Patients-Controlled Epidural Analgesia After Gastric Bypass for Morbid Obesity Using Morphine-Levobupivacaine Regimens

Study Overview
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Brief Summary
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Adequate postoperative analgesia can facilitate recovery following gastric bypass surgery for morbid obesity. The efficacy and safety of intravenous patient - controlled analgesia has been studied, but up to date no data are available concerning the use of thoracic epidural patient-controlled analgesia regarding the use of levobupivacaine combined with morphine in morbidly obese patients. The investigators' aim in this prospective, randomized, double-blinded study was to compare the analgesic effectiveness, the dose requirements and side effects of thoracic epidural patient controlled analgesia 0.1% and 0.2% levobupivacaine combined with a continuous epidural administration of morphine, with or without a loading dose, after open gastric bypass for morbid obesity.

Detailed Description
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Morbidly obese patients (BMI > 50 kg/m2) planned to undergo open variant of biliopancreatic diversion with Roux-en-Y gastric bypass (BPD-RYGBP) received standardized general anesthesia (intravenous propofol combined with remifentanyl and muscle relaxation). Preoperatively, in all patients an epidural catheter in the thoracic spine level will be placed between T5 and T8 interspace. All patients will be randomly allocated to six groups: Group A patients will receive intra-operatively (45 min before the estimated end of the surgery) a bolus dose 2 ml of normal saline, epidurally. Postoperatively, immediately after extubation patient controlled epidural anesthesia (PCEA)with 0.1% levobupivacaine (5ml, lockout interval 10min) , combined with a continuous epidural infusion of morphine 0.2 mg/h will be administered, Group B patients will receive an epidural bolus dose of 1mg of morphine intra-operatively (45 min before the estimated end of the surgery) and postoperatively the same levobupivacaine and morphine regimen as Group A, Group C patients will receive an epidural bolus dose 2 mg of morphine intra-operatively and thereafter the same levobupivacaine and morphine regimen as Group A. Group D patients will receive intra-operatively an epidural bolus dose of 2 ml of normal saline. Postoperatively, the patients will receive PCEA in a dose of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h, Group E patients will receive intra-operatively an epidural bolus dose of 1mg of morphine intra-operatively and postoperatively the same regimen as Group D. Group F patients will receive intra-operatively an epidural bolus dose of 2 mg of morphine intra-operatively and thereafter the same regimen as Group D. Pain assessment will be performed using visual analogue scale (VAS, 10cm scale) at rest, at mobilization and at cough. Furthermore, total local anesthetic and morphine consumption, side effects on cardiovascular, respiratory and gastrointestinal systems, including blood pressure,blood gases, spirometric values Forced Expiratory Volume at 1 sec (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow Rate (PEFR), incidents of postoperative nausea and vomiting (PONV), pruritus, time to first flatus, postoperative ambulation will be recorded for up to 6 days.

Official Title
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Postoperative Thoracic Epidural Analgesia in Super Obese Patients ( BMI 60 kg m-2) Undergoing Open Weight Loss Surgery :Does the Addition of Morphine to 0.1% and 0.2% Levobupivacaine Affect Postoperative Pain Relief, Perioperative Lung Function, Return of Normal Gastrointestinal Mobility and Ambulation?

Conditions
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Morbid Obesity, Postoperative Pain, Postoperative Bowel Function, Postoperative Ambulation

Intervention / Treatment
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* Drug: GROUP A : 0 mg MORPHINE-0.1% LEVOBUPIVACAINE
* Drug: GROUP B : 1 mg MORPHINE- 0.1% LEVOBUPIVACAINE
* Drug: GROUP C : 2 mg MORPHINE-0.1% LEVOBUPIVACAINE
* Drug: GROUP D : 0 mg MORPHINE- 0.2% LEVOBUPIVACAINE
* Drug: GROUP E : 1 mg MORPHINE-0.2 % LEVOBUPIVACAINE
* Drug: GROUP F : 2 mg MORPHINE- 0.2% LEVOBUPIVACAINE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) > 50 Age < 50 Patients written consent to participate in the study Exclusion Criteria: Cardiovascular disease (valvular and ischemic heart disease) Patients refusal to participate in the study Contraindication to epidural catheter placement (e.g anticoagulation, anti- platelets medication) Active psychiatric disease requiring treatment Redo surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GROUP A : 0 mg MORPHINE-0.1% LEVOBUPIVACAINE<br>Group A patients receive intra-operatively (45 min before the estimated end of the surgery) a bolus dose 2 ml of normal saline. Postoperatively, patients receive PCEA of 0.1% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h. | Drug: GROUP A : 0 mg MORPHINE-0.1% LEVOBUPIVACAINE<br>* Patients receive intra-operatively (45 min before the estimated end of the surgery) a bolus dose 2 ml of normal saline, epidurally. Postoperatively, immediately after extubation, patients receive patient controlled epidural analgesia (PCEA) of 0.1% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h.<br>* Other names: Chirocaine 5 mg/ml - Levobupivacaine;|
| Active Comparator: GROUP B : 1 mg MORPHINE- 0.1% LEVOBUPIVACAINE<br>Group B patients receive an epidural bolus dose of 1mg of morphine intra-operatively (45 min before the estimated end of the surgery). Postoperatively, patients receive PCEA of 0.1% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h | Drug: GROUP B : 1 mg MORPHINE- 0.1% LEVOBUPIVACAINE<br>* Patients receive intraoperatively(45 min before the estimated end of the surgery)an epidural bolus dose of 1mg of morphine.Postoperatively, immediately after extubation, patients receive patient controlled epidural analgesia (PCEA) of 0.1% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h.<br>* Other names: Chirocaine 5 mg/ml - Levobupivacaine;|
| Active Comparator: GROUP C : 2 mg MORPHINE-0.1% LEVOBUPIVACAINE<br>Group C patients receive an epidural bolus dose 2 mg of morphine intra-operatively (45 min before the estimated end of the surgery).Postoperatively, patients receive PCEA of 0.1% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h | Drug: GROUP C : 2 mg MORPHINE-0.1% LEVOBUPIVACAINE<br>* Patients receive intraoperatively (45 min before the estimated end of the surgery) a bolus dose 2 mg of morphine, epidurally. Postoperatively, immediately after extubation, patients receive patient controlled epidural analgesia (PCEA) of 0.1% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h.<br>* Other names: Chirocaine 5 mg/ml - Levobupivacaine;|
| Active Comparator: GROUP D : 0 mg MORPHINE- 0.2% LEVOBUPIVACAINE<br>Group D patients receive intra-operatively (45 min before the estimated end of the surgery) a bolus dose of 2 ml of normal saline, epidurally. Postoperatively,patients receive PCEA of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h | Drug: GROUP D : 0 mg MORPHINE- 0.2% LEVOBUPIVACAINE<br>* Patients receive intra-operatively (45 min before the estimated end of the surgery) a bolus dose of 2 ml of normal saline epidurally. Postoperatively, immediately after extubation, patients receive patient controlled epidural analgesia (PCEA) of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h.<br>* Other names: Chirocaine 5 mg/ml - Levobupivacaine;|
| Active Comparator: GROUP E : 1 mg MORPHINE-0.2 % LEVOBUPIVACAINE<br>Group E patients receive intra-operatively (45 min before the estimated end of the surgery) an epidural bolus dose of 1mg of morphine.Postoperatively, patients receive PCEA of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h | Drug: GROUP E : 1 mg MORPHINE-0.2 % LEVOBUPIVACAINE<br>* Patients receive intra-operatively (45 min before the estimated end of the surgery) a bolus dose of 1mg of morphine, epidurally.Postoperatively, immediately after extubation, patients receive patient controlled epidural analgesia (PCEA) of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h.<br>* Other names: Chirocaine 5 mg/ml - Levobupivacaine;|
| Active Comparator: GROUP F : 2 mg MORPHINE- 0.2% LEVOBUPIVACAINE<br>Group F patients receive intra-operatively (45 min before the estimated end of the surgery) an epidural bolus dose of 2 mg of morphine. Postoperatively, patients receive PCEA of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h | Drug: GROUP F : 2 mg MORPHINE- 0.2% LEVOBUPIVACAINE<br>* Patients receive an epidural bolus dose of 2 mg of morphine intra-operatively (45 min before the estimated end of the surgery).Postoperatively, immediately after extubation, patients receive patient controlled epidural analgesia (PCEA) of 0.2% levobupivacaine (5ml, lockout interval 10min) combined with a continuous epidural infusion of morphine 0.2 mg/h.<br>* Other names: Chirocaine 5 mg/ml - Levobupivacaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pain Scores (Visual Analogue Scale) | Pain scores at rest and on cough using a 10cm Visual Analogue Scale(0=no pain, 10=worst possible pain) were assessed up to 48h postoperatively. | up to 48 h postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Postoperative Bowel Recovery | Time to postoperative recovery of bowel function assessed by first flatus or stool, noticed by the patient | up to 6 days | 
| Time to First Postoperative Ambulation | Time to being able to walk without assistance within the room or outside the room | up to 6 days | 
| Consumption of Levobupivacaine at 24h and 48 h Postoperatively | Cumulative consumption of levobupivacaine administered via patients controlled epidural analgesia pump( PCEA) at 24h and 48 h postoperatively | up to 48 hours postoperatively | 
| Cumulative Consumption of Epidural Morphine at 24h and 48h Postoperatively | Cumulative consumption of epidural morphine administered as loading dose, intraoperatively, of 1mg(groups B and E)or 2mg (groups C and F) and as continuous infusion of 0,2mg/h ( all groups) at 24h and 48h postoperatively.All participants in each Group received the same dose of epidural morphine, as no participant missed a scheduled dose. | up to 48 hours postoperatively | 
| Change From Baseline of Spirometric Values | Preoperatively, after a detailed demonstration, baseline spirometry measurements of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate (PEFR) were measured, using a bedside spirometer (PowerCubeΤΜ, Ganshorn Medizin Electronic, Germany), on-line connected to a PC. Spirometry was standardized with each patient in a 30o head-up position and it was performed at least three times and the best measurement was recorded, according to the criteria of the European Respiratory Society .Postoperatively, spirometric values (FVC= Forced Vital Capacity, FEV1=Forced Expiratory Volume at 1 sec , PEFR= Peak Expiratory Flow Rate)were recorded at 12, 24, 36, 48, 72, 144 hours . Data are expressed as percentage of preoperative values, which are 100%. | up to 6th day postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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open gastric by-pass, super morbidly obese patients, postoperative thoracic epidural analgesia, different drug regimens (morphine and levobupivacaine), Lung function tests, Postoperative Bowel recovery, Postoperative Ambulation