Kidney Transplant; Complications, Postoperative Residual Curarization, Postoperative Residual Weakness
Conditions
Brief summary
The purpose of this study is to compare two medications that reverse muscle paralysis at the end of kidney transplant surgery with the goal of reducing residual muscle weakness and insufficient respiratory function after surgery.
Detailed description
This is a prospective randomized double-blind single center study on patients with severe kidney failure undergoing kidney transplantation surgery. Patients will have their muscles paralyzed during general anesthesia for surgery. At the end of surgery, muscle paralysis will be reversed with either neostigmine (control group) or sugammadex (intervention group). Residual muscle weakness and respiratory function will be monitored after surgery with a quantitative train-of-four (qTOF) monitor and a noninvasive continuous ventilation monitor. The investigators hypothesize that patients receiving sugammadex will have less residual muscle weakness and better respiratory function than patients receiving neostigmine. Respiratory and kidney function parameters and any adverse events will be collected during the hospital stay. Patients will contacted for a study follow up around 2 weeks after their surgery.
Interventions
DRUGSugammadex
Administration of Sugammadex intravenously at a dose appropriate for the reversal of neuromuscular blockade (usually 2-4 mg/kg) at the end of the surgery before tracheal extubation
DRUGNeostigmine
Administration of Neostigmine intravenously at a dose appropriate for the reversal of neuromuscular blockade (usually 0.03-0.07 mg/kg) at the end of the surgery before tracheal extubation
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* At least 18 years or older * Diagnosed with severe kidney dysfunction (defined by plasma creatinine clearance \<30 mL/min) * Planning on kidney transplantation surgery at the University of Colorado Hospital.
Exclusion criteria
* Patients unable to sign the informed consent * Pregnant women * Body Mass Index (BMI) \> 40 kg/m2 * Pre-existing oxygen or ventilatory dependency (24h use of oxygen or other noninvasive or invasive ventilatory support) * Patients with any pulmonary, neuromuscular or other disease that severely limits their respiratory functional status (e.g. unable to achieve 4 Metabolic Equivalent of Tasks, METs, such as climbing up 1 flight of stairs) * Presence of any contraindication for any of the study-related medications or interventions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Hypoventilation in Post-anesthesia Care Unit (PACU) | Within up to 3 hours after the end of surgery | Presence of one or more episodes of hypoventilation in PACU, adjusted to qTOF and other confounders |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Presence of qTOF <0.9 in PACU | Within up to 3 hours after the end of surgery | Incidence of qTOF \<0.9 in PACU |
| Number of Participants With Kidney Graft Dysfunction | Within up to 3 postoperative days and at 14 +/- 3 days after surgery | Predefined kidney graft negative outcomes including: postoperative increasing ClCr, reduced daily urine output, need for dialysis postoperatively, and/or diagnosis of delayed graft function or kidney graft rejection. |
| Rate of Adverse Events Related to NMBR Medications | Within up to 3 postoperative days | Adverse events related to NMBR medications, including hypersensitivity and any other adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex Sugammadex
Sugammadex: Administration of Sugammadex intravenously at a dose appropriate for the reversal of neuromuscular blockade (usually 2-4 mg/kg) at the end of the surgery before tracheal extubation | 42 |
| Neostigmine Neostigmine
Neostigmine: Administration of Neostigmine intravenously at a dose appropriate for the reversal of neuromuscular blockade (usually 0.03-0.07 mg/kg) at the end of the surgery before tracheal extubation | 42 |
| Total | 84 |
Baseline characteristics
| Characteristic | Sugammadex | Neostigmine | Total |
|---|---|---|---|
| Age, Continuous | 48 years | 53 years | 50 years |
| Preoperative hemodialysis | 19 Participants | 19 Participants | 38 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino | 9 Participants | 7 Participants | 16 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other | 3 Participants | 9 Participants | 12 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 30 Participants | 26 Participants | 56 Participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 32 Participants |
| Sex: Female, Male Male | 31 Participants | 21 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 42 |
| other Total, other adverse events | 2 / 42 | 1 / 42 |
| serious Total, serious adverse events | 4 / 42 | 4 / 42 |
Outcome results
Primary
Number of Patients With Hypoventilation in Post-anesthesia Care Unit (PACU)
Presence of one or more episodes of hypoventilation in PACU, adjusted to qTOF and other confounders
Time frame: Within up to 3 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sugammadex | Number of Patients With Hypoventilation in Post-anesthesia Care Unit (PACU) | 22 Participants |
| Neostigmine | Number of Patients With Hypoventilation in Post-anesthesia Care Unit (PACU) | 23 Participants |
Secondary
Number of Participants With Kidney Graft Dysfunction
Predefined kidney graft negative outcomes including: postoperative increasing ClCr, reduced daily urine output, need for dialysis postoperatively, and/or diagnosis of delayed graft function or kidney graft rejection.
Time frame: Within up to 3 postoperative days and at 14 +/- 3 days after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sugammadex | Number of Participants With Kidney Graft Dysfunction | 2 Participants |
| Neostigmine | Number of Participants With Kidney Graft Dysfunction | 4 Participants |
Secondary
Number of Patients With Presence of qTOF <0.9 in PACU
Incidence of qTOF \<0.9 in PACU
Time frame: Within up to 3 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sugammadex | Number of Patients With Presence of qTOF <0.9 in PACU | 13 Participants |
| Neostigmine | Number of Patients With Presence of qTOF <0.9 in PACU | 25 Participants |
Secondary
Rate of Adverse Events Related to NMBR Medications
Adverse events related to NMBR medications, including hypersensitivity and any other adverse events
Time frame: Within up to 3 postoperative days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sugammadex | Rate of Adverse Events Related to NMBR Medications | 0 Participants |
| Neostigmine | Rate of Adverse Events Related to NMBR Medications | 0 Participants |