Medium Molecular Weight Hydroxyethyl Starch Research Articles

A pilot study on impact of use of medium molecular weight hydroxyethyl starch in granulocyte apheresis using Spectra Optia

IntroductionGranulocyte transfusion (GT) is a therapeutic option for prolonged neutropenic patients with severe bacterial or fungal infections. Efficient apheresis based granulocyte collection may be better achieved by infusion of high-molecular-weight (HMW) hydroxyethyl starch (HES). But multiple adverse incidents have been reported with HMW-HES. Due to availability issues and adverse incidents related to it, use of HMW-HES has become limited. Few studies have mentioned about medium molecular weight HES (MMW-HES) (130 kDa) as efficient for this purpose with minimal adverse incidents. So, the aim was to assess the impact of the use of MMW-HES in granulocyte apheresis when using Spectra Optia. MethodologyIn this observational study, donors who received MMW-HES during granulocyte harvest were included in HES group and another group who did not receive HES were grouped as non-HES. Injection G-CSF 10 microgram/kg and tablet dexamethasone 8 mg given 12 h before for non-HES group and 6 – 8 h in case of HES group blood donors. Number of adverse incidents observed were noted. Donor/procedure parameters were compared using Mann–Whitney U test / unpaired t test. ResultsGranulocyte yield was significantly higher in the HES group (2.5 × 1010 vs. 1.75 × 1010, p < 0.01) and was attributed to the difference in collection efficiency (22.61% vs. 10.15%, p < 0.01). There were no significant differences in occurrence of adverse events between HES and non-HES groups. ConclusionOur results clearly indicate that sufficient number of granulocytes can be harvested by using MMW-HES in Spectra Optia apheresis system even after short interval between mobilization to harvest.

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.

Retrospective analysis of treatment for severe ovary hyperstimulation syndrome complicated by pleural effusion and ascites

To investigate the effectiveness of treatment for severe ovary hyperstimulation syndrome (OHSS) complicated by pleural effusion and ascites after in vitro fertilization preembryo transfer (IVF-ET). One hundred and thirty-two patients with severe OHSS in our hospital (from January 2007 to December 2010) were retrospectively analyzed and the efficacy of three therapeutic methods was compared. Twenty-five patients in group I were treated with low-molecular dextran and albumin, 67 patients in group II were treated with 6% medium molecular-weight hydroxyethyl starch, and 40 patients in group III were treated with active aspiration of pleural effusion and ascites. All three therapies improved the symptoms of OHSS and various blood biochemical parameters. The duration of hospitalization of group III [(7.4±4.5) d] was significantly less than those of group I [(21.4±9.2) d] or II [(15.6±6.7) d], and the cost of group III [(2656.2±1882.8) Yuan] was also significantly lower than that of group I or II [(11937.6±7989.8) and (5182.7±2991.7) Yuan, respectively]. Abdominal B ultrasonography-guided trans-abdominal wall aspiration of pleural effusion and ascites combined with blood volume maintenance is an effective and economical way to treat OHSS.

Influence of colloid infusion on coagulation during off-pump coronary artery bypass grafting

This study was conducted to determine the influence of colloid infusion on coagulation in patients undergoing off-pump coronary artery bypass grafting (OP-CABG). Thirty patients undergoing elective OP-CABG received medium molecular weight hydroxyethyl starch group I (MMW-HES 200/0.5), low molecular weight hydroxyethyl starch group II (LMW-HES 130/0.4) or gelatin group III (GEL) in a prospective randomized trial. Blood samples were assessed for hemoglobin (Hb), activated coagulation time (ACT), prothrombin time (PT), activated partial thromboplastin time (aPPT), platelet count, fibrinogen and von Willebrand factor (vWF) at specified intervals. Total volume of the colloid infused and postoperative chest-time drainage was also measured. There was a significant decrease in Hb, platelet count, fibrinogen levels in all these groups, which did not warrant blood transfusion. After the colloid infusion, vWF decreased significantly to 67% from baseline in group I as compared to 85 and 79% in group II and group III, respectively. vWF levels remained lower than the baseline value in the first 24 hours in group I, whereas this factor level increased above the baseline values in groups II and III, 6 hours postoperatively. Postoperative chest tube drainage in 24 hours was significantly higher in group I (856 ± 131 ml) as compared to group II (550 ± 124 ml) and group III (582 ± 159 ml). LMW-HES 130/0.4 was superior to MMW-HES 200/0.5 and gelatin in patients undergoing OP-CABG, in terms of better preservation of coagulation associated with enhanced volume effect.

Effects of hydroxyethyl starch resuscitation on extravascular lung water and pulmonary permeability in sepsis-related acute respiratory distress syndrome *

Hydroxyethyl starch (HES) has greater volume expansion effect and longer intravascular persistence than crystalloids. HES also decreases microvascular permeability and capillary leakage by biophysically plugging endothelial leaks, exerting an anti-inflammatory effect, and decreasing activation of endothelial cells. The aim of our study was to determine whether medium molecular weight HES (pentastarch) resuscitation in the early stage of acute respiratory distress syndrome (ARDS) simultaneously increases cardiac output without worsening pulmonary edema and whether it attenuates pulmonary vascular permeability. Prospective observational study. Twenty-bed medical intensive care unit of a tertiary medical center. Twenty patients with early-stage ARDS. Volume expansion with a 500-mL infusion of 10% pentastarch (HES 200/0.5) at a rate of 10 mL/kg/hr. Baseline hemodynamics including systemic and pulmonary artery blood pressures, central venous pressure, pulmonary artery occlusion pressure, and cardiac output were obtained from an online HP Component Monitoring System and a pulmonary artery catheter. Intrathoracic blood volume (ITBV), global end-diastolic volume, extravascular lung water (EVLW), and pulmonary vascular permeability (EVLW/ITBV) were measured with a PiCCOplus monitor. Hemodynamic measurements were repeated immediately and 2, 4, and 6 hours after volume expansion. Pentastarch loading significantly increased central venous pressure, pulmonary artery occlusion pressure, pulmonary arterial pressures, and cardiac output. Pulmonary mechanics, venous admixtures, and EVLW values remained unchanged throughout the study. EVLW/ITBV significantly decreased immediately after the pentastarch infusion. In patients with early ARDS, pentastarch resuscitation significantly improved their hemodynamics and cardiac output without worsening pulmonary edema and pulmonary mechanics. It even attenuated pulmonary vascular permeability.

Hydroxyethyl Starch Interferes with Human Blood Ex Vivo Coagulation, Platelet Function and Sedimentation

Hydroxyethyl starch (HES) solutions are widely used for intravascular volume expansion. In Taiwan, the medium molecular weight of HES 200/0.5 and HES 130/0.4 solutions are most commonly used. It has been demonstrated that HES may affect coagulation and platelet function significantly. However, the differential effects of each medium molecular weight HES on platelets remain poorly reported. Therefore, we studied the influence of the two HES solutions on platelet function in vitro by mixing whole blood with different proportions of HES 130 kD, HES 200 kD, and saline to determine the differences. Human blood samples for platelet function analyzer (PFA), aggregometry and blood/HES mixed test were drawn from the antecubital vein and put into test tubes containing 3.2% trisodium citrate (blood:citrate, 9:1). The specimens were divided into four groups, designated as whole blood, 10%, 20%, and 30% dilution with normal saline (N/S), HES130 or HES200 solution. The platelet function of each sample was measured by both PFA and platelet aggregometry. The results showed that the PFA-100 closure times CEPI-CT and CADP-CT were significantly prolonged in the samples diluted with normal saline, HES130 and HES200 than in the controls. The ADP triggered whole blood aggregometry showed that attenuated impedance was observed in samples of 20% diluted with HES130 and HES200 groups. The blood/HES mixed sedimentation test showed significantly increased proportion of the upper liquid layer in the HES200 group than in other groups. Our data demonstrated that HES200 and HES130 possess noticeably inhibitory effects on platelet function, especially when the HES replaced proportion was more than 20%. HES200 has a greater effect on blood cells and plasma separation than does HES130.

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.

Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation

Development of hydroxyethyl starches (HES) with a low impact on blood coagulation but a long intravascular persistence is of clinical interest. A previous in vitro study showed that low substituted high molecular weight HES does not compromise blood coagulation more than medium molecular weight HES. In the present study we assessed the individual effects on blood coagulation of molar substitution and C2/C6 ratio of a high molecular weight HES. Blood was obtained from 30 healthy patients undergoing elective surgery and mixed with six high molecular weight (700 kDa) HES solutions differing in their molar substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40 and 60% dilution. Blood coagulation was assessed by Thrombelastograph analysis (TEG) and plasma coagulation tests. Data were compared using a three-way analysis of variance model with repeated measures on the three factors. Higher molar substitution compromised blood coagulation most (for all TEG parameters, P<0.05). The lowest C2/C6 ratio was associated with the lowest effect on blood coagulation; r (P<0.001), angle alpha (P=0.003) and coagulation index (P<0.001). No effect on k and maximum amplitude was observed (P for both >0.50). The higher molar substitution was associated with a lesser increase in PT (P=0.007) and a greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von Willebrand factors were not significantly influenced by molar substitution (P for all >0.20). No significant differences between solutions with the same molar substitution but different C2/C6 ratios were found in plasma coagulation parameters (P for all >0.05). TEG analysis indicates that high molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the lowest effect on in vitro human blood coagulation.

The Influence of Two Different Hydroxyethyl Starch Solutions (6% HES 130/0.4 and 200/0.5) on Blood Viscosity

We performed the current study to investigate the influence of 2 different hydroxyethyl starch (HES) solutions, the novel medium molecular weight HES 130/0.4 (6%) and HES 200/0.5 (6%), on plasma and whole blood viscosity in vitro and ex vivo in patients with severe head injury. For the in vitro experiments, blood was incubated with increasing concentrations (0%-50% vol/vol plasma) of either 6% HES 130/0.4 or 6% HES 200/0.5 solution. Plasma viscosity and whole blood viscosity (hematocrit [Hct] 45%) at high (94.5 s(-1)) and low (0.1 s(-1)) shear rates were determined. Both HES solutions increased plasma viscosity, but HES 130/0.4 to a lesser extent than HES 200/0.5. Whole blood viscosity was significantly less with HES 130/0.4 than with HES 200/0.5 at concentrations of 37.5% and larger. In the ex vivo study on 31 patients with severe cranio-cerebral trauma treated randomly with either HES 130/0.4 or HES 200/0.5 over several days, frozen plasma samples were thawed and plasma viscosity was determined. Blood was reconstituted with normal erythrocytes (0, Rh neg, Hct 45%) for whole blood viscosity measurements. In both groups plasma and blood viscosity tended to increase over time without statistical significance. Although the prominent effects found in vitro are not in keeping with the ex vivo data, they are likely to reflect the true clinical situation during repetitive, large-dose HES administration. We therefore conclude that HES 130/0.4 may have hemorheological advantages over conventional HES 200/0.5 when used in large quantities.

Volume expanders for spontaneous bacterial peritonitis: Are we comparing oranges with oranges?

Volume expanders for spontaneous bacterial peritonitis: Are we comparing oranges with oranges?

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.

Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding

Background. This meta-analysis tested the hypothesis that cumulative blood loss during the first 24 hours after cardiopulmonary bypass is lower in patients exposed to albumin than hydroxyethyl starch (HES). Methods. Randomized controlled trials comparing albumin and HES in cardiopulmonary bypass patients were identified by bibliographic database searches and other methods. Results. Sixteen trials involving 653 randomized patients were included. In 88% of randomized comparisons, postoperative bleeding was lower in the albumin group, and the standardized mean difference in bleeding favoring albumin across all trials (−0.24; 95% confidence interval, −0.40 to −0.08) was statistically significant. Bleeding differences between albumin and either high or medium molecular weight HES were similar. In trials of adults, the pooled mean blood loss in the albumin group was 693 ± 350 mL compared with 789 ± 487 mL in the HES group. The estimated proportion of adult albumin group patients with blood loss of more than 1,000 mL was 19% compared with 33% of adult HES group patients. Conclusions. Postoperative blood loss is significantly lower in cardiopulmonary bypass patients exposed to albumin than HES.

Effects on general safety and coagulation after long-term, high-dose volume therapy with 6% hydroxyethyl starch 130/0.4 in patients with acute ischemic stroke. Results of a randomized, placebo-controlled, double-blind study

In the past, high-molecular weight, highly substituted hydroxyethyl starch (HES) 450/0.7, which is mostly used in the United States, has been implicated in bleeding complications, some of them lethal. In Europe, medium-molecular weight HES with a low degree of substitution (0.5) has been preferred. The present study investigated, whether a long-term, high-dose volume therapy with a newly developed 6% HES 130/0.4 (Voluven®) is safe in patients suffering from acute ischemic stroke. In particular, the effects on hemostaseology were examined.

Plasma substitutes for volume replacement in hemorrhagic shock: comparison of low and medium molecular weight hydroxyethyl starch

ObjectiveThe aim of this study was to assess the relative efficacy of 2 volume replacement therapies in a canine model of induced hemorrhagic shock. MethodsAnesthetized dogs were bled to maintain mean arterial pressure (mAP) at 50 mm Hg for 30 minutes and then administered a single bolus injection of 6% hydroxyethyl starch (HES) with a molecular weight of 70 kd (HES70 group) or 200 kd (HES200 group) at a volume equivalent to the blood withdrawn. We examined the efficacy of both therapies in maintaining hemodynamic variables and splanchnic organ blood flow (ie, blood flow through the renal cortex, renal medulla, liver, and pancreas). ResultsAfter resuscitation, hemodynamic variables were better maintained in the HES200 group than in the HES70 group. In particular, HES200 better preserved mAP, cardiac index, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, left ventricular stroke work index, and maximum rate of left ventricular pressure change. In both groups splanchnic organ blood flows decreased significantly after hemorrhagic shock but increased after volume replacement resuscitation. After resuscitation splanchnic organ blood flow was significantly greater in the HES200 group than in the HES70 group (P< 0.05). ConclusionsThe results of this study suggest that HES200 is more effective than HES70 as volume replacement therapy in a canine model of hemorrhagic shock, as measured by improvements in hemodynamic variables and splanchnic organ blood flow.

Crystalloids or colloids for fluid resuscitation – is that the question?

Fluid resuscitation is the most commonly applied treatment to critically ill patients and both crystalloids and colloids have saved thousands of lives. The debate of all crystalloids versus all colloids is increasingly irrelevant and misguided. Colloids are enormously variable and meta-analyses putting all colloids together into one group versus crystalloids are misleading. Critically ill patients form a very heterogeneous group and evidence is mounting which supports early subdivision into clinical entities and a more individualized treatment approach. All patients with hypovolaemia need water and salt, but when, how much and in what concentration? We should match the fluids used to the patient's condition. In patients with evidence of systemic capillary leak syndrome, modern medium molecular weight hydroxyethyl starches have shown definite advantages over albumin and low-molecular-weight gelatines.

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.

Cost Analysis of Different Volume Replacement Strategies in Anesthesia

Objective: Varying regimens of volume replacement are available. In today’s climate of cost consciousness and cost contain-ment it appears to be of interest to assess effective costs associated with the different fluid therapies. Design: Prospective, randomized study. Setting: Single-institutional, clinical investigation in an urban, university-affiliated hospital. Patients and Methods: 150 patients undergoing major abdominal surgery were divided into three groups. Perioperatively and until the first postoperative day, patient group 1 (n = 50) received 6% low-molecular weight hydroxyethyl starch (HES) (mean molecular weight (MW) 70 kDa, degree of substitution (DS) 0.5; HES 70/0.5), patient group 2 (n = 50) 6% medium-molecular weight HES (MW 200 kDa, DS 0.5; HES 200/0.5), and patient group 3 (n = 50) 3% modified fluid gelatin (MW 35 kDa) to keep mean arterial blood pressure (MAP) >70 mm Hg and central venous pressure (CVP) between 10 and 14 mm Hg. Results: The patients did not differ with regard to biometrics, type of surgery, and postoperative care. Hemodynamics (MAP, CVP), degree of hemodilution (hemoglobin), kidney (creatinine plasma level), liver (cholinesterase), and pulmonary function (paO₂/FIO₂) were without significant differences within the study. No differences were seen concerning blood loss, use of packed red blood cells (PRBC) and fresh frozen plasma (FFP). Significantly more gelatin (2,590 ± 500 ml) than HES 70/0.5 (2,130 ± 460 ml) and HES 200/0.5 (1,680 ± 430 ml) was given during the study period. Entire costs for volume replacement (in EUR and in USD) were significantly highest in the HES 70/0.5 group (118.25 EUR/patient, 134.45 USD/patient), whereas costs in the HES 200/0.5 (99.66 EUR/patient, 113.35 USD/patient) and the gelatin group (98.57 EUR/patient, 112.06 USD/patient) did not differ. Conclusions: Maintaining quality of patients’ care and simultaneously lowering costs represents a challenge. The type of fluid used for volume replacement continues to be debated. From the economic point of view, the use of gelatin offers no advantage compared to the use of HES 200/0.5. Only using HES 70/0.5 for volume therapy may result in some increases in costs.

The Influence of Different Intravascular Volume Replacement Regimens on Renal Function in the Elderly

Elderly patients are at risk of developing renal dysfunction. Synthetic colloids are often used perioperatively, but they may have detrimental effects on renal function. In a prospective, randomized study, we assessed the influence of different intravascular volume replacement regimens on renal function in elderly (>65 yr) and younger (< 65 yr) patients without preoperative renal dysfunction who were undergoing major abdominal surgery. Either 6% low molecular weight hydroxyethyl starch (HES) solution (mean molecular weight 70,000 D, degree of substitution 0.5; HES 70/0.5) [each group n = 10]), 6% medium-molecular weight HES (molecular weight 200,000 D, degree of substitution 0.5 (HES 200/0.5) [each group n = 10]), or modified gelatin (molecular weight 35,000 D [each group n = 10]) was administered to maintain mean arterial blood pressure >65 mm Hg and central venous pressure between 10 and 14 mm Hg. After the induction of anesthesia (T0); at the end of surgery (T1); 4 h after surgery (T2); and on the first (T3), second (T4), and third postoperative days (T5), alpha1-microglobulin (alpha1-M), N-acetyl-beta-glucosaminidase, fractional sodium clearance, and creatinine clearance (CC) were measured. Colloids (1300-3000 mL) were infused until the first postoperative day. At T0, urine concentrations of alpha1-M were higher in the elderly than in the younger patients in all groups (P < 0.05). alpha1-M remained increased only in the gelatin group. N-acetyl-beta-glucosaminidase and fractional sodium clearance were not affected during the study period in any groups. At baseline, CC was significantly higher in the younger than in the elderly patients, but CC did not decrease in any of the intravascular volume replacement groups. We conclude that intravascular volume therapy with gelatin and two different HES preparations did not adversely affect renal function in elderly patients without preoperative renal malfunction. We studied the influence of three different intravascular volume replacement regimens on renal function in elderly patients without renal dysfunction who were undergoing major abdominal surgery. Two hydroxyethyl starch and one gelatin preparation were administered perioperatively to maintain stable hemodynamics. As assessed by sensitive markers of renal function, all three regimens can be used safely for volume replacement without risking significant renal dysfunction.