High Molecular Weight Hydroxyethyl Starch Research Articles

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch.

Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.

Resuscitation Fluids in Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials.

The aim of this study was to assess the efficacy and safety of various resuscitation fluids in septic shock by adopting a network meta-analysis (NMA). Randomized controlled trials (RCTs) comparing resuscitation fluids in septic shock were carried out by retrieving electronic databases. NMAs of 28-day mortality, 90-day mortality, incidence of acute kidney injury (AKI), and the need for renal replacement therapy (RRT) were conducted using the STATA 15.0 software. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the optimal resuscitation fluid. Inconsistencies were evaluated by node-splitting analysis and a loop-specific approach. Furthermore, publication bias was analyzed by funnel plots. A total of 13 RCTs were enrolled in the analysis. The NMA results revealed that no significant differences were detected in the outcomes of 28-day mortality and 90-day mortality among various resuscitation fluids. The SUCRAs (the first indicates the best) of 28-day mortality showed that the hypertonic sodium chloride/hydroxyethyl starch 40 solution ranked the highest (93.8%), followed by the balanced solution (BS) (69.6%), and albumin (61.9%). On the other hand, the SUCRAs of 90-day mortality revealed that gelatin (GEL) ranked the highest (75.1%), followed by BS (55.1%), and NS (52.4%). The NMA results of AKI demonstrated that high-molecular-weight hydroxyethyl starch (H-HES) was associated with increased risk of AKI in comparison with GEL, BS, and L-HES. The SUCRAs of AKI showed that GEL ranked the highest (74.4%), followed by NS (64.9%), and BS (58.3%). In addition, the NMA results of RRT revealed that H-HES was associated with an increased need for RRT in comparison with BS and NS, and L-HES was associated with increased need of RRT in comparison with BS. The SUCRAs of RRT revealed that NS ranked the highest (91.6%), followed by BS (74.4%) and L-HES (36.1%). No significant inconsistencies were shown by the node-splitting analysis and no publication bias was demonstrated in the funnel plots. In conclusion, BS was determined as the preferred resuscitation fluid for septic shock. Moreover, the use of GEL requires further evaluation. H-HES was associated with a significant risk of AKI and RRT, whereas L-HES with an increased need for RRT compared with BS. Thus, both resuscitation fluids should be avoided for septic shock.

Successful granulocyte apheresis using medium molecular weight hydroxyethyl starch.

Granulocyte transfusion (GTX) is a therapeutic option for severe bacterial or fungal infection in patients with sustained neutropenia after chemotherapy or stem cell transplantation. However, high molecular weight hydroxyethyl starch (HES), which has been used for selective sedimentation of red blood cells during apheresis, is not easily available in many countries including Japan. In this study, we evaluated the efficiency of granulocyte collection using medium molecular weight HES (130kDa) in combination with the Spectra Optia apheresis system. Apheresis was performed for 2 consecutive days from seven donors and the mean total neutrophil yield from the first and second apheresis was 5.27 ± 3.10 × 1010 and 2.91 ± 2.92 × 1010, respectively. Infusion of concentrates from the first apheresis resulted in a significant neutrophil count increase and concentrates from the second apheresis were enough for maintenance of the neutrophil counts in all the recipients. Although the number of cases is limited, our results clearly show that sufficient number of granulocytes can be harvested by using medium molecular weight HES and this strategy is a safe and effective clinical practice in countries where high molecular weight HES is not available.

Intra-operative hydroxyethyl starch is not associated with post-craniotomy hemorrhage.

BackgroundIntraoperative intravascular volume expansion with hydroxyethyl starch-based colloids is thought to be associated with an increased risk of post-craniotomy hemorrhage. Evidence for this association is limited. Associations between resuscitation with hydroxyethyl starch and risk of repeat craniotomy for hematoma evacuation were examined.MethodsUsing a retrospective cohort of neurosurgical patients at Duke University Medical Center between March 2005 and March 2012, patient characteristics were compared between those who developed post-craniotomy hemorrhage and those who did not.ResultsA total of 4,109 craniotomy procedures were analyzed with 61 patients having repeat craniotomy for post-operative hemorrhage (1.5%). The rate of reoperation in the group receiving 6% High Molecular Weight Hydroxyethyl Starch (Hextend®) was 2.6 vs. 1.3% for patients that did not receive hetastarch (P = 0.13). The reoperation rate for those receiving 6% hydroxyethyl Starch 130/0.4 (Voluven®) was 1.4 vs. 1.6% in patients not receiving Voluven (P = 0.85).ConclusionsIn this retrospective cohort, intra-operative hydroxyethyl starch was not associated with an increased risk of post-craniotomy hemorrhage.

Perioperative clinical and economic outcomes associated with replacing first-generation high molecular weight hydroxyethyl starch (Hextend®) with low molecular weight hydroxyethyl starch (Voluven®) at a large medical center

BackgroundSeveral plasma volume expander alternatives exist to enhance intravascular volume status in patients undergoing surgery. The optimal intravascular volume expander in the perioperative setting is currently unknown. Low molecular weight hetastarch, Voluven® (130/0.4), may have a better safety profile than high molecular weight hetastarch, Hextend® (450/0.7). We examined the clinical and cost outcomes of converting from Hextend® to Voluven® in a large tertiary medical center.MethodsUsing a large electronic database, we retrospectively compared two different time periods (2009 and 2010) where the availability of semisynthetic colloids changed. Perioperative and postoperative outcomes including the use of red blood cells (RBC), platelets and coagulation factors, length of stay in the postoperative acute care unit (PACU), intensive care unit and hospital, as well as 30-day and 1-year mortality were compared. In addition, direct acquisition costs of all intraoperative and PACU colloids and crystalloid use were determined.ResultsA total of 4,888 adult subjects were compared of which 1,878 received Hextend® (pre-conversion) and 2,759 received Voluven® (post-conversion) during two separate 7-month periods within 1 year apart, with the remainder receiving Plasmanate. The patients were similar in terms of patient demographics, preoperative comorbidities, ASA status, emergency surgery, types of surgery, intraoperative, and PACU times. In unadjusted outcomes, patients in the Hextend® group received more lactated Ringer’s than in the Voluven® group (2,220 + 1,312 vs. 1,946 ± 1,097 ml; P < 0.0001). The use of albumin (Plasmanate) was reduced from 10.5% of patients to 1.1% when Voluven® was substituted for Hextend®. Unadjusted outcomes were similar in each group including hospital LOS, percent change from baseline creatinine and receipt of intraoperative and PACU blood product administration. However, overall unadjusted total fluid costs were greater in the Voluven® compared to Hextend® group ($116.7 compared to $59.3; P < 0.001).ConclusionsConversion from Hextend® to Voluven® in the perioperative period resulted in decreased albumin use and was not associated with changes in clinical outcomes and short- and long-term mortality. The conversion was associated with decreases in crystalloid use and an increase in colloid use and hence IV fluid acquisition costs in the Voluven® group.

The effect of colloid formulation on colloid osmotic pressure in horses with naturally occurring gastrointestinal disease.

BackgroundNaturally occurring gastrointestinal disease is an important cause of acute hypoproteinemia in adult horses and hydroxyethyl starch colloid fluid treatment is a component of supportive care in these cases to improve plasma volume and maintain colloid osmotic pressure (COP). The objectives of the present study were to compare 2 formulations of high molecular weight hydroxyethyl starch and their relative effect on COP, acid-base status, and survival of horses with acute hypoproteinemia secondary to gastrointestinal disease.MethodsTwenty adult horses, ≥ 1 year of age, were prospectively enrolled, with informed client consent, if they developed acute hypoproteinemia, defined as a plasma total protein <5.0 g/dL or albumin <2.2 g/dL during hospitalization while undergoing treatment for gastrointestinal disease. Horses were randomly assigned to receive a rapid infusion of either 6% hydroxyethyl starch in 0.9% saline or 6% hydroxyethyl starch in lactated ringers solution at a dose of 10ml/kg. Venous blood gas analysis, COP, and PCV were evaluated before and after colloid administration.ResultsFor both groups, average COP prior to treatment was 11.0 mmHg (9.7 – 12.2 mmHg) and post colloid treatment was 13.2 mmHg (12.0 -14.7 mmHg) [Normal range 18 – 22 mmHg]. COP was significantly increased with colloid treatment (p<0.001) but this increase was not significantly different between treatment groups. Venous pH did not change significantly with treatment. Twelve horses survived to hospital discharge and survival did not differ significantly between treatment groups.ConclusionsPost-treatment COP improved approximately 20% regardless of the formulation used, however, values did not reach the normal range of COP observed in healthy horses. Acid-base parameters were not significantly impacted by either treatment. Further study is needed to determine how these two products compare with regards to other outcome measures. Evaluation of the relative effects of colloid formulation in horses with clinical disease is a future area of interest.

Cardiovascular, Colloid Osmotic Pressure, and Hemostatic Effects of 2 Formulations of Hydroxyethyl Starch in Healthy Horses

BackgroundLower molecular weight and molar substitution formulations of hydroxyethyl starch (HES) solutions might maximize cardiovascular function and colloid osmotic pressure (COP) and minimize adverse effects on coagulation.Hypothesis/ObjectivesTo compare effects of 1 low and 1 high molecular weight and molar substitution HES solution on cardiovascular variables, COP, and hemostasis in normal horses.AnimalsEight healthy adult horses.MethodsRandomized, crossover designed study: 10 mL/kg bolus of 6% HES (600/0.75) (hetastarch) (HS), 6% HES (130/0.4) tetrastarch (TS), and 0.9% NaCl (NS). Variables recorded included central venous pressure (CVP), noninvasive arterial blood pressure, packed cell volume (PCV), COP, and automated platelet analysis (CT).ResultsCentral venous pressure was increased for 8 hours after all treatment (baseline = 8.4 ± 3.8; 8 hours = 10.3 ± 3.5 cm H2O; P < .001). HS and TS produced an increase in systolic arterial pressure (HS = 109.1 ± 11.9; TS = 109.5 ± 10.9 mmHg) and mean arterial pressure (HS = 80.4 ± 13.0; TS = 82.3 ± 10.1 mmHg) compared to NS (SAP = 103.2 ± 13.2 [P = .023]; MAP = 74.2 ± 11.4 mmHg [P = .048]). PCV decreased transiently with HS (baseline = 37.1 ± 4.4%; 1.5 hours = 31.6 ± 3.9%) and TS (baseline = 38.4 ± 3.9%; 1.5 hours = 32.2 ± 3.3%), but not NS (P = .007). COP was greater with HS (1 hour; 24.0 ± 2.1 mmHg) and TS (8 hours; 25.9 ± 2.1 mmHg) than NS (1 hour = 20.8 ± 2.6; 8 hours = 22.9 ± 3.1 mmHg; P < .001). CT was greater at 8 (HS = 178.6 ± 36.9; TS = 121.9 ± 33.3; NS = 108.3 ± 23.6 seconds) and 24 hours (HS = 174.2 ± 41.7; TS = 100.8 ± 26.0; NS = 118.7 ± 38.7 seconds; P < .001) in horses receiving HS than TS or NS.Conclusion and Clinical ImportanceBoth TS and HS resulted in more effective volume expansion and arterial pressure support than NS. TS produced a more sustained effect on COP with shorter duration of adverse effects on platelet function than HS.

Intraoperative Hydroxyethyl Starch 70/0.5 Is Not Related to Acute Kidney Injury in Surgical Patients

Although high-molecular-weight hydroxyethyl starch (HES) has been reported to cause acute kidney injury (AKI), it is not clear whether low-molecular-weight HES (6% HES 70/0.5) can be a risk for AKI or not. We hypothesized that intraoperative 6% HES 70/0.5 administration is not related to postoperative AKI. A retrospective chart review was conducted to identify adult surgical patients with intraoperative blood loss of ≥1000 mL at a university hospital. AKI was defined as >50% increase in serum creatinine from the preoperative value within 7 days after the operation according to the RIFLE (Risk, Injury, Failure, Loss, or End-stage kidney disease) criteria. We compared the incidence of AKI between patients with and without intraoperative HES administration. Multivariate logistic regression analysis and propensity score matching were also conducted to elucidate the impact of HES on postoperative AKI. Among 14,332 surgical cases, 846 patients met the inclusion criteria. In patients given HES (a median dose of 1000 mL, n = 635), 12.9% developed AKI, compared with 16.6% (-3.7%, -1.7% to 9.1%) in patients without HES (n = 211). Multivariate logistic regression analysis showed that HES was not an independent risk factor for postoperative AKI (odds ratio: 0.76, 0.48-1.21). Using the propensity score, 179 pairs were matched. In patients with HES, 12.3% developed AKI, compared with 14.5% in patients without HES (-2.2%, -4.9% to 9.3%). In this uncontrolled retrospective chart review, intraoperative 6% HES 70/0.5 in a low dose was not related to postoperative AKI in patients with major intraoperative blood loss. Randomized controlled trials are warranted to further evaluate the safety and efficacy of low-molecular-weight HES.

Impact of the mobilization regimen and the harvesting technique on the granulocyte yield in healthy donors for granulocyte transfusion therapy

Granulocyte mobilization and harvesting, the two major phases of granulocyte collection, have not been standardized. The data on 123 granulocyte collections were retrospectively investigated for the effect of the mobilization regimen and the harvesting technique. After a single subcutaneous dose (600 µg) of granulocyte-colony-stimulating factor (G-CSF) with (n = 68) or without (n = 40) 8 mg of orally administered dexamethasone, 108 granulocyte donors underwent granulocyte collections. Moreover, 15 peripheral blood stem cell (PBSC) donors who had received 400 µg/m2 or 10 µg/kg G-CSF for 5 days underwent granulocyte collections on the day after the last PBSC collections (PBSC-GTX donors). Granulocyte harvesting was performed by leukapheresis with (n = 108) or without (n = 15) using high-molecular-weight hydroxyethyl starch (HES). Granulocyte donors who received mobilization with G-CSF plus dexamethasone produced significantly higher granulocyte yields than those who received G-CSF alone (7.2 × 10(10) ± 2.0 × 10(10) vs. 5.7 × 10(10) ± 1.7 × 10(10) , p = 0.006). PBSC-GTX donors produced a remarkably high granulocyte yield (9.7 × 10(10) ± 2.3 × 10(10) ). The use of HES was associated with better granulocyte collection efficiency (42 ± 7.8% vs. 10 ± 9.1%, p < 0.0001). G-CSF plus dexamethasone produces higher granulocyte yields than G-CSF alone. Granulocyte collection from PBSC donors appears to be a rational strategy, since it produces high granulocyte yields when the related patients are at a high risk for infection and reduces difficulties in finding granulocyte donors. HES should be used in apheresis procedures.

Intravenous infusion of Hb‐vesicles (artificial oxygen carriers) after repetitive blood exchange with a series of plasma expanders (water‐soluble biopolymers) in a rat model

Hemoglobin‐vesicles (HbV) are artificial oxygen carriers developed for use as a transfusion alternative. The extremely high concentration of the HbV suspension (solutes, ca. 16 g/dl; volume fraction, ca. 40 vol%) provides a sufficient oxygen carrying capacity to maintain oxygen metabolism. A suspension of HbV has no colloid osmotic pressure (COP). Consequently, a combination of a plasma expander is necessary for a massive dose of HbV. Clinically available plasma expanders include hydroxyethyl starch (HES), modified gelatin (MFG), or recombinant human serum albumin (rHSA). Our previous studies confirmed that these water‐soluble biopolymers interact with HbV to induce flocculation of HbV reversibly by depletion interaction, especially with MFG and high molecular weight HES. It remains unknown whether such flocculate formation in blood might affect animal's hemodynamics. Using a rat model, we tested infusion of a series of plasma expander to maintain the blood volume (level of blood exchange led to 60%) at repeated hemorrhages and the subsequent infusion of HbV (20 ml/kg, 36% of blood volume). All rats survived for 4 hr after the infusion of HbV; hemodynamic and respiratory functions were preserved, indicating that the flocculation does not induce capillary embolism. Blood exchange with rHSA and subsequent infusion of HbV showed more stable systemic parameters because of the longer retention of rHSA in blood than other plasma substitutes, indicating that rHSA is suitable for combination with HbV in this experimental model. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial

BackgroundBy tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis.Methods/DesignThe 6S trial will randomise 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%.DiscussionThe 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed.Trial RegistrationClinicalTrials.gov: NCT00962156

Carbon monoxide releasing molecule-2 enhances coagulation and attenuates fibrinolysis by two mechanisms: insights gained with colloid dilution

Carbon monoxide releasing molecule-2 (CORM-2, tricarbonyldichlororuthenium (II) dimer) enhances coagulation and attenuates vulnerability to fibrinolysis. Our goal was to further define the CORM-2-mediated mechanisms using colloids with known effects on coagulation/fibrinolytic proteins. Plasma diluted 0 or 30% with 0.9% NaCl, 5% human albumin, low molecular weight hydroxyethyl starch (130 kDa) or high molecular weight hydroxyethyl starch (450 kDa) was exposed to 0 or 100 μmol/l CORM-2 before activation with tissue factor (n = 8 per condition). A second identically diluted series of experiments were performed with the addition of tissue-type plasminogen activator. Thrombelastographic data were collected until clot strength stabilized or clot lysis occurred. Dilution resulted in fluid-specific decreases in velocity of clot growth, strength and clot growth time with progressive increases in macromolecule size. CORM-2 exposure significantly increased the velocity of clot formation and strength (thin fibrin fiber promoting), but not clot growth time, under all conditions. Fibrinolysis was enhanced to the greatest extent by hydroxyethyl starch (antiα2-antiplasmin effect), and CORM-2 addition attenuated fibrinolysis in all conditions (α2-antiplasmin enhancement). CORM-2 exposure attenuated the decrease in coagulation kinetics mediated by hemodilution by two different mechanisms based on kinetic profile differences between the diluents tested. Further laboratory-based investigation is warranted to further define the molecular mechanisms responsible for CORM-2-mediated effects on coagulation and fibrinolysis.

Increased viscosity of hemoglobin-based oxygen carriers retards NO-binding when perfused through narrow gas-permeable tubes

Increased fluid viscosity of a solution of hemoglobin-based oxygen carriers (HBOCs) reduces vasoconstrictive effects because increased shear stress on the vascular wall enhances the production of vasorelaxation factors such as NO. Nevertheless, on a microcirculatory level, it remains unclear how viscosity affects the reaction of HBOCs and NO. In this study, different HBOCs were perfused through narrow gas-permeable tubes (25 μm inner diameter at 1 mm/s centerline velocity; hemoglobin concentration [Hb] = 5 g/dL). The reaction was examined microscopically based on the Hb visible-light absorption spectrum. When immersed in a NO atmosphere, the NO-binding of deoxygenated Hb solution (viscosity, 1.1 cP at 1000 s − 1 ) in the tube occurred about twice as rapidly as that of red blood cells (RBCs): 1.6 cP. Binding was reduced by PEGylation (PEG-Hb, 7.7 cP), by addition of a high molecular weight hydroxyethyl starch (HES) (2.8 cP), and by encapsulation to form Hb-vesicles (HbVs, 1.5 cP; particle size 279 nm). However, the reduction was not as great as that shown for RBCs. A mixture of HbVs and HES (6.2 cP) showed almost identical NO-binding to that of RBCs. Higher viscosity and particle size might reduce lateral diffusion when particles are flowing. The HbVs with HES showed the slowest NO-binding. Furthermore, Hb encapsulation and PEGylation, but not HES-addition, tended to retard CO-binding. Increased viscosity reportedly enhances production of endothelium NO. In addition, our results show that the increased viscosity also inhibits the reaction with NO. Each effect might mitigate vasoconstriction.

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system. Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest specific vasodilators [corrected] under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention. The online version of this article (doi:10.1007/s00134-009-1678-y) contains supplementary material, which is available to authorized users.

Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven®)

BackgroundA range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven®), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood. MethodsClot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130–670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulphonic acid) buffer; or by reducing temperature to 32°C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits. ResultsHaemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES. ConclusionsEfficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia.

Coagulation and biochemical effects of balanced salt‐based high molecular weight vs saline‐based low molecular weight hydroxyethyl starch solutions during the anhepatic period of liver transplantation

The anhepatic period of liver transplantation is generally marked by a decrease in preload, and the infusion of hydroxyethyl starch (HES) solution is often an effective way to restore volume deficits in non-anaemic patients. However, the infusion of even limited amounts of HES solution during the anhepatic period may result in a worsening coagulopathy. Moreover, lactate-containing HES solution may cause some degree of biochemical derangements in compromised recipients. Therefore, we compared two different types of HES solutions: a balanced salt-based high molecular weight HES solution (670/0.75; high MW group) and a saline-based low molecular weight HES solution (130/0.4; low MW group) with respect to coagulation and biochemical profiles. First, in an in vitro study (n = 48), thromboelastography was performed to determine the effects of two HES solutions on coagulation after diluting (11%) the recipient's blood sample with each HES solution. Second, in an in vivo study, 500 ml of one of the two 6% HES solution was administered to 74 recipients (n = 37, each group) for 30 min after starting the anhepatic period. The coagulation profiles, including thromboelastography, and biochemical profiles were measured before and 30 min after the end of infusion. Less impairment in the thromboelastography profiles and aPTT was observed in the high MW group. A higher calcium concentration and less reduction in platelet count were noted in the high MW group, but lactate accumulation was greater. In conclusion, a balanced salt-based high molecular weight HES solution is a more effective volume replacement during the anhepatic period of liver transplantation with respect to coagulation than a saline-based low molecular weight HES solution, although lactate accumulation is a possible concern.

A Comparative Coagulopathic Study for Treatment of Vasospasm by Using Low- and High-molecular Weight Hydroxyethyl Starches.

High-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than does low-molecular-weight HES. We compared the effects of low- and high-molecular-weight HES for the treatment of vasospasm and investigated the dose relationship with each other. Retrospectively, in a series of consecutive 102 patients with subarachnoid hemorrhage (SAH), 35 patients developed clinical symptoms of vasospasm of these fourteen patients were treated with low-molecular-weight HES for volume expansion while the other 21 received high-molecular-weight HES as continuous intravenous infusion. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level, and platelet count were all measured prior to initiation, during treatment and after termination of therapy for symptomatic vasospasm. The total dose of HES ranged from 5 L to 14 L and median infusion duration was 10 days. A more pronounced PTT prolongation was observed in high-molecular-weight HES group compared with low-molecular-weight HES group. No other coagulation parameters were altered. Dosage (=duration) shows a positive correlation with PTT. Clinically, significant bleeding episodes were noted in four patients who received high-molecular-weight HES. Coagulopathy was developed in direct proportion to molecular weight of starch and dosages. We propose the extreme caution in the administration of HES solution for the vasospasm treatment.

The effects of high molecular weight hydroxyethyl starch solutions on platelets.

Physicochemical characteristics of hydroxyethyl starch (HES) molecules determine their side effects on hemostasis. Our aim in the present experiments was to test the antiplatelet effect of novel high molecular weight HES. Citrated whole blood was hemodiluted in vitro (0% and 20%) with either HES 550 (Hextend), HES 600 (6%Hetastarch-Baxter), HES 200 (Elohäst), or the solvent of Hextend in its commercially available solution. The availability of glycoprotein IIb-IIIa was assessed on nonstimulated and on agonist-induced platelets using flow cytometry. Glycoprotein IIb-IIIa availability increased significantly after hemodilution with Hextend and its solvent by 23% and 24%, respectively, but decreased in the presence of 6% Hetastarch-Baxter and Elohäst by 18% and 15%, respectively, with no significant difference between the latter two colloids. This study shows that Hextend does not inhibit platelet function as anticipated by its high molecular weight and degree of substitution. The unexpected platelet stimulating effect of Hextend is unique among the currently available HES preparations and may, at least in part, be induced by its solvent containing calcium chloride dihydrate (2.5 mmol/L). The platelet-inhibiting effect of 6%Hetastarch-Baxter was not significantly different from that of medium molecular weight HES 200.

Effects of high molecular weight hydroxyethyl starch solutions on platelets

Effects of high molecular weight hydroxyethyl starch solutions on platelets

Hyperaggregating effect of hydroxyethyl starch components and University of Wisconsin solution on human red blood cells: a risk of impaired graft perfusion in organ procurement?

The standard preservation solution used during organ procurement and preservation of most organs is the University of Wisconsin (UW) solution. Despite its superiority over other cold storage solutions, the inclusion of hydroxyethyl starch (HES) as one of the components of the UW solution has been both advocated and denied. This study determined whether HES had any effect on red blood cell (RBC) aggregability and correlated aggregation parameters with HES molecular weight. Human RBC aggregability and deformability were investigated in vitro, at 4 degrees C, with a laser-assisted optical rotation cell analyzer. The study of RBC aggregation in a binary HES-HES system gave an indication about the nature of HES-RBCs interactions. Bright field microscopy and atomic force microscopy were used to morphologically characterize the aggregates size and form. High molecular weight HES and UW solution had a potent hyperaggregating effect; low molecular weight HES had a hypoaggregating effect on RBC. RBC aggregates were of large size and their resistance to dissociation by flow-induced shear stress was high. The authors' in vitro experiments conclusively showed that the physiologic function of RBCs to form aggregates is significantly affected in the presence of HES. The use of high molecular weight HES in UW solution accounts for extended and accelerated aggregation of erythrocytes that may result in stasis of blood and incomplete washout of donor organs before transplantation.