Severe Normovolemic Hemodilution Research Articles

The Liver and Small Intestine Can Partly Compensate Severe Normovolemic Hemodilution in a Rat Model

BackgroundKnowing the individual critical hematocrit for every organ is essential in operative scenarios in which extensive blood losses are expected. In the past, experimental settings were very heterogeneous resulting in the publication of widely differing values even for one organ in the same species. This study aimed to investigate the compensatory capacity of the liver and the small intestine in a rat model of severe normovolemic hemodilution. Materials and MethodsMale rats were subjected to a stepwise hemodilution with a succinylated gelatin-containing solution to a final hematocrit of 10%, being observed for additional 150 min. During the course of the experiment, blood glucose and L-lactate, as well as D-lactate and intestinal fatty acid-binding protein-2 measurements, were performed eight times in total. The amino acids alanine and glutamine were measured during dilution and at the end of the experiment (four times in total). Hemodilutional effects on the blood and oxygen supply of the liver and the small intestine were measured in a minimally invasive manner. ResultsIn the liver and the small intestine, there were no substantial changes in the blood flow of the microcirculation. Plasma glucose and lactate levels rose transiently, whereas lactate values did not exceed the upper threshold of aerobic metabolism. Plasma levels of the amino acids alanine and glutamine rose significantly and stayed elevated, whereas D-lactate and intestinal fatty acid-binding protein-2 were not significantly increased at any point during the whole experimental time compared to the initial value. ConclusionsSevere hemodilution with a succinylated gelatin-containing solution is tolerated at a profoundly low hematocrit value of 10% during the experimental phase of 150 min.

Prompt rise in urinary ammonium excretion suffices to mitigate metabolic acidosis in an experimental animal model of severe normovolemic hemodilution.

Recently, we have established a model of severe stepwise normovolemic hemodilution to a hematocrit of 10 % in rats employing three different colloidal volume replacement solutions (Voluven, Volulyte and Gelafundin) that are routinely used in clinical practice at present. We did not see severe dilutional acidosis as to be expected, but a decline in urinary pH. We here looked on further mechanisms of renal acid excretion during normovolemic hemodilution. Bicarbonate, which had been removed during normovolemic hemodilution, was calculated with the help of the Henderson-Hasselbalch equation. The urinary amount of ammonium as well as phosphate was determined in residual probes. The absolute amount of free protons in urine was obtained from the pH of the respective samples. The amount of protons generated during normovolemic hemodilution was approximately 0.6 mmol. During experimental time (5.5 h), distinct urinary ammonium excretion occurred (Voluven 0.52 mmol, Volulyte 0.39 mmol and Gelafundin 0.77 mmol). Proton excretion via the phosphate buffer constituted 0.04 mmol in every experimental group. Excretion of free protons was in the range of 10(-6) mmol. The present data prove that the prompt rise in urinary ammonium excretion is also valid for acute metabolic acidosis originating from severe normovolemic hemodilution.

Acid-Base and Electrolyte Status during Normovolemic Hemodilution with Succinylated Gelatin or HES-Containing Volume Replacement Solutions in Rats

BackgroundIn the past, several studies have compared different colloidal replacement solutions, whereby the focus was usually on the respective colloid. We therefore systematically studied the influence of the carrier solution’s composition of five approved colloidal volume replacement solutions (Gelafundin, Gelafusal, Geloplasma, Voluven and Volulyte) on acid-base as well as electrolyte status during and following acute severe normovolemic hemodilution. The solutions differed in the colloid used (succinylated gelatin vs. HES) and in the presence and concentration of metabolizable anions as well as in their electrolyte composition.MethodsAnesthetized Wistar rats were subjected to a stepwise normovolemic hemodilution with one of the solutions until a final hematocrit of 10%. Subsequent to dilution (162 min), animals were observed for an additional period (150 min). During dilution and observation time blood gas analyses were performed eight times in total. Additionally, in the Voluven and Volulyte groups as well as in 6 Gelafundin animals, electrolyte concentrations, glucose, pH and succinylated gelatin were measured in urine and histopathological evaluation of the kidney was performed.ResultsAll animals survived without any indications of injury. Although the employed solutions differed in their respective composition, comparable results in all plasma acid-base and electrolyte parameters studied were obtained. Plasma pH increased from approximately 7.28 to 7.39, the plasma K+ concentration decreased from circa 5.20 mM to 4.80-3.90 mM and the plasma Cl− concentration rose from approximately 105 mM to 111–120 mM. Urinary analysis revealed increased excretion of K+, H+ and Cl−.ConclusionsThe present data suggest that the carrier solution’s composition with regard to metabolizable anions as well as K+, Ca2+ only has a minor impact on acid-base and electrolyte status after application of succinylated gelatin or HES-containing colloidal volume replacement solutions.

LOW HEMATOCRIT IMPAIRS GASTRIC MUCOSAL CO2 REMOVAL DURING EXPERIMENTAL SEVERE NORMOVOLEMIC HEMODILUTION

The net effects of acute normovolemic hemodilution with different hemoglobin levels on splanchnic perfusion have not been elucidated. The hypothesis that during moderate and severe normovolemic hemodilution, systemic and splanchnic hemodynamic parameters, oxygen-derived variables, and biochemical markers of anaerobic metabolism do not reflect the adequacy of gastric mucosa, was tested in this study. Twenty one anesthetized mongrel dogs (16 +/- 1 kg) were randomized to controls (CT, n = 7, no hemodilution), moderate hemodilution (hematocrit 2 5% +/- 3%, n = 7) or severe hemodilution (severe hemodilution, hematocrit 15% +/- 3%, n = 7), through an isovolemic exchange of whole blood and 6% hydroxyethyl starch, at a 20 mL/min rate, to the target hematocrit. The animals were followed for 120 min after hemodilution. Cardiac output (CO, L/min), portal vein blood flow (PVF, mL/min), portal vein-arterial and gastric mucosa-arterial CO2 gradients (PV-artCO2 and PCO2 gap, mm Hg, respectively) were measured throughout the experiment. Exchange blood volumes were 33.9 +/- 3.3 and 61.5 +/- 5.8 mL/kg for moderate hemodilution and severe hemodilution, respectively. Arterial pressure and systemic and regional lactate levels remained stable in all groups. There were initial increases in cardiac output and portal vein blood flow in both moderate hemodilution and severe hemodilution; systemic and regional oxygen consumption remained stable largely due to increases in oxygen extraction rate. There was a significant increase in the PCO2-gap value only in severe hemodilution animals. Global and regional hemodynamic stability were maintained after moderate and severe hemodilution. However, a very low hematocrit induced gastric mucosal acidosis, suggesting that gastric mucosal CO2 monitoring may be useful during major surgery or following trauma.

Critical hematocrit in intestinal tissue oxygenation during severe normovolemic hemodilution.

A critical point in oxygen supply for microvascular oxygenation during normovolemic hemodilution has not been identified. The relation between organ microvascular oxygen partial pressure (microPO2) and organ oxygen consumption (VO2) during a decreasing oxygen delivery (DO2) is not well understood. The present study was designed to determine the systemic hematocrit and organ DO2 values below which organ microPO2 and VO2 cannot be preserved by regulatory mechanisms during normovolemic hemodilution. Eighteen male Wistar rats were randomized between an experimental group (n = 12), in which normovolemic hemodilution was performed with pasteurized protein solution (PPS), and a control group (n = 6). Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal microPO2 was measured using the oxygen-dependent quenching of palladium-porphyrin phosphorescence. Baseline values in hemodilution and control group were similar. Hemodilution decreased hematocrit to 6.2 +/- 0.8% (mean +/- SD). Constant central venous pressure measurements suggested maintenance of isovolemia. Despite an increasing mesenteric blood flow, intestinal DO2 decreased immediately. Initially, microPO2 was preserved, whereas mesenteric venous PO2 (P(mv)O2) decreased; below a hematocrit of 15%, microPO2 decreased significantly below P(mv)O2. Critical DO2 was 1.5 +/- 0.5 ml x kg(-1) x min(-1) for VO2, and 1.6 +/- 0.5 ml x kg(-1) x min(-1) for microPO2. Critical hematocrit values for VO2 and microPO2 were 15.8 +/- 4.6% and 16.0 +/- 3.5%, respectively. Intestinal microPO2 and VO2 were limited by a critical decrease in DO2 and hematocrit at the same time. Beyond these critical points not only shunting of oxygen from the microcirculation could be demonstrated, but also a significant correlation between intestinal microPO2 and VO2.

Superiority of Colloid over Electrolyte Solution for Severe Normovolemic Hemodilution (NVHD) in Concurrent Treatment of Hemorrhage

Treatment of severe hemorrhage with adequate concurrent administration of plasma substitutes leads to acute normovolemic hemodilution (NVHD). Advantages of hemodilution include: l) reduced risk of infection; 2) decreased thromboembolic phenomena; 3) improved microcirculation; and 4) less use of banked blood resulting in reduced patient cost.In the 1960's, Takaori and Safar described the types of response to various degrees of hemodilution (HD) and demonstrated that dogs survived when hemodiluted with dextrans to a hematocrit (hct) of 10%. In contrast, HD with Lactated Ringers (LR) was unable to support survival.