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A novel hydroxyethyl starch (Voluven) for effective perioperative plasma volume substitution in cardiac surgery.

PURPOSE: To compare the new hydroxyethyl starch HES 130/0.4 (Voluven) and the standard HES 200/0.5 (pentastarch) regarding effectiveness for plasma volume substitution and safety of large volumes in heart surgery. METHODS: Fifty-nine patients scheduled for coronary artery bypass grafting were enrolled in a prospective, randomised, double-blind, parallel-group, multicentre, clinical, phase III study. Hydroxyethyl starch was used as the exclusive artificial colloid for acute normovolemic hemodilution, priming of the heart lung machine, and for intra- and postoperative plasma volume substitution from induction of anesthesia until 16 hr after the end of surgery. Efficacy was evaluated by comparing the amount of colloid infused, hemodynamics, and colloid osmotic pressure (COP). Safety endpoints were blood loss, the use of allogeneic blood products, coagulation variables, and adverse events. RESULTS: Effectiveness, as assessed by the total amount of infused HES volumes within the treatment period, was similar between HES 130/0.4 and HES 200/0.5 (2,550 mL +/- 561 mL vs 2,466 mL +/- 516 mL). Also, no differences were found for the use of other colloids (pasteurised plasma), hemodynamics, and COP In HES 130/0.4 patients, the postoperative increase of von-Willebrand factor (vWF) was higher (P < 0.01), blood loss was lower, and less packed red blood cells were transfused. CONCLUSION: Hydroxyethyl starch 130/0.4 is an effective plasma volume expander in heart surgery and may be used as the sole artificial colloid to cover the perioperative period. We found a reduced influence of HES 130/0.4 on the physiologic postoperative increase of vWF.

Aged↗

Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings.

OBJECTIVE: The perioperative use of colloidal plasma substitutes is still under discussion. We therefore conducted a prospective randomised study with three commonly used plasma substitutes to examine their histamine releasing effects in 21 volunteers. MATERIAL OR SUBJETS: 21 male volunteers were enrolled in this prospective, randomised, controlled clinical study. Endpoints were the incidence of early and late histamine release and the time course of the release kinetics. Normovolemic hemodilution technique was used with hydroxyethyl starch (n = 6), human albumin (n = 6) and polygeline (n = 9). Measurement and observation period was 240 min after the start of the plasma substitute infusion. Heart rate, blood pressure, SaO(2), clinical symptoms/signs and plasma histamine were measured during the observation period. RESULTS: The incidence of histamine release over the whole observation period in all three groups was 100%. Histamine release occurred frequently in all three groups until 30 min (50%-78%) and up to 240 min (late release reaction: 67%-83%) after the start of infusion. Surprisingly even hydroxyethyl starch, which is regarded as a generally safe and effective plasma substitute, caused high incidences of late histamine release (67%). Histamine release is a well known side effect of polygeline and - to a lesser extent - also of albumin, but was a novel finding for hydroxyethyl starch. CONCLUSIONS: We demonstrated for the first time histamine releasing effects of hydroxyethyl starch over a long period of time after administration. This perioperatively and for intensive care possibly relevant finding should make clinicians aware of late side effects not yet connected with the clinical use of these colloidal plasma substitutes.

Adult↗

The effect of In vitro hemodilution with gelatin, dextran, hydroxyethyl starch, or Ringer's solution on Thrombelastograph.

UNLABELLED: To determine the effects of progressive in vitro hemodilution with various plasma substitutes on whole blood coagulation, blood was obtained from six healthy volunteers. The Thrombelastograph((R)) (TEG; Haemoscope Corp., Morton Grove, IL) variables of reaction time, coagulation time, maximum amplitude, and growth angle were determined. The following plasma substitutes were tested: two gelatin solutions (4% gelatin polysuccinate and 5.5% oxypolygelatin); two dextrans (10% dextran 40 and 6% dextran 60); and five hydroxyethyl starch (HES) preparations (6% HES 70/0.5-0.55, 3% HES 200/0.5, 6% HES 200/0.5, 10% HES 200/0.5, and 6% HES 450/0.7). Ringer's solution was also tested to assist analyzing the intrinsic effect of colloid molecules on blood coagulation. The dilution ratios of citrated blood volume to plasma substitute volume were 10:2, 10:4, and 10:10. Blood coagulation was affected by plasma substitutes when the dilution ratios of citrated blood volume to colloid solution volume were 10:4 and 10:10. TEG variables did not change significantly after in vitro hemodilution with lactated Ringer's solution. The tested gelatin solutions showed less intrinsic effect on blood coagulation than other plasma substitutes. All HES preparations showed similar intrinsic effects as 6% dextran 60. The plasma substitute of 10% dextran 40 had the strongest effect on coagulation. Coagulation time was the most markedly affected TEG variable. Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation, 10% dextran 40 has the strongest effect on coagulation. IMPLICATIONS: Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation than hydroxyethyl starch or dextran, 10% dextran 40 has the strongest effect on coagulation.

Blood Coagulation↗

[Efficacy and tolerance of Elohes in plasma exchanges].

This study aimed to compare two plasma substitution regimens used during plasma exchanges (PE). It was a prospective cross-over randomized trial. Each patient (n = 12) had two PE at a 48 h interval. During one PE, only albumin was administered (PEA), and during the other one, equal volumes of albumin and low molecular weight hydroxyethylstarch (HES) (Elohes) were given (PEA+E). The order in which these different protocols were used was random. Plasma was separated by filtration, and the total volume extracted was one and a half the plasma volume. The parameters recorded every 15 min until 1 h after the end of PE, were heart rate, blood pressure and central venous pressure (CVP). Plasma volume, calculated from the mean body haematocrit and blood volume, was measured before and after PE. The clinical and biological tolerance of the rapid infusion of a large volume of HES was also assessed. PE characteristics were similar in both groups. For PEA and PEA+E, PE lasted 152 +/- 21 min and 154 +/- 25 min; the plasma volume extracted was 3,907 +/- 772 ml and 3,933 +/- 717 ml; the volume of plasma substitute infused was 4,097 +/- 617 ml and 3,933 +/- 717 ml, respectively. As haemodynamic and biochemical values were not significantly different in both groups, they were pooled together irrespective of the order of PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Blood transfusion in heart surgery].

We have studied the effect of blood-saving measures in open heart surgery. Such measures were introduced in 1987. All fluids administered on the day of operation and on the first postoperative day were registered in all cardiac patients operated during one month in 1986, 1987, 1988. In 1986 the patients were exposed to a median of 21 donors while in 1988 they were exposed to a median of 2 donors. The reduction in transfusions was achieved by substituting plasma by polygeline, by giving thrombocytes only when there was a low thrombocyte count and by accepting a hemoglobin value of 9 g/100 ml before transfusion of erythrocytes. In 1988 most postoperatively drained blood was retransfused using a Sorensen retransfusion set. The reduction in transfusions has reduced the cost of each open heart operation by NOK 11,662.

Blood Donors↗

Lack of evidence for immunological reactions to polygelatin.

Gelatin-based plasma substitutes resemble denatured collagen in that sequence dependent antigenic sites of collagen may be preserved in these preparations and cause side reactions of such plasma substitutes. We have measured the binding of 125I-collagen in denatured conformation to antibodies and to cold-insoluble globulin (CIG) in sera of patients undergoing orthopedic surgery. About two thirds of the sera bound significant amounts of denatured collagen to immunoglobulins and to CIG. Yet, there was no correlation in individual patients or in groups of patients between the collagen binding capacity of sera and the occurrence of allergic reactions upon infusions of Haemaccel. Furthermore, antibodies to denatured collagen induced in animals did not cross-react with gelatin-based plasma substitutes. Thus, it is not likely that side reactions after infusion of gelatin-based plasma substitutes are caused by immunological reactions between antigens and performed antibodies.

Antibodies↗

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. Searches were conducted of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts and conference proceedings. 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. In one small study, there were no significant differences in outcomes between hypotensive infants who received colloid (albumin) or crystalloid (saline). REVIEWER'S 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 would 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 trial comparing colloid (albumin) and crystalloid (saline) in hypotensive preterm infants found no benefit in using a more expensive blood product compared to saline, but is insufficiently powered to detect an important clinical difference.

Blood Volume↗

[Albumin kinetics in superior mesenteric artery shock in rats].

1. After 1-hour-tourniquet of the arteria mesenterical superior of the rat the result is a loss of intravasal fluid into the small intestine. After 2-hour-tourniquet the loss of fluid into the samll intestine can be higher than the volume of plasma circulating at the start of the experiment. During therapy with plasma substitute on base of gelatine (Haemaccel) the volume of content of the small intestine increases further. 2. After 1-hour-tourniquet the content of intravasal albumin is diminished by 26%, after 2-hour-tourniquet by 46%. Under therapy with a plasma substitute the loss of intravasal albumin increases further. 3. After 1-hour-tourniquet a transient accumulation of albumin was found in the wall of the samll intestine which was reduced after 2-hour-tourniquet. 4. The intravasal albumin is excreted in the small and the large intestine. After 1-hour-tourniquet 46% of excreted albumin was found in the small intestine after 2-hour-tourniquet 61%. It can be demonstrated, that under replacement with plasma substitute the result is mainly an "albumin dilution effect". The wall of the small intestine becomes permeable to high-molecular weight substances with an average molecular weight below 60.000. An effective therapy with the plasma substitute of the AMS-shock should, therefore, contain carrier substances with a molecular weight higher than 60.000.

Animals↗

Hemodynamics of preeclampsia.

A review of the English literature reveals considerable disagreement regarding the cardiovascular hemodynamics of preeclampsia as measured by both noninvasive and invasive techniques. In the untreated patient, most of the data suggest the presence of low CO, low PCWP, and elevated SVR as compared to normotensive pregnancy. In contrast, in patients receiving treatment prior to the measurements, the majority of the data indicate the presence of normal to elevated CO, PCWP, and SVR. There is general agreement that plasma colloid oncotic pressure is markedly reduced in patients with severe disease, and this reduction is more dramatic in the postpartum period especially in those receiving excessive crystalloid therapy. As a result, these patients are at increased risk for pulmonary edema. Several studies recommended using plasma and plasma substitutes to correct the reduced plasma volume and PCWP prior to the use of vasodilator therapy in such pregnancies. This management requires the use of invasive hemodynamic monitoring, and its benefit is transient and not well established. Finally, the true cardiovascular hemodynamics of preeclampsia remain unknown.

Blood Pressure↗

LH pattern in ovariectomised rats after continuous blood withdrawal: effects of different substitutions.

Plasma concentrations of LH and of sodium, potassium, total protein and haemoglobin were measured in ovariectomised rats during continuous blood withdrawal up to 180 min; 0.45 ml blood samples were taken every 10 min, the total volume of blood removed not exceeding 9 ml. Four groups of animals were studied: group A received no substitution (controls), group B was substituted with 0.9% NaCl-solution, group C with 3.5% polypeptide solution (Haemaccel), and group D with a suspension of washed erythrocytes from the blood removed. During blood withdrawal, the mean values of LH concentrations as well as the amplitudes of the rhythmic LH pulses remained constant in all the animals. However, the rate of pulses was reduced in the control animals and in the group receiving 0.9% NaCl-solution during the period between 90 and 180 min; in contrast no change was observed in the groups C and D during the whole period. The results presented here show that the characteristic LH pattern in ovariectomised rats is not affected by volume depletion, provided the blood is replaced by a solution containing either a polypeptide or a suspension of washed erythrocytes.

Animals↗

Hydroxyethyl starches, dextran and balanced salt solution in correction of hypotension during epidural anaesthesia.

A low molecular weight (Mw 38 000) and a medium molecular weight (Mw 125 000) hydroxyethyl starch and a medium molecular weight dextran (Mw 70 000) solution were compared with a balanced salt solution in 123 patients undergoing operations of the lower extremities in epidural anaesthesia; 500 ml of the studied solutions were infused during 15 min after the injection of the epidural anaesthetic. The need for etilefrine hydrochloride as a vasoconstrictor in correcting hypotensive reactions was recorded. Changes in haemoglobin (Hb), haematocrit (Hct), serum total protein and serum albumin concentrations were measured. The number of patients given etilefrine hydrochloride in the plasma-substitute groups was smaller than in the control group. The differences were, however, not statistically significant. The fall in blood pressure cannot be totally inhibited by administration of 500 ml plasma substitute. According to the differences in Hb, Hct, serum protein and albumin values, the hydroxyethyl starch solutions were significantly more effective plasma substitutes than the balanced salt solution and as effective as dextran. No side-effects attributable to the solutions used were observed.

Adolescent↗

[Anaphylactic shock due to modified fluid gels: 2 case reports].

UNLABELLED: Colloid solutions can give severe anaphylactic accidents. We are reporting two cases from our department. FIRST CASE: a sixty eight years old man perfused with Plasmion solution (Gelatin plasma substitute) before spinal anesthesia, presented sudden hypotension and diffuse skin rush. Second case: a twelve years old girl, receiving a Plasmion solution to correct a hypovolemic shock in I.C.U, presented a severe bronchospasm and a worsening of the hypotension. These accidents are explained by immunologic reactions or by direct histamine release. Their incidence is between 0.01 and 0.8 percent depending on the used solution. They are prevented by an antihistaminic premedication for the gelatin plasma substitutes and by an haptenic inhibition for Dextran (polysaccharide plasma substitutes). The new colloid solutions, based on hydroxyethylstarch, seems to give much less allergic reactions.

Aged↗

In vitro colloid osmotic pressure of commonly used plasma expanders and substitutes: a study of the diffusibility of colloid molecules.

The rational choice of a plasma substitute for states of hypovolaemia depends partly on its colloid osmotic pressure (COP). We have measured the COP of 108 samples of plasma substitute across selectively permeable membranes which retain molecules greater than 10,000 dalton (COP10) and 50,000 dalton (COP50) the ratio COP50/COP10 providing a potential index of diffusibility of the smaller molecules across capillary membranes. 6% Hespan solution showed a particularly favourable COP50/COP10 ratio at 0.58 indicating a potential for good retention in the circulation whilst 3.5% Haemaccel showed a COP50/COP10 ratio of 0.18 indicating a potential for marked transcapillary diffusion, especially in states of capillary leak. In patients with normal capillary permeability both Gelofusine and Dextran 110 are likely to show adequate retention in the circulation with a COP50/COP10 ratio of 0.37 and 0.39 respectively. These are comparable to the retention of 4.5% human albumin (0.36) but all of the plasma substitutes tested, with the exception of Haemaccel, provided a higher COP across both membranes than 4.5% human albumin solution. An in vivo comparison of these plasma substitutes is required to confirm the advantages of macromolecular colloids in states of capillary leak.

Colloids↗

Assessment of histocompatibility of different hemoglobin solutions using mesenteric perfusion on the small bowel of the male Wistar rat.

Histocompatibility assessment of 70 g/l stroma-free hemoglobin solutions pyridoxylated or not, and purified or not, was carried out using vascular perfusion of the intestine of rats. Mechanical and ultrastructural changes in the organ and the arteriovenous difference of PO2 were compared to those obtained with albumin, gelatin and dextran. Overlapping epithelium conserves its structure in the presence of hemoglobin, whereas it is partially or totally destroyed with the plasma substitutes. Nevertheless, with non pyridoxylated hemoglobin there is a strong detachment of the epithelium from the lamina propria. The intestine, irrigated by the hemoglobin solutions shows efficient peristalsis, but this totally disappears with plasma substitutes. For similar arterial PO2, for all the solutions, the arteriovenous difference was of 100 mmHg for the hemoglobin solutions, whereas they never exceeded 60 mmHg for the plasma substitutes. Hemoglobin pyridoxylation led to an arteriovenous difference significantly superior (p less than 0.001) to those obtained using non modified hemoglobin. With their O2 supply hemoglobin solutions appear able to limit the development of hypoxia in the tissue. The continuation of peristalsis and the weak ultrastructural modifications confirm the slight histological improvement gained when using pyridoxylated hemoglobin. Nevertheless an extravasation appeared constantly, as well as flow reduction during perfusion with the hemoglobin solutions.

Animals↗