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High doses of hydroxyethyl starch and human albumin have similar effects on monocyte function and oncotic pressure.

The accumulation of hydroxyethyl starches (HES) in monocytes/macrophages has raised concern over their potential detrimental effects on host defences. We assessed prospectively the function of circulating monocytes isolated from patients treated with plasma exchange (PE) using HES. The study was carried out in the medical intensive care unit of a university hospital. Eight patients underwent PE for neurological disorders. Each patient underwent three PEs, 48 h apart. The total exchange volume was 4 L per PE. Only 4% human albumin was used for the first PE. In the second and third PEs, the plasma substitute was 2 L of HES (200,000/6%/0.62) and 2 L of albumin. Mononuclear cells were collected before and immediately after each PE and 48 h after the last PE. They were placed in suspension culture and incubated with lipopolysaccharide (LPS). Monocyte function was assessed in terms of procoagulant activity (PCA) and tumour necrosis factor alpha (TNF-alpha) production. LPS-stimulated PCA increased after the first PE (P < 0.05). Stimulated TNF-alpha production increased, but not significantly so. Similar effects were observed after the second and third PE (P < 0.05 for stimulated TNF-alpha). Values 48 h after the last PE were similar to those obtained before the second PE, suggesting that repeated infusions of HES had no detrimental effect on monocyte function. Furthermore, plasma oncotic pressure was preserved after PE with HES. These results support the partial replacement of costly human albumin with HES during repetitive PE, and suggest that HES might be a safe plasma expander in septic patients.

Adult↗

[Clinical experience with voluven solution used as a basic component for pump oxygenator filling during operations on the cardiac valves and coronary arteries].

The present study comparatively analyzed the clinical effects of three solutions used to fill an extracorporeal circulatory circuit (ECCC). The arterial and venous blood samples taken from patients operated on for valvular disease and coronary heart disease were studied. All patients (n = 61) were divided into 3 groups according to the basic component of the primary volume of ECCC filling: 1) Ringer's crystalloid solution; 2) gelofusin; 3) the hydroxyethyl starch 130/0.4 Voluven. The resultant samples were examined for the following parameters: a) hematological: the levels of formed blood elements, hemoglobin, erythrocytic hemoglobin, and free hemoglobin and the histograms of leukocytes, erythrocytes, and platelets; b) physicochemical: arterial and venous blood pH, pO2, pCO2, SatO2; c) biochemical: blood electrolytic balance and lactate levels. The values of hemoglobin, hematocrit, and blood gas composition were used to calculate oxygen consumption (ml/min x m2). The parameters of central hemodynamics and the temperatures in the rectum, esophagus, and venous oxygenator port were continuously monitored during extracorporeal circulation (EC). At its end, overall diuresis and water balance were determined. The plasma-substituting effect of Voluven was found to be highly effective during a clinical study. The found beneficial properties of the agent may be particularly attractive while applying EC to the surgery of acquired heat diseases when the duration of an operation and, accordingly, extracorporeal support forces the physician to administer large solution doses many times.

Acid-Base Equilibrium↗

[Clinico-morphological characteristics of the family of diseases: cytomegalic inclusion disease, iatrogenic thesaurismosis and septicemia].

The clinicomorphological manifestations of iatrogenic thesaurismosis that developed because of infusion therapy of patients with plasma substitutes were studied using autopsy and operative material from 44 deceased and 2 operated children aged 1 month to 3 years. An experimental disease was obtained in 16 rabbits. Cytomegalia was discovered in 23 deceased children with iatrogenic thesaurismosis and sepsis in 18 children. In 12 cases, sepsis was of iatrogenic nature. An assumption is worded about the three-member family of those diseases undergoing substantial pathomorphism.

Animals↗

[Plasmapheresis in the treatment of critical stages of ischemia in diabetic angiopathy of the lower extremities].

The authors have used gravitation plasmapheresis in the treatment of 26 patients with diabetic angiopathies of lower extremities. It was established that continuous gravitation plasmapheresis facilitated the immediate correction of most of the altered biochemical and coagulation parameters of blood, in patients with diabetes mellitus. The use of rheopolyglucinum is followed by stable central hemodynamics and stabilization of the general state of the patients during continuous plasmapheresis which allows to recommend rheopolyglucinum as the main plasma-substituting solution for fractionation of blood in patients with diabetic angiopathies. The gravitation plasmapheresis used in the treatment of critical degrees of ischemia in patients with diabetic angiopathies of lower extremities is thought by the authors to allow to preserve the extremity or to make the level of its amputation lower in most patients.

Aged↗

[Pharmacotherapy in acute tinnitis. The special role of hypoxia and ischemia in the pathogenesis of tinnitis].

Hypoxia/ischemia may play an important role in the pathogenesis of sensorineural tinnitus due to the characteristics of the cochlear blood supply. In addition, hypoxia modulates molecular processes both in the acute and chronic forms of tinnitus. Transcription factor HIF-1 (hypoxia-inducible factor) may play a key role in the cells' adaptation to hypoxia and ischemia, while under hypoxic/ischemic conditions, HIF-1 induces changes in the gene expression which may contribute to the remodeling of particular structures within the cochlea. Disturbances in the cochlear blood supply may result in membrane changes, perineural edema, inflammation, disturbances in ion homeostasis and in the formation of reactive oxygen species. Thus, the pharmacotherapy of acute tinnitus may be aimed at the improvement of cochlear blood supply and the prevention of acute processes leading to cell damage. Pharmacotherapies with colloidal plasma substitutes, vasodilators, calcium antagonists, procaine, and cortisone have been described in the literature and are discussed here. Many of the pharmacological treatments have not been validated in double blind studies. Although it is impossible to deduce the cause of tinnitus from a drug's efficiency, there is some evidence that it can be effectively suppressed by improving blood supply, at least at certain stages. The aim is to achieve an improved pharmacotherapy by means of sophisticated diagnostic instruments for classifying particular types of tinnitus.

Anesthetics, Local↗

Perioperative volume effect of HES 120/0.7 compared with dextran 70 and Ringer acetate.

Hydroxyethyl starch 120 (HES 120/0.7, Plasmafusin) is the smallest medium molecular weight HES preparation used as a plasma substitute for all clinical purposes. We compared the volume and colloid osmotic effect of 6% HES 120 with 6% dextran 70 and Ringer's solution during and after surgery with minimal blood loss. Patients (n = 48) having general anaesthesia were randomly divided into six groups. A thirty-minute bolus infusion was started at the induction of anaesthesia, and thereafter the infusions were continued at two different rates for five hours. The volume of the bolus was 10% and 30% of the calculated volume (CPV) in colloid and Ringer groups, respectively. The constant infusion rates were 2% and 6% of the CPV for the colloids, and 10% and 20% for the two Ringer groups. Blood samples for the measurement of serum proteins and colloid osmotic pressure (COP) were obtained before induction, after the bolus, and thereafter hourly throughout the study. Albumin, prealbumin and total serum protein concentrations were used to calculate relative plasma volumes. After the bolus infusion, plasma volumes increased significantly in all six groups and the increments were sustained throughout the study. At the lower infusion rates of the volume changes of HES and Ringer groups were almost identical and comparable to dextran group up to the third floor. At the higher infusion rates, dextran 70 produced greater plasma volume expansions than HES 120, and the volume effect of Ringer's solution was clearly exceeded by both colloids. The hourly estimated half-lives of dextran were constantly longer compared with HES. With both infusions rates the COPs of dextran and HES groups were higher compared with Ringer groups. There were no differences in COP between the dextran and HES groups. It is concluded, that in this clinical setting the volume effect of 6% dextran 70 exceeds that of the HES 120/0.7, and that both colloids are superior to Ringer's solution.

Adult↗

Successful (?) therapy of hemolytic-uremic syndrome with factor H abnormality.

We report a patient with continuously recurring hemolytic-uremic syndrome due to factor H deficiency. First at the age of 3 months he showed signs of hemolytic anemia, thrombocytopenia and renal insufficiency, often recurring concomitantly with respiratory tract infections, despite weekly to twice weekly plasma substitution (20 ml/kg body weight). Now at the age of 3.5 years glomerular filtration rate is approximately 50 ml/min/1.73 m(2) and psychomotoric development is normal. Since factor H is mainly synthesized in the liver, hepatic transplantation has been proposed as curative treatment. Before justification of liver transplantation as the ultimate treatment for these patients, an international registry should be developed to optimize and standardize therapeutic alternatives.

Child, Preschool↗

[Clinical experience with the use of gelofusin (gelatin) in anesthesiology, resuscitation and intensive care].

Published reports on the use of colloid plasma substitute gelofusin, widely used in practical anesthesiology, intensive care, and resuscitation, are analyzed. The drug is characterized by positive effects on the hemodynamic status and oxygen-transporting function of circulation, with the minimum side effects. It can be used for blood loss compensation, planned normovolemic hemodilution, afferent procedures, and filling the artificial circulation device. Gelofusin is preferable for use in patients with cardiac failure and marked dehydration. No negative effect on renal function and blood clotting system, even in infusions in high volume, are its positive qualities.

Anesthesia↗

[A comparative study of the effectiveness of 5% human albumin and 10% hydroxyethyl starch (HAES-steril) for correcting hemodynamics and O2 transport in surgical interventions].

Forty patients subjected to cavitary operations were examined. A high risk of hemodynamic disorders necessitated invasive monitoring; with this aim in view a catheter was inserted for measuring arterial pressure and the Swan-Ganz catheter for measuring the pressure in the pulmonary artery, in which helped monitor the hemodynamics and oxygen transport in the course of hypervolemic hemodilution. Plasma substitutes (one of two) were selected at random. After catheterization of the left radial artery and insertion of the Swan-Ganz catheter in the pulmonary artery through the internal right jugular vein the patients were infused either 5% human albumin or 10% hydroxyethyl starch in a dose of 125 ml every 5 min. The parameters of hemodynamics and oxygen transport were recorded after 500 ml of the solution was infused and the wedge pressure of 18 mm Hg attained. Both agents appreciably improved the mean arterial pressure, central nervous pressure, and wedge pressure. Cardiac index, left ventricular output, and stroke volume increased in both groups, and the pulmonary vascular resistance decreased. Both agents improved oxygen utilization and appreciably decreased hemoglobin level. The positive effect of hydroxyethyl starch on cardiac index, pulmonary vascular resistance, left ventricular output, and oxygen utilization was more expressed; moreover, a lesser dose of this drug was needed than of 5% human albumin (Behringwerke, Marburg, Germany). Loss of plasma caused by surgical intervention was better compensated for with synthetic colloid solutions, such as 10% HAES-steril (Fresinium, Oberurzel, Germany), provided that plasma protein level was at least 3-4 g/dl. The effect of 10% HAES-steril as regards the increase of circulating blood volume is 145%. Due to the hyperoncotic direction of its action it has a positive impact on the hemodynamics and oxygen transport and is needed in lower doses than other colloid solutions.

Aged↗

Effect of dextran infusion on the phagocytic and metabolic functions of the reticuloendothelial system in man.

The reticuloendothelial system (RES) is part of the host defence and consequently plays an important role in shock and trauma, conditions often requiring volume replacement. Experimental studies have shown that the functions of the RES are hampered by plasma substitutes such as gelatin, starch and dextran. In this study six patients undergoing elective cholecystectomy were given 500 ml dextran just before the operation. At the end of the operation the phagocytic and metabolic functions were tested with microaggregated human serum albumin labelled with I125. The results indicate that there is a significant impairment of the phagocytic activitity of the RES in patients given dextran compared to controls not given dextran but saline. The metabolic activity was not significantly affected by dextran, however, suggesting that moderate dosage of dextran is not of great disadvantage to patients undergoing major surgery.

Cholecystectomy↗

Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects.

OBJECTIVE: Impairment of haemostasis has been described with slowly degradable medium molecular weight hydroxyethyl starch (MMW-HES), whereas rapidly degradable MMW-HES is generally considered to have no important effects on blood coagulation. This study was undertaken to investigate the effects of a rapidly degradable MMW-HES plasma substitute on primary haemostasis and blood coagulation in human subjects. DESIGN: Randomised, cross-over study. SETTING: Research unit of a university hospital. PARTICIPANTS: Nine healthy, adult male volunteers. INTERVENTIONS: A 60-min intravenous infusion of 1 l HES 200/0.5/6 (HAES-steril 6%) or 4% albumin (control). MEASUREMENT AND RESULTS: The infusion of HES resulted in decreased circulating levels of von Willebrand factor antigen (from 85+/-8% to 59+/-6% after HES vs from 80+/-7% to 69+/-8% after albumin, p<0.05) and ristocetin cofactor activity (from 93+/-4 to 67+/-4% after HES vs from 79+/-5 to 75+/-5% after albumin, p<0.01). This was associated with an impairment of in vitro platelet function as determined with the PFA-100 platelet function analyser (closure time with collagen/epinephrine from 120+/-7 to 159+/-14 s after HES vs from 121+/-7 to 137+/-10 s after albumin, p<0.05; with collagen/ADP from 88+/-3 to 116+/-9 s and from 103+/-4 to 114+/-7 s after HES and albumin, respectively, p=0.01). CONCLUSIONS: The infusion of 1 l of HES 200/0.5/6 in healthy human subjects results in moderately decreased plasma levels of von Willebrand factor associated with impairment of platelet function.

Adult↗

The effects of colloid solutions on hemostasis.

PURPOSE: Colloid solutions are widely used to prevent or to correct hypovolemia in surgical patients. Although more efficacious than crystalloids, they are more expensive and can be associated with adverse effects, in particular when they interfere with the hemostatic system. METHODS: This narrative review focuses on the effects of albumin and synthetic colloids on the biological markers of coagulation and their clinical consequences. RESULTS: All colloidal plasma substitutes interfere with the physiological mechanisms of hemostasis either through a non-specific effect correlated to the degree of hemodilution or through specific actions of these macromolecules on platelet function, coagulation proteins, and the fibrinolytic system. Albumin has the least effect, while high molecular weight (Mw) dextrans and hydroxyethyl starches (HES) have the most significant effects. Gelatins and medium Mw HES with a low molar substitution ratio have moderate and, probably, comparable effects. The use of dextrans and high in vivo Mw HES may be associated with increased bleeding, while gelatins and low in vivo Mw HES are unlikely to have such an effect. CONCLUSIONS: In most cases, the clinical consequences of the biological effects of colloids on hemostasis are limited, provided that safety considerations are observed (maximum daily dosage, duration of treatment, patient's hemostatic status, clinical conditions). The implications may be different in patients with hemostatic disorders, either inherited or related to preoperative antiplatelet or anticoagulant treatment. In these patients, crystalloids, gelatins or even albumin solutions should be preferred when hemodilution exceeds 30% of the circulating blood volume.

Animals↗

[Reducing of unwanted side effects of modified fluid gelatin by promethazine: controlled clinical trial with orthopaedic patints (author's transl)].

In order to determine the undesirable side effects of standard commercially available plasma substitutes, 450 stationary patients covering 5 age groups were randomly allocated to various methods of pre-medication and 3 batches of modified fluid gelatin (Neo-Plasmagel). The incidence of allergoid and anaphylactoid reactions depended on the pre-medication (p less than 0.025). Atosil proved to be an strong histamine blocker: the incidence of reactions between the control and the promethazine group was p less than 0.005. Seen as a whole reactions among females were greater than with males (p less than 0.025). No relationship could be determined statistically between the different batches and the incidence of side-effects. -The prophylactic use of Neo-Plasmagel in orthopaedic patients is therefore dependent on a sufficient blockade of histamine receptors.

Adult↗

[Infusiontherapy with colloidal volumesubstitutes (author's transl)].

All colloidal plasma substitutes carry the risk of anaphylactoid complications with a general incidence of 0.03%. This incidence seems low; however severe complications may occur after infusion of colloids, including also human albumin solutions. In spite of the risk of anaphylactoid reactions, however, colloids should not be ommited from volume replacement therapy. When choosing a colloid for volume replacement the solution-specific risk of anaphylactoid complications has to be taken into consideration. From an increasing number of recent case reports the impression of a rising rate of complications has emerged; this impression was not substantiated by a prospective controlled trial performed in 1975. Since dextran in addition to its safe volume effect possesses well documented antithrombotic properties, it cannot be replaced by any other colloid without the addition of another thromboprophylactic agent.

Anaphylaxis↗

Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related.

Tissue deposits occur after administration of plasma substitutes. After hydroxyethyl starch (HES), deposits may last for months, causing pruritus and impairment of function. Because elimination of HES deposits has not been demonstrated in humans, we studied 26 patients, for up to 7 yr after HES administration, to assess HES storage. HES dose ranged from 0.34 to 15.00 g kg-1 body weight, and administration intervals from 1 day to 7 yr. Biopsies of the liver, muscle, spleen, intestine or skin were studied using light and electron microscopy and immunohistochemistry. HES storage was dose-dependent, decreased in all organs with time and was greater in patients suffering from pruritus. We conclude that tissue deposition of HES is transitory and dose-dependent, with differences between subjects in severity and duration.

Adult↗

[Hypertonic circulatory response to clinical haemodilution (author's transl)].

Preoperative haemodilution was performed in 46 patients. By exchange of 1785 ml of patient's blood with plasma substitutes, haematocrit was lowered to 24.8% mean. Cardiac output rose, the other circulatry parameters remained constant on average. 8 patients experienced, however, a circulatory reaction with acute systemic and pulmonary hypertension, peripheral vasoconstriction, and ST-depression in ECG. These cases showed a decrease in oxygen uptake. In further 42 patients haemodilution was limited to haematocrit 27%, and only three weak hypertonic reactions were observed. Therefore we recommend haemodilution to be limited to this hematocrit. Saving homologous blood transfusions is the major goal of haemodilution. In comparable surgical procedures 60-70% of patients without haemodilution are given homologous blood. In our two patient groups with haemodilution blood transfusions were necessary in 15 and 21%, respectively. Thus, haemodilution is a valuable mean of hepatitis prophylaxis by saving homologous blood transfusions. This advantage outweighs the possible risks of circulatory reactions.

Blood Transfusion, Autologous↗

The role of perfusion washout in limb revascularization procedures.

Amputated rat hindlimbs were subjected to either normothermic (26 degrees C) or hypothermic (4 degrees C) ischemia. Experimental limbs had their microcirculation washed out (either before or after the ischemic insult) with a physiologic acellular plasma substitute previously reported to enhance flap survival following extended periods of warm ischemia. Control limbs were not washed out; i.e., stagnant blood remained in these limbs. Following the ischemic interval, amputated limbs were replanted. Monastral blue B, a colloidal pigment capable of labeling leaky blood vessels, was administered systemically to all rats just prior to vascular declamping. Limb biopsies of skin and muscle were harvested 30 minutes following revascularization in order to assess Monastral labeling and, therefore, the functional integrity of the microcirculation. Results confirm that stagnant blood under conditions of warm ischemia is detrimental to the functionality of the microcirculation in both skin (p less than 0.03) and muscle (p less than 0.007). Accordingly, perfusion washout, when performed prior to the ischemic period, enhances limb survival following 6 hours of warm ischemia (p less than 0.01). Hypothermia protects against the detrimental effects of stagnant blood; perfusion offers no benefit if hypothermic conditions prevail. Physiologic mechanisms responsible for these findings are discussed.

Animals↗

[Hyperchloremic acidosis druing plasma volume replacement].

OBJECTIVES: Review of the physiological and clinical consequences of hyperchloraemic acidosis observed during plasma volume replacement using crystalloids and colloids. DATA SOURCES: Data were searched in the Medline database after 1990 using the following key words: metabolic acidosis, crystalloids, colloids, albumin, gelatin, hydroxyethyl starch. DATA EXTRACTION: Publications before 1990 were selected for their historical value. Most of articles published after 1990 and all types including case report were accepted. DATA SYNTHESIS: Large volume infusion of isotonic solution can cause hyperchloraemic acidosis. Colloid plasma substitutes using saline solvent may be responsible for the same kind of acidosis with acidaemia. The anion gap is not modified in this case because of chloride increase. Physiological mechanism may be described using the Henderson-Hasselbach equation or the strong ion difference decrease (Stewart concept). Excessive chloride infusion is a major factor in this acid-base disorder and the term hyperchloraemic acidosis should be preferred to dilutional acidosis. When perioperative acidosis occurs, careful and complete analysis of acid-base disturbance should be made. The association of a normal anion gap, normal lactatemia, hyperchloraemia and acidaemia does not need specific treatment. Acidosis corrects spontaneously and slowly following chloride normalization. But any factor that may increase acidosis should be avoided. CONCLUSION: The use of balanced solution like lactated-Ringer solution instead of isotonic saline solution for fluid resuscitation, except for specific contra-indication as intracranial hypertension, may avoid hyperchloraemic acidosis. Potential risk of this acidosis led to the conception of a new colloid using balanced crystalloids solution as the solvent (Hextend).

Acidosis↗