Remote Ischemic Conditioning in Abdominal Surgery

STUDY GOALS AND OBJECTIVES:

1. To obtain preliminary data regarding postoperative complications in subjects undergoing
abdominal surgery and receiving remote limb ischemic or sham conditioning.

2. To test whether remote limb ischemic conditioning (RIC) decreases systemic inflammatory
response in patients undergoing major abdominal surgery.

HYPOTHESiS:

The central hypothesis of the research is that pre- and post-operative RIC in patients
undergoing major abdominal surgery would decrease the systemic inflammatory response to major
abdominal surgery and decrease postoperative complications.

STUDY DESIGN:

A prospective, randomized, double - masked clinical trial of RIC will be conducted in adult
patients undergoing major abdominal surgery at University Hospital in Newark, NJ.
Participants will be randomized into two groups: RIC and No RIC. RIC will be induced at three
time points - the first after anesthesia induction but before commencement of surgery, and
the second and the third on post-operative days 1 and 2, respectively. The RIC intervention
consists of 5 minutes of inflation of a pneumatic tourniquet placed mid-thigh followed by 5
minutes of deflation, repeated for 3 cycles. The pressure used will be 250 mmHg for the
pre-operative intervention. Subsequent tourniquet pressures will be 50 mmHg above the
patient's systolic blood pressure. The No RIC group will receive a sham intervention at all
the same time points. The thigh tourniquet will be inflated to only 20 mmHg. A Doppler probe
will be used to assess pedal arterial flow in both groups. Blood samples will be collected at
baseline, 1hr after skin closure, and 1hr after interventions 2 and 3.

STUDY POPULATION:

Adults (> 18 years of age) of both sexes scheduled for elective major abdominal surgery at
University Hospital will be considered for inclusion. Major abdominal surgery is defined as
peritoneal, retroperitoneal and pelvic surgery expected to last >/= 120 minutes (from
incision to closure) with an expected hospital stay >/= 2 days. A list of surgeries
considered for inclusion is included as Appendix A. Additional operations will be considered
for inclusion if the study team and primary surgical team both agree that the procedure is a
major abdominal surgery and that the duration of surgery is likely to be > 2 hours.

RISKS AND BENEFITS

1. Risks to Subjects During inflation of the tourniquet in awake patients (post-op), there
is a risk of pain secondary to tourniquet inflation. The investigators believe this risk
is small, and if it occurs, the patient will have the option to discontinue the
intervention.

There is a theoretical risk of injury to the limb receiving the RIC stimulus. However,
such occurrences have not been reported to date in other clinical studies.

During collection of blood samples, there is a theoretical risk of bleeding from the
venipuncture site; however this risk is no greater than routine blood draw. The amount
of blood drawn for study purposes will be small (less than 50 mL total anticipated).

2. Benefits to Subjects The anticipated benefit to subjects is fewer complications after
major abdominal surgery. However, no such benefit may accrue. In addition, the study is
expected to provide valuable information regarding how RIC might modulate stress
response to major surgery.

Inclusion Criteria:

1. Adults (> 18 years of age)

2. Both genders

3. Undergoing major abdominal surgery as above

4. Elective surgeries

5. Both outpatients and in-hospital patients

6. Post-op length of stay expected to be at least 2 days by the primary surgical service

Exclusion Criteria:

1. Subjects with lower extremity paralysis

2. Lower extremity amputees

3. Known, documented peripheral arterial disease

4. Body mass index > 45

5. Pregnancy

6. Trauma patients

7. Organ transplant recipients

8. Prior major surgery during current hospitalization (for instance, a patient undergoing
re-laparotomy for a complication from a previous procedure)

9. Patient taking sulfonylureas or nitrates prior to or during admission (listed in
Appendix B)

a. These subjects are excluded because sulfonylureas are shown to abrogate the RIC
effect whereas nitrates are shown to mimic the RIC effect in animal models.

10. Non-elective surgeries (urgent or emergent surgeries)

11. General surgical procedures with no planned intra-abdominal component