A triple-blinded randomized trial comparing the hemostatic effects of large-dose 10% hydroxyethyl starch 264/0.45 versus 5% albumin during major reconstructive surgery. Use of modified fluid gelatin and hydroxyethyl starch for colloidal volume replacement in major orthopaedic surgery. Hetastarch increases the risk of bleeding complications in patients after off-pump coronary bypass surgery: a randomized clinical trial. Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock. Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin. Influence of different strategies of volume replacement on the activity of matrix metalloproteinases: an in vitro and in vivo study. Influence of crystalloid and colloid replacement solutions on hemodynamic variables during acute normovolemic hemodilution. Hemodynamic comparison of albumin and hydroxyethyl starch in postoperative cardiac surgery patients. 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. [Volume replacement with a new hydroxyethyl starch preparation (3 percent HES 200/0.5) in heart surgery]. Therapeutic influence of 20 % albumin versus 6% hydroxyethylstarch on extravascular lung water in septic patients: a randomized controlled trial. Influence of hydroxyethyl starch on coagulation in patients during the perioperative period. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. [A comparison of the hemodynamic effect of Haemaccel and diluted albumin in the immediate postoperative period after heart surgery]. Is 6% hydroxyethyl starch 130/0.4 safe in coronary artery bypass graft surgery? Fluid resuscitation with colloids of different molecular weight in septic shock. Effects of polygeline and hydroxyethyl starch solutions on liver functions assessed with LIMON in hypovolemic patients. [Comparison of postoperative volume therapy in heart surgery patients]. [Effect of hydroxyethyl starch HES 450/0.7 and 5% human albumin on the colloid osmotic pressure and hemodynamic parameters in hypovolemic patients after major abdominal procedures]. Does the type of volume therapy influence endothelial-related coagulation in the critically ill? Effects of colloid or crystalloid administration on pulmonary extravascular water in the postoperative period after coronary artery bypass grafting. Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration. Volume therapy in the critically ill: is there a difference? A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations. Hydroxyethyl starch versus albumin for colloid infusion following cardiopulmonary bypass in patients undergoing myocardial revascularization. [Coagulation changes during aortofemoral bifurcation bypass: is volume and plasma substitution possible with hydroxyethyl starch alone?]. The effects of perioperatively administered crystalloids and colloids on concentrations of molecular markers of activated coagulation and fibrinolysis. Postoperative complications after blood replacement with or without plasma. A trial in elective surgery. Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for volume expansion in cardiac surgery patients: the effects on perioperative bleeding and transfusion needs. Colloid solutions in the critically ill. A randomised comparison of albumin and polygeline. 1. Outcome and duration of stay in the intensive care unit. Replacement of major surgical blood loss by hypo-oncotic or conventional plasma substitutes. [Comparison of effects of Elohes and albumin on hemostasis in orthopedic surgery]. Clinical study of a formula for delayed rapid fluid resuscitation for patients with burn shock. Randomized clinical trial comparing the effects on renal function of hydroxyethyl starch or gelatine during aortic aneurysm surgery. Fluid resuscitation with Haemaccel vs. human albumin following coronary artery bypass grafting. Fluid balance and pulmonary functions during and after coronary artery bypass surgery: Ringer's acetate compared with dextran, polygeline, or albumin. Effects of three colloid solutions on plasma volume and hemodynamics after coronary bypass surgery. Short-term effectiveness of different volume replacement therapies in postoperative hypovolaemic patients. HES 130/0.4 (Voluven) or human albumin in children younger than 2 yr undergoing non-cardiac surgery. A prospective, randomized, open label, multicentre trial. Influence of dextran-70 on systemic inflammatory response and myocardial ischaemia-reperfusion following cardiac operations. A comparison of 10% pentastarch and 5% albumin in patients undergoing open-heart surgery. Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery. Why albumin may still work. Effects of hetastarch and albumin on coagulation in patients with septic shock. Infusion of albumin attenuates changes in serum protein binding of drugs in surgical patients compared with volume replacement with HAES. Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion. Comparison of the hemodynamic and oxygen transport responses to modified fluid gelatin and hetastarch in critically ill patients: a prospective, randomized trial. Cardiac response is greater for colloid than saline fluid loading after cardiac or vascular surgery. Comparison of hetastarch with albumin for postoperative volume expansion in children after cardiopulmonary bypass. A comparison of 4.5% human albumin solution and Haemaccel in neonates undergoing major surgery. Peri-operative tolerance to large-dose 6% HES 200/0.5 in major urological procedures compared with 5% human albumin. [Comparison of volume substitutes 5 percent human albumin and 6 percent hydroxyethyl starch (40,000/0.5) in pediatric anesthesia]. [Comparison of 5% human albumin and 6% 200/0.5 HES as exclusive colloid components in large surgical interventions]. Large-dose administration of 6% hydroxyethyl starch 200/0.5 total hip arthroplasty: plasma homeostasis, hemostasis, and renal function compared to use of 5% human albumin. The influence of volume therapy and pentoxifylline infusion on circulating adhesion molecules in trauma patients. Influence of different volume therapy regimens on regulators of the circulation in the critically ill. The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients. Randomized study comparing the effects of hydroxyethyl starch solution with Gelofusine on pulmonary function in patients undergoing abdominal aortic aneurysm surgery. Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery. Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial. Effects of albumin 5% and artificial colloids on clot formation in small infants. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Alternatives to albumin administration in hepatocellular carcinoma patients undergoing hepatectomy: an open, randomized clinical trial of efficacy and safety. Effects of acute hypervolemic fluid infusion of hydroxyethyl starch and gelatin on hemostasis and possible mechanisms. Influence of different intravascular volume therapies on platelet function in patients undergoing cardiopulmonary bypass. Randomized trial of hydroxyethyl starch versus gelatine for trauma resuscitation. Hydroxyethyl starch: an alternative to plasma for postoperative volume expansion after cardiac surgery. Complement activation by polystarch and gelatine volume expanders. Giving both enoxaparin and dextran increases the need for transfusion in revision hip arthroplasty. Assessment of hemodynamic and gastric mucosal acidosis with modified fluid versus 6% hydroxyethyl starch: a prospective, randomized study. Hemodynamic effects of 6% and 10% hydroxyethyl starch solutions versus 4% albumin solution in septic patients. 3.5% urea-linked gelatin is as effective as 6% HES 200/0.5 for volume management in cardiac surgery patients. Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery. Clinical comparison of hetastarch and albumin in postoperative cardiac patients. Comparison of hetastarch to albumin for perioperative bleeding in patients undergoing abdominal aortic aneurysm surgery. A prospective, randomized study. Effect of intraoperative fluid administration and colloid osmotic pressure on the formation of intestinal edema during gastrointestinal surgery. The safety of modern hydroxyethyl starch in living donor liver transplantation: a comparison with human albumin.
In Canada, hydroxyethyl starch 264/0.45 (HES 264/0.45; molar weight 264 kDa, molar substitution 0.45) has largely replaced albumin as the colloidal fluid of choice for perioperative intravascular volume expansion. The maximum recommended dose of HES 264/0.45 is 28 mL/kg; however, there are no clinical data supporting this limit. In this study we compared the hemostatic effects of HES 264/0.45 versus 5% albumin in doses up to 45 mL/kg over 24 h during major reconstructive head and neck surgery. Fifty patients were randomized to receive HES 264/0.45 or 5% human albumin from the induction of anesthesia until 24 h thereafter. Both albumin and HES 264/0.45 effectively maintained physiologic variables in the perioperative and postoperative periods. The partial thromboplastin time and international normalized ratio were significantly increased in the HES 264/0.45 group compared with the albumin group after infusion of 30 mL/kg and 45 mL/kg (P < 0.05). Factor VIII activity and von Willebrand factor level were significantly reduced in the HES 264/0.45 group compared with the albumin group after infusion of 15 mL/kg, 30 mL/kg, and 45 mL/kg (P < 0.05). Significantly more subjects in the HES 264/0.45 group received allogeneic red blood cell transfusions (P < 0.02). We conclude that HES 264/0.45 infusions >30 mL/kg over 24 h impair coagulation to a greater extent than albumin, possibly leading to more allogeneic transfusions. 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. Hetastarch is an artificial colloid widely used intraoperatively in fluid-replacement regimens. Previous studies have found that the intraoperative administration of hetastarch may increase the risk of postoperative bleeding in patients who undergo coronary artery bypass graft surgery with cardiopulmonary bypass. Previous published reports have not examined this risk in patients who underwent coronary artery bypass grafting without cardiopulmonary bypass.
                In a randomized clinical trial, 156 patients undergoing off-pump coronary artery bypass grafting were assigned to receive either 1 liter of hetastarch or 1 liter of albumin as part of intraoperative volume replacement. Sample recruitment was halted in a review per protocol by the study's Data Safety Monitoring Committee. We assessed the rate of postoperative bleeding by monitoring the number of units of blood products transfused in the first 24 postoperative hours in the intensive care unit and the hourly chest tube drainage in the first 12 postoperative hours.
                Intraoperative administration of 1 liter of hetastarch was associated with statistically significant increases in 3 measures: transfusion requirements on postoperative day 1 (red blood cells, 1.14 vs 0.40 units, P = .017; fresh-frozen plasma, 0.57 vs 0.15, P = .009; platelets, 0.35 vs 0.10, P = .013); the overall likelihood of receiving transfusion on postoperative day 1 (46.2% vs 25.6%, P = .012); and the volume of chest tube drainage in the first 12 hours postoperatively (732.0 vs 563.6 mL, P < .001).
                In patients undergoing off-pump coronary artery bypass, the intraoperative administration of hetastarch increases the postoperative transfusion requirement and the volume of blood drained postoperatively. 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. Stable haemodynamics is often achieved by administration of colloids after cardiac surgery. We conducted a prospective, randomized, open-label study comparing haemodynamics and acid-base equilibrium after infusion of two rapidly degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac surgical patients.
                45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 6% HES (mW 130 kDa, n = 15), 6% HES (MW 200 kDa, n = 15) or 4% HA (MW 69 kDa, n = 15) after on-pump cardiac surgery.
                Left ventricular filling pressures assessed using pulmonary artery catheter responded similarly in all groups. mean (SD) cardiac index was higher in HES130 [3.5 l min(-1) m(-2) (0.7) ] and HES200 [3.5 l min(-1) m(-2) (0.5)] than in HA [2.8 l min(-1) m(-2) (0.6)] group after completion of infusion (P = 0.002) but no differences were detected at 2 and 18 hours. Oxygen delivery increased in both HES groups but not in HA group. After cessation of infusion base excess was the most negative in Ha group. At 2 hours mean (SD) base excess was higher in HES130 [0 (1.32)] than in HES200 [-1.32 (2.27) ] and HA [-2.3 (1.3)] group (P = 0.002, between the groups).
                We conclude that the effect of albumin on cardiac performance is inferior than that of HES130 or HES200 in early postoperative phase after cardiac surgery. HES130 induces no alterations in acid-base equilibrium whereas a negative base excess was observed after HA infusion. Excessive production of matrix metalloproteinase 9 (MMP-9) is linked to tissue damage and anastomotic leakage after large bowel surgery. Hence, the aim of this study was to verify whether different strategies of fluids administration can reduce MMP-9 expression.
                In the in vitro experiment, the authors tested the hypothesis of a direct inhibition of MMP-9 by the fluids used perioperatively, i.e., lactated Ringer's solution, 3.4% poligeline, and hydroxyethyl starch 130/0.4. In the in vivo experiment, 36 patients undergoing surgery for colon cancer were randomly assigned to three groups to receive lactated Ringer's solution, poligeline, or hydroxyethyl starch. MMP-9 and tissue inhibitor of metalloproteinases were measured from venous blood samples; the MMP-9/tissue inhibitor of metalloproteinases ratio was calculated as an index of equilibrium between the action of MMP-9 and its inhibition.
                In the in vitro experiment, the presence of hydroxyethyl starch 130/0.4 in the MMP-9 assay system showed a strong inhibition of the enzymatic activity compared with lactated Ringer's solution. In the in vivo experiment, MMP-9 and tissue inhibitor of metalloproteinases plasma levels did not differ among the three groups at baseline, whereas those levels increased significantly at the end of surgery. At that time, the MMP-9 plasma levels and the MMP-9/tissue inhibitor of metalloproteinases ratio were significantly higher in the lactated Ringer's solution and poligeline groups than in the hydroxyethyl starch group. These results were confirmed 72 h after surgery.
                This study demonstrates that hydroxyethyl starch 130/04 decreases the circulating levels of MMP-9 in patients undergoing abdominal surgery. To determine whether, in maintaining normovolemia during acute normovolemic hemodilution, replacement fluid choice influences intraoperative hemodynamic variables.
                Prospective, randomized, single-blinded study.
                Operating room of a tertiary-care university hospital.
                40 adult, ASA physical status I, II, and III patients scheduled for acute normovolemic hemodilution during radical prostatectomy.
                Patients were randomly assigned to four replacement fluid groups to receive 1) Ringer's lactate, 2) 5% albumin, 3) 6% dextran 70, or 4) 6% hetastarch. A standardized general anesthetic was used, and patients underwent moderate hemodilution to a target hemoglobin of 9 gm/dL.
                Hemodynamic variables were recorded using standard monitors, 5-lead electrocardiography, radial arterial catheter, and pulmonary artery catheter. Red blood cell loss for the entire hospitalization was calculated.
                Demographic and clinical outcome data were similar among the groups. During acute normovolemic hemodilution, heart rate and pulmonary capillary wedge pressure were unchanged from baseline in all groups, but patients receiving Ringer's lactate or albumin had greater declines in mean arterial pressure at the end of acute normovolemic hemodilution. Cardiac and oxygen consumption indexes were stable during acute normovolemic hemodilution, but oxygen extraction increased.
                During hemodilution, anesthetized patients maintain whole body oxygenation by increasing oxygen extraction. The administration of hetastarch or dextran as the replacement fluid during acute normovolemic hemodilution is associated with a more stable mean arterial pressure, but overall acute normovolemic hemodilution is well tolerated irrespective of the replacement fluid used. The hemodynamic effects of 2 plasma volume expanders were compared in postoperative open heart surgery patients. Albumin 5% (A) or hydroxyethyl starch 6% (HES) solutions were infused according to indications based on cardiac index (CI) and pulmonary wedge pressure (WP), and their effects evaluated by physiologic profile measurements. Both groups demonstrated significant increases with volume infusion in CI (A from 2.37 to 2.84; HES from 1.97 to 2.49 L/min X m2) and WP (A from 9.4 to 13.7 mm Hg; HES from 11.9 to 13.2 mm Hg). Stroke index and stroke work increased similarly. Mean systemic arterial pressure (MAP) and mean pulmonary arterial pressure (MPAP) remained unchanged. No significant difference for any variable was demonstrated between the A and HES groups. In the volume used, from 250 to 750 ml, HES caused no bleeding abnormalities. HES is as effective as A as a plasma volume expander in postoperative cardiac surgery patients. 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. In a randomized study including 55 patients undergoing elective aorto-coronary bypass surgery efficacy of a low concentrated hydroxyethylstarch (3% HES 200/0.5) was tested after extracorporeal circulation (ECC). All patients received 1,000 ml autologous washed erythrocytes (cell saver) and 400 ml fresh frozen plasma (FFP). Thereafter patients were randomized into 4 groups. Hemodynamic parameters, laboratory parameters as well as extravascular lung water (EVLW - double indicator dilution technique) were measured before ECC as well as before and after infusion therapy. With regard to hemodynamic efficiency and the change in laboratory data no relevant differences between group I, II and III could be seen. EVLW-measurement demonstrated the lowest increase in lung water after infusion of HES; simultaneously pulmonary gas exchange was less compromised in comparison to the other infusion groups. 3% HES 200/0.5 solution can be considered as an effective volume substitute with short intravascular retention time, which seems to be of advantage in patients coming off extracorporeal circulation. Recent studies demonstrated that extravascular lung water (EVLW) is a reliable and independent marker for outcome. The primary therapeutically goal in critically ill patients is to resuscitate and retain adequate organ perfusion by fluid administration, where is necessary to achieve adequate intravascular filling, but avoid initiation of pulmonary edema.
                Patients with severe sepsis were randomly allocated to a group treated with 20% Albumin 100 ml every 12 hours (ALB; n = 30) or with 6% hydroxyethylstarch 130/0, 4 250 ml every 6 hours (HES; n = 26). Both treatments were completed by crystalloids or norephinephrin as necessary. We analyzed amount of developed EVLW, and relation with mortality, PaO2/FiO2 and alveolo-arterial oxygen difference.
                We observed significantly greater decrease of EVLW when compared with baseline during whole monitored period of 72 hours in ALB group in contrast to HES patients (p < 0.05). Despite no significant changes of EVLW in HES group, we noted improve of PaO2/FiO2 and AaDO2 in both groups. We did not observed significant difference in mortality.
                The present study results show can summarize that albumin reduces in a higher amount and earlier the extravascular lung water than HES, but this reduction was not associated with improvement of oxygenation functions, which was better in HES group. The perioperative use of hydroxyethyl starch (HES) has been implicated as a possible cause of intracranial bleeding. The purpose of this study was to compare the influence on blood coagulation of the isovolemic replacement of 1-L blood loss with either 6% HES (molecular weight [MW] average: 450,000) or 5% human albumin during neurosurgery or lower abdominal surgery. Twenty patients scheduled for brain tumor surgery and 20 patients undergoing transabdominal hysterectomy were studied. The activated partial thromboplastin time, prothrombin time, fibrinogen concentration, factor VIII coagulant, von Willebrand factor antigen, platelet count, and the activated clotting time were compared after induction of anesthesia, after administration of 500 and 1000 mL of colloid solution, and 24 and 48 h postoperatively. All measured coagulation variables remained within physiologic range. Changes in coagulation indices were identical in neurosurgical and hysterectomy patients, except for a larger increase in fibrinogen concentration 24 and 48 h after hysterectomy. The acute phase reaction of factor VIII coagulant and von Willebrand factor, which plays a role in postoperative hypercoagulability, was attenuated by the use of HES. We conclude that isovolemic replacement of 1-L blood loss with either 6% HES (MW average: 450,000) or 5% human albumin does not interfere with normal hemostasis during and after neurosurgery or lower abdominal surgery. 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. nan The aim of this study was to compare 6% hydroxyethyl starch 130/0.4 with 4% succinylated gelatin for priming the cardiopulmonary bypass circuit and as volume replacement in patients undergoing coronary artery bypass, in terms of postoperative bleeding, blood transfusion requirements, renal function, and outcome after surgery. Forty-five patients received 6% hydroxyethyl starch 130/0.4 (Voluven) and another 45 were given 4% succinylated gelatin (Gelofusine) as the priming solution for the cardiopulmonary bypass circuit as well as for volume replacement. Postoperative bleeding was quantified from the hourly chest drainage in the first 4 h and at 24 h postoperatively. The baseline characteristics of both groups were similar. In the hydroxyethyl starch group, the total amount of colloid used was 1.9 +/- 1.0 L, while the gelatin group had 2.0 +/- 0.7 L. There was no significant difference in hourly chest drainage between groups. Blood transfusion requirements, estimated glomerular filtration rate, extubation time, intensive care unit and hospital stay were similar in both groups. It was concluded that 6% hydroxyethyl starch 130/0.4 is a safe alternative colloid for priming the cardiopulmonary bypass circuit and volume replacement in patients undergoing coronary artery bypass surgery. The aim of this study was to investigate the short-term effect of fluid resuscitation with 4% modified fluid gelatine (GEL) versus 6% hydroxyethyl starch (HES) on haemodynamics and oxygenation in patients with septic shock and acute lung injury (ALI).
                Prospective randomised clinical trial.
                Twenty-bed intensive care unit in a university hospital.
                Thirty hypovolemic patients (intrathoracic blood volume index, ITBVI <850 ml/m(2)) in septic shock with ALI were randomised into HES (mean molecular weight: 200,000 Dalton, degree of substitution 0.6) and GEL (mean molecular weight: 30,000 Dalton) groups (15 patients each).
                For fluid resuscitation 250 ml/15 min boluses (max. 1,000 ml) were given until the end point of ITBVI >900 ml/m(2) was reached. Repeated haemodynamic measurements were done at baseline (t(b)), at the end point (t(ep)) then at 30 min and 60 min after the end point was reached (t(30), t(60)). Cardiac output, stroke volume, extravascular lung water (EVLW), and oxygen delivery was determined at each assessment point. For statistical analysis two-way ANOVA was used.
                ITBVI, cardiac index, and oxygen delivery index increased significantly at t(ep) and remained elevated for t(30) and t(60), but there was no significant difference between the two groups. The increase in the ITBVI by 100 ml of infusion was similar in both groups (HES: 26+/-19 ml/m(2) vs GEL: 30+/-19 ml/m(2)). EVLW, remained unchanged, and there was no significant difference between the groups (HES, t(b): 8+/-6, t(60): 8+/-6; GEL, t(b): 8+/-3, t(60): 8+/-3 ml/kg). The PaO(2)/FiO(2) did not change significantly over time or between groups (HES, t(b): 207+/-114, t(60): 189+/-78; GEL, t(b): 182+/-85, t(60): 182+/-85 mmHg).
                The results of this study indicate that both HES and GEL infusions caused similar short-term change in ITBVI in septic shock, without increasing EVLW or worsening oxygenation. Hypovolemia is a common clinical entity in critical patients, and adequate volume replacement therapy seems to be essential for maintaining tissue perfusion. However, it is still uncertain which solution is most appropriate for fluid resuscitation.
                The aim of this study was to investigate the effects of fluid resuscitation with 3.5% polygeline versus 6% hydroxyethyl starch solutions on hemodynamic functions and liver functions assessed with a noninvasive liver function monitoring system (LIMON) in hypovolemic patients.
                This study is a prospective randomized clinical trial.
                Thirty hypovolemic patients (intrathoracic blood volume index, <850 mL/m(2)) were randomized into hydroxyethyl starch (mean molecular weight, 130,000 Da) and polygeline (mean molecular weight, 30,000 Da) groups (15 patients each). Indocyanine green plasma disappearance elimination (ICG-PDR) were conducted concurrently using LIMON. A dose of 0.3 mg/kg ICG was given through a cubital fossa vein as a bolus. For fluid resuscitation, 500 mL of colloid was given to the patients. Repeated hemodynamic and ICG-PDR measurements were done at baseline, after infusion, and then at 30 minutes after infusion.
                Intrathoracic blood volume index and systolic, diastolic, and mean blood pressures increased significantly after infusion and remained elevated for 30 minutes after infusion, but there was no significant difference between the 2 groups. Indocyanine green plasma disappearance elimination values were similar in both groups with no significant difference between the two.
                Increasing intrathoracic blood volume index and hemodynamic variables by fluid loading is not associated with a significant change in ICG-PDR.
                Copyright (c) 2010 Elsevier Inc. All rights reserved. Patients who have undergone cardiac surgery with use of extracorporeal circulation frequently reveal marked hypovolaemia in spite of a highly positive fluid balance. This is thought to be due to transient microvascular damage and extravascular fluid shift. Further volume replacement to achieve haemodynamic stability in the postoperative period may cause fluid overload and congestive heart failure. The present study was designed to investigate whether this fluid overload could be avoided by using a hypertonic-hyperoncotic solution (group I: HHL, 10% hydroxyethylstarch 200/0.5 in 7.2% saline) instead of two different standard colloid solutions (group II: HA, 5% albumin; group III: HES, 6% hydroxyethylstarch in 0.9% saline).
                Twenty-one patients meeting our criteria for hypovolaemia immediately after cardiac surgery were randomly assigned to three groups. Patients in group I received HHL in increments of 150 ml, while patients in group II and group III were given HA and HES respectively in increments of 500 ml until hypovolemia was corrected. Haemodynamic assessment was done using a pulmonary artery thermodilution catheter. Intra- and extravascular volumes, including extravascular lung water (EVLW), intrathoracic blood volume (ITBV), and total blood volume (TBV) were measured by the double indicator technique using lung water software (COLD-System, Pulsion, Munich, Germany).
                Correction of hypovolaemia-related haemodynamic parameters and restoration of normal TBV were achieved by 236 +/- 80 ml of HHL (group I), 857 +/- 244 ml of HA (group II) and 1000 +/- 0 ml of HES (group III) respectively. TBV increased significantly in each group, compared to baseline values. EVLW did not change significantly in any group. We found that the volume-augmenting effect of HHL per millilitre infused solution was more than four times that of HA and HES, primarily as a result of increasing plasma osmolality due to an increase of plasma sodium levels. This pronounced effect on intravascular volume of HHL lasted for only 2 h following infusion, however, and did not lead to any unwanted side effects. In the period between 2 and 20 h after primary volume replacement, further fluid therapy with colloids and crystalloids, guided by clinical signs of hypovolaemia, was necessary in each group of patients. The overall fluid requirements for the first 20 h after operation did not differ among the three resuscitation regimens.
                We found that HHL is a safe and effective solution for acute correction of hypovolaemia after cardiac surgery. The advantages of a smaller initial volume load by HHL cannot be maintained for longer than 2 h. In a randomized study 20 patients with hypovolemia following abdominal surgery for malignoma were treated with 500 ml HES 450/0.7 or human albumin 5% during the first 24 h after operation. COP and various blood- and hemodynamic parameters were measured immediately before and after infusion as well as 2, 4 and 6 h after infusion. After HES-infusion COP increased from 20.2 to about 22 mmHg and remained at a significantly higher level (p less than 0.01) for 6 h. After albumin-infusion COP increased from 19.7 to 20.7 mmHg, but already returned to starting level within 2 h. CVP in the HES-group increased from 2.8 to 6.3 cmH2O after infusion, and then gradually dropped to 4 cmH2O during 6 h. In the albumin-group CVP increased from the same starting level only to 4.2 cmH2O, and then dropped back to 3.2 cmH2O after 6 h (no significant difference to the starting level). The other blood- and hemodynamic parameters measured showed no significant differences between the two groups. The results show that a quick and reliable improvement of hypovolemia can be obtained in both groups immediately after infusion, but that the COP- and volume-stabilizing effects of HES-infusion are more distinct and remained for a significantly longer period of time than the effects of albumin 5%-infusion. The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin (TM). The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospective, randomized study. Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10% low-molecular weight (LMW) hydroxyethylstarch solution (HES-trauma, n = 15; HES-sepsis, n = 15) or 20% human albumin (HA-trauma, n = 15; HA-sepsis, n = 15) for 5 days to maintain central venous pressure (CVP) between 12 and 16 mm Hg. Plasma concentrations of TM, protein C, (free) protein S and thrombin-antithrombin (TAT) were measured in arterial blood samples obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days. There were no differences between HA- and HES-treated trauma patients. Protein C and protein S also did not differ between HA- and HES-treatments. At baseline, TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only. In the HA-sepsis group, TM increased significantly (from 48.1 (SD 13.9) to 68.4 (13.0) micrograms litre-1), whereas it remained almost unchanged in the HES-sepsis group. In HES-sepsis patients, protein C (from 51.0 (10.1) to 71.9 (8.9)%) and protein S (from 19.0 (6.0) to 40.8 (11.4)%) increased significantly during the study, whereas both remained reduced in HA-patients. TAT (indicating intravascular coagulation) did not differ between the two fluid groups. We conclude that in trauma patients, the type of volume therapy had no influence on the TM-protein C-protein S system. In sepsis patients, volume therapy with HES was beneficial, whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation. The effect of postoperative fluid management on pulmonary extravascular thermal volume (ETVL) as in index of pulmonary extravascular water after coronary artery bypass grafting was compared, using the thermal-dye technique, among five patients who received 5% albumin (group A), five patients who received 6% hydroxyethyl starch (group H), and five who received lactated Ringer's solution (group C). Intraoperatively, all patients received lactated Ringer's solution intravenously, and the cardiopulmonary bypass (CPB) circuit prime included 5% albumin. No statistically significant changes in ETVL occurred postoperatively in any group, nor did ETVL differ significantly between groups. After CPB, colloid osmotic pressure (COP) significantly decreased and pulmonary artery wedge pressure (WP) and the WP-COP gradient significantly increased in each group, implying an increase in transcapillary fluid flux. Cardiac index changed variably. Pulmonary shunt fraction (Qsp/Qt) did not change in groups A and C but decreased during CPB in group H (from 0.22 +/- 0.03 to 0.16 +/- 0.11). Postoperatively, patients in the three groups received similar volumes of fluids and had similar perioperative weight gains. By the next morning (AM1), COP increased in all groups, returning to levels noted before CPB in group C, and exceeding these levels in groups A and H. Wedge pressure was similar in all three groups on AM1. PaO2 decreased significantly, and alveolar-arterial oxygen partial pressure difference increased significantly in all groups on AM1. In Group H, Qsp/Qt returned to levels observed before CPB by AM1 (0.27 +/- 0.09). We conclude that in patients without postoperative increases in WP, ETVL changes minimally during CPB and is not influenced by the type of fluid administered as the primary volume replacement in the postoperative period. To explore whether disturbed fibrin polymerization is the main problem underlying dilutional coagulopathy and can be reversed by fibrinogen administration, we conducted a prospective study using modified thrombelastography (ROTEM).
                Sixty-six orthopedic patients randomly received modified gelatin solution, hydroxyethyl starch 130/0.4, or exclusively Ringer lactate solution. ROTEM analysis was performed, concentrations of coagulation factors and markers of thrombin generation were measured. Fibrinogen concentrate (Hemocomplettan) was administered (30 mg/kg) when thrombelastographically measured fibrinogen polymerization was critically decreased.
                The alpha angle, clot firmness, and fibrinogen polymerization (median [min to max]) significantly decreased in the patients receiving hydroxyethyl starch (area under the curve minus baseline (-5 [-9 to -2]), followed by gelatin solution (-3 [-8 to 0]), with the least reductions seen for Ringer lactate solution (-2 [- 4 to 1]) (colloids versus Ringer lactate P < 0.0001). Thirteen patients in the colloid groups but none in the Ringer lactate group needed fibrinogen concentrate to maintain borderline clot firmness. Activity of FVII, FVIII, FIX, and von Willebrand ristocetin activity decreased significantly with colloids. Thrombelastographically measured coagulation time, molecular markers of thrombin generation, and activity of all other coagulation factors were comparable in all groups.
                Disturbance of fibrinogen/fibrin polymerization is the primary problem triggering dilutional coagulopathy during major orthopedic surgery. The magnitude of clot firmness reduction is determined by the type of fluid used, with hydroxyethyl starch showing the most pronounced effects. These undesirable effects of intravascular volume therapy can be reversed by increasing fibrinogen concentration by administering fibrinogen concentrate, even during continuing blood loss and intravascular volume replacement. 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. 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 or hetastarch (HES), a synthetic colloid for intravascular volume expansion, was compared with albumin after coronary artery operations in 30 patients (15 in each study group). Cardiac index, atrial pressures, heart rate, and systolic blood pressure were similar in both groups. There were no differences in cumulative urine output at 24 hours or in weight change during the first 7 postoperative days. Values for colloid osmotic pressure, as well as for this variable minus left atrial pressure, were lowest soon after bypass but returned to baseline within 4 hours, with no difference between groups in the first 24 hours or 7 days after operation. Coagulation variables were similar, but prothrombin and partial thromboplastin times were higher 12 hours postoperatively and fibrinogen level was lower 7 days postoperatively in the patients receiving HES. There was no clinical evidence of excessive bleeding, although cumulative chest drainage at 12 and 24 hours was slightly higher in the HES group (p = 0.09 and 0.08, respectively). We conclude that hetastarch is a safe and effective colloid to use following coronary operations. The study explored the possibility of eliminating the need for plasma replacement with expensive human albumin (HA) and fresh frozen plasma (FFP) and instead using hydroxyethyl starch (HES). Patients undergoing infrarenal aortofemoral bifurcation grafting were randomly assigned to one group, which received FFP and HA, or another group, which received HES as volume replacement. Blood specimens were collected at five time intervals: preoperatively, prior to cross-clamping of the aorta, prior to declamping, at the end of the operation, and 6 h postoperatively. Preoperative coagulation values were all within normal limits. The basic coagulation tests were generally affected by the standardized heparin dose of 5000 IU administered during the clamping phase. Euglobulin lysis demonstrated a perioperative climb that was particularly marked within the HES group at the time of clamping. Values returned to initial levels 6 h postoperatively. Plasminogen, fibrinogen, antithrombin III, and antiplasmin concentrations fell significantly in both groups; 10% to 20% lower values were determined within the HES group due to the lack of factor substitution. The reduction in the coagulation factors can be explained as a dilution effect, but there are also signs of a consumption reaction taking place at the onset of the operation involving activation of coagulation and fibrinolysis. Restricting the use of FFP and simultaneously increasing HES administration is justifiable in procedures involving the abdominal aorta with moderate blood loss. To explore whether intravenous administration of routinely used crystalloid or colloid solutions differently affects the coagulation system, we investigated orthopaedic patients. Since crystalloid solutions might cause hypercoagulability, we here present our results on molecular markers of coagulation and fibrinolysis. Patients undergoing knee replacement surgery randomly received isovolemic amounts of lactated Ringer's solution, 6% hydroxyethyl starch 200/0.5 or 4% modified gelatine. Arterial blood samples for determination of specific molecular markers of activated coagulation (thrombin/antithrombin complex, D-dimer, prothrombin fragment F1 + 2), fibrinolysis (plasmin/alpha 2-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1), and concentrations of coagulation factor XIII were obtained at baseline, before tourniquet release, at the end of surgery and 2 h after operation. During the observation period, thrombin/antithrombin complex increased from 4.8 to 54.7 microg/l, D-dimer increased from 0.3 to 6.0 mg/ml, prothrombin fragment F1 + 2 increased from 1.7 to 5.9 nmol/l, tissue plasminogen activator decreased from 7.3 to 6.7 ng/ml, plasminogen activator inhibitor-1 increased from 68.4 to 71.0 ng/ml, plasmin/alpha 2-antiplasmin complex increased from 281.5 to 884 microg/l and factor XIII decreased from 89.0 to 58.5%. All parameters changed significantly but without any detectable difference in the response profile between the groups receiving different intravenous fluids. During knee replacement surgery a pronounced activation of the coagulation/fibrinolytic system was observed, regardless of whether patients received crystalloid or colloid fluids. Thus, these results cannot confirm the hypothesis that crystalloid fluids per se cause hypercoagulability in vivo. A prospective, controlled and randomized study of 275 patients undergoing major surgery was performed to investigate if postoperative complications were influenced by restrictive use of plasma to replace operative blood loss. All patients were given 6% dextran (Macrodex) for thromboprophylaxis and haemodilution. The "Dextran Group" received equal amounts of 6% dextran and electrolyte solution as substitution for plasma loss. The need for red-cell transfusion (60% suspension in saline-adenine-glucose-mannitol storage medium) averaged 5.8 units in this group and 5.2 in the "Plasma Group". The respective mean totals of infused plasma and dextran were 400 ml and 1,383 ml in the Dextran Group, compared with 1,099 and 619 ml in the Plasma Group. The mean total electrolyte infusion in the first postoperative week was c. 7,500 ml in both groups. Serum albumin decreased considerably in both groups, but significantly more in the Dextran Group. The incidence and pattern of postoperative complications were similar in both groups. When blood loss is up to 50-60% of the total volume, Macrodex can be used in preference to plasma, unless administration of plasma protein is specifically indicated. 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. All patients admitted to an Intensive Care Unit were randomised to receive all volume replacement fluid as either human albumin solution or a synthetic colloid. A total of 475 patients were admitted during the study period. Patients' age, sex, APACHE score and calculated risk of death were assessed on admission. Outcome was assessed as length of Intensive Care stay and mortality. There was no difference between the groups. Subgroups of patients with APACHE score greater than 10, calculated risk of death greater than 50% and length of stay greater than 5 days were also evaluated but not significant differences were found between treatment groups. The use of albumin rather than 3.5% polygeline for volume replacement in the Intensive Care Unit has no influence on outcome. The purpose of the study was to examine the effects of hypooncotic 4% hydroxyethyl starch 120/0.7, 3% dextran 70, 5% albumin and hyperoncotic 6% hydroxyethyl starch 120/0.7 on the perioperative colloid osmotic pressure (COP), albumin and protein concentrations and fluid balance. The plasma substitutes were used with red cell concentrates to replace blood loss with equal volume in sixty major abdominal or urological surgeries. A special effort was made to keep replacements and losses at even volumes constantly and to avoid fluctuation of blood volume. The blood specimen were obtained before induction, after each 20% blood loss, at the end of the recovery room phase and on the three following postoperative mornings. There were significant differences in the peroperative and immediate postoperative COPs. However, these differences had vanished by the first postoperative morning. COP was preserved above 16 mmHg in all groups throughout the study. The identical peroperative albumin and protein concentrations of the synthetic colloid groups suggests that their volume effect was the same, regardless of the varying COP. During the observation period there were no significant differences among the groups concerning the diuresis and the fluid balances. We conclude, that the hypooncotic 4% HES 120 and 3% dextran 70 solutions provide the same clinical effect as 6% HES 120 solution. Consequently less colloid is needed, which allows the use of greater volumes of the dilute colloid solutions in replacement therapy. A prospective study was carried out to determine the effects of Elohes, a low molecular weight hydroxyethylstarch, on haemostasis. Sixteen patients due to undergo total hip replacement were randomly assigned to one of two groups: group A, who were to receive up to 21 of 4% albumin to replace blood loss, and group E, 1.51 of Elohes. Patients were then given concentrated red cell packs (RCP) and lactated Ringer's solution so as to have a haematocrit value of 30%, up to the fifth postoperative day. The amount of blood lost intraoperatively was calculated by weighing the swabs and measuring the volume aspirated. Haemostasis was investigated on the eve of surgery, 3 hours afterwards, and then every second day (days 1, 3 and 5). Total blood loss and the number of RCP transfused were similar in both groups: 1,517 +/- 425 ml and 3.5 RCP, and 1,428 +/- 250 ml and 3.25 RCP in groups A and E respectively. Blood albumin concentrations fell in group E as expected, the starch diluting blood proteins. Bleeding time (Simplate), activated partial thromboplastin time, prothrombin time changed in the same way in both groups throughout the study period after infusion of either Elohes or albumin. The concentrations in factors II, V, VII and X fell by 30% three hours after surgery. Values returned to normal between days 1 and 3, the concentrations of some factors rising to values greater than preoperative values because of the postoperative inflammatory process (fibrinogen, factor VIII von Willebrand). However, there were no significant differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) To explore a suitable formula of delayed rapid fluid resuscitation for patients with burn shock.
                Twenty patients with burns over 40% of total body surface area (TBSA) admitted 4-8 h after injury were studied. Plasma was used as colloid in 9 cases in the infused patients (the plasma group, PG) and gelofusine was used as colloid in 11 cases in the infused patients (the gelofusine group, GG). Rapid fluid resuscitation was administered under strict hemodynamic monitoring immediately after admission. Hemodynamic indexes including pulmonary arterial pressure (PAP), pulmonary artery wedge pressure (PAWP), cardiac output (CO), pulmonary vascular resistance (PVR), and systemic vascular resistance (SVR), hemorheological parameters such as blood viscosity and plasma viscosity, and tissue oxygenation indices oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction (O2ext), lactic acid (LA) and base deficiency of arterial blood (AD) were determined in order to monitor function in or damage to important viscera.
                The amount of fluid rapidly infused in the first 2 h after hospitalization accounted for 38.8+/-6.0% of the required fluid amount for the first 24 h as calculated from the formula. When the amount of fluid infused into the patient before admission to our hospital was added, the total amount accounted for 48.3+/-5.0% of the fluid amount for the first 24 h. The actual amount of fluid infused in the first 24 h was 31.4+/-8.9% more than that of the amount calculated with the Evans' formula. The amount of fluid infused in the second 24 h was nearly equal to the amount calculated with the Evans' formula. After fast fluid replacement therapy, all the parameters determined were markedly improved.
                It is suggested on the basis of our study that the fluid amount for delayed rapid fluid resuscitation in patients with burn shock should be calculated as follows: (1) in the first 24h, the amount of fluid (ml) is equal to TBSA (%) x body weight (kg) x 2.6. The ratio between colloid and electrolytes is 1:1, each of the two fluid types is 1.3 ml per (%) TBSA per kg body weight. The volume of water required is 2000 ml. Half of the total amount of fluid is proposed should be infused in the first 2 h after hospitalization under strict monitoring of hemodynamic indices. (2) In the second 24 h, the amount of fluid (ml) is equal to TBSA (%) x body weight (kg) x 1. The ratio between colloid and electrolytes 1:1, each of the two is 0.5 ml. Water volume is 2000 ml. 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. Several colloid preparations are available for fluid resuscitation following heart surgery. We conducted a randomized prospective trial to compare a polygeline infusion versus human albumin with respect to hemodynamic and pulmonary function. 20 patients were randomly assigned to receive either Haemaccel or human albumin using a standardized protocol for the first 8 hours following heart surgery. The double-indicator dilution method was used to measure total blood volume index (TBVI), intrathoracic blood volume index (ITBVI) and extravascular lung water index (EVLWI) three times during the study period. Pulmonary shunt fraction, time on ventilator, and chest tube drainage were measured as well. Hemodynamic stability was achieved in both groups throughout the study period, as judged from mean arterial pressure, pulmonary capillary wedge pressure, and cardiac index. ITBV and TBVI were higher in the albumin group, although only significant at 4 hours for TBVI. There was no significant difference in EVLWI, pulmonary shunt fraction, and time on mechanical ventilation. Likewise, chest tube drainage was not significantly different in both groups. Haemaccel is effective in maintaining hemodynamic stability following heart surgery without ill effects of lung function or chest tube drainage. Treatment costs are substantially lower compared to human albumin. The effects on fluid balance, pulmonary functions and economics were evaluated in a randomized comparison of one colloid free and three colloid containing fluid regimens, for 48 hours during and after coronary artery bypass (CAB) surgery. A standard regimen for anaesthesia, extracorporeal circulation and monitoring was used. Only Ringer's acetate (RAc) was used as priming solution for extracorporeal circulation. Forty patients were randomized to receive either RAc, polygeline 35 mg.ml-1 (Haemaccel), dextran 70 (Macrodex) 60 mg.ml-1, or albumin 40 mg.ml-1 in saline whenever fluid volume was needed to stabilize haemodynamics. At the end of the operation, fluid retention was significantly lower in patients receiving polygeline and dextran 70, compared with patients receiving RAc. At 48 hours, however, there were no differences in cumulative fluid balance. Patients in the colloid groups postoperatively had a higher serum colloid osmotic pressure (s-COP), but a higher net lung capillary filtration pressure (delta P) only on the second postoperative day than the RAc group. However, this did not adversely affect intrapulmonary venous admixture, arterial oxygen tension, or time on respirator in the RAc group compared with the colloid groups. The most expensive colloid fluid regimen (albumin) cost about 230 US$ more per patient than the RAc fluid regimen. We conclude that Ringer's acetate for volume replacement to stabilize haemodynamics during and after CAB surgery is associated with increased fluid retention only during the intraoperative period, compared with dextran 70 or polygeline, and with a lower serum colloid osmotic pressure and net lung capillary filtration pressure postoperatively, compared with all three colloid groups. This does not affect pulmonary functions adversely.(ABSTRACT TRUNCATED AT 250 WORDS) The effects of 4% plasma protein solution (group P), 6% dextran-70 (group D), and 5.5% oxypolygelatin (group G) on plasma volume and hemodynamics were compared with each other and with controls (group C) who received only maintenance infusion 20 h after coronary bypass surgery. After infusing 10 ml/kg of colloid at 1 g/min, the immediate increases in plasma volume were 6.1 ml/kg in group P, 8 ml/kg in group D, and 7.9 ml/kg in group G. After one hour, the corresponding increases were 4.2 ml/kg (group P), 8.2 ml/kg (group D), and 6.2 ml/kg (group G). The increases in pulmonary capillary wedge pressure and stroke index were greatest and most persistent in group D, second largest but shortest in duration in group G, and lowest in group P. In conclusion, the volume effects of these three colloid solutions in coronary bypass patients are comparable to those obtained in other elective surgical patients. To examine the kinetics of volume loading with crystalloid and colloid infusions in critically ill patients after major surgery, using the pulse contour cardiac output (PiCCO) monitoring technique.
                This prospective, randomized, multicentre study of 11 ICUs involved 200 mixed postoperative hypovolaemic patients (50 patients per group) in Hungary. Patients received 10 ml kg of lactated Ringer's solution, succinylated gelatin 4% w/v, 130/0.4 hydroxyethyl starch 6% w/v (HES) or human albumin 5% w/v over 30 min. A complete haemodynamic profile was obtained at 30, 45, 60, 90 and 120 min after baseline. The peak haemodynamic effects, the 120 min changes compared with baseline, the area under the curve (AUC) for the haemodynamic parameters over 120 min and the haemodilution effect of the solutions were analysed. The primary outcome was to compare the AUCs and the secondary outcome was to evaluate the haemodynamic changes at 120 min.
                There were significant differences in the AUCs of the haemodynamic parameters between colloids and lactated Ringer's solution in the cardiac index and global end-diastolic volume index (GEDVI); human albumin vs. lactated Ringer's solution in stroke volume variation (SVV); and succinylated gelatin, HES vs. lactated Ringer's solution in the oxygen delivery index (DO2I). Colloid infusions (mainly HES and human albumin) at 120 min caused significant changes in central venous pressure, cardiac index, GEDVI, SVV, DO2I and central venous oxygen saturation compared with baseline. The haemodilution effect was significantly greater in colloids vs. lactated Ringer's solution.
                In postoperative hypovolaemic patients, lactated Ringer's solution can significantly improve haemodynamics at the end of volume loading, but this effect completely disappears at 120 min. Ten millilitres per kilogram of colloid bolus (especially HES) improved the haemodynamics at 120 min; however, this was by only 5-25% compared with baseline. The colloids caused significantly larger AUCs than lactated Ringer's solution, but only in the cardiac index, GEDVI and DO2I, plus human albumin in the SVV. For perioperative volume therapy in infants and young children, human albumin has frequently been the colloid of choice. Recently, HES 130/0.4 (6% hydroxyethyl starch, Voluven; Fresenius Kabi, Bad Homburg, Germany) was developed, which demonstrated improved pharmacokinetics and a favourable safety profile in adults compared with hydroxyethyl starch products with a less rapid metabolization.
                Our prospective, controlled, randomized, open, multicentre pilot study was designed to obtain data on the effects of HES 130/0.4 compared with human albumin 5% with regard to haemodynamics in children <2 yr scheduled for elective non-cardiac surgery.
                A total of 81 patients were treated. Comparable amounts of both study solutions (16.0 mL kg(-1) hydroxyethyl starch 130/0.4 vs. 16.9 mL kg(-1) human albumin 5%) as well as add-on crystalloids were used until 4-6 h postoperatively. No differences were detected between the two treatment groups regarding perioperative stabilization of haemodynamics, coagulation parameters, blood gas analyses or other laboratory values. Blood loss was 96 +/-143 mL for hydroxyethyl starch and 145+/- 290 mL for human albumin (P > 0.05). There were no relevant differences in the amount of red blood cells, fresh frozen plasma or platelet concentrates in both treatment groups. Median length of ICU stay was 3.5 days (range 1-57 days, mean +/- SD 7.6 +/- 11.5 days) in the hydroxyethyl starch group and 6.0 days (range 1-71 days; mean +/- SD 9.1 +/- 14.2 days) in the human albumin group. There was no difference for hospital stay (median: 12 days for both groups).
                Both HES 130/0.4 and human albumin 5% were effective for haemodynamic stabilization in non-cardiac surgery of young infants with no adverse impact on coagulation or other safety parameters in our study population. Experimental studies have demonstrated that dextran-70 reduces the leukocyte-endothelium interaction, but clinical evidence is still lacking. Our objective was to justify the anti-inflammatory effect of dextran-70 following cardiac operations.
                Forty patients undergoing coronary bypass surgery (n = 32) or aortic valve replacement (n = 8) were enrolled in this prospective, randomized, double-blind study. Two groups were formed. In group A (n = 20), dextran-70 infusion was administered at a dose of 7.5 ml/kg before the initiation of cardiopulmonary bypass and at a dose of 12.5 ml/kg after the cessation of cardiopulmonary bypass. Group B served as a control with identical amounts of gelatin infusion (n = 20). The plasma concentration of procalcitonin, C-reactive protein, IL 6, IL 6r, IL 8, IL 10, soluble endothelial leukocyte adhesion molecule-1, soluble intercellular adhesion molecule-1, cardiac troponin-I and various haemodynamic parameters were measured in the perioperative period. Multivariate methods were used for statistical analysis.
                In group A, lower peak (median) plasma levels of procalcitonin (0.2 versus 1.4, p < 0.001), IL 8 (5.6 versus 94.8, p < 0.001), IL 10 (47.2 versus 209.7, p = 0.001), endothelial leukocyte adhesion molecule-1 (88.5 versus 130.6, p = 0.033), intercellular adhesion molecule-1 (806.7 versus 1,375.7, P = 0.001) and troponin-I (0.22 versus 0.66, p = 0.018) were found. There was no significant difference in IL 6, IL-6r and C-reactive protein values between groups. Higher figures of the cardiac index (p = 0.010) along with reduced systemic vascular resistance (p = 0.005) were noted in group A.
                Our investigation demonstrated that the use of dextran-70 reduces the systemic inflammatory response and cardiac troponin-I release following cardiac operation.
                ISRCTN38289094. Colloids are useful in cardiac surgery to increase preload and improve cardiac output without the risks associated with blood transfusions. Pentastarch is a new low-molecular weight hydroxyethyl starch compound under investigation for this purpose. The authors compared, in a randomized fashion, 12 patients who received pentastarch and 17 patients who received albumin for volume expansion after open-heart surgery. During the 24-hour study period there was no significant difference between the two groups with respect to systemic blood pressure, mean arterial pressure, cardiac index, right atrial pressure, and pulmonary capillary wedge pressure, with the exception of a higher mean arterial pressure and systolic blood pressure at 4 hours in the albumin group and higher heart rate at 12 hours in the pentastarch group. In addition, postoperative prothrombin time, partial thromboplastin time, fibrinogen, platelets, and factor VIII levels were not significantly different between the two groups. There were no complications attributed to colloid administration. The hemodynamic parameters were further evaluated in a subset of 6 pentastarch and 9 albumin patients who received the first 500 mL of colloid in a similar time frame and under similar clinical conditions. The patients who received pentastarch showed a significantly greater increase in cardiac index than did the patients who received albumin. No significant change in other parameters were noted between the two groups. The authors conclude that pentastarch is as safe as albumin and may be a more effective volume expander than albumin when used in open-heart surgery patients. We investigated the effect of postoperative administration of colloids on hemostasis in 45 patients after cardiac surgery. Patients were randomized to receive 15 mL kg(-1) of either 4% albumin, 4% succinylated gelatin, or 6% hydroxyethyl starch (molecular weight of 200 kDa/degree of substitution 0.5) as a short-term infusion. There was a comparable decrease in maximum clot firmness of thromboelastometry tracings in gelatin and hydroxyethyl starch groups immediately after completion of the infusion, whereas these values remained unchanged in the albumin group. The impairment in clot strength persisted up to 2 h, although the values partly recovered. Postoperative bleeding correlated inversely with the clot strength in pooled data of the artificial colloids. Fibrin formation (clot formation time, alpha-angle) and fibrinogen-dependent clot strength (maximum clot firmness and shear elastic modulus) were more disturbed in the hydroxyethyl starch group than in the gelatin group. We conclude that after cardiopulmonary bypass surgery, both gelatin and hydroxyethyl starch impair clot strength and fibrin buildup, which may predispose patients to increased blood loss. The greatest impairment in hemostasis was seen after hydroxyethyl starch administration, whereas albumin appeared to have the least effect on hemostatic variables. nan The effect of 6% hydroxyethyl starch (hetastarch) and 5% human serum albumin (albumin) infusion on coagulation in 12 patients with septic shock was evaluated. Patients were randomly assigned to receive either albumin (N = 6) or hetastarch (N = 6) infusion over a 24-hour study interval. The prothrombin time (PT), partial thromboplastin time (PTT), and quantitative platelet count (PC) were obtained prior to and following 24 hours of fluid infusion. Hetastarch patients received 4934 +/- 1354 mL and albumin patients received 3067 +/- 256 mL over the study interval. After hetastarch infusion, the PT increased 2.2 +/- 0.7 seconds, PTT increased 20.0 +/- 4.1 seconds (P less than .01), and PC decreased 158 +/- 36 X 10(3)/mm3 (P less than .02). After albumin administration, the PT decreased 1.2 +/- 1.7 seconds, PTT increased 20.5 +/- 10.6 seconds and PC decreased 100 +/- 34 X 10(3)/mm3. There were no significant differences in the changes in PT, PTT, or PC between the groups. The authors conclude that hetastarch infusion does not result in increased bleeding in patients with septic shock compared with albumin infusion, despite moderate effects on the hemostatic coagulation profile. In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs.
                A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin.
                During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged.
                Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters. Twenty consecutive patients with severe sepsis were randomized to fluid challenge with 5% albumin or 10% low MW hydroxyethyl starch (pentastarch) solutions. Fluid challenge was administered iv as 250 ml of test colloid every 15 min until the pulmonary artery wedge pressure (WP) was greater than or equal to 15 mm Hg or a maximum dose of 2000 ml was infused. Hemodynamic, respiratory, and coagulation profiles were measured before and after fluid infusion. The amount of colloid required to achieve a WP of 15 mm Hg was comparable between groups. Both colloid infusions resulted in similar increases in cardiac output, stroke output, and stroke work. The effect of fluid infusion with pentastarch on coagulation was not significantly different from albumin, although pentastarch was associated with a 45% decrease in factor VIII:c. We conclude that pentastarch is equivalent to albumin for fluid resuscitation of patients with severe sepsis. To compare the hemodynamic and oxygen transport responses to a rapid (< 10-min) infusion of 500 mL of modified fluid gelatin (group A) or hydroxyethyl starch (group B) in patients suffering from acute hypovolemia.
                Prospective, randomized, noncrossover study.
                University hospital, general intensive care unit.
                Twenty-eight patients with hypovolemia mechanically ventilated for concurrent acute respiratory failure.
                Patients were mechanically ventilated. Pulmonary and femoral artery catheters were used for hemodynamic monitoring.
                Hemodynamic and oxygen transport variables were determined at baseline, 15 mins, and 30 mins after the infusion of each fluid. In both groups pulmonary artery occlusion pressure, stroke volume, and cardiac index significantly increased. In neither group did heart rate decrease. Oxygen delivery increased significantly in group A patients but not in group B patients. This result was due to greater hemodilution in group B patients.
                There are no significant differences in the hemodynamic responses to hydroxyethyl starch or modified fluid gelatin. The hemodynamic and oxygen transport effects of artificial colloid solutions may not be entirely predictable and should be monitored in critically ill patients. To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery.
                A single-centre, single-blinded, randomized clinical trial at the intensive care unit of a university hospital.
                Patients (n=67) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin 4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics (transpulmonary thermodilution) were measured.
                An amount of 1800 (1300-1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was infused. Colloid osmotic pressure (COP) decreased in the saline group and increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18 to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001). Cardiac index increased by median 13% (ns) in the saline group and by 22% in the colloid groups (P<0.005). The rise in left ventricular stroke work index was greater in the colloid than in the saline groups. The different colloids were equally effective. The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume, confirming plasma volume and preload augmentation by the fluid loading.
                After cardiac or major vascular surgery, the pressure- and time-guided fluid response is dependent on the type of fluid used. Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline, because of greater plasma volume expansion following an increase in plasma COP. Hetastarch has been studied as a volume expander in adults after cardiopulmonary bypass (CPB) and in recommended dosages has not altered coagulation studies or increased clinical bleeding. Hetastarch was compared with albumin in children after CPB to determine whether hetastarch use was associated with increased clinical bleeding or alteration of coagulation studies.
                Randomized double-blinded study.
                University-affiliated children's hospital.
                Forty-seven children age 1 year or greater (mean 72.8 months; range 12 months to 15.5 years) scheduled for repair of congenital heart disease with moderate hypothermia were randomized to receive hetastarch or albumin as a postoperative volume expander during the first 24 hours after surgery.
                Thirty-eight children required colloid replacement therapy. Blood pressure, central venous pressure, urine output, and chest tube drainage were used to determine colloid requirement.
                Clinical bleeding and laboratory studies of coagulation were evaluated as were requirements for colloid, crystalloid, and blood products. Twenty children received 6% hetastarch, and 18 received 5% albumin. No differences were found in the amount of replacement fluids required, or in coagulation parameters in children receiving 20 mL/kg or less of either colloid replacement therapy. An increase in prothrombin time was demonstrated in children who received greater than 20 mL/kg of 6% hetastarch (p = 0.006); however, no difference in clinical bleeding or blood product requirement was demonstrated between the hetastarch or albumin groups receiving more than 20 mL/kg.
                This study demonstrated that 6% hetastarch is safe and an effective plasma volume expander in the postoperative management of children, using volumes up to 20 mL/kg. Close laboratory monitoring and careful evaluation of clinical bleeding are suggested when larger doses of hetastarch are administered because of prolongation of the prothrombin time with more than 20 mL/kg of hetastarch. In a randomized blinded study we compared two colloid solutions in 30 neonates undergoing major surgery. Fifteen neonates received 4.5% Human albumin solution (HAS) (mean volume 25.6 ml.kg-1, SD 9.5) and the others received Haemaccel (Hoechst) (24.9 ml.kg-1, SD 10). Pre and postoperative plasma albumin and haemoglobin concentrations and plasma colloid osmotic pressure (COP) were compared. In the group given Haemaccel there was an appreciable and statistically significant decrease in the mean plasma albumin concentration from 34.27 to 28.27 g.1(-1) (mean difference 6, CI 3.38 to 8.62) and the mean COP decreased significantly from 22.2 to 19.9 mmHg (mean difference 2.3, CI 0.3 to 4.5). In the HAS group there was no significant change in either the plasma albumin concentration or COP. There was a small but significant decrease in the mean haemoglobin concentration from 15.92 to 14.35 g.dl-1 (mean difference 1.56, CI 0.57 to 2.55) after HAS. We conclude that HAS is the superior colloid for volume replacement in neonates undergoing surgery. 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. Human albumin 5% (HA), frequently used in paediatric anaesthesia as a human plasma substitute, could be replaced by hydroxyethyl starch 6% (HES) 40,000/0.5 provided its use would not entail any disadvantages but rather advantages instead. This problem was studied by examining 30 children (mean body weight 32.5 kg) in general anaesthesia. During about 3 hours of surgery the patients lost up to 15 per cent (approx. 400 ml) of blood volume. In a randomised study the blood loss was compensated either via HA or HES with 14 ml/kg body weight each, respectively. Blood pressure and pulse rate remained within the normal range. Haemodilution was represented by a drop in the erythrocyte count to about 3 million/microliter, haematocrit (HCT) to about 30% and haemoglobin to approx. 10 g/100 ml. Slight metabolic acidosis (Bodansky unit = -4 mmol/l) was found to be statistically not significant (= n.s.) with both methods, as was the difference in serum albumin and during serum electrophoresis. Serum [Na+] was reduced in those children who had been treated with HES, to 137.33 +/- 33.30 mmol/l; however, in those children who received HA with low sodium content (statistically significant difference = s.s.) the corresponding level was 134.15 +/- 2.36 mmol/l. Serum creatinine rose in each case from 60 to 80 mmol/l (s.s.), renal function being slightly impaired probably due to the anaesthesia and surgery. The value according to Quick's test and the partial thromboplastin time (PTT) remained in the normal range both with HA and HES treatment (in each case over 70% and below 25s, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) It was the purpose of the following study to compare effects of 6% hydroxyethyl starch 200/0.5 (HES) and albumin 5% (HA5) on haemostasis, haemodynamics, oncotic function and plasmatic homoeostasis.
                In 2 randomised groups of 20 patients each undergoing large surgery (criteria of exclusion: anaemia, renal, liver, and coagulation disorders, ASA classification > III) we treated up to 1000 ml with colloid solution, from 1000 ml up to 5000 ml with packed red blood cells (PRBC) and colloid solution (1:1) and above 5000 ml with PRBC and fresh frozen plasma (1:1). Group HES received HES and group HA5 albumin as exclusive colloid component and both continuously lactated Ringers' at a rate of 500 ml/h. We measured the parameters before operation, after each 1000 ml colloid up to 3000 ml application and at the end of operation and we registered total blood output/intake.
                We found comparable amounts of blood loss and blood intake (mean total amount of colloid solution: HES 2044 +/- 579 ml; HA5 2547 +/- 980 ml). We didn't find any differences in haemodynamics nor in haematocrit, platelets or global coagulation parameters which only showed dilutional influences. Differences existed in total serum protein (HES 32.8 +/- 6.5 gr/l; HA5 54 +/- 5.5 gr/l at OP's end); however COP was maintained in both groups during the whole study period at normal ranges. Plasmatic haemostasis showed to a large extent corresponding values. Remarkable was the development of a metabolic acidosis in the HA5 group.
                Regarding total blood output/intake, haemodynamic functions, haematological parameters, coagulation, oncotic function, and plasmatic homoeostasis, HES is a safe colloid if contra-indications are taken into account, capable of replacing albumin 5% entirely as a colloid component of treatment of even large blood losses intraoperatively above the recommended dose of 20 ml/kg BW/d. Within a daily dose of 20 mL/kg, medium-molecular hydroxyethyl starch (HES) is a safe and effective colloid for intravascular blood volume replacement. The effect of large doses on coagulation and renal function is unknown. We prospectively studied 41 patients undergoing total hip arthroplasty during the perioperative period. Inevitable blood loss was replaced with HES (HES group) or albumin (ALB group) in combination with packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelets. Hemodynamic, oncotic, coagulation, and renal functions were compared initially, at the end of surgery, during the postoperative period (1, 3, and 6 h), and also with respect to the volume of colloid solution administered (1500, 2000, and 3000 mL). Total intake and output balances, as well as the costs of blood replacement therapy, were registered at the end of the study. We found differences in oncotic variables even at 6 h after surgery (total serum proteins [TSP]:HES 36.4 +/- 7.9 g/L versus ALB 55.6 +/- 6.1 g/L, P < 0.01; serum albumin:HES 25.5 +/- 5.3 g/L versus ALB 42.0 +/- 5.6 g/L, P < 0.01). Colloid osmotic pressure (COP) and hemodynamic, coagulation, and renal functions were comparable, as was total blood loss (HES 4247 +/- 2090 mL versus ALB 4051 +/- 2830 mL). Total requirements for colloid solutions (HES 35.9 +/- 7.4 mL/kg versus ALB 33.9 +/- 10.5 mL/kg), PRBC, FFP, or platelets were comparable, whereas total cost of blood replacement therapy was 33% less in the HES group. With respect to efficacy and side effects on coagulation and renal function, medium molecular HES is an appropriate and economic alternative to albumin at daily doses of up to at least 36 mL/kg. Adhesion molecules appear to play a pivotal role in tissue damage secondary to the inflammatory process. Besides neutrophil- and endothelial-bound adhesion molecules, soluble forms have been detected in the circulating blood. They seem to be good markers of endothelial damage, but they may also have other biological functions. Plasma concentrations of soluble adhesion molecules (endothelial leucocyte adhesion molecules (sELAM-1), intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and granule membrane protein 140 (sGMP-140) were serially measured over 5 days by enzyme-linked immunosorbent assays (ELISA) in 45 consecutive trauma patients. These received, by random allocation, only either hydroxyethylstarch solution 10% (mean molecular weight 200,000 daltons) (n = 15) or human albumin 20% (n = 15) for volume therapy. Another 15 patients without defined volume therapy received pentoxifylline continuously (1.2 mg.kg-1.h-1). Measurements were carried out on the day of admission to the intensive care unit (baseline) and during the next 5 days. At baseline, plasma concentrations of all adhesion molecules were similar in all groups. In the hydroxyethyl starch group, sELAM-1 and sICAM-1 concentrations decreased significantly (p < 0.05) reaching normal values during the study period whereas the mean (SD) values increased in the pentoxifylline group (sELAM-1: 71.1 (16.7) to 91.6 (17.8) ng.ml-1) and the albumin group (sICAM-1: 400 (81) to 749 (101) ng.ml-1) (p < 0.05). sVCAM-1 increased outside the normal range only in the human albumin group (to 760 +/- 69 ng.ml-1) (p < 0.05). sGMP-140 plasma concentration increased only in those receiving albumin (432 (85) to 550 (93) ng.ml-1) and this was significantly different to the other groups (p < 0.05). None of the other haemodynamic or laboratory factors could be correlated with plasma concentrations of the adhesion molecules. We conclude that volume therapy with hydroxyethyl starch resulted in a decrease in circulating adhesion molecules in our trauma patients. In contrast, volume therapy with albumin did not exert this effect. Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules. Various vasoactive substances are involved in the regulation of the macro- and microcirculation. We have investigated if these regulators change during long-term volume therapy with human albumin (HA) or hydroxyethylstarch solution (HES) in trauma and sepsis patients. To maintain pulmonary capillary wedge pressure (PCWP) at 10-15 mm Hg, either 20% HA (HA-trauma, n = 14; HA-sepsis, n = 14) or 10% low-molecular weight HES solution (HES-trauma, n = 14; HES-sepsis, n = 14) were infused for 5 days, otherwise patient management did not differ between the two groups (trauma/sepsis). Mean arterial pressure (MAP), heart rate (HR), PCWP and cardiac index (CI) were monitored in all patients. Liver function was assessed using the monoethylglycinexylidide (MEGX) test, and gastric intramucosal pH (pHi) was monitored by tonometry to assess splanchnic perfusion. Plasma concentrations of vasopressin, endothelin-1, adrenaline, noradrenaline, atrial natriuretic peptide and 6-keto-prostaglandin F1 alpha were measured from arterial blood samples. All measurements were carried out on the day of admission to the intensive care unit (trauma patients) or on diagnosis of sepsis, and daily over the next 5 days at 12:00. MAP, HR and PCWP did not differ between the corresponding subgroups (trauma/sepsis). Cl increased significantly more in the HES than in the HA groups. pHi and MEGX plasma concentrations did not differ in the trauma patients throughout the study. Both were lower than normal in the sepsis groups and increased more markedly in the HES than in the albumin-treated patients (P < 0.05). In the trauma patients, concentrations of all vasoactive regulators were very similar in both groups. In both sepsis groups, vasopressors (vasopressin, endothelin-1, noradrenaline and adrenaline) were significantly increased above normal at baseline and decreased more markedly in HES than in HA patients. Concentrations of atrial natriuretic peptide increased only in the HA patients (from 159 (SD 31) to 215 (38) pg ml-1 on day 2). Plasma concentrations of 6-keto-prostaglandin F1 alpha decreased significantly only in the HES sepsis patients (from 112 (25) to 47 (15) pg ml-1). Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy. Restoring blood flow to ischaemic tissue can cause lung damage with pulmonary oedema. Hydroxyethyl starch (HES) solution, when used for volume replacement, may modify and reduce the degree of ischaemia-reperfusion injury. We compared the effects of HES solution with those of Gelofusine solution on pulmonary function, microvascular permeability and neutrophil activation in patients undergoing elective infrarenal abdominal aortic aneurysm surgery.
                Forty patients were randomized into two groups. The anaesthetic technique was standardized. Lung function was assessed with the PO(2)/FI(O(2)) ratio, respiratory compliance, chest x-ray and a score for lung injury. Microvascular permeability was determined by measuring microalbuminuria. Neutrophil activation was determined by measurement of plasma elastase.
                Four hours after surgery, the median (quartile values) PO(2)/FI(O(2)) ratio was 40.3 (37.8, 53.1) kPa for the HES-treated patients compared with 33.9 (31.2, 40.9) kPa for the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The respiratory compliance was 80 (73.5, 80) ml cm(-1) H(2)O in the HES-treated patients compared with 60.1 (50.8, 73.3) ml cm(-1) H(2)O in the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The lung injury score 4 h after surgery was less for the patients treated with HES compared with the patients treated with Gelofusine (0.33 vs 0.71, P=0.01, Wilcoxon rank sum test). Mean (SD) plasma elastase was less in the HES-treated patients on the first postoperative day (1.96 (0.17) vs 2.08 (0.24), P<0.05). The log mean microalbuminuria was less in the HES-treated patients (0.41 vs 0.91 mg mmol(-1), P<0.05). This difference in microvascular permeability was associated with different volumes of colloid required to maintain stable cardiovascular measurements in the two groups of patients studied (3000 vs 3500 ml, P<0.01, Mann-Whitney test).
                Compared with Gelofusine, the perioperative pulmonary function of patients treated with HES after abdominal aortic aneurysm surgery was better. A prospective randomized double-blind study was performed to determine the effects of three colloids, Haemaccel, Gelofusine and albumin, and also saline on platelet activation, platelet aggregation (induced by adenosine diphosphate (ADP), epinephrine, collagen) platelet agglutination by ristocetin and other hemostatic variables in 55 patients undergoing primary unilateral total hip replacement. The fluids were administered according to normal clinical practice and assessments were made immediately before, at the end, and 2 h after the end of surgery. Surgery was accompanied by thrombin generation (increases in thrombin/antithrombin III complex, prothrombin F1 +2 fragment) platelet activation (betaTG) and compromised coagulation. Generally, the platelet activation appeared to result in platelet desensitization and brought about a persistent reduction in platelet aggregation to ADP and epinephrine, irrespective of the fluid used. Additionally, Haemaccel and Gelofusine inhibited ristocetin-induced platelet agglutination and albumin inhibited collagen-induced platelet aggregation. Gross inhibitory effects of Haemaccel that had been predicted from an earlier in vitro study did not occur. Particular fluids had selective additional effects on the hemostatic system. Albumin infusion served to maintain plasma albumin at normal concentrations postsurgery. The two gelatin preparations, Haemaccel and Gelofusine, maintained plasma viscosity. All three colloids led to a transient increase in activated partial thromboplastin time postsurgery and also a transient fall in the concentration of factor VIII, which were accompanied by a transient increase in bleeding time, but there was no measurable increase in blood loss. Inhibition of platelet aggregation by certain colloids may provide additional protection against the increased thrombotic risk in patients following major surgery. Previous studies have shown that in children with severe malaria, resuscitation with albumin infusion results in a lower mortality than resuscitation with saline infusion. Whether the apparent benefit of albumin is due solely to its colloidal properties, and thus might also be achieved with other synthetic colloids, or due to the many other unique physiological properties of albumin is unknown. As albumin is costly and not readily available in Africa, examination of more affordable colloids is warranted. In order to inform the design of definitive phase III trials we compared volume expansion with Gelofusine (succinylated modified fluid gelatin 4% intravenous infusion) with albumin.
                This study was a phase II safety and efficacy study.
                The study was conducted at Kilifi District Hospital, Kenya.
                The participants were children admitted with severe falciparum malaria (impaired consciousness or deep breathing), metabolic acidosis (base deficit > 8 mmol/l), and clinical features of shock.
                The interventions were volume resuscitation with either 4.5% human albumin solution or Gelofusine.
                Primary endpoints were the resolution of shock and acidosis; secondary endpoints were in-hospital mortality and adverse events including neurological sequelae.
                A total of 88 children were enrolled: 44 received Gelofusine and 44 received albumin. There was no significant difference in the resolution of shock or acidosis between the groups. Whilst no participant developed pulmonary oedema or fluid overload, fatal neurological events were more common in the group receiving gelatin-based intervention fluids. Mortality was lower in patients receiving albumin (1/44; 2.3%) than in those treated with Gelofusine (7/44; 16%) by intention to treat (Fisher's exact test, p = 0.06), or 1/40 (2.5%) and 4/40 (10%), respectively, for those treated per protocol (p = 0.36). Meta-analysis of published trials to provide a summary estimate of the effect of albumin on mortality showed a pooled relative risk of death with albumin administration of 0.19 (95% confidence interval 0.06-0.59; p = 0.004 compared to other fluid boluses).
                In children with severe malaria, we have shown a consistent survival benefit of receiving albumin infusion compared to other resuscitation fluids, despite comparable effects on the resolution of acidosis and shock. The lack of similar mortality benefit from Gelofusine suggests that the mechanism may involve a specific neuroprotective effect of albumin, rather than solely the effect of the administered colloid. Further exploration of the benefits of albumin is warranted in larger clinical trials. Albumin is often cited in textbooks as the gold standard for fluid replacement in paediatrics, but in practice artificial colloids are more frequently used. Although one concern with the use of artificial colloids is their intrinsic action on haemostasis, the available data in children are inconclusive for 6% hydroxyethyl starch 130/0.4 (HES) and no data exist for gelatine solution with respect to coagulation. A total of 42 children (3-15 kg) undergoing surgery and needing colloid replacement were randomly assigned to receive 15 mlxkg(-1) of either albumin 5%, 4% modified gelatine solution or 6% hydroxyethyl starch 130/0.4 solution. Standard coagulation tests and modified thrombelastography (ROTEM) were performed. After colloid administration, routine coagulation test results changed significantly and comparably in all groups, although activated partial thromboplastin time values increased more with gelatine and HES. Coagulation time was unchanged in the children who received albumin or gelatine but other activated modified thrombelastography values were significantly impaired in all groups. After gelatine and after albumin the median clot firmness decreased significantly but remained within the normal range. Following HES, coagulation time increased significantly, and clot formation time, alpha angle, clot firmness, and fibrinogen/fibrin polymerisation were significantly more impaired than for albumin or gelatine, reaching median values below the normal range. From a haemostatic point of view it might be preferable to use gelatine solution as an alternative to albumin; HES showed the greatest effects on the overall coagulation process. Twenty-six consecutive patients in hypovolemic shock were randomized to fluid challenge with 5% albumin (A), 6% hetastarch (H), or 0.9% saline (S) solutions. Fluid challenge consisted of 250 ml of test fluid every 15 min until the pulmonary artery wedge pressure (WP) reached 15 mm Hg. Thereafter, WP was maintained at 15 mm Hg for an additional 24 h with infusions of the same test fluid. Vital signs, hemodynamic and respiratory variables, as well as arterial lactate and colloid osmotic pressure (COP) were monitored according to protocol. Chest x-rays were performed by standardized technique before fluid challenge and at 12 and 24 h of maintenance fluid therapy and were evaluated for evidence of pulmonary edema. Cardiac function and hemodynamic stability were restored by fluid challenge with A, H, and S. Two to 4 times the volume of S as A or H was required to achieve similar hemodynamic endpoints. COP was increased by fluid challenge with A or H but was markedly reduced by fluid challenge with S and throughout the 24-h maintenance period. Fluid challenge resulted in reductions in COP-WP gradient of 62% in the A, 43% in the H, and 125% in the S groups. Resuscitation with S resulted in a significantly higher incidence of pulmonary edema (87.5%) than did resuscitation with A (22%) or H (22%). Urine output was not different among the groups at any time during the study. We conclude that 6% H performs as well as 5% A as a resuscitative fluid and that resuscitation with either of these colloids is associated with a lower incidence of pulmonary edema than is resuscitation with 0.9% S. The value of artificial colloids in treating patients with liver disease is controversial. The effects of intravascular volume replacement regimens on liver function secondary to alteration of the postoperative inflammatory response are not known. In this study, we evaluated the effects of different volume replacement regimens in hepatocellular carcinoma patients undergoing hepatectomy to clarify whether albumin administration can be replaced by other volume replacement products.
                Ninety consecutive hepatocellular carcinoma patients scheduled for hepatectomy were prospectively randomized to receive 20% human albumin (HA), 6% hydroxyethyl starch (HES) or lactated Ringer's solution (LR) for postoperative volume replacement. Hemodynamic, liver function and inflammatory response parameters were recorded on postoperative days one, three, and five throughout the investigation period.
                Significantly less volume was required in the HA and the HES groups. Although patients in all groups had similar baseline values, the plasma osmolality was significantly higher in the HA and HES groups. Total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) increased from baseline in all groups, and did not differ significantly between groups. C-reactive protein (CRP) was significantly lower in the HES group compared with the other groups.
                In hepatocellular carcinoma patients undergoing hepatectomy, HA can be replaced by HES or LR in well selected patients. Hemodynamic stability, liver function, and postoperative clinical outcomes could be equivalently achieved in the HES group; also, HES may exert more favorable effects on the acute phase response. The purpose of this study was to investigate the effects of acute hypervolemic fluid infusion (AHFI) of 6% hydroxyethyl starch (HES) 130/0.4 or 4% succinylated gelatin (GEL) on hemostasis and the possible mechanisms.
                Thirty-six gastric cancer patients were randomized to receive AHFI of either HES, GEL or lactated Ringer's (RL) solution at the rate of 30 mL x kg(-1) x h( -1) from 20 minutes before to 40 minutes after induction of general anesthesia.
                Group HES and GEL had significantly prolonged PT and aPTT, decreased VIII:C and vWF immediately after AHFI. Statistically prolonged reaction time and coagulation time, and decreased growth angle were seen immediately after HES infusion. Maximum amplitude decreased significantly in group HES and GEL immediately after and 4 hours after AHFI.
                Gelatin reduced clot quality associated with derangements of fibrin polymerization and HES 130/0.4 delayed initiation of sufficient thrombin generation to convert fibrinogen to fibrin and impaired platelet function. The influence of four different kinds of intravascular volume replacement on platelet function was investigated in 60 patients undergoing elective aortocoronary bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, high-molecular weight hydroxyethyl starch solution (HMW-HES, mean molecular weight [Mw] 450,000 d), low-molecular weight HES (LMW-HES, Mw 200,000 d), 3.5% gelatin or 5% albumin were infused preoperatively to double reduced filling pressure (pulmonary capillary wedge pressure [PCWP] < 5 mm Hg). Fifteen untreated patients served as a control. Platelet function was assessed by aggregometry using turbidometric technique (inductors: ADP, epinephrine, collagen). Maximum aggregation, maximum gradient of aggregation, and platelet volume were measured before, during, and after CPB until the first postoperative day. HMW-HES 840 +/- 90 mL, LMW 850 +/- 100 mL, gelatin 950 +/- 110 mL, and albumin 810 +/- 100 mL were given preoperatively. Maximum platelet aggregation (ranging from -23% to -44% relative from baseline value) and maximum gradient of platelet aggregation (ranging from -26% to -45% relative from baseline values) were reduced only in the HMW-HES patients. After CPB, aggregometry also was impaired most markedly in these patients. The other volume groups showed less reduction in platelet aggregation and were similar to the untreated control. On the first postoperative day, aggregation variables had returned almost to baseline in all patients. Platelet volume was the same among the groups within the investigation period. Postbypass blood loss was highest in the HMW-HES group (890 +/- 180 mL). There was significant (P < 0.04) correlation in this group between blood loss and change in platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS) 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. Hydroxyethyl starch (HES) is a recently developed synthetic volume expander. Forty patients undergoing coronary artery surgery were randomized to receive either HES or plasma protein fraction (PPF) as non-blood volume replacement according to standard haemodynamic criteria. The two groups were comparable in all respects. The median colloid use in the first 24 h was 950 ml (range 500-1500) in the HES group and 975 ml (350-2000) in the PPF group (not significant). There was no difference in blood use, urine output or blood loss between the two groups. Tests of coagulation showed the postoperative changes usual in cardiac surgical patients. There was no difference between the two groups in thrombin time, prothrombin time, activated partial thromboplastin time, or fibrinogen concentration. Similarly, tests of platelet function and Factor VIII and von Willebrand Factor activity showed no difference between the two groups. We conclude that HES is a safe and effective volume expander, and its relative lack of expense and ease of availability make its routine use after cardiac surgery an attractive proposition. nan To find out if the need for transfusion was increased by volume substitution with dextran 70 in patients receiving prophylaxis against thrombosis with low molecular weight heparin.
                Open randomised controlled trial.
                University hospital, Sweden.
                40 patients undergoing revision hip arthroplasty.
                Enoxaparin 40 mg was given daily. Intraoperative normovolaemia was maintained with albumin (n = 20) or dextran 70 (n = 20). Intraoperative autotransfusion was used. Packed cell volume was kept above 0.29, if necessary with homologous blood.
                External blood loss, red cell balance.
                Dextran patients received 0.64 (0.2) g/kg of dextran (mean (SD)) and required more (p < 0.05) homologous blood (3.8 (2.4) units) than those receiving albumin (2.3 (1.6) units). The initial and final packed cell volumes were similar (0.40 and 0.32 compared with 0.41 and 0.32, respectively). The calculated loss of red cells was larger in the dextran group (1401 (511) compared with 1077 (374); p < 0.05).
                The combination of enoxaparin and dextran appreciably increased the need for transfusion compared with enoxaparin alone. To investigate the effect of 4 % succinylated modified fluid gelatin (MFG) versus mean weight, highly substituted 6% hydroxyethyl starch (HES) on hemodynamic and gastric mucosal acidosis variables, in septic hypovolemic patients.
                Prospective, randomized, clinical investigation.
                University hospital intensive care unit.
                Thirty-four septic hypovolemic ventilated and hemodynamically controlled patients.
                Invasive hemodynamic and gastric tonometric measurements.
                Hemodynamic and tonometric parameters were recorded at baseline and 60 min after infusion of 500 ml of each colloid. In all patients central venous pressure, pulmonary artery occlusion pressure, cardiac index and mean arterial pressure increased significantly with both colloids, and hemoglobin concentration decreased by the same amount while oxygen delivery remained stable. Gastric intramucosal pH increased from 7.27 +/- 0.08 to 7.31 +/- 0.07 (p < 0.001) with MFG and decreased non-significantly from 7.26 +/- 0.11 to 7.22 +/- 0.08 (ns) with HES. Carbon dioxide gastric mucosal arterial gradient decreased from 18 +/- 9 to 13 +/- 9 mmHg (p < 0.0005) in the MFG group and rose non-significantly from 18 +/- 11 to 21 +/- 11 mmHg with HES.
                Although MFG and 6% HES have the same hemodynamic effects, their physicochemical properties induce different responses on gastric mucosal acidosis in septic, hypovolemic and ventilated patients. These effects of MFG and HES on gastric mucosa need to be considered in patient management. To compare the hemodynamic effects of two different concentrations of pentastarch hydroxyethyl starch (HES; 200/0.5) solutions with a 4% human albumin solution for fluid resuscitation.
                Open-label, randomized, controlled study.
                Medical-surgical intensive care unit.
                34 consecutive, hemodynamically stable, adult patients with sepsis and suspected hypovolemia.
                Patients received a 400 mL infusion of either 10% HES (n = 11), 6% HES (n = 10), or 4% albumin (n = 13) over 40 minutes.
                Hemodynamic and blood data were collected 40, 70, 100, and 160 minutes after the start of the fluid challenge.
                Cardiac index, stroke volume index, and left ventricular stroke work index increased more in the 10% HES group than the 6% HES or albumin groups (P < 0.05). Oxygen delivery increased only in the 10% HES group. A decrease in hemoglobin concentration occurred in all three groups but was greatest in the 10% HES group.
                HES is as effective as albumin for volume resuscitation in septic patients. To compare the efficacy of volume expansion with 3.5% gelatin and 6% hydroxyethyl starch 200/0.5 in patients undergoing cardiac surgery. The second objective was to compare the two colloids in terms of blood losses and allogeneic blood transfusion exposure rate.
                In this open-label controlled study, patients were randomly allocated to receive either 3.5% urea-linked gelatin (GEL group: n = 55) or 6% hydroxyethyl starch 200/0.5/5.1 (HES group: n = 55) for per- (including priming of the bypass machine) and postoperative volume management with a maximum dosage of 30 +/- 3 mL.kg(-1).day(-1). Volume replacement was guided according to routine per- and postoperative care based on cardiac index, mixed venous oxygen saturation, and diuresis. If additional colloid was required, 4.5% albumin had to be given. The study period comprised per- and postoperative investigations up to 18 hr after surgery.
                All hemodynamic variables were comparable in both groups. Total study drug was 25.8 +/- 4.8 mL.kg(-1) in the GEL group and 24.5 +/- 6.0 mL.kg(-1) in the HES group. There was no difference in the number of patients receiving albumin solution or in the amount of albumin administered. Total blood loss was higher in the HES than in the GEL group (11.0 +/- 7.8 mL.kg(-1) vs 8.7 +/- 4.0 mL.kg(-1); P < 0.05) resulting in a higher need for allogeneic blood transfusion (HES: nine patients received 12 units, GEL two patients received 3 units; P = 0.026).
                In the conditions of the present study, HES was not associated with a better plasma expansion effect than GEL. HES could result in a higher need for allogeneic blood transfusion. The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer's acetate on cardiac and stroke volume index after cardiac surgery.
                Three consecutive boluses (each 7 mL·kg(-1)) of either 6% HES 130/0.4, 4% gelatine, or Ringer's acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg(-1)) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg(-1).
                Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min(-1)·m(-2) (0.7), 34.1 (6.7) ml·m( -2)] than in the gelatine group [2.2 L·min(-1)·m( -2) (0.6), 25.8 (7.2) ml·m(-2)] after completion of 7 mL·kg(-1) of study solution. At this stage, the effect of gelatine did not differ from Ringer's acetate. After completion of 14 mL·kg(-1) and 21 mL·kg(-1) of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer's acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer's acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer's acetate group. 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. The effects of hetastarch and human albumin solutions on perioperative bleeding and coagulation parameters during abdominal aortic aneurysm repair were compared. In two randomized groups of 20 patients, albumin 5% (group 1) or hetastarch 6% (group 2) 1 g/kg was given during surgery. The remaining perioperative fluids consisted of lactated ringers and packed red blood cells. Perioperative coagulation measurements included partial thromboplastin time, prothrombin time, activated clotting time, platelet count, and bleeding time. Estimated blood loss and the total amount of crystalloid and blood infused were also measured. The surgeon, blind to the colloid used, subjectively rated bleeding on a scale of 1 to 10. There was no significant difference between groups for any measured parameter at any time. Measurements of coagulation function were within normal limits for both groups. Hetastarch does not cause clotting disorders in patients undergoing abdominal aortic aneurysm repair, at least if the quantities used in this study are not exceeded. The effects of intraoperative changes in plasma colloid osmotic pressure (COP) on the formation of intestinal edema were studied in patients during modified Whipple's operation (hemipancreato-duodenectomy). Eighteen patients (ASA physical status I or II) were randomly assigned to one of three groups. They received either lactated Ringer's (RL group, n = 6), 10% hydroxyethyl starch (HES group, n = 6), or 20% human albumin (HA group, n = 6) as a volume replacement solution, which was given to maintain central venous pressure (CVP) at the preoperative level. Jejunal specimens were obtained after the first transsection of the jejunum and prior to the jejuno-jejunostomy. Their water fraction (g H2O/g tissue dry weight) was measured gravimetrically. COP was determined prior to induction of anesthesia and upon removal of the second jejunal sample. In the RL group, 3,850 +/- 584 ml (data are means +/- SEM) of volume replacement solution were infused from induction of anesthesia to removal of the second jejunal sample. In the HES group, 1,358 +/- 45 ml were infused, and in the HA group, 463 +/- 49 ml were infused. During this time, COP decreased from 20.3 +/- 0.5 mmHg to 14.1 +/- 0.6 mmHg in the RL group, remained at 22.0 +/- 0.9 mmHg in the HES group, and increased from 20.7 +/- 0.9 mmHg to 28.1 +/- 0.9 mmHg in the HA group.(ABSTRACT TRUNCATED AT 250 WORDS) Intravascular volume replacement therapy is an important issue in the perioperative management of liver transplantation. There is paucity of data on the safety of hydroxyethyl starch (HES) in patients undergoing liver transplantation. We evaluated the safety of a new HES 130/0.4 in the perioperative management of liver transplantation, with a special emphasis on renal function.
                Forty patients undergoing living donor liver transplantation were prospectively randomized into two groups. Patients in the ALB group (n = 20) received 5% human albumin. Patients in the HES group (n = 20) received third generation HES (6% HES 130/0.4). Total colloid administration was limited to 50 mL x kg(-1) x d(-1). The volume was given to maintain pulmonary artery occlusion pressure or central venous pressure between 5 and 7 mm Hg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Serum creatinine and cystatin C plasma levels were measured from arterial blood samples after induction of anesthesia, at the end of surgery, and on the first 4 postoperative days.
                All 40 enrolled patients completed the study. Demographic and intraoperative variables were comparable in both groups. Postoperatively, the mean +/- sd volume was 6229 +/- 1140 mL and 4636 +/- 1153 mL in HES and ALB groups, respectively (P = 0.003). There was significantly greater [corrected] net cumulative fluid balance in the HES [corrected] group 3047 +/- 2000 [corrected] mL compared with the ALB group 1100 +/- 900 [corrected] mL, P = 0.029. Serum creatinine, creatinine clearance, and cystatin C plasma levels showed no significant differences between the two groups. One patient in each group developed acute renal failure requiring renal replacement therapy.
                The use of HES 130/0.4 as an alternative to human albumin resulted in equivalent renal outcome after liver transplantation.
From this review, there is no evidence that one colloid solution is more effective or safe than any other, although the CIs were wide and do not exclude clinically significant differences between colloids. Larger trials of fluid therapy are needed if clinically significant differences in mortality are to be detected or excluded.