Best Management of Muscle Relaxation- Objective Monitoring

Best Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex

The purpose of this study is to demonstrate that the investigators can reduce residual paralysis to a very low incidence, and that the investigators can do this while preserving a role for the older and less expensive reversal agent neostigmine. The investigators consider this an evidence-based approach because previous reports clearly indicate that neostigmine is effective for reversal of the most shallow neuromuscular blocks, a level of block now referred to as minimal block. The Investigators also know from previous data that a substantial proportion of patients have minimal block. Sugammadex will be used when the block to be reversed is deeper than minimal, specifically when the objectively measured TOF-ratio is <40%.

The investigators hypothesize that this protocol will be associated with an incidence of residual paralysis of less than 3%. The investigators plan is to study 200 patients.

Study Overview

• Status: Completed
• Conditions: Residual Paralysis, Post Anesthesia
• Intervention / Treatment: Combination product: Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex

Detailed Description

This study implements a standardized protocol for NMBD (neuromuscular blocking drug) management that is currently used by some providers at UWMC and HMC to help prevent residual paralysis in surgical patients. While this protocol is within the scope of routine care that an anesthesiologist could follow in his/her clinical practice, it is not consistently used throughout HMC and UWMC. This protocol follows clinical best practices for NMBD management in a surgical population and adheres to the recommendations from the P&T committee on reversal drug choice and recommendations from the Department of Anesthesiology and Pain Medicine on neostigmine dosing. While this protocol is in line with best practices, the investigators are continuing to systematically evaluate it in the setting of prospective research. All drugs will be administered for clinical care only. This research does not add additional medications. The study will take place at UWMC and HMC and will follow a standardized research protocol for the timing, dosing, and monitoring surrounding muscle relaxants and reversal, and makes use of objective TOF monitors. If a patient agrees to participate in this study, the following research protocol will occur:

Before Surgery:

1. TOF measurements before surgery: A study investigator will perform the routine clinical train-of-four measurements with an objective monitor at baseline after the clinical induction of general anesthesia but before the administration of the NMBD. Information will be recorded for research purposes. Research staff will leave the operating room after obtaining the baseline measurement and will return to the operating room at the end of the surgical procedure, to be available for TOF ratio measurements at the time that reversal of paralysis is planned as well as for the primary outcome measurement, i.e. at time of extubation.

2. Dose calculation of initial NMBD: A study investigator will assist the anesthesia provider with calculation of the recommended intubating dose of rocuronium (an NMBD). The dose will be calculated per this research protocol based on Ideal Body Weight (IBW).

   1. For women 45.5 kg plus 2.3 kg/inch over 5 feet of height
   2. For men 50 kg plus 2.3 kg/inch over 5 feet of height.
   3. For routine intubations, the recommended dose for intubation will be a maximum of Rocuronium 0.6 mg/kg.
   4. The intubating dose will be reduced by 15% for females.
   5. Higher intubating dose may be used at the discretion of the anesthesia provider

During Surgery:

1. Additional dose calculation of NMBD: Each additional dose of rocuronium will be 25% of the recommended intubating dose and will be administered when the TOF count has returned to at least 2, the aim is to maintain an intraoperative TOF count of 1-2 unless the anesthesia provider has deemed deep paralysis to be necessary in which case a TOF count of 0 will be maintained. An attempt will be made to avoid administration of rocuronium during the last 30 minutes of the procedure.

After Surgery:

1. Patients will receive reversal drugs for their routine care that will help reverse the effects of their muscle relaxant. In this study, the decision of reversal drug use will follow institutional guidelines. The timing and dose calculation of the reversal drug will follow the research protocol as follows:
2. Timing of neostigmine or sugammadex: Based on the results of the clinical pre-reversal TOF assessment, reversal with neostigmine will be administered if the objective TOF-ratio is between 40%-90%. If the block is deeper than this, then sugammadex will be used for reversal (This is per institutional guidance on choice of reversal drug).

3. Dose calculation of neostigmine and sugammadex: For this study, the dose of neostigmine will be calculated based on the IBW. The dose of sugammadex will be calculated based on patients' actual body weight.

   For all subjects enrolled in this study, the investigators will follow a dose schedule which is based on clinical TOF monitoring and is in accordance with institutional recommendations for dosing of neostigmine.

4. Timing of extubation: The patient's trachea will not be extubated before routine objective monitoring confirms recovery to a TOF-ratio 90%. However, in the case that objective monitoring cannot be obtained by the provider then the following will happen:

   1. For subjects who receive neostigmine for their routine care, it is recommended that the patient's trachea will not be extubated earlier than 10 minutes after the administration of this drug.
   2. For subjects who receive sugammadex for routine care, it is recommended that the patient's trachea will not be extubated earlier than 3 minutes after drug administration.
5. TOF measurements after surgery (extubation): The TOF-ratio will be measured by a study investigator or provider at the time of extubation. Information will be recorded for research purposes. If the investigators miss obtaining research measurements at the time of extubation, they will obtain TOF measurements on the patient's arrival to the PACU.
6. Collection of data from EMR: the investigators will collect information from the patient's medical record including the intraoperative TOF counts, ASA class, surgical procedure, times of the surgical procedure, time and dose of administered medications, and the patient's temperature in the operating room and PACU.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are 18 years or older
• Undergoing surgery expected to last less than 6 hours at HMC or UWMC
• Have ASA physical status I-III
• Scheduled to have general anesthesia with at least 1 dose of nondepolarizing NMBD for endotracheal intubation or intraoperative neuromuscular block (NMB)

Exclusion Criteria:

• Allergy to NMBDs, neostigmine, or sugammadex
• Patients with neuromuscular disease (myasthenia gravis or muscular dystrophy)
• Pregnant or lactating women
• Non English speaking
• Unable to provide informed consent
• Severe renal failure with eGFR less than 20 ml/min

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Protocol; Patients will have perioperative neuromuscular block managed by protocol. The protocol includes specified appropriate rocuronium dosing and reversal with either neostigmine or sugammadex depending on depth of block as assessed objectively at adductor pollicis with quantitative neuromuscular monitoring.	Combination product: Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex; The protocol includes specified appropriate rocuronium dosing and a valid pre-reversal assessment of the adductor pollicis response guides optimal neostigmine vs. sugammadex reversal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Postoperative Residual Neuromuscular Blockade at Time of Extubation	Train-of-four ratio <0.9 as measured by electromyography or <1.0 measured by acceleromyography	Within two minutes of extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Severe Postoperative Residual Neuromuscular Blockade at Time of Extubation	Train-of-four ratio <0.7 as measured by electromyography	Within two minutes of extubation

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Stephan R Thilen, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: May 17, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 21, 2019

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Paralysis; Delayed Emergence from Anesthesia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Neuromuscular Agents; Cholinesterase Inhibitors; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Parasympathomimetics; Rocuronium; Neostigmine
• Other Study ID Numbers: STUDY00007084

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