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[Effect of kidney function on the elimination and action of colloidal plasma substitutes].

Hypovolemia and prophylaxis of thrombosis are the main indications for colloidal plasma substitutes. This is also true for patients with renal failure. Due to their difference in molecular structure colloidal plasma substitutes, which are in clinical use--dextran, hydroxyethyl starch, gelatin--, are eliminated tbrough different pathways. However, the kidney plays an important role in the elimination of all three substances. Therefore pharmacokinetics and pharmacodynamics of colloidal plasma substitutes, which are based on dextran, hydroxyethyl starch and gelatin, were studied in patients with normal or impaired renal function. Renal insufficiency proved to affect the elimination and therapeutic efficacy of these colloids in different and characteristic ways. Consequently this requires special indications and dosage recommendations for patients with renal insufficiency.

Anuria

[Effect of various plasma substitutes on blood groups].

In order to test the influence of the plasma substitutes Macrodex 6%, Plasmasteril and Expafusin on subsequent blood-typing and serologic tolerance tests, blood specimens of known donors of blood group 0 Rh negative were incubated with the respective plasma substitutes in various dilutions and serologic tests performed. In the AB0 and Rh system, none of the plasma substitutes tested caused falsely positive agglutinations. Reading of cross-match in the albumin test was not impeded in any of the substitutes. The higher molecular dextran Macrodex 6% and the high molecular hydroxyethylene starch Plasmateril appeared to have positive blood-group serologic reactions. With the low molecular hydroxyethylene starch Expafusin no irritations occurred in all tests of cross-matching.

ABO Blood-Group System

[Indications and contraindications for plasma substitutes in surgery].

The indication for the infusion of plasma substitutes has been considerably limited as the result of a series of grave incidents. Prior to each application, differential-therapeutic deliberations must decide on the choice of plasma substitute bringing about the desired success in accordance with its physico-chemical characteristics and clinical values. The type and severity of a probable anaphylactoid incident and its therapy should also be considered.

Anaphylaxis

[The effect of the plasma substitutes hydroxyethyl starch and dextrane-60 on the kidney function of dogs in acute haemorrhagic shock (author's transl)].

In 14 dogs during experimentally induced haemorrhagic shock the effects of 6% solutions of hydroxyethyl starch and Dextran-60 were compared. As main parameters of the renal function the arterial and venous pressures, renal blood flow, creatinine-clearance as measure of the glomerular filtration rate, urinary flow rate and urinary excretion of sodium and potassium were estimated. After complete substitution of the lost blood volume both plasma substitutes increased the renal blood flow by 50%. Glomerular filtration rate returned to control values, urinary volume and potassium output increased whereas sodium output decreased slightly. If only 50% of the lost volume was substituted, the renal blood flow and filtration rate remained at or below control values. Hydroxyethyl starch and Dextran-60 proved to be almost equally effective in restoring renal function.

Animals

[Efficacy of plasma substitutes of different molecular weight in acute haemorrhagic shock in dogs (author's transl)].

Dogs were bled into haemorrhagic shock. They were then given isovolaemic infusions of dextran 60 and 40 and of hydroxyethyl starch with an average molecular weight of 200,000 and 40,000 respectively with a view of assessing the haemodynamic efficacy of these plasma substitutes. Solutions of high molecular weight hydroxyethyl starch (HES 400) were retained in the circulation for about the same length of time as was dextran 60. HES 40 (molecular weight 40,000) was retained for about 3-4 hours as measured by cardiac output. For normalizing a relative hypovolaemia, e.g. during anaesthesia or in some emergencies, colloidal plasma substitutes which will be retained for only a short time are entirely satisfactory.

Acid-Base Equilibrium

Rational use of albumin and plasma substitutes.

Salt-poor human albumin (25 g/dl) is a safe and effective colloid for increasing intravascular volume. It is usually given together with saline solutions at a final concentration of 5 g albumin per 100 ml infusion volume. Although relatively nontoxic, albumin costs about $120 per liter, more than ten times the cost of artificial macromolecular colloids used as "plasma substitutes". Hydroxyethyl starch (6 g/dl NaCl) is a new polysaccharide volemic colloid similar in effect to dextran-70; 70% of an infused volume remains intravascular at 3 hours and 30% at 24 hours. It is nonallergenic, causes no anaphylactoid reactions, and interferes with coagulation less than dextran-70 or dextran-40. Bleeding may be observed when doses of more than 1500 ml are given without blood replacement, especially in thrombocytopenic patients. The effects of dextran-70 and dextran-40 on inhibiting thrombogenesis and facilitating blood flow in small vessels are due largely to hemodilution; the relative efficacy of hydroxyethyl starch for these purposes has not yet been established. Hydroxyethyl starch is a safe and effective colloidal solution for replacement of lost blood and augmentation of blood volume.

Blood Viscosity

[The influence of different plasma substitutes on blood clotting and platelet function during and after operations (author's transl)].

It has been shown in clinical experiments that plasma substitutes generally have a specific-colloidal influence on special parts of the clotting system. These changes are predominant after infusion of dextran, since on one hand there is an inhibition of platelet function, and on the other hand a decrease in the activity of plasmatic clotting factors. It is to be emphasized that hydroxyethyl starch and with some restrictions even gelatins cause a comparable inhibition of platelet function. These reactions are due to colloid-specific effects only, which have been unknown up to now. Activities of plasmatic clotting factors, however, are not influenced by these substitutes.

Blood Coagulation

[Comparative study on the immunogenicity of plasma substitutes with gelatin base in animal experiments].

The immune response of rabbits and guinea pigs to gelatin and to three commercial plasma substitutes based on gelatin (oxypolygelatin [OPG], di-isocyanate cross-linked gelatin [DCG], modified fluid gelatin [MFG]) has been reevaluated. Passive hemagglutination, passive cutaneous anaphylaxis and active anaphylaxis have been used to detect the response of animals immunized in complete Fruend's adjuvant or in aluminium hydroxide. Marked immune responses were observed with DCG and MFG which were to a large extent specific for the immunizing antigen (i.e. the corresponding chemically modified gelatin). Gelatin and OPG induced weak responses. In contrast to DCG and MFG in systemic anaphylactic shock experiments no anaphylactic shock could be elicited with gelatin and OPG. A limited series of immunizations in guinea pigs of various strains demonstrated that responses to weak immunogens, such as modified gelatins, are markedly influenced by genetic factors.

Amino Acids

[Formation of high-molecular aggregates between serum amylase and colloidal plasma substitutes (author's transl)].

The distribution of molecular weights of human serum amylase was studied by gel filtration of serum, obtained before and after infusion of the colloidal plasma substitutes hydroxyethyl starch, dextran and gelatin, respectively. Both in serum, drawn after intravenous infusion of hydroxyethyl starch, and in a solution of hydroxyethyl starch with serum we observed a significant increase in the molecular weight of serum amylase. The occurrence of this "macroamylase" may be explained by the formation of aggregates between hydroxyethyl starch and amylase. Because of its high molecular weight the elimination of this, presumably, enzyme-substrate-complex is retarded, thus leading to the observed increase of serum amylase activity. In contrast to these observations concerning hydroxyethyl starch no change in the apparent molecular weight of serum amylase was observed following the infusion of either gelatin or dextran or their solutions with serum.

Amylases

Alterations in brain and muscle oxygenation during hypovolemia and replacement with plasma substitutes in rats.

A study was conducted on the effects of mild hemorrhage-induced hypovolemia and subsequent replacement with lactated Ringer's dextran or hemoglobin solution in 52 pentobarbital-anesthesized rats. Blood loss of 1.25% of body weight had no significant effect on the blood flow or relative tissue PO2 of the white matter of the cerebral cortex. Blood flow and relative tissue PO2 of the biceps brachii muscle were lowered during hypovolemia. Volume replacement with any of the three plasma substitutes had no effect on blood flow or relative tissue PO2 of cortical white matter. They all caused partial restoration of blood flow and relative tissue PO2 in the biceps brachii muscle. Full return in the muscle was not achieved, nor were there any significant differences between the treatment groups.

Animals

[The influence of different plasma substitutes on blood clotting in isovolaemic haemodilution (author's transl)].

In a clinical study, the influence of 6 per cent Dextran 60 and 6 per cent hydroxyethyl starch (HES) on blood clotting was measured in 2 comparable groups of surgical patients. Haematocrit, platelets, thromboplastin time according to Quick, partial thromboplastin time and fibrinogen level were determined before and after isovolaemic haemodilution, and subsequently during a period of 14 days. There was no significant difference between the diluents with regard to their effect on blood clotting. Changes within each group may be ascribed to the diluting effect of the plasma substitutes.

Blood Cell Count

[Hydroxy-ethyl-starch as plasma substitute in transurethral prostatectomy with the "cold-punch" method (author's transl)].

Each of 24 patients undergoing transurethral prostatectomy under spinal anaesthesia received 1000 ml HES and, depending from the clinical situation, some patients received blood-transfusion. Afterwards two groups were formed: group A (11 patients), who received HES only, and group B (13 Patients) with additional blood-transfusions. The following parameters were monitored simultaneously: blood pressure, heart rate, stroke index, cardiac output, active blood volume, hemoglobin and hematocrit in whole blood as well as in the irrigatin fluid of the bladder. They showed HES to be a useful plasma substitute for older patients. It is well tolerated and has a slow stabilising effect on circulation, which was effective for several hours. Furthermore, HES-infusion reduced the average need of bloodtransfusion by 500 ml.

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