Intra-Peritoneal Local Anaesthesia After Cytoreductive Surgery

Study Overview
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Brief Summary
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Can perioperative administration of intra-peritoneal local anaesthetics further reduce postoperative pain, inflammation and outcome in patients undergoing major abdominal surgery (cytoreductive surgery) and managed with thoracic epidural analgesia? - Multicenter study.

Detailed Description
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The aim of this study is to measure the efficacy of local anesthetics (LA) administered into the intra-peritoneal cavity compared to placebo. Our hypothesis is that the injection of local LAs intra-peritoneally would reduce post-operative pain and the inflammatory process caused by the massive release of cytokines during extensive cytoreductive surgery. The study is a controlled, parallel group, double blind, prospective, randomized and performed at Sahlgrenska University Hospital in Goteborg, Sweden . Twenty mL of ropivacaine or saline would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen according to group randomization in order to double blind patients and all personnel involved in the study. The parameters that would be evaluated are inflammatory markers, postoperative morbidity, pain intensity, consumption of morphine, cognitive function and progression-free survival.

Official Title
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Peroperative Analgesia Following Cytoreductive Surgery. A Randomized, Double-blind, Comparison Between Intra-peritoneal Local Anesthesia and Placebo - Multicenter Study

Conditions
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Pain

Intervention / Treatment
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* Drug: Ropivacaine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients with widespread malignant intra-abdominal ovary cancer stadium III-IV and are operated by extensive resection of intra-abdominal viscera as well as the parietal peritoneum (cytoreductive surgery, CRS) Exclusion Criteria: Body mass index > 35 American Society of Anesthesiologists classification > 3 Renal dysfunction Allergic to acetylsalicylic acid Unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group R<br>Ropivacaine is instillated through one multi-hole catheter wich would be inserted percutaneously in all patients and tunnelled about 1-2 cm lateral to the abdominal incision and the tip of the catheter placed in the intra-peritoneal cavity. The catheter would not be ligated and fixed in situ intra-peritoneally. Twenty ml of Ropivacaine would be injected subcutaneously along both sides of the incision prior to skin closure. Additionally, 20 ml of Ropivacaine (1mg/mL) would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen. | Drug: Ropivacaine<br>* Active Group<br>* Other names: Narop;|
| Placebo Comparator: Group P<br>Saline is instillated through one multi-hole catheter wich would be inserted percutaneously in all patients and tunnelled about 1-2 cm lateral to the abdominal incision and the tip of the catheter placed in the intra-peritoneal cavity. The catheter would not be ligated and fixed in situ intra-peritoneally. Twenty ml of Saline would be injected subcutaneously along both sides of the incision prior to skin closure. Additionally, 20 ml of Saline would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen. | Drug: Saline<br>* Placebo Comparator<br>* Other names: Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Markers | Analysis of the following inflammatory markers with Multiplex: IL(interleukin)-1β, IL-1rα, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, zBasic FGF (Fibroblast Growth Factor), Eotaxin, G-CSF (granulocyte colony stimulating factor), GM-CSF granulocyte macrophage colony stimulating factor), IFN-γ (interferon), IP-10 (immune protein), MCP-1 (monocyte chemotactic protein), MCAF (monocyte chemotactic and activating factor), MIP-1α (macrophage inflammatory protein), MIP-1β, PDGF-BB (platelet-derived growth factor), RANTES (regulated on activation, normal T cell expressed and secreted), TNF-α (tumor necrosis factor), VEGF (vascular endothelial growth factor) | 0-48 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Morphine consumption | Total amount of Morphine consumed during the first 48 hours after surgery | 0-48 hours postoperatively | 
| Pain Intensity | Pain Intensity is measured with Numeric Rating Score 0-10 | 0-48 hours postoperatively | 
| Cognitive Function | Patients will complete the following neurophysiological tests upon entering the study and within one month after surgery: Verbal Learning Test (VLT), Concept Shifting Test (CST), Letter-Digit Coding, Verbal Learning Test - Delayed Recall (VLT-D) | 0-1 month postoperatively | 
| Progression-free Survival | Progression-free Survival measures the length of time after treatment during which the cancer being treated does not get worse. | 0-3 years postoperatively | 
| Postoperative Morbidity/Complications | Measuring the numbers of Postoperative Morbidity/Complications within one month after surgery: Morbidity: Local infections Urinary infection (urine culture) Pneumonia (X-ray, C-reactive protein, Fever) Sepsis (Fever, Leucocyte count in blood, Heart Rate, Respiratory Rate) Pleural fluid (X-ray verified) Deep Vein Thrombosis (D-dimer, ultrasound verified) Pulmonary embolism (Computed Tomography/ Scint-X) Acute Myocardial Infarction (Electrocardiography, Troponin I) Atrial fibrillation or serious arrhythmia during the first 48 hours after surgery (Electrocardiography) Respiratory failure (prolonged mechanical ventilation) Renal failure (Serum Creatinine, Diuresis, AKIN criteria) Inotropic needs > 12 hours after surgery Surgical Complications: Intraabdominal bleeding Leakage from anastomosis Abdominal abscess Paralytic ileus Pancreatic leakage (requiring drainage) | 0-30 days postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Analgesia, Local infiltration analgesia, Pain, relief, Pain, Postoperative, Intra-peritoneal analgesia, Ropivacaine, Saline, Therapeutic Uses, Analgesics, Non-Narcotic, Analgesics, Opioids, Morphine, Pain, Postoperative Complications, Physiological Effects of Drugs, Anesthetics, Local, Anesthetic, Cytoreductive, Surgery, Cancer