Hydroxyethyl Starch Group Research Articles

Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study

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.

Alteration of anion gap during almost total plasma replacement with synthetic colloids in piglets

In ten piglets (body weight 8.2-11.6 kg), acid base, electrolyte and anion gap changes were investigated during almost total plasma replacement with hydroxyethyl starch (HES) and modified fluid gelatin (GEL) in saline solution using a cell saver autotransfusion technique. During the study, there were only moderate acid base changes, but marked disturbances in anion balance. At study end, the mean chloride concentration was significantly higher (mmol/l: normal values 97-108, HES 116 +/- 1.5, GEL 108 +/- 1.1, p < 0.01) and the mean anion gap was significantly lower in the HES group in comparison to the GEL group (mmol/l: normal values 5-14, HES 3 +/- 1.7, GEL 11.9 +/- 0.9, p < 0.01). It is concluded that plasma replacement with electroneutral HES, but not with negatively charged GEL, can lower the anion gap irrespective of the underlying disease. This can be misleading when the anion gap is used for differential diagnosis of metabolic acidosis in patients after large volume infusion of synthetic colloids.

Activity of blood coagulation and fibrinolysis during and after hydroxyethyl starch (HES) colloidal volume replacement

Objectives: To examine the effect of medium molecular weight hydroxyethyl starch on protein C levels and the changes in the activation state of blood platelets, coagulation and fibrinolyis during and after 5 day of its infusion. Design and Methods: Fifty male patients (mean age: 47 years, range 45–50 years) who required prostatectomy for benign prostatic hyperplasia were divided into two equal groups. One group was given 15 mL/kg body weight (mean volume 1000 mL ± 100 mL) of 6% hydroxyethyl starch (HES) 200/0.5, the other received an equal volume of 5% human albumin during the operation. Blood samples were collected immediately before infusion (baseline values) and at 20, 40, 60, 90, 240, and 480 min after the infusion started then daily for the next 5 days postoperatively. Hematocrit, factor VIII:C, thrombin-antithrombin III complex; the anticoagulant protein C levels; the fibrinolytic parameters tissue type plasminogen activator (t-PA), and the fibrinolytic product D-Dimer and the platelet aggregation activity were measured. Results: The data obtained did not detect any significant differences between HES and human albumin in the plasma levels of thrombin-antithrombin III complex, protein C, tissue-type plasminogen activator and the fibrin split products D-Dimer. Factor VIII:C and platelet aggregation were significantly lower in the hydroxyethyl starch group in comparison with albumin. Baseline values were attained postoperatively for factor VIII:C and platelet aggregation by the first and fifth days, respectively. Conclusion: The lowering effect of medium molecular weight hydroxyethyl starch on factor VIII:C would not be attributed to increased proteolytic activity of protein C on this coagulation cofactor because there is a nonsignificant change in protein C levels.

Rebound intracranial hypertension in dogs after resuscitation with hypertonic solutions from hemorrhagic shock accompanied by an intracranial mass lesion.

We compared intracranial pressure (ICP) and cerebral blood flow (CBF) in dogs after inflating a subdural intracranial balloon to increase ICP to 20 mm Hg, inducing hemorrhagic shock (mean arterial pressure [MAP] of 55 mm Hg), and infusing a single bolus of fluid consisting of either 54 mL/kg of 0.8% saline (SAL), 6 mL/kg of 7.2% hypertonic saline (HS), 20% hydroxyethyl starch (HES) in 0.8% SAL, or a combination fluid (HS/HES) containing 20% HES in 7.2% saline. Twenty-six dogs were ventilated with 0.5% halothane in N2O and O2 (60:40 ratio). As ICP was maintained at 20 mm Hg, rapid hemorrhage reduced MAP to 55 mm Hg (time interval of zero [T0]) which was maintained at that level for 30 minutes (until T30). Subsequently, over a 5-minute interval (T30-T35), one of the four randomly assigned resuscitation fluids was infused. Data were collected at baseline; after subdural balloon inflation; at T0, T30, T35, and 30-minute intervals thereafter for 2 hours (T65, T95, T125, and T155). CBF and ICP were compared using repeat-measure ANOVA. Cerebral blood flow was greater at T35 in the HS and HS/HES groups than in the HES group (P = .025). In the SAL group, ICP increased significantly from T0 to T35, remaining unchanged thereafter. At T35, ICP in the HS group was significantly lower than in the SAL group (P < .05) but subsequently increased. ICP in the HS/HES group exceeded that in all other groups at T95 and T125 (P < .05). After a severe reduction in cerebral perfusion pressure (CPP), HS solutions (both HS and HS/HES) were associated with a delayed rise in ICP and did not improve global forebrain CBF in comparison with conventional saline solutions.

Lactated Ringer's Solution versus Hydroxyethyl Starch for Volume Replacement in Autologous Blood Donors with Cardiovascular Disease: A Controlled, Randomized Trial

Abstract Background and Objectives: The study was designed to evaluate whether volume replacement following blood donation can prevent arterial hypotension in autologous blood donors with cardiovascular disease. Materials and Methods: One hundred nineteen autologous blood donors with known cardiovascular disease were randomly allocated to receive, following withdrawal of 500 ml of blood, either no infusion (control group) or a 25 ml/min intravenous infusion of either 1,500 ml of lactated Ringer's solution (LRS) or 500 ml of 6% hydroxyethyl starch (HES). Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 min until 90 min after donation. Results: Group means showed little difference between the groups in blood pressure throughout the monitoring period. The proportion of patients who at least once had a ≥20% decrease from baseline in systolic blood pressure was 3–5 times greater in the control group than in the LRS and the HES group (50 vs. 10 and 15%, respectively; p &lt; 0.001 on χ2 analysis for a 2 × 3 table). Systolic hypertensive episodes (≥ 20% increase over baseline) were observed more frequently in the LRS group than in the control and the HES group (41 vs. 10 and 18%, respectively; p=0.003). Conclusion: Both LRS and HES, administered at a volume ratio to blood loss of 3:1 and 1:1, respectively, significantly reduced the incidence of systolic hypotensive episodes in autologous blood donors with cardiovascular disease. LRS at a 3:1 volume ratio to blood loss was associated with a high rate of systolic hypertension.

Lactated Ringer’s Solution versus Hydroxyethyl Starch for Volume Replacement in Autologous Blood Donors with Cardiovascular Disease: A Controlled, Randomized Trial

Background and Objectives: The study was designed to evaluate whether volume replacement following blood donation can prevent arterial hypotension in autologous blood donors with cardiovascular disease. Materials and Methods: One hundred nineteen autologous blood donors with known cardiovascular disease were randomly allocated to receive, following withdrawal of 500 ml of blood, either no infusion (control group) or a 25 ml/min intravenous infusion of either 1,500 ml of lactated Ringer’s solution (LRS) or 500 ml of 6% hydroxyethyl starch (HES). Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 min until 90 min after donation. Results: Group means showed little difference between the groups in blood pressure throughout the monitoring period. The proportion of patients who at least once had a ≥ 20% decrease from baseline in systolic blood pressure was 3–5 times greater in the control group than in the LRS and the HES group (50 vs. 10 and 15%, respectively; p < 0.001 on χ² analysis for a 2 × 3 table). Systolic hypertensive episodes (≥ 20% increase over baseline) were observed more frequently in the LRS group than in the control and the HES group (41 vs. 10 and 18%, respectively; p = 0.003). Conclusion: Both LRS and HES, administered at a volume ratio to blood loss of 3:1 and 1:1, respectively, significantly reduced the incidence of systolic hypotensive episodes in autologous blood donors with cardiovascular disease. LRS at a 3:1 volume ratio to blood loss was associated with a high rate of systolic hypertension.

High oxygen delivery and extraction by perfluorocarbon-primed extracorporeal membrane oxygenation do not prevent anaerobic metabolism in rabbits

Purpose : This study was designed to evaluate the advantage of perfluorocarbon (PFC) emulsion priming for venoarterial extracorporeal membrane oxygenation (ECMO) by comparison with hydroxyethyl starch (HES) solution in rabbits (2.8 to 3.9 kg). Results : ECMO initiation was accompanied by a profound decrease in hematocrit (from 40.1% to 14.9%) in both groups. The arterial and the right atrial oxygen contents in the PFC group (n = 4; 38.5 and 11.5 mL/dL) were greater than in the HES group (n = 5; 7.0 and 5.1 mL/dL). Right atrial oxygen tension in the PFC group increased at the beginning of ECMO (from 38.4 to 51.2 mm Hg; P = .031) and remained higher than in the HES group for 60 minutes. These results indicate that oxygen supply and extraction in the PFC group were much greater than in the HES group. However, plasma lactate increased progressively during the 120-minute ECMO procedure in both groups (from 1.8 to 14.5 in the HES group, and from 2.3 to 12.2 in the PFC group). Conclusion : Perfluorocarbon priming for ECMO, although providing high oxygen delivery and extraction, does not prevent anaerobic metabolism.

A controlled, randomised study of the effects of 7.5% hypertonic saline / 6% hydroxyethyl starch on haemodynamic, oxygen transport and metabolic parameters in patients undergoing abdominal aortic reconstruction

Objective: To evaluate the effects of 7.5% hypertonic saline / 6% hydroxyethyl starch (HES) against 6% HES as control on haemodynamics, oxygen transport patterns and selected metabolic parameters in patients undergoing abdominal aortic reconstruction. Design: Prospective, randomised controlled study. Setting: Operating theatre and general intensive care unit in a university hospital. Subjects: Fifty patients undergoing abdominal aortic reconstruction were randomised to receive either 7.5% hypertonic saline/6% HES (HTS-HES group, n=25) or 6% HES (HES group, n=25) after aortic clamp release. Measurements and main results: Compared to 6% HES, 7.5% NaCl/6% HES produced a significant increase in cardiac index (3.6±0.9 versus 3.0±0.8 l/min/M2, p<0.05) and a significantly higher mean arterial pressure at the end of surgery (103±14 versus 94±14 mmHg). Oxygen consumption index (VO2I) was significantly higher in the control group of patients given 6% HES after infusion and at the end of surgery (102±23 versus 83...

The Influence of Resuscitation on Hemodynamics and Oxygen Radical-Induced Reperfusion Injury after Arterialized Liver Transplantation in the Rat

Extended hemodynamic monitoring during arterialized rat liver transplantation procedure and the effects of resuscitation with albumin, starch-desferrioxamine-conjugated hydroxyethyl starch (HES-DFO), or hydroxyethyl starch (HES) on hemodynamics are presented. Livers from SPRD rats were stored for 20 hr in ice-cold UW solution and were orthotopically transplanted with reconstruction of the hepatic artery under hemodynamical monitoring applying invasive measurement of mean arterial blood pressure (MAP) and cardiac output (CO). Comparable amounts of albumin, HES-DFO, and HES were given in a randomized and blinded fashion after transplantation. Ringer's solution was given additionally when blood pressure was below 65 mmHg. Fifteen, 60, and 90 min after surgical procedure blood samples were taken to determine acid base status, blood gases, and blood cell count. Oxygen radical-induced reperfusion injury was determined by thiobarbituric acid reactive substances (TBARS) in serum and total glutathione in liver tissue 90 min after surgery. During the anhepatic period CO was reduced to 20% of baseline and MAP to 40 mmHg. In all groups, declamping led to a transient recovery of hemodynamic situation, whereas during further reperfusion, CO and MAP were significantly reduced in the HES- and HES-DFO-treated group in contrast to the group receiving albumin. Animals of the HES group required significantly more Ringer's solution to maintain blood pressure (2.6 ± 0.9 ml; 4 of 6 animals needed additional resuscitation) than animals given albumin (0.4 ± 0.3 ml,P< 0.05, 2/9 needed further supplementation) or HES-DFO (1.2 ± 0.5 ml; 5/10 required additional resuscitation), respectively. Animals treated with HES or HES-DFO failed to restore base excess and serum lactate in contrast to resuscitation with albumin. However, TBARS was mitigated by resuscitation with HES-DFO compared to albumin and HES, whereas no significant differences were observed in respect to tissue glutathione of transplanted livers. In conclusion the model described allows intensive monitoring of hemodynamic parameters and metabolic status during arterialized rat liver transplantation procedure. Moreover, the results indicate that resuscitation with albumin could maintain central hemodynamics and restore homeostasis during the early reperfusion period after transplantation in contrast to resuscitation with HES or HES-DFO, respectively. Although resuscitation with HES-DFO resulted in mitigation of lipid peroxides determined by TBARS, no significant improvement of hemodynamics and homeostasis could be observed during reperfusion as it can be observed with albumin.

Large-Dose Administration of 6% Hydroxyethyl Starch 200/0.5 for Total Hip Arthroplasty

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. (Anesth Analg 1996;83:262-8)

Acute effects of complete blood exchange with ultra-purified hemoglobin solution or hydroxyethyl starch on liver and kidney in the animal model

The present animal study investigates the influence of an acute and almost complete isovolaemic haemodilution with a new ultrapurified polymerized bovine haemoglobin (UPBH) on hepatic and renal function and histology in comparison to hydroxyethylstarch (HES). Eighteen anaesthetized dogs underwent progressive isovolaemic haemodilution with either HES (group 1) or UPBH (group 2) to haematocrit target levels of 15, 10 and < 5%. Haemodynamics, arterial and mixed-venous blood gases and blood chemistry were determined at each measurepoint. With a haematocrit value < 5%, biopsies were taken from the liver and kidneys and prepared for light and electron microscopic analysis. One dog without haemodilution figured as control animal. Statistical analysis was performed using ANOVA, with p < 0.05 considered significant. In group 1, the cardiac output was increased in parallel to a decreasing vascular resistance, while in group 2 haemodynamic parameters remained unchanged. In group 1, avDO2 and final DO2 and VO2 were decreased. In contrast, avDO2 and oxygen extraction ratio were increased, while VO2 remained stable under decreasing DO2 in group 2. In both groups, coagulation values and blood chemistry showed dilution dependent changes. Colloid osmotic pressure and plasma viscosity were increased in both groups but COP was higher in group 1 compared to group 2. A lower urine output in comparison to group 1 and a maximal concentration of 0.27 g/dl of free haemoglobin in urine were seen in group 2. Liver biopsies showed no severe histological changes in both groups. Renal histology revealed severe alterations of proximal tubules after haemodilution with HES. In contrast, no histological indications for acute toxic or ischaemic lesions in the kidneys were seen after UPBH treatment. The high degree of purification and polymerization of bovine haemoglobin associated with adequate tissue oxygenation by increased oxygen extraction resulted in normal histological and functional findings after acute and almost complete blood exchange with UPBH. In contrast, HES-treated animals showed severe histological changes of renal tubuli caused by isovolaemic anaemia.

Ultrapure polymerized bovine hemoglobin improves structural and functional integrity of the isolated perfused rat kidney.

Since it became evident that organ dysfunctions after acute hemolysis are not induced by hemoglobin per se, but by stroma-contaminated hemoglobin, solutions of ultrapure stroma-free hemoglobins were regarded to be possible substitutes for blood in transfusion medicine. We tested one of the recently developed modified bovine hemoglobins (Ultrapure polymerized bovine hemoglobin 1; UPPBHb1) in the isolated perfused rat kidney (IPRK) model, using a recirculating system. Control kidneys were perfused with a substrate-enriched Ringer solution containing hydroxyethyl starch (HES) to produce isoncotic conditions. In the experimental group HES was substituted in part by UPPBHb1 (34 g/l). For determination of functional parameters, the kidneys were perfused for 180 min. A separate set of kidneys of both groups was perfusion fixed after 80 min of perfusion which is the period of optimal function. Light and electron microscopic analysis revealed major alterations only for the outer medulla of HES kidneys. Only these suffered from a considerable extent of proximal tubular S3 damage, exhibiting condensed tubular epithelia. In the inner stripe of the outer medulla, which is the zone of greatest sensitivity to damage in the isolated perfused kidney, severe hydropic degeneration, cell detachment, and necrotic destruction of the medullary thick ascending limb were seen in the HES-perfused group, too. In the UPPBHb1 group, the medullary thick ascending limb was well preserved, and S3 showed only a minor degree of damage. UPPBHB1 kidneys were further characterized by the occurrence of intracapillary and interstitial precipitates of UPPBHb1 in inner stripe of the outer medulla and inner medulla. The glomerular filtration rate was significantly higher in UPPBHb1-perfused kidneys (870 +/- 80 vs. 630 +/- 55 microliters/min/g kidney weight for HES). Absolute reabsorption of sodium paralleled the behavior of the glomerular filtration rate. The values for renal perfusate flow and urinary flow rate did not differ significantly between both groups. Renal autoregulation was better preserved in UPPBHb1-perfused kidneys (74 +/- 6% of full autoregulatory response) than in HES-perfused controls (42 +/- 4%). Our results suggest that perfusion of isolated rat kidneys with UPPBHb1 improves kidney function and morphology, providing better oxygenation than in control kidneys. UPPBHb1 does not exert additional nephrotoxic effects on the IPRK that will exceed the noxious potential of the method itself. Thus, it must be concluded that UPPBHb1 may be an oxyphoretic blood substitute with nephroprotective characteristics when compared with nonoxyphoretic substitutes. At least, UPPBHb1 seems to be a promising candidate as oxyphoretic additive to perfusates for the IPRK model.

Rheologic Effects of Plasma Substitutes Used for Preoperative Hemodilution

This study was designed to compare the influence of various plasma substitutes, administered for preoperative hemodilution, on blood rheology. We studied 40 patients, ASA grade I, who underwent elective facial reconstructive surgery and received 4% albumin (n = 10), 3.5% dextran 40 (n = 10), gelatin (n = 10), or hydroxyethyl starch (HES) (n = 10). Ten patients, undergoing the same surgical procedure without hemodilution, were chosen as controls. After hemodilution, hematocrit was decreased approximately 30%. Fibrinogen decreased in all tested groups except in the gelatin group. Plasma viscosity decreased with albumin (1.13 +/- 0.05 to 1.06 +/- 0.03 mPa.s; P < 0.01) and increased with HES (1.15 +/- 0.04 to 1.22 +/- 0.05 mPa.s; P < 0.01). At a high shear rate, the blood viscosity decreased in all groups. In contrast, at a low shear rate and at 40% corrected hematocrit, the blood viscosity decreased in the albumin (15.9 +/- 1.9 to 13.1 +/- 2.1 mPa.s; P < 0.01) and the dextran 40 (16.9 +/- 2.9 to 12.8 +/- 2.5 mPa.s; P < 0.01) groups and was unchanged in the gelatin and the HES groups. Erythrocyte aggregation (measured with primary aggregation time) was markedly decreased in the albumin (3.27 +/- 1.74 to 7.03 +/- 2.95 s; P < 0.01) and in the dextran 40 (2.72 +/- 0.58 to 6.24 +/- 2.55 s; P < 0.001) groups, unchanged with HES, and increased with gelatin (2.41 +/- 0.90 to 1.55 +/- 0.33 s). These findings suggest that albumin and dextran 40 may be the plasma substitutes of choice for preoperative hemodilution when this technique aims to improve rheologic conditions.

Effect of hydroxyethyl starch on the activity of blood coagulation and fibrinolysis in healthy volunteers

The aim of this study was to investigate whether hydroxyethyl starch of medium molecular weight (200 daltons), compared with albumin, has specific effects on blood coagulation and fibrinolysis. A prospective, randomized, double-blind, crossover trial. Laboratory at a university hospital. Ten healthy male volunteers, 23 to 39 yrs old, with no history of hypersensitivity, who had normal physical examinations, and were free of a bleeding disorder. All patients did not ingest any medications for > or = 2 wks before or during the study period. Each volunteer received either 500 mL of hydroxyethyl starch (6% wt/vol, average molecular weight 200 kilodaltons, molar substitution 0.5 [ratio hydroxyethyl groups/glucose units] in 0.9% sodium chloride; average molecular weight of 200 kilodaltons) or a control of 500 mL of human albumin (5% albumin solution). After a washout period of 4 wks, subjects crossed over to the alternate treatment. Blood samples were taken immediately before infusion and 20, 45, 75, 105, 165, 285, 405, and 1485 mins after the infusion started. Hematocrit, the blood coagulation parameters fibrinogen, activated partial thromboplastin time, factor VIII:C, thrombin-antithrombin III complexes, and the fibrinolytic parameters fibrin-split product D-Dimer, tissue type plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor, and plasmin-antiplasmin complexes were measured. Except for factor VIII:C levels, which were significantly lower in the hydroxyethyl starch group, no other significant differences in the plasma levels of the parameters mentioned were detected between hydroxyethyl starch and albumin infusions. In one volunteer, who had a low initial factor VIII:C level of 51%, a decrease to 28% at 165 mins during hydroxyethyl starch infusion was found (corresponding albumin value at 165 mins was 41%). a) Medium molecular weight hydroxyethyl starch has a specific lowering effect on factor VIII:C concentrations; this phenomenon may be hazardous to patients who need full hemostatic competence and who receive medium molecular weight hydroxyethyl starch (e.g., as a plasma expander). b) Medium molecular weight hydroxyethyl starch does not specifically influence the activity of the fibrinolytic system.

L'hydroxyéthylamidon peut-il être utilisé lors de la réanimation des sujets en état de mort cérébrale pour don d'organe ?

In France, most of the kidney grafts are obtained from brain dead organ donors. Brain death induces numerous changes, especially in haemodynamic status, requiring the infusion of large volumes of fluid. The aim of this study was to evaluate the effect of hydroxyethyl starch (HES) on the organ donors and the kidney graft function in recipients. We compared two groups of brain dead organ donors and the kidney grafts, differing by the infused solutions : either a combination of HES (Elohes®, Biosedra) and 4 % human albumin solutions (HES group), or albumin alone in the control group (Albumin group). In the two groups, sex-ratio, age, cause of brain death and duration of therapy were similar. Fluid requirements were identical in the two groups : respectively 2,211 ± 1,512 mL in the Albumin group vs 2,452 ± 1,094 mL in the HES group (p = 0.17). However, the volume of albumin was significantly decreased in the HES group : 711 ± 822 mL (p = 0.0001). Therefore the cost was lower in the latter : 638 ± 633 vs 1766 ± 788 FF. The coagulation status was not significantly different between the two groups. Amylasemia was higher in the HES group, but the difference was not significant. In the Albumin group, urinary output increased, but not significantly and creatinemia was decreased : 113.9 ± 62 vs 131.5 ± 44 μmol · L −1 (p < 0.05). The two groups of recipients were also similar for sex-ratio, age, kind of graft, cause of the chronic renal failure and ischaemia times. The lowest creatininemias during the first week were respectively : 167 ± 127 vs 146 ± 67 μmol · L −1 (p = 0.55). No dialysis was required. Four renal biopsies in the HES group showed an osmotic nephrosis without any deleterious consequence on the renal function. It is concluded that HES can be used safely for renal harvesting in brain dead patients and that it decreases the cost of organ donation.

Effect of Hydroxyethyl Starch on Alveolar Flooding in Acute Lung Injury in Dogs

The efficacy of hydroxyethyl starch (HES) in limiting alveolar flooding after acute lung injury was investigated using ethchlorvynol (ECV)-induced low pressure pulmonary edema in dogs. Harvested autologous plasma (PL) (control, n = 8) or 6% HES (n = 8) was infused (25 ml/kg) along with packed cells to result in an isovolemic, normochromic preparation before the administration of ECV. Extravascular thermal volume significantly increased after ECV administration in both groups of animals (6.6 to 13.4 ml/kg in PL, 6.5 to 15.0 ml/kg in HES). Systemic arterial PO2 decreased from 216 +/- 4 to 113 +/- 20 mm Hg, and venous admixture increased from 2.8 to 12.8% in the PL group but was not significantly changed in the HES group (219 +/- 5 to 203 +/- 8 mm Hg, and 2.9 to 4.4%, respectively). Epithelial lining fluid volumes after ECV administration increased in both groups but were elevated in the PL group to a greater extent than in the HES group (13.5 ml in HES versus 24.8 ml in PL). In the HES group there appeared to be no difference in the ability of plasma proteins to move across the alveolar epithelium. These results suggest that HES attenuates the flooding of the alveolar space and the resulting alterations in gas exchange during the development of low pressure pulmonary edema. The replacement of the plasma proteins with HES and the apparent inability of HES to cross the epithelial barrier into the alveoli may account for the protective effect of HES in these experiments.

Free polymerized hemoglobin versus hydroxyethyl starch in resuscitation of hypovolemic dogs.

Polymerized bovine hemoglobin (PBH) was compared with hydroxyethyl starch (HES) in a hypovolemic shock model. Eighteen dogs were subjected to hemorrhage; systolic arterial blood pressure was maintained at 40 mm Hg for 30 min (mean blood pressure 37.8 +/- 4.7 [SD] mm Hg). Resuscitation was conducted by infusing their own shed blood (control group) or 6% HES (mol wt 200,000) in 0.9% NaCl (HES group) or PBH (PBH group), both in an equal amount to the shed blood. Directly after infusion, oxygen delivery and consumption returned to prehemorrhage levels in all three groups. In the HES group, the lowered arterial oxygen content was compensated by a 158% increase in cardiac output, in contrast to an increase of 31% and 9%, respectively, in the control and PBH groups. Early recovery from hypovolemic shock with regard to oxygen transport and delivery in the PBH group seemed to be comparable to the control group, without the increase in cardiac output seen with HES infusion.

The importance of a colloid in canine pancreas preservation.

The role of hydroxyethyl starch (HES), the colloid component of the UW solution, was tested in canine pancreas preservation. Segmental pancreatic autografts were preserved for 48 hr cold storage with UW solution with HES (group 1) or UW solution without HES (group 2). After preservation, the pancreas was transplanted, and survival, serum glucose, serum amylase, intravenous glucose tolerance tests, tissue water content, and histology were compared between groups. In group 1 (with HES), 9/10 dogs were long-term survivors with one dog dying due to causes unrelated to preservation failure. In group 2 (without HES), 3/6 dogs died due to graft loss within one week posttransplant (P = 0.01). No graft failure occurred in group 1 (0/9) versus graft loss in 4/6 dogs in group 2 (P = 0.04). All animals in group 1 (with HES) showed normal serum glucose and amylase concentrations postoperatively, normal tissue water values after preservation, k values comparable to those observed after segmental autotransplantation without preservation, and relatively good histology. In group 2 (without HES), in 4/6 dogs graft failure occurred that led to the death (3 dogs) of the animals or to a diabetic state (1 dog). After 48-hr cold storage without HES, a significant increase in tissue water content, glucose and amylase levels was seen. After transplantation, hyperglycemia, hyperamylasemia, and clinical diabetes were observed in 4/6 dogs. Autopsy and histological evaluation showed evidence of thrombosis and ischemic insult. Two of 6 dogs in group 2 remained normoglycemic during follow-up with borderline k values. The results suggested that for consistently successful 48-hr preservation of the pancreas, HES is an important component of the UW solution. Although a colloid may not be essential for short-term preservation of kidney and liver, it appears to be an important factor in successful pancreas preservation.

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate(PHP) and stroma free hemoglobin(SFH) on pulmonary vascular responsiveness to various vasoactive substances in isolated perfused rat lungs.

Pulmonary vascular responsiveness to norepinephrine(NE), angiotensin-II (ANG-II), acetylcholine(ACh) and nitroglycerin (NG) was examined in isolated perfused rat lungs. The lungs were perfused with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), a newly introduced modified hemoglobin, stroma free hemoglobin (SFH) or hydroxyethyl starch (HES) at a constant flow rate. Perfusion pressure (PP) and intra-tracheal pressure (ITP) were measured. Effects of intrapulmonary arterial injection of NE, ANG-II, ACh and NG on PP were examined. NE and ANG-II produced a dose dependent increase in PP in all groups. The response to NE in PHP or SFH perfused group was significantly greater than that in HES-perfused group. ACh induced a dose dependent decrease in PP in HES and PHP groups, while in the SFH group, ACh produced a dose dependent increase in PP. NG produced a dose dependent decrease in all groups. Results showed that stroma free hemoglobin (SFH) inhibits relaxation induced by endothelium-derived relaxation factor (EDRF), but PHP dose not exert inhibitory action on vascular relaxation induced by EDRF.

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate(PHP) on renal circulation in isolated perfused rat kidneys.

We examined effects of perfusion of the kidney with pyridoxalated hemoglobin polyoxyethylene conjugate(PHP) solution on rat renal vascular responsiveness to norepinephrine(NE), angiotensin-II (AN-II), acethylcholine(ACh) and nitroglycerine(NG). The rat kidney was perfused with hydroxyethylstarch(HES) or PHP at a constant flow rate, using a pump. Perfusion pressure was monitored by a pressure transducer. Changes in PP induced by NE, AN-II, ACh and NG was examined. NE and AN-II applied intra-arterially induced a dose-related increase in PP in rat kidney perfused with both HES and PHP perfused groups. ACh and NG produced a dose dependent decrease in PP in both HES and PHP-perfused groups. There was no significant difference in response to ACh and NG between both groups. Results suggests that in rat vascular beds, PHP dose not interfere vascular relaxation caused by release of EDRF induced by ACh.