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[Clinical experiences with a 6% hydroxyethyl starch 40000 solution; metabolic parameters and tolerance].

A 6% hycroxyethyl starch solution with a mean molecular weight of 40 000 and a degree of substitution of 0.5--0.55 was tested under controlled conditions at 79 clinics in West Germany. The following parameters were evaluated: tolerance, circulation effectiveness, influence on serum electrolytes, hemoglobin and hematocrit. A total of 779 patients received either 6% HES 40 000 alone, 6% HES 40 000 and electrolyte solution or 6% HES 40 000 solution and other volume effective plasma substitutes for treatment of hypovolemia. The results show that stable circulation can be achieved in 4 to 6 hours during narcosis as well as in the subsequent phase with a sufficient supply of fluid through 6% HES 40 000 solution. One case of flush and a slight chill were reported as side effects related to the hydroxyethyl starch.

Fever↗

H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs.

Histamine release by drugs used in anaesthesia and surgery has been often demonstrated in human volunteers, but only occassionally in patients. Three questions arose from these studies. (1) Is the incidence of histamine release high in patients during routine anaesthesia and surgery? (2) Can the clinical effects of histamine release in man be prevented by H1 + H2-receptor antagonists? (3) Are there any side-effects of such a premedication? These problems were investigated in patients and volunteers by randomized controlled clinical trials using only one of the histamine-liberating drugs in man, the plasma substitute Haemaccel. This drug was chosen because it causes a reproducible histamine release in man and because its mechanism of action in man is largely known. (1) Out of 600 orthopaedic patients 30 (5%) showed anaphylactoid reactions following Haemaccel infusion. 26 of these had a histamine release of more than 1 ng histamine/ml plasma. Using predictive values this gives an efficiency of the test by nearly 98%. (2) In volunteers the combination of an H1-plus H2-receptor antagonist (dimethypyrindene and cimetidine) completely prevented the clinical effects of histamine release by Haemaccel (9 allergoid and anaphylactoid reactions in the control group, none in the H1 + H2-group). The incidence of histamine release, however, remained unchanged. (3) The premedication was found to release histamine itself. Cimetidine was effective when given alone but especially in combination with chlorpheniramine (4 events out of 7 applications). The clinical side-effects of these premedication were mild since apparently the free histamine was largely blocked at the receptor sites. It is concluded that premedication with a combination of H1- and H2-receptor antagonists is indicated due to the high incidence of histamine release during anaesthesia and surgery induced by various drugs and treatments. Such premedication is effective but associated with mild side-effects. For this reason more extended clinical trials with dimethpyrindene plus cimetidine in patients are necessary before this premedication can be generally recommended.

Adolescent↗

[The concept of blood components in surgical hemotherapy ].

During the past 7 years, 85% of all red cell units have been transfused as concentrates (RCC) with a haematocrit of 70% at our University Hospital. The basic concept is to exploit the differing critical levels of various parameters in the circulation of the patient. In per cent of normal, we have: blood volume 100%, haematocrit 80%, total serum protein 60%, plasmatic coagulation factors 35%, and platelets 25%. This permits the stepwise use of a plasma substitute, RCC, 5% albumin, and fresh frozen plasma or whole blood. A retrospective, but carefully controlled study of 372 patients showed that this system has no negative effects on the postoperative course. Its logistic advantage is that the plasma from the blood donations used to treat about 80% of surgical patients can be diverted to fractionation into specific derivatives, whereas it does not increase the needs for albumin.

Blood Pressure↗

Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates.

The purpose of this study was to assess the change of platelet and fibrinogen concentrations and the change of activities of prothrombin and factors V and VII when major surgical blood loss was replaced with plasma-poor red cell concentrates (RCCs) and colloid plasma substitutes. Sixty patients were studied. The average blood loss was 65% +/- 41% of the calculated blood volume (CBV). Blood loss was monitored carefully and replaced without delay to ensure stable blood volume. Blood samples were obtained at the induction of anesthesia and at the end of the recovery room period, or before the patient was given fresh frozen plasma. In addition, a platelet count was determined after each 20% blood loss. The results were converted to relative values, and simple linear regression with logarithmic transformation was applied. The initial platelet concentration was 257 +/- 89 x 10(3)/mm3 and the extrapolation of the regression line intercepted the critical level of 50 x 10(3)/mm3 at 230% (confidence interval 169%-294%) blood loss. The initial fibrinogen concentration was 3.7 +/- 1.1 g/L and the hemostatically significant level of 1.0 g/L was already reached at 142% (117%-169%) blood loss (r2 = 0.90). Activities of prothrombin and coagulation factors V and VII reached their critical levels at 201% (160%-244%), 229% (167%-300%), and 236% (198%-277%) blood loss, respectively. We conclude that deficiency of fibrinogen develops earlier than any other hemostatic abnormality when plasma-poor RCCs are used for the replacement of major blood loss.

Albumins↗

Influence of a new hydroxyethylstarch preparation (HES 130/0.4) on coagulation in cardiac surgical patients.

OBJECTIVE: To compare volume therapy with HES 130/0.4, a new hydroxyethylstarch (HES) solution with a gelatin-based fluid replacement strategy. DESIGN: Prospective, randomized, safety study. SETTING: Urban, university-affiliated hospital (single institution). PARTICIPANTS: Forty-two patients undergoing elective cardiac surgery. INTERVENTIONS: Patients were prospectively randomized into 2 groups: In group 1 (n = 21), gelatin was given perioperatively for volume support until the 1st postoperative day to keep the central venous pressure (CVP) between 10 and 14 mmHg; in group 2 (n = 21) HES 130/0.4 was administered using the same protocol as in group 1. MEASUREMENTS AND MAIN RESULTS: Standard coagulation variables and modified thromboelastography (TEG) were used. Using different activators for extrinsic and intrinsic activation and heparin inactivation by heparinase, the onset of coagulation (coagulation time), kinetics of clot formation (clot formation time), and maximum clot firmness were measured. Measurements were performed after induction of anesthesia (T0), at the end of surgery (T1), 4 hours after surgery (T2), and on the morning of the 1st postoperative day (T3). A total of 3310 +/- 810 mL of gelatin and 3070 +/- 570 mL of HES 130/0.4 were used in the 2 groups during the study period. The 2 groups did not differ with regard to postoperative bleeding or in use of packed red blood cells or fresh frozen plasma. Standard coagulation variables were similar between the 2 groups. All TEG variables were within the normal range at baseline. Coagulation time and clot formation time data were significantly elevated after surgery and in the intensive care unit, without showing specific differences between the 2 volume replacement groups. Intrinsic TEG and heparinase TEG clot formation times remained significantly higher until the end of the study period. No differences were seen between HES-treated and gelatin-treated patients. CONCLUSIONS: Volume replacement with the new HES preparation was as safe as gelatin-based volume replacement with regard to coagulation in cardiac surgical patients. HES 130/0.4 is an alternative plasma substitute to treat volume deficits.

Aged↗

Effects of resuscitation with hydroxyethyl starch (HES) on pulmonary hemodynamics and lung lymph balance in hemorrhagic sheep; comparative study of low and high molecular HES.

Synthetic starch solution, such as hydroxyethyl starch (HES), has been used clinically to restore cardiovascular volume in patients with hemorrhagic shock. Several HES solutions are available clinically, but each HES has a broad range of molecular mass fractions. We performed comparative studies of extremely low and high molecular HES to evaluate the effects of these HES solutions on lung lymph filtration during resuscitation. We prepared awake sheep with vascular monitoring and lung lymph fistulas. After baseline measurements, animals were bled from an arterial line to maintain shock. After 2 h of hemorrhagic period, the following three solutions were infused over 1 h, respectively. Experiment (Exp) 1 (n=6); low molecular HES; (molecular weight (MW) 70000, substitution fractions 0.5-0.55, Exp 2 (n=6); high molecular HES; (MW 450000, substitution fractions 0.65). Exp 3 (n=6); normal saline (NS). The quantity of solution was determined as the same volume of blood lost to induce hemorrhagic situation in each animal (Exp 1; 940+/-36 ml, Exp 2; 910+/-50 ml, Exp 3; 920+/-42 ml). Both low and high molecular HES could restore the systemic artery pressure and cardiac output, and significantly increased pulmonary microvascular pressure equally, which were significantly higher than those in normal saline. However, actual oncotic pressure gradient (plasma-lymph) rose transiently during low molecular HES infusion, while high molecular HES widened the oncotic pressure gradient even after the cessation of the infusion. Lung lymph flow during and after resuscitation with low molecular HES and NS rose significantly from the pre-shock baseline. There was no significant difference in increased lung lymph flow between low molecular HES and NS. However, lung lymph flow after high molecular HES was significantly less than that after low molecular HES. These data suggest that low molecular HES is as useful a plasma substitute as high molecular HES, but has a possibility to increase lung lymph filtration during the early phase of resuscitation.

Analysis of Variance↗

An international view of hydroxyethyl starches.

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.

Blood Coagulation↗

[Pathophysiologic studies in acute blood loss].

The authors induced acute blood loss in dogs and examined the changes in hemodynamics, hemodilution, blood coagulation acid-base balance and tissue respiration. They found that the most favourable hours for initial renimation were the first two hours. They used the Bulgarian plasma substitute reoisodex with very good effect on the indicated parameters and microcirculation. As a result of this the time for the appearence of irreversible stage in grave hypovolemia was prolonged with hours.

Acid-Base Equilibrium↗

Technical and clinical aspects of cascade filtration plasma exchange (CFPE).

Cascade filtration plasma exchanges (CFPE) were realized using an hemofiltration system (HFS) coupled to 2 filters with different pore sizes. The first one (F1 = plasma-separator; Asahi plasmaflo HI-05) separates plasma from whole blood, the second one (F2 = plasma filter; Asahi XK-60, Kuraray EVAL 2A or 4A) filtrates high molecular weight (MW) components from the separated plasma. F2 filtrate returns to patient mixed with blood cells and 4% Albumin solution or Plasmion R replacing plasma discarded (about 0.5-0.8 I for 1-1.5 plasma mass (PM) treated). The HFS is able i) to modulate the different pressures (venous pressure, F1 and F2 transmembrane pressures (TMp] using pumps speed variators, ii) to recirculate and concentrate extracted plasma and iii) to know F2 treated PM. Blood pressure, pulse rate and electrocardiogram were monitored during each CFPE session. Nineteen CFPE were performed for 8 patients selected among our PE indications, this selection taking into account presence or not of risk factors linked to disease e and/or to patient. Anti-histamine drugs were always infused before CFPE session. On a biological point of view, the problem lies into F2 selectivity which is relatively good for low (as Albumin) and high (as IgM) MW molecules which are returned to patient or discarded, but should be improved for the intermediate ones (as IgG). On a technical point of view, the plasma substitute quantity is reduced about six times. But the control of F2 TMp is not perfectly and the PM to be treated has to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hemodynamic and oxygen transport effects of pentastarch in burn resuscitation.

If nonprotein colloid plasma expanders could be demonstrated to be safe and efficacious in burn resuscitation, a significant cost benefit would result. This study was a randomized cross-over comparison of 500 ml of 5% albumin and 500 ml of 10% pentastarch, a new hydroxyethyl starch, in acute burn resuscitation. Pentastarch was an effective plasma expander, resulting in increases of preload, cardiac output, oxygen delivery, and oxygen consumption; the hemodynamic effects of pentastarch infusion were equal or superior to those of albumin. Both albumin and pentastarch infusions resulted in increased bleeding and clotting times; these effects were most likely dilutional. Pentastarch is a promising plasma substitute for burn resuscitation; the effects of a 500 ml infusion are equal or superior to those of albumin. Further study is necessary to assess the safety of larger infusion volumes.

Adult↗

Use of a gelatin solution in hypovolaemia and toxaemia in small animals.

Intravenous gelatin given as a plasma substitute to cases of road traffic accidents, cystic endometritis and haemorrhagic gastroenteritis appeared to enhance the chances of recovery. Method, rate, volume and temperature of administration was not apparently critical. There seemed to be no other pharmacological interaction with other drugs or replacement fluids using gelatin.

Animals↗

Fatal course in severe meningococcemia: clinical predictors and effect of transfusion therapy.

OBJECTIVE: To investigate whether the administration of fresh-frozen plasma to patients with systemic meningococcal disease is associated with an increased mortality rate compared with the administration of plasma substitutes. DESIGN: Seventeen-year case-control study. SETTING: Intensive care units and departments of internal medicine and pediatrics of one university hospital and one local hospital. PATIENTS: A total of 336 patients with culture-proven meningococcemia or symptoms characteristic of meningococcemia who were admitted to two hospitals in northern Norway between 1974 and 1991. MEASUREMENTS AND MAIN RESULTS: High-risk patients were selected on the basis of two different scoring systems (Niklasson's score and clinical score) and classified according to the type of intravenous fluid regimen (fresh-frozen plasma, blood, or colloids). For comparison between groups, analysis of variance and chi-square tests were used. Assessments of adjusted effects on mortality rate were done by multiple logistic regression. Administration of blood or plasma was significantly associated with a fatal course, both in the total patient population (p < .01) and in the high-risk group (p = .02), while using colloids alone was negatively associated with death, although not reaching statistical significance. A significantly lower mortality rate was found in one of the hospitals where colloids were used instead of plasma or blood in the last part of the period studied (p < .05). CONCLUSION: The results support our hypothesis that the use of fresh-frozen plasma may negatively influence outcome in systemic meningococcal disease.

Adolescent↗

14 years of therapeutic plasma exchange in France.

The French Registry for plasma exchange (PE) was set up in 1985. For 14 years it has allowed analysis of the techniques used along with the indications and complications. Recent analysis shows a slight fall in activity as some studies have ended, while the neurological disorders remain the most frequent indications for PE. The important changes observed over the years are the increased use of the centrifugation technique, the development of plasma and whole blood treatment and plasma substitution using a mixture of albumin and pentastarch. The French Registry for PE is the largest such database which, along with the Canadian Registry for therapeutic hemapheresis, allows both retrospective and prospective studies.

Anticoagulants↗

Delayed microcirculatory hyperpermeability following perfusion washout.

Recent experimental data have demonstrated improved flap survival following perfusion washout with a synthetic, chemically defined, mammalian plasma. In an effort to define the physiology responsible for the efficacy of perfusion, the method of "labeling" hyperpermeable blood vessels with Monastral blue B in rat epigastric vascular island flaps was utilized. Results confirmed that capillary and venular hyperpermeability is an early and progressive pathophysiologic event in ischemic flap tissue and one which is reversible prior to a critical ischemic period. Perfusion washout with a physiologic, acellular plasma substitute delays the onset of vascular hyperpermeability. This may be a mechanism responsible for improving tissue survival following extended periods of warm ischemia (12 hours). It is implied that stagnant blood and products of hemolysis in the microcirculation may be detrimental to the functional and anatomic integrity of the endothelial wall.

Animals↗

[Microclots of perfusion mixtures during open heart surgery with artificial circulation].

During 9 experimental and 93 clinical operations on the open heart under circulatory bypass the authors studied microclots of multicomponent perfusion mixtures. They observed an increased number of microclots after infusion of high-molecular plasma-substituting solutions and long-term intraapparatus recirculation. During the bypass there was an increased number of microclots in the "machine-patient" system. The complex of measures suggested by the authors contributes to a delay in additional formation of microclots during the perfusion and also reduces the number of posttransfusion complications.

Blood Preservation↗

[Treatment of coronary shock].

A brief characteristics of the main therapeutic methods for shock in acute myocardial infarction cases is presented, including fast infusion of plasma-substitutes, noradrenalin, isoproterenol, alpha-adrenergic bocking agents, steroid hormones, intra-aortal balloon counter-pulsation, oxygen therapy, acidbase balance correction, etc. It is emphasized that proper therapy based on the evaluation of the nature of circulatory disorders in every particular case proves effective in some cases.

Adrenergic beta-Antagonists↗

[Perioperative transfusion strategy].

Tactics in blood transfusion have evolved considerably during the last ten years. Awareness of infectious risks and economic considerations have lead legislators to draw the guidelines for a safer transfusion. Their aim is to promote a better transfusion in smaller quantities at a lower risk. The goal of perioperative blood replacement is to maintain hemoglobin, blood volume and coagulation factors at an adequate level. This can be carried out by either homologous or autologous transfusion. Fresh frozen plasma transfusion is only required in severe bleeding where coagulation factors are depleted. The plasma substitutes must be used according to their intrinsic properties and their cost. The choice of an autologous technique depends on the type of surgical procedure, the expected blood loss and the economic resources available. Autologous blood transfusion may be optimized by the association of various techniques. This transfusion strategy must be elaborated by all the medical protagonists implicated in transfusion procedures.

Blood Transfusion↗