Intraperitoneal ropivacaine reduces time interval to initiation of chemotherapy after surgery for advanced ovarian cancer: randomised controlled double-blind pilot study.

BACKGROUND: Advanced-stage ovarian cancer has a poor prognosis; surgical resection with the intent to leave no residual tumour followed by adjuvant chemotherapy is the standard treatment. Local anaesthetics (LA) have anti-inflammatory and analgesic effects. We hypothesised that intraperitoneal LA (IPLA) would lead to improved postoperative recovery, better pain relief, and earlier start of chemotherapy. METHODS: This was a prospective, randomised, double-blind, placebo-controlled pilot study in 40 women undergoing open abdominal cytoreductive surgery. Patients were randomised to receive either intraperitoneal ropivacaine (Group IPLA) or saline (Group Placebo) perioperatively. Except for study drug, patients were treated similarly. Intraoperatively, ropivacaine 2 mg ml-1 or 0.9% saline was injected thrice intraperitoneally, and after operation via a catheter and analgesic pump into the peritoneal cavity for 72 h. Postoperative pain, time to recovery, home discharge, time to start of chemotherapy, and postoperative complications were recorded. RESULTS: No complications from LA administration were recorded. Pain intensity and rescue analgesic consumption were similar between groups. Time to initiation of chemotherapy was significantly shorter in Group IPLA (median 21 [inter-quartile range 21-29] vs 29 [inter-quartile range 21-40] days; P=0.021). Other parameters including time to home readiness, home discharge and incidence, and complexity of postoperative complications were similar between the groups. CONCLUSIONS: Intraperitoneal ropivacaine during and for 72 h after operation after cytoreductive surgery for ovarian cancer is safe and reduces the time interval to initiation of chemotherapy. Larger studies are warranted to confirm these initial findings. CLINICAL TRIAL REGISTRATION: NCT02256228.

Does intraperitoneal ropivacaine reduce postoperative inflammation? A prospective, double-blind, placebo-controlled pilot study.

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.