scholarly journals A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
W. Joseph Herring ◽  
Yuki Mukai ◽  
Aobo Wang ◽  
Jeannine Lutkiewicz ◽  
John F. Lombard ◽  
...  
Keyword(s):  
Sinus Tachycardia ◽  
Sinus Bradycardia ◽  
Neuromuscular Block ◽  
Tolerability Profile ◽  
Double Blind ◽  
Link Type ◽  
Cardiac Arrythmias ◽  
Deep Neuromuscular Block ◽  
American Society ◽  
The Impact

Abstract 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/m2, 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.

scholarly journals The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial — EURO-RELAX TRIAL

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Maarten Honing ◽  
Gabby Reijnders-Boerboom ◽  
Salome Dell-Kuster ◽  
Monique van Velzen ◽  
Chris Martini ◽  
...  
Keyword(s):  
Laparoscopic Surgery ◽  
Adverse Events ◽  
Working Conditions ◽  
Neuromuscular Block ◽  
Double Blind ◽  
Randomized Controlled ◽  
Link Type ◽  
Deep Neuromuscular Block ◽  
The Impact ◽  
International Multicenter

Abstract Background Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block yields superior surgical working conditions compared to a standard NMB in laparoscopic surgery, however, a robust association to other (safety) outcomes has not yet been established. Methods Trial design: an international multicenter randomized controlled double-blind strategy trial. Trial population: 922 patients planned for elective, laparoscopic or robotic, abdominal surgery. Intervention: Patients will be randomized to a deep NMB (post-tetanic count 1–2 twitches) or standard care (single-dose muscle relaxant administration at induction and repeated only if warranted by surgical team). Main trial endpoints: Primary endpoint is the difference in incidence of intraoperative adverse events during laparoscopic surgery graded according to ClassIntra® classification (i.e., ClassIntra® grade ≥ 2) between both groups. Secondary endpoints include the surgical working conditions, 30-day postoperative complications, and patients’ quality of recovery. Discussion This trial was designed to analyze the effect of deep neuromuscular block compared to standard neuromuscular block on intra- and postoperative adverse events in patients undergoing laparoscopic surgery. Trial registration ClinicalTrials.gov NCT04124757(EURO-RELAX); registration URL: https://clinicaltrials.gov/ct2/show/NCT04124757, registered on October 11th, 2019. 

scholarly journals A Clinical Comparison of Atracurium and Vecuronium in Women Undergoing Laparoscopy

1987 ◽  
Vol 15 (3) ◽  
pp. 310-316 ◽  
Author(s):  
M. A. Raynes ◽  
R. Chisholm ◽  
D. F. Woolner ◽  
J. M. Gibbs
Keyword(s):  
Sinus Bradycardia ◽  
Neuromuscular Block ◽  
Randomised Trial ◽  
Neuromuscular Monitoring ◽  
Double Blind ◽  
Duration Of Action ◽  
Prospective Randomised Trial ◽  
Clinical Comparison ◽  
Intraoperative Hypotension ◽  
Significant Difference

In a double blind, prospective, randomised trial in 30 women undergoing laparoscopy, atracurium and vecuronium were compared in equipotent (2 X ED95) doses. In the atracurium group, first twitch depression was significantly greater at one minute, and degree of fade significantly greater at one and two minutes, but thereafter neuromuscular monitoring showed no significant difference between the groups. Clinically there was no significant difference between the drugs. Mild intraoperative hypotension was equally common in both groups as was sinus bradycardia. Reversal and recovery were comparable in the two groups. Neostigmine was required in all patients and in three (one atracurium, two vecuronium) a second dose was administered on clinical grounds. Antagonism of the neuromuscular block is required with surgery of this duration despite the intermediate duration of action of the relaxant drugs.

scholarly journals Impact of galcanezumab on total pain burden: findings from phase 3 randomized, double-blind, placebo-controlled studies in patients with episodic or chronic migraine (EVOLVE-1, EVOLVE-2, and REGAIN trials)

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jessica Ailani ◽  
J. Scott Andrews ◽  
Mallikarjuna Rettiganti ◽  
Robert A. Nicholson
Keyword(s):  
Chronic Migraine ◽  
Migraine Headache ◽  
Pain Severity ◽  
Life Questionnaire ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Link Type ◽  
Total Pain ◽  
Maximum Pain ◽  
The Impact

Abstract Background Focus on the frequency of migraine pain may undervalue the total burden of migraine as pain duration and severity may present unique, additive burden. A composite measure of total pain burden (TPB; frequency, severity, and duration) may provide a more comprehensive characterization of pain burden and treatment response in patients with episodic migraine (EM) or chronic migraine (CM). The impact of galcanezumab versus placebo on TPB among patients with EM or CM was analyzed. Methods Patients from randomized, double-blind, placebo-controlled episodic (two 6-month studies pooled) and chronic migraine (3-month) studies received once-monthly subcutaneous injection of galcanezumab 120 mg or placebo. A post hoc analysis of TPB for a given month was calculated as severity-weighted duration by multiplying duration (hours) and maximum pain severity (0 = none, 1 = mild, 2 = moderate, 3 = severe) of migraine for each day and summing these over the days in a month. Least square mean change from baseline in monthly TPB across Months 1–6 (EM, N = 444 galcanezumab, N = 894 placebo) and Months 1–3 (CM, N = 278 galcanezumab, N = 558 placebo) were compared using a mixed-model repeated measures model. Correlation of the Migraine Specific Quality of Life Questionnaire (MSQ) and Migraine Disability Assessment Scale (MIDAS) to TPB at baseline was assessed. Results At baseline, the duration of migraine on a given migraine headache day accounted for the greatest unique proportion of variability (EM, 57.4% and CM, 61.1%) to TPB after adjusting for frequency of migraine headache days and maximum pain severity. The decrease from baseline in monthly TPB was greater with galcanezumab than placebo for patients with EM (68.6 versus 36.2) and CM (102.6 versus 44.4). The average percent reduction of TPB from baseline was significantly greater with galcanezumab compared with placebo in patients with EM (50.8% versus 17.2%) and CM (29.7% versus 11.0%). In patients with EM and CM, TPB correlated with MSQ total score (r = − 0.35 and r = − 0.37) and MIDAS (r = 0.34 and r = 0.32). Conclusions Greater reduction in TPB was seen in patients with EM and CM treated with galcanezumab 120 mg once-monthly injection relative to placebo. Discussing TPB supports patient-centric conversations regarding treatment expectations when clinicians are evaluating options for migraine prevention. Trial registration ClinicalTrials.gov: #NCT02614183 (I5Q-MC-CGAG; EVOLVE-1), #NCT02614196 (I5Q-MC-CGAH; EVOLVE-2), and #NCT02614261 (I5Q-MC-CGAI; REGAIN) – all 3 trials were registered on 23 November 2015.

scholarly journals A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol

2016 ◽  
Vol 48 (2) ◽  
pp. 320-330 ◽  
Author(s):  
Steven J. Pascoe ◽  
David A. Lipson ◽  
Nicholas Locantore ◽  
Helen Barnacle ◽  
Noushin Brealey ◽  
...  
Keyword(s):  
Treatment Period ◽  
Inhaled Corticosteroids ◽  
Controlled Trial ◽  
Phase Iii ◽  
Chronic Obstructive ◽  
Impact Study ◽  
Double Blind ◽  
Link Type ◽  
Long Acting ◽  
The Impact

Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017.

scholarly journals Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jay C. Horrow ◽  
Wen Li ◽  
Manfred Blobner ◽  
John Lombard ◽  
Marcel Speek ◽  
...  
Keyword(s):  
Body Weight ◽  
Recovery Time ◽  
Neuromuscular Block ◽  
Ideal Body Weight ◽  
Rank Test ◽  
Morbidly Obese ◽  
Double Blind ◽  
Link Type ◽  
Safety Outcomes ◽  
Ideal Body

Abstract Background This randomized, double-blind trial evaluated sugammadex-mediated recovery time from rocuronium- or vecuronium-induced moderate (M-) or deep (D-) neuromuscular block in morbidly obese adults dosed by actual (ABW) or ideal body weight (IBW). Methods Adults with BMI ≥40 kg/m2 were randomized to 1 of 5 groups: M-neuromuscular block, sugammadex 2 mg/kg ABW; M-neuromuscular block, sugammadex 2 mg/kg IBW; M-neuromuscular block, neostigmine 5 mg, and glycopyrrolate 1 mg; D-neuromuscular block, sugammadex 4 mg/kg ABW; or D-neuromuscular block, sugammadex 4 mg/kg IBW. Supramaximal train of four (TOF) stimulation of the ulnar nerve (TOF-watch SX®) monitored recovery. Primary endpoint was time to TOF ratio ≥ 0.9 for ABW and IBW groups pooled across neuromuscular blocking agent (NMBA)/blocking depth, analyzed by log-rank test stratified for agent and depth. Prespecified safety outcomes included treatment-emergent bradycardia, tachycardia, and other arrhythmias, and adjudicated hypersensitivity and anaphylaxis. Results Of 207 patients randomized, 188 received treatment (28% male, BMI 47 ± 5.1 kg/m2, age 48 ± 13 years). Recovery was 1.5 min faster with ABW vs IBW dosing. The sugammadex 2 mg/kg groups recovered 9-fold faster [time 0.11-fold, 95% CI 0.08 to 0.14] than the neostigmine group. ABW (5.3%) and IBW (2.7%) groups had similar incidences of recovery time > 10 min (95% CI of difference: − 4.8 to 11.0%); 84% for neostigmine group. Re-curarization occurred in one patient each in the 2 mg/kg IBW and neostigmine groups. Prespecified safety outcomes occurred with similar incidences. Conclusions ABW-based sugammadex dosing yields faster reversal without re-curarization, supporting ABW-based sugammadex dosing in the morbidly obese, irrespective of the depth of neuromuscular block or NMBA used. Trial registration Registered on November 17, 2017, at ClinicalTrials.gov under number NCT03346070.

scholarly journals Deep Neuromuscular Block Improves Surgical Conditions during Bariatric Surgery and Reduces Postoperative Pain: A Randomized Double Blind Controlled Trial

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167907 ◽  
Author(s):  
Bart Torensma ◽  
Chris H. Martini ◽  
Martijn Boon ◽  
Erik Olofsen ◽  
Bas in ‘t Veld ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Postoperative Pain ◽  
Neuromuscular Block ◽  
Controlled Trial ◽  
Double Blind ◽  
Deep Neuromuscular Block ◽  
Surgical Conditions

scholarly journals Reliable and rapid smooth extubation after Ketofol for induction of general anesthesia in Laparoscopic Drilling of polycystic ovary: A randomized controlled trial.

2020 ◽  
Author(s):  
Atef Mohamed Sayed Mahmoud ◽  
Safaa Gaber Ragab ◽  
Joseph Makram Botros
Keyword(s):  
General Anesthesia ◽  
Polycystic Ovary ◽  
Controlled Trial ◽  
Controlled Study ◽  
Double Blind ◽  
Randomized Controlled ◽  
Airway Response ◽  
American Society ◽  
American Society Of Anesthesiologists ◽  
The Impact

Abstract Background: The impact of ketofol on the hemodynamics and the airway response during the induction of general anesthesia has been studied before. However, its effect on the smoothness of extubation has not been studied before. Thus, we aimed to assess the effect of ketofol on the smoothness of extubation and compare it with propofol for the induction of general anesthesia.Methods: This double-blind, randomized, and controlled study was conducted on 106 class I and II female patients with the “American Society of Anesthesiologists Physical Status (ASA PS),” aged 18–40 years and scheduled for laparoscopic drilling for polycystic ovary disease under general anesthesia. The patients were assigned to one of two groups of (53) patients each; group KP = ketofol and group P = propofol. Results: There was a good sedation score during suction and extubation in the ketofol group. Airway response and smoothness of extubation were better in the ketofol than in the propofol group.Conclusion: Ketofol as an induction anesthetic agent was effective in attenuating the airway response during extubation more than only propofol.Trial registration: This trial was retrospectively registered at the Clinical Trial.gov with the Identification Number: NCT04365686.

scholarly journals A Randomized Trial Evaluating Actual Versus Ideal Body Weight Dosing of Sugammadex in Morbidly Obese Patients 

2020 ◽  
Author(s):  
Jay C. Horrow ◽  
Wen Li ◽  
Manfred Blobner ◽  
John Lombard ◽  
Marcel Speek ◽  
...  
Keyword(s):  
Body Weight ◽  
Recovery Time ◽  
Neuromuscular Block ◽  
Ideal Body Weight ◽  
Rank Test ◽  
Morbidly Obese ◽  
Double Blind ◽  
Safety Outcomes ◽  
Deep Neuromuscular Block ◽  
Ideal Body

Abstract Background: This randomized, double-blind trial evaluated sugammadex-mediated recovery time from rocuronium- or vecuronium-induced moderate (M-) or deep neuromuscular block (D-NMB) in morbidly obese adults dosed by actual (ABW) or ideal body weight (IBW). Methods: Adults with BMI ≥40 kg/m2 were randomized to 1 of 5 groups: M-NMB, sugammadex 2 mg/kg ABW; M-NMB, sugammadex 2 mg/kg IBW; M-NMB, neostigmine 5 mg, and glycopyrrolate 1 mg; D-NMB, sugammadex 4 mg/kg ABW; or D-NMB, sugammadex 4 mg/kg IBW. Supramaximal train of four (TOF) stimulation of the ulnar nerve (TOF-watch SX®) monitored recovery. Primary endpoint was time to TOF ratio ≥0.9 for ABW and IBW groups pooled across NMB agent (NMBA)/blocking depth, analyzed by log-rank test stratified for agent and depth. Prespecified safety outcomes included treatment-emergent bradycardia, tachycardia, and other arrhythmias, and adjudicated hypersensitivity and anaphylaxis. Results: Of 207 patients randomized, 188 received treatment (28% male, BMI 47±5.1 kg/m2, age 48±13 years). Recovery was 1.5 min faster with ABW vs IBW dosing. The sugammadex 2 mg/kg groups recovered 9-fold faster [time 0.11-fold, 95% CI 0.08 to 0.14] than the neostigmine group. ABW (5.3%) and IBW (2.7%) groups had similar incidences of recovery time >10 min (95% CI of difference: -4.8% to 11.0%); 84% for neostigmine group. Re-curarization occurred in one patient each in the 2 mg/kg IBW and neostigmine groups. Prespecified safety outcomes occurred with similar incidences. Conclusions: ABW-based sugammadex dosing yields faster reversal without re-curarization, supporting ABW-based sugammadex dosing in the morbidly obese, irrespective of the depth of NMB or NMBA used. Trial registration: Registered on November 17, 2017, at ClinicalTrials.gov under number NCT03346070. https://clinicaltrials.gov/ct2/show/results/NCT03346070?term=NCT03346070&draw=2&rank=1

scholarly journals Consumption of Enriched Yogurt with PAF Inhibitors from Olive Pomace Affects the Major Enzymes of PAF Metabolism: A Randomized, Double Blind, Three Arm Trial

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Lipid Mediator ◽  
Olive Pomace ◽  
Double Blind ◽  
Promising Alternative ◽  
Catabolic Enzymes ◽  
Platelet Activating Factor Acetylhydrolase ◽  
The Impact ◽  
By Products ◽  
Apparently Healthy

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

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