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Background: Optimal infusion rate of colloids in patients with suspected hypovolemia is unknown, and the primary objective of the present study was to test if plasma volume expansion by 5% albumin is greater if fluid is administered slowly rather than rapidly., Methods: Patients with signs of hypoperfusion after major abdominal surgery were randomized to intravenous infusion of 5% albumin at a dose of 10 ml/kg (ideal body weight) either rapidly (30 min) or slowly (180 min). Plasma volume was measured using radiolabeled albumin at baseline, at 30 min, and at 180 min after the start of infusion. Primary outcome was change in plasma volume from the start of infusion to 180 min after the start of infusion. Secondary outcomes included the change in the area under the plasma volume curve and transcapillary escape rate (TER) for albumin from 180 to 240 min after the start of albumin infusion., Results: A total of 33 and 31 patients were included in the analysis in the slow and rapid groups, respectively. The change in plasma volume from the start of infusion to 180 min did not differ between the slow and rapid infusion groups (7.4 ± 2.6 vs. 6.5 ± 4.1 ml/kg; absolute difference, 0.9 ml/kg [95%CI, - 0.8 to 2.6], P = 0.301). Change in the area under the plasma volume curve was smaller in the slow than in the rapid infusion group and was 866 ± 341 and 1226 ± 419 min ml/kg, respectively, P < 0.001. TER for albumin did not differ and was 5.3 ± 3.1%/h and 5.4 ± 3%/h in the slow and in the rapid infusion groups, respectively, P = 0.931., Conclusions: This study does not support our hypothesis that a slow infusion of colloid results in a greater plasma volume expansion than a rapid infusion. Instead, our result of a smaller change in the area under the plasma volume curve indicates that a slow infusion results in a less efficient plasma volume expansion, but further studies are required to confirm this finding. A rapid infusion has no effect on vascular leak as measured after completion of the infusion., Trial Registration: EudraCT2013-004446-42 registered December 23, 2014.

Background: Administration of fluids to restore normovolaemia is one of the most common therapeutic interventions performed peri-operatively and in the critically ill, but no study has evaluated the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid. The present study is designed to test the hypothesis that a slow infusion of resuscitation fluid results in better plasma volume expansion than a rapid infusion., Methods/design: The study is a single-centre, assessor-blinded, parallel-group, randomised prospective study. Patients over 40 years of age admitted to the post-operative care unit after a Whipple procedure or major gynaecological surgery and presenting with signs of hypovolaemia are eligible for inclusion. Patients are randomised in a 1:1 fashion with no stratification to either rapid (30 minutes) or slow (180 minutes) infusion of 5% albumin at a dose of 10 ml/kg ideal body weight. Plasma volume is measured using 125 I human serum albumin at baseline (prior to albumin infusion) as well as at 30 minutes and 180 minutes after infusion start. The primary endpoint is change in plasma volume from baseline to 180 minutes after the start of 5% albumin infusion. Secondary endpoints include the integral of plasma volume over time from baseline to 180 minutes after the start of the infusion and transcapillary escape rate of albumin (%/h) from 180 minutes to 240 minutes after the start of albumin infusion. In addition, diuresis, change in central venous oxygen saturation, lactate and blood pressure will be evaluated. A total of 70 patients will be included in the study, and the study has 80% power to detect a difference of 4 ml/kg in plasma volume expansion between the two groups., Discussion: The present study is the first clinical investigation of the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid., Trial Registration: EudraCT identifier: 2013-004446-42 . Registration date: 20 December 2013. ClinicalTrials.gov identifier: NCT02728921 . Registration date: 31 March 2016.

One of the many unresolved questions regarding the permeability of the glomerular filtration barrier is the reason behind the marked difference in permeability between albumin and polysaccharide probe molecules such as Ficoll and dextran of the same molecular size. Although the differences in permeability have been mainly attributed to charge effects, we have previously shown that this would require a highly charged filtration barrier, having a charge density that is -10 times more than that on the albumin molecule. In this article, the classic two-pore model was extended by introducing size distributions on the solute molecules, making them conformationally flexible. Experimental sieving data for Ficoll from the rat glomerulus and from precision-made silicon nanopore membranes were analyzed using the model. For the rat glomerulus a small-pore radius of 36.2 Å and a geometric standard deviation (gSD) for the Ficoll size-distribution of 1.16 were obtained. For the nanopore membranes, a gSD of 1.24 and a small-pore radius of 43 Å were found. Interestingly, a variation of only -16% in the size of the polysaccharide molecule is sufficient to explain the difference in permeability between albumin and Ficoll. Also, in line with previous data, the effects of applying a size distribution on the solute molecule are only evident when the molecular size is close to the pore size. Surely there is at least some variation in the pore radii, and, likely, the gSD obtained in the current study is an overestimation of the "true" variation in the size of the Ficoll molecule. [ABSTRACT FROM AUTHOR]

The turnover of albumin is increased in both peritoneal dialysis (PD) and hemodialysis (HD) due to increased external losses, normally leading to compensatory increases in the hepatic albumin synthesis. The normal rate of albumin synthesis is on the order of 12 g/day corresponding to an equally large albumin fractional catabolic rate of ~4% daily. Most albumin catabolism is assumed to occur in the endothelium, but there is also renal and hepatic catabolism and leakage into the gastrointestinal tract. In PD the daily losses are on the order of 5 g/day. There are also external albumin losses in HD, particularly when high-performance membranes are used, the losses per session ranging between 1 and 8 g (or more). The dialytic albumin losses cannot be detected by assessing the transcapillary escape rate of albumin from the plasma compartment to the interstitium. In PD, tracer albumin that has been injected into the peritoneal fluid is absorbed to the tissues surrounding the peritoneal cavity without much edema formation, due to the process of "volume recirculation". A small fraction of the dialysate albumin tracer (0.2-0.3 ml/minute) is directly reabsorbed to the plasma via the lymphatics. A significant portion of dialysis patients are affected by chronic inflammation, such as in the malnutrition inflammation and atherosclerosis syndrome, which is also associated with cardiovascular mortality and fluid overload. These patients usually have a reduced ability to compensate for external losses of albumin, which may result in hypoalbuminemia. Reduced plasma albumin levels in dialysis patients may thus be regarded as a sign of chronic inflammation rather than reflecting malnutrition. [ABSTRACT FROM AUTHOR]