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Optimal glucose control and fluid resuscitation in patients with septic shock remain a challenge. In this study involving more than 500 patients, the potential benefit of maintaining euglycemia through intensive insulin therapy and optimal fluid resuscitation with either pentastarch or Ringer's lactate was assessed. There was no benefit in the intensive-therapy group with respect to either 28-day survival or organ function; there was more severe hypoglycemia in the intensive-therapy group and more acute renal failure in the pentastarch group. The potential benefit of maintaining euglycemia through intensive insulin therapy and optimal fluid resuscitation was assessed. There was no benefit in the intensive-therapy group with respect to either 28-day survival or organ function. In a study by Van den Berghe et al. involving critically ill surgical patients, intensive insulin therapy to maintain euglycemia (glucose level, 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) lowered in-hospital mortality from 10.9% to 7.2%, mostly by reducing deaths from multiple organ failure with a proven septic focus. 1 This beneficial effect occurred predominantly in cardiac surgical patients who received high glucose challenges immediately after surgery (8 to 12 g of glucose intravenously per hour) and was associated with an unusually high rate of death (5.1%) among controls. Furthermore, in a follow-up study by Van . . .

Goal-directed fluid therapy (GDFT) improves postoperative outcomes in various surgeries, but the optimal fluid choice between balanced salt solutions (BSS) and hydroxyethyl starch (HES) remains debated. This meta-analysis compared postoperative outcomes of GDFT using BSS versus 6 ​% HES in elective major abdominal surgery. Comprehensive database searches identified eight RCTs (1739 patients) published between 2000 and 2024. No significant differences were found in overall postoperative complications [RR 1.04 (95 ​% CI 0.90–1.20); p ​= ​0.59], including renal, cardiovascular, respiratory complications, or mortality. However, BSS required significantly higher intraoperative fluid volumes [SMD 0.61 (95 ​% CI 0.42–0.80); p ​< ​0.001] and led to greater postoperative fluid balance [SMD 0.39 (95 ​% CI 0.20–0.59); p ​< ​0.001]. 6 ​% HES should not be used routinely. GDFT using BSS achieves the same outcomes at a lower cost and without the risk of bleeding. •Meta-analysis compares BSS and 6 ​% HES in GDFT for major abdominal surgery.•No significant differences in postoperative complications or mortality.•BSS requires higher intraoperative fluid volumes than 6 ​% HES.•Evidence highlights the cost-effectiveness of BSS for equivalent outcomes.

Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs. HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated. Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice. HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.

The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. A retrospective cohort study. This study was conducted at one tertiary care hospital in China. We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. After matching, hydroxyethyl starch use [8.5 (IQR: 7.5–10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74–1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75–1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41–0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95–1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only. •Hydroxyethyl starch 130/0.4 use was not associated with postoperative acute kidney injury.•Postoperative hospitalization slightly longer in hydroxyethyl starch group by median 0.5 days.•No significant difference was found in RRT incidence or ICU transfers.

ABSTRACT Background Transfusion with fresh frozen plasma (FFP) or hetastarch 6% (HES) is an option for managing decreased colloid oncotic pressure (COP) associated with hypoproteinemia. The effectiveness of HES compared to plasma has not been reported in calves and goats. Hypothesis Hetastarch increases COP to levels similar to FFP. There will be no significant adverse clinicopathological changes after administration of HES. Animals Seven healthy preweaned calves and 7 juvenile goats from university herds. Methods Cohort, clinical trial in a two‐way crossover design. Hetastarch and FFP were administered intravenously at 10 and 20 mL/kg, respectively, once. Plasma COP was measured re‐transfusion, at 0, 1, 2, 4, 6, 12, 24, 36, 72 h, and 7 days after each transfusion. Coagulation variables were analyzed pre‐transfusion, at 0, 24, and 72 h after transfusion. The effects of treatment and time on COP and coagulation variables were determined by multivariate analysis of variance. Results Transfusion with FFP and HES increased the COP in calves and goats, with FFP increasing the COP to a greater magnitude in calves (least square mean difference of 1.6 vs. 1 mmHg; p = 0.03) but not in goats (least square mean difference of 3.0 vs. 3.0 mmHg; p = 0.99). There were no significant changes (p > 0.05) in coagulation variables detected after transfusion with FFP or HES. Conclusions and Clinical Importance Hetastarch is an alternative colloid to FFP in calves and goats. Adverse changes were not observed in goats and calves after HES administration.

Purpose To determine whether fluid resuscitation of acutely ill adults with 6 % hydroxyethyl starch (6 % HES 130) with a molecular weight of 130 kD and a molar substitution ratio of approximately 0.4 (6 % HES 130) compared with other resuscitation fluids results in a difference in the relative risk of death or treatment with renal replacement therapy (RRT). Methods Systematic review and meta-analysis of randomized controlled trials comparing intravascular fluids for resuscitation of hospitalised adults that reported mortality or treatment with RRT. The risk of bias was assessed independently by two reviewers and meta-analysis was performed using random effects. Results Thirty-five trials enrolling 10,391 participants were included. The three largest trials had the lowest risk of bias, were published (or completed) in 2012, and together enrolled 77 % of all participants. Death occurred in 928 of 4,691 patients (19.8 %) in the 6 % HES 130 group versus 871 of 4,720 (18.5 %) in the control fluid groups relative risk (RR) in the 6 % HES 130 group 1.08, 95 % confidence interval (CI) 1.00 to 1.17, I 2  = 0 %). Treatment with RRT occurred in 378 of 4,236 patients (8.9 %) in the 6 % HES 130 group versus 306 of 4,260 (7.2 %) in the control fluid group (RR in the 6 % HES 130 group 1.25, 95 % CI 1.08 to 1.44, I 2  = 0 %). Conclusions The quality and quantity of data evaluating 6 % hydroxyethyl starch (130/0.4 and 130/0.42) as a resuscitation fluid has increased in the last 12 months. Patients randomly assigned to resuscitation with 6 %HES 130 are at significantly increased risk of being treated with RRT.

A physician with nearly 100 retracted papers may have misrepresented risks of an intravenous fluid. In biomedical science, most papers that lead to retractions don't threaten anyone's life. But a troubling exception arose after investigators found fabrication and other misconduct in nearly 100 papers co-authored by German anesthesiologist Joachim Boldt. Many of those studies supported the effectiveness of intravenous solutions containing hydroxyethyl starch, or hetastarch, to stabilize the blood pressure of patients during and after surgery or trauma. U.K. medical societies relied on four of Boldt's papers in issuing guidelines about the treatments; many patients may have been put at risk by his findings. A meta-analysis that excluded them found that such fluids posed modest but statistically significantly greater risks of kidney damage and death.

Fluid resuscitation is a key intervention in sepsis, but the type of fluids used varies widely. The aim of this meta-analysis is to determine whether resuscitation with hydroxyethyl starches (HES) compared with crystalloids affects outcomes in patients with sepsis. Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 2013. Studies that compared resuscitation with HES versus crystalloids in septic patients, and reported incidence of acute kidney injury (AKI), renal replacement therapy (RRT), transfusion of red blood cell (RBC) or fresh frozen plasma and/or mortality. Three investigators independently extracted data into uniform risk ratio measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. Ten trials (4624 patients) were included. An increased incidence of AKI (risk ratio [RR], 1.24 [95% Confidence Interval {CI}, 1.13-1.36], and need of RRT (RR, 1.36 [95% CI, 1.17-1.57]) was found in patients who received resuscitation with HES. Resuscitation with HES was also associated with increased transfusion of RBC (RR, 1.14 [95% CI, 1.01-1.93]), but not fresh frozen plasma (RR, 1.47 [95% CI, 0.97-2.24]). Furthermore, while intensive care unit mortality (RR, 0.74 [95% CI, 0.43-1.26]), and 28-day mortality (RR, 1.11 [95% CI, 0.96-1.28]) was not different, resuscitation with HES was associated with higher 90-day mortality (RR, 1.14 [95% CI, 1.04-1.26]). Fluid resuscitation practice with HES as in the meta-analyzed studies is associated with increased an increase in AKI incidence, need of RRT, RBC transfusion, and 90-day mortality in patients with sepsis. Therefore, we favor the use of crystalloids over HES for resuscitation in patients with sepsis.

Background Intravenously infused hydroxyethyl starch (HES) can be found in urine, plasma and tissues. HES remaining in plasma and tissues is thought to increase the risk of clinical complications. HES solutions of lower molecular weight and substitution have been developed to increase urinary excretion and reduce plasma persistence. However, their effect on tissue uptake of HES has not been investigated in human subjects. Objective Our objective was to test the hypothesis that lower molecular weight and substitution decrease tissue uptake of HES. Data sources Computer searches were performed of MEDLINE; EMBASE; the Cochrane Library; meeting abstract databases in surgery, anaesthesiology and intensive care; ClinicalTrials.gov; and Google. Supplementary sources were reference lists and electronic tables of journal contents. No time period or language restrictions were imposed. Study Selection Clinical studies were eligible for inclusion in the meta-analysis, if data were reported both for cumulative urinary excretion of HES over 24 hours after infusion and for plasma HES concentration at 24 hours. Data Extraction Data were extracted on 24-hour urinary excretion of HES, 24-hour HES plasma concentration, plasma volume, HES molecular weight and substitution, study design, type and demographics of subjects, indication for fluid infusion, and HES infusion regimen. Tissue uptake of HES was computed as the difference between the infused dose and the sum of urinary excretion and residual plasma HES at 24 hours. Data Synthesis Twenty-five clinical studies totalling 287 subjects were included. Tissue uptake of low-molecular-weight HES (≤200 kD) was 42.3% (95% confidence interval [CI] 39.6, 45.0) compared with 24.6% (CI 17.8, 31.4) for high-molecular-weight HES (p<0.001). Similarly, tissue uptake of lower-substitution HES (≤0.5) was 42.4% (CI 39.5, 45.3) versus 26.6% (CI 19.6, 33.6) for higher-substitution HES (p<0.001). Among the three most often investigated single HES solutions, tissue uptake of 130/0.4 (42.6%; CI 35.0, 50.2) and HES 200/0.5 (43.3%; CI 39.4, 47.2) closely coincided, whereas uptake of HES 450/0.7 (22.2%; CI 14.8, 29.6) was lower (p = 0.001 and p<0.001, respectively). Conclusions This meta-analysis did not support the hypothesis that lower molecular weight and substitution decrease tissue uptake of HES. Further clinical studies of HES tissue uptake are needed.