Incomplete Reversal of Neuromuscular Block
Conditions
Brief summary
This study will compare patient recovery measures after reversal of neuromuscular blockade with neostigmine or sugammadex after surgery. Measures include pulmonary function, muscle strength, time to extubation and quality of recovery in the post anesthesia care unit.
Detailed description
Sugammadex has been shown to have a faster onset and more reliable reversal of neuromuscular blockade when compared to neostigmine as measured by return of Train-of-four (TOF) ratio to \>0.9. (Breuckmann, 2015) The investigator's hypothesis is that sugammadex will be associated with improved deep breathing as measured by incentive spirometry in the PACU. The investigators also hypothesize that patients reversed with sugammadex will have shorter times to extubation and better recovery profiles in the PACU as measured by strength, PACU discharge readiness and quality of recovery scores. Residual neuromuscular blockade after surgery can result in airway compromise, pulmonary complications, and possible need for reintubation and can be a negative experience for patients. Reintubation after surgery is currently a quality measure in NSQIP (National Surgery Quality Improvement Program) A TOF ratio of \<0.9 has been identified as a marker of residual neuromuscular blockade in the PACU. (Farhan 2013) Several clinical trials have shown that reversal of neuromuscular blockade with sugammadex results in a faster and more reliable return to TOF ratio of \>0.9 when compared to neostigmine. However most of these studies primarily report on TOF ratios. There are scant data on clinical outcomes after reversal with neostigmine versus sugammadex. Incentive spirometry is a clinically meaningful measurement of postoperative pulmonary function, i.e the ability to breath deeply, which minimizes atelectasis and risk of postoperative pneumonia. The investigators will compare recovery profiles of patients who have received sugammadex or neostigmine for reversal of neuromuscular blockade after surgery. The primary outcome will be incentive spirometry volumes after surgery as a measure of pulmonary function. The secondary measures include hand grip measured using a dynamometer, time to extubation, time to PACU discharge, time to sit independently, and quality of recovery 15 survey scores. This will be a single-center, prospective, randomized, assessor blinded, controlled trial. Patients will be randomized to either receive sugammadex or neostigmine for the reversal of neuromuscular blockade. The anesthesiologist will be unblinded to the study drug however the assessor in the PACU will be blinded.
Interventions
DRUGSugammadex
Sugammadex will be given for reversal of neuromuscular blockade.
DRUGNeostigmine
Neostigmine will be given for reversal of neuromuscular blockade.
Sponsors
Merck Sharp & Dohme LLC
Stony Brook University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be willing and able to provide written informed consent for the study * Participant must be greater than or equal to 18 years of age * Participant must be ASA (American Society of Anesthesiologists) class I, II or III * Planned use of neuromuscular blocking drugs * Planned use of endotracheal intubation * Planned for extubation to occur in the OR
Exclusion criteria
* ASA (American Society of Anesthesiologists) Class IV * Age \< 18 years old * Inability to give oral or written consent * Known or suspected neuromuscular disorder impairing neuromuscular function * True allergy to muscle relaxants * A (family) history of malignant hyperthermia * A contraindication for neostigmine or sugammadex administration * Serum creatinine level of greater than 2.0 mg/dL * Surgery where the patient's arm is not available for neuromuscular monitoring * A plan to extubate under deep anesthesia * Pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incentive Spirometry, Change From Baseline and Recovery Profile - 30 Minutes | 30 Minutes | Incentive spirometry measurements will be done at 30, 60 and 120 minutes after surgery. The change from baseline and recovery profile will be measured. |
| Incentive Spirometry, Change From Baseline and Recovery Profile - 60 Minutes | 60 Minutes after reversal | Incentive spirometry measurements will be done at 30, 60 and 120 minutes after surgery. The change from baseline and recovery profile will be measured. |
| Incentive Spirometry, Change From Baseline and Recovery Profile - 120 Minutes | 120 minutes after reversal | Incentive spirometry measurements will be done at 30, 60 and 120 minutes after surgery. The change from baseline and recovery profile will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Extubation | Immediately after surgery, up to 30 minutes | Measured time between surgery end and time of extubation (removal of breathing tube) |
| Train of Four Ratio > 90% During PACU Admission | At PACU admission, approximately within one hour of reversal of neuromuscular blockade reversal. | Train of four ratio (TOFR) is the ration of the twitch height of the 4th twitch compared to the 1st twitch during train of four neuromuscular stimulation. This measurement was performed using a TOF Watch, which in an accelemyographer. Electric current is applied to the ulnar nevre and the twitches are measured in the thumb. Adequate reversal of neuromuscular blockade is defined as a TOFR \>90%. |
| Grip Strength, Change From Baseline and Recovery Profile 30 Min | 30 minutes | Grip strength will be measured with a hand dynamometer |
| Time to Readiness for Post Anesthesia Care Unit (PACU) Discharge (Aldrete Score >9) | Within 4 hours from the end of surgery | Measured time between PACU admission and meeting PACU discharge readiness. PACU discharge was defined as when the patient had an Aldrete score of 9 or higher as determined by the PACU nurse. The Aldrete score is a measure of post anesthesia recovery. 0 is poor condition and 10 is excellent condition. There are 5 assessment items (able to move voluntary, breathing, consciousness, circulation (BP) and spO2) which are graded on a 0-2 point scale with 0 being poor and 2 being excellent. |
| Quality of Recovery 15 Survey | Postoperative day number one | 15 question survey to assess patient's overall quality of recovery after anesthesia/surgery. Quality of Recovery 15 Survey. Minimum: 0 Maximum: 150 Higher Scores mean a better outcome and better quality of recovery. Part A: How have you been feeling in the last 24 hours? 0 = none of the time (poor), 10 = all of the time (excellent). Examples: able to breath easily, able to enjoy food, feeling rested. etc. Part B: Have you had any of the following in the last 24 hours? 10 to 0, where 10 = none of the time (Excellent) and 0 = all of the time (poor). Examples: moderate pain, nausea or vomiting, feeling worried or anxious, etc. |
| Grip Strength, Change From Baseline and Recovery Profile 60 Min | 60 minutes after reversal | Grip strength will be measured with a hand dynamometer |
| Grip Strength, Change From Baseline and Recovery Profile 120 Min | 120 minutes after surgery | Grip strength will be measured with a hand dynamometer |
Countries
United States
Participant flow
Pre-assignment details
18 patients were excluded after enrollment. The reasons were (1) no longer met inclusion criteria (n =10), declined to participate (n=3), change in surgical date & logistical issues (n=5)
Participants by arm
| Arm | Count |
|---|---|
| Neostigmine Patients in this arm will receive neostigmine for reversal of neuromuscular blockade. Neostigmine is historically the medication that has been used for this purpose.
Neostigmine: Neostigmine will be given for reversal of neuromuscular blockade. | 31 |
| Sugammadex Patients in this arm will receive sugammadex for reversal of neuromuscular blockade. Sugammadex is a newer, FDA approved, medication for this purpose.
Sugammadex: Sugammadex will be given for reversal of neuromuscular blockade. | 31 |
| Total | 62 |
Baseline characteristics
| Characteristic | Sugammadex | Total | Neostigmine |
|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 13.5 | 53.8 years STANDARD_DEVIATION 13.2 | 53.16 years STANDARD_DEVIATION 13.2 |
| Hand Grip Strength | 74.4 psi STANDARD_DEVIATION 27.6 | 75.8 psi STANDARD_DEVIATION 27.5 | 77.11 psi STANDARD_DEVIATION 27.8 |
| Incentive Spirometry Volume | 2650 mL | 2500 mL | 2500 mL |
| Preoperative ability to sit up | 31 Participants | 62 Participants | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 28 Participants | 56 Participants | 28 Participants |
| Sex: Female, Male Female | 17 Participants | 33 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 29 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 2 / 31 | 2 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 |
Outcome results
Primary
Incentive Spirometry, Change From Baseline and Recovery Profile - 120 Minutes
Incentive spirometry measurements will be done at 30, 60 and 120 minutes after surgery. The change from baseline and recovery profile will be measured.
Time frame: 120 minutes after reversal
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Incentive Spirometry, Change From Baseline and Recovery Profile - 120 Minutes | -400 mL |
| Sugammadex | Incentive Spirometry, Change From Baseline and Recovery Profile - 120 Minutes | -850 mL |
Primary
Incentive Spirometry, Change From Baseline and Recovery Profile - 30 Minutes
Incentive spirometry measurements will be done at 30, 60 and 120 minutes after surgery. The change from baseline and recovery profile will be measured.
Time frame: 30 Minutes
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Incentive Spirometry, Change From Baseline and Recovery Profile - 30 Minutes | -700 mL |
| Sugammadex | Incentive Spirometry, Change From Baseline and Recovery Profile - 30 Minutes | -862 mL |
Primary
Incentive Spirometry, Change From Baseline and Recovery Profile - 60 Minutes
Incentive spirometry measurements will be done at 30, 60 and 120 minutes after surgery. The change from baseline and recovery profile will be measured.
Time frame: 60 Minutes after reversal
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Incentive Spirometry, Change From Baseline and Recovery Profile - 60 Minutes | -500 mL |
| Sugammadex | Incentive Spirometry, Change From Baseline and Recovery Profile - 60 Minutes | -1150 mL |
Secondary
Grip Strength, Change From Baseline and Recovery Profile 120 Min
Grip strength will be measured with a hand dynamometer
Time frame: 120 minutes after surgery
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neostigmine | Grip Strength, Change From Baseline and Recovery Profile 120 Min | 7.84 psi | Standard Deviation 21.32 |
| Sugammadex | Grip Strength, Change From Baseline and Recovery Profile 120 Min | 11.85 psi | Standard Deviation 14.53 |
Secondary
Grip Strength, Change From Baseline and Recovery Profile 30 Min
Grip strength will be measured with a hand dynamometer
Time frame: 30 minutes
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neostigmine | Grip Strength, Change From Baseline and Recovery Profile 30 Min | 24.15 PSI | Standard Deviation 20.54 |
| Sugammadex | Grip Strength, Change From Baseline and Recovery Profile 30 Min | 21.38 PSI | Standard Deviation 20 |
Secondary
Grip Strength, Change From Baseline and Recovery Profile 60 Min
Grip strength will be measured with a hand dynamometer
Time frame: 60 minutes after reversal
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to perform this measure at this time point either due to significant sedation or significant pain
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neostigmine | Grip Strength, Change From Baseline and Recovery Profile 60 Min | 12.68 psi | Standard Deviation 22.12 |
| Sugammadex | Grip Strength, Change From Baseline and Recovery Profile 60 Min | 17.69 psi | Standard Deviation 15.76 |
Secondary
Quality of Recovery 15 Survey
15 question survey to assess patient's overall quality of recovery after anesthesia/surgery. Quality of Recovery 15 Survey. Minimum: 0 Maximum: 150 Higher Scores mean a better outcome and better quality of recovery. Part A: How have you been feeling in the last 24 hours? 0 = none of the time (poor), 10 = all of the time (excellent). Examples: able to breath easily, able to enjoy food, feeling rested. etc. Part B: Have you had any of the following in the last 24 hours? 10 to 0, where 10 = none of the time (Excellent) and 0 = all of the time (poor). Examples: moderate pain, nausea or vomiting, feeling worried or anxious, etc.
Time frame: Postoperative day number one
Population: The discrepancy between the number of participants analyzed and participate flow module is because patients were unable to reach these patients on postoperative day number one.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Quality of Recovery 15 Survey | 117 scores on a scale |
| Sugammadex | Quality of Recovery 15 Survey | 105 scores on a scale |
Secondary
Time to Extubation
Measured time between surgery end and time of extubation (removal of breathing tube)
Time frame: Immediately after surgery, up to 30 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Time to Extubation | 8 minutes |
| Sugammadex | Time to Extubation | 7 minutes |
Secondary
Time to Readiness for Post Anesthesia Care Unit (PACU) Discharge (Aldrete Score >9)
Measured time between PACU admission and meeting PACU discharge readiness. PACU discharge was defined as when the patient had an Aldrete score of 9 or higher as determined by the PACU nurse. The Aldrete score is a measure of post anesthesia recovery. 0 is poor condition and 10 is excellent condition. There are 5 assessment items (able to move voluntary, breathing, consciousness, circulation (BP) and spO2) which are graded on a 0-2 point scale with 0 being poor and 2 being excellent.
Time frame: Within 4 hours from the end of surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Time to Readiness for Post Anesthesia Care Unit (PACU) Discharge (Aldrete Score >9) | 109 minutes |
| Sugammadex | Time to Readiness for Post Anesthesia Care Unit (PACU) Discharge (Aldrete Score >9) | 112 minutes |
Secondary
Train of Four Ratio > 90% During PACU Admission
Train of four ratio (TOFR) is the ration of the twitch height of the 4th twitch compared to the 1st twitch during train of four neuromuscular stimulation. This measurement was performed using a TOF Watch, which in an accelemyographer. Electric current is applied to the ulnar nevre and the twitches are measured in the thumb. Adequate reversal of neuromuscular blockade is defined as a TOFR \>90%.
Time frame: At PACU admission, approximately within one hour of reversal of neuromuscular blockade reversal.
Population: The discrepancy between the number of participants analyzed and participate flow module is because we were unable to obtain TOFR data for these patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neostigmine | Train of Four Ratio > 90% During PACU Admission | 25 Participants |
| Sugammadex | Train of Four Ratio > 90% During PACU Admission | 25 Participants |