscular Blockade; Neuromuscular Diseases; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 27463265
DOI: 10.1080/17425255.2016.1215426 -
Hospital Pharmacy Oct 2021Sugammadex (Bridion) was approved by the US Food and Drug Administration (FDA) in December 2015 for the reversal of neuromuscular block (NMB) induced by rocuronium and...
Sugammadex (Bridion) was approved by the US Food and Drug Administration (FDA) in December 2015 for the reversal of neuromuscular block (NMB) induced by rocuronium and vecuronium bromide in adults undergoing surgery and approved for use in both adults and children in the European Union in 2008. Sugammadex use in children has been reported in the United States, but to what extent is not clear. The aim was to describe the utilization pattern of NMB agents and factors associated with the use of reversal agents (neostigmine and sugammadex) in US children. Cross-sectional study of children with exposure to NMB agents between 2015 and 2017 in the Cerner Health Facts database, which is an electronic health record (EHR) database across 600 facilities in the United States. Logistic regression estimated factors associated with the use of sugammadex vs neostigmine. A total of 27 094 pediatric clinical encounters were exposed to neuromuscular blocking agents (NMBAs), in which 21 845 were exposed to rocuronium (76%), vecuronium (18%), or both (6%). Among children with exposure to rocuronium and vecuronium, the use of sugammadex was 1.7% in 2016 and 7.6% in 2017. The multivariable logistic model suggested that children who were older (age 12-17 years vs 0-1 year; odds ratio [OR] 1.96; 95% confidence interval [CI], 1.36-2.83), Hispanic or Latino ethnicity and other ethnicities (vs non-Hispanic or Latino; OR 2.03 and 1.56; 95% CI, 1.55-2.67 and 1.15-2.13, respectively), in teaching facilities (OR 1.26; 95% CI, 1.00-1.59), or admitted through emergency departments (OR 1.65; 95% CI, 1.06-2.58) were independently more likely to receive sugammadex than neostigmine after controlling for other covariates. In Cerner Health Facts database 2015 to 2017, among children, rocuronium was more commonly used than vecuronium, and sugammadex use was observed since 2016. Sugammadex and neostigmine users varied by demographic, clinical, and site-level characteristics.
PubMed: 34720141
DOI: 10.1177/0018578720918332 -
Journal of Intensive Care Medicine Feb 2023Previous studies analyzing neuromuscular blocking agents (NMBAs) in acute respiratory distress syndrome (ARDS) have evaluated the benefit of cisatracurium with...
PURPOSE
Previous studies analyzing neuromuscular blocking agents (NMBAs) in acute respiratory distress syndrome (ARDS) have evaluated the benefit of cisatracurium with conflicting results, and data evaluating other NMBAs remains limited. The objective of this study was to compare the efficacy and safety of cisatracurium to vecuronium in ARDS.
MATERIALS AND METHODS
A single-center, retrospective, propensity matched review of patients who received cisatracurium or vecuronium continuous infusions between October 1, 2017 and June 30, 2020 for ARDS was conducted. The primary endpoint was duration of mechanical ventilation. Secondary endpoints included change in PaO/FiO ratio at 48 h, intensive care unit (ICU) and hospital mortality, and ICU and hospital length of stay (LOS). Safety endpoints included newly developed myopathy, presence of bradycardia or hypotension, and newly developed barotrauma or volutrauma.
RESULTS
Twenty-nine patients were included in each group. There was no statistically significant difference in the primary endpoint of ventilator days between cisatracurium and vecuronium groups (mean 15.9 vs. 20.5 days respectively; = .2). No statistically significant differences were found in secondary endpoints of ICU mortality (51.7% vs. 51.7%) or length of stay (18.7 vs. 23.9 days, ), hospital mortality (51.7% vs. 55.2%, ) or length of stay (22 vs. 30.6 days, ), or mean change in PaO/FiO (29.8 vs. 36.6; ). Statistically significant differences were not observed in safety endpoints of myopathy (37.9% vs. 37.9%), barotrauma or volutrauma (13.8% vs. 3.5%; = .16), bradycardia (31% vs. 13.8%; = .12), or hypotension (96.6% vs. 82.8%; = .08).
CONCLUSIONS
No significant differences were seen in efficacy or safety endpoints between cisatracurium or vecuronium groups, suggesting that vecuronium may be a safe alternative agent for neuromuscular blockade in ARDS. Results of this analysis warrant confirmation in a larger, randomized study.
Topics: Humans; Muscular Diseases; Respiratory Distress Syndrome; Retrospective Studies; Vecuronium Bromide
PubMed: 35821572
DOI: 10.1177/08850666221113504 -
Asian Journal of Anesthesiology Dec 2023Deep neuromuscular blockade (d-NMB) is an essential requirement for carboperitoneum during laparoscopy surgery. However, sustaining d-NMB till the completion of surgery... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Deep neuromuscular blockade (d-NMB) is an essential requirement for carboperitoneum during laparoscopy surgery. However, sustaining d-NMB till the completion of surgery delays the reversal of the residual block. Therefore, there is a merit in exploring the effect of synergistic vecuronium-atracurium combination on the duration-of-action of d-NMB during "laparoscopic" surgery when we compare intubating bolus non-depolarizers (atracurium, vecuronium) administered alone. This study aims to evaluate whether the synergistic effect atracurium-vecuronium combination increases duration-of-action of d-NMB "laparoscopic" surgery settings.
METHODS
Forty-eight patients (18-60 years, American Society of Anesthesiologists physical status- II/III, either sex) undergoing laparoscopic cholecystectomy were randomly allocated to receive vecuronium (vecuronium group, n = 16) or atracurium (atracurium group, n = 16) or vecuroniumatr-acurium combination (vecuronium-atracurium combination group, n = 16) and analyzed for the effects on the duration-of-action (primary objective); onset-of-action, reversibility, and quality of intubating conditions (secondary objectives) profile of neuromuscular blockade in patients undergoing laparoscopic cholecystectomy.
RESULTS
Duration-of-action of neuromuscular blockade was significantly longer in patients who received atracurium-vecuronium combination (53.9 ± 9.7 minutes) versus atracurium-alone (41.1 ± 3.8 minutes) or vecuronium-alone (43.5 ± 9.2 minutes) (P = 0.000). No difference was found for the time to onset-of-action (vecuronium [198.1 ± 34.9 seconds], atracurium [188.5 ± 50.6 seconds], or atracurium-vecuronium combination [196.3 ± 46.3 seconds] [P = 0.829]); time for the reversal of muscle relaxation effect (vecuronium [559.9 ± 216.2 seconds], atracurium [584.7 ± 258.3 seconds], and atracurium-vecuronium combination [555.0 ± 205.4 seconds] [P = 0.925]); and quality-of-intubating conditions (vecuronium group [9.6 ± 1.3]; atracurium group [10.0 ± 0.0]; atracurium-vecuronium group [10.0 ± 0.0] [P = 0.182]).
CONCLUSION
The synergistic effect of the atracurium-vecuronium combination leads to an increased duration-of-action of d-NMB during laparoscopic cholecystectomy without impacting onset-of-action, quality of intubating conditions, and reversal of muscle relaxant effect.
Topics: Humans; Atracurium; Male; Female; Vecuronium Bromide; Adult; Middle Aged; Neuromuscular Nondepolarizing Agents; Neuromuscular Blockade; Laparoscopy; Young Adult; Adolescent; Cholecystectomy, Laparoscopic; Drug Therapy, Combination; Drug Synergism
PubMed: 38695065
DOI: 10.6859/aja.202312_61(4).0001 -
Journal of Visualized Experiments : JoVE May 2022The objective of this protocol is to set up a rat heterotopic heart transplantation model with donation after circulatory death (DCD) donor hearts. There are two setups...
The objective of this protocol is to set up a rat heterotopic heart transplantation model with donation after circulatory death (DCD) donor hearts. There are two setups for this protocol: heart donor setup and recipient setup. In the heart donor setup, Sprague Dawley rats are anesthetized, endotracheally intubated, and ventilated. The right carotid artery is cannulated to deliver heparin and the paralytic agent vecuronium-bromide. The DCD process is initiated by terminating the ventilation. After 20 min, the heart is exposed and the aorta distal to the brachiocephalic branch is clamped. At 25 min from terminating the ventilator, ice-cold University of Wisconsin (UW) solution is perfused through the carotid catheter to flush the heart. The heart is procured by dividing the aorta, pulmonary artery, venae cavae, and pulmonary veins and stored in UW solution for implantation. In the recipient setup, the Lewis rat is anesthetized with isoflurane. Slow-release buprenorphine is administered subcutaneously to facilitate a smooth postoperative recovery. Through a midline abdominal incision, the infra-renal aorta and the inferior vena cava are isolated and clamped with an atraumatic vascular clamp. The donor heart aorta and pulmonary artery are sutured to the recipient abdominal aorta and vena cava, respectively, with a running 8-0 Prolene. The vascular clamp is removed to reperfuse the heart. The abdominal wall is closed and the rat is recovered. After a set interval (24 h to 2 weeks), the recipient rat is anesthetized, the transplanted heart is exposed, and a balloon-tip-catheter is inserted into the left ventricle via the apex to record developed pressure and dP/dt using a data acquisition system. The heart tissue is collected for histology, immunology, or molecular analysis. A successful DCD donor rat heart transplantation model will allow further studies on the cardioprotective approaches to improve heart transplantation outcomes from DCD donors.
Topics: Adenosine; Allopurinol; Animals; Glutathione; Heart; Heart Transplantation; Humans; Insulin; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Tissue Donors; Transplantation, Heterotopic
PubMed: 35661103
DOI: 10.3791/63844 -
Anesthesiology Feb 2023The clinical actions of sugammadex have been well studied, but the detailed molecular mechanism of the drug encapsulation process has not been systematically documented....
BACKGROUND
The clinical actions of sugammadex have been well studied, but the detailed molecular mechanism of the drug encapsulation process has not been systematically documented. The hypothesis was that sugammadex would attract rocuronium and vecuronium via interaction with the sugammadex side-chain "tentacles," as previously suggested.
METHODS
Computational molecular dynamics simulations were done to investigate docking of sugammadex with rocuronium and vecuronium. To validate these methods, strength of binding was assessed between sugammadex and a heterogeneous group of nine other drugs, the binding affinities of which have been experimentally determined. These observations hinted that high concentrations of unbound sugammadex could bind to propofol, potentially altering its pharmacokinetic profile. This was tested experimentally in in vitro cortical slices.
RESULTS
Sugammadex encapsulation of rocuronium involved a sequential progression down a series of metastable states. After initially binding beside the sugammadex molecule (mean ± SD center-of-mass distance = 1.17 ± 0.13 nm), rocuronium then moved to the opposite side to that hypothesized, where it optimally aligned with the 16 hydroxyl groups (distance, 0.82 ± 0.04 nm) before entering the sugammadex cavity to achieve energetically stable encapsulation by approximately 120 ns (distance, 0.35 ± 0.12 nm). Vecuronium formed fewer hydrogen bonds with sugammadex than did rocuronium; hence, it was less avidly bound. For the other molecules, the computational results showed good agreement with the available experimental data, showing a clear bilogarithmic relation between the relative binding free energy and the association constant (R2 = 0.98). Weaker binding was manifest by periodic unbinding. The brain slice results confirmed the presence of a weak propofol-sugammadex interaction.
CONCLUSIONS
Computational simulations demonstrate the dynamics of neuromuscular blocking drug encapsulation by sugammadex occurring from the opposite direction to that hypothesized and also how high concentrations of unbound sugammadex can potentially weakly bind to other drugs given during general anesthesia.
Topics: Sugammadex; Vecuronium Bromide; Rocuronium; gamma-Cyclodextrins; Neuromuscular Nondepolarizing Agents; Androstanols; Propofol; Dose-Response Relationship, Drug; Neuromuscular Blockade
PubMed: 36512718
DOI: 10.1097/ALN.0000000000004442 -
Anesthesia and Analgesia Dec 2021Neuromuscular blockade (NMB) is a critical part of many surgical procedures. Data on practice patterns of NMB agents (NMBAs) and NMB reversal in recent years in the US...
BACKGROUND
Neuromuscular blockade (NMB) is a critical part of many surgical procedures. Data on practice patterns of NMB agents (NMBAs) and NMB reversal in recent years in the US ambulatory surgical care setting are limited.
METHODS
This retrospective analysis of US adult outpatients was conducted using the Premier Healthcare Database. We describe anesthesia practice trends in NMB management and assess the association of patient, procedural, and site characteristics with NMB reversal approach using multivariable logistic regression.
RESULTS
Approximately 5.2 million outpatient surgical encounters involving NMB and 4.6 million involving rocuronium or vecuronium between January 2014 and June 2019 were included. Following the introduction of sugammadex to US clinical practice (~2016), there was an increased use of rocuronium or vecuronium and a decrease in succinylcholine alone. Before 2016, NMB was pharmacologically reversed with neostigmine in approximately two-thirds of outpatient encounters. Over time, active reversal increased; by 2019, 42.3% and 36.0% of encounters were reversed by neostigmine and sugammadex, respectively, with 21.7% undergoing spontaneous recovery. Choice of NMBA (rocuronium or vecuronium alone), time since 2016, obesity, peripheral vascular disease, and procedures on the digestive, ocular, and female genital systems (vs musculoskeletal procedures) were independently and positively associated with pharmacologic reversal (versus spontaneous reversal). Conversely, advanced age; Western geography; and cardiovascular, endocrine, hemic/lymphatic, respiratory, and ear, nose, and throat procedures were independently and negatively associated with pharmacologic reversal of NMB.Among pharmacologic reversals, time since 2016 was positively and independently associated with sugammadex compared with neostigmine (odds ratios [ORs], ranged from 1.8 in 2017 to 3.2, P < .0001 in 2019). Those administered rocuronium or vecuronium without succinylcholine, with increased age and history of certain comorbidities, and those undergoing ocular or respiratory procedures (compared with musculoskeletal) were positively associated with reversal with sugammadex and endocrine procedure negatively and independently associated with reversal with sugammadex. There was variability in the association of several factors with NMB reversal choices by geographic region, particularly in patients' race, ethnicity, and size of affiliated hospital.
CONCLUSIONS
Overall, active pharmacological reversal of NMB increased in US adult outpatients following the introduction of sugammadex, although there remains significant practice variability. The multifactorial relationship between patient-, procedural-, and environmental-level characteristics and NMB management is rapidly evolving. Additional research on how these anesthesia practice patterns may be impacted by the shift to the ambulatory care setting and how they may impact patient outcomes and health disparities is warranted.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Surgical Procedures; Anesthesia Recovery Period; Comorbidity; Databases, Factual; Ethnicity; Female; Humans; Male; Middle Aged; Neostigmine; Neuromuscular Blockade; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Retrospective Studies; Rocuronium; Succinylcholine; Sugammadex; United States; Vecuronium Bromide; Young Adult
PubMed: 34784330
DOI: 10.1213/ANE.0000000000005657