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In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O(2) content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dt(min)) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (tau) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock., (Copyright 2001 S. Karger AG, Basel)

This study was designed to compare the effectiveness of intramuscular progesterone with that of intravenous albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). Ninety-six patients at high risk to develop OHSS (estradiol concentration >9, 000 pmol/l on the day of hCG administration and over 20 follicles of a diameter larger than 14 mm observed by transvaginal ultrasonography) and undergoing in vitro fertilization-embryo transfer were enrolled. They were randomly treated with intramuscular progesterone (200 mg/day) or 100 ml of 20% intravenous albumin in order to estimate the difference in the incidence of OHSS. A significant difference in the incidence of moderate OHSS and no cases of severe OHSS were observed between the groups. Our data show the effectiveness in preventing OHSS with high doses of progesterone., (Copyright 2000 S. Karger AG, Basel)

The enormous progress made in biotechnology and purification of plasma proteins (pp) and the demands to avoid risks of transmitting HIV, hepatitis and other virus infections by these have resulted in the development of numerous recombinant human (rh) pp, which are now about to be used as replacement therapy in transfusion medicine. Human rh albumin has been used in clinical trials last year, a competition to serum albumin can be expected in the next time. During the last decade, the genes or cDNA have been cloned and characterized for all relevant pp involved in blood coagulation. Beside the rh factor VIII (rh FVIII) which has been introduced clinically in 1991, the rh FVIIa is under investigation in patients with hemophilia A and inhibitors. After establishing of rhFIX in triple transgenic mice, the industrial potential will be evaluated in terms of scale up culturing and production. The valuation of advantages and drawbacks of the current rh pp in comparison to conventional pp will have to be determined in the last decade of our century.

In 24 patients undergoing transurethral resection (TUR) of the prostate, sodium, potassium, calcium, magnesium, osmolarity and protein in serum were measured every 15 min. Depending on the composition of the electrolyte solution, there is a sharp fall in serum sodium and osmolarity caused by the leakage of irrigation fluid into the patients circulation. There is also a rise in central venous pressure and a fall of serum protein. There is a correlation between the fall of serum sodium and osmolarity and the rise of central venous pressure. Our results allow the conclusion that a restricted infusion programme with high sodium concentrations can be recommended. Depending on the patients serum protein, preoperative albumin solutions (20%) can be necessary to prevent a dangerous fall of oncotic pressure intraoperatively. The pathophysiology of the TUR syndrome and the importance of an adequate infusion therapy are discussed.

HES products should be designated by both their number average of molecular weight (that determines colloidal activity) and molar substitution ratios. In addition to the original HES-70/70 developed in 1960, a rapidly excreted HES-50/50 has been available since 1977. HES-70/70 and human albumin are equivalent in both healthy and hypoalbuminemia subjects in regard to maximal and total effects on plasma volume, intravascular colloidal activity and plasma concentration of ingested colloid. Albumin and HES-70/70 are extravasated at nearly equal rates. Albumin elimination is predominantly monoexponential. HES-70/70 however, is partly metabolized and partly excreted in urine at rates that decrease progressively as the amount remaining in the body decreases. HES-50/50 has maximal effects on plasma volume and colloidal activity similar to those of dextran-40, but it is eliminated twice as rapidly and unlike dextran-40, does not accumulate on repeated ingestion of large doses. HES ingestion increases apparent serum activity of alpha amylase by slowing enzyme elimination. Anaphylactoid reactions have been infrequent and mild, even on repetitive ingestion in recurrent "Phoresis" donors. The effect of HES on coagulation in urine but does not slow urine flow by hyperviscosity. Hydroxyethylation of waxy starches yields safe colloids with the advantage of permitting selective control of drug effects by altering independently molecular size and rate of enzymatic hydrolysis, tailoring drug kinetics to specific uses.

Home parenteral nutrition is indicated in the short bowel syndrome, chronic inflammatory bowel disease and as an adjunct to cancer therapy. For venous access the cannulation of a collateral of the subclavian vein and the central venous silastic catheter have proved helpful. Our own experience with 19 patients shows, that with careful supervision home parenteral nutrition can be performed with low risk.

Up to day the control of brain oedema is not yet solved. The role of protein level and oncotic pressure in the maintenance of adequate plasma volume are explained. We discuss all factors worsening cerebral oedema. The haemodynamic aspects of oncotic therapy are presented. Our choice of drugs used in oncotic therapy is human albumin. The beneficial influence of human albumin on the development of cerebral oedema is accentuated.

Since the commissioning of the Scottish National Blood Transfusion Service's Protein Fractionation Centre in 1975 840 batches (in excess of 150,000 bottles) of stable purified protein solution (SPPS), prepared by the continuous small volume mixing (CSVM) method, have been used clinically. Each bottle contains approximately 400 ml of a solution of 4.3 g% total protein of which greater than 85% is albumin (mean 89%). Prekallikrein activator (PKA) estimations on the last 120 batches have revealed a mean value 8.0% +/- 6.1 with reference to the U.S.A. (B.O.B.) Reference Standard (Ref. 1). Using gel filtration techniques and UV Absorption at 280 nm approximately 7% of the albumin is in polymer form. It has been calculated that there have been in excess of 40,000 separate patient exposures. SPPS has been used in the cardiac bypass situation and in large volume plasma exchange using cell separators. Clinical colleagues consider its clinical efficacy in the management of hypovolaemic patients to be of a high order. The issue of SPPS for clinical purposes is controlled by the Regional Transfusion Centres either directly or through their peripheral blood banks. Because there is close and active liaison in the reporting of adverse reactions to routine blood transfusion, similar conditions apply to all plasma products, including SPPS. In the period under retrospective review adverse reactions to isolated bottles in two batches (3 patients) of SPPS have been reported (an incidence of 0.24% batches produced). None of these reactions was fatal and none was explained. It is concluded that the SPPS produced by our Protein Fractionation Centre, using the CSVM technique, appears to have a satisfactory record with regard to efficacy and safety.

In 44 cases with nonimmunologic hydrops fetalis (NIHF), perinatal management was performed based on our protocol. Twenty-one cases were treated by albumin and/or packed red blood cell (PRC) injection into the fetal abdominal cavity, and 8 cases were treated by transplacental digitalization. Among the cases treated by albumin and/or PRC injection, 5 of 7 cases without pleural effusion recovered in utero, and all 5 cases are alive at the time of writing. However, of 14 cases with pleural effusion, none recovered in utero, and only 1 case is alive. Of 8 cases treated by transplacental digitalization, 2 cases recovered in utero, and 1 case is alive. All fetuses with congenital heart anomaly died. This evidence indicates that albumin and/or PRC injection into the fetal abdominal cavity is an effective procedure for in utero treatment of NIHF without pleural effusion, but suggests that in NIHF resulting from either congenital heart anomaly and/or heart failure, the survival rate may not be increased by transplacental digitalization.

Medical indications for the use of human albumin (HA) by the clinician have been described in the past. They were invariably based on the knowledge of the function of the HA molecule and its feasible role in circulation. So these indications in fact became recommendations to the clinician. In recent years various authorities were faced with the necessity to review requirements for HA, wherever they existed, or to define new requirements, where none were considered before. IABS was, therefore, asked to find out if and how the recommended indications were accepted by physicians of various disciplines. Using a questionnaire more than 800 replies were received. These answers and their evaluation permitted the statement that the clinical use of HA is not limited to the recommended one, but used for additional and newer indications with obvious success. In addition it was noted that present requirements by control authorities do not seem to cover sufficiently the needs of the patients.