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[Studies on extracorporeal circulation with large volume hemodilution using lactate ringer's solution and low molecular weight dextran: alterations of acid-base balance associated with intentional hemodilution (author's transl)].

Twenty mongrel dogs, weighing between 7.5 and 13.0 kg were used to investigate the percentage limits permissible for hemodilution using a double-helical reservoir heart-lung machine which has a 1,100 ml of priming volume. In both 40 and 50 per cent groups of intentional hemodilution by 30 minute extracorporeal circulation, remarkable anemia was inevitable and recovery was extremely slow, especially in the 50 per cent dilution group. In both 40 and 50 per cent groups of intentional hemodilutions by 30 minute extracorporeal circulation, metabolic acidosis was observed. In 50 per cent group of intentional hemodilution, no improvement of metabolic acidosis was observed even after perfusion. When sodium bicarbonate was administered to 40 per cent hemodilution group, minimum alterations of acid-base balance and of serum electrolytes were observed during and after extracorporeal perfusion. When sodium bicarbonate was administered to 50 per cent hemodilution group, metabolic acidosis was more evident than in 40 per cent hemodilution group accompanied with an increase in serum sodium concentration and a decrease in serum chloride concentration. These data qualify the use of 40 per cent intentional hemodilution using Lactate Ringer's solution or low molecular weight dextran for 30 minute extracorporeal circulation when sodium bicarbonate is administered in adequate amounts.

Acid-Base Equilibrium

High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants.

Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants.

Age Factors

[Clinical hemodilution].

UNLABELLED: Acute hemodilution has been performed in 46 patients immediately before major gastrointestinal surgery. Clinical, hemodynamic, respiratory and metabolic parameters have been studied and compared with results in 66 patients, submitted to similar operations under equal conditions without hemodilution. Two kinds of hemodilution have been used: normovolamic hemodilution by bloodexchange with 5% human albumin and moderate hypervolamic hemodilution by bloodexchange with equal parts of Dextran 60 and PPL. RESULTS: 1. The first mentioned kind of hemodilution and method of blood-exchange was superior in regard to stability of cardiovascular behavior. 2. The general tolerance of anesthesia and surgical trauma was superior in the nonhemodiluted group, but was good or tolerable also in the hemodiluted group in 82,6%. Side effects, more frequently and more pronounced in the hemodiluted group concerned to hypo- and hypertensive reactions, vasoconstriction, hypokaliemie and cardial arrhythmics. Exclusively in the hemodiluted group ST-lowering in the EKG has been stated in some patients. These reactions have been estimated as a sign of marginal compensatory capacity in the individual cardial situation and were reversibel by blood transfusion. These observations strengthen the necessity for accurate monitoring in hemodiluted patients. Moreover it is recommended to restrict hemodilution in the level of Hk 27-28%. Under these conditions acute normovolamic hemodilution is recommended further for a wider clinical use.

Abdomen

Hemodynamic and metabolic consequences of hemodilution with different diluents.

Hemodilution was performed with the crystalloid Ringer's lactate (n = 6) and the colloid Haemaccel (n = 5) in dogs during automatically controlled total cardiopulmonary bypass with constant arterial and venous pressures. Single observations were made with Macrodex and Rheomacrodex hemodilution. Hemoglobin concentration and hematocrit were used as parameters for hemodilution. Total plasma protein proved to be unsuitable. The volume needed to induce the same level of hemodilution with lactated Ringer's and Haemaccel was twice the volume needed with Macrodex and Rheomacrodex. The volume shift from intravascular to extravascular was larger during Ringer's lactate hemodilution than during Haemaccel hemodilution. The amount of volume shift was clearly related to changes in colloid osmotic pressure. Lowering of total peripheral vascular resistance, with increased arterial line flow during controlled constant arterial and venous pressures was seen during hemodilution with each of the above materials. Potassium and calcium concentrations in the blood increased significantly during hemodilution with Haemaccel. Base excess was constant during hemodilution with lactated Ringer's but decreased in all other cases. A decrease in oxygen consumption was common, and most pronounced during hemodilution with Haemaccel.

Animals

A randomized trial of perioperative hemodilution versus transfusion of preoperatively deposited autologous blood in elective surgery.

Hemodilution, one of several methods proposed to decrease homologous blood transfusion in elective surgery, has not been studied in a prospective controlled trial to determine if it is successful. A prospective, randomized controlled study was conducted to determine if hemodilution can serve as an alternative to preoperative autologous blood donation. Fifty patients were randomized to preoperatively deposit 3 units of autologous blood or to undergo hemodilution immediately before elective radical retropubic prostatectomy. All patients were treated under a standard protocol, including surgery performed by a single surgeon. The preoperative deposit groups received a mean of 2.44 +/- 1.0 units of blood; 2 of 25 patients required homologous blood transfusion for blood loss of 2600 mL and 1700 mL. The hemodilution group received a mean of 2.88 +/- 0.4 units of autologous blood: no hemodilution patient received homologous blood. At discharge, the mean hematocrit for the preoperative deposit group was 35.5 +/- 4.9 (0.35 +/- 0.05), and that for the hemodilution group was 31.8 +/- 4.7 (0.32 +/- 0.05) (p less than 0.001). There were no differences in perioperative morbidity in the treatment groups. The best predictor of discharge hematocrit was the initial hematocrit of the patient. It can be concluded that hemodilution can safely replace or at least augment preoperative autologous donations as a means of decreasing homologous blood transfusion in study patients. These results can be applied to any elective surgery procedure in which a 1000-mL blood loss is anticipated. Other advantages of hemodilution, including convenience, lower cost, and better preservation of all components of autologous blood, suggest that this practice deserves wider application.

Blood Transfusion, Autologous

Evaluation of long-term outcome and safety after hemodilution therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: In a previous single-center, randomized controlled trial including 102 patients treated in a stroke unit, we showed that rapid, modest hemodilution improved short-term clinical outcome in ischemic stroke patients. I now evaluate the long-term outcome and potential risks of this combined venesection/dextran 40 therapy in the same 52 treated and 50 control patients. METHODS: Mortality, need for institutional care, and recurrent strokes were registered during 1 year following inclusion in the trial, and a final evaluation of functional outcome was performed at 12 months after the stroke. Cerebrospinal fluid was analyzed for protein content and hemorrhagic admixture at two occasions during the acute phase. RESULTS: Thirty-six hemodiluted and 30 control patients survived the first year following the stroke (difference not significant). One year after the stroke, persistent neurological deficits were less frequent among the hemodiluted patients and a larger proportion of hemodiluted survivors was independent in walking (92% versus 73%, p less than 0.05). Two hemodiluted patients (6%) and nine control patients (30%) were totally dependent in the activities of daily living (p less than 0.05). Three hemodiluted patients (8%) and eight control patients (27%) remained hospitalized 1 year after the stroke (p less than 0.05). With the possible exception of patients with a medical history of congestive heart failure, subset analyses revealed a tendency toward improved outcome for hemodiluted patients in all clinically important subgroups compared with the controls. When analyzing cerebrospinal fluid, signs of blood-brain barrier breakdown and hemorrhagic admixture to the cerebrospinal fluid during the acute phase were less frequent in the hemodiluted subjects. CONCLUSIONS: These results suggest that, when applied in a stroke unit, the combination of venesection and dextran 40 administration is a clinically safe, therapeutic regimen in the treatment of acute cerebral infarction that improves long-term clinical outcome.

Activities of Daily Living

The effects of cardiopulmonary bypass with crystalloid and colloid hemodilution on myocardial extravascular water.

The effect of cardiopulmonary bypass (CPB) on myocardial extravascular water (MEW) was evaluated with crystalloid and colloid hemodilution. Heart water was measured gravimetrically and by the double-indicator and thermal methods. CPB without hemodilution resulted in a 5.7 per cent increase in the wet : dry weight ratio of the left ventricle obtained by desiccation to stable weight. CPB with colloid hemodilution to a hematocrit of 10.7 +/- 0.4 per cent resulted in a 5.4 per cent increase in the wet:dry weight ratio. Crystalloid hemodilution to a hematocrit of 9.5 +/- 0.8 per cent resulted in a marked increase in myocardial water with a wet:dry weight ratio 30.3 per cent greater than the controls. Hypothermic (22 degrees C.) crystalloid hemodilution resulted in a 37.4 per cent increase in the wet:dry weight ratio. MEW was also measured by the double-indicator method with Evans blue dye and tritiated water. This method measured 85 per cent of the gravimetrically measured water. Although it indicated the increase in heart water in the crystalloid group, it proved less reliable in the measurement of MEW in this dynamic situation. The thermal heart water was also measured with an impedance and thermistor-bearing catheter similar to that used to measure thermal lung water. This proved ineffective in measuring heart water. Colloid hemodilution was thus found to prevent the development of myocardial edema which occurred with crystalloid hemodilution (p less than 0.01) with and without hypothermia. These findings support the addition of colloid to the hemodilution prime used for cardiopulmonary bypass.

Animals

Mechanism of cerebral blood flow augmentation by hemodilution in rabbits.

BACKGROUND AND PURPOSE: Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. METHODS: Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. RESULTS: In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. CONCLUSIONS: Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia.

Animals

Redistribution of red blood cell flow in microcirculatory networks by hemodilution.

The effect of isovolemic hemodilution on red blood cell flow distribution was studied in complete self-contained microvessel networks of the rat mesentery. Hematocrit, diameter, and length of all vessel segments as well as the topological structure were determined in control networks (systemic hematocrit, 0.54) and after hemodilution (systemic hematocrit, 0.30). Hemodilution was performed by exchanging blood with hydroxyethyl starch (MW 450,000; 6%) or homologous plasma. With hemodilution, the decrease of microvessel hematocrit exceeded that of systemic hematocrit. The average discharge hematocrit in capillaries was 79% of systemic hematocrit in the control group and 73% with hemodilution (p less than 0.001). The heterogeneity of capillary hematocrit within the network, expressed by the coefficient of variation, increased from 0.4 to 0.7. By using the morphological and topological data of four networks, the distribution of hematocrits was also calculated using a hydrodynamic flow model. The modeling results were found to be in close agreement with the experimental data. This indicates that the observed changes can be deduced from established rheological phenomena, most of all phase separation at arteriolar bifurcations. The changes in hematocrit distribution after hemodilution are accompanied by a redistribution of red blood cell flow within the network: relative to total red blood cell flow, red blood cell flow in the distal capillaries of the network increases by about 40% at the expense of the proximal capillaries that are close to the feeding arteriole and that exhibit the highest red blood cell flow under control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Influence of normovolemic hemodilution on the respiratory and circulatory systems].

We studied respiratory and circulatory kinetics of normovolemic hemodilution in adult mongrel dogs. The dogs were divided into two groups; Dextran-40 (group A) and SALIN-HES (group B). No difference in PaO2 and PaCO2 was noted between the two groups. MPA and CI during normovolemic hemodilution were higher in group A than in group B. However, MPA, Qs/Qt and ETVI during normovolemic hemodilution were largely influenced in group A. L/P during normovolemic hemodilution was more influenced in group B than in group A. The compensatory effect with increase of the cardiac output during normovolemic hemodilution was noted until S3 (Hct = 10%), but it was not noted at S4 (Hct = 5%) and S5 (just before death). SvO2 is the most sensitive index indicating the risk of normovolemic hemodilution.

Animals

The effects of mild normovolemic hemodilution on regional flow, oxygenation, and small vessel blood content in the rabbit heart subjected to acute coronary occlusion.

The effect of mild hemodilution (hematocrit, 19%) on ischemic and nonischemic regions of myocardium during acute coronary occlusion was studied in 41 pentobarbital-anesthetized, open-chest New Zealand white rabbits. Blood flow in the control area determined with radioactive microspheres was unaffected by occlusion and increased 61.8% following hemodilution. The endo/epi ratio remained at about 1.0. Occlusion decreased flow in the affected region to 41% of the control myocardium, and endo/epi ratio decreased significantly to 0.76. Hemodilution raised flow in this area 84.3%. Occlusion increased small vessel blood content (a measure of open capillary density) in the ischemic region significantly. Hemodilution further significantly increased this volume in the occluded area, although the increase in the control region was not significant. Relative tissue pO2, measured polarographically, declined significantly following occlusion in the affected area. Isovolemic hemodilution did not affect relative O2 tension in either area. The data indicate that during mild hemodilution, the O2 supply-demand status of both the occluded and nonoccluded myocardial regions is maintained.

Animals

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

Lung water accumulation with acute hemodilution in dogs.

Extravascular lung water content was determined in vivo, gravimetrically, and histologically in severely hemodiluted (Ringer's lactate), supine, spontaneously breathing, halothane-anesthetized dogs. One group of dogs was studied immediately after undergoing hemodilution to a hematocrit value of less than 10 per cent; a second group was studied after hemodilution and 1 hour of circulatory maintenance with Ringer's lactate; and a third group was evaluated after hemodilution, maintenance for one hour with Ringer's lactate, and reconstitution of oncotic pressure with 75 Gm human salt-poor albumin. Lung water content was increased significantly from a normal of 3.88 Gm water per gram of dry weight to 4.70 Gm per gram of dry weight by hemodilution; it was increased further to 5.71 tgm per gram of dry weight during 1 hour of maintenance with Ringer's lactate. Reconstitution of oncotic pressure decreased the water content significantly to 4.96 and decreased the units demonstrating perivascular-peribronchial cuffing from 81 to 23 per cent. Double indication-dilution measurement of PEVW failed to reliably reflect changes in lung water. Arterial PO2 with the animals breathing 100 per cent oxygen was unchanged in all of the groups. We made the following conclusions: (1) lung water accumulation occurs during severe hemodilution and serum protein depletion; (2) this may be partially reversed by restoration of oncotic pressure; (3) double indicator-dilution PEVW measurements do not reliably reflect changes in extravascular lung water of less than 47 per cent; and (4) interstitial edema of this magnitude does not interfere with blood-gas exchange.

Animals

The effect of blood oxygen content and the no-reflow phenomenon on the subendocardial ultrastructural reversibility following anoxic arrest using hemodilution variables in the experimental model.

Hemodilution is an accepted modality for the conduct of cardiopulmonary bypass. The degree of hemodilution clinically employed has been in the range of 20 per cent of the initial hematocrit levels. This study was designed to evaluate the effects of hemoglobin levels and oxygen content on the reversibility of the damaged or altered ultrastructure of the endocardial layer of the ventricle and the possible role of the no-reflow phenomenon. Two series of mongrel dogs were subjected to cardiopulmonary bypass at normothermic levels and a standard period of ischemic arrest. One series was with hemoglobin levels between 5 and 10 grams (mean 7.25 grams) designated as moderate hemodilution (MH). The second series was of hemodilution with less than 5 grams of hemoglobin (mean 4.8 grams) designated as severe hemodilution (SH). The ultrastructural alteration gradient (UAG) between the epicardium and endocardium was studied with its relationship to reversibility of myocardial function and animal survival. The study demonstrated a definitive relationship between oxygen content and the reversibility of myocardial damage under normothermic conditions and anoxic arrest. The poor survival results in the SH group; two of 12 are attributed to the low oxygen availability possibly triggering the no-reflow phenomenon which prevents reversibility of the myocardial ultrastructural damage and ultimately the functional integrity of the ventricle.

Animals

The effects of isovolumic hemodilution on ocular blood flow.

Techniques by which retinal blood flow may be increased safely are potentially important in the treatment of retinal vascular disease. It was hypothesized that hemodilution, which increases cerebral blood flow, would also increase retinal blood flow. To investigate the physiological effects of hemodilution in the eye, ocular blood flow was measured in 14 cats using the radioactively labeled microsphere method. After the animals were anesthetized with halothane and oxygen, intraocular and systemic arterial pressure were recorded; blood flows were measured before and after isovolumic hemodilution to a hematocrit of 20-22% using 6% hydroxyethyl starch (a synthetic plasma expander with a molecular weight of 450 in 0.9% saline). In hemodiluted cats, retinal blood flow increased 71% from its baseline value (36.7 +/- 6.4 ml 100 g-1 min-1 to 62.9 +/- 6.4 ml 100 g-1 min-1, mean +/- S.E.M., P < 0.0001). Calculated retinal O2 delivery remained approximately constant, as the increased blood flow countered a significant decrease in arterial O2 content. Choroidal blood flow decreased (1297 +/- 140 ml 100 g-1 min-1 to 1051 +/- 144 ml 100 g-1 min-1) but the change was not statistically significant. Blood flows in the iris and sclera were not significantly altered. Hemodilution increased retinal blood flow without causing a redistribution in ocular blood flow.

Animals

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF.

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0-10 and 11-20 ml 100 g-1 min-1. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 +/- 0.3 vs. 9/Hct, 13.6 +/- 0.4 [mean +/- SD, ml 100 g-1 min-1]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.

Animals

Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

OBJECTIVE: This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. DESIGN: Prospective, nonrandomized study. SETTING: Operating room in a university hospital. PATIENTS: Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. METHODS: Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. CONCLUSIONS: Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.

Blood Transfusion, Autologous