Hydroxyethyl Starch 130/0.4 Binds to Neutrophils Impairing Their Chemotaxis through a Mac-1 Dependent Interaction.
Ontology highlight
ABSTRACT:
SUBMITTER: Trentini A
PROVIDER: S-EPMC6413098 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:It is heavily debated whether or not treatment with hydroxyethyl starch 130/0.4 contributes to the development of acute kidney failure in patients with severe sepsis. In the previous issue of Critical Care, Muller and colleagues report no association between initial resuscitation with hydroxyethyl starch 130/0.4 and renal impairment in a cohort of septic patients. Can we then consider hydroxyethyl starch 130/0.4 a safe intervention? The answer is no - observational data should be interpreted with caution and should mainly be used to identify risks, while safety must be assessed in randomised clinical trials. With these factors in mind, Muller's data associate the use of vasopressors with poor outcome, underlining the need for further randomised clinical trials to assess the potential harmful effects of common interventions in the critically ill.
| S-EPMC3681340 | biostudies-other
Project description:The turnover of Ringer´s solutions is greatly dependent on the physiological situation, such as the presence of dehydration or anaesthesia. The present study evaluates whether the kinetics is affected by previous infusion of colloid fluid.Ten male volunteers with a mean age of 22 years underwent three infusion experiments, on separate days and in random order. The experiments included 10 mL/kg of 6% hydroxyethyl starch 130/0.4 (Voluven™), 20 mL/kg of Ringer's acetate, and a combination of both, where Ringer´s was administered 75 minutes after the starch infusion ended. The kinetics of the volume expansion was analysed by non-linear least- squares regression, based on urinary excretion and serial measurement of blood haemoglobin concentration for up to 420 minutes.The mean volume of distribution of the starch was 3.12 L which agreed well with the plasma volume (3.14 L) estimated by anthropometry. The volume expansion following the infusion of starch showed monoexponential elimination kinetics with a half-life of two hours. Two interaction effects were found when Ringer´s acetate was infused after the starch. First, there was a higher tendency for Ringer´s acetate to distribute to a peripheral compartment at the expense of the plasma volume expansion. The translocated amount of Ringer´s was 70% higher when HES had been infused earlier. Second, the elimination half-life of Ringer´s acetate was five times longer when administered after the starch (88 versus 497 minutes, P<0.02).Starch promoted peripheral accumulation of the later infused Ringer´s acetate solution and markedly prolonged the elimination half-life.ClinicalTrials.gov: NCT01195025.
| S-EPMC4057308 | biostudies-literature
Project description:BackgroundBoth severe stenosis and completed occlusion in internal carotid artery or its distal branches have been considered the main reasons of cerebral hypoperfusion, which contributes to the washout disturbances of embolism in low perfusion territories distal to stenosis. An aggravated hypoperfusion state in certain brain region may induce ischemic stroke and further cognitive decline. However, the effective medication for cerebral hypoperfusion is largely unsettled.Methods/designBy using computed tomography perfusion (CTP) imaging, the trial will evaluate the effectiveness, safety and tolerability of hydroxyethyl starch (HES) 130/0.4 for patients with extra-/intra-cranial artery stenosis and cerebral hypoperfusion. From 5 neurological inpatient wards, 300 patients will be randomly recruited for administered routine medications plus intravascular volume therapies using the equal volume of HES 130/0.4 or 0.9% sodium chloride solution. Cerebral hypoperfusion state after 7-day intervention is the primary outcome measure. The secondary outcome measures includes, impaired renal function, abnormal heart function, hematological changes, neurological dysfunctions and cerebrovascular events in peri-intervention period and/or 3-month follow-up. The sample size will allow the detection of a two-sided 5% significance level between groups in the endpoint with a power of 80%.DiscussionThe trial would provide important efficacy and safety data on the intravascular administration of HES 130/0.4 in patients with unilateral cerebral hypoperfusion. The effects on kidney function, heart function, coagulation, neurological function and cerebralvascular events will be assessed.Trial registrationClinicalTrials.gov (Identifier: NCT01192581).
| S-EPMC3557161 | biostudies-literature
Project description:Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES.
| S-EPMC9558523 | biostudies-literature
Project description:There are limited data on the efficacy of early fluid resuscitation with third-generation hydroxyethyl starch (HES 130) in burn injury. Adverse effects of HES on survival and organ function have been reported.In this randomized, controlled, double-blind trial, 48 patients with severe burn injury were assigned to receive either lactated Ringer's solution plus 6% HES 130/0.4 in a ratio of 2:1 or lactated Ringer's solution with no colloid supplement for the first 72 hours. Primary outcome parameter was the group difference of administered total fluid from intensive care unit (ICU) admission up to day 3. Secondary outcomes included kidney and lung injury and failure, length of stay, and mortality.Three-day totals of administered resuscitation fluid (medians) were 21,190 mL in the lactated Ringer's group and 19,535 mL in the HES group (HES: -1,213 mL; P?=?0.39). Creatinine levels from day 1 to 3 (HES: +0.4 ?mol/L; 95% confidence interval (CI) -18.7 to 19.5; P?=?0.97) and urinary outputs from day 1 to 3 (HES: -58 mL; 95% CI -400 to 283; P?=?0.90) were not different. Six patients in each group developed acute respiratory distress syndrome (ARDS) (risk ratio 0.96; 95% CI 0.35 to 2.64; P?=?0.95). Length of ICU stay (HES vs. lactated Ringer's: 28 vs. 24 days; P?=?0.80) and length of hospital stay (31 vs. 29 days; P?=?0.57) were similar. Twenty-eight-day mortality was 4 patients in each group (risk ratio 0.96; 95% CI 0.27 to 4.45; P?=?0.95), and in-hospital mortality was 8 in the HES group vs. 5 patients in the lactated Ringer's group (hazard ratio 1.86; 95% CI 0.56 to 6.19; P?=?0.31).There was no evidence that early fluid resuscitation with balanced HES 130/0.4 (6%) in addition to lactated Ringer's solution would lead to a volume-sparing effect in severe burn injury. Together with the findings that early renal function, incidence of ARDS, length of stay, and mortality were not negatively influenced by HES in this setting, balanced HES 130/0.4 (6%) plus lactated Ringer's solution could not be considered superior to lactated Ringer's solution alone.ClinicalTrials.gov NCT01012648.
| S-EPMC4057504 | biostudies-literature
Project description:BackgroundIncreased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice.Methods6% HES 130/0.4 or a balanced electrolyte solution (20 ml/kg) was administered intravenously 1 h after cecal ligation and puncture (CLP) or LPS inhalation. Sham-treated animals receiving 6% HES 130/0.4 or the electrolyte solution served as controls. The thickness of the endovascular glycocalyx was visualized by intravital microscopy in lung (LPS inhalation model) or cremaster muscle (CLP model). Syndecan-1, hyaluronic acid, and heparanase levels were measured in blood samples. Vascular permeability in the lungs, liver, kidney, and brain was measured by Evans blue extravasation.ResultsBoth CLP induction and LPS inhalation resulted in increased vascular permeability in the lung, liver, kidney, and brain. 6% HES 130/0.4 infusion led to significantly reduced plasma levels of syndecan-1, heparanase, and hyaluronic acid, which was accompanied by a preservation of the glycocalyx thickness in postcapillary venules of the cremaster (0.78 ± 0.09 μm vs. 1.39 ± 0.10 μm) and lung capillaries (0.81 ± 0.09 μm vs. 1.49 ± 0.12 μm).ConclusionsThese data suggest that 6% HES 130/0.4 exerts protective effects on glycocalyx integrity and attenuates the increase of vascular permeability during systemic inflammation.
| S-EPMC5930811 | biostudies-literature
Project description:Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase-associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin-18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non-inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase-associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1-68 [0-996]) ng.ml-1 ) vs. albumin (5 (2-74 [0-1604]) ng.ml-1 ), although not non-inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin-18 concentrations were reduced, but interleukin-18 and kidney injury were again not non-inferior. Of 11 individual coagulation measures, platelet count and function, nine were non-inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid-induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non-inferiority. Long-term mortality and kidney function appeared similar between starch and albumin.
| S-EPMC9291605 | biostudies-literature
Project description:BackgroundThe safety of perioperative intravenous hydroxyethyl starch (HES) products, specifically HES 130/0.4, continues to be the source of much debate. The aim of this meta-analysis was to update the existing evidence and gain further insight into the clinical effects of HES 130/0.4 on postoperative outcomes for volume replacement therapy in surgical patients.MethodsMEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2020 for relevant randomized controlled trials (RCTs) on perioperative use of HES 130/0.4 in adult surgical patients. The primary outcome was postoperative mortality and secondary outcomes were the incidence of acute kidney injury (AKI) and requirement for renal replacement therapy (RRT). The analysis was performed using the random-effects method and the risk ratio (RR) with a 95% confidence interval (CI). We performed the risk-of-bias assessment of eligible studies and assessed the overall quality of evidence for each outcome.ResultsTwenty-five RCTs with 4111 participants were finally included. There were no statistical differences between HES 130/0.4 and other fluids in mortality at 30 days (RR 1.28, 95% CI 0.88 to 1.86, p = 0.20), the incidence of AKI (RR 1.23, 95% CI 0.99 to 1.53, p = 0.07), or requirement for RRT (RR 0.75, 95% CI 0.37 to 1.53, p = 0.43). Overall, there was a moderate certainty of evidence for all the outcomes. There was no subgroup difference related to the type of surgery (p = 0.17) in the incidence of AKI. As for the type of comparator fluids, however, there was a trend that was not statistically significant (p = 0.06) towards the increased incidence of AKI in the HES 130/0.4 group (RR 1.22, 95% CI 0.97 to 1.54) compared with the crystalloid group (RR 1.21, 95% CI 0.27 to 3.91). Subgroup analyses according to the type of surgery demonstrated consistent findings.ConclusionsThis systematic review and meta-analysis suggests that the use of HES 130/0.4 for volume replacement therapy compared with other fluids resulted in no significant difference in postoperative mortality or kidney dysfunction among surgical patients. Given the absent evidence of confirmed benefit and the potential trend of increased kidney injury, we cannot recommend the routine clinical use of HES 130/0.4 for volume replacement therapy in surgical patients from the perspective of benefit/risk profile. However, the results need to be interpreted with caution due to the limited sample size, and further well-powered RCTs are warranted.Trial registrationPROSPERO registry reference: CRD42020173058.
| S-EPMC8111748 | biostudies-literature
Project description:BackgroundThe application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine.MethodsAn isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups.ResultsCompared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces.ConclusionA vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small intestine.
| S-EPMC4370845 | biostudies-literature
Project description:BackgroundThe application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine.MethodsAn isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-topyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups.ResultsCompared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces.ConclusionA vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small intestine.
| S-EPMC4408121 | biostudies-literature