MOrphine-bupivacaine intermittent bolus versus Ropivacaine-Fentanyl INfusion through epidural route after gastrointestinal oncosurgery: a randomized clinical trial

Adequate dynamic pain control is a keystone of an enhanced recovery after surgery (ERAS) pathway. Evidence indicates that pain management in the postoperative period can affect the outcome of the surgery reducing cardiac, pulmonary and metabolic complications. The analgesic efficacy of thoracic epidural analgesia (TEA) for open colorectal surgeries has been shown to be superior to intravenous opioids. TEA also improves the postoperative pulmonary function due to reduced sedation and improved analgesia.Gastrointestinal function was reported in several studies to return 48 to 72 hours earlier in patients receiving thoracic epidural analgesiacompared topatients receiving intravenous analgesics.Ropivacaine has less toxicity on the cardiovascular and central nervous system. However, continuous infusion of epidural ropivacainemay cause motor block and hypotension, increasing the fluid requirement which may lead to fluid imbalance, anastomotic leakage, bowel edema etc. An alternative strategy is the use of intermittent bolus of epidural Morphine, which is a potent opioid analgesic that provides effective and long-lasting postoperative analgesia. Bupivacaine as an additive to morphine has been shown to reduce the incidence of postoperative nausea, vomiting and quality of analgesia. Moreover, requirement of morphine is much less when it is given through epidural route than intravenous route. More importantly, a chance of hypotension is much less when intermittent epidural bolus of morphine with low concentration bupivacaine is used as postoperative analgesic. No previous study has been conducted comparing the efficacy of intermittent bolus of epidural bupivacaine-morphine versus epidural infusion of ropivacaine- fentanyl.Therefore this study was designed to compare the analgesic efficacy and side effects of Buipvacaine-Morphine intermittent bolus versus Ropivacaine- Fentanyl infusion through epidural route after gastrointestinal (GI)oncosurgery. Our hypothesis is epidural bupivacaine morphine intermittent bolus will provide equivalent analgesia like epidural ropivacaine fentanyl infusion.Patients will be randomized either in the epidural bupivacaine-morphine group (group MOR) or epidural ropivacaine-fentanyl group (Group ROP). Epidural catheter will be placed as per incision congruent technique before induction in all patients. Placement of the catheter will be checked by 3 ml of 2% lignocaine with adrenaline (1:200000).

In group MOR, epidural analgesia will be provided by Morphine 0.05 mg/kg diluted to 10 ml with Bupivacaine 0.1% solution [3 mg Morphine (1 ml) + 2ml Bupivacaine 0.5%+ NS 8 ml] approximately 15 min before surgical incision. The dose will be repeated in every 8-24 hrs depending on optimal response during perioperative period till postoperative day 5. Initially drug will be given 12 hrly, if pain relief not adequate it can be given 8 hrly. If analgesia is adequate and patient become sedated, drug will be administered 24 hrly.

In group ROP epidural analgesia will be provided by Ropivacaine 0.2% + Fentanyl 2 mcg/ml at 3-6 ml /hr during perioperative period till postoperative day 5. Infusion rate will be titrated depending on response.

All patients will receive GA after placement of epidural catheter. In both the groups anaesthesia will be induced with propofol 2 mg/kg, fentanyl 2 mcg/kg and rocuronium 0.6 mg/kg. During intraoperative period, even after highest dose of epidural analgesia as per group allocation, if the patient’s heart rate or BP increases above 20% and that rise is clinically judged to be due to inadequate analgesiarescue analgesia will be administered with fentanyl 25 mcg. Anesthesia will be maintained with sevoflurane in a mixture of medical air 60% and O2 40%. End-tidal concentration of sevoflurane will be adjusted depending upon the vital parameters. Systolic blood pressure(SBP) will be maintained within 20% of baseline values, and hypotension (SBP<90 mmof Hg) will be treated with fluid bolus and/or vasopressors as per institutional protocol. A thermal blanket will be positioned over the exposed parts of the body to maintain perioperative normothermia. All patients will receive IV infusion of balanced salt solution (BSS) at a rate of 4 ml/kg/hour. Thirty minutes before termination of anesthesia intravenous paracetamol at the dose of 15mg/kg will be administered.In the postoperative period, if patient’s NRS becomes greater than 3 even after highest dose of epidural analgesia, IV fentanyl bolus 25 mcg will be given. If fentanyl consumption exceeds 100 mcg (4 bolus) in 4 hr, IV fentanyl infusion will be started with 20 mcg/hr. Adequate pain relief will be achieved by increasing fentanyl infusion by 5mcg/hr in every 30 min. If rescue fentanyl consumption exceeds 50 mcg/hr, IV Diclofenac 75 mg, will be administered 12 hourly as multimodal analgesia. If patient becomes sedated fentanyl infusion will be stopped. In the postoperative period all patients will receive maintenance intravenous fluid with balanced salt solution (BSS) at the rate of 1.5 ml/kg/hr. If there is hemodynamic compromise [hypotension (SBP< 90mm of Hg), urine output < 0.5ml/kg/hr] intravenous fluid bolus with 5ml/kg will be infused. If hypotension persists even after fluid bolus, vasopressors will be given as per institutional protocol. In both groups multimodal analgesia included intravenousparacetamol 15mg/kg, 3 times a day.