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Different Effects of Albumin and Hydroxyethyl Starch on Low Molecular-Weight Solute Permeation through Sodium Hyaluronic Acid Solution.

ABSTRACT: Hyaluronic acid (HA), a high-molecular-weight linear polysaccharide, restricts solute transport through the interstitial space. Albumin and hydroxyethyl starch (HES) solutions are used to correct the decrease of blood volume during surgery, but may leak into the interstitial space under inflammation conditions. Given the possibility that the structure of HA may be affected by adjacent macromolecules, this study tested whether albumin and HES (M_w 130,000) exert different effects on solute permeation through sodium hyaluronic acid (NaHA: M_w 1.3 × 10⁶) solution. To this end, permeation of Orange G, a synthetic azo dye (M_w 452), into NaHA solutions containing albumin or HES over time was assessed. The amount of time it took for the relative absorbance of Orange G to reach 0.3 (T_0.3) was determined in each NaHA solution relative to the reference solution (i.e., colloid solution without NaHA). Relative T_0.3 values of albumin were larger than those of HES for 0.1% NaHA solution (3.33 ± 0.69 vs. 1.16 ± 0.08, p = 0.006, n = 3) and 0.2% NaHA solution (1.95 ± 0.32 vs. 0.92 ± 0.27, p = 0.013, n = 3). This finding may help in the selection of an appropriate colloid solution to control drug delivery into the interstitial space of cancer tissue under inflammation conditions.

SUBMITTER: Tatara T

PROVIDER: S-EPMC7914834 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Different Effects of Albumin and Hydroxyethyl Starch on Low Molecular-Weight Solute Permeation through Sodium Hyaluronic Acid Solution.

Tatara Tsuneo T

Polymers 20210209 4

Hyaluronic acid (HA), a high-molecular-weight linear polysaccharide, restricts solute transport through the interstitial space. Albumin and hydroxyethyl starch (HES) solutions are used to correct the decrease of blood volume during surgery, but may leak into the interstitial space under inflammation conditions. Given the possibility that the structure of HA may be affected by adjacent macromolecules, this study tested whether albumin and HES (<i>M</i><sub>w</sub> 130,000) exert different effects ...[more]

PMID: 33572079

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Project description:Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, Madsen KR, Møller MH, Elkjær JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjældgaard AL, Fabritius ML, Mondrup F, Pott FC, Møller TP, Winkel P, Wetterslev J; 6S Trial Group; Scandinavian Critical Care Trials Group: Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012, 367:124-34.Hydroxyethyl starch (HES) is widely used for fluid resuscitation in ICUs, but its safety and efficacy have not been established in patients with severe sepsis.To assess the effects of HES 130/0.4 compared with a balanced crystalloid solution on mortality and end-stage kidney failure in patients with severe sepsis.Multicenter, parallel-group, blinded, randomized clinical trial, in patients with severe sepsis.Patients with severe sepsis admitted to the ICU received fluid resuscitation with either 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate at a dose of up to 33 ml per kilogram of ideal body weight per day.Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval (CI), 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal replacement therapy compared with those receiving Ringer's acetate.

Project description:ObjectiveTo assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis.DesignSystematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data sourcesCochrane Library, Medline, Embase, Biosis Previews, Science Citation Index Expanded, CINAHL, Current Controlled Trials, Clinicaltrials.gov, and Centerwatch to September 2012; hand search of reference lists and other systematic reviews; contact with authors and relevant pharmaceutical companies.Study selectionEligible trials were randomised clinical trials comparing hydroxyethyl starch 130/0.38-0.45 with either crystalloid or human albumin in patients with sepsis. Published and unpublished trials were included irrespective of language and predefined outcomes.Data extractionTwo reviewers independently assessed studies for inclusion and extracted data on methods, interventions, outcomes, and risk of bias. Risk ratios and mean differences with 95% confidence intervals were estimated with fixed and random effects models.ResultsNine trials that randomised 3456 patients with sepsis were included. Overall, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin did not affect the relative risk of death (1.04, 95% confidence interval 0.89 to 1.22, 3414 patients, eight trials), but in the predefined analysis of trials with low risk of bias the relative risk of death was 1.11 (1.00 to 1.23, trial sequential analysis (TSA) adjusted 95% confidence interval 0.95 to 1.29, 3016 patients, four trials). In the hydroxyethyl starch group, renal replacement therapy was used more (1.36, 1.08 to 1.72, TSA adjusted 1.03 to 1.80, 1311 patients, five trials), and the relative risk of acute kidney injury was 1.18 (0.99 to 1.40, TSA adjusted 0.90 to 1.54, 994 patients, four trials). More patients in the hydroxyethyl starch group were transfused with red blood cells (1.29, 1.13 to 1.48, TSA adjusted 1.10 to 1.51, 973 patients, three trials), and more patients had serious adverse events (1.30, 1.02 to 1.67, TSA adjusted 0.93 to 1.83, 1069 patients, four trials). The transfused volume of red blood cells did not differ between the groups (mean difference 65 mL, 95% confidence interval -20 to 149 mL, three trials).ConclusionIn conventional meta-analyses including recent trial data, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin increased the use of renal replacement therapy and transfusion with red blood cells, and resulted in more serious adverse events in patients with sepsis. It seems unlikely that hydroxyethyl starch 130/0.38-0.45 provides overall clinical benefit for patients with sepsis.

Dataset Information

Different Effects of Albumin and Hydroxyethyl Starch on Low Molecular-Weight Solute Permeation through Sodium Hyaluronic Acid Solution.

Publications

Different Effects of Albumin and Hydroxyethyl Starch on Low Molecular-Weight Solute Permeation through Sodium Hyaluronic Acid Solution.

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