Does Depth of Neuromuscular Blockade (NMB) Affect Surgical Conditions in Obese Patients Undergoing Robotic Surgery

Study Procedures:

Anesthesia will be induced with propofol (2 mg/kg), fentanyl (1-2 µg/kg) and rocuronium (0.6
mg/kg) to facilitate intubation. A #8 endotracheal tube in males and #7endotracheal tube in
females will be inserted in the trachea and secured at 22 cm. Anesthesia will be maintained
with sevoflurane to maintain the BIS value between 40 and 60. Analgesia will be provided with
fentanyl at 1-2 µg/kg/h or remifentanil 0.5-2 µg/kg/min. Anesthesia will continue until
surgery is completed.

Patients will be randomized to either deep neuromuscular blockade (NMB) or moderate NMB as
described below.

Rocuronium will be administered to keep NMB deep or moderate NMB according to the
randomization.

Deep NMB: Rocuronium will be given as a continuous infusion for deep block. Train of four
(TOF) will be maintained at 0 (zero) with at least one post-tetanic count (PTC). Patients'
paralysis will be continued through the anesthesia period. At the end of surgery, deep Block
patients' will receive 4 mg/kg sugammadex and the patient's trachea will be extubated
according to routine extubation criteria.

Moderate NMB: Rocuronium will be used as bolus doses to achieve a moderate block. TOF will be
maintained between 1 to 3 twitches. PTC will not be counted. Paralysis will be continued
throughout the anesthesia period. At the end of surgery, patients will receive 2 mg/kg
sugammadex in the moderate NMB and the patient's trachea will be extubated according to
routine extubation criteria.

NMB will be assessed by acceleromyography (STIMPOD NMS410 Peripheral Nerve Stimulator, Xavant
Technology (Pty) Ltd. Silverton, Pretoria, South Africa)

The ventilator will be set at pressure-controlled mode and patients will be ventilated with
an airway pressure corresponding to a tidal volume of 8 mL/kg up to a maximum airway pressure
of 35 cmH20. Inspired oxygen will be kept near 50% but will be increased if necessary to
maintain a hemoglobin oxygen saturation ≥95%. PEEP will be set at 5 cmH20. Respiratory rate
will be 12 breaths per minute.

Patients' will have a small finger cuff (finger plethysmography) with a transducer and
continuous real-time cardiovascular monitor (Edwards, Life Science, Irvine, CA) The patient
may also receive an arterial catheter (radial artery) for continuous real-time cardiovascular
monitoring based on the clinicians' preference. Arterial waveform will be recorded
continuously. A pulse oximeter (LNOP Adt, Masimo Corp, Irvine, CA) will be attached to the
index finger of the patient's same hand and connected to a bedside monitor (Radical 7, Masimo
Corp, Irvine, CA); the oximeter will be wrapped to prevent interference from outside light.
Perfusion variability index (PVI) calculates the respiratory variations in the
plethysmography waveform amplitude (Perfusion index [PI]) using the maximum and minimum PI
values over a given time period.

Intraoperative fluid management will be performed with normosol 2 mL/kg/h. Fluid boluses will
be given as guided by stroke volume variation (SVV). Hetastarch will be given as a bolus in
250 mL increments to a maximum of 50 mL/kg. The fluid bolus will be given over 2 minutes. A
bladder (foley) catheter will be inserted after induction of anesthesia. This is part of
conventional care and allows for more accurate fluid volume tracking.

Once the patient is in Trendelenburg position and should a measurement yield that SVV is
staying above 10%, a fluid bolus of 250 mL of hetastarch will be given over 2 minutes and
repeated until the SVV falls below 10%.

During abdominal CO2 insufflation, the intra-abdominal pressure will be kept at 15 cmH2O. The
Trendelenburg position will be 30º, which corresponds to the maximum inclination of the OR
table.

Postoperatively, patients will receive a bilateral transverse abdominal plane (TAP) block
with ropivacaine in the post-operative area. Patients will receive a PCA pump with
hydromorphone for pain management.(This is all standard practice).

Measurements:

A) Measurements that will be recorded once the patient is brought into the operating room and
throughout the intraoperative period include:

1. Hemodynamic data; Systolic, diastolic and mean arterial blood pressure in mmHg, Cardiac
Output and Cardiac Index in liters per minute, Stroke Volume Variation in percent, Pulse
Pressure Variation in percent, Perfusion Index (number from 0.1-10, no units), Perfusion
Variability Index in percent

Time points the data will be recorded include:

1. After patients placement on operative table, while still awake, lying flat for one
minute but prior to induction.

2. Intraoperative, one minute after induction of anesthesia and intubation

3. Intraoperative, one minute after initiation of pneumoperitoneum, with just one trocar
placed

4. Intraoperative, one minute after positioning the patient in Trendelenburg position but
before the surgeon begins

5. Intraoperative, every 15 minutes during the surgical procedure.

6. Intraoperative, when the surgeon states the surgery is completed.

7. Intraoperative, after surgery completed and one minute after reversal of Trendelenburg
position.

8. Intraoperative, while the patient is still on the operative table, one minute after
deflation of the peritoneum.

9. Intraoperative; additional measurements (as referred to above) may be recorded to
capture observed changes that occurred during surgery.

B) Measurements that will be recorded after general anesthesia has been induced and
throughout the intraoperative period include (same time points as above minus time point
one):

2. Assessment of NMB

C) A 5-point surgical rating scale will be used to assess surgical conditions every 15
minutes:

1. The surgeon and the surgical assistant will be asked about surgical conditions every 15
minutes. Surgical conditions will be assessed by the Leiden surgical rating scale (Martini
BJA 2014; 112:498).

1. Extremely poor conditions: The surgeon is unable to work due to coughing or due to the
inability to obtain a visible laparoscopic field because of inadequate muscle
relaxation. Additional muscle relaxants must be given.

2. Poor conditions: There is a visible laparoscopic field but the surgeon is severely
hampered by inadequate muscle relaxation with continuous muscle contractions and/or
movements with the hazard of tissue damage. Additional muscle relaxants must be given.

3. Acceptable conditions: There is a wide visible laparoscopic field but muscle
contractions and/or movements occur regularly causing some interference with the
surgeon's work. There is the need for additional muscle relaxants to prevent
deterioration.

4. Good conditions: There is a wide laparoscopic working field with sporadic muscle
contractions and/or movements. There is no immediate need for additional muscle
relaxants unless there is the fear for deterioration.

5. Optimal conditions: There is a wide visible laparoscopic working field without any
movement or contractions. There is no need for additional muscle relaxants.

2. Intraoperatively; The Intra-abdominal pressures (mmHg) will be recorded every 15 minutes
during the surgery. The amount of flow and the total amount of CO2 (in liters) will be
recorded.

3. Forearm - fingertip temperature gradients will be measured by Mon-a-thermometer
(Mallinckrodt Medical, Inc. St. Louis, MO) and disposable Mon-a-therm thermocouples.
Vasoconstriction will be identified when forearm - fingertip temperature gradient is ≥ 00 Cº
and PI < 1.

D) Additional assessments:

1. Intraoperatively; the surgical assistant will report any episode(s) of abdominal
contractions throughout the surgery.

2. The degree of the patients' Trendelenburg position will be measured intra-operatively
with an angle ruler.

3. The amount of rocuronium received intraoperatively, during the course of surgery, will
be recorded.

Subjects demographic information will be collected at the time of consent. This will include,
age, gender, weight in kilograms, height in centimeters, BMI in kg/m^2, waist-to hip ratio,
surgical procedure and co-morbidities.

E) Post-operative assessments:

1. Pain assessments will be completed using the "visual pain analogue scale" (VAS scale
from 1 to 100 mm, with 1 meaning no pain at all to 100 rated as the worst pain
imaginable). Assessments will be completed by a study team member. Patients will be
asked about their pain level by visual analogue scale at the following time points:

1. Baseline; in pre-operative holding area

2. One hour after admission to PACU, post-operatively

3. Six hours postoperatively

4. Post-operative day one (next morning) between 0600 and 1000

2. Postoperative hydromorphone PCA requirement will be recorded up until the post-operative
DAY ONE (Overall amount of hydromorphone measured in milligrams total). Pain assessment
will be completed between 0600 and 1000 am.

All other pain management (rescue) medications the patient received up to the time of the
"AM" post-operative assessment will be recorded.

Inclusion Criteria:

1. Patients scheduled for elective robotic gynecological or urologic surgery under
general anesthesia.

2. Patients are willing and sign an IRB approved consent

3. Patients will be 18 years or older

Exclusion Criteria:

1. Patients with atrial fibrillation

2. Other significant arrhythmia (Lown grade 3 or greater)

3. Patients with aortic regurgitation

4. Unable to receive or refuses to usehydromorphone for pain management post-operatively
(allergic, bad experience previously with use)