Jane Hayden1, Anil Gupta2, Sven-Egron Thörn1, Pontus Thulin3, Linda Block1, Jonatan Oras1. 1. Department of Anesthesiology and Intensive Care, Institute of Clinical sciences, Sahlgrenska Academy, University of Gothenburg, Västra Götalandsregionen, Sahlgrenska University Hospital, Gothenburg, Sweden. 2. Institute of Physiology and Pharmacology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. 3. Department of Clinical Immunology and Transfusion Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Abstract
BACKGROUND: Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti-inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines. METHODS: This was a, randomized, double blind, placebo-controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi-port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin. RESULTS:Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53-250) compared to placebo, median 440 nmol/L (IQR 115-885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations. CONCLUSION: In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans.
RCT Entities:
BACKGROUND:Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti-inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines. METHODS: This was a, randomized, double blind, placebo-controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi-port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin. RESULTS: Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53-250) compared to placebo, median 440 nmol/L (IQR 115-885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations. CONCLUSION: In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans.