Neuromuscular Blockade, Renal Impairment
Conditions
Brief summary
This study is intended to be a single-site, prospective, randomized, double-blinded study that intends to enroll a total of 60 patients with severe renal impairment undergoing surgery with general endotracheal anesthesia at Parkland Hospital. Patients will be randomized to receive either neostigmine (for reversal of cisatracurium) or sugammadex (for reversal of rocuronium). A standardized anesthetic protocol that is usual and customary for the type of operation the patient is having will be provided to the anesthesia teams of enrolled subjects. The remainder of the anesthetic care of the subject will not deviate from the standard of care. All patients will be monitored with continuous pulse oximetry postoperatively for 24 hours.
Detailed description
This will be a prospective, randomized, double-blinded study of surgical patients with severe renal impairment that seeks to address the following: Specific Aim: To determine whether rocuronium-induced moderate neuromuscular blockade and reversal with sugammadex achieves recovery of neuromuscular function (TOF ≥ 0.9) faster than reversal of cisatracurium-induced moderate neuromuscular blockade and reversal with neostigmine in patients with severe renal impairment. Primary Hypothesis: Patients with severe renal impairment who are reversed with sugammadex after rocuronium will achieve a TOF ≥0.9 within a time frame that is one-third of the time it takes for reversal with neostigmine after cisatracurium.
Interventions
DRUGCisatracurium + Neostigmine
Maintenance neuromuscular blockade with boluses of cisatracurium to keep train-of-four (TOF) 1-2 twitches. For reversal, neostigmine with glycopyrrolate
Maintenance neuromuscular blockade with boluses of rocuronium to keep TOF 1-2 twitches. For reversal, sugammadex
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double blinded
Intervention model description
single site, randomized, controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-80 years old * Severe renal impairment (CrCl \< 30 mL/min) * Undergoing non-emergent surgery that requires neuromuscular blockade * Planned extubation in the operating room immediately after surgery * American Society of Anesthesiologists (ASA) physical status classification 3 to 4 * Willing and able to consent in English or Spanish * No personal history of neuromuscular disease
Exclusion criteria
* Age less than 18 or older than 80 * Patient does not speak English or Spanish * Planned postoperative intubation/ventilation * Allergy to sugammadex, neostigmine, glycopyrrolate, cisatracurium, or rocuronium * Family or personal history of malignant hyperthermia * Patient refusal * Pregnant or nursing women * Stat (emergent) cases * Pre-existing muscle weakness of any etiology * Patients on toremifene (a selective estrogen receptor modulator) * Women on oral contraceptives who do not wish to use a non-hormonal method of contraception for 7 days following surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Until Complete Reversal of Neuromuscular Blockade | In the operating room, the amount of time after administration of the reversal syringe to reach recovery of neuromuscular function (TOFR ≥ 90%) assessed up to 30 minutes. | Measure how long it takes to return from a TOF of 2 to a TOF ≥ 0.9. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cisatracurium + Neostigmine Patients in the cisatracurium/neostigmine group will receive 0.2 mg/kg of cisatracurium for neuromuscular paralysis during induction. Additional cisatracurium will be given to keep the patient at a neuromuscular depth of 1 twitch throughout the surgery until the last 30 minutes, during which the patient will be kept at 2 twitches.
Cisatracurium + Neostigmine: Maintenance neuromuscular blockade with boluses of cisatracurium to keep train-of-four (TOF) 1-2 twitches. For reversal, neostigmine with glycopyrrolate | 23 |
| Rocuronium + Sugammadex Patients in the rocuronium/sugammadex group will receive 0.6 mg/kg of rocuronium for neuromuscular paralysis during induction. Additional rocuronium will be given to keep the patient at a neuromuscular depth of 1 twitch throughout the surgery until the last 30 minutes, during which the patient will be kept at 2 twitches.
Rocuronium + Sugammadex: Maintenance neuromuscular blockade with boluses of rocuronium to keep TOF 1-2 twitches. For reversal, sugammadex | 26 |
| Total | 49 |
Baseline characteristics
| Characteristic | Cisatracurium + Neostigmine | Rocuronium + Sugammadex | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 26 Participants | 49 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 | 10 Participants | 11 Participants | 21 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 | 12 Participants | 12 Participants | 24 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 23 participants | 26 participants | 49 participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 22 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 26 |
| other Total, other adverse events | 0 / 23 | 0 / 26 |
| serious Total, serious adverse events | 0 / 23 | 0 / 26 |
Outcome results
Primary
Time Until Complete Reversal of Neuromuscular Blockade
Measure how long it takes to return from a TOF of 2 to a TOF ≥ 0.9.
Time frame: In the operating room, the amount of time after administration of the reversal syringe to reach recovery of neuromuscular function (TOFR ≥ 90%) assessed up to 30 minutes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cisatracurium + Neostigmine | Time Until Complete Reversal of Neuromuscular Blockade | 14.8 Minutes | Standard Deviation 6.1 |
| Rocuronium + Sugammadex | Time Until Complete Reversal of Neuromuscular Blockade | 3.5 Minutes | Standard Deviation 1.6 |