Neuromuscular Blockade
Conditions
Brief summary
The investigators propose a randomized trial comparing sugammadex and neostigmine for the reversal of neuromuscular blocks induced by rocuronium or vecuronium in adults having general anesthesia with muscular block for noncardiac surgery.
Detailed description
All patients will be asked to void before they are transferred to the operating room. Patients will be seen shortly before anesthetic induction (baseline, Visit 1). As this is a pragmatic trial, no restrictions to anesthetic management other than the random allocation to sugammadex or neostigmine are planned. As part of local standards, it is recommended to maintain a moderate block of 1 to 2 twitch responses to train-of-four (TOF) stimulation throughout surgery. Randomized treatments will be implemented by clinicians in collaboration with research personnel. Patients will be randomized shortly before the reversal of the neuromuscular block. At the time of randomization, the administration of either neostigmine or sugammadex need to be possible. If e.g. the neuromuscular block is too deep to be reversed with neostigmine, patients will not be randomized and excluded from the study. The anesthesiologist in charge will be informed on the patient's allocation to either the sugammadex or neostigmine group by an unblinded investigator. Patients will be monitored for twitch responses towards the end of surgery to determine the timing and dose for the reversal agent. The twitch response will be measured using a quantitative, acceleromyographic monitoring device. For sugammadex, 4 mg/kg is recommended if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to (TOF) stimulation. Alternatively, 2 mg/kg is recommended if spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation. In the neostigmine group, neostigmine 2.5 mg with glycopyrrolate 0.5 mg will be administered as an initial dose. Neostigmine and glycopyrrolate are to be administered in a fixed ratio, and only if the second twitch in response to TOF stimulation has appeared. The initial dose can be repeated up to a ceiling dose of 5 mg neostigmine with 1 mg of glycopyrrolate. However, the final decision of the dose will be up to the attending anesthesiologist. The administered dose will be recorded. All patients are required to have a documented TOF ratio \> 0.9 before extubation Visit 2 is one hour after surgery in the post anesthesia care unit (PACU). The third Visit is within 4 to 6 hours after surgery on the regular ward. Visit 4 and 5 will be in the morning and afternoon of the first day after surgery (postoperative day (POD) 1). Visit 5 on the afternoon of POD 1 will be the last follow-up and the end of a patient's participation in the study. Thereafter, data will be recorded from electronical medical records until POD 4 or discharge, whichever comes first.
Interventions
Administration by intravenous infusion
Administration by intravenous infusion
Sponsors
Study design
Eligibility
Inclusion criteria
* Informed Consent as documented by signature; * Adults having noncardiac surgery with expected surgery duration ≥ 2 hours; * General anesthesia requiring endotracheal intubation and neuromuscular block with rocuronium or vecuronium; * Planned administration of sugammadex or neostigmine for reversal of the neuromuscular block at the end of surgery; * American Society of Anesthesiologists (ASA) physical status 1-3; * Age ≥ 65 years.
Exclusion criteria
* Contraindications to the class of drugs under study; * Preoperative urinary catheter; * Planned intraoperative insertion of a urinary catheter; * Neurosurgery (except spine surgery), intraabdominal or retroperitoneal surgeries including but not limited to any kind of laparoscopies, or surgeries in kidneys, ureters or urine bladder. * Planned postoperative admission to the ICU; * Severe preoperative hepatic impairment (≥3 times increase in aspartate aminotransferase or alanine aminotransferase as per reference range) or renal impairment (estimated GFR \< 30 ml/min or end-stage renal disease requiring scheduled dialysis.); * History of bladder cancer; * Presence of a sacral nerve stimulator; * Current use of anticholinergic medications such as antihistamines, phenothiazines, antidepressants or antipsychotics; * Urinary tract infections or other urogenital comorbidity (incontinence, cysto-ureteric reflux, known bladder retention) or conditions which promote urinary retention; * Known or suspected neurological conditions such as Alzheimer's disease, stroke, poliomyelitis, cerebral palsy, multiple sclerosis, spinal lesions, or Parkinson's disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine Residual in PACU | 1 hour after surgery, which started from out of operation room | The primary outcome of urinary retention is assessed by post-void bladder volume. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Needed a Urinary Catheter | within 24 hours after out of operation room | participants who needed a urinary catheter within 24 hours after surgery |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participants Having Urinary Tract Infections | during postoperative hospital stay, which from out of operation room to discharge from the hospital, an average of 1 week | patients having urinary tract infections during the hospitalization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neostigmine Reversal of Neuromuscular Block by Neostigmine.
Neostigmine with glycopyrrolate: Administration by intravenous infusion | 23 |
| Sugammadex Reversal of Neuromuscular Block by Sugammadex.
Sugammadex: Administration by intravenous infusion | 27 |
| Total | 50 |
Baseline characteristics
| Characteristic | Neostigmine | Total | Sugammadex |
|---|---|---|---|
| Age, Continuous | 72.1 years STANDARD_DEVIATION 4.7 | 72.1 years STANDARD_DEVIATION 5 | 72.1 years STANDARD_DEVIATION 7 |
| ASA score 1 | 1 Participants | 2 Participants | 1 Participants |
| ASA score 2 | 3 Participants | 5 Participants | 2 Participants |
| ASA score 3 | 18 Participants | 42 Participants | 24 Participants |
| ASA score unknown | 1 Participants | 1 Participants | 0 Participants |
| BMI | 26.1 kg/m2 | 27 kg/m2 | 28.6 kg/m2 |
| cardiac disease | 16 Participants | 31 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 46 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| kidney disease | 2 Participants | 5 Participants | 3 Participants |
| Metabolic equivalent 2.0 | 1 Participants | 1 Participants | 0 Participants |
| Metabolic equivalent 3.0 | 1 Participants | 2 Participants | 1 Participants |
| Metabolic equivalent 3.5 | 1 Participants | 2 Participants | 1 Participants |
| Metabolic equivalent >4 | 10 Participants | 24 Participants | 14 Participants |
| Metabolic equivalent 4.0 | 10 Participants | 21 Participants | 11 Participants |
| neurological disease | 10 Participants | 19 Participants | 9 Participants |
| previous surgery | 22 Participants | 47 Participants | 25 Participants |
| pulmonary disease | 6 Participants | 16 Participants | 10 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 | 1 Participants | 2 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 48 Participants | 26 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 13 Participants | 31 Participants | 18 Participants |
| Substance abuse -alcohol abuse | 0 Participants | 2 Participants | 2 Participants |
| Substance abuse-illegal drug use | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 27 |
| other Total, other adverse events | 0 / 23 | 0 / 27 |
| serious Total, serious adverse events | 0 / 23 | 0 / 27 |
Outcome results
Urine Residual in PACU
The primary outcome of urinary retention is assessed by post-void bladder volume.
Time frame: 1 hour after surgery, which started from out of operation room
Population: A total of 50 patients were included in data analysis based on the modified intent-to-treat rule
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neostigmine | Urine Residual in PACU | 219 ml |
| Sugammadex | Urine Residual in PACU | 222 ml |
Number of Participants Who Needed a Urinary Catheter
participants who needed a urinary catheter within 24 hours after surgery
Time frame: within 24 hours after out of operation room
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neostigmine | Number of Participants Who Needed a Urinary Catheter | 5 Participants |
| Sugammadex | Number of Participants Who Needed a Urinary Catheter | 2 Participants |
Participants Having Urinary Tract Infections
patients having urinary tract infections during the hospitalization
Time frame: during postoperative hospital stay, which from out of operation room to discharge from the hospital, an average of 1 week
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neostigmine | Participants Having Urinary Tract Infections | 0 Participants |
| Sugammadex | Participants Having Urinary Tract Infections | 0 Participants |