Molecular Weight Hydroxyethyl Starch Solution Research Articles

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.

Protective roles of hydroxyethyl starch 130/0.4 in intestinal inflammatory response and survival in rats challenged with polymicrobial sepsis

BackgroundThe gut is considered an important target organ of injury after severe insult such as sepsis, trauma and shock. Hydroxyethyl starch (HES) 130/0.4 has been developed to improve the pharmacokinetics of current medium molecular weight HES solutions. We investigated the protective effects of HES 130/0.4 on intestinal inflammatory response and survival in a rat polymicrobial sepsis model induced by cecal ligation and puncture. MethodsAnimals were treated with HES 130/0.4 or saline at 4, 10, 16 or 22 h after the induction of sepsis or sham-operation and were sacrificed 2 h after resuscitation. Intestines were harvested for measurement of tumour necrosis factor alpha (TNF-α), interleukin (IL)-10 and macrophage inflammatory protein-2 (MIP-2) production by EELISA; intercellular adhesion molecule-1 (ICAM-1) mRNA expression by reverse-transcription PCR; nuclear factor-kappa B (NF-κB) by electrophoretic mobility shift assay; neutrophil sequestration by myeloperoxidase (MPO) assay; intestinal permeability by fluorescein isothiocyanate-labeled dextran assay. In addition, the role of HES 130/0.4 in rat survival was observed. ResultsIntestinal permeability was significantly decreased after HES 130/0.4 administration in septic rats, which was associated with a reduction in inflammatory mediators and NF-κB activation. Furthermore, early administration of HES 130/0.4 after septic insult resulted in greater decrease in inflammatory mediators. In addition, HES 130/0.4 co-administrated with antibiotics not HES 130/0.4 alone greatly improved the survival of septic rats. ConclusionsHES 130/0.4 reduced intestinal permeability by modulating inflammatory response and had a promising effect on survival together with antibiotics under septic conditions.

Effects of Hydroxyethyl Starch 130/0.4 on Pulmonary Capillary Leakage and Cytokines Production and NF-κB Activation in CLP-Induced Sepsis in Rats

Sepsis and resulting multiple system organ failure are the leading causes of mortality in intensive care units. Hydroxyethyl starch (HES) 130/0.4 was a novel preparation, developed to improve the pharmacokinetics of current medium molecular weight HES solutions. This study was designed to explore the effects of HES 130/0.4 on pulmonary capillary permeability (PCP), production of cytokines, and activation of transcription factor in septic rats induced by cecal ligation and puncture (CLP). Adult male Sprague Dawley rats were randomly divided into six groups (six rats/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively), and HES alone (30 ml/kg). Mean arterial blood pressure and heart rate were monitored during the experiment process. Myeloperoxidase (MPO) activity, wet/dry weight ratio, PCP, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-10, and nuclear factor-kappa B (NF-kappaB) were investigated at 6 h. We demonstrated that CLP could provoke significant injury in lung, characterized by increase in PCP, wet/dry weight ratio, MPO activity, TNF-alpha, IL-6, and IL-10 level, and NF-kappaB activation. Without obvious influence on systemic macro-hemodynamics, HES 15 ml/kg and 30 ml/kg significantly reduced CLP-induced elevation of pulmonary capillary permeability, wet/dry weight ratio, and production of IL-6. Meanwhile, HES 15 ml/kg increased IL-10 level and HES 7.5, 15, and 30 ml/kg suppressed MPO activity, TNF-alpha level, and NF-kappaB activation. HES 130/0.4 can inhibit CLP-induced PCP by attenuating pulmonary inflammation and NF-kappaB activation in vivo.

The Effects of Low Molecular Weight Hydroxyethyl Starch Replacement Solution in Acute Normovolemic Hemodilution

Background: Unlikely crystalloid, hydroxyethyl starch (HES) solution as a replacement fluid during acute normovolemic hemodilution (ANH) compromises hemodilution-mediated hypercoagulability. However a new HES [130/0.4] preparation may influence hemostasis minimally due to an improved molecular distribution in plasma. This study was designed to estimate the effect of low molecular weight HES solutions (HES [70/0.55] and HES [130/0.4]) during ANH. Methods: Twenty healthy patients scheduled for spine surgery were randomly enrolled in HES 70 and HES 130 groups. All patients underwent moderate ANH before the induction of anesthesia. While whole blood ( ) was being procured, blood deficits were replaced with the same volume of the respective HES solutions. Hematocrit, platelet count, plasma fibrinogen concentration, ionized calcium level, and factor VIII activity were assayed and thrombelastography (TEG) was performed before and after ANH. Statistical tests were conducted to determine the effect of each HES solution. Results: Hematocrit, platelet count, plasma fibrinogen concentration and factor VIII activity were lower than baseline in each group after ANH. According to TEG findings, MA was lower in both groups but R shortened and enhanced in the HES 130 group alone. Comparisons between the HES 70 and HES 130 groups showed that hematocrit, R, and MA changes during ANH differed significantly between the two (repectively, P = 0.019, 0.043, 0.023 and 0.019). Conclusions: HES [130/0.4] solution administered for ANH impairs the hemostatic system to a lesser extent than HES [70/0.55] solution. However, because the volume effect of HES [130/0.4] solution persists for a few hours, a chance of hypovolemia remains during ANH.

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

In Vitro Effects of Different Medium Molecular Hydroxyethyl Starch Solutions and Lactated Ringer’s Solution on Coagulation Using SONOCLOT

Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. HES solutions differ from each other with regard to molecular weight and mode of hydroxyl substitution (degree of hydroxylation, C2:C6 hydroxyethyl ratio, concentration), factors which may have varying effects on coagulation. We studied, in vitro, three different HES preparations (molecular weight/degree of hydroxylation/concentration/C2:C6 ratio of substitution 70.000/0. 5/6%/3.2; Pharmacia & Upjohn Co., Erlangen, Germany; 130.000/0. 4/6%/11.2 and 200.000/0.5/6%/4.6; Fresenius Co., Bad Homburg, Germany) and, for comparison, lactated Ringer's solution (RL) at 33% and 66% dilution with whole blood. The influence of hemodilution was measured by using routine laboratory variables and SONOCLOT (Sonoclot II Coagulation and Platelet Function Analyzer, Sienco Co.) analysis, using a viscoelastic test, on the cellular as well as on the plasmatic hemostatic system. For statistical analysis of quantitative data, we used nonparametric analysis of variance and adequate post hoc tests. Qualitative data were analyzed by using the nonparametric Kruskal-Wallis test. A P value below 0.05 was considered significant. In contrast to the control group with RL, the liquid phase of coagulation (activated clotting time) was slightly affected by the 33% diluted HES solutions. HES 70.000, 130. 000, and 200.000 interfered significantly with the early stage of coagulation as expressed by the clot rate (gel/fibrin formation). Clot maturation and speed of maturation (time to peak) were strongly affected by HES 70.000 at all grades of dilution. HES 130.000 showed a faster clot formation process compared with the other HES solutions. HES 130.000 diluted 33% showed a better clot retraction as compared with the other HES solutions. In conclusion, in vitro hemodilution comparing different medium molecular weight HES solutions reveals that HES 130.000 seems preferable regarding some aspects of clot formation and retraction. RL affected clot formation only minimally, except for the early activation of clotting, which was measured by a shortened activated clotting time. We investigated the effect of different hydroxyethyl starch (HES) solutions (70.000, 130.000, 200.000) on coagulation. Regarding clot formation and retraction, HES 130.000 had some advantages over the other tested HES solutions. Lactated Ringer's solution affected coagulation only minimally, except for the early stage of clot formation.

In Vitro Effects of Different Medium Molecular Hydroxyethyl Starch Solutions and Lactated Ringer’s Solution on Coagulation Using SONOCLOT

Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. HES solutions differ from each other with regard to molecular weight and mode of hydroxyl substitution (degree of hydroxylation, C2:C6 hydroxyethyl ratio, concentration), factors which may have varying effects on coagulation. We studied, in vitro, three different HES preparations (molecular weight/degree of hydroxylation/concentration/C2:C6 ratio of substitution 70.000/0.5/6%/3.2; Pharmacia & Upjohn Co., Erlangen, Germany; 130.000/0.4/6%/11.2 and 200.000/0.5/6%/4.6; Fresenius Co., Bad Homburg, Germany) and, for comparison, lactated Ringer’s solution (RL) at 33% and 66% dilution with whole blood. The influence of hemodilution was measured by using routine laboratory variables and SONOCLOT (Sonoclot II Coagulation and Platelet Function Analyzer, Sienco Co.) analysis, using a viscoelastic test, on the cellular as well as on the plasmatic hemostatic system. For statistical analysis of quantitative data, we used nonparametric analysis of variance and adequate post hoc tests. Qualitative data were analyzed by using the nonparametric Kruskal-Wallis test. A P value below 0.05 was considered significant. In contrast to the control group with RL, the liquid phase of coagulation (activated clotting time) was slightly affected by the 33% diluted HES solutions. HES 70.000, 130.000, and 200.000 interfered significantly with the early stage of coagulation as expressed by the clot rate (gel/fibrin formation). Clot maturation and speed of maturation (time to peak) were strongly affected by HES 70.000 at all grades of dilution. HES 130.000 showed a faster clot formation process compared with the other HES solutions. HES 130.000 diluted 33% showed a better clot retraction as compared with the other HES solutions. In conclusion, in vitro hemodilution comparing different medium molecular weight HES solutions reveals that HES 130.000 seems preferable regarding some aspects of clot formation and retraction. RL affected clot formation only minimally, except for the early activation of clotting, which was measured by a shortened activated clotting time. Implications We investigated the effect of different hydroxyethyl starch (HES) solutions (70.000, 130.000, 200.000) on coagulation. Regarding clot formation and retraction, HES 130.000 had some advantages over the other tested HES solutions. Lactated Ringer’s solution affected coagulation only minimally, except for the early stage of clot formation.

Volume loading with hypertonic saline solution: Endocrinologic and circulatory responses

Hypertonic saline solution appears to be an attractive method of volume expansion. In 45 patients undergoing elective aorto-coronary bypass grafting, endocrinologic and circulatory responses to volume loading with hypertonic saline solution prepared in low molecular weight (MW) hydroxyethyl starch (HES) solution (72 g/L NaCl, HES concentration: 6%; MW: 200,000 D; degree of substitution [DS]: 0.5) (HS-HES) was compared randomly to patients who had received low molecular weight HES solution (LMW-HES). A group of patients without volume loading served as a control. Volume was infused to double the low pulmonary capillary wedge pressure (PCWP < 5 mmHg) after induction of anesthesia. Plasma levels of atrial natriuretic peptide (ANP), endothelin, vasopressin, and catecholamines were measured before, during, and after cardiopulmonary bypass (CPS) until the first postoperative day. In addition to systemic circulatory changes, capillary skin blood flow was measured by laser Doppler flowmetry. ANP plasma concentration increased in both volume groups (HS-HES: +79%; HES: +32%), whereas it decreased in the control (−20%). Infusion of HS-HES resulted in an increase in plasma endothelin concentration before and after CPS (from 3 to 6 pg/mL). Five hours after CPB, both treatment groups had higher endothelin plasma concentrations than the control patients ( P < 0.05). Epinephrine and norepinephrins plasma levels increased most markedly in the control patients and were highest in the postbypass period in these patients. Cl increased most after infusion of HS-HES (+65%) ( P < 0.05). In the postbypass period, Cl remained significantly higher in both volume groups than in the controls. SVR decreased most in the HS-HES patients (−44%) and was lowest after CPS in these patients. Laser Doppler flow was most increased in the HS-HES patients before as well as after CPS. It is concluded that both kinds of volume given before CPS resulted in an improvement in hemodynamics into the postbypass period. Infusion of HSHES led to the most improved systemic and microcirculatory perfusion, which cannot be explained by the endocrinologic response alone.

RETRACTED: VOLUME REPLACEMENT WITH HYDROXYETHYL STARCH SOLUTION IN CHILDREN

In 30 consecutive children undergoing cardiac surgery, two different types of fluid were given randomly for volume replacement in the pre-bypass period. In group 1 (n = 15), low molecular weight hydroxyethyl starch solution (LMW-HES) (6% HES; mean molecular weight 200,000 Da, molar substitution 0.5) and in group 2 (n = 15) 20% albumin (HA) was infused from the induction of anaesthesia until the start of cardiopulmonary bypass (CPB). In addition to haemodynamic values, various laboratory variables were measured before and after CPB until the morning of the 1st day after operation. The patients did not differ in diagnosis and conduct of CPB (lowest rectal temperatures: group 1 29.0 (SD 1.1) degrees C; group 2 29.4 (1.0) degrees C). Haemodynamic data (MAP, HR, CVP), anti-thrombin-III, fibrinogen, platelet count and coagulation variables were comparable between the groups until the 1st day after operation. Postoperative blood loss and the use of homologous blood or blood products were similar in all children. Albumin concentration increased after infusion of albumin (35-47 g litre-1) and was significantly greater until the end of the operation compared with the LMW-HES-treated children. Colloid osmotic pressure, however, was similar in the two groups and returned to baseline values on the 1st day after operation (LMW-HES group 19.31 (1.2) mm Hg; HA group 18.0 (1.3) mm Hg). Post-bypass urine output and creatinine values also did not differ between the groups. Anaphylactic reactions were not observed in any of the patients. It can be concluded that LMW-HES solution can be used effectively and safely for volume replacement in the pre-bypass period in small children undergoing cardiac surgery.

Acute preoperative hemodilution in cardiac surgery: Volume replacement with a hypertonic saline-hydroxyethyl starch solution

Preoperative hemodilution (HD) is a recommended practice in cardiac surgery that conserves blood and reduces the complications of homologous blood transfusion. In 45 patients undergoing myocardial revascularization, HD was performed preoperatively. Withdrawn volume (10 mL/kg) was replaced either by a new hypertonic saline (HS) solution prepared in hydroxyethyl starch (HES) (2,400 mOsm/L, HS-HES group, n = 15) or by a standard low molecular weight hydroxyethyl starch solution (6% HES 200/0.5, HES group, n = 15) to maintain baseline PCWP (acute normovolemic hemodilution [ANH]). Fifteen comparable patients without HD served as controls. Significantly less HS-HES (210 ± 20 mL) than HES 6% (890 ± 90 mL) was necessary to sustain hemodynamics during HD. Stable cardiocirculatory conditions were obtained even after termination of bypass. Fluid balance during cardiopulmonary bypass as well as in the postoperative period was significantly lower in HS-HES-treated patients. With regard to hemodynamics, CI increased most in the HS-HES group (+36%), whereas systemic vascular resistance was lower in these patients. Right ventricular ejection fraction increased only in HS-HES patients (+15%). However, sodium concentration as well as osmolarity increased after volume replacement with HS-HES, without exceeding normal values. None of the patients suffered from organ failure. Pulmonary gas exchange (Pa0 2) was less compromised in the HS-HES patients. There were no renal function differences between the groups. In conclusion, HS solution prepared in HES is an attractive alternative for blood substitution in cardiac patients undergoing acute hemodilution for blood conservation.

Acute plasmapheresis during cardiac surgery: Volume replacement by crystalloids versus colloids

Acute plasmapheresis (APP) is an additional tool for blood conservation during cardiac surgery. In a randomized study of 60 aortocoronary bypass patients undergoing APP, the influence of replacement of the withdrawn autologous plasma (10 mL/kg) by either colloids (low molecular weight hydroxyethyl starch solution [6% HES 200/0.5]) or crystalloids (Ringer's solution) was investigated. APP was performed by means of a centrifugation technique producing platelet-poor plasma. During and after cardiopulmonary bypass (CPB), either a cell saver (CS) or a hemofiltration (HF) device was also used for blood concentration. Almost three times as much crystalloid as HES solution was necessary for replacement of autologous plasma. Fluid balance during CPB was significantly more positive in the crystalloid patients, particularly when a CS was used. Blood loss was highest in the crystalloid patients in whom a CS was used in addition to APP, and these were the only patients who needed packed red cells. The platelet count, AT-III and fibrinogen plasma concentrations, colloid osmotic pressure, albumin, and total protein were significantly less compromised in the patients with colloid volume replacement. These parameters were closest to control values in patients receiving colloid replacement and HF. It is concluded that colloid is preferred for replacement of autologous plasma withdrawn by APP, and HIP is superior to the CS when the combined technique for blood conservation is used.