Level Of Hemodilution Research Articles

Clinical Implications of Detection and Clearance of Post-Induction Residual Disease in 2119 Children and Young Adults with AML: Children's Oncology Group Studies AAML0531 and AAML1031

Background: Measuring residual disease (RD) by multidimensional flow cytometry (MDF) predicts patient outcome following the first induction cycle and is a prognostic indicator in AML, particularly those patients lacking prognostic genetic lesions (i.e. standard risk; SR).Objective: To assess prevalence of RD after induction 1 (EOI1) and induction 2 (EOI2) and correlate presence of RD with clinical outcome.Patients and Methods: COG AML trials AAML0531 and AAML1031 collectively enrolled 2119 patients of whom 1929 met eligibility requirements (AAML0531, N=844, AAML1031, N=1085) and 1642 submitted a specimen for RD at the end of initial induction therapy (EOI1) and continued to subsequent therapy, while 1299 patients submitted a specimen at the end of second induction (EOI2) and continued on therapy. Detection of RD by MDF was determined with a standard panel of reagents applying a “difference from normal” algorithm (1). The clinical cutoff of the assay was 0.1% of total non-erythroid cells. The lower level of detection of the assay was 0.02% of non-erythroid cells. RD was not reported for specimens that were inadequate based on cellularity, level of hemodilution, and constitution of the myeloid compartment. COG AAML0531 and AAML1031 both utilized an MRC backbone but differed in total number of chemotherapy courses, SCT allocation and preparative regimen. Since AAML1031 includes a sorafenib treatment arm that is ongoing, all patients with FLT3/ITD-High allelic ratio were excluded from this analysis.Results: In the combined cohort of 1642 patients with validated RD data, RD was detected in 420 patients at EOI1 (25.6%) and in 110/1299 patients (8.5%) at EOI2. Overall survival from EOI1 (Fig. 1A) and EOI2 (Fig. 1B) is presented below. Actuarial 3 year OS from EOI1 was 47.8 ± 5.2% and 75.1 ± 2.6% for those with and without RD (p<0.001). Corresponding OS from EOI2 as 53.5 ± 10.6% and 74.3 ± 2.7% for those with and without RD (p<0.001). We further inquired whether clearance of RD from EOI1 to EOI2 provides clinical benefit and improved outcome. In the combined cohort, of the 248 RDpos patients at EOI1, 155 patients (62.5%) did not have detectable disease (RDpos/neg) whereas 93 patients had persistent RD (RDpos/pos; 37.5%). Correlation of clinical outcome based on clearance of RD from EOI1 to EOI2 showed that those with RD at EOI1 had similar outcomes regardless of resolution of RD at EOI2 with actuarial overall survival at 3 years from EOI2 of 54.7 ± 11.8% for the RDpos/pos vs. that of 56.4 ± 8.4% in RDpos/neg patients (p=0.755; Fig. 1C). Given that AAML0531 and AAML1031 had different second induction course of therapy, we also compared the rate of clearance of RD between the two study populations and the resultant clinical outcome. In similarly matched standard risk patients with EOI1 and EOI2 RD data, RD conversion rate (RDpos to RDneg) was 13.3% in AAML0531 vs. 17.2% in AAML1031(p=0.262). In AAML0531, those with RD clearance (RDpos/RDneg) had 3 year OS from EOI2 of 46.9 ± 17.6%, nearly identical OS of 42.4 ± 17.2% compared to those with persistent RD (RDpos/RDpos), p=0.485. Similarly, in AAML1031, those with and without RD clearance had similar OS (41.5 ± 13.4% vs. 45.6 ± 17.2%, p=0.144).Conclusions: Persistence of RD detected by MDF after one course of therapy is highly associated with adverse outcome in AML. We further demonstrate that clearance of RD from EOI1 to EOI2 is not associated with improve outcome on two sequential COG trials with similar but not identical therapy. Therefore, reducing leukemia burden after EOI1 may not translate into better survival.Reference:1) Loken MR et. al. Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children's Oncology Group. Blood. 2012 Aug 23;120(8):1581-8. [Display omitted] DisclosuresBrodersen:Hematologics Inc: Employment. Loken:Hematologics Inc: Employment, Equity Ownership.

The impact of crystalloid versus colloid on coagulation as measured by thromboelastometry in term parturients: an in vitro study

Objective A pilot study to examine the impact of crystalloid versus albumin hemodilution in vitro on coagulation using thromboelastometry in pregnant patients. Methods This prospective, observational pilot study included seventy-six pregnant patients at term (≥37 weeks) without history of bleeding or clotting disorder or on anticoagulation. Blood was collected and diluted with either Plasma-Lyte or albumin at the following levels: 0%, 20%, 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%. Thromboelastometry was performed to assess for coagulation changes. Results There was a small, statistically significant difference in the FIBTEM A5 between the Plasma-Lyte and albumin samples. However, the predicted probability of coagulopathy, using FIBTEM A5 less than 12 mm, was not different between the groups at any dilution. There was no difference in EXTEM clotting time at low-moderate levels of hemodilution. At dilutions above 40%, the albumin group had a significantly greater prolongation in clotting time compared to the Plasma-Lyte group. Conclusion When albumin is used at low-moderate levels of hemodilution in vitro in parturients there is no additional risk of coagulopathy compared to hemodilution with crystalloid. Given that colloids are frequently used to restore intravascular volume during massive hemorrhage, these results support that during early stages of hemorrhage, albumin may not contribute to additional coagulopathy beyond that of hemodilution, although further in vivo studies are needed.

Hemodilution causes glycocalyx shedding without affecting vascular endothelial barrier permeability in rats

The consequences of acute normovolemic hemodilution (ANH) following different types of fluids on the different components of the glycocalyx and on vascular barrier permeability (VBP) remain unknown. The aim of the study was to investigate whether the microcirculatory disruption and glycocalyx shedding induced by ANH alters VBP and whether this is affected by the composition and volume of the resuscitation fluid. Anesthetized Wistar albino rats (n=24) underwent stepwise ANH at hematocrit levels of 35%, 25%, 20%, and 15% induced by the exchange of blood with 6% balanced hydroxyethyl starch (1:1), balanced crystalloid (1:3), and normal saline (NS) (1:3). Glycocalyx-shed products were measured at each level of hemodilution. VBP was reflected in the decay of fluorescence dyes of different molecular size and their plasma retention ratios. Edema was assessed by measuring organ water content and muscle microcirculation by hand-held videomicroscopy. NS caused increased degradation of heparan sulfate and hyaluronan compared with the control group (P=0.003, P=0.004, respectively). Neither VBP nor tissue edema was affected by the fluid used. The total and perfused vessel densities within the microcirculation of muscle tissue decreased at hematocrit 15% in the balanced crystalloid (P=0.02) and NS groups only (P<0.0001, P=0.0003, respectively) compared with baseline. Balanced colloid solution preserved the glycocalyx layer better than balanced and unbalanced crystalloid solutions while maintaining the microcirculatory function associated with an improved total intravascular volume. Among the fluids tested, NS caused the most microcirculatory alterations. While ANH caused the degradation of glycocalyx components regardless of fluid, it did not disrupt the vascular barrier as indicated by macromolecular leakage. The results of this study provide insight into the choice of fluid for optimal perioperative fluid management and the consequences of fluid type on the vascular barrier, glycocalyx, and microcirculation.

Inflammation and coagulation following minimally invasive extracorporeal circulation technologies.

Minimally invasive extracorporeal perfusion technologies are based on the use of a minimally invasive extracorporeal circulation (MiECC) system. This includes a closed CPB circuit; biologically inert blood contact surfaces; reduced priming volume; a centrifugal pump; a membrane oxygenator; a heat exchanger; a cardioplegia system; a venous bubble trap/venous air removing device; and a shed blood management system. Some of these items, alone or in combination, are able to modify the blood activation usually elicited by cardiopulmonary bypass (CPB). The hemostatic system activation is less activated and lower degrees of thrombin generation and platelet activation have been found in numerous studies. Additionally, the reduced level of hemodilution plays an important role in preserving clot firmness after CPB with MiECC. These biochemical changes are reflected by a blood loss containment, a reduced need for allogeneic blood transfusions, and, in some studies, by a lower thromboembolic complications rate. The activation of the inflammatory cascade is in turn limited by MiECC, both directly (through a blunting of the contact-phase activation) and indirectly (through a limited thrombin generation, platelet activation, and consequent lower release of pro-inflammatory cytokines). The clinical consequences of this are mainly demonstrated by a lower rate of postoperative atrial fibrillation; other inflammation-derived outcomes appear favorably affected by MiECC (lung function, acute kidney injury) but the multi-factorial nature of these complications makes difficult to clearly attribute this pattern to a lower degree of inflammation. Overall, the existing body of evidence is in favor of MiECC with respect to standard CPB.

Gestion de la volémie durant la circulation extracorporelle en chirurgie cardiaque

The management of blood volume during major surgical procedures as cardiac surgery during extracorporeal circulation (ECC) is crucial in maintaining the homeostasis of the patient [1]. Currently, the perfusionnist has few medical or perfusion data based on the evidence (EBM and EBP) in this area. It's only the relationship between the level of hemodilution and the restriction or absence of homologous blood transfusion and mortality or postoperative morbidity that is supported by EBM and EBP [2-7]. The adequate control is not only limited to the miniaturization of the cardio pulmonary circuits ; it implies, on a practical standpoint, a circuit design and a choice of components combining safety, biocompatibility and reduced priming volume and dilution. The clinical and therapeutic constraints are dependent on the patient [8]. These ones require an analysis of the useful blood volume upstream and downstream the E.C.C. sequence [8].

Specific requirements for bloodless cardiopulmonary bypass in neonates and infants; a review

A miniaturized cardiopulmonary bypass circuit enables the safe performance, in selected pediatric patients, of bloodless open heart surgery. As the latest survival rates in neonatal and infant cardiac surgery have become satisfactory, investigators have concentrated upon the improvement of existing procedures. Institutional guidelines and multidisciplinary efforts undertaken in the pre- and postoperative periods are of great importance, concerning bloodless CPB and should be seriously pursued by all involved caregivers. This review reflects upon the selective, most relevant requirements for success of asanguinous neonatal and infant CPB: acceptable level of hemodilution during the CPB, patient preoperative hematocrit value and volume of CPB circuit. We present an assessment of practical measures that were also adapted in our institution to achieve an asanguinous CPB for neonatal and infant patients.

The effect of hemodilution during normothermic cardiac surgery on renal physiology and function: a review

Although the definitions of renal dysfunction vary, loss of renal function is a common complication following cardiac surgery using cardiopulmonary bypass (CPB). When postoperative dialysis is required, mortality is approximately 50%. CPB-accompanied hemodilution is a major contributing factor to renal damage as it notably reduces oxygen delivery by reducing the oxygen transport capacity of the blood as well as disturbing the microcirculation. To minimize hypoxemic damage during CPB, lowering of body temperature is applied to reduce the patient's metabolic rate. At present, however, temperature management during elective adult cardiac surgery is shifting from moderate hypothermia to normothermia. To determine whether the currently accepted levels of hemodilution during CPB can suffice the normothermic patient's high oxygen demand, we focused this study on renal physiology and postoperative renal function. Hemodilution reduces the capillary density through a diminished capillary viscosity, thereby, redistributing blood from the renal medulla to the renal cortex. As the physiology of the renal medulla makes it a hypoxic environment, this part of the kidney appears to be especially at risk for hypoxic damage caused by a hemodilution-induced lowered oxygen transport and oxygen delivery. In addition, hemodilution is also likely to disturb the hormonal systems regulating renal blood distribution. Clinical studies, mostly of retrospective or observational nature, show that perioperative nadir hematocrit levels lower than approximately 24% are associated with an increased risk to develop postoperative renal failure. A better comprehension of the cause-and-effect relation between low perioperative hematocrits and loss of postoperative renal function may enable more effective renal protective strategies.

Influence of Intraoperative Fluid Volume on Cardiopulmonary Bypass Hematocrit and Blood Transfusions in Coronary Artery Bypass Surgery

A hematocrit (Hct) of less than 25% during cardiopulmonary bypass (CPB) and transfusion of homologous packed red blood cells (PRBC) are each associated with an increased probability of adverse events in cardiac surgery. Although the CPB circuit is a major contributor to hemodilution intravenous (IV) fluid volume may also significantly influence the level of hemodilution. The objective of this study was to explore the influence of asanguinous IV fluid volume on CPB Hct and intraoperative PRBC transfusion. After Institutional Review Board approval, a retrospective chart review of 90 adult patients that had undergone an elective, isolated CABG with CPB was conducted. Regression analysis was used to determine if pre-CPB fluid volume was associated with the lowest CPB Hct and the incidence of an intraoperative PRBC transfusion. In separate multivariate analyses, higher pre-CPB fluid volume was associated with lower minimum CPB Hct (p&lt; .0001), and higher minimum CPB Hct was associated with a decreased probability of PRBC transfusion (p&lt; .0001). Compared to patients that received &lt;1600 mL (n= 55) of pre-CPB fluid, those that received &gt;1600 mL (n= 35) had a decreased mean low CPB Hct (22.4% vs 25.6%,p&lt; .0001), an increased incidence of a CPB Hct &lt;25% (74% vs. 38%,p= .0008) and PRBC transfusion (60% vs. 16%,p&lt; .0001), and increased median PRBC units transfused (2.0 vs 1.0,p= .1446) despite no significant difference in gender, age, patient size, baseline Hct, or CPB prime volume. Patients that received a PRBC transfusion (n= 30) received a significantly higher volume of pre-CPB fluid than nontransfused patients (1800 vs. 1350 mL,p= .0039). These findings suggest that pre-CPB fluid volume can significantly contribute to hemodilutional anemia in cardiac surgery. Optimizing pre-CPB volume may preserve baseline Hct and help limit intraoperative hemodilution.

Risk Factors Profile for Acute Kidney Injury after Cardiac Surgery Is Different According to the Level of Baseline Renal Function

Acute kidney injury (AKI) occurs frequently after cardiac surgery. Although numerous variables were identified as predictors for AKI, there is a lack of information about possible differences in risk factors according to the level of preoperative renal function. Preoperative, intraoperative, and postoperative data from 4118 adult patients submitted to cardiac surgery from January 1, 2000, to December 31, 2005, were included in the study. AKI was defined by an increase in serum creatinine (SCr) ≥ 0.3 mg/dL after surgery. Patients were stratified into two groups: group 1, CCr ≥ 60 mL/min/1.73 m2 BSA; group 2, CCr < 60 mL/min/1.73 m2 BSA. Risk factors were assessed using a multiple logistic regression model. In all, 749 patients (42.5%) developed AKI. The mortality rate of the entire population was a 5.2%. In patients of group 1 (n = 2678), the variables independently associated with the onset of AKI were age, diabetes, preoperative use of diuretics, non-scheduled surgery, cardiopulmonary by-pass (CPB) time, CPB mean arterial pressure, hemodilution, and postoperative use of norepinephrine. Baseline SCr was associated with AKI only in patients of group 2 (n = 1440). Age, EuroSCORE, non-coronary surgery, hemodilution, and postoperative use of vasoactive drugs were also predictors of AKI in this group of patients. The mortality rate was significantly higher in group 2 than group 1 (8.5% vs. 3.6%, p = 0.000). In conclusion, the present study demonstrated a difference in variables associated with postoperative AKI, according to baseline renal function. The degree of preoperative renal function was a predictor of AKI only in patients with CKD stages 3–4, as well as other risk factors. In addition to other well known risk factors for AKI in this setting, the use of diuretics in patients of group 1 and the level of hemodilution during CPB in both groups should be emphasized, as they are potentially modifiable.

Does OxyVita, a New-Generation Hemoglobin-Based Oxygen Carrier, or Oxyglobin Acutely Interfere With Coagulation Compared With Normal Saline or 6% Hetastarch? An Ex Vivo Thromboelastography Study

Because hetastarches have deleterious effects on coagulation that increase with molecular weight (MWt), risk of coagulopathy associated with a high MWt hemoglobin-based oxygen carrier (HBOC) was studied. Preliminary laboratory study of donor blood using thromboelastography (TEG). University laboratory. Volunteer donor blood. Experiments simulated hemodilution during clinical resuscitation of hemorrhagic shock with varying doses of HBOCs. Coagulopathy related to 1:11, 1:5, 1:2, or 1:1 dilution of whole blood with normal saline, 6% hetastarch (670 kilodaltons [kD]), hemoglobin glutamer-200 (HBOC-200, 200 kD), or OxyVita (OXYVITA Inc, New Windsor, NY) (a new-generation, zero-link polymerized bovine hemoglobin-based oxygen carrier, 33 megadaltons) were analyzed. At 2 lower levels of hemodilution, hetastarch, HBOC-200, and OxyVita produced equivalent reductions in maximum clot strength (TEG-MA and TEG-G) that reached statistical significance compared with whole blood and normal saline. At 2 higher dilutions, OxyVita and HBOC-200 impaired maximum clot strength compared with whole blood, normal saline, and hetastarch. Dilution with hetastarch had a greater effect on clot propagation (K and alpha) than either HBOC. OxyVita and HBOC-200, HBOCs with different MWt, had similar effects on coagulation as measured by TEG. The impairment of coagulation by HBOCs and hetastarch occurred at doses corresponding to 12 mL/kg or a blood volume replacement of 17%. The use of HBOCs at doses corresponding to 23 mL/kg or a blood volume replacement of 33% significantly decreased coagulation to levels associated with increased clinical bleeding in this preliminary study. Minimal coagulopathic effects are expected with use of OxyVita at the manufacturer's anticipated effective dose of 10 g or 2 to 3 mL/kg.

Point of care hematocrit and hemoglobin in cardiac surgery: a review

The use of point-of-care blood gas analyzers in cardiac surgery has been on the increase over the past decade. The availability of these analyzers in the operating room and post-operative intensive care units eliminates the time delays to transport samples to the main laboratory and reduces the amount of blood sampled to measure such parameters as electrolytes, blood gases, lactates, glucose and hemoglobin/hematocrit. Point-of-care analyzers also lead to faster and more reliable clinical decisions while the patient is still on the heart lung machine. Point-of-care devices were designed to provide safe, appropriate and consistent care of those patients in need of rapid acid/base balance and electrolyte management in the clinical setting. As a result, clinicians rely on their values to make decisions regarding ventilation, acid/base management, transfusion and glucose management. Therefore, accuracy and reliability are an absolute must for these bedside analyzers in both the cardiac operating room and the post-op intensive care units. Clinicians have a choice of two types of technology to measure hemoglobin/hematocrit during bypass, which subsequently determines their patient's level of hemodilution, as well as their transfusion threshold. All modern point-of-care blood gas analyzers measure hematocrit using a technology called conductivity, while other similar devices measure hemoglobin using a technology called co-oximetry. The two methods are analyzed and compared in this review. The literature indicates that using conductivity to measure hematocrit during and after cardiac surgery could produce inaccurate results when hematocrits are less than 30%, and, therefore, result in unnecessary homologous red cell transfusions in some patients. These inaccuracies are influenced by several factors that are common and unique to cardiopulmonary bypass, and will also be reviewed here. It appears that the only accurate, consistent and reliable method to determine hemodilution and establish transfusion thresholds based on nadir hematocrits during cardiopulmonary bypass, and immediately post cardiac surgery, is with the use of co-oximetry.

Study of the diagnostic value of iron in fresh water drowning

The aim of our study was to test the diagnostic value of iron (Fe) in fresh water drowning by investigating the postmortem levels of hemodilution in drowning cases compared to control cases. Twenty-six typical fresh water drowning cases were selected from 128 immersion cases autopsied in our Department of Forensic Pathology between 1998 and 2004. The exclusion criteria were a long postmortem interval and other causes of death than drowning. For all selected cases, the diagnosis of drowning was based on the presence of autopsy findings and positive diatom test. A control population of 12 cases was also selected. For each drowning and control case, iron blood levels were measured in the left ventricle (LV) and right ventricle (RV) of the heart. The mean difference of iron concentration (RVFe–LVFe) between the drowning group and the control group was statistically compared. Furthermore, iron measurements were performed in 19 drowning cases showing advanced putrefaction. The mean difference of iron concentration was significantly higher in the drowning cases compared with controls ( P < 0.001). All drowning cases showed hemodilution. No overlap was found in the RVFe–LVFe levels between the two groups. Resuscitation attempts seemed to have no effect on the results. In cases of drowning showing advanced putrefaction, the iron test was not reliable because biochemical iron measurement was often prevented by no sufficient blood in the heart or postmortem clots. In conclusion, according to our results, iron seems to be a good biochemical marker in fresh water drowning with a short postmortem interval.

On-Line Electrical Impedance Measurement for Monitoring Blood Viscosity during On-Pump Heart Surgery

Background: The viscosity of blood (η) as well as its electrical impedance at 20 kHz at high shear rate depends on hematocrit, temperature, concentration of macromolecules and red cell deformability. The aim of our study was to investigate the relation between viscosity and electrical impedance in a heart-lung machine-like set-up, because during on-pump heart surgery considerable viscosity changes occur. Methods: Blood of 10 healthy volunteers was examined under temperature variation between 18.5 and 37°C at four different levels of hemodilution. Blood viscosity was examined with a golden-standard technique, i.e. a Contraves LS 30 Couette viscometer, and the results were compared with measurements of the electrical resistivity (R) at 20 kHz by a specially designed device in series with the tubing system of a heart-lung machine. All measurements were performed at a shear rate of 87 s^–1. Results: Using stepwise multiparameter regression analysis (SPSS) a highly significant correlation was found (r² = 0.882) between viscosity (η) and resistivity (R). Adding the variables sodium ([Na⁺]) and fibrinogen ([Fibr]) concentration the coefficient of correlation further improved to r² = 0.928 and the relation became: η = –0.6844 + 0.038 R + 0.038 [Na⁺] + 0.514 [Fibr]. All coefficients showed a statistical significance of p < 0. 001. Conclusions: Electrical impedance measurement is feasible in a heart-lung machine-like set-up and allows accurate continuous on-line estimation of blood viscosity; it may offer an adequate way to record and control viscosity changes during on-pump heart surgery.

Effects of hemodilution and phenylephrine on cerebral blood flow and metabolism during cardiopulmonary bypass

Objective: Hypotension resulting from hemodilution on cardiopulmonary bypass is often treated by pressor (eg, phenylephrine) infusion. The effect of phenylephrine on cerebral blood flow (CBF) in this setting is not clear. It was hypothesized that phenylephrine might decrease CBF. Measurements and Main Results: Six different radioactively labeled microspheres (15 μm) were used to measure CBF at 6 time points (T) in 9 pigs (mean body weight 11.3 ± 1.2kg): T1 baseline before bypass (mean arterial pressure [MAP] 76 ± 5 mmHg), T2 on mildly hypothermic CPB (34°C, pump flow 100 mL/kg/min, hematocrit 30%, MAP 79 ± 7 mmHg), T3 after moderate hemodilution with crystalloid (hematocrit 20%, resulting MAP 62 ± 6 mmHg), T4 after phenylephrine administration to increase MAP to baseline values (hematocrit 20%), T5 after severe hemodilution (hematocrit 10%, resulting MAP 41 ± 4 mmHg), and T6 after phenylephrine administration to normalize MAP (hematocrit 10%). In addition, blood flow to liver, small bowel and skeletal muscle, and pH of jugular venous blood were measured at each time point. After institution of CPB, the CBF (mL/min/100 g tissue) increased significantly to 53 ± 9 (baseline levels 44 ± 8, T1 v T2, p = 0.03). Hemodilution resulted in significant increases in CBF on CPB to 65 ± 9 and 90 ± 9 at hematocrit 20% and hematocrit 10%, respectively (T2 v T3, p = 0.03; T3 v T5, p = 0.01) and a progressive fall in jugular venous pH. At each level of hemodilution, phenylephrine resulted in an additional increase in CBF (T4, 74 ± 8; T6, 108 ± 12; T3 v T4, p = 0.04; T5 v T6, p = 0.01) but did not improve jugular venous pH. Changes in liver blood flow after hemodilution and vasopressor injection showed a similar pattern to CBF. However, the blood flow to small bowel and skeletal muscle increased with hemodilution but decreased significantly with phenylephrine administration. Conclusions: Phenylephrine redirects blood flow from the bowel and muscle to the brain and liver. Hemodilution increases CBF and pressor administration further increases CBF by elevating perfusion pressure. Maintenance of a higher hematocrit on CPB increases MAP and should decrease the need for vasopressor administration.

Radial displacement of red blood cells during hemodilution and the effect on arteriolar oxygen profile.

In this study, we assessed the magnitude of the erratic deviations in the radial position of red blood cells (RBCs) in the laminar flow regime of arterioles in a hamster window preparation and the intraluminal Po(2) profile to determine whether this variability affects the intraluminal distribution of oxygen in conditions of normal hematocrit and hemodilution. A gated image intensifier was used to visualize fluorescently labeled RBCs in tracer quantities and obtain multiple measurements of RBC radial and longitudinal positions at time intervals on the order of 5 ms within single arterioles (diameter range 40-95 microm). RBCs in the velocity range of 0.3-14 mm/s exhibit a mean coefficient of variation of velocity of 16.9 +/- 10.5% and a SD of the radial position of 1.98 +/- 0.98 microm. Both quantities were inversely related to hematocrit, and the former was significantly lowered by hemodilution. Our experimental results presented very similar values and shape compared with the intraluminal oxygen profile derived theoretically for normal hematocrit, suggesting that shear-augmented diffusion due to the measured radial displacement of RBCs did not significantly affect oxygen diffusion from blood into the arteriolar vessel wall. Po(2) profiles in the arterioles assumed an increasingly parabolic configuration with increasing levels of hemodilution.

Microvascular PO2 and blood velocity measurements in rat brain cortex during hemodilution with a plasma expander (Hespan) and a hemoglobin-based oxygen carrier (DCLHb).

Hemodilution is widely used in various fields of clinical medicine such as vascular and cardiac surgery, orthopedics, etc. Replacing whole blood with a crystalloid fluid reduces blood viscosity, improves cerebral blood flow and enhances oxygen delivery to tissue, minimizing disturbances at the microcirculatory levell,2. Brain tissue possesses powerful regulatory mechanisms to maintain O2 delivery, and for the undamaged circulation an adequate oxygen supply can be sustained even during severe anemia3−5. Oxygen supply to tissue may be impeded at profound levels of hemodilution, because the compensatory hyperemic response may be exhausted at low levels of arterial oxygen capacity6. Few studies, however, have focused on the effect of anemia on oxygenation at the level of brain microvessels, where most of the oxygen exchange between blood and tissue takes place7−9.KeywordsOxygen TensionBlood VelocityExchange TransfusionPlasma ExpanderTissue Oxygen TensionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Acute normovolemic hemodilution improves oxygenation in ischemic flap tissue.

The flaps used in reconstructive surgery are prone to ischemia and hypoxia, which imply a considerable risk of wound-healing complications. During normovolemic hemodilution, the oxygenation may further deteriorate because of the lack of erythrocytes or improve because of increased microcirculatory blood flow. The aim of this study was to investigate the net effect of normovolemic hemodilution of various degrees on the microcirculation and oxygenation in ischemic flap tissue in adult minipigs. A rectangular flap was raised in the middle of the epigastrium, consisting of an adequately perfused portion and a partly ischemic portion. The animals were randomly assigned to either the control group (n = 10) or the experimental group (n = 10) receiving graded normovolemic hemodilution with 6% hydroxyethyl starch 200-0.5. Normovolemic hemodilution caused a significant linear increase in total blood flow to the flap (measured by transit time flowmetry). In the ischemic flap tissue, both oxygen tension (measured by polarographic cells) and venous base excess were transiently improved during hemodilution (F = 4.79 and P = 0.019 for the regression of tissue oxygen tension on hemoglobin and hemoglobin squared, and F = 4.18 and P = 0.029 for base excess). The expected values reached a peak at hemoglobin concentrations of 9.1 and 8.5 g/dl, respectively. The measured values at this level of hemodilution were 17 +/- 10.7 mmHg (mean +/- SD) versus 7.6 +/- 1.9 mmHg (baseline) for oxygen tension and -1.7 +/- 3.4 versus -5.6 +/- 4.1 mM for venous base excess. Our results suggest that the oxygenation in ischemic and hypoxic flap tissue may be improved by normovolemic hemodilution. The maximal benefit may be expected at a hemoglobin concentration at or slightly less than 9 g/dl.

Influence of cell-free Hb on local tissue perfusion and oxygenation in acute anemia after isovolemic hemodilution.

Oxygen-carrying solutions are intended to eliminate the blood transfusion trigger. Their ability to maintain microvascular perfusion and to deliver oxygen to tissue when they replace the RBCs as oxygen carriers has not been directly measured. Microvascular response to exchange transfusion with a polymerized bovine cell-free Hb (PBH) solution after acute isovolemic hemodilution with a plasma expander was investigated by using the hamster window model. In vivo functional capillary density (FCD), blood flow, and high-resolution oxygen distribution in microvascular networks were measured by noninvasive methods. Exchange transfusion of PBH solution after a 60-percent isovolemic hemodilution with dextran 70 (MW, 70 kDa) resulted in a Hct of 11 percent and a Hb content of 6.7 g per dL. FCD was 0.37 of baseline. Interstitial pO2 was reduced from 21.0 mm Hg to 0.3 mmHg. Arteriolar and venular blood flows were ratios of 0.75 and 0.76 relative to baseline. In a previous study, tissue pO2 after hemodilution to 5.6 g of Hb per dL with dextran 70 was 23.0 mmHg. Hypervolemic injection of PBH solution increased blood pressure and caused vasoconstriction. Using PBH solution to replace RBC oxygen-carrying capacity during low Hb content conditions (<50%) causes abnormally low tissue oxygenation and FCD, while the same level of hemodilution with dextran maintains normal microvascular conditions.

Hemodilution - an overview of current canadian practices.

Background. Transplant teams evaluate potential organ and tissue donors to exclude donation of tissues at risk for disease transmission. Standards dictate that serological tests be performed on every donor to assess the presence of transmissible diseases including: Human Immunodeficiency Virus 1 & 2, Human T Lymphotropic Virus 1 & 2, Hepatitis C, Hepatitis B surface Antigen, Hepatitis B core Antibody and Syphilis. A limitation of serological testing is the risk of false negative results due to the dilution of the serum. Hemodilution results from the transfusion of fluids (blood products, colloids and/or crystalloid). Confidence in the accuracy and sensitivity of donor serology testing is of utmost importance to ensure the provision of safe organs and tissues for transplantation.Methods. In order to determine the preferred and validated methodology for determining hemodilution, if any; and to determine the level of hemodilution that jeopardizes serologic test results, we reviewed the literature and current testing practices. Tissue banks throughout Canada as well as accrediting bodies were contacted regarding the hemodilution algorithm they utilize.Results. In the absence of a pretransfusion sample, hemodilution calculations are the prevalent methodology for assessing sensitivity of serology testing. A literature search and personal communications provided no documentation on the validation of any hemodilution algorithm or evidence that 50% hemodilution is an acceptable level for accurate serology testing.Conclusion. A validation of hemodilution algorithms and the acceptable or unacceptable rate of hemodilution is required. The utilization of a validated algorithm should be mandated in standards to ensure continuity of practice by all transplantation centres. If validation cannot be obtained, alternative methodologies for serology testing should be investigated.

Cerebral Response to Hemodilution During Hypothermic Cardiopulmonary Bypass in Adults

We examined the cerebral response to changing hematocrit during hypothermic cardiopulmonary bypass (CPB) in 18 adults. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and cerebral oxygen delivery (CDO2) were determined using the nitrous oxide saturation technique. Measurements were obtained before CPB at 36 degrees C, and twice during 27 degrees C CPB: first with a hemoglobin (Hgb) of 6.2 +/- 1.2 g/dL and then with a Hgb of 8.5 +/- 1.2 g/dL. During hypothermia, appropriate reductions in CMRO2 were demonstrated, but hemodilution-associated increases in CBF offset the reduction in CBF seen with hypothermia. At 27 degrees C CPB, as the Hgb concentration was increased from 6.2 to 8.5 g/ dL, CBF decreased. CDO2 and CMRO2 were no different whether the Hgb was 6.2 or 8.5 g/dL. In eight patients in whom the Hgb was less than 6 g/dL, CDO2 remained more than twice CMRO2. This study suggests that cerebral oxygen balance during cardiopulmonary bypass is well maintained at more pronounced levels of hemodilution than are typically practiced, because changes in cerebral blood flow compensate for changes in hemoglobin concentration.