Efficacy Of Hydroxyethyl Starch Research Articles

PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study

BackgroundTrauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care.MethodsTETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1–β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT.DiscussionThis pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients.Trial registrationRegistered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

Cryopreservation of feline red blood cells in liquid nitrogen using glycerol and hydroxyethyl starch.

The objective of this study was to evaluate the techniques and short-term effects of cryopreservation of feline red blood cells (RBCs) in liquid nitrogen using glycerol or hydroxyethyl starch (HES) as a cryoprotectant. Feline RBCs were manually mixed with either 20% glycerol or 12.5% HES and frozen for 24 h in liquid nitrogen. The samples were thawed and glycerolized samples were manually washed. Success of the freeze/thaw process was determined by recovery rate of RBCs and evaluation of morphological changes using scanning electron microscopy (SEM). A unit of canine packed RBCs was also subjected to the same methodology to evaluate the cryopreservation handling technique. Feline RBCs preserved with 20% glycerol had a high recovery rate (94.23 ± 1.25%) immediately after thawing. However, the majority of the cells were lost during the washing process, with a final packed cell volume of <1%. A recovery rate was unable to be assessed for samples preserved with HES owing to the high viscosity of the mixture. SEM revealed significant morphological changes after glycerol was added to the feline RBCs. Although these morphological changes were partially reversed after thawing, the majority of the RBCs were lost during the washing process. Minimal morphological changes were noted in the HES sample. Similar results were noted with the canine RBCs. The described manual technique for cryopreservation using glycerol was not able to successfully preserve feline or canine RBCs. In the present study, it was difficult to make conclusions about the efficacy of HES. Further studies evaluating HES as a cryoprotectant are warranted.

Hydroxyethyl Starch- Friend or Foe?

Resuscitation with intravenous fluid therapy is considered a corner stone in the management of critically ill patients in most acute conditions. In daily practice, the assessment of individual thresholds in order to optimize cardiac preload and avoid hypovolemia or deleterious fluid overload remains a challenge. The choice of fluids for intravascular volume replacement has been debated for decades. More recently, this debate has focused not only on colloids versus crystalloids, but more specifically on the choice of colloid solutions. Hydroxyethyl starch (HES) solutions, developed as less-expensive alternatives to albumin, are commonly employed for volume resuscitation in the perioperative period as well as in ICU patients. However, lately, the resuscitation with HES has become controversial due to its adverse effect regarding impaired coagulation, renal insufficiency and mortality. Therefore, a narrative review of recent literature was undertaken to establish the current utility and efficacy of HES in clinical practice. Prospective randomized controlled trials published between January 2008 and March 2015 with measures of outcome/mortality and adverse effects of HES administration were included. This review aims at increasing awareness amongst anesthetists and critical care specialist about correct and careful fluid administration. Review Article

「ヒドロキシエチルスターチの安全性と有効性」に関して

「ヒドロキシエチルスターチの安全性と有効性」に関して

Comparison of low molecular weight hydroxyethyl starch and human albumin as priming solutions in children undergoing cardiac surgery

Human albumin is the conventional cardiopulmonary bypass circuit primer. However, it has high manufacturing costs. Crystalloid and colloid solutions have been developed as alternatives, including a new generation of non-ionic hydroxyethyl starch (HES). The efficacy of hydroxyethyl starch with a 130 molecular weight and substitution degree of 0.4 (hydroxyethyl starch 130/0.4) was compared with human albumin for use in cardiopulmonary bypass surgery in American Society of Anesthesiologists' grade I-II pediatric congenital heart disease patients. Efficacy was evaluated by comparing perioperative hemodynamic parameters, including plasma colloid osmotic pressure, renal function, blood loss, allogeneic blood volumes and plasma volume substitution. The hydroxyethyl starch group exhibited significantly higher preoperative colloid osmotic pressure (p<0.01) and significantly lower operative renal function and postoperative allogeneic blood volumes than the human albumin group. No significant differences were observed in serum creatinine, glucose, hematocrit or lactic acid levels (p>0.05). Our results indicate that hydroxyethyl starch may be a viable alternative to human albumin in pediatric patients undergoing relatively simple cardiopulmonary bypass surgeries.

ヒドロキシエチルスターチの安全性と有効性

ヒドロキシエチルスターチの安全性と有効性

Equivalent Efficacy of Hydroxyethyl Starch 130/0.4 and Human Serum Albumin

Equivalent Efficacy of Hydroxyethyl Starch 130/0.4 and Human Serum Albumin

Crystalloids vs. colloids: KO at the twelfth round?

Expanded abstractCitationMyburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group: Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012, 367:1901-1911.BackgroundThe safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported.MethodsWe randomly assigned 7,000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kDa and a molar substitution ratio of 0.4 (130/0.4, Voluven; Fresenius Kabi AG, Bad Homburg vor der Höhe, Germany) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal replacement therapy.ObjectiveWe conducted a large-scale randomized controlled trial to evaluate the safety and efficacy of 6% HES (130/0.4) in 0.9% saline as compared with 0.9% saline alone for fluid resuscitation in a heterogeneous population of adult patients in the ICU.DesignThe Crystalloid versus Hydroxyethyl Starch Trial (CHEST) was an investigator-initiated, multicenter, prospective, blinded, parallel-group, randomized controlled trial.SettingThe study was set at 32 hospitals in Australia and New Zealand.SubjectsThe subjects were adult patients (>18 years) who were admitted to the ICU and who required intravenous fluid above maintenance requirements determined by the treating clinician and supported by at least one objective physiological criterion. Patients were excluded if they received more than 1 L of 6% HES within 24 hours of screening or had one of the following: dialysis-dependent or impending dialysis renal failure, computed tomography evidence of non-traumatic intracranial hemorrhage (ICH) or severe traumatic ICH, creatinine of more than 3.9 mg/dL or urine output of less than 10 mL/hour for 12 hours, sodium of more than 160 meq/L, or chloride of more than 130 meq/L. Also excluded were females of childbearing age (unless proven not to be pregnant) and patients who had post-cardiac surgery status, liver transplant, or burns and those whose death was judged to be imminent or whose underlying disease process indicated a life expectancy of less than 90 days.InterventionIf fluid was deemed necessary by the treating clinician by the parameters described above, the patient received 'study' fluid with identical packaging and appearance. The fluid was either 6% HES (130/0.4) in saline (Voluven) or 0.9% saline.OutcomesThe primary outcome was death within 90 days. Secondary outcomes were acute kidney injury (AKI) and failure and treatment with renal replacement therapy.ResultsA total of 597 (18.0%) of 3,315 patients in the HES group and 566 (17.0%) of 3,336 in the saline group died (relative risk (RR) in the HES group 1.06, 95% confidence interval (CI) 0.96 to 1.18; P = 0.26). There was no significant difference in mortality in six predefined subgroups. AKI - defined by RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria - occurred in few patients receiving HES (34.6%) compared with saline (38%) (RR 0.91, 95% CI 0.85 to 0.97). However, renal replacement therapy was used in 235 (7.0%) of 3,352 patients in the HES group and 196 (5.8%) of 3,375 in the saline group (RR 1.21, 95% CI 1.00 to 1.45; P = 0.04). HES was significantly associated with more adverse events (5.3% versus 2.8%; P <0.001).ConclusionsIn patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with6% HES (130/0.4) or saline. However, despite a lower overall rate of AKI, more patients who received resuscitation with HES were given renal replacement therapy. (The study was supported by the National Health and Medical Research Council of Australia; the Ministry of Health, New South Wales Government, Australia; and Fresenius Kabi; and by a Practitioner Fellowship from the National Health and Medical Research Council of Australia (to Drs Myburgh and Bellomo), by a Principal Research Fellowship from the National Health and Medical Research Council of Australia (to Dr Cass), and by a Practitioner Fellowship from the Medical Research Foundation of the Royal Perth Hospital (to Dr Webb); CHEST ClinicalTrials.gov number NCT00935168.)

Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: how to guide fluid therapy?

We argue that assessing the hemodynamic effi cacy of hydroxyethyl starch (HES) versus NaCl in patients with severe sepsis requires an algorithm to direct the timing and amount of fl uid resuscitation. Such an algorithm may include hemodynamic fl ow parameters. In a recent issue of Critical Care, Guidet and colleagues [1] reported that a smaller amount of 6% HES 130/0.4 versus 0.9% NaCl was required to achieve hemodynamic stability (HDS) during the initial phase of fl uid resuscitation in patients with severe sepsis. Th e target parameters indicating HDS included central venous pressure (CVP) (8 to 12 mm Hg), a poor indicator of fl uid responsiveness [2], and a large urine output (>2 mL/kg per hour), and therefore pose a risk of over-infusion. Other authors have reported that over-infusion, elevated CVP, and excessive fl uid resuscitation with HES are associated with increased mortality in patients with sepsis [3,4]. In contrast, after initial HDS was achieved, no such target parameters were defi ned, and so the cumulative volumes of study drug infused over the course of four consecutive days in the intensive care unit (ICU) were similar for the HES (2,615 mL) and NaCl (2,788 mL) groups. No diff erences in mortality, hospital length of stay, or kidney function were found. Th is study may be showing only that, in the absence of an algorithm to guide fl uid resuscitation, intensivists use an unvarying amount of fl uids, but it is impossible to know whether these fl uids were, in fact, indicated. In patients undergoing major abdominal surgery, hemodynamic algorithms that guide the timing and amount of fl uid administration have helped determine the clinical effi cacy of fl uid therapy [5]. Th e negative results reported by Guidet and colleagues suggest that hemodynamic algorithms for patients with sepsis are urgently required to accurately compare the hemodynamic effi cacy, safety, and outcome of HES versus NaCl fl uid replacement.

Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care

BackgroundThe safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported.MethodsWe randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy.ResultsA total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (4.6% vs. 3.3%, P=0.006).ConclusionsIn patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.)

Hydroxyethyl starch 130/0.4 versus modified succinylated gelatin for volume expansion in pediatric cardiac surgery patients: the effects on perioperative bleeding and transfusion needs

SUMMARYVolume therapy and maintenance of stable hemodynamics is crucial in children undergoing cardiac surgery on cardiopulmonary bypass (CPB). The clinical use of hydroxyethyl starch (HES) 130/0.4 is limited by the possibility of adverse hemostatic effects which could potentially increase the risk of perioperative bleeding and transfusion requirements. We conducted this study to evaluate the safety and efficacy of HES in comparison with modified succinylated gelatin (MSG). Forty‐nine children were randomly assigned to receive either HES (n = 28) or MSG (n = 21) during the pre‐bypass period. Coagulation was assessed with thromboelastography (TEG) and the transfusion requirements up to the first postoperative day were documented. Both groups were comparable with respect to age, weight, CPB duration as well as hematological and biochemical laboratory investigations. TEG parameters were not deranged up to the first postoperative period in either group and there was a trend of reduced blood loss and transfusion requirements in HES groups although there was no statistically significant difference. Our study shows that HES 130/0.4 is safe and effective for volume replacement in pediatric cardiac surgery patients.

Update on transfusion solutions during surgery: review of hydroxyethyl starches 130/0.4.

ObjectivesRestoration of circulation is crucial in the surgical patient management. Colloids and crystalloids are widely used for blood volume therapy. We reviewed recent trials to evaluate efficacy and safety of hydroxyethyl starch (HES) 130/0.4 during surgery.Material and methodsA subjective, not systematic, review of literature was performed. Papers were searched to answer questions about efficacy of HES, its impact on coagulation and inflammation and its effects on pulmonary mechanics and renal function.ConclusionsHES 130/0.4 is effective for volume therapy and is less expensive than human albumin. Its effects on coagulation and renal function are manageable; it may ameliorate pulmonary permeability and reduce inflammation.

Efficacy of hydroxyethyl starch and haemaccel for the treatment of severe ovarian hyperstimulation syndrome

The ovarian hyperstimulation syndrome (OHSS) is the most serious complication of ovarian stimulation. It has been estimated that the incidence of severe OHSS in patients undergoing ovarian stimulation for IVF is about 2% (1). Only supportive rather than curative therapy is available, and there are no clinical characteristics that are completely reliable in predicting OHSS. In addition, none of the strategies aimed at prevention are ideal; at best, they may slightly reduce the incidence of OHSS, but at a high emotional and financial cost.

Effect of Hydroxyethyl Starch on Alveolar Flooding in Acute Lung Injury in Dogs

The efficacy of hydroxyethyl starch (HES) in limiting alveolar flooding after acute lung injury was investigated using ethchlorvynol (ECV)-induced low pressure pulmonary edema in dogs. Harvested autologous plasma (PL) (control, n = 8) or 6% HES (n = 8) was infused (25 ml/kg) along with packed cells to result in an isovolemic, normochromic preparation before the administration of ECV. Extravascular thermal volume significantly increased after ECV administration in both groups of animals (6.6 to 13.4 ml/kg in PL, 6.5 to 15.0 ml/kg in HES). Systemic arterial PO2 decreased from 216 +/- 4 to 113 +/- 20 mm Hg, and venous admixture increased from 2.8 to 12.8% in the PL group but was not significantly changed in the HES group (219 +/- 5 to 203 +/- 8 mm Hg, and 2.9 to 4.4%, respectively). Epithelial lining fluid volumes after ECV administration increased in both groups but were elevated in the PL group to a greater extent than in the HES group (13.5 ml in HES versus 24.8 ml in PL). In the HES group there appeared to be no difference in the ability of plasma proteins to move across the alveolar epithelium. These results suggest that HES attenuates the flooding of the alveolar space and the resulting alterations in gas exchange during the development of low pressure pulmonary edema. The replacement of the plasma proteins with HES and the apparent inability of HES to cross the epithelial barrier into the alveoli may account for the protective effect of HES in these experiments.