Role of Sugammadex as Reversal Agent in Patients Extubated Immediately After Isolated Coronary Artery Bypass Grafting Surgery

The purpose of this study is to examine whether the use of Sugammadex will reduce time from reversal to extubation and improve other post extubation outcomes in Coronary artery bypass grafting patients. This study is a prospective, clinical interventional, randomized single blinded single-center design. The nurses in the cardiac intensive care unit will be blinded to treatment allocation (Group 1 or 2).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Surgery
• Intervention / Treatment: Drug: Rocuronium; Drug: Neostigmine; Drug: Glycopyrrolate; Drug: Sugammadex

Detailed Description

Enhanced recovery pathways and early extubation of subjects undergoing cardiac procedures has now become mainstay, especially with the advent of minimally invasive procedures .

To facilitate optimal recovery after extubation; muscle strength is vital to prevent reintubation, improved deglutition and quicker transition to lower oxygen requirements, and better respiratory and cardiac hemodynamics. It also expedites de-escalation of acuity of care. Several studies have shown residual muscle weakness after full reversal with neostigmine and glycopyrrolate. Sugammadex is a direct reversal agent and can provide superior muscle strength, which optimizes respiratory function thereby preventing atelectasis, hypoxia and potentially avoiding reintubation.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • WVU Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 - 70 years
• American Society of Anesthesiology physical status I-4
• Isolated coronary artery bypass graft surgery (CABG)
• Ability to give written informed consent

Exclusion Criteria:

• Any other surgical procedure concomitant to CABG surgery
• Known or suspected neuromuscular disease/pre-existing weakness
• Creatinine clearance less than 30 ml/min
• Bradycardia of less than 40 beats/min
• Pregnancy, breastfeeding women
• Known or suspected allergy to BRIDION® (sugammadex),neostigmine, or rocuronium
• Patients with contraindications towards sugammadex, neostigmine, or rocuronium
• Patients included in another trial within the last 30 days
• Patients with legal guardians or surrogate decision-making
• Female Patients who refuse to use non-hormonal contraceptive method or back-up method of contraception (such as condoms and spermicides) for the next 7 days if receiving sugammadex.
• Patients undergoing emergency surgery
• Patient refusal
• Patients with ejection fraction <30%
• Patients with restrictive and obstructive lung disease
• Patients with obstructive sleep apnea
• Patients with Body Mass Index greater than 40

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neostigmine/Glycopyrrolate; Group 1: Intubation with rocuronium at 1.0-1.2 mg/kg (vitals maintained within 20% of baseline). Subjects may be re-dosed with rocuronium at 0.1-0.4 mg/kg during the procedure to maintain 1-2 twitches on train of four (TOF) watch monitor reading recorded every 15 minutes. Group 1 (control) will receive reversal with neostigmine (0.04-0.07 mg/kg up to 5 mg maximal dosage) and glycopyrrolate (0.07-0.015mg/kg up to 1 mg maximal dosage).	Drug: Rocuronium; Intubation with Rocuronium 1.0-1.2 mg/kg (vitals maintained within 20% of baseline. Subjects may be re-dosed with rocuronium at 0.1-0.4 mg/kg during the procedure.; Drug: Neostigmine; Reversal with neostigmine (0.04-0.07 mg/kg up to 5 mg maximal dosage); Drug: Glycopyrrolate; Reversal glycopyrrolate (0.07-0.015mg/kg up to 1 mg maximal dosage)
Active Comparator: Sugammadex; Group 2: Intubation with rocuronium at 1.0-1.2 mg/kg (vitals maintained within 20% of baseline). Subjects may be re-dosed with rocuronium at 0.1-0.4 mg/kg during the procedure to maintain 1-2 twitches on train of four (TOF) watch monitor reading recorded every 15 minutes. Group 2 (treatment) will receive reversal with Sugammadex (2mg/kg).	Drug: Rocuronium; Intubation with Rocuronium 1.0-1.2 mg/kg (vitals maintained within 20% of baseline. Subjects may be re-dosed with rocuronium at 0.1-0.4 mg/kg during the procedure.; Drug: Sugammadex; Reversal with Sugammadex (2mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Extubation	Time to extubation: West Virginia University Hospitals use an electronic medical record (EMR) to chart "procedure stop." The definition for "time to extubation" is from the time the investigators chart "procedure stop" to the time of "extubation".	0 minutes of study drug to 3 days after study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tidal Volume	Tidal volume post-reversal prior to extubation	between 30 minutes to 1 hour after extubation
Peak Flow Rate	Peak flow rate - measured by peak flow meter post-extubation at 30-60 mins	30-60 minutes post-extubation
Heart Rate	Heart rate post-reversal prior to extubation	0 minutes to 2 hours after study drug administration
Blood Pressure (First Measurement of Systolic Blood Pressure Post Reversal)	Blood pressure; measure of systolic blood pressure of subject is obtained post-reversal prior to extubation of trachea	0 minutes to 2 hours after study drug administration
Swallowing Capacity	In the intensive care unit: If the patient awake and alert, is able to be positioned, can cough when asked, able to follow command to lick top and bottom lip, and is able to breathe freely then a registered nurse bedside swallowing/dysphagia screen is performed at a time point somewhere between 30 and 60 minutes following the operating room extubation. To perform the screen, a teaspoon is used to place distilled water on each subject's tongue, 3 mL each time 2 consecutive times. Then 3 ounces of water intake. The patient is asked to swallow the water to evaluate the swallowing ability. Aspiration of fluid (choking) subjectively divided into 4 categories: normal, no choking or hoarse voice after swallowing; mild, no choking but slight hoarseness of voice; moderate, no choking but a clearly identifiable hoarseness of voice; severe, choking.	Between 30 and 60 minutes post-extubation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-extubation Oxygen Requirements	Post-extubation Oxygen requirements in subsequent 2 hours	2 hours post-extubation
Reintubation Incidence	Reintubation incidence in the first 24 hours post-extubation	24 hours post-extubation
Oxygen Saturation	Oxygen saturation post-extubation	30 minutes post-extubation
Length of Stay Cardiac Intensive Care Unit	Length of stay in the cardiac intensive care from onset of reversal drugs	0 days after study drug to 100 days after study drug
Occurrence of Postoperative Respiratory Complications	Postoperative respiratory complication including re-intubation	0 hours after study drug to 24 hours after study drug
Occurrence of Postoperative Cardiac Complications	Postoperative cardiac complications including myocardial infarction, arrythmias	from 0 hours after study drug to 2 hours after study drug

Collaborators and Investigators

• Sponsor: West Virginia University

Publications and helpful links

General Publications

• Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Vender JS, Parikh KN, Patel SS, Patel A. Residual Neuromuscular Block in the Elderly: Incidence and Clinical Implications. Anesthesiology. 2015 Dec;123(6):1322-36. doi: 10.1097/ALN.0000000000000865. Erratum In: Anesthesiology. 2016 May;124(5):1201.
• Herbstreit F, Zigrahn D, Ochterbeck C, Peters J, Eikermann M. Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure. Anesthesiology. 2010 Dec;113(6):1280-8. doi: 10.1097/ALN.0b013e3181f70f3d.
• Badhwar V, Esper S, Brooks M, Mulukutla S, Hardison R, Mallios D, Chu D, Wei L, Subramaniam K. Extubating in the operating room after adult cardiac surgery safely improves outcomes and lowers costs. J Thorac Cardiovasc Surg. 2014 Dec;148(6):3101-9.e1. doi: 10.1016/j.jtcvs.2014.07.037. Epub 2014 Jul 31.
• Subramaniam K, DeAndrade DS, Mandell DR, Althouse AD, Manmohan R, Esper SA, Varga JM, Badhwar V. Predictors of operating room extubation in adult cardiac surgery. J Thorac Cardiovasc Surg. 2017 Nov;154(5):1656-1665.e2. doi: 10.1016/j.jtcvs.2017.05.107. Epub 2017 Jun 13.
• Murphy GS, Kopman AF. "To Reverse or Not To Reverse?": The Answer Is Clear! Anesthesiology. 2016 Oct;125(4):611-4. doi: 10.1097/ALN.0000000000001280. No abstract available.
• Boon M, Martini C, Broens S, van Rijnsoever E, van der Zwan T, Aarts L, Dahan A. Improved postoperative oxygenation after antagonism of moderate neuromuscular block with sugammadex versus neostigmine after extubation in 'blinded' conditions. Br J Anaesth. 2016 Sep;117(3):410-1. doi: 10.1093/bja/aew246. No abstract available.
• Pongracz A, Szatmari S, Nemes R, Fulesdi B, Tassonyi E. Reversal of neuromuscular blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation. Anesthesiology. 2013 Jul;119(1):36-42. doi: 10.1097/ALN.0b013e318297ce95.
• Paton F, Paulden M, Chambers D, Heirs M, Duffy S, Hunter JM, Sculpher M, Woolacott N. Sugammadex compared with neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a systematic review and economic evaluation. Br J Anaesth. 2010 Nov;105(5):558-67. doi: 10.1093/bja/aeq269. Epub 2010 Oct 8.
• Park ES, Lim BG, Lee WJ, Lee IO. Sugammadex facilitates early recovery after surgery even in the absence of neuromuscular monitoring in patients undergoing laryngeal microsurgery: a single-center retrospective study. BMC Anesthesiol. 2016 Aug 2;16(1):48. doi: 10.1186/s12871-016-0221-2.
• Chambers D, Paulden M, Paton F, Heirs M, Duffy S, Craig D, Hunter J, Wilson J, Sculpher M, Woolacott N. Sugammadex for the reversal of muscle relaxation in general anaesthesia: a systematic review and economic assessment. Health Technol Assess. 2010 Jul;14(39):1-211. doi: 10.3310/hta14390.
• Chambers D, Paulden M, Paton F, Heirs M, Duffy S, Hunter JM, Sculpher M, Woolacott N. Sugammadex for reversal of neuromuscular block after rapid sequence intubation: a systematic review and economic assessment. Br J Anaesth. 2010 Nov;105(5):568-75. doi: 10.1093/bja/aeq270. Epub 2010 Oct 11.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: February 2, 2019
• First Submitted That Met QC Criteria: May 3, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 23, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Sugammadex; Coronary Artery Bypass Grafting Surgery
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Adjuvants, Anesthesia; Neuromuscular Agents; Cholinesterase Inhibitors; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Parasympathomimetics; Glycopyrrolate; Rocuronium; Neostigmine
• Other Study ID Numbers: 1806161309

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No