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PubMed1975

Coagulation, hemostasis, and plasma expanders:a quarter century enigma.

Despite more than 2 decades of research, the explanation of the long-known hemostatic failure consequent to the use of some natural and synthetic macromolecular agents as plasma substitutes remains obscure. Conventional clotting parameters are not significantly affected in vivo or in vitro. Dextran, hydroxyethyl starch, and many other colloid macromolecules precipitate Factors I and VIII, fibrin monomer, and perhaps v. W. (von Willebrand) factor(s) from plasma, rendering at least the first three insoluble, in relation to the molecule size and concentration of the colloid, and for dextran, its intrinsic viscosity. The precipitate, rich in Factors VIII and I, redissolves on warming, and reprecipitates on cooling, behaving as a cryo-Factor I. In composition it closely resembles the cryoprecipitate obtained by slow-thawing of plasma. Both clot faster with thrombin than the parent plasma. The amount precipitated from plasma by dextran or hydroxyethyl starch varies very widely from individual to individual. Cryo- of dextran-precipitable material can be obtained by interacting purified Factor I with a miniscule amount of thrombin. Dextran, hydroxyethyl starch, polyvinyl pyrrolidone, some forms of gelatin, and several polyamino acids accelerate thrombin clotting of normal plasma, several dysfibrinogenemic plasmas, or Factor I. Albumin, hemoglobin, some modified gelatins do not. Poor platelet thromboplastic function appears some hours after dextran infusion, associated with morphologic capillary abnormalities that strikingly resemble those in v. W. disease. We postulate that the hemostatic defect associated with the use of plasma substitutes is a form of induced v. W. disease or disseminated intravascular clotting, ensuing from precipitation and removal of v. W. factor(s), Factors VIII and I, microcirculatory abnormality, and platelet malfunction. The latter two supervene some time after administration of dextran. It reported antithrombotic activity is perhaps referable to the same action.

Adolescent↗
PubMed1981

[Human albumin or dextran 60 for the restoration of the blood volume, with special reference to the colloid osmotic pressure (author's transl)].

The high cost and limited availability of human albumin as a plasma substitute make it desirable to limit its use to special cases and to replace it by inexpensive and easily obtainable colloids. Patients about to undergo major abdominal surgery were given either human albumin or dextran 60 during the operation and for three days afterwards. Although both groups received the same quantity of colloidal plasma substitutes they differed significantly in respect to the serum albumin and protein concentrations. However, the osmotic pressure, for the maintenance of which the albumin fraction is mainly responsible, showed a marked fall in both groups, indicating that human albumin is not superior to dextran. All other parameters, particularly the clotting mechanism, remained within the normal range and did not differ between the two groups. The results of the study, in conjunction with the known facts regarding the metabolism and function of albumin, suggest that dextran 60 can adequately replace human albumin in a large number of cases. Great importance belongs to measurement of the colloid osmotic pressure.

Blood Proteins↗
PubMed1989

[Correction of disorders of systemic hemodynamics and rheologic indices of the blood in patients with chronic kidney failure during hemodialysis].

During hemodialysis, 44 patients with terminal chronic renal failure were examined for the systemic hemodynamics and blood rheological properties as well as for the possibility of their correction by infusion of the plasma substitutes: polyglucine, rondex or 10% albumin at a volume of 400 ml per administration. It was established that patients on hemodialysis manifested pronounced hemodynamic and rheological disorders. During hemodialysis, the hemodynamic disorders correlated with the changes in the rheological properties of the blood (r = 0.23-0.45, p less than 0.05). It is indicated that to treat the hypotensive states occurring in the course of hemodialysis, infusions of the plasma expanders, rondex, 10% albumin and polyglucine may be used at a limited volume. The plasma substitute rondex ensures a more favorable hemodynamic and rheological effect, comparing very favourably with other preparations investigated.

Adolescent↗
PubMed1984

[Prevention of complications following abdominal surgical urologic interventions by plasma protein substitutes].

A prospective randomised trial in 94 patients undergoing urological abdominal surgery has been carried out to evaluate the effect of postoperatively administered plasma proteins. A significant difference between the treatment group and the control group has been found in the incidence of bronchopulmonary complications. This may be due to the substitution of Alpha-1 antitrypsin as could be shown by determination of the activity of Alpha-1 antitrypsin levels. A positive trend but no significant differences could be demonstrated for wound healing and the need of antibiotics postoperatively.

Abdomen↗
PubMed1975

[Randomised study on histaminelike side-effects of 5 common plasmasubstitutes in orthopedic surgery (author's transl)].

Preceding anaesthesia 750 randomised patients, sub-divided into 5 different age groups, were given 500 ml of a standard plasma-substitute at a flow rate of 25-30 ml/min. There was direct correlation (p=0.1%) of the frequency of side-effects to the substance used; none, however, to the age or general surgical risk. Side-effects were observed in 21.3% with derivates of gelatin as compared to 3.7% with Macrodex and Plasmasteril combined. The rate of more serious anaphylactoid reactions was 6% with Haemaccel, 1.3% with Gelifundol-S, 0.67% with Macrodex and less than 0.67% with Neo-Plasmagel. The study reveals that serious side-effects may be expected in orthopaedictic patients after application of plasma substitutes. As a prophylactic procedure for those patients we recommend, therefore, the application of these substances only after careful consideration of the indications for their use.

Adult↗
PubMed1982

Hydroxyethyl starch in priming fluid for cardiopulmonary bypass.

The physiochemical characteristics of hydroxyethyl starch make it suitable for use as a colloidal blood plasma substitute. In high doses, this drug may interfere with blood coagulation. Because of its effectiveness and low cost, we have used hydroxyethyl starch rather than albumin in the priming fluid for cardiopulmonary bypass: 500 ml of 6% hydroxyethyl starch and 2,000 ml of lactated Ringer's solution. To determine if excessive bleeding has been associated with the use of hydroxyethyl starch, we reviewed 760 cardiac operations. The patients were 49.9 +/- 0.5 years old (mean +/- SEM) and weighed 73 +/- 1 kg. Blood loss during the first postoperative day was 578 +/- 25 ml, and 4.0 +/- 0.2 units of bank blood were utilized in the perioperative period. We have used an improved method of administering heparin and protamine for the past 3 years. In the 461 patients operated upon since then, blood loss was 437 +/- 21 ml, 2.9 +/- 0.1 units of bank blood were used, and excessive postoperative bleeding necessitated re-exploration in nine patients (2.0%). These results compare favorably with other recently published series in which hydroxyethyl starch was not used in the pump prime. Thus the dose of hydroxyethyl starch in our priming fluid does not appear to be associated with excessive bleeding. In view of its safety and low cost, hydroxyethyl starch is a suitable colloidal blood plasma substitute for use during cardiopulmonary bypass.

Cardiopulmonary Bypass↗
PubMed1998

Comparison of three plasma expanders used as priming fluids in cardiopulmonary bypass patients.

Ten per cent low molecular weight hydroxyethyl starch is a plasma substitute only recently used as priming solution in an extracorporeal circuit, in contrast to human albumin and gelatin. To evaluate the effect of priming solutions on haemodynamics and colloid osmotic pressure, we studied 36 patients elected for cardiopulmonary bypass (CPB). They were randomly assigned to 2.5% hydroxyethyl starch, 3% gelatin or 4% human albumin priming solution. Total blood loss (perioperative + intensive care unit period) was higher in the gelatin group than in the albumin and hydroxyethyl starch groups. During CPB, the colloid osmotic pressure was best preserved in the gelatin group, although no excessively low colloid osmotic pressures were measured in the other two groups. Due to the extended half-life and the additional postoperative colloid administration, the hydroxyethyl starch group had a higher colloid osmotic pressure in the postoperative phase. We conclude that, next to human albumin, 2.5% hydroxyethyl starch is a safe CPB priming solution additive and is effective as plasma substitute. Its somewhat longer half-life requires adaptation of the routine protocol for transfusion of colloids and blood products.

Cardiac Surgical Procedures↗
PubMed1996

[Substances responsible for peranesthetic anaphylactic shock. A third French multicenter study (1992-94)].

Since 1989, the epidemiological survey of anaphylactoid reactions occurring during anaesthesia is obtained in France with repeated inquiries by the Perioperative Anaphylactic Reactions Study Group. The members of this group collect during the study period the cases of patients having suffered from an anaphylactoid reaction and tested in their allergo-anaesthetic outpatient clinic, their characteristics (age, gender), the results of the allergological tests (mechanism, agents responsible for the reactions). The two previous surveys published in the Annales françaises d'anesthesie et de réanimation in 1990 and 1993 included 1,240 and 1,585 patients respectively. The current survey concerned 1,750 patients tested in 27 diagnostic centres, from January 1992 to June 1994. The reactions occurred at all ages, predominantly between 10 and 50 years, the sex-ratio (F/M) was 2.4. Allergological tests carried out to diagnose an immune mechanism for the shock were cutaneous tests in all centres (prick-tests in 21 centres, intradermal tests in 27 centres) using the same dilutions for the tested agents and the same threshold for positivity. Specific IgE antibodies against muscle relaxants, thiopentone and propofol, were measured by radio immunoassays in 20 centres. The leucocyte histamine release test was used in 10 centres. The immune origin of the shock--IgE dependent anaphylaxis--was diagnosed in 1,000 patients (57.8%) and due to 1,030 agents muscle relaxants (59.2%), latex (19%), hypnotics (5.9%), benzodiazepines (2.1%), opioids (3.5%), plasma substitutes (5%), antibiotics (3.1%) and other drugs given during anaesthesia such as aprotinine and protamine (2.2%). Suxamethonium was responsible for 39.3% of muscle relaxant anaphylaxis, vecuronium for 36%, atracurium for 14.5%, pancuronium for 4.8%, gallamine for 3.1% and alcuronium for 2.3%. The latter has been withdrawn from the French market in 1993. These differences in the incidence of reactions are correlated with the clinical use of muscle relaxants in France for vecuronium and atracurium, however not for suxamethonium, responsible for 39% of the reactions but representing only 5% of the muscle relaxants sold in France. The comparison with the two previous surveys confirms that the mechanism of more than half of the anaphylactoid reactions occurring during anaesthesia is of immune origin, due to specific IgE antibodies. It is therefore essential to systematically carry out an allergologic assessment several weeks after the reaction, in order to discard for the subsequent anaesthetics the agent(s) responsible for anaphylaxis. If the muscle relaxants remain the first drugs involved in shock occurring at induction, there is a significant increase in latex shock, as demonstrated by the three epidemiological surveys (0.5%, 12.5% and now 19%). The incidence of other anaesthetic agents, antibiotics and plasma substitutes remains unchanged.

Adolescent↗
PubMed1998

Impaired haemostasis by intravenous administration of a gelatin-based plasma expander in human subjects.

The aim of this study was to investigate the effects of a gelatin-based plasma expander on blood coagulation and haemostasis in human subjects. Six healthy men were studied in a randomised, controlled cross-over study to investigate the effects of a 60 min intravenous infusion of either 1 l gelatin-based plasma substitute (Gelofusine) or 0.9% NaCl (control). The infusion of gelatin resulted in a 1.7 fold increase in bleeding time at 60 min and a 1.4 fold increase at 120 min, while saline had no effect (p <0.05). Aggregation studies revealed a significant impairment of ristocetin-induced platelet aggregation (p <0.05), associated with a substantial decrease of vWF:ag (-32% vs. -5%, p <0.05) and ristocetin co-factor (-29% vs. +1%, p <0.05) and without in vitro impairment of the platelet glycoprotein 1b receptor. Gelatin caused a decrease in thrombin-antithrombin complexes (-45% vs. -4%, p <0.05) and F1+2 (-40% vs. +1%, p <0.05). The decrease in circulating levels of vWF:ag, vWF R:Co, thrombin-antithrombin complexes and F1+2 was more than could be expected by the calculated plasma-dilution generated by Gelofusine. Our results demonstrated that the administration of a gelatin-based plasma substitute results in a significant impairment of primary haemostasis and thrombin generation. The defect in primary haemostasis appears to be related to a gelatin-induced reduction in von Willebrand factor, whereas the decreased thrombin generation may be due to the dilution of coagulation factors induced by Gelofusine.

Adult↗
PubMed1995

In vitro effect of dextran-benzene-tetra-carboxylate hemoglobin on human blood rheological properties.

While conducting pharmacological investigations into oxygen carriers, it is important to study the in vitro and in vivo rheological behavior of blood cells in the presence of such preparations. With regard to the original nature of human hemoglobin bound to benzene tetracarboxylate substituted dextran (Dex-BTC-Hb), it seemed necessary to study its rheological effect in a simulated in vitro hemorrhagic shock compensated by a blood substitute. The viscosity of substitutes was determined as well as several rheological parameters after 0, 3 and 6 hours incubation periods of red blood cells with substitutes: viscosity of blood-substitute mixtures at different levels of plasma substitution erythrocyte aggregation of blood-substitute mixtures by determining the velocity of rouleau formation and the cohesion of rouleau network. This work yielded several observations: The viscosity of Dex-BTC-Hb was slightly higher than those of solutions of native Hb, Dex-BTC T10, Dextran 40 (Plasmacair, modified fluid gelatin (Plasmion and hydroxyethyl starch 200 (Elohes). The substitution of a blood volume with Dex-BTC-Hb, corresponding to a compensated 45% hemorrhagic shock, slightly increased the viscosity of hemodiluted blood as compared to other substitutes. In the presence of Dex-BTC-Hb, the aggregation of erythrocytes appears to be increased as compared to standard solutions. Yet, the effect was close to that of Plasmion or Elohes.

Blood Flow Velocity↗
PubMed2004

Early volume expansion for prevention of morbidity and mortality in very preterm infants.

BACKGROUND: Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. OBJECTIVES: In very preterm infants, does early volume expansion reduce morbidity and mortality. If volume expansion is effective, what type of volume expansion is most effective. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. See Review Group details for more information. This was supplemented by additional searches of the Oxford Database of Perinatal Trials, and updated search performed of the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library Issue 1, 2004), MEDLINE (1996-January 2004), EMBASE (1980-January 2004), previous reviews including cross references (all articles referenced), abstracts and conferences (Perinatal Society of Australia and New Zealand, and Pediatric Academic Societies and American Academy of Pediatrics meetings 1998-2003). SELECTION CRITERIA: Randomised trials of early volume expansion with normal saline, fresh frozen plasma, albumin, plasma substitutes or blood compared to no treatment or another form of volume expansion in preterm infants < 32 weeks gestation or < 1500g were included. Volume expansion was defined as at least 10 mls/kg given in the first 72 hours of life. DATA COLLECTION AND ANALYSIS: Standard methods of the Neonatal Review Group with use of relative risk (RR), risk difference (RD) and weighted mean difference (WMD). The fixed effects model using RevMan 4.1 was used for meta-analysis. Data from individual studies were only eligible for inclusion if a least 80% of infants were reported for that outcome. MAIN RESULTS: Seven studies were included. Five studies, four with data for mortality, compared volume to no treatment. Most studies enrolled very preterm infants on the basis of gestation or birthweight. Two studies comparing different types of volume expansion enrolled very preterm infants with hypotension. No study enrolled infants on the basis of low blood flow. One study examined the effect of volume expansion on blood flow but in normotensive very preterm infants. Comparing volume and no treatment, 4 studies with a total of 940 very preterm infants reported no significant difference in mortality (RR 1.11, 95% CI 0.88, 1.40). The large NNNI 1996 study reported no significant difference in severe disability (RR 0.80, 95% CI 0.52, 1.23), cerebral palsy (RR 0.76, 95% CI 0.48, 1.20) and combined death or severe disability (RR 1.00, 95% CI 0.80, 1.24). Although one small study (Beverley 1985) reported reduced P/IVH with volume expansion, this was not supported by any other study. No significant difference was reported in grade 3-4 P/IVH and combined death or grade 3-4 P/IVH. One study (NNNI 1996) reported no significant difference in the incidence of hypotension. The finding of decreased necrotising enterocolitis and increased sepsis in infants who received fresh frozen plasma compared to a gelatin-based plasma substitute or no treatment in one study should be treated with caution. No significant differences in mortality or disability were found in this study. Comparing albumin and saline in hypotensive infants, one study (Lynch 2002) reported a significant increase in mean BP and reduced incidence of treatment failure (persistent hypotension). The other study (So 1997) and the meta-analysis of the two studies found no significant difference in treatment failure (RR 0.75, 95% CI 0.53, 1.06) or in any other clinical outcome. REVIEWERS' CONCLUSIONS: There is no evidence from randomised trials to support the routine use of early volume expansion in very preterm infants without cardiovascular compromise. There is insufficient evidence to determine whether infants with cardiovascular compromise benefit from volume expansion. There is insufficient evidence to determine what type of volume expansion should be used in preterm infants (if at all) or for the use of early red cell transfusions. The significance of the finding of a significant increase in blood pressure in hypotensive preterm infants in one trial comparing albumin and saline is unclear, but the overall meta-analyses found no other significant clinical benefit in using albumin compared to saline.

Blood Volume↗
PubMed1996

Retention and distribution of polygeline (Haemaccel) in the rat.

The plasma substitute polygeline (Haemaccel registered) contains a large fraction of molecules sufficiently small to cross the capillary and glomerular membranes. Plasma volume expansion, tissue extravasation and renal elimination of this artificial colloid were quantified using 125I-labelled polygeline molecules. In pentobarbital anaesthetized rats, either 10 ml 3.5% polygeline (n = 8) or 10 ml 0.9% saline (n = 8) was infused intravenously over 60 min. The plasma volume was assessed by the 3 min distribution volume for I-albumin and the plasma volume changes over time were calculated from erythrocyte volume fractions. The plasma volume increased by 4.6 (2.0) ml (mean (SD)) at the end of the Haemaccel infusion compared with 2.1 (1.8) ml after the saline infusion (P = 0.02). One hour later the increase was 2.4 (1.5) and 1.6 (1.0) ml respectively, not significantly different (P = 0.20). Extravasation of labelled polygeline was greatest in the kidney, possibly due to cellular uptake. Skin and skeletal muscle contained 4-5 times more polygeline than could be attributed to intravascular radioactivity, but still uptake in these tissues did not reach one percent of the amount injected. Following a 60 min infusion and a 60 min interval, 23 (4)% of the polygeline was recovered intravascularly, 43 (9)% had been excreted in urine, leaving 33% to other compartments. Thus, more polygeline was distributed to the interstitium than remained in the circulation. This calls for further investigations into the handling and effect of polygeline in this extravascular compartment.

Animals↗
PubMed2001

Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy.

BACKGROUND: The impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently. METHODS: Before surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion. RESULTS: More than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 +/- 328 ml (group I) and 603 +/- 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume. CONCLUSIONS: The double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 +/- 21% and 43 +/- 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.

Adult↗
PubMed1986

Prophylaxis of complications after urological abdominal surgery by substitution of plasma proteins.

A prospective randomized trial on 94 patients undergoing urological-abdominal surgery has been carried out to evaluate the effect of postoperatively administered plasma proteins. A significant difference in the incidence of bronchopulmonary complications has been found between the treatment group and the control group. This may be due to the substitution of alpha 1-antitrypsin as indicated by assaying alpha-antitrypsin activity. A positive trend, but no significant differences, could be demonstrated for wound healing and the need for antibiotics, postoperatively.

Anti-Bacterial Agents↗
PubMed1978

[Prevention of severe hypotension caused by epidural anaesthesia for transurethral resection of the prostate (author's transl)].

Severe art. hypotensions are one of the most frequent complications of epidural anaesthesia. In 62 geriatric patients undergoing transurethral prostatic resection two methods of prophylaxis for hypotension were investigated: 1. 500ml HES before epidural anaesthesia and supine position until operation. 2. Lithotomy position immediately after EDA without plasma substitute. Blood pressure, heart rate and necessity for the application of vasoactive substances show that the lithotomy position immediately after EDA is the statistically better method. The problem of plasma substitutes in transurethral prostatic resection will be discussed.

Aged↗
PubMed1986

[Comparative study of low molecular dextran or hydroxyethyl starch as a volume substitute in hemodilution therapy].

Rheological therapy, as an immediate treatment in conjunction with physical therapy and the removal of risk factors, plays a significant role in the management of patients with peripheral vascular disease experiencing reduced walking tolerance. An essential element of rheological therapy is hemodilution. Currently, is still uncertain which plasma substitute solution would be the most appropriate in such cases. This study compared the effectiveness of low molecular hydroxyethyl starch to low molecular dextran during a 16-day hemodilution in combination to physical therapy. The clinical improvement observed with both plasma substitute solutions was comparable, yet in view of the cardiac volume overload, dextran demonstrates greater circulatory stress due to the transient pressure increase and more side effects. For this reason, we prefer to administer low or middle molecular hydroxyethyl starch in the dilution treatment of peripheral arterial occlusive disease as a chronic degenerative vascular disease.

Adult↗