Sugammadex Titration in Cardiac Surgery Patients

Sugammadex Titration for Reversal of Rocuronium or Vecuronium in Cardiac Surgery Patients

Sugammadex is frequently used to reverse the effects of neuromuscular blocking drugs. The recommended doses are 2 mg/kg or 4 mg/kg depending upon the depth of neuromuscular blockade. Clinical studies and experience have suggested that smaller doses may be effective. The purpose of this observational study is to determine the minimal effective dose of sugammadex by administering 50 mg every 5 minutes until the train-of-four ratio is 0.9 in a cohort of cardiac surgery patients, and to determine the duration of action by measuring the train-of-four every hour for up to 6 hours following reversal.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Heart Failure; Valvular Heart Disease; Aorta Disease
• Intervention / Treatment: Drug: Sugammadex administration

Detailed Description

Neuromuscular blocking drugs are used frequently during general anesthesia. The effects of neuromuscular blocking drugs are measured using a twitch monitor, that stimulates the ulnar nerve and measures the evoked response of the adductor pollicis muscle (thumb flexion), or other intrinsic hand muscle. When a series of 4 twitches is administered, the ratio of the first to the fourth twitch (train-of-four ratio) may be used to gauge the degree of muscle relaxation. A train-of-four ratio of 0.9 or greater is considered to represent adequate recovery from neuromuscular blockade. At the end of surgery, antagonists of neuromuscular blockade are commonly administered to reverse any remaining muscle relaxation. Sugammadex is a highly effective reversal agent of the aminosteroid neuromuscular blockings drugs rocuronium and vecuronium, which are the most commonly used neuromuscular blocking drugs. The recommended dose of sugammadex depends upon the degree of neuromuscular blockade. When at least 1 twitch of the train-of-four is present, the recommended dose of sugammadex is 2 mg/kg. When there are no twitches of the train-of-four present, but at least 1 count of the post tetanic count is present, the recommended dose of sugammadex is 4 mg/kg. However, in several dose ranging studies of sugammadex, and in using sugammadex clinically, we and others have determined that smaller doses of sugammadex, often much less than 2 mg/kg, may be effective producing a train-of-four ratio of 0.9 or greater. Sugammadex binds (encapsulates) aminosteroid neuromuscular blocking drugs tightly and the sugammadex-aminosteroid complex is subsequently cleared by the kidney. Therefore we do not expect that recurrence of neuromuscular blockade would occur, even after small doses of sugammadex, as long as the dose of sugammadex is adequate to produce a train-of-four ratio of 0.9. However, additional studies are needed to confirm that recurrence of neuromuscular blockade does not occur after small doses of sugammadex. The purpose of the proposed study is to test the hypothesis that when sugammadex is titrated in 50 mg increments until the train-of-four ratio is 0.9 or greater, that this train-of-four ratio is maintained and there is no recurrence of neuromuscular blockade.

Neuromuscular blockade will be monitored with EMG (electromyography)-based quantitative twitch monitoring (TwitchView). At the end of cardiac surgery, sugammadex will be administered to reverse neuromuscular blockade, as defined by a train-of-four ratio of 0.9 or greater. The patient will then transported asleep, intubated and ventilated to the intensive care unit where the train-of-four ratio of 0.9 or greater will be confirmed on arrival by the respiratory therapist.

Instead of administering a standard dose of sugammadex 2 mg/kg or 4 mg/kg, sugammadex will be titrated in 50 mg increments every 5 minutes until a train-of-four ratio of 0.9 or greater is reached. Train-of-four ratio will be measured on arrival in the intensive care unit and then hourly for 6 hours or until extubation if extubation occurs in <6 hours. If the train-of-four ratio is less than 0.9 at any time, additional sugammadex will be administered until the train-of-four ratio is 0.9 or greater. The twitch monitoring results in the operating room just prior to reversal, following reversal and hourly in the intensive care unit will be recorded, along with sugammadex doses. The total dose of rocuronium or vecuronium and the time period of neuromuscular blocking drug will also be recorded. Data will either be recorded in real time by study assistants or retrieved from the electronic medical record. The patient's age, gender, and weight will be recorded.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• All cardiac surgery patients

Exclusion Criteria:

• Allergic or other adverse response to sugammadex

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardiac surgery patients; Patients undergoing cardiac surgery	Drug: Sugammadex administration; Sugammadex will be given in 50 mg increments every five minutes for reversal of neuromuscular blockade until reaching a train-of-four ratio of 0.9

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Dose of Sugammadex Required to Produce a Train-of-four Ratio of >0.9, Categorized as Greater Than or Less Than the Manufacturers Recommended Dose Based on the Train-of-four or Post Tetanic Response Prior to Administration of Sugammadex	Sugammadex will be administered in 50 mg increments every 5 minutes until a train-of-four ratio of at least 0.9 is reached. The total dose of sugammadex for each patient will be categorized as greater than or less than the manufacturers recommended dose	At the completion of surgery and prior to transport to the intensive care unit. The elapsed time from completion of surgery to arrival in the intensive care unit is 30 min to 1 hour
Duration of Action of Reversal	The train-of-four ratio will be determined upon arrival to the ICU and every hour for 6 hours or until extubation (whichever is less) and categorized as remaining greater than or equal of 0.9, or declining to <0.9 (described as "recurrent" neuromuscular blockade)	On arrival to the intensive care unit and hourly thereafter for 6 hours or until extubation, whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total dose of rocuronium or vecuronium	The total dose of rocuronium or vecuronium administered during the surgical procedure	Intraoperative (From "anesthesia start" until "surgery end" times)
Time period of rocuronium or vecuronium administration	The total interval over which the total dose of rocuronium or vecuronium is administered	Intraoperative (The time period from "anesthesia start" until "surgery end" time)

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: T. Andrew Bowdle, MD, PhD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): November 10, 2022
• Study Completion (Actual): November 10, 2022

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: rocuronium; neuromuscular blockade; monitoring; sugammadex; vecuronium
• Additional Relevant MeSH Terms: Myocardial Ischemia; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Heart Valve Diseases
• Other Study ID Numbers: STUDY00013925

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be shared based on the policy of the journal in which the work is published

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