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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.
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:
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.
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).
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:
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:
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).
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.
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:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Protocol | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Protocol for Management of Muscle Relaxation With Rocuronium Using Objective Monitoring and Reversal With Neostigmine or Sugammadex | Combination Product | The protocol includes specified appropriate rocuronium dosing and a valid pre-reversal assessment of the adductor pollicis response guides optimal neostigmine vs. sugammadex reversal. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephan R Thilen, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37171989 | Derived | Thilen SR, Sherpa JR, James AM, Cain KC, Treggiari MM, Bhananker SM. Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring. Anesth Analg. 2024 Sep 1;139(3):536-544. doi: 10.1213/ANE.0000000000006511. Epub 2023 May 12. |
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200 subjects were enrolled in the study. However, only 189 subjects started and completed the study cute due to surgeries being cancelled, no Rocuronium given, missing data, or monitor malfunction.
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| ID | Title | Description |
|---|---|---|
| FG000 | Subjects Undergoing Elective Surgery Involving the Intraoperative Use of Rocuronium | Subjects undergoing elective surgery requiring neuromuscular blockade. Subjects all receive the neuromuscular blockade drug Rocuronium based on study protocol. Depending on depth of block (objectively assessed by TOF response), Neostigmine, Sugammadex, or no reversal drug is used to reverse block prior to extubation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Subjects Undergoing Elective Surgery Involving the Intraoperative Use of Rocuronium | Subjects undergoing elective surgery requiring neuromuscular blockade. Subjects all receive the neuromuscular blockade drug Rocuronium based on study protocol. Depending on depth of block (objectively assessed by TOF response), Neostigmine, Sugammadex, or no reversal drug is used to reverse block prior to extubation. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Count of Participants | Participants | Within two minutes of extubation |
|
|
Adverse event data was collected through the study duration which was for less than 1 day (from the beginning of surgery to discharge from the PACU after surgery).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Subjects Undergoing Elective Surgery Involving the Intraoperative Use of Rocuronium | Subjects undergoing elective surgery requiring neuromuscular blockade. Subjects all receive the neuromuscular blockade drug Rocuronium based on study protocol. Depending on depth of block (objectively assessed by TOF response), Neostigmine, Sugammadex, or no reversal drug is used to reverse block prior to extubation. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Research Coordinator | University of Washington | 206-744-4634 | ajames1@uw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 8, 2019 | Feb 24, 2022 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 8, 2019 | Feb 24, 2022 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 8, 2019 | Feb 24, 2022 | ICF_003.pdf |
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| ID | Term |
|---|---|
| D055191 | Delayed Emergence from Anesthesia |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002985 | Clinical Protocols |
| D009388 | Neostigmine |
| D000077122 | Sugammadex |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D016020 | Epidemiologic Study Characteristics |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
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|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Counts |
|---|
| Participants |
|
|
| Secondary | Incidence of Severe Postoperative Residual Neuromuscular Blockade at Time of Extubation | Train-of-four ratio <0.7 as measured by electromyography | Posted | Count of Participants | Participants | Within two minutes of extubation |
|
|
|
| 0 |
| 189 |
| 0 |
| 189 |
| 0 |
| 189 |
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| D017530 | Health Care Quality, Access, and Evaluation |
| D050338 | Phenylammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009861 | Onium Compounds |
| D047408 | gamma-Cyclodextrins |
| D003505 | Cyclodextrins |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D003912 | Dextrins |
| D013213 | Starch |
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |