Use of modified fluid gelatin and hydroxyethyl starch for colloidal volume replacement in major orthopaedic surgery. A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations. Equivalence of hydroxyethyl starch HES 130/0. 4 and HES 200/0. 5 for perioperative volume replacement in major gynaecological surgery. Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. Randomized trial of hydroxyethyl starch versus gelatine for trauma resuscitation. Volume therapy with a new hydroxyethyl starch solution in cardiac surgical patients before cardiopulmonary bypass. Volume efficacy and reduced influence on measures of coagulation using hydroxyethyl starch 130/0.4 (6%) with an optimised in vivo molecular weight in orthopaedic surgery : a randomised, double-blind study. Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for volume expansion in cardiac surgery patients: the effects on perioperative bleeding and transfusion needs. The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery. Clinical comparison of hetastarch and albumin in postoperative cardiac patients. Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal function: a comparison with human albumin. A total balanced volume replacement strategy using a new balanced hydoxyethyl starch preparation (6% HES 130/0.42) in patients undergoing major abdominal surgery. Comparison of the effects of gelatin and a modern hydroxyethyl starch solution on renal function and inflammatory response in elderly cardiac surgery patients. Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5. Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial. Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial. Peri-operative tolerance to large-dose 6% HES 200/0.5 in major urological procedures compared with 5% human albumin. Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. A novel hydroxyethyl starch (Voluven) for effective perioperative plasma volume substitution in cardiac surgery. [Tactics of infusion therapy in the acute period of intracranial hemorrhages]. Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. The influence of different intravascular volume replacement regimens on renal function in the elderly. Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Volume replacement with hydroxyethyl starch solution in children. Large-dose hydroxyethyl starch 130/0.4 does not increase blood loss and transfusion requirements in coronary artery bypass surgery compared with hydroxyethyl starch 200/0.5 at recommended doses. Randomized clinical trial comparing the effects on renal function of hydroxyethyl starch or gelatine during aortic aneurysm surgery. Hydroxyethyl starch (HES) does not directly affect renal function in patients with no prior renal impairment. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Volume therapy in the critically ill: is there a difference?
We have compared 6% hydroxyethyl starch (HES 200/0.5) with 3% modified fluid gelatin (MFG) for volume replacement in major orthopaedic surgery and studied the effects on haemodynamic state, colloid osmotic pressure, blood clotting and plasma homeostasis. Using a controlled, randomized, single-blind clinical design, we studied 46 consecutive patients undergoing major elective orthopaedic hip surgery. The two groups were comparable in age, body weight and duration of surgery. Patients were maintained haemodynamically stable using both HES and MFG over the entire study. Fluid balance and colloidal replacement volumes were comparable in both groups (median perioperative infusion volume: HES 2500 ml, MFG 2400 ml). Laboratory variables were not clinically different. We conclude that both colloidal solutions were comparable in volume efficacy and effects on plasma oncotic pressure, clotting and plasma homeostasis. In the small number of patients studied, 6% HES 200/0.5 was found to be safe when administered in amounts corresponding to the currently accepted maximum daily dose in Germany and France of 33 ml/kg body weight and 2.0 g/kg body weight, respectively. Pentastarch is a hydroxyethyl starch similar to hetastarch, but with a lower average molecular weight (264,000 versus 450,000) and fewer hydroxyethyl groups (molar substitution ratio = 0.45 versus 0.70). These characteristics result in enhanced enzymatic hydrolysis, faster renal elimination (initial intravascular half-life = 2.5 versus 25.5 hours), and less effect on coagulation. We report on a randomized clinical trial comparing the clinical efficacy and safety of 10% pentastarch (group P) for plasma volume expansion after cardiac operations with that of 5% serum albumin (group A). During the first 24 hours after arrival of the patient in the intensive care unit, colloid was infused to maintain a cardiac index of 2.0 L/m2 or more and a mean arterial pressure within 10% of the preinduction value. Group P (n = 50) received 1706 +/- 393 ml of colloid (mean +/- standard deviation) during this period, and group A (n = 44), 1794 +/- 341 ml (p = no significant difference). Hemodynamic responses to infusion were similar for both groups, although in group P a greater increase in both cardiac index (0.5 +/- 0.5 versus 0.3 +/- 0.5 L/min/m2 in group A, p less than 0.01) and left ventricular stroke work index (10.8 +/- 8.0 versus 5.8 +/- 6.0 gm-m/m2, p less than 0.01) was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters (alveolar-arterial oxygen gradient, estimated shunt fraction, and effective pulmonary compliance). Hemodilution with colloid significantly reduced serum protein levels in group P by 24 hours postoperatively (4.0 +/- 0.6 versus 5.0 +/- 0.7 gm/dl in group A, p less than 0.05), although mean serum colloid osmotic pressure was similar (15.4 +/- 2.6 [P] versus 15.5 +/- 2.7 mmHg [A], p = no significant difference). There were no significant between-group differences in prothrombin time, activated partial thromboplastin time, platelet count, bleeding time, or coagulation factors (fibrinogen, V, VII, VIII, or IX) on postoperative days 1 and 7. Perioperative fluid balance, weight change, chest tube output, red blood, platelet, or fresh frozen plasma usage, reexploration for bleeding, and clinical outcome were also similar. These findings indicate that pentastarch is as safe and effective s 5% albumin for plasma volume expansion after cardiac operations with no apparent adverse effects on coagulation. If commercially available at a lower cost than albumin, it would appear to be a reasonable first choice for colloid therapy in this setting. Hydroxyethyl starch solutions (HES) are increasingly used for the compensation of surgical blood loss. The objective of this clinical trial was to compare a novel 6% HES 130/0.4 solution with a favourable pharmacological profile and a standard 6% HES 200/0.5 solution for maintenance of haemodynamic stability in major gynaecological surgery.
                Sixty female patients aged 18-80 years undergoing major gynaecological surgery with indication for perioperative colloidal volume replacement were enrolled in this prospective, randomized double-blinded clinical study. The administration of study medication was dependent on individual requirements to maintain haemodynamic stability. The amount of study medication required from induction of anaesthesia until 6 h postoperatively served as the primary investigative parameter.
                The two one-sided test procedure by Westlake demonstrated equivalence of mean infused volumes between HES 130/0.4 and HES 200/0.5 during the study period (1224 +/- 544 ml and 1389 +/- 610 ml, respectively, P < 0.05). Perioperatively, haemodynamics did not differ significantly between treatment groups. While none of the mean values of coagulation parameters shifted outside the normal range, the degree of haemodilution revealed reduced haematocrit values in HES 200/0.5 treated patients at 6 h postoperatively (P < 0.05). Moreover, prothrombin time (PT) was higher and consequently international normalized ratio (INR) was lower at the same time point for patients who received HES 130/0.4 (P < 0.05).
                This clinical trial demonstrated therapeutic equivalence of this novel low-substituted HES 130/0.4 solution and a standard HES 200/0.5 solution for perioperative volume replacement. Moreover, both HES preparations were equally well-tolerated and safe. A prospective trial of 6% hetastarch (HES) v 5% plasma protein fraction (PPF) as the colloid component of intravenous (IV) fluid resuscitation was conducted in 32 patients with multisystem trauma and/or hemorrhagic shock. Patient age, mechanism and pattern of injury, and IV fluid requirements were similar in both groups. No intergroup differences were noted in indexes of hepatic, pulmonary, or renal function or in the incidence of infection. The frequency of other complications, including bleeding diatheses, and mortality were identical in the two groups. Although this investigation should be viewed as a pilot study, our results suggest that, compared with PPF, HES in large volumes is a safe, effective colloid solution in the resuscitation of patients with multisystem trauma and/or hemorrhagic shock. Further study of HES in a larger number of patients is warranted by these findings. The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.
                In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.
                The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.
                The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)
                2008 Massachusetts Medical Society Previous studies have demonstrated the rapid increase in systemic capillary permeability after blunt trauma and its association with poor outcome. There are theoretical advantages in resuscitation with colloid fluids, which are well retained in the vascular compartment during times of capillary leak. The aim of this study was to compare the effects of posttrauma resuscitation with hydroxyethyl starch (HES) (molecular mass, 250 kDa) or gelatine (molecular mass, 30 kDa), the hypothesis being that HES would reduce capillary leak.
                Forty-five patients suffering blunt trauma were randomized on admission to receive either gelatine (Gelofusine) (n = 21) or HES (Pentaspan) (n = 24) for the first 24 hours, after which the choice of fluid was at the discretion of the clinician. The mean Injury Severity Score for the HES and gelatine groups were 20.0 (range, 9-41) and 18.1 (range, 9-32), respectively (p = 0.43). Capillary permeability was assessed by urine albumin excretion rate for the first 24 hours. For 5 days the daily mean P(O2)/F(IO2) ratio, serum C-reactive protein, hemoglobin, white cell and platelet counts, prothrombin, and activated partial thromboplastin time were recorded.
                Capillary permeability was lower in HES-treated patients during the first 24 hours. Log mean (95% confidence interval) albumin excretion rate for gelatine and HES groups at 6 hours were 117.5 (84.9) and 46.8 (24.3) microg/min (p = 0.011), at 12 hours were 54.9 (30.0) and 17.2 (7.6) microg/min (p = 0.001), and at 24 hours were 50.5 (23.4) and 23.6 (16.3) microg/min (p = 0.030), respectively. The mean (95% confidence interval) P(O2)/F(IO2) ratio for the HES and gelatine groups 48 hours after admission were 324 (44) and 267 (43) mm Hg, respectively (p = 0.03). The mean (95% confidence interval) serum C-reactive protein in the HES and gelatine groups 24 hours after admission were 72.4 (19.2) and 105.7 (30.1) mg/L, respectively (p = 0.03). There were no significant differences in any of the hematologic parameters during the first 48 hours.
                The results suggest that compared with gelatine, resuscitation with HES reduces posttrauma capillary leak. To compare the hemodynamic efficacy of a new hydroxyethyl starch (HES) preparation (130/0.4) with an HES 200/0.5 solution.
                Prospective, randomized, double-blind, phase II study.
                An urban, university-affiliated hospital.
                Twenty patients undergoing elective first-time cardiac surgery.
                After induction of anesthesia and before the start of surgery, a new HES 130/0.4 (molecular weight, 130,000 d; degree of substitution, 0.4) (n = 10) or HES 200/0.5 (molecular weight, 200,000 d; degree of substitution, 0.5) (n = 10) was infused (10 mL/kg) within 30 minutes when pulmonary capillary wedge pressure was less than 10 mmHg.
                Extensive hemodynamic monitoring was performed 30 and 60 minutes after the end of infusion. Then surgery was started. Standard laboratory parameters were measured before surgery and on the 1st postoperative day. A similar amount of HES was given in both groups (HES 130, 795+/-75 mL; HES 200, 820+/-90 mL). Filling pressures (central venous pressure, pulmonary capillary wedge pressure) and cardiac index increased similarly in both groups and remained significantly elevated 60 minutes after the end of infusion. All other hemodynamic parameters were similar between the two volume groups. Renal (creatinine) and hepatic function (aspartate aminotransferase, alanine aminotransferase) and hemostasis (platelet count, activated partial thromboplastin time, blood loss) were without group differences until the morning of the 1st postoperative day.
                The new 6% HES 130/0.4 was as effective as a 6% HES 200/0.5 preparation in regard to hemodynamic efficacy. No negative side effects on organ function were seen. The 6% HES 130/0.4 solution may become an alternative strategy for volume therapy in cardiac surgery. Different types of hydroxyethyl starch (HES) affect blood coagulation differently. We studied the effects of HES 130/0.4 on coagulation in major orthopaedic surgery in relation to the pharmacological parameter in vivo molecular weight.
                52 patients were randomly allocated to either HES 130/0.4 (6%, mean molecular weight 130 kDa, molar substitution 0.4) or HES 200/0.5 (6%, control) in a double-blind fashion. Colloidal volume requirements for intra- and postoperative haemodynamic stabilisation were compared. Safety analyses of this pharmacological study included a comparison of coagulation factor tests, in vivo molecular weight, and HES plasma concentrations.
                The colloidal volumes given were similar at the end of surgery (1602 +/- 569 for HES 130/0.4 vs 1635 +/- 567mL for HES 200/0.5), 5h later (1958 +/- 467 vs 1962 +/- 398mL), and up to the first postoperative day (2035 +/- 446 vs 2000 +/- 424mL). HES in vivo molecular weight at the end of surgery was 88,707 +/- 13,938 versus 158,374 +/- 33,933Da (p < 0.001) and 5h later was 86,663 +/- 16,126 versus 136,299 +/- 26,208Da (p < 0.001). In parallel to the lower in vivo molecular weight, factor VIII and von Willebrand factor returned to almost normal in the HES 130/0.4 group up to 5h postoperatively, but not in the control group (p < 0.05). Residual HES plasma concentrations after 24h were low in the HES 130/0.4 group (1.0 mg/mL), but higher in the control group (2.6 mg/mL).
                HES 130/0.4 and HES 200/0.5 were found to be similar with regard to volume efficacy. Sensitive coagulation parameters returned more rapidly to normal in the HES 130/0.4 group. Lower in vivo molecular weight and more rapid excretion of HES 130/0.4 are the likely explanations for the smaller influence on coagulation in this group. In this prospective, randomized, open controlled study we compared the effects on net red blood cell loss of 6% hydroxyethyl starch 130/0.4 (HES: n = 64) and 3% modified fluid gelatin (GEL: n = 68) administered for intravascular volume management in patients undergoing coronary surgery. Blood losses were calculated from determination of circulating blood volume and measurement of preoperative and postoperative hematocrit. Amount of colloids that could be administered was limited to 50 mL/kg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Both groups were similar with regard to demographic and intraoperative variables. Total study drug was 48.9 +/- 17.2 mL/kg in the HES group and 48.9 +/- 14.6 mL/kg in the GEL group. Total red blood cell loss was 544 +/- 305 mL in the HES group and 504 +/- 327 mL the GEL group. Measured blood losses were also similar in both groups (HES, 19.4 +/- 12.3 mL/kg; GEL, 19.2 +/- 14.5 mL/kg). Exposure to allogeneic blood product was comparable in both groups. In the conditions of the present study, HES 130/0.4 up to 50 mL/kg is a valuable alternative to modified fluid gelatin for plasma volume expansion during and after cardiac surgery. The value of human albumin (HA) for treating hypovolemia is controversial. Less expensive alternatives such as hydroxyethyl starch (HES) are sometimes refused because of unwanted side effects. We prospectively randomized 50 patients older than 70 years old undergoing major abdominal surgery to receive either 5% HA (n = 25) or a third generation HES preparation (6% HES 130/0.4; n = 25) when mean arterial blood pressure was <60 mm Hg and central venous pressure was <10 mm Hg. Hemodynamics, inflammation (interleukin-6), endothelial activation-integrity (adhesion molecules), coagulation (thrombelastography), and renal function (including kidney-specific proteins) were monitored after the induction of anesthesia, after surgery, 5 h in the intensive care unit, and on the first postoperative day. HA patients received 3960 +/- 590 mL of HA and 5070 +/- 1030 mL of Ringer's lactate solution, and HES patients received 3500 +/- 530 mL of HES and 4550 +/- 880 mL of Ringer's lactate solution. Total protein remained normal only in the HA-treated patients. No significant differences (P > 0.1) between the groups were seen with regard to hemodynamics, coagulation, and kidney function. Plasma levels of interleukin-6 and soluble adhesion molecules were significantly (P < 0.05) higher in the HA- than in the HES-treated patients. We conclude that HA in elderly patients undergoing major abdominal surgery can easily be replaced by a modern HES preparation. Because of the decreased inflammatory response and endothelial activation-injury, HES 130/0.4 seems to be the more appropriate fluid strategy for these patients. Hetastarch, 6% hydroxyethyl starch solution, is an artificial colloid proposed for use as a volume expander. There is concern that hetastarch, like dextran, may adversely affect coagulation. To compare the effects of hetastarch with 5% albumin in postoperative patients, 60 consecutive patients who underwent coronary artery bypass were prospectively randomized into two study groups. Both groups were comparable in all respects preoperatively. Group 1 (27 patients) received a mean of 1,241 ml of 5% albumin and Group 2 (33 patients) a mean of 1,210 ml of hetastarch as volume replacement within the first 24 postoperative hours. Indices of postoperative hepatic, renal, and pulmonary function did not differ significantly between the groups immediately postoperatively, at 24 hours postoperatively, or at 7 days postoperatively. Hematocrits, platelet counts, prothrombin times, partial thromboplastin times, and serum fibrinogen levels were comparable between the two groups at all times. The mean volume of chest tube drainage did not differ between the groups (Group 1, 495 +/- 216 ml; Group 2, 637 +/- 402 ml; not significant), and no patient required reexploration for bleeding. Eighteen percent of Group 1 and 15% of Group 2 patients received banded blood during their hospitalization and required similar amounts (Group 1, 0.37 unit per patient; Group 2, 0.36 unit per patient; not significant). The use of hetastarch as a postoperative volume expander after myocardial revascularization is safe and effective, and results in substantial financial savings. There is continuing concern about the influence of hydroxyethylstarch on renal function in patients with compromised kidney function.
                Prospective, randomized, single-center study.
                University-affiliated hospital.
                Fifty patients undergoing elective, first-time coronary artery bypass grafting using cardiopulmonary bypass with a preoperative serum creatinine between 1.5 and 2.5 mg/dL.
                According to a prospective, randomized sequence, the patients received either hydroxyethylstarch with a low molecular weight (mean molecular weight 130 kD) and a low molar substitution (0.4) (6% hydroxyethylstarch 130/0.4) (n = 25) or 5% human albumin (n = 25). Volume was added to the priming (500 mL) and given perioperatively until the second postoperative day to keep pulmonary artery occlusion pressure or central venous pressure between 12 and 14 mm Hg.
                Serum creatinine and cystatin plasma levels were measured from arterial blood samples. From urine specimens, N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and neutrophil gelatinase-associated lipocalin were measured. Measurements were performed after induction of anesthesia, at the end of surgery, 5 hrs after surgery, and on the first and second postoperative days. A follow-up after discharge from the hospital (60 days) was also done. Similar amounts of hydroxyethylstarch and albumin were infused. Serum creatinine, glomerular filtration rate, and cystatin C plasma levels were without significant differences between the groups. Concentrations of kidney-specific proteins were elevated at baseline and increased significantly after surgery without showing group differences. Urinary levels of neutrophil gelatinase-associated lipocalin increased more in the albumin- than in the hydroxyethylstarch-treated patients. None of the patients developed acute renal failure requiring renal replacement therapy during the hospital stay and thereafter.
                A hydroxyethylstarch preparation with a low molecular weight and a low molar substitution given in cardiac surgery patients with preoperative compromised kidney function did not negatively influence kidney integrity compared with a human albumin-based volume replacement strategy. The kind of fluid for correcting hypovolaemia is still a focus of debate. In a prospective, randomized, controlled and double-blind study in patients undergoing major abdominal surgery, a total balanced volume replacement strategy including a new balanced hydroxyethyl starch (HES) solution was compared with a conventional, non-balanced fluid regimen.
                In Group A (n = 15), a new balanced 6% HES 130/0.42 was given along with a balanced crystalloid solution; in Group B (n = 15), an unbalanced conventional HES 130/0.42 plus an unbalanced crystalloid (saline solution) were administered. Volume was given when mean arterial pressure (MAP) was <65 mmHg and central venous pressure (CVP) minus positive end-expiratoric pressure (PEEP) level was <10 mmHg. Haemodynamics, acid-base status, coagulation (thrombelastography (TEG)) and kidney function (including kidney-specific proteins, N-acetyl-beta-d-glucosaminidase (beta-NAG) and alpha-1-microglobulin) were measured after induction of anaesthesia, at the end of surgery, 5 and 24 h after surgery.
                Group A received 3533 +/- 1302 mL of HES and 5333 +/- 1063 mL of crystalloids, in Group B, 3866 +/- 1674 mL of HES and 5966 +/- 1202 mL of crystalloids were given. Haemodynamics, laboratory data, TEG data and kidney function were without significant differences between the groups. Cl- concentration and base excess (-5 +/- 2.4 mmol L-1 vs. 0.4 +/- 2.4 mmol L-1) were significantly higher in patients of Group B than of Group A.
                A complete balanced volume replacement strategy including a new balanced HES preparation resulted in significantly less derangement in acid-base status compared with a non-balanced volume replacement regimen. The new HES preparation showed no negative effects on coagulation and kidney function. The effects of hydroxyethylstarch (HES) 130/0.4 6% and gelatin 4% on inflammation, endothelial integrity, and renal function after cardiac surgery were compared.
                Sixty patients aged >80 yr undergoing cardiac surgery were randomized to receive gelatin (n=30) or HES 130/0.4 (n=30). The colloid was used in the priming of the cardiopulmonary bypass circuit (500 ml) and for volume replacement until the second postoperative day (POD). Serum creatinine, creatinine clearance, IL-6, IL-10, intercellular adhesion molecule-1 (sICAM-1), urinary glutathione transferase-alpha, and neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Serum creatinine was also reported approximately 60 days after discharge.
                The mean(sd) volume of gelatin infused was 4180(440) ml, which was greater than the volume of HES infused 2910(330) ml (P=0.002). The mean(sd) volume of serum creatinine on the first POD was 151(24) micromol litre(-1) in the gelatin group and 126(13) micromol litre(-1) in the HES group (P=0.004). Values for the second POD were 161(0.26) and 133(16) micromol litre(-1), respectively (P=0.004). Creatinine clearance was lower in the gelatin group on the first POD [37(7) vs 46(8) ml min(-1) 1.73 m2 (P=0.004)] and the second POD [32(8) vs 45(10) ml min(-1) 1.73 m2 (P=0.002)]. Kidney function approximately 60 days after discharge did not differ between the groups. IL-6, IL-10, and sICAM-1 were significantly lower in the HES group than in the gelatin group on the first and second PODs. Urinary alpha-GST increased in both groups to a comparable extent. Urinary NGAL concentrations were higher in the gelatin than in the HES patients 5 h after surgery and on the first and second PODs.
                In cardiac surgery patients aged >80 years, volume therapy with HES 130/0.4 6% was associated with less marked changes in kidney function and a less marked endothelial inflammatory response than gelatin 4%. Hydroxyethyl starch (HES) solutions are effective plasma volume expanders. Impairment of coagulation occurs with large HES volumes infused perioperatively. Therefore, a lower substituted novel HES (Voluven; Fresenius Kabi, Bad Homburg, Germany) was developed to minimize hemostatic interactions, and was compared with HAES-steril (Fresenius Kabi) (pentastarch) regarding safety and efficacy. We performed a prospective, randomized, double-blinded study in 100 major orthopedic surgery patients. Because the 95% confidence interval (-330 mL; +284 mL) for the treatment contrast Voluven-HAES-steril was entirely included in the predefined equivalence range (+/- 500 mL), comparable efficacy was established. Voluven interfered significantly less than HAES-steril with coagulation factor VIII levels and partial thromboplastin time postoperatively. Total amounts of red blood cells transfused were comparable between the Voluven and HAES-steril groups, but a significantly reduced need for homologous red blood cells was observed in the Voluven group. We conclude that in large-blood-loss surgery, Voluven has a comparable efficacy with HAES-steril and may reduce coagulation impairment, possibly leading to a smaller number of allogeneic blood transfusions.
                Hydroxyethyl starches are common plasma volume expanders, but may interfere with coagulation at large doses. We tested a novel hydroxyethyl starch specification (Voluven; Fresenius Kabi, Bad Homburg, Germany) which was developed to reduce hemostatic interactions while preserving its efficacy in restoring plasma volume in comparison to HAES-steril (pentastarch; Fresenius Kabi) in major orthopedic surgery. Patients with impaired renal function are at risk of developing renal dysfunction after abdominal aortic surgery. This study investigated the safety profile of a recent medium-molecular-weight hydroxyethyl starch (HES) preparation with a low molar substitution (HES 130/0.4) in this sensitive patient group.
                Sixty-five patients were randomly allocated to receive either 6% hydroxyethyl starch (Voluven); n = 32) or 3% gelatin (Plasmion); n = 33) for perioperative volume substitution. At baseline, renal function was impaired in all study patients as indicated by a measured creatinine clearance < 80 mL min(-1). The main renal safety parameter was the peak increase in serum creatinine up to day 6 after surgery.
                Both treatment groups were compared for non-inferiority (pre-defined non-inferiority range hydroxyethyl starch < gelatin + 17.68 micromol L(-1) or 0.2 mg dL(-1). Other renal safety parameters included minimum postoperative creatinine clearance, incidence of oliguria and adverse events of the renal system. Baseline characteristics, surgical procedures and the mean total infusion volume were comparable. Non-inferiority of hydroxyethyl starch vs. gelatin could be shown by means of the appropriate non-parametric one-sided 95% CI for the difference hydroxyethyl starch-gelatin [-infinity, 11 micromol L(-1)]. Oliguria was encountered in three patients of the hydroxyethyl starch and four of the gelatin treatment group. One patient receiving gelatin required dialysis secondary to surgical complications. Two patients of each treatment group died.
                As we found no drug-related adverse effects of hydroxyethyl starch on renal function, we conclude that the choice of the colloid had no impact on renal safety parameters and outcome in patients with decreased renal function undergoing elective abdominal aortic surgery. It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.
                At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after >or= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.
                Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.
                The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock. We studied the long-term efficacy and safety of medium-molecular-weight hydroxyethyl starch (HES) administered in doses above 20 ml.kg-1 during major blood replacement therapy. Blood replacement for 50 patients used 6% HES 200/0.5 (HES group) or 5% albumin (ALB group) and additional blood components according to a defined protocol. We compared safety, efficacy and costs in 4 peri-operative days. Colloid administration on the day of surgery was 38.4 ml.kg-1 (HES group) and 35.1 ml.kg-1 (ALB group). Haemodynamic, coagulation and renal function parameters were similar. Although total serum protein was still different on the third postoperative day (53.45 gl-1 (HES group) and 60.6 gl-1 (ALB group) (p < 0.01)) the colloid osmotic pressure always remained above 19.5 (2.5) mmHg (HES group). Blood loss (3810 (1632) ml (HES group) and 3455 (1733) ml (ALB group)) and the requirement for blood components was comparable. Costs were reduced by 35% (p < 0.05) in the HES group. We conclude that using 6% HES 200/0.5 as the only colloid for treatment even of large blood loss is a safe and economic alternative to albumin. Large-volume paracentesis associated with plasma volume expansion with albumin is an effective, safe, but costly therapy for ascites in patients with cirrhosis. The aim of this study was to compare the use of a synthetic plasma expander, hydroxyethyl starch (HES), with that of albumin.
                Sixty cirrhotic patients with ascites were studied. Patients were randomly assigned to be infused with either albumin (8 g/l of ascites removed, n = 33) or HES (200 ml/l of ascites removed, n = 27). None of the patients was treated with diuretics or had renal impairment or hyponatremia at entry. Clinical and laboratory data were obtained before and 1, 3 and 15 days after treatment.
                There were no significant differences in clinical and laboratory parameters between the two groups at entry into the study. None of the patients developed renal impairment during the trial. One patient (HES group) presented with hyponatremia. Plasma atrial natriuretic factor and aldosterone levels did not differ between the two groups at baseline or at 1 and 3 days after paracentesis. The volume of ascites removed did not differ between the albumin (7.9 +/- 4.4 l) and HES (6.9 +/- 5.3 l) groups. However, there was a significant difference in weight loss between the albumin and HES groups (7.9 +/- 5.2 kg vs 4.7 +/- 3.4 kg; p = 0.01). Clinical and laboratory parameters indicated that HES was well tolerated except for hypoalbuminemia.
                HES is well tolerated in patients with cirrhosis. There is no difference between HES and albumin in the prevention of complications related to large-volume paracentesis. The lesser degree of weight loss observed with HES needs further study. There is continuing concern on the influence of hydroxethyl starch (HES) on renal function.
                Prospective, randomized study.
                University-affiliated medical center.
                Forty consecutive patients aged >70 years undergoing cardiac surgery using cardiopulmonary bypass.
                Either low-molecular HES (mean molecular weight: 130 kD) with low degree of substitution (0.4) (6% HES 130/0.4) (n=20) or gelatin ( n=20) was given after induction of anesthesia until the 2nd postoperative day (POD) to keep central venous pressure between 12-14 mmHg.
                Creatinine clearance (CC) and fractional sodium clearance (FSC) were measured. N-acetyl-beta-D-glucosamidase, alpha-1-microglobulin, glutathione transferase-pi, and glutathione transferase-alpha were measured from urine specimens. Measurements were made after induction of anesthesia, at the end of surgery, and at the first and the second POD. More gelatin (total: 4150+/-490 ml) than HES 130/0.4 (total: 3450+/-450 ml) was infused within the study. CC and FSC were without differences between the two groups. All measured kidney-specific proteins were almost within normal range at baseline. They increased significantly after surgery, however, without significant group differences. At the 2nd POD, kidney-specific proteins had returned almost to normal values. None of the patients developed acute renal failure.
                Sensitive markers of kidney dysfunction increased in our elderly patients indicating moderate alterations in kidney integrity during cardiac surgery. The two volume replacement regimens did not differ with regard to kidney integrity in elderly patients undergoing cardiac surgery. To compare the new hydroxyethyl starch HES 130/0.4 (Voluven) and the standard HES 200/0.5 (pentastarch) regarding effectiveness for plasma volume substitution and safety of large volumes in heart surgery.
                Fifty-nine patients scheduled for coronary artery bypass grafting were enrolled in a prospective, randomised, double-blind, parallel-group, multicentre, clinical, phase III study. Hydroxyethyl starch was used as the exclusive artificial colloid for acute normovolemic hemodilution, priming of the heart lung machine, and for intra- and postoperative plasma volume substitution from induction of anesthesia until 16 hr after the end of surgery. Efficacy was evaluated by comparing the amount of colloid infused, hemodynamics, and colloid osmotic pressure (COP). Safety endpoints were blood loss, the use of allogeneic blood products, coagulation variables, and adverse events.
                Effectiveness, as assessed by the total amount of infused HES volumes within the treatment period, was similar between HES 130/0.4 and HES 200/0.5 (2,550 mL +/- 561 mL vs 2,466 mL +/- 516 mL). Also, no differences were found for the use of other colloids (pasteurised plasma), hemodynamics, and COP In HES 130/0.4 patients, the postoperative increase of von-Willebrand factor (vWF) was higher (P < 0.01), blood loss was lower, and less packed red blood cells were transfused.
                Hydroxyethyl starch 130/0.4 is an effective plasma volume expander in heart surgery and may be used as the sole artificial colloid to cover the perioperative period. We found a reduced influence of HES 130/0.4 on the physiologic postoperative increase of vWF. The paper deals with the determination of infusion therapy tactics in critically ill patients with intracranial hemorrhages on the basis of invasive measurements of systemic hemodynamics. The routine hemodynamic parameters (blood and central venous pressures, heart rate) are noted to fail to assess the volemic status of the patients in full. Unlike the use of colloidal solutions, infusion therapy with physiological sodium chloride is not shown to correct systemic hemodynamics. It has been ascertained that in acute intracranial hemorrhages, infusion therapy with crystalloidal solutions leads to impaired pulmonary gas exchange and increased pulmonary extravascular fluid and the use of a combination of crystalloidal solutions and a colloidal agent in a 1:1 ratio can correct the volemic status of the patients and is not followed by lung dysfunctions. Hydroxyethylstarch used as a plasma-volume expander in brain-dead kidney donors has been suggested to induce osmotic-nephrosis-like lesions. We have studied its effect on kidney-transplant function.
                52 patients who had received hydroxyethylstarch of iodinated contrast-media before brain death were excluded. 69 other brain-dead patients were prospectively included over 18 months and randomised into two groups. In the hydroxyethylstarch-gelatin group, patients received hydroxyethylstarch up to 33 mL/kg for colloid plasma-volume expansion, and afterwards received modified fluid gelatin. In the gelatin-only group, patients received only modified fluid gelatin as colloid plasma-volume expander. Multiple organs were procured in 29 cases, which included the kidneys in 27 cases (hydroxyethylstarch-gelatin 15, gelatin-only 12).
                There were no significant differences in the characteristics of patients between the two groups of kidney donors or of recipients (except for a small imbalance in sex in the recipients). During the first 8 days after transplantation, nine of 27 (33%) patients required extrarenal haemodialysis or haemodiafiltration in the hydroxyethylstarch-gelatin group compared with one of 20 (5%) in the gelatin-only group (p = 0.029). Serum creatinine concentrations were significantly lower in the gelatin-only group than in the other group (p = 0.009). 10 days after transplantation, mean (SD) serum creatinine was, respectively, 145 (70) and 312 (259) mumol/L.
                These data suggest that hydroxyethylstarch used as a plasma-volume expander in brain-dead donors impairs immediate renal function in kidney-transplant recipients. 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. In this prospective, controlled, randomized, single-center study, we investigated the safety of repetitive large-dose infusion of a novel hydroxyethyl starch solution (6% HES 130/0.4) in cranio-cerebral trauma patients. Patients were randomized to receive either HES 130/0.4 (n = 16) at repetitive doses of up to 70 mL x kg(-1) x d(-1) (which is the largest HES dose reported in the literature) or the control HES 200/0.5 (n = 15) up to its approved dose limit of 33 mL x kg(-1) x d(-1) followed by human albumin up to a total dose (HES 200/0.5 + albumin) of 70 mL x kg(-1) x d(-1). We found no differences between groups in mortality, renal function, bleeding complications, and use of blood products. There were also no major differences in coagulation variables. However, at some time points, factor VIII, von Willebrand factor, and ristocetin cofactor were higher in the HES 130/0.4 group despite the large HES doses administered. We conclude that HES 130/0.4 can safely be used in critically ill head trauma patients over several days at doses of up to 70 mL x kg(-1) x d(-1).
                There are concerns that infusion of certain hydroxyethyl starch (HES) types for plasma volume expansion may influence coagulation and renal function. We investigated the safety of the novel HES 130/0.4 in patients with severe cranio-cerebral trauma. The repetitive HES doses administered in this study are the largest reported in the literature. The administration of albumin improves circulatory function, prevents hepatorenal syndrome, and reduces hospital mortality in patients with cirrhosis and spontaneous bacterial peritonitis. This randomized unblinded pilot study compared the effect of albumin (10 patients) and the synthetic plasma expander hydroxyethyl starch 200/0.5 (10 patients) on the systemic hemodynamics of patients with spontaneous bacterial peritonitis. Baseline measurements were performed within 12 hours after diagnosis of infection. Patients then received 2 doses of the volume expander (1.5 g/kg body weight after baseline measurements and 1 g/kg body weight on day 3). Measurements were repeated after infection resolution. Treatment with albumin was associated with a significant increase in arterial pressure and a suppression of plasma renin activity, indicating an improvement in circulatory function. This occurred in the setting of a significant expansion of central blood volume (increase in cardiopulmonary pressures and atrial natriuretic factor) and an increase in systolic volume and systemic vascular resistance. In contrast, no significant changes were observed in these parameters in patients treated with hydroxyethyl starch. Von Willebrand-related antigen plasma levels significantly decreased in patients treated with albumin but not in those treated with hydroxyethyl starch. Serum nitrates and nitrites increased in patients treated with hydroxyethyl starch but not in those treated with albumin. These data suggest an effect of albumin on endothelial function. In conclusion, albumin but not hydroxyethyl starch improves systemic hemodynamics in patients with spontaneous bacterial peritonitis. This effect is due not only to volume expansion but also to an action on the peripheral arterial circulation. 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. Hydroxyethyl starch (HES) 130/0.4 may impair blood coagulation less than other HES solutions and, thus, may be used at larger doses without increasing the risk of postoperative bleeding. This study tested the hypothesis that volume replacement with 6% HES 130/0.4 at a dose of up to 50 ml/kg does not increase blood loss and transfusion requirements in elective coronary artery bypass surgery compared with 6% HES 200/0.5 at a dose of up to 33 ml/kg.
                One hundred twenty adult patients scheduled for elective coronary artery bypass surgery were randomized to receive up to 50 ml/kg of 6% HES 130/0.4 or up to 33 ml/kg of 6% HES 200/0.5 for volume replacement during surgery and until 24 h thereafter. Volume requirements in excess of the respective maximum dose of HES were treated with gelatin. Colloid use was at the discretion of the attending physicians and not dictated by protocol. The primary outcome variable was chest tube drainage volume during the first 24 h after surgery.
                The data from 117 patients (HES 130/0.4, 59 patients; HES 200/0.5, 58 patients) who completed the study according to protocol were analyzed. The median volumes of HES administered were 49 and 33 ml/kg in the HES 130/0.4 and HES 200/0.5 groups, respectively (P < 0.001). Consequently, patients in the HES 130/0.4 group required less gelatin in addition to HES than those in the HES 200/0.5 group (medians: 7 ml/kg vs. 20 ml/kg, P < 0.001). The combined volumes of HES and gelatin were similar for both groups (P = 0.21). The 24-h chest tube drainage (medians: 660 ml vs. 705 ml, P = 0.60) did not differ significantly between the groups, nor did transfusion outcome.
                Six percent HES 130/0.4 at a median dose of 49 ml/kg did not increase blood loss and transfusion requirements in coronary artery bypass surgery compared with 6% HES 200/0.5 at a median dose of 33 ml/kg. The optimal colloid for renal protection during abdominal aortic aneurysm (AAA) surgery is not known. This study compared the effects of two hydroxyethyl starch (HES) solutions and gelatine on perioperative renal function.
                Sixty-two patients undergoing AAA surgery were randomized to 6 per cent HES of molecular weight 200/0.62 kDa or 130/0.4 kDa, or 4 per cent gelatine for plasma expansion. Measurements were taken of serum urea and creatinine to mark glomerular filtration, urinary immunoglobulin G : creatinine ratio to mark glomerular membrane function and alpha(1)-microglobulin : creatinine ratio to mark tubular dysfunction before, and for 5 days after, surgery.
                Serum urea was lower in both HES groups than the gelatine group. Serum creatinine was lower with HES 130/0.4 compared with gelatine at days 1, 2 and 5 after surgery (P = 0.020, P = 0.045 and P = 0.045 respectively). Urinary alpha(1)-microglobulin : creatinine ratio was lower with HES 200/0.62 compared with gelatine at 4 and 8 h (P < 0.050) and lower with HES 130/0.4 compared with gelatine at 4 to 24 h, and on days 4 and 5 (P < 0.050). Urinary immunoglobulin G : creatinine was lower in both HES groups compared with gelatine. There was no difference between the two starch groups.
                Compared with gelatine, volume expansion with both types of HES during AAA surgery improved renal function and reduced renal injury. To examine the effects of hydroxyethyl starch (HES) on renal function.
                Randomized, controlled trial.
                Operating theatre of a university hospital.
                60 ASA physical status I and II male patients undergoing middle ear surgery.
                Patients received either lactated Ringer's solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringer's solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour.
                Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously.
                There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups.
                Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation. Hydroxyethylstarch used for volume restoration in brain-dead kidney donors has been associated with impaired kidney function in the transplant recipients. We undertook a multicentre randomised study to assess the frequency of acute renal failure (ARF) in patients with severe sepsis or septic shock treated with hydroxyethylstarch or gelatin.
                Adults with severe sepsis or septic shock were enrolled prospectively in three intensive-care units in France. They were randomly assigned 6% hydroxyethylstarch (200 kDa, 0.60-0.66 substitution) or 3% fluid-modified gelatin. The primary endpoint was ARF (a two-fold increase in serum creatinine from baseline or need for renal replacement therapy). Analyses were by intention to treat.
                129 patients were enrolled over 18 months. Severity of illness and serum creatinine (median 143 [IQR 88-203] vs 114 [91-175] micromol/L) were similar at baseline in the hydroxyethylstarch and gelatin groups. The frequencies of ARF (27/65 [42%] vs 15/64 [23%], p=0.028) and oliguria (35/62 [56%] vs 23/63 [37%], p=0.025) and the peak serum creatinine concentration (225 [130-339] vs 169 [106-273] micromol/L, p=0.04) were significantly higher in the hydroxyethylstarch group than in the gelatin group. In a multivariate analysis, risk factors for acute renal failure included mechanical ventilation (odds ratio 4.02 [95% CI 1.37-11.8], p=0.013) and use of hydroxyethylstarch (2.57 [1.13-5.83], p=0.026).
                The use of this preparation of hydroxyethylstarch as a plasma-volume expander is an independent risk factor for ARF in patients with severe sepsis or septic shock. There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution (HES) in critically ill patients. The effects of volume replacement with HES over 5 days on hemodynamics, laboratory data, and organ function were compared with volume therapy using human albumin (HA).
                Prospective, randomized study.
                Clinical investigations on a surgical intensive care unit (ICU) of a university hospital.
                150 traumatized patients (injury severity score > 15) and 150 postoperative patients with sepsis were analyzed.
                Either 10% low-molecular weight HES (HES-trauma, n = 75; HES-sepsis, n = 75) or 20% HA (HA-trauma, n = 75; HA-sepsis, n = 75) was given for 5 days to maintain the pulmonary capillary wedge pressure (PCWP) between 12 and 15 torr. The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen.
                In addition to extensive cardiorespiratory monitoring, several routine laboratory parameters for assessing pulmonary, renal, hepatic, and coagulation function were analyzed from arterial blood samples on the day of admission to the ICU and on the day of sepsis diagnosis, respectively ("baseline" value) and daily over the following 5 days. Mortality during and after the study did not differ significantly between the infusion groups. There were also no differences between the incidence of pulmonary, renal, or hepatic failure in the two subgroups. Mean arterial pressure, heart rate, and PCWP were similar in both subgroups, whereas cardiac index, oxygen delivery index, oxygen consumption index, and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups. Standard coagulation parameters did not differ, albumin concentration increased significantly in both HA groups, and lactate concentrations decreased only in the HES-sepsis patients (from 2.8 +/- 0.5 to 1.5 +/- 0.4 mg/dl). Volume replacement using albumin was significantly (p < 0.001) more costly than therapy with HES.
                Volume therapy with 10% HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20% albumin. Volume replacement using HES may even be associated with improved hemodynamics. HES appears to be a valuable and significantly cheaper alternative to albumin--even for prolonged volume therapy in the critically ill patient.
Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products.