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The majority of women with ovarian cancer are diagnosed at an advanced stage with extensive dissemination of tumour to the mesothelial lining of the abdomen, the peritoneum. Moreover, large amounts of ascites are often prevalent. Best chance of prolonged survival comprises the combination of cytoreductive surgery (CRS) and adjuvant chemotherapy. The aim of CRS is to resect all visible tumour to achieve complete macroscopic resection, which often necessitates high complexity surgery with risk of substantial fluid shifts and risk of postoperative complications that prolongs (or inhibits) the time-interval to adjuvant chemotherapy. A prolonged time interval to adjuvant chemotherapy has been associated with inferior survival. Local anaesthetics have anti-inflammatory properties and when applied at site of injury in the abdomen, phase II and III trials have demonstrated an improved postoperative recovery after abdominal surgery and reduced time-interval to adjuvant chemotherapy during CRS. Previous observational studies suggests that scheduling of surgery earlier on the week may be associated with improved outcomes and for ovarian cancer the ability to achieve complete macroscopic resection is increased. In the IPLA-OVCA trial, a Swedish multicenter randomised double-blind, placebo-controlled trial, women with advanced epithelial ovarian cancer (aEOC) were randomised to receive Ropivacaine (local anaesthetics) or Saline (placebo) intraperitoneally during and for 72 hours postoperative. Participating hospitals were Karolinska University hospital and Skåne University hospital, Lund. Primary endpoint was time (days), 173 women were included in the intention-to-treat (ITT) and 166 women in the Per Protocol (PP) analyses. There were no differences between groups in mean time between surgery and start of chemotherapy in the ITT (0.4 days (95% CI: -2.4 to 3.2; p=0.77) or the PP analyses, 0.5 days (95% CI: -2.4 to 3.4; p=0.77). Moreover, there was no difference in postoperative

Aims A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery. Methods An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1(st) day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individual-specific covariates were added in sequence. Results The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k(21)), but it also increased losses of fluid from the kinetic system (k(b)). The balance between k(21) and k(b) maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k(10)) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates. Conclusions There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers., Funding Agencies|Mats Kleberg Foundation

BACKGROUND: Injury (shedding) of the endothelial glycocalyx layer, which alters local blood flow and microvascular permeability, is assessed by measuring components of this layer in circulating blood. The influence of renal function on their concentrations is unknown. METHODS: Plasma and urine concentrations of three shedding products (syndecan-1, hyaluronic acid, and heparan sulfate) and creatinine were measured over 5 hours in 15 healthy volunteers and 15 postoperative patients; this guaranteed a spread of kidney functions. Renal clearances were calculated. RESULTS: Low renal clearances of syndecan-1 (mean 3.5 mL/min) and hyaluronic acid (0.8 mL/min) correlated inversely with the 6-fold variability in the plasma concentrations of these substances (r = -0 . 45 and-0.49). Low creatinine clearance correlated inversely (r = -0.60) and plasma creatinine directly (r = 0.52) with the two-fold variability in heparan sulfate, which was the only shedding substance that also correlated with C-reactive protein (r= 0.51) and, therefore, showed higher concentrations after surgery. CONCLUSIONS: The present explorative study suggests that a 6-fold variability in the plasma concentrations of three commonly measured endothelial shedding products can be understood by the kidneys ability to excrete them. This finding has implications when interpreting results of studies where shedding is assessed.