Comparison of Pneumoinsufflation Modes and Pressure Settings in Gynecology

This is a randomized-controlled double-blinded trial examining outcomes from total
laparoscopic hysterectomies performed under low and high pressure pneumoperitoneum with
either a novel pressure-barrier insufflator (AirSeal®) or conventional insufflator. All
patients scheduled for total laparoscopic hysterectomy (without robotic-assistance) will be
screened for eligibility in the study. If eligible, a standard informed consent process will
ensue.

All research activities will commence on the day of surgery, in the pre-operative preparation
area. Enrolled subjects will undergo standard registration and pre-operative preparation by
the staff preoperative nurse, including placement of intravenous access line and
administration of standard pre-operative intravenous medications (typically ondansetron,
dexamethasone, and ketorolac). While in the pre-operative area, and prior to any sedative
drug administration by anesthesia, the patient will complete an 11-point Numeric Rating Scale
(NRS) for baseline pain, as well as a baseline 18-question quality of life survey with the
Abdominal Surgery Impact Scale (ASIS). Both study instruments will be self-administered by
the patients and collected by the research team. A baseline blood collection will be
performed in the pre-operative area by the research team assistant and sent for inflammatory
markers.

The subject will be moved to the operating room and the anesthesia team will apply the pads
for use with the Cheetah Non-Invasive Cardiac Output Monitoring (NICOM) system, in addition
to other standard anesthesia monitoring equipment. The Cheetah NICOM will be activated for
baseline measurements prior to anesthesia induction. Induction, intubation, and anesthesia
administration will be performed according to standard practice by a dedicated group of
anesthesia providers. A second set of hemodynamic measurements from the Cheetah NICOM will be
measured after intubation, prior to pneumoperitoneum. A select group of anesthesia providers
familiar with the protocol will administer anesthesia using non-depolarizing muscle relaxants
continuously adjusted to be no less than one twitch during pneumoperitoneum.

Prior to any incision, preoperative prophylactic antibiotics and surgical sterile preparation
will be performed per usual technique. Bilateral upper extremities will be placed in a tucked
position, and no shoulder pads will be used in any case. An 18g peripheral IV (ideally
antecubital) will be placed to allow intra-operative blood draws. This may be placed before
or after anesthesia induction, but prior to arm tucking.

Randomization will occur after the patient is anesthetized, but prior to surgical start time
to allow proper equipment to be opened on the surgical field without waste. Randomization
will be into one of four groups with equal allocation to each (1:1:1:1 ratio):

1. Conventional insufflation at 15mmHg intra-abdominal pressure. (Group 1)

2. Conventional insufflation at 9mmHg intra-abdominal pressure (Group 2)

3. AirSeal® insufflation at 15mmHg intra-abdominal pressure (Group 3)

4. AirSeal® insufflation at 9mmHg intra-abdominal pressure (Group 4) If randomized to an
AirSeal® group, the tri-lumen filtered tube set and dedicated access trocar will be
opened and placed on the surgical field. If randomized to the conventional insufflation
group, conventional insufflation tubing with an additional conventional trocar will be
opened and placed on the surgical field. The patient will remain blinded to
randomization throughout the study, as will the research team assistant responsible for
blood draws and administration of NRS and ASIS questionnaires.

Laparoscopic entry will typically be obtained by optical trocar in the periumbilical region,
but placement may be modified at the surgeon's discretion. Initial pneumoperitoneum will be
established through this trocar to a pressure of 15mmHg for all groups. Pressure will remain
at this setting during Trendelenburg positioning and placement of other necessary
laparoscopic trocars. Data will be recorded for the third time from the Cheetah NICOM at this
point. Once all trocars are inserted, the AirSeal® system will be activated if necessary
based on group randomization, and pressure will be decreased to 9mmHg if indicated based on
randomization. Additional recordings of data from the Cheetah NICOM will occur 10 minutes and
30 minutes after pressure decrease, and the surgery will proceed according to the surgeon's
preferred technique. Any surgeon-directed modifications of intra-abdominal pressure at any
time for surgery completion and/or patient safety will be recorded.

Thirty minutes after pneumoperitoneum is established, the research team assistant will
perform the second blood draw for inflammatory markers. The surgery will be completed per
typical fashion, and total operative time and estimated blood loss will be recorded. A final
Cheetah NICOM recording will be made 5 minutes after deflation of pneumoperitoneum.

The patient will emerge from anesthesia under their usual monitoring and be transferred to
the post-anesthesia care unit (PACU) when meeting appropriate routine criteria. A staff PACU
nurse will care for the subject in the PACU and administer pain medications as necessary
and/or per patient request. All pain medication administration in the hospital will be
recorded in the Epic electronic health record (EHR). The amount of each patient's narcotic
administration will be recorded from the EHR and documented in study files. The staff PACU
nurse will be blinded to subject group allocation.

The research team assistant will administer a NRS pain survey to the patient two hours
post-operatively and inquire regarding presence of shoulder pain. The third blood draw will
also occur at this timepoint by the research team assistant. All patients will undergo
planned same-day discharge to home. If unable to be discharged, they will stay overnight in
the hospital with documented rationale.

On the day after surgery, the subject will be contacted by the research team assistant who
will administer a NRS pain survey by telephone (or in person if still in hospital) and ask
patient to report number of narcotic pain pills used since discharge and dosage of each.
Presence of shoulder pain will again be asked. If patient is still in the hospital, narcotic
usage will be collected from the EHR.

Per standard routine, the patients will be asked to return to clinic two weeks
post-operatively for evaluation and examination. The 18-question ASIS will be administered at
this visit by the blinded research team assistant. If the patient cannot complete the
"two-week visit" within 1-3 weeks after surgery, the research team assistant will administer
the ASIS by telephone. The patient will exit the study after this visit. Blinding of the
patient will be broken after administration of the ASIS, as it is standard practice to
provide the patient with a copy of the operative report during this visit, which will
describe the pneumoperitoneum settings used during their case.

Inclusion Criteria:

- Subjects must meet the following inclusion criteria to be eligible for the study.

1. Understand and voluntarily sign an informed consent form.

2. Female gender ages 18-65

3. Scheduled for total laparoscopic hysterectomy for benign indications with or
without oophorectomy (standard of care involves bilateral salpingectomy).

Exclusion Criteria:

- Meeting any of the following exclusion criteria will make the subject ineligible for
the study.

1. Anticipated removal of uterus through any route except vagina (transvaginal
morcellation is acceptable)

2. Planned concomitant procedures including but not limited to resection of deep
endometriosis, plastic surgery procedures, or bowel resection.

3. Daily narcotic pain medication use for greater than 30 days leading into surgery

4. Use of da Vinci® robot surgical assistance