Emma Hasselgren

Prospective Assessment of Clinically Relevant Fluid Balance Thresholds Associated With Postoperative Complications in Advanced Ovarian Cancer

ABSTRACTBackgroundReliable data on optimal fluid management in the perioperative period for patients with advanced ovarian cancer undergoing cytoreductive surgery is limited. These patients often present with malignant ascites and are prone to significant fluid shifts perioperatively. For this reason, our objective was to define clinical targets for optimal fluid balance and determine whether initial ascites should be included in fluid‐loss calculations by examining the association between perioperative fluid balance and major postoperative complications.MethodsThis prospective, observational study conducted in a centralized and public healthcare system setting in Sweden between 2020 and 2023 included patients with advanced ovarian cancer, > 18 years of age, scheduled for upfront cytoreductive surgery, an ASA physical status I–III with no speech/language issues. The primary outcome was major postoperative complication within 30 days of surgery. The measurements of fluid input and output, cut‐offs for fluid balance, perioperative time, and postoperative complications were defined a priori. The association between fluid balance and major postoperative complications was assessed by multivariable regression, adjusted for predefined covariates, yielding odds ratios (OR) with 95% confidence intervals (CI).ResultsOf 175 enrolled patients, 162 were included in the final analysis. In the adjusted analysis, there was a significant association between fluid balance of 1750–2700 mL, OR 3.40 (95% CI 1.06–10.9; p = 0.04) and > 2700 mL, OR 3.91 (95% CI 1.33–11.5; p = 0.01) and major postoperative complications. When including initial ascites as fluid loss, a balance of > 2700 mL was associated with major postoperative complications, OR 2.59 (95% CI 1.01–6.66, p = 0.047).ConclusionAn optimal target for perioperative fluid balance to decrease the odds of major postoperative complications is suggested to be < 1750 mL. If initial ascites is included as loss in the calculation of balance, the optimal target of fluid balance is suggested to be < 2700 mL. These results provide practical clinical reference values that may assist anesthesiologists and surgical teams in optimizing perioperative fluid management in advanced ovarian cancer.Editorial CommentThis secondary analysis of a trial ovarian cancer operative cohort assessed the relation of the estimated fluid balance over the operative day 24 h to major postoperative complications. The findings showed that the groups where the fluid balance was in the categories higher and also most positive had higher odds for having a major complication compared to the group with lowest fluid balance. Ascities fluid was an issue in this cohort, which was managed in the analysis.Trial Registration: ClinicalTrials.gov: NCT04065009

Effect of intraperitoneal ropivacaine during and after cytoreductive surgery on time-interval to adjuvant chemotherapy in advanced ovarian cancer: a randomised, double-blind phase III trial

In a previous phase II trial, intraperitoneal local anaesthetics shortened the time interval between surgery and adjuvant chemotherapy, an endpoint associated with improved survival in advanced ovarian cancer. Our objective was to test this in a phase III trial. A double-blind, phase III parallel superiority trial was conducted at two university hospitals in Sweden, within a public and centralised healthcare system. Women >18 yr with advanced ovarian cancer scheduled for cytoreductive surgery, an ASA physical status of 1-3 with no speech/language issues, were eligible. Participants were randomly assigned using a central computerised system to receive either ropivacaine 0.2% or saline 0.9% (placebo) intraperitoneally during and after surgery. The primary endpoint was time to return to intended oncologic therapy (RIOT), analysed using t-test and linear regression adjusted for centre. Of the 225 women randomised between August 2020 and December 2023 (ropivacaine n=113; placebo n=112), 175 were included in the modified intention-to-treat analysis (ropivacaine n=86; placebo n=89). Median age: ropivacaine group 64 yr (56-73 yr), placebo group: 66 yr (57-74 yr). The mean RIOT in the ropivacaine group was 26.5 days vs 25.8 days in the placebo group, with a mean difference of 0.7 days (-2.2 to 3.4 days; P=0.65). Per-protocol analysis of 166 women yielded similar results, mean difference of 0.5 days (-2.4 to 3.4 days; P=0.74) days. There were no differences in short-term recovery or postoperative morbidity. Intraperitoneal local anaesthetic did not shorten the time to RIOT among women undergoing surgery for advanced ovarian cancer in this trial. ClinicalTrials.gov (NCT04065009), European Union Clinical Trials Register (2019-003299-38/SE).

The IPLA-OVCA Trial, Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

Surgery and chemotherapy combined constitute first line treatment in women with advanced ovarian cancer. The aim of surgery apart from staging is cytoreduction, i.e. surgical resection of tumour. Radical resection of all tumour visible by the naked eye followed by adjuvant chemotherapy is associated with best chance of prolonged survival. However, because of tumour dissemination in the peritoneal cavity, radical surgery is often very extensive with surgery in all quadrants of the abdomen and multi-organ resection with substantial risk of postoperative severe complications and subsequent delay in administration of adjuvant chemotherapy. Longer time-interval between surgery to start of adjuvant chemotherapy has been associated with decrease in survival. Surgery presents opportunities not only for eradicating tumours but, paradoxically, also for proliferation and invasion of residual cancer cells. It increases the shedding of malignant cells into the blood and lymphatic circulations, inhibits their apoptosis and potentiates their invasion capacity. Additionally, the immune system, the inflammatory system and the neuroendocrine system react to surgery with important changes, which have been proven to promote progression of cancer. Several anaesthesia-related factors play an important role in perioperative tumorigenesis such as inhalational anaesthetics, opiate analgesics, local anaesthetics and regional anaesthesia, all of which may impact short-term morbidity and long-term mortality. A previous randomized placebo-controlled pilot study suggests that women who receive local anesthetics intraperitoneally preoperatively have a significantly decreased time-interval to initiation of adjuvant chemotherapy. In a prospective, randomised, multi-centre study, we plan to further assess if intraperitoneal local anaesthetics administered perioperatively during 72 h leads to early start of chemotherapy compared to placebo in patients undergoing cytoreductive surgery for FIGO stage III-IV ovarian cancer.