Molecular size and origin do not influence the harmful side effects of hydroxyethyl starch on human proximal tubule cells (HK-2) in vitro.

BACKGROUND: Recently, clinical trials revealed renal impairment induced by hydroxyethyl starch (HES) in septic patients. In prior studies, we managed to demonstrate that HES accumulated in renal proximal tubule cells (PTCs). The related pathomechanism has not yet been discovered. To validate our hypothesis that the HES molecule itself is harmful, regardless of its molecule size or origin, we conducted a comprehensive study to elucidate the influences of different HES preparations on PTC viability in vitro. METHODS: Cell viability of human PTC was measured with a cytotoxicity assay, quantifying the reduction of tetrazolium salt to colored formazan. Experiments were performed by assessing the influence of different carrier solutions of HES (balanced, nonbalanced, culture medium), different average molecular weights (70, 130, 200 kDa), different origins (potato or corn derived), and various durations of incubation (2-21 hours). Furthermore, HES 130/0.4 was fractionated by ultrafiltration, and the impact on cell viability of average single-size fractions with <3, 3 to 10, 10 to 30, 30 to 50, 50 to 100, and >100 kDa was investigated. We also tested the possible synergistic effects of inflammation induced by tumor necrosis factor-α. RESULTS: All tested HES solutions, regardless of origin or carrier matrix, decreased cell viability in an equivalent, dose-dependent manner. Coincubation with tumor necrosis factor-α did not reduce HES-induced reduction of cell viability. Minor differences were detected comparing 70, 130, and 200 kDa preparations. Analysis of fractionated HES revealed that each fraction decreased cell viability. Even small HES molecules (10-30 kDa) were significantly deleterious. CONCLUSIONS: For the first time, we were able to show that only the total mass of HES molecules applied is responsible for the harmful impact on renal PTC in vitro. Neither molecular size nor their origin showed any relevance.

[Is there any place for hypertonic saline for fluid resuscitation in septic shock]. / Il y a-t-il une place pour le sérum salé hypertonique dans les états septiques graves?

Fluid loading is the first step, necessary to care for severe sepsis. Two main classes of solutions are currently available: crystalloids and colloids. The concept of small volume resuscitation with hypertonic saline has emerged these last years in the care of traumatic haemorrhagic shock. The main benefits are the restoration of intravascular volume, improvement of cardiac output and improvement of regional circulations. Many experiments highlight modulation of immune and inflammatory cascades. We report the mechanisms of action of hypertonic saline based on experimental human and animal studies, which advocate its use in septic shock.

Efeitos cardiovascular e metabólico da reposição volêmica com hidroxietilamido 130/0, 4 em felinos domésticos com hipovolemia induzida / Cardiovascular and metabolic effects of volemic expansion with hydroxyethyl starch 130/0, 4 in domestic cats with induced hypovolemia

O objetivo deste estudo foi comparar os efeitos da expansão volêmica produzida pelo hidroxietilamido 130/0,4 (HES 130/0,4) ou pelo sangue em gatas com hipovolemia induzida. Foram utilizadas 12 gatas adultas, sem raça definida (SRD), com peso médio de 2,85±0,28kg e hígidas. Os animais foram induzidos à anestesia geral com isofluorano a 5V por cento, intubados e conectados a um sistema sem reinalação de gases. Após a instrumentação, os animais foram mantidos sob anestesia com isoflurano em 1,3V por cento e mantidos em ventilação mecânica, ciclada a pressão. Em seguida, foi induzida a hipovolemia por meio da retirada de 30ml kg-1 de sangue da artéria femoral. Após 60 minutos da estabilização do paciente, os tratamentos foram iniciados. No grupo hidroxietilamido (GH, n=06), os animais receberam, como reposição volêmica, o hidroxietilamido 130/0,4 no mesmo volume de sangue retirado e, no grupo sangue (GS, n=06), os animais receberam o próprio sangue retirado, sendo considerado grupo controle. A pressão arterial sistólica, a diastólica e a média e a pressão venosa central aumentaram após a reposição volêmica em ambos os grupos. Observou-se, para o GH, aumento da PaCO2 no T15, no T30 e no T60. Houve redução do pH no T30 e no T45 e de íons Na+ no T90 para GH. A restauração das pressões arteriais com a administração de HES 130/0,4 foi similar ao grupo controle. A reposição volêmica com HES 130/0,4 produz aumento acentuado da PVC; e o uso do HES 130/0,4 em gatas submetidas à hipovolemia não produziu alterações clinicamente significativas no equilíbrio ácido-básico.

The aim of this study was to compare the volemic expansion effects produced by hydroxyethyl starch 130/0.4 (HES 130/0.4) or blood, in female cats with induced hypovolemia. Twelve healthy adult female cats, crossbreed and weighing an average of 2.85±0.28kg were used. They were induced into general anesthesia with isofluorane at 5V percent, intubated and connected to a non-rebreathing system. After instrumentation, the animals were maintained under anesthesia with isofluorane at 1.3V percent and maintained on pressure cycled mechanic ventilation. Afterwards, hypovolemia was induced by withdrawal of 30ml kg-1 of blood from the femoral artery. After 60 minutes of stabilization of the patient, the treatments were initiated. In the hydroxyethyl starch group (GH, n=06) the animals received hydroxyethyl starch 130/0.4 as volemic expansion at the same volume of blood withdrawed, in the blood group (GS, n=06) the animals received their own withdrawed blood, being considered the control group. The systolic, diastolic and mean arterial pressures and central venous pressure increased after volemic expansion in both groups. An increase of PaCO2 at T15, T30 and T60 in GH was observed. In addition, there was reduction of pH at T30 and T45 and Na+ ions at T90 in GH. The arterial pressure restoration with the use of HES 130/0.4 was similar to the control group; the volemic expansion with HES 130/0,4 produces accentuated increase of CVP; the use of HES 130/0,4 in female cats submitted to hypovolemia did not produce clinically significant alterations in acid-base equilibrium.

Initial administration of hydroxyethyl starch vs lactated Ringer after liver trauma in the pig.

BACKGROUND: This study tested the circulatory effectiveness of post-trauma administration of a large intravascular volume expander, hydroxyethyl starch 130/0.4 (HES), vs standard lactated Ringer's solution (RL). METHODS: Liver injury was inflicted in 14 pigs [31 (4) kg; mean (sd)] and treatment simulated an acute pre-hospital event: after a standard first-respond delay (7 min), volume administration was provided in three phases to simulate increasing intravascular access. In the first two phases, the fluid was administered either by HES or by RL and, during the last phase, all animals received HES to stabilize the intravascular volume. RESULTS: The liver trauma severed an equal number of 1-3 mm diameter blood vessels [1.4 (0.6)] and after 7 min, the blood loss was 184 (127) ml and mean arterial pressure had decreased by 19 (13) mm Hg (P<0.01). The intravascular volume expansion effect was 115 (25)% for HES and 76 (21)% for RL (P<0.05), yet oxygen uptake was maintained in zero of seven vs three of seven pigs and the survival was three of seven vs seven of seven, respectively (P<0.05). In these animals, the initial administration of HES provoked uncontrolled bleeding, whereas the administration of RL was associated with attenuated bleeding: total blood loss 2455 (1919) vs 311 (208) ml, respectively (P<0.01), reflecting that bleeding ceased in six of the pigs administered RL. CONCLUSIONS: After injury, the intravascular volume expanding effect of HES was larger than that for RL. However, initial administration of HES provoked uncontrolled haemorrhage, suggesting that prioritizing intravascular volume expansion did not result in stabilization of the circulation after haemorrhage.

Hydroxyethyl starch-induced pruritus relieved by a combination of menthol and camphor.

Hydroxyethyl starch is a key component of many colloid volume expanders used in hypovolemic shock and otologic disease. Pruritus is a common side effect. Histopathology reveals multiple cytoplasmic vacuoles in dermal macrophages, endothelial cells, and perineural cells with electron-dense foreign material within the said vacuoles. Although classically refractory to treatment with corticosteroids and antihistamines, some benefit has been achieved with capsaicin, ultraviolet light therapy, and oral naltrexone. We present a case responsive to menthol and camphor and discuss the possible therapeutic mechanism.

Acute normovolemic hemodilution.

BACKGROUND: The inherent risks of blood transfusion have led to concerted efforts to find alternatives to allogeneic blood transfusion. Among these alternatives are supplementation with iron and treatment with erythropoietin, autologous pre-donation before major elective surgery, intraoperative blood salvage (particularly for emergency cases or when major blood loss is unanticipated), acute normovolemic hemodilution, and artificial blood substitutes. METHODS: Review of pertinent English-language literature. RESULTS: Autologous pre-donation of the patient's own blood, even if supplemented with iron and erythropoietin, is increasingly out of favor for several reasons. Autologous pre-donation is an added out-of-pocket expense for the patient. The major cause of incompatible blood transfusion, namely clerical error, is not eliminated. Moreover, autologous pre-donated blood is not released to the general blood supply; therefore, autologous blood that is not returned to the patient by infusion is wasted. Acute normovolemic hemodilution is a safe alternative that eliminates the risk of mistransfusion, minimizes the shed red cell mass when bleeding occurs, and reduces the risk of perioperative transfusion as shown in patients undergoing radical prostatectomy. CONCLUSIONS: Acute normovolemic hemodilution achieves equivalent outcomes at lower cost compared with autologous pre-donation. Patient safety is increased, and if pharmacologic strategies are combined with acute normovolemic hemodilution, allogeneic blood transfusion may be eliminated entirely.

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 > or = 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 chi 2 analysis for a 2 x 3 table). Systolic hypertensive episodes (> or = 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.

Effects of colloidal resuscitation fluids on reticuloendothelial function and resistance to infection after hemorrhage.

The effects of three resuscitation fluids, hydroxyethyl starch (HES), Haemaccel, and fresh autologous blood, on reticuloendothelial system phagocytic and catabolic functions and resistance to infection after 40% hemorrhages in BALB/c mice were studied. The mice, anesthetized with isoflurane, were bled over a 10-min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. The uptake and catabolism of intravenously injected double-labelled sheep erythrocytes (51Cr-125I-SRBC) in liver and spleen were determined at 1 and 48 h after hemorrhage. No significant changes in the uptake or catabolism of SRBC in liver or spleen were found at 1 h after hemorrhage and resuscitation with any of the fluids. However, at 48 h a significant increase in liver uptake of SRBC was seen in animals resuscitated with either Haemaccel or HES compared to that in animals resuscitated with shed blood or in animals subjected to a sham operation. The increase in liver uptake was accompanied by a small decrease in spleen uptake in animals resuscitated with Haemaccel but not with HES. No great changes in catabolic activity were seen at 48 h, although activity levels tended to be higher in animals resuscitated with Haemaccel. Separate groups of animals were challenged by an intraperitoneal injection with live Escherichia coli at 1 or 48 h after hemorrhage and resuscitation. Sixty-four percent of the animals resuscitated with shed blood survived the challenge with E. coli at 1 h after hemorrhage, whereas only 10 and 0% survival was seen for animals resuscitated with Haemaccel and HES, respectively. At 48 h survival was 80% for shed-blood-resuscitated animals and 60 and 70% for Haemaccel- and HES-resuscitated animals, respectively.

Controversies in shock research: hypertonic resuscitation--pros and cons.

The proper fluid resuscitation of hemorrhagic shock is still controversial. Hypertonic saline has been suggested for prehospital resuscitation of hemorrhagic shock, because of its superior ability to expand blood volume and elevate systemic blood pressure and cardiac output in a small volume and during a short time period. We have defined two types of hemorrhagic shock: controlled hemorrhagic shock (CHS), where the bleeding source is immediately occluded following hemorrhage, and uncontrolled hemorrhagic shock (UCHS), where bleeding is induced by injury to blood vessels that are left unoccluded. It was observed that hypertonic saline (HTS) treatment of controlled hemorrhagic shock leads to an increase in blood pressure and cardiac output, while HTS treatment of UCHS leads to increased bleeding from injured blood vessels, hemodynamic deterioration, and increased mortality. Conversion of UCHS to CHS by tourniquet, military antishock trousers, or surgical hemostasis prevented excessive bleeding and mortality following HTS. Several clinical studies have used hypertonic saline dextran (HSD) or hypertonic saline (HS) for treatment of trauma casualties, but to date no significant improvement in mortality has been demonstrated by either HS or HSD. A more favorable effect but still not statistically significant effect has been demonstrated in patients with a Glasgow Coma Scale of 8 or less. The efficacy of HS has not clearly been established in clinical trials, in all of which HS was used in combination with conventional crystalloid therapy. Further human trials are required to better define the patient population that would benefit most from the prehospital administration of HS.

[Conservation of the blood]. / La conservation du sang

Many factors already contribute to limit the amount of bank blood available for therapeutic use; a possible reduction in the amount of available blood could stem from the relative indifference of young people towards the gift of blood and the increase in the size of the pool of positive carriers of Australian antigen. Moreover, new operations appear (coronary by-pass) which increase the demand for blood. It is imperative that we adopt attitudes and practice techniques that will contribute to the conservation of blood. This paper discusses the advantages of an active blood bank committee which, alone, can reduce the consumption of blood by 20 percent. Moreover, actual techniques for conservation of blood are reviewed: controlled hypotension, haemodilution and intraoperative blood salvage.