Trial Information

Regional Anesthesia and Endometrial Cancer Recurrence

This is a Phase III, multi-center study of patients having open hysterectomies for
endometrial cancer. Patients will be randomly assigned to 1) epidural anesthesia/analgesia
with propofol sedation; or 2) general anesthesia combined with postoperative
patient-controlled morphine analgesia. There will be a total (maximum) of 1700 patients
enrolled over a 5 year enrollment.

All patients will be premedicated with 1-3 mg IV midazolam and 1-2 µg/kg fentanyl. Patients
will be randomly assigned to epidural anesthesia & analgesia with propofol sedation or to
sevoflurane general anesthesia and postoperative opioid analgesia after they have met the
inclusion/exclusion criteria and consent to the study.

In patients assigned to general anesthesia and opioid analgesia (General Anesthesia Group),
general anesthesia will be induced with 1-3 µg/kg fentanyl and 2-4 mg/kg propofol. Tracheal
intubation will be facilitated by succinylcholine or a non-depolarizing muscle relaxant;
alternatively, a supraglottic airway (such as a laryngeal mask) will be used. Additional
non-depolarizing muscle relaxant will be administered as deemed necessary by the attending
anesthesiologist.

Anesthesia will be maintained with sevoflurane in 80% oxygen, balance nitrogen, and
fentanyl. Sevoflurane and fentanyl administration will be adjusted to maintain blood
pressure and heart rate within 20% of pre-operative values. The lungs will be mechanically
ventilated to maintain end-tidal PCO2 near 35 mm Hg. When surgery is complete, muscle
relaxant will be antagonized, if necessary, and the trachea extubated. Post-operative
analgesia will be morphine, provided as needed IV or via patient-controlled pump. The
initial pump setting will be for 1 mg boluses with a 6-minute lockout period and no
background infusion. Additional morphine will be provided as necessary to maintain good pain
control, either as needed or by changing the pump settings. Morphine will be the first-line
drug; but hydromorphone will be substituted at one-fifth the morphine dose in patients who
do not tolerate morphine. When pain is adequately controlled without much morphine (usually
on the second postoperative day), patients will be transitioned to acetaminophen and
non-steroidal anti-inflammatory analgesics; oral opioids will also be permitted if
necessary.

In the Epidural Anesthesia and Analgesia group, a T8-10 epidural catheter will be inserted
using a standard technique. After negative aspiration for blood, patients will be given a
test dose of 3 ml of 1.5% lidocaine and 1:200,000 epinephrine. The catheter will be
re-inserted or repositioned as necessary until both aspiration and test dose are negative.
Each patient will be given an additional 12-18 ml bolus of 0.5% bupivacaine or 0.5%
ropivacaine to provide intraoperative analgesia. The catheter will be repositioned or
reinserted as necessary if a sensory block to temperature cannot be confirmed in the
surgical dermatomes. Additional 5-10 ml boluses of the same solution will be given hourly
during surgery to maintain anesthesia; additional boluses will be permitted at the
discretion of the attending anesthesiologist.

Postoperative epidural analgesia will be supplemented with acetaminophen and/or NSAIDs if
needed, or per individual sites' routine protocol. Supplemental morphine will be provided
only if pain relief is inadequate, either "as needed" or by patient-controlled infusion. As
soon as practical, usually on the second postoperative day, patients will be transitioned to
acetaminophen and/or non-steroidal analgesics and, if necessary, oral opioids.