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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 -
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 -
The Journal of Pediatric Pharmacology... 2022Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium...
Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium is one neuromuscular blocking agent used for this purpose; however, there are limited data regarding its use in pediatric patients with renal failure. Although predominantly considered to be metabolized by the liver, there are numerous adult cases and 1 pediatric case report that have described extended paralysis from vecuronium due to renal failure. The proposed mechanism is accumulation of renally cleared active metabolites. This case report describes an infant with vecuronium exposure during continuous renal replacement therapy who experienced prolonged neuromuscular blockade for several days after the agent was stopped. This highlights the importance of considering renal function when selecting neuromuscular blocking agent.
PubMed: 35558355
DOI: 10.5863/1551-6776-27.4.400 -
PloS One 2022Drug-induced QT prolongation is one of the most common side effects of drug use and can cause fatal outcomes such as sudden cardiac arrest. This study adopts the...
Drug-induced QT prolongation is one of the most common side effects of drug use and can cause fatal outcomes such as sudden cardiac arrest. This study adopts the data-driven approach to assess the QT prolongation risk of all the frequently used drugs in a tertiary teaching hospital using both standard 12-lead ECGs and intensive care unit (ICU) continuous ECGs. We used the standard 12-lead ECG results (n = 1,040,752) measured in the hospital during 1994-2019 and the continuous ECG results (n = 4,835) extracted from the ICU's patient-monitoring devices during 2016-2019. Based on the drug prescription frequency, 167 drugs were analyzed using 12-lead ECG data under the case-control study design and 60 using continuous ECG data under the retrospective cohort study design. Whereas the case-control study yielded the odds ratio, the cohort study generated the hazard ratio for each candidate drug. Further, we observed the possibility of inducing QT prolongation in 38 drugs in the 12-lead ECG analysis and 7 drugs in the continuous ECG analysis. The seven drugs (vasopressin, vecuronium, midazolam, levetiracetam, ipratropium bromide, nifedipine, and chlorpheniramine) that showed a significantly higher risk of QT prolongation in the continuous ECG analysis were also identified in the 12-lead ECG data analysis. The use of two different ECG sources enabled us to confidently assess drug-induced QT prolongation risk in clinical practice. In this study, seven drugs showed QT prolongation risk in both study designs.
Topics: Adult; Aged; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Humans; Intensive Care Units; Long QT Syndrome; Male; Middle Aged; Retrospective Studies
PubMed: 35100302
DOI: 10.1371/journal.pone.0263117 -
Paediatric Anaesthesia Mar 2022Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants.
AIM
To assess sugammadex for reversal of neuromuscular blockade in pediatric participants.
METHODS
This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17 years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4 mg/kg) or neostigmine (50 µg/kg; for moderate neuromuscular blockade only). Predefined adverse events of clinical interest, including clinically relevant bradycardia, hypersensitivity, and anaphylaxis, were monitored. The primary efficacy endpoint was time to recovery to a train-of-four ratio of ≥0.9 in participants receiving sugammadex 2 mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age.
RESULTS
Of 288 randomized participants, 272 completed the study and 276 were included in the analyses. Clinically relevant bradycardia was experienced by 2.0%, 1.6%, and 5.9% of participants in the sugammadex 2 mg/kg, sugammadex 4 mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2 mg/kg was faster than neostigmine (1.6 min, 95% CI 1.3 to 2.0 vs. 7.5 min, 95% CI 5.6 to 10.0; p < .0001) and was comparable to sugammadex 4 mg/kg (2.0 min, 95% CI 1.8 to 2.3).
CONCLUSIONS
Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2 mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4 mg/kg was consistent with that of moderate neuromuscular blockade reversal. No meaningful differences in clinically relevant bradycardia, hypersensitivity, or anaphylaxis were seen with sugammadex vs neostigmine. These results support the use of sugammadex for reversal of moderate and deep rocuronium- and vecuronium-induced neuromuscular blockade in patients aged 2 to <17 years.
CLINICAL TRIAL REGISTRATION
NCT03351608/EudraCT 2017-000692-92.
Topics: Anaphylaxis; Anesthetics; Bradycardia; Child; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 34878707
DOI: 10.1111/pan.14370 -
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 -
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 -
BMC Anesthesiology Oct 2021The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest.
METHODS
Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias.
RESULTS
Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study.
CONCLUSIONS
Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03346057 .
Topics: Aged; Bradycardia; Cholinergic Agents; Double-Blind Method; Female; Glycopyrrolate; Humans; Male; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Tachycardia; Vecuronium Bromide
PubMed: 34711192
DOI: 10.1186/s12871-021-01477-5 -
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 -
Drug Design, Development and Therapy 2021High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the... (Review)
Review
High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.
Topics: Humans; Laparoscopy; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Robotic Surgical Procedures; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 34548781
DOI: 10.2147/DDDT.S328682