The Effect of Sugammadex Versus Neostigmine During Neuromuscular Blockade Reversal

This is a single-center, randomized, double arm prospective clinical trial involving adult
patients undergoing outpatient surgeries at The OSUWMC. Institutional review board (Office of
Responsible Research practices) approval is mandatory preceding the start of the clinical
trial. Written informed consent will be obtained from all eligible patients participating in
this trial, and signed prior to the initiation of any study-related procedures. The study
will be conducted in accordance with the principles of Good Clinical Practice and will be
approved by the appropriate institutional review boards at OSUWMC. An individual with
appropriate human subjects protection and HIPAA education will undertake the consent process
in the surgeon's office or other appropriate location (e.g. preoperative clinics).
Researchers will utilize the electronic medical record (EMR) to screen and identify surgical
cases based on study inclusion criteria. These cases will be reviewed together with the
surgical team to determine whether all inclusion and exclusion criteria are met, prior to
approaching the patient. Prior surgery, a study-team investigator will approach the patient
to discuss the nature of the study, its requirements, and potential risks. Written informed
consent will be obtained from every subject prior to the start any study related procedures
and enough time will be allowed for the subject to ask questions and receive answers. The
inclusion and exclusion criteria will be reviewed in order to ascertain whether a patient
qualifies for this study. Subjects must meet all the inclusion criteria and none of the
exclusion criteria to qualify for the study.

- All medication taken 7 days prior surgery will be recorded. Demographic information,
previous medical history, vital signs, urine pregnancy test, and a physical examination
will be performed at this time as a standard of care and results will be recorded.

- Study medication dosages will be calculated prior to surgery by using total body weight
(TBW) by the research team, following standard operational procedures.

II.4.B. Intraoperative phase

- Pre-induction: intravenous midazolam (2 - 4 mg) if required.

- Induction of general anesthesia: anesthesia will follow the standard of care protocols
set by our center. Therefore, preoxygenation will be achieved with 100% oxygenation for
at least 5 full Tidal Volume and suggested dosage of anesthetic drugs will be as
follows: propofol 1-2 mg/kg, lidocaine IV 40-100 mg, fentanyl IV 1-2 μg/Kg, and
sevoflurane 0.5-1 MAC (if needed). Additionally, rocuronium (0.3-0.7 mg/kg) will be used
for neuromuscular blockade in all patients.

- Maintenance of general anesthesia: balanced anesthesia will be administered for
maintenance at the anesthesiologists' discretion. We suggest the following regimen:
sevoflurane (0.5-1 MAC), remifentanil IV 0.05-0.25 μg/kg/min, and propofol IV 20-75
μg/kg/min. In accordance with guidelines for Good Clinical Practices in pharmacodynamic
studies of NMBA, neuromuscular monitoring will be assessed via the train-of-four (TOF)
stimulation. TOF device will be placed on the ulnar nerve to illicit twitches in the
adductor pollicis. The response to TOF stimulation will be assessed by the
anesthesiologist every 30 minutes, starting at intubation. If second response reappears
in the TOF stimulation, supplemental doses of rocuronium will be administered at
anesthesiologists' discretion.

- Neuromuscular blockade reversal: after peritoneal (port sites) closure, TOF will be
assessed. Exact doses of the study medications (previously determined by total body
weight) will be administered as following:

- Sugammadex:

- If spontaneous recovery has reached second twitch after TOF: 2 mg/kg

- If spontaneous recovery has reached between 1-2 post-tetanic counts but no
twitch responses to TOF: 4 mg/kg

- When there is a clinical need to reverse NMB within 3 min of a single dose of
rocuronium (1.2 mg/kg): 16 mg/kg

- Neostigmine: 50 µg. Kg-1 will be administered after spontaneous recovery has
reached fourth twitch after TOF in accordance with our institutional standard
procedures and published literature [10, 11]

- After IP administration, TOF will be assessed every 30 seconds during the first 3
minutes and every minute afterwards to TOF value ≥ 0.9

- The following variables will be collected:

- Time from peritoneal closure (port sites) to anesthesia readiness for OR discharge
to PACU

- Time from IP administration to extubation

- Time from IP administration to TOF ≥ 0.9

- Time from IP administration to anesthesia readiness for OR discharge to PACU
II.4.C. Postoperative phase (Postoperative Care Unit)

- The modified Aldrete score will be documented in the EMR.

- Time to discharge-readiness from the OR to PACU, admission time to PACU, and time to
discharge from the hospital will be recorded.

- Perioperative incidence of IP related adverse events (i.e. bradycardia, anaphylaxis,
nausea and vomiting, and hypotension) Summary statistics will be calculated and reported
as means (standard deviations) or medians [inter-quartile ranges] for continuous
variables and as frequencies (percentages) for categorical variables. Study groups will
be compared using Student's t-tests or Wilcoxon Rank-Sum tests for continuous variables
and chi-squared or Fisher's exact tests for categorical variables where appropriate.
Primary hypotheses comparing time from peritoneal closure (port sites) to anesthesia
readiness for OR discharge to PACU between study groups will be tested using Student's
unpaired t-tests (on the natural log transformed outcomes if necessary) at the 5% type I
error rate. All analyses will be conducted using SAS version 9.4 (SAS Institute, Cary,
N.C.) The study will last approximately one year including recruitment, analysis of the
data and writing of the manuscript.

Inclusion Criteria:

1. Subjects undergoing outpatient surgeries (laparoscopic cholecystectomy, laparoscopic
hernia repair, laparoscopic appendectomy) under general anesthesia requiring
rocuronium-induced neuromuscular blockade

2. Male or female patient 18 years and older

3. Able to consent

4. American Society of Anesthesiologist (ASA) physical status of I, II, or III

Exclusion Criteria:

1. Participating in another interventional study drug within 30 days prior to their
recruitment

2. Special population (Pregnant, Inmate, Breastfeeding)

3. History of allergy to sugammadex or rocuronium

4. Any medication known to interfere with NMBA or sugammadex

5. Presence of any clinical condition as determined by the investigator that exclude the
patient from the trial such as COPD, CKD, and neuromuscular or neurodegenerative
diseases