Reversal of Neuromuscular Blockade and Perioperative Arrhythmias
Primary Purpose
Neuromuscular Blockade
Status
Completed
Phase
Not Applicable
Locations
Turkey
Study Type
Interventional
Intervention
Neostigmine
Sugammadex
Sponsored by
About this trial
This is an interventional prevention trial for Neuromuscular Blockade focused on measuring Bradycardia, Cardiac Arrhythmias, Neostigmine, Neuromuscular Blockade, Sugammadex, Train-of-Four Monitoring
Eligibility Criteria
Inclusion Criteria:
- Planned abdominopelvic surgery under general anesthesia
- ASA II-IV
- Willing to give consent
Exclusion Criteria:
- Significantly impaired left ventricular systolic function (ejection fraction < 40%)
- Significant ongoing arrhythmia (sinus bradycardia with a heart rate below 40 beats/min, Mobitz Type II or 3rd-grade atrioventricular block, persistent or permanent atrial flutter or fibrillation, bigeminal or trigeminal ventricular premature beats, documented ventricular tachycardia)
- Severely reduced renal function (glomerular filtration rate < 30 ml/min/1.73 m2)
- Severe respiratory diseases, neuromuscular disorders, and known allergy to anesthetic agents or adjuvants
- Pregnancy and breastfeeding
- Observing the typical signs of a channelopathy (short QT syndrome, long QT syndrome, Brugada syndrome, etc.) and history of recent medical therapy with agents exhibiting a high probability of QT prolongation
Sites / Locations
- Istanbul Medipol University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Group N
Group S
Arm Description
Neostigmine was used for the reversal of neuromuscular blockade.
Sugammadex was used for the reversal of neuromuscular blockade.
Outcomes
Primary Outcome Measures
Significant arrhythmic event
Pause (no waves on ECG recording at least for 3 seconds), significant bradycardia (sinus bradycardia persisted at least for 30 seconds with a rate below 50 beats/min), high-grade atrioventricular block (2nd-degree Mobitz Type II or 3rd degree), supraventricular tachycardia (sudden onset tachycardia with narrow QRS complexes persisted over 30 seconds), atrial flutter or fibrillation (sustained over 30 seconds), Frequent premature ventricular beats (≥30 beats/hour).
Secondary Outcome Measures
Full Information
NCT ID
NCT04720573
First Posted
January 19, 2021
Last Updated
January 19, 2021
Sponsor
Basaksehir Cam & Sakura Şehir Hospital
Collaborators
Medipol University
1. Study Identification
Unique Protocol Identification Number
NCT04720573
Brief Title
Reversal of Neuromuscular Blockade and Perioperative Arrhythmias
Official Title
Influence of the Neuromuscular Blockade and Its Reversal on Perioperative Arrhythmias
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
June 1, 2019 (Actual)
Primary Completion Date
October 1, 2019 (Actual)
Study Completion Date
November 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Basaksehir Cam & Sakura Şehir Hospital
Collaborators
Medipol University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Patients scheduled for elective abdominopelvic laparoscopic surgery under general anesthesia were included. Rocuronium was used for the neuromuscular blockade (NMB) and the level of NMB was monitored with train-of-four (TOF) measurements. The participants from whom informed consent had been received were allocated to two groups according to the agent used for reversal of NMB, sugammadex, or neostigmine. The ECG recordings of the subjects were followed with a rhythm Holter device throughout the procedure until the postoperative 12th hour. Additionally, preoperative and immediate postoperative 12-lead ECGs were evaluated for corrected QT calculations and QT dispersion. Proarrhythmogenicity was assessed with QT related measurements. The documented arrhythmic events on the Holter monitoring were designated as clinical end-points.
Detailed Description
Eighty consecutive patients, to whom an elective abdominopelvic surgery under general anesthesia was planned, were included in the study. Participants were allocated to two groups considering the agent to be used for the reversal of neuromuscular blockade by closed-envelope randomization. Neostigmine was used for this purpose in Group N, while sugammadex was used in Group S. Demographic features including hypertension, diabetes mellitus, presence of coronary artery disease, heart failure, and previous arrhythmia were noted. Body mass index was calculated with the Du Bois method. In the operation room, heart rate, blood pressure, body temperature, arterial oxygen saturation, and TOF ratio were recorded. General anesthesia was induced with midazolam, fentanyl, and propofol; and maintained by remifentanil and sevoflurane. In Group N, 50 mcg/kg neostigmine and 20 mcg/kg atropine were used for NMB reversal. In Group S, reversal was achieved by the administration of sugammadex at a dose of 2 mg/kg. QT interval was measured in leads DII or V5 and adjusted to the heart rate by the Bazzett formula. QTc values at the baseline and postoperative ECGs were recorded and presented with milliseconds. An increase of over 60 ms in QTc interval or a postoperative measurement over 500 ms were assumed to be distinctly abnormal. QT dispersion was calculated by extracting the minimum QT length from the maximum QT length in 12-lead ECG. In rhythm holter monitoring, minimum and mean heart rates and specific arrhythmic events were recorded. In the heart rate variability analysis, the standard deviation of the interbeat intervals of normal sinus beats (SDNN) and the root mean square of successive differences between normal heartbeats (rMSSD) were calculated. The following events were designated as clinical end-points.
Pause (no waves on ECG recording at least for 3 seconds)
Significant bradycardia (sinus bradycardia persisted at least for 30 seconds with a rate below 50 beats/min)
High-grade atrioventricular block (2nd-degree Mobitz Type II or 3rd degree)
Supraventricular tachycardia (sudden onset tachycardia with narrow QRS complexes persisted over 30 seconds)
Atrial flutter or fibrillation (sustained over 30 seconds)
Frequent premature ventricular beats (≥30 beats/hour)
Any ventricular tachycardia (wide QRS complexes)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromuscular Blockade
Keywords
Bradycardia, Cardiac Arrhythmias, Neostigmine, Neuromuscular Blockade, Sugammadex, Train-of-Four Monitoring
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
1:1 randomization
Masking
Investigator
Masking Description
The investigator assessing the ECGs, and rhythm holter recordings was blinded to randomization.
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group N
Arm Type
Active Comparator
Arm Description
Neostigmine was used for the reversal of neuromuscular blockade.
Arm Title
Group S
Arm Type
Active Comparator
Arm Description
Sugammadex was used for the reversal of neuromuscular blockade.
Intervention Type
Drug
Intervention Name(s)
Neostigmine
Intervention Description
50 mcg/kg neostigmine was used under the guidance of TOF monitoring after cessation of anesthesia.
Intervention Type
Drug
Intervention Name(s)
Sugammadex
Intervention Description
2 mg/kg sugammadex was used under the guidance of TOF monitoring after cessation of anesthesia.
Primary Outcome Measure Information:
Title
Significant arrhythmic event
Description
Pause (no waves on ECG recording at least for 3 seconds), significant bradycardia (sinus bradycardia persisted at least for 30 seconds with a rate below 50 beats/min), high-grade atrioventricular block (2nd-degree Mobitz Type II or 3rd degree), supraventricular tachycardia (sudden onset tachycardia with narrow QRS complexes persisted over 30 seconds), atrial flutter or fibrillation (sustained over 30 seconds), Frequent premature ventricular beats (≥30 beats/hour).
Time Frame
Up to 12 hours after surgical procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Planned abdominopelvic surgery under general anesthesia
ASA II-IV
Willing to give consent
Exclusion Criteria:
Significantly impaired left ventricular systolic function (ejection fraction < 40%)
Significant ongoing arrhythmia (sinus bradycardia with a heart rate below 40 beats/min, Mobitz Type II or 3rd-grade atrioventricular block, persistent or permanent atrial flutter or fibrillation, bigeminal or trigeminal ventricular premature beats, documented ventricular tachycardia)
Severely reduced renal function (glomerular filtration rate < 30 ml/min/1.73 m2)
Severe respiratory diseases, neuromuscular disorders, and known allergy to anesthetic agents or adjuvants
Pregnancy and breastfeeding
Observing the typical signs of a channelopathy (short QT syndrome, long QT syndrome, Brugada syndrome, etc.) and history of recent medical therapy with agents exhibiting a high probability of QT prolongation
Facility Information:
Facility Name
Istanbul Medipol University
City
Istanbul
ZIP/Postal Code
34214
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22063382
Citation
Lorentz MN, Vianna BS. Cardiac dysrhythmias and anesthesia. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):798-813. doi: 10.1016/S0034-7094(11)70090-3. English, Multiple languages.
Results Reference
background
PubMed Identifier
19455040
Citation
Dahl V, Pendeville PE, Hollmann MW, Heier T, Abels EA, Blobner M. Safety and efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in cardiac patients undergoing noncardiac surgery. Eur J Anaesthesiol. 2009 Oct;26(10):874-84. doi: 10.1097/EJA.0b013e32832c605b.
Results Reference
background
PubMed Identifier
26796612
Citation
Kizilay D, Dal D, Saracoglu KT, Eti Z, Gogus FY. Comparison of neostigmine and sugammadex for hemodynamic parameters in cardiac patients undergoing noncardiac surgery. J Clin Anesth. 2016 Feb;28:30-5. doi: 10.1016/j.jclinane.2015.08.002. Epub 2015 Nov 11.
Results Reference
background
PubMed Identifier
24305646
Citation
Staikou C, Stamelos M, Stavroulakis E. Impact of anaesthetic drugs and adjuvants on ECG markers of torsadogenicity. Br J Anaesth. 2014 Feb;112(2):217-30. doi: 10.1093/bja/aet412. Epub 2013 Dec 3.
Results Reference
result
PubMed Identifier
27871504
Citation
Carron M, Zarantonello F, Tellaroli P, Ori C. Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials. J Clin Anesth. 2016 Dec;35:1-12. doi: 10.1016/j.jclinane.2016.06.018. Epub 2016 Aug 4.
Results Reference
result
PubMed Identifier
29280475
Citation
Hristovska AM, Duch P, Allingstrup M, Afshari A. The comparative efficacy and safety of sugammadex and neostigmine in reversing neuromuscular blockade in adults. A Cochrane systematic review with meta-analysis and trial sequential analysis. Anaesthesia. 2018 May;73(5):631-641. doi: 10.1111/anae.14160. Epub 2017 Dec 27.
Results Reference
result
PubMed Identifier
30218410
Citation
Yamashita Y, Takasusuki T, Kimura Y, Komatsuzaki M, Yamaguchi S. Effects of Neostigmine and Sugammadex for Reversal of Neuromuscular Blockade on QT Dispersion Under Propofol Anesthesia: A Randomized Controlled Trial. Cardiol Ther. 2018 Dec;7(2):163-172. doi: 10.1007/s40119-018-0119-9. Epub 2018 Sep 14.
Results Reference
result
Links:
URL
https://www.fdanews.com/ext/resources/files/11-15/110615-merck.pdf?1515434323
Description
Sugammadex briefing document
Learn more about this trial
Reversal of Neuromuscular Blockade and Perioperative Arrhythmias
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