Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade at the End of Kidney Transplantation Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Double-blind, Randomized, Parallel Study to Compare the Efficacy of Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade at the End of Kidney Transplantation Surgery in Patients With Severe Kidney Dysfunction

Conditions
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Kidney Transplant; Complications, Postoperative Residual Curarization, Postoperative Residual Weakness

Intervention / Treatment
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* Drug: Sugammadex
* Drug: Neostigmine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex<br>Sugammadex | Drug: Sugammadex<br>* 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<br>|
| Active Comparator: Neostigmine<br>Neostigmine | Drug: Neostigmine<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoventilation in post-anesthesia care unit (PACU) | Presence of one or more episodes of hypoventilation in PACU, adjusted to qTOF and other confounders | Within up to 3 hours after the end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from NMBR administration to adequate NMBR | Intraoperative minutes from NMBR administration to qTOF T4/T1 equal or greater than 0.9 | Within minutes from NMBR administration intraoperatively | 
| Time from NMBR administration to tracheal extubation | Intraoperative minutes from NMBR administration to tracheal extubation | Within minutes from NMBR administration intraoperatively | 
| Duration of surgery | Intraoperative minutes from surgical incision to closure (duration of surgery) | During operating room stay | 
| Duration of anesthesia | Intraoperative minutes from tracheal intubation to tracheal extubation (duration of anesthesia) | During operating room stay | 
| Presence of qTOF <0.9 in PACU | Incidence of qTOF <0.9 in PACU | Within up to 3 hours after the end of surgery | 
| Number of events of hypoventilation in PACU | Number of events of hypoventilation lasting 1 minute or longer in PACU | Within up to 3 hours after the end of surgery | 
| Accumulated minutes of hypoventilation in PACU | Accumulated minutes of hypoventilation in PACU | Within up to 3 hours after the end of surgery | 
| Delayed postoperative hypoventilation | Presence of one or more episodes of hypoventilation in postoperative floor, adjusted to qTOF and other confounders | Within up to 3 postoperative days, counting from PACU discharge | 
| Number of events of delayed postoperative hypoventilation | Number of events of hypoventilation lasting 1 minute or longer in the postoperative floor | Within up to 3 postoperative days, counting from PACU discharge | 
| Accumulated minutes of delayed postoperative hypoventilation | Accumulated minutes of hypoventilation in the postoperative floor | Within up to 3 postoperative days, counting from PACU discharge | 
| qTOF <0.9 in postoperative floor | Delayed detection of qTOF <0.9 in postoperative floor | Within up to 3 postoperative days, counting from PACU discharge | 
| Presence of postoperative pulmonary complications | Presence of predefined postoperative pulmonary complications, including respiratory failure, reintubation, ARDS, pneumonia, pneumothorax, atelectasis, pleural effusion or bronchospasm. | Within up to 3 postoperative days and at 14 +/- 3 days after surgery | 
| Dyspnea functional limitation | Score on standardized Patient-Reported Outcomes Measurement Information System (Promis) dyspnea functional limitation questionnaire score, compared to patient's baseline. Functional measurements include walking, lifting and activities of daily living. The higher the score on this instrument the more functional limitation (scale range is from 0 to 30) | Within up to 14 +/- 3 days after surgery | 
| Kidney graft function as measured by postoperative plasma clearance of creatinine (ClCr) | Predefined kidney graft function based on postoperative ClCr | Within up to 3 postoperative days and at 14 +/- 3 days after surgery | 
| 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. | Within up to 3 postoperative days and at 14 +/- 3 days after surgery | 
| Rate of adverse events | Adverse events related to NMBR medications, including hypersensitivity and any other adverse events | Within up to 3 postoperative days | 
| Hospital resources utilization: total operating room time | Hospital resources utilization parameters, including total operating room time | During operating room stay | 
| Hospital resources utilization: PACU stay duration | Hospital resources utilization parameters, including total PACU stay duration | During PACU stay | 
| Hospital resources utilization: Hospital length of stay | Hospital resources utilization parameters, including total hospital stay duration | Within up to 14 +/- 3 days after surgery | 
| Hospital resources utilization: Rate of ICU admission | Hospital resources utilization parameters, including the need of ICU admission | Within up to 14 +/- 3 days after surgery | 
| Hospital resources utilization: ICU length of stay | Hospital resources utilization parameters, including total ICU stay duration | Within up to 14 +/- 3 days after surgery |