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Hypervolemic hemodilution: an alternative to acute normovolemic hemodilution? A mathematical analysis.

BACKGROUND: Hypervolemic hemodilution has been proposed as an alternative to normovolemic hemodilution to reduce homologous blood transfusions. So far, convincing data supporting this concept are unknown. MATERIALS AND METHODS: We therefore present a mathematical model calculating the efficacy of hypervolemic, normovolemic, and "no" hemodilution. Hypervolemic hemodilution constituted volume expansion (20% of estimated blood volume) maintained throughout surgery. Normovolemic hemodilution contained isovolemic exchange of blood (40% of estimated blood volume) vs colloid as well as retransfusing blood plus colloid to maintain minimal acceptable hematocrit, e.g., transfusion trigger. To determine the efficacy of each technique maximal allowable blood loss and final postoperative hematocrit were calculated. Maximal allowable blood loss referred to the amount of blood lost during surgery after which homologous blood transfusion became necessary. RESULTS: Recalculating published clinical data strongly validated the formulas used for our model. Hypervolemic hemodilution always revealed lowest maximal allowable blood losses. Normovolemic hemodilution constantly ensured highest maximal allowable blood losses. For blood losses <40% of blood volume, hypervolemic and normovolemic hemodilution provided almost identical final postoperative hematocrits. But in contrast to normovolemic hemodilution, hypervolemic hemodilution did not carry the risk of severe transient, retransfusion-induced hypervolemia. "No" hemodilution always gave lowest final postoperative hematocrits. CONCLUSIONS: Thus, hypervolemic hemodilution cannot replace normovolemic hemodilution to reduce homologous transfusions, but for blood losses <40% of blood volume hypervolemic hemodilution appears to be superior.

Blood Loss, Surgical

[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

A computer model comparing normovolemic hemodilution, hypervolemic hemodilution, and neither on intraoperative blood loss and final hematocrit.

Homologous blood transfusion, while frequently life-saving, is attended by risks and complications. Autologous blood transfusions have become an increasingly common alternative. Volume expansion, which is simpler, also is used. This study was designed to construct computer models of hypervolemic hemodilution and normovolemic hemodilution to compare them with each other and with normal (neither hypervolemic nor normovolemic hemodilution). Each model started with blood volume (BV) equal to 5,000 mL. Initial hematocrits (HCTs) were varied from 25% to 50%. Following phlebotomy and hemodilution or volume expansion, which ranged from 0 to 2,500 mL (50% of initial BV), the models were then bled 250 to 2,500 mL (5% to 50% of initial BV). In the phlebotomy model, the autologous blood was then returned. Final HCTs were then calculated. Preoperative phlebotomy of 500 to 1,000 mL, an amount commonly withdrawn, provides a minimally higher final HTC. Volume expansion by hypervolemic hemodilution provides almost the same low level of benefit. Benefits (3% higher HCT) are not seen until larger volumes are phlebotomized or hemodiluted and accompanied by large intraoperative blood losses. Autologous blood drawn by preoperative phlebotomy for intraoperative transfusion should not be used until studies show that these large volumes are safe and actually save blood.

Blood Loss, Surgical

[Evaluation of the tolerance to hemorrhagic shock--comparison between hemodilution and non-hemodilution].

We induced various degrees of bleedings in adult mongrel dogs to determine their tolerance to bleedings. The dogs were divided into two groups: the hemodilution group (Group A: Hct 11.1 +/- 1.9%) and the non-hemodilution group (Group B: Hct 36.8 +/- 6.6%). The Group A tended to show higher tolerance to bleedings than the Group B, although the difference was not significant. Throughout the period of increasing degrees of bleedings, MAP remained higher in Group B than in Group A, but CI was higher in Group A than Group B. DO2I was kept higher in Group B than in Group A. Both PaO2 and PaCO2 showed no difference between the two groups. The results of our study indicate that hemodilution group tends to be more tolerant to bleeding than non-hemodilution group. The reason is probably that under hemodilution the oxygen delivery is maintained through an increase in cardiac output in the presence of decreased arterial oxygen content. In addition, it is considered that the safety is obtained through various factors such as preferential blood distribution to important organs (in particular to the myocardium), more efficient extraction of oxygen from the blood, and the decreased work load resulting from a reduced blood viscosity.

Animals

Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs.

BACKGROUND: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system. STUDY DESIGN AND METHODS: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an intraoperative volume-compensated blood loss was simulated. The efficacy of three therapeutic regimens in maintaining tissue oxygenation was compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of autologous RBCs; 2) PFC group (n = 7): bolus application of a second-generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and tissue oxygenation were assessed. RESULTS: Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood loss. In the PFC and control groups, heart rate and cardiac index increased significantly in response to further ANH. Tissue oxygenation was not different in the PFC and the RBC groups. Direct comparison of the PFC and control groups revealed better tissue oxygenation in the PFC group, as reflected by significantly higher mixed venous, coronary venous, and local tissue pO2 on liver and skeletal muscle. CONCLUSION: Bolus intravenous administration of 60-percent (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to one of 3 g per dL were as effective as autologous RBC transfusion in maintaining tissue oxygenation during volume-compensated blood loss designed to mimic surgical bleeding.

Animals

Preoperative acute hypervolemic hemodilution with hydroxyethylstarch: an alternative to acute normovolemic hemodilution?

Acute normovolemic hemodilution (ANH) may help to reduce demand for homologous blood but requires extra time and apparatus. A more simple procedure is acute hypervolemic hemodilution (HHD), where hydroxyethylstarch is administered preoperatively without removal of blood. In a prospectively randomized study we compared ANH (preoperatively 15 mL/kg autologous blood removal and replacement with 15 mL/kg of hydroxyethylstarch with HHD (15 mL/kg of hydroxyethylstarch administered preoperatively) in 49 patients undergoing hip arthroplasty. To avoid excessive intravascular volume, we used the vasodilating effect of isoflurane. No significant differences were found between groups (ANH, n = 23; HHD, n = 26) for intraoperative blood loss (ANH versus HHD, median [minimum-maximum]); 545 [295-785] mL versus 520 [315-825] mL) and postoperative blood loss (730 [525-945] mL versus 780 [495-895] mL), postoperative hemoglobin, hemotocrit, platelet count or coagulation variables, and transfusion requirements (ANH 43% versus HHD 35% of patients received homologous blood) (P > 0.05). Heart rate did not change significantly in either group. In the ANH group mean arterial blood pressure (MAP) decreased after hemodilution (P < 0.05) while in the HHD group MAP did not change over time. Mean time required to perform ANH was 58 (46-62) min versus HHD 16 (12-19) min (P < 0.05). Costs for ANH were $63.60 USD and for HHD $32.75 USD (labor costs not included). In orthopedic patients undergoing hip replacement with a predicted blood loss of about 1000 mL, HHD seems to be a simple as well as time- and cost-saving alternative for ANH.

Adult

Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. The Hemodilution in Stroke Study Group.

Patients with acute ischemic stroke were randomized less than 24 hours after onset to standard (S) therapy (n = 43) or to hypervolemic hemodilution (HH) with pentastarch (n = 45). The therapeutic goal of hypervolemic hemodilution was to rapidly reduce hematocrit to 33%, to raise cardiac output, and to continue hypervolemic hemodilution for 3 days. A graded neurologic examination was scored by a blinded observer at randomization (baseline), at the end of treatment or after 72 hours, and at a 3-month follow-up; each patient was also rated using Barthel's disability scale at the 3-month follow-up. Group demographics and results of the graded neurologic examination were similar at baseline, except that the HH group contained twice the number of patients with severe strokes and fewer patients randomized within 12 hours compared with the S group. The HH group improved an average of 7 points in neurologic score from baseline to the end of treatment (the S group deteriorated 1 point) and 24 points by the 3-month follow-up (the S group improved 16 points; p = 0.11). The HH group reached an average Barthel disability scale index of 85 while the S group averaged 70 (p = 0.8). Deaths associated with cerebral edema occurred in five patients with severe stroke (four in the HH group vs. one in the S group, p = 0.36). The following subgroups of HH patients showed better overall improvement in neurologic scores: patients entered within 12 hours after stroke onset, patients with a 15% decrease in hematocrit, and patients with a 10% increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial (MAHST).

BACKGROUND AND PURPOSE: Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS: MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial. RESULTS: Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event. CONCLUSIONS: Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.

Aged

[Perfusion changes in hemodilution. The effect of extensive isovolemic hemodilution with gelatin and hydroxyethylstarch solutions on cerebral blood flow velocity and cutaneous microcirculation in humans].

OBJECTIVE: Quantifying the influence of extreme isovolemic hemodilution (NH) with different colloids on cerebral blood flow velocities (transcranial Doppler sonography) and cutaneous microcirculatory blood flow (laser Doppler flowmetry) in healthy, non-premedicated volunteers was the aim of this study. METHODS: In seven volunteers (randomized cross-over design) 20 ml/kg blood was withdrawn within 30 min and simultaneously replaced with 6% hydroxyethyl starch (200,000/0.5, HES) or 3% gelatin (GEL). Thirty minutes later, the autologous blood was retransfused (RT) within 30 min. Due to a severe allergic reaction to gelatin in one volunteer, only 6 GEL-NH were evaluated. Recorded parameters were: mean blood flow velocities (Vm-MCA) as well as the pulsatility index (PI) and the resistance index (RI) over the middle cerebral artery. In addition laser Doppler flux (FLUX), cell velocity (SPEED), mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb) and hematocrit (Hc) were monitored. RESULTS: NH resulted in a withdrawal volume of 1498 +/- 85 ml (HES) and 1493 +/- 95 ml (GEL), (mean +/- SD) and induced a decrease in hemoglobin from 40.9 to 29.0% (HES) and from 39.8 to 30.0% (GEL). RT increased Hc to 34.2% (HES) and 34.5% (GEL). MAP and HR showed no significant alterations in both groups. Following NH, Vm-MCA rose almost the same way in either case (26% HES), 21% (GEL), but decreased continuously again during RT. After completing RT, only in the HES group Vm-MCA still remained higher than baseline values (14% HES, only 3% GEL). Similar inverse regression lines were found for the two groups between Hc and Vm-MCA: [Vm-MCAHES (cm/s) = -1.27 x Hc + 110.9; r = 0.98, P < 0.001 and Vm-MCAGEL (cm/s) = -1.32 x Hc + 110.9; r = 0.91, P < 0.001]. Furthermore, as a result of NH, FLUX and SPEED increased about 61% and 38% in the HES group and remained on higher values in comparison with starting positions (21% FLUX, 13% SPEED). However, the results in the GEL group were of a different kind: FLUX and SPEED increased stupendously to 291% and 114% combined with NH, but both were reduced by RT on a large scale (39 and 27% below baseline values). Whereas RI showed no group differences, there was a remarkable drop in PI during RT (17% HES, 12% GEL). CONCLUSION: The two plasma expanders studied show a close inverse correlation between the alterations of blood flow velocities in the middle cerebral artery and systemic hemoglobin and hematocrit values. In both groups the change in blood flow velocities is comparable. For the first time the results of relative changes in blood flow velocities following hemodilution and retransfusion in healthy volunteers are described that correspond closely by relative cerebral blood flow alterations found in animal studies as well. Moreover, a non-linear correlation of cutaneous microcirculation was shown by means of HES, but also by GEL. Obviously, there was the GEL group to be responsible for pronounced differences in cutaneous circulation.

Adult

[Hypervolemic hemodilution as a means of preventing homologous blood transfusion. A simple alternative to acute normovolemic hemodilution].

PROBLEM: Acute normovolenic hemodilution (ANH) is timeconsuming and complicated, and has only a small effect in reducing the need for homologous blood. A simpler procedure is hypervolemic hemodilution (HHD). In the present prospective, randomized study, HHD is compared with ANH for its blood-saving effect. STUDY DESIGN: Forty-nine patients undergoing total hip replacement were admitted. Group I (ANH): Withdrawal of 15 ml/kg bodyweight autologous blood and isovolemic replacement by hydroxyethyl starch (200/0.5). Group II (HHD): Infusion of 15 ml/kg bodyweight hydroxyethyl starch (200/0.5). RESULTS: No significant differences were found between the groups in terms of Hb, hematocrit and coagulation. The blood loss (intra-operative+drainage losses) was comparable in the two groups at 1274 +/- 310 ml (HHD) and 130 +/- 335 ml (ANH). During the period under investigation, 66% of the patients in the HHD group and 57% in the ANH group required no homologous blood. CONCLUSION: HHD is just as effective as ANH for reducing homologous blood requirements, and is much simpler to apply.

Blood Loss, Surgical

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