Regional Anesthesia and Endometrial Cancer Recurrence
Summary
The purpose of this study is to determine whether recurrence of local and metastatic cancer after open hysterectomy for stage 1 or 2 endometrial cancer is reduced when patients receive epidural anesthesia/analgesia combined with propofol sedation rather than sevoflurane anesthesia and opioid analgesia.
Description
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.
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Conditions
Cancer
Intervention
propofol general anesthesia, Sevoflurane
Location
Cleveland Clinic
Cleveland
Ohio
United States
44129
Status
Terminated
Source
Outcomes Research Consortium
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00531349
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Delayed Emergence From Anesthesia
Abnormally slow pace of regaining CONSCIOUSNESS after general anesthesia (ANESTHESIA, GENERAL) usually given during surgical procedures. This condition is characterized by persistent somnolence.
Propofol
An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.
Anesthesia Recovery Period
The period of emergence from general anesthesia, where different elements of consciousness return at different rates.
Thiamylal
A barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. (From Martindale, The Extra Pharmacopoeia, 30th ed, p919)
Anesthetics, General
Agents that induce various degrees of analgesia; depression of consciousness, circulation, and respiration; relaxation of skeletal muscle; reduction of reflex activity; and amnesia. There are two types of general anesthetics, inhalation and intravenous. With either type, the arterial concentration of drug required to induce anesthesia varies with the condition of the patient, the desired depth of anesthesia, and the concomitant use of other drugs. (From AMA Drug Evaluations Annual, 1994, p.173)
Clinical Trials
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Evaluation of Different Anesthesia for Uterine Curettage
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PubMed Articles
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Sevoflurane to alleviate pain on propofol injection.
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Effects of sevoflurane and propofol on cultured bone-marrow mesenchymal stem cells of rats.
Objective: Bone marrow mesenchymal stem cell (BMSC) is a potentially effective vehicle for the cell and gene therapy in clinical disease treatment. We studied whether the most commonly used anesthetic...
Summary Background: Emergence delirium (ED) is a frequent postoperative complication in young children undergoing ENT procedures and it may be exacerbated by sevoflurane anesthesia whereas propofol ma...
Sevoflurane, one of the most commonly used inhalation anesthetics, induces apoptosis and oxidative stress in lymphocytes. Propofol, an intravenous anesthetic, exhibits antiapoptotic and antioxidative...
