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Hemodilution.

The dilution of whole blood leads to a significant improvement of its rheologic properties based on a decrease in hematocrit and, hence, blood viscosity. Under conditions of normovolemia and an adequate response of the cardiorespiratory system, the acute dilution of blood will enhance the venous return to the heart and thereby improve total and capillary blood flow significantly. In the hematocrit range of 25 to 30 per cent (limited hemodilution), this increase in flow rate is able to compensate fully for the diminished oxygen content of the blood. Changes in oxygen extraction or in oxygenhemoglobin affinity are only encountered at hematocrits below 20 per cent or if hemodilution is associated with hypovolemia. Since normovolemia is the condition sine qua non for the heart to increase its output compensatorily, intentional hemodilution should preferably be performed with colloid solutions which are capable of maintaining the colloid osmotic pressure of plasma and the circulating volume in normal limits. Limited normovolemic hemodilution with its beneficial effects on microcirculatory flow and tissue nutrition is emphasized for the treatment of impaired microcirculation as occurring in shock and low flow states, polycythemia, and high viscosity syndromes. Acute preoperative hemodilution is a means of reducing the use of bank blood and of avoiding the risks of blld transfusions in patients undergoing major elective surgery. Extreme hemodilution and total body washout in hypothermia appear to be effective clinical tools.

Animals↗

Platelet aggregation during abdominal surgery in an experimental pig model: the effects of presurgical antibiotic protocols and volume replacement with hydroxyethyl starch.

The effect of presurgical antibiotic protocols in combination with hemodilution on platelet aggregation was studied. Thirty pigs were randomly assigned to three groups. Group 1 received amoxicillin/clavulanic acid, group 2 metronidazole+cefuroxime, and group 3, as a control, sodium chloride. They underwent laparotomy, massive blood loss, and volume replacement with hydroxyethyl starch 200, followed by an anaphylactoid reaction. Platelet aggregation was measured by the turbidometric method. Neither antibiotic protocols had any effect on platelet aggregation as compared with the control group. In all three groups, aggregation to ADP and collagen was significantly reduced after volume replacement with hydroxyethyl starch. In contrast, the sensitivity to the aggregating effects of collagen was increased as assessed by a higher frequency of responses to low concentrations of collagen and a shortened latency of the aggregation response after collagen addition. Further in vitro studies revealed that dilution of plasma with hydroxyethyl starch specifically induced the changes seen after in vivo volume replacement. The results suggest that the plasma substitute hydroxyethyl starch 200 increases the sensitivity to low doses of collagen, an effect never described before and considered of clinical relevance.

Abdomen↗

Accumulation of hydroxyethyl starch (HES) in the liver of patients with renal failure and portal hypertension.

Hydroxyethyl starch (HES) has gained wide clinical acceptance as a colloidal plasma substitute. We were able to study the liver biopsies of two patients with renal failure who developed ascites after repeated infusions of HES. All types of liver cells displayed massive accumulation of HES with the morphologic resemblance to a storage disease. These changes could be distinguished clearly from the lesions of a hereditary disorder by light and electron microscopy. Although it is difficult to establish a causative role for HES in the development of ascites on the bases of morphological changes alone, one should be cautious about giving HES to patients with renal failure until exact data from further experimental studies are available.

Female↗

Cardiopulmonary bypass after prolonged cardiac arrest in dogs.

Ventricular fibrillation (VF) cardiac arrest of more than ten minutes can be survived by cerebral neurons, but restoration of spontaneous circulation (ROSC) by external CPR is unreliable. Cardiopulmonary bypass (CPB) permits control of pressure, flow, oxygenation, temperature, and composition of blood. After 12 1/2 minutes of normothermic VF cardiac arrest, CPB was used as a research tool for reperfusion and assisted circulation for two hours in ten dogs without thoracotomy, with plasma substitute priming, and without preceding CPR (a deliberately nonclinical scenario). Recovery was compared with that in ten control dogs in which standard CPR with advanced life support (ALS) for up to 30 minutes was used to achieve ROSC. Both groups subsequently had blood pressure, blood gases, ventilation, and other parameters controlled for 20 hours, and intensive therapy to 72 hours. CPB achieved ROSC more successfully (ten of ten vs six of ten controls) (P less than .05), and more rapidly, with fewer defibrillation attempts and with less epinephrine (P less than .05). CPB improved 72-hour survival (seven of ten vs two of ten controls) (P = .025). Between two and 24 hours, of those with ROSC, intractable cardiogenic shock killed four of six control dogs (NS). CPB was followed by fewer arrhythmias. CPB increased recovery of consciousness (five of ten CPB vs zero of six controls with ROSC) (P = .037), but achieved neurologic normality in only one of ten. Cardiac arrest and CPB (without CPR) resulted in less myocardial morphologic damage than did standard CPR (P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Management and monitoring of severe preeclampsia.

Preeclampsia is associated with increased maternal and perinatal morbidity and mortality. Preeclampsia is more than pregnancy-induced hypertension. The hypertension is only one manifestation of an underlying multifactorial, multisystem disorder, initiated early in pregnancy. In established severe disease there is volume contraction, reduced cardiac output, enhanced vascular reactivity, increased vascular permeability and platelet consumption. Medical treatment of severe hypertension in pregnancy is required. The more controversial issues are the role of pharmacological treatment in conservative management of severe preeclampsia aiming at prolongation of pregnancy, the ability of such therapy to modify the course of the underlying systemic disorder and the effects on fetal and maternal outcome. This paper presents an overview concerning the current developments in management and monitoring of severe preeclampsia. Controversial topics such as the role of plasma volume expansion in preeclampsia, expectant versus aggressive management of severe preeclampsia remote from term, and pharmacological interventions in the management of eclampsia and the HELLP syndrome are addressed.

Adrenal Cortex Hormones↗

[Demonstration and semi-automatic assay of gelatin in serum].

We suggest a semi-automatic method for the determination of gelatin. The measured concentration of gelatin is not dependant for the amino-acid composition of that plasma substitute preparation. Plasmatic proteins are separated previously from gelatin by precipitation using trichloracetic acid (5 p. cent; vol/vol). Modified gelatin lower in molecular weight than proteins can be found in the supernatant. It is determined by Lowry method with an automatic continuous flow system. Standardization must be realized using gelatin's solution since the developped coloration intensity with proteins is stronger. At electrophoresis, gelatin migrates essentially towards beta-globulins. beta-globulins increased with the gelatin level in serum. Percentage of variation for beta globulins and other fractions must be determinated in function of the protein level before perfusion. So it is possible to study the percentage of variation of these electrophoretic fractions independantly of the altered protein level.

Autoanalysis↗

Assay for levormeloxifene, a selective estrogen receptor modulator, in human and monkey plasma employing high-performance liquid chromatography and solid-phase extraction.

Assays for levormeloxifene, a new selective estrogen receptor modulator, and its 7-desmethyl metabolite in human and cynomolgus monkey plasma are described. Plasma was extracted on mixed-mode bonded sorbent material (C8/SCX) and the extracts were analysed by high-performance liquid chromatography with fluorescence detection. Recoveries of levormeloxifene and the metabolite exceeded 70%. Within and total assay precision calculated as a coefficient of variation (C.V.) were <8% for both compounds at all concentration levels, except at the limit of quantitation (LOQ) where the C.V. was 15%. Within and total-assay accuracy calculated as a percentage of the nominal value were between 90 and 114% for both analytes. The LOQ was for levormeloxifene and 7-desmethyllevormeloxifene, respectively, 1.5 and 2.5 ng/ml (man) and 5.2 and 6.9 ng/ml (monkey). In the monkey plasma assay, human plasma could substitute monkey plasma as blank plasma.

Animals↗

Perioperative nonspecific histamine release: a new classification by aetiological mechanisms and evaluation of their clinical relevance.

As a consequence of the performance of a randomized controlled clinical trial on perioperative histamine release and cardiovascular and respiratory disturbances, several types of increases in plasma histamine had to be distinguished instead of only two which existed at the beginning of the study: drug-induced allergic and pseudoallergic reactions. First of all, the new classification by aetiology (clinical epidemiology) was derived from a meta-analysis (secondary analysis) of the most recent literature. According to that histamine release in the perioperative period has several, different causes and is involved in several, different disease manifestations. A clear distinction (classification), however, is necessary if histamine release as an unwanted (adverse) effect has to be recognized, value judged according to its clinical relevance and therefore also prevented by histamine antagonists. Histamine release by neuro-endocrine and neuro-inflammatory mechanisms, cytotoxic histamine release and local, cytokine induced histamine release have been distinguished from pseudoallergic histamine release, but its functions are not yet clear. It has been analysed in prospective trials which used special clinical situations as models: patients on a normal ward or before and during upper GI endoscopy without premedication, but also in specific phases of laparoscopic cholecystectomy (trocar phase and dissection phase). Their existence in the clinical reality is now very likely, but new trials must investigate the pathophysiological effects such as in metabolism, coagulation, pulmonary haemodynamics (shunt volume) and gastric acid secretion. Histamine release by pseudoallergic mechanisms, however, was identified in the very vulnerable post-induction phase of anaesthesia up to skin incision. Its incidence was much higher than ever expected and its clinical relevance was demonstrated by the severity of reactions and the intervention strategies of the anaesthetists who were blinded concerning the type of the plasma substitute given and the prophylaxis with antihistamines. Pseudoallergic histamine release was clearly unwanted (adverse). Its occurrence in the other phases of anaesthesia has to be further evaluated in the tedious procedure of data analysis of the Mainz-Marburg-trial. The overall incidence of histamine release in the trial was so incredible high (72% of all patients, some of them with up to 4 episodes of histamine release) that a distinction between pseudoallergic (unwanted) and other types of histamine release (possibly less unwanted or even beneficial) is urgently needed. In the phase of steady state (maintenance) of anaesthesia the H1-(+)H2-prophylaxis was highly effective. Further analysis must show whether this is also the case during the phases of induction of anesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Treatment of fulminant falciparum malaria with erythrapheresis].

Ten days after his return from Cameroon, a twenty-six year old Frenchman, serving on voluntary service overseas, presented with fulminant falciparum malaria: shock, altered consciousness, haemolytic anaemia, threatening disseminated coagulation (platelets less than 150 X 10(-6).l-1; prothrombin time and Stuart factor less than 50%; fibrinogen less than 1.5 g.l-1). In spite of quinine therapy, parasitaemia increased from 4 to 35% within 24 h. Using an Haemonetics V50, the exchange of one and a half red blood cell masses was carried out with 17 red blood cell packs. Calcium gluconate was used to prevent the hypocalcaemia induced by the anticoagulant solution. The patient's platelets and plasma were completely reinjected. The result was very satisfactory. This kind of exchange, well tolerated clinically and biologically, would seem better than the classical exchange transfusion. When 10% of the red blood cells are infected by Plasmodium falciparum, it is necessary to exchange from one and a half to two blood masses. Lesser exchanges are always associated with important relapses and quinine therapy must be carried on during and after the exchange. Restricting this exchange only to red blood cells enabled the patient to benefit from his own coagulation factors, antibodies and platelets, and consequently to reduce the number of blood donors involved. However, metabolites (especially bilirubin and circulating immune complexes) were not eliminated. Partial plasmapheresis may be associated with erythropheresis using human albumin as plasma substitute. This technique needs to be assessed, in order to optimize immediate efficiency and post-transfusion infectious risk.

Adult↗

[Effects of different loading solutions on plasma osmolality].

OBJECTIVE: As hydratation of the normal brain is much more dictated by osmotic gradients than by hydrostatic or oncotic pressures, this study aimed to compare the effect of the infusion of currently used volume loading solutions on plasma osmolality. STUDY DESIGN: Randomized, comparative trial. PATIENTS: Thirty ASA 1-2 patients, scheduled for lumbar intervertebral disc surgery were randomly allocated to three groups receiving either 2,000 mL of lactated Ringer's solution (RL, n = 10), 750 mL of hydroxyethylstarch 6% (HEA, n = 10) or 2,000 mL of normal saline (NaCl, n = 10). METHODS: Baseline osmolality, natraemia, glycaemia and protidaemia were measured before induction of anaesthesia (T1), after the infusion of 375 mL of hydroxyethylstarch or 1,000 mL of crystalloids (T2) and at the end of the infusion (T3). RESULTS: The three groups were identical for age, weight, initial plasma osmolality and natraemia. However, osmolality in the RL group was decreased at T2 and T3 compared to T1 (respectively: 299 +/- 5 mOsm.kg-1, 295 +/- 4 mOsm.kg-1 and 292 +/- 5 mOsm.kg-1. Osmolality at T2 and T3 was also lower in the RL group compared to the HEA and NaCl groups (respectively: 301 +/- 6 mOsm.kg-1 and 304 +/- 13 mOsm.kg-1 for T2 and T3 in the HEA group, and 299 +/- 5 mOsm.kg-1 and 298 +/- 5 mOsm.kg-1 in the NaCl group). In the HEA and NaCl groups, osmolality was unchanged at T2 and T3 compared to T1. CONCLUSION: Both normal saline and hydroxyethylstarch 6% maintain plasma osmolality, whereas Ringer lactate tends to decrease it. For that reason normal saline and hetastarch 6% but not lactated Ringer's solution, may be administered in patients experiencing blood-brain barrier damage.

Blood Glucose↗

Evaluation of a new hydroxyethyl starch solution (HES 130/0.4) in patients undergoing preoperative autologous blood donation.

STUDY OBJECTIVE: To compare the tolerance and efficacy of the new hydroxyethyl starch (HES) 130/0.4 with a current HES solution (HES 200/0.5) in patients undergoing preoperative autologous blood donation as a model of surgical blood loss. HES 130/0.4 is expected to be a plasma substitute as efficacious as current HES solutions while offering such advantages as more complete renal elimination and reduced tissue storage. DESIGN: Controlled, randomized, double-blind, phase II clinical trial. SETTING: 1500-bed university hospital. PATIENTS: 60 ASA physical status II and III patients scheduled for elective cardiac and noncardiac surgery, and meeting selection criteria for autologous blood donors. INTERVENTIONS: Collection of 500 mL of blood with simultaneous intravenous (IV) infusion of 500 mL of either HES 130/0.4 or HES 200/0.5 (mean molecular weight 130 kD and 200 kD, degree of substitution 0.4 and 0.5, respectively). MEASUREMENTS: Noninvasive measurements of heart rate and arterial blood pressure were obtained every 5 minutes until 1 hour after blood donation and infusion of the study drugs; laboratory studies (complete blood counts, electrolytes, markers of renal and liver function) were performed; and follow-up assessment of adverse events was undertaken by questionnaire 24 hours after blood donation and infusion of the study drugs. MAIN RESULTS: Both hemodynamics and laboratory test results did not differ significantly between the groups at any time. Hemodynamics remained stable in each group, and no adverse event was observed in any patient until one hour after blood donation and infusion of the study drugs. Adverse events elicited by postphlebotomy questionnaire were mild and probably unrelated to HES infusion. CONCLUSIONS: Intravenous infusion of 500 mL of the new HES 130/0.4 was tolerated well and maintained cardiovascular stability in patients undergoing preoperative autologous blood donation. HES 130/0.4 proved equivalent to HES 200/0.5 in every measured respect. Its pharmacokinetic profile may render HES 130/0.4 an attractive alternative to current HES solutions.

Adult↗

Preoperative autologous plasmapheresis--9 years experience in orthopedic surgery.

Since nine years preoperative autologous plasmapheresis (PPH) is an essential part of a comprehensive autologous transfusion program in the Rehabilitation Hospital/Orthopedic University Clinic of Ulm. After v. Finck's recommendation in 1984 we started plasma-predeposit by centrifugation-plasmapheresis (PCSR, Haemonetics Comp.) in all elective orthopedic-surgical patients expecting a blood loss > 1,000 ml. Primarily this procedure was used for intra- and postoperative hemostasis stabilization and for having the ideal component to recomplete the harvested red cells by the Cell SaverR to full blood units. By clinical experience the strategy of routinely combining plasma-predeposit and wound-blood salvaging instead of full blood- or red cell's-predeposit was recognized as not only being highly effective in saving of banked blood but furthermore as being the best way of getting free from all time related problems due to the limited preservation period of red cells because donated platelet poor plasma (PPP) can easily be frozen and stored up to one year at least. In addition there is one more decisive aspect in favour of autologous fresh frozen plasma (AFFP): it may be used for the best and most physiological kind of volume replacement. In combination with a short acting artificial plasma substitute (e.g. Polygelin) for intraoperative replacement AFFP is best suitable for reestablishing and maintaining postoperative normovolemia which is essential for any kind of hemodilution practicing like we routinely do when accepting low hemoglobin concentrations (> 7,0 g/dl) to avoid homologous blood transfusions and to reduce the risk of thromboembolic complications at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion, Autologous↗

Acute hypervolemia lengthens red cell pulmonary transit time during exercise in endurance athletes.

The purpose was to determine if acute plasma volume expansion (PVE) changed red-cell pulmonary transit time (PTT) during severe exercise. Twelve endurance athletes performed 6.5 min of severe cycling exercise on different days. Pentaspan [(500 ml, infusion condition, I] or placebo [(60 ml saline), non-infusion condition, N] were infused prior to exercise. Blood gas tensions, PTT, multigated acquisition (MUGA) derived cardiac output, and oxygen uptake were measured during exercise. PTT was measured during minute 3 of exercise by radionuclide cardiography. Arterial P(O(2)) (Pa(O(2))), and alveolar-arterial oxygen pressure difference (AaD(O(2))) at minute 3 of exercise did not differ between conditions. Mean PTT at minute 3 of exercise was 0.3 sec longer in the I condition (P=0.002). However, the change in PTT between conditions was not correlated to the change in either Pa(O(2)) or AaD(O(2)). We conclude that PVE slows (lengthens) PTT without affecting pulmonary gas exchange. Therefore, rapid PTT may not be related to hypoxemia during exercise.

Animals↗

Initial distribution volume of glucose is correlated with intrathoracic blood volume in hypovolaemia and following volume loading in dogs.

BACKGROUND AND OBJECTIVE: Initial distribution volume of glucose (IDVG) reliably measures the central extracellular fluid volume in the presence of fluid gain or loss. We hypothesized that IDVG has a close relationship with intrathoracic blood volume (ITBV), which has recently been used as an indicator of cardiac preload. We therefore examined whether IDVG can correlate with ITBV in various fluid volume states. METHODS: Fourteen anaesthetized mongrel dogs were mechanically ventilated. ITBV and cardiac output were measured by single transpulmonary thermodilution technique. IDVG and indocyanine green derived plasma volume (PV-ICG) were determined by the administration of 100 mg kg(-1) glucose and 0.5 mg kg(-1) indocyanine green solutions, respectively, and calculated by applying a one-compartment model. Three sets of measurements were performed before and after haemorrhage (30 mL kg(-1) and subsequent fluid volume loading (90 mL kg(-1) of lactated Ringer's solution). RESULTS: A linear correlation was observed between IDVG and ITBV (r2 = 0.52, n = 42, P < 0.001) and between PV-ICG and ITBV (r2 = 0.44, n = 42, P < 0.001) throughout the procedures. A linear correlation was also observed between changes in IDVG and those in ITBV (r2 = 0.76, n = 28, P < 0.001). The ITBV/IDVG ratio during normovolaemia was 0.26 +/- 0.04, which remained unchanged during the procedure. CONCLUSION: Results showed that that IDVG has a linear correlation with ITBV, and support the concept that IDVG measurement has potential as a surrogate measure of ITBV in various fluid volume states.

Animals↗

Transfusion therapy during war and peace in Sarajevo.

OBJECTIVE: To investigate surgical blood usage during the siege of Sarajevo. METHODS: Data on blood usage and pre-transfusion hematocrit (Hct) values from blood transfusion request forms in 250 wartime emergency surgical procedures during August through October 1992 (experimental group), and in 146 peacetime elective surgical procedures (control group) during April through June 1991 at the State Hospital of Sarajevo, were reviewed. RESULTS: The mean number of blood units transfused per patient (blood usage rate) was 1.13 in the experimental group versus 2.56 in the control group (p < 0.001). During the war, for blood conservation, normovolemic hemodilution was practiced widely. A significantly lower mean pre-transfusion Hct value of 0.21 was observed in the experimental group versus 0.27 in the control group (p < 0.001). CONCLUSION: Blood-usage rate was lower during emergency surgical procedures in war than during elective surgical procedures in peacetime without apparent adverse patient outcome. This decrease in blood-usage rate in the face of increased numbers of trauma victims was the result of a planned blood-conservation program which included: stringent blood-usage criteria, and widespread implementation of casualty resuscitation using normovolemic hemodilution with colloid and crystalloid plasma substitutes.

Adult↗