Hydroxyl Ethyl Starch (HES) Preserves Intrarenal Microcirculatory Perfusion Shown by Contrast-Enhanced Ultrasound (Ceus), and Renal Function in a Severe Hemodilution Model in Pigs

Abstract

Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of blood and purposed to cause renal injury in perioperative setting. It is best accomplished in a perioperative setting by a colloid such as hydroxyl ethyl starch (HES) due its capacity to fill the vascular compartment and maintain colloidal pressure. However, alterations of intra renal microvascular perfusion, flow and its effects on renal function and damage during ANH has not been sufficiently clarified. Based on the extensive use of HES in the perioperative setting we tested the hypothesis that the use of HES during ANH is able to perfuse the kidney microcirculation adequately without causing renal dysfunction and injury in pigs. Hemodilution (n ¼ 8) was performed by stepwise replacing blood with HES to hematocrit (Hct) levels of 20% (T1), 15% (T2), and 10% (T3). Seven control animals were investigated. Systemic and renal hemodynamics were monitored. Renal microcirculatory perfusion was visualized and quantified using contrast-enhanced ultrasound (CEUS) and laser speckle imaging (LSI). In addition, sublingual microcirculation was measured by handheld vital microscopy (HVM). Intrarenal mean transit time of ultrasound contrast agent (IRMTT-CEUS) was reduced in the renal cortex at Hct 10% in comparison to control at T3 (1.4 AE 0.6 vs. 2.2 AE 0.7 seconds, respectively, P < 0.05). Although renal function was preserved, the serum neutrophil gelatinase-associated lipocalin (NGAL) levels was higher at Hct 10% (0.033 AE 0.004 pg/mg protein) in comparison to control at T3 (0.021 AE 0.002 pg/mg protein. A mild correlation between CO and IRMTT (renal RBC velocity) (r À0.53; P ¼ 0.001) and CO and NGAL levels (r 0.66; P ¼ 0.001) was also found. Our results show that HES induced ANH is associated with a preserved intra renal blood volume, perfusion, and function in the clinical range of Hct (<15%). However, at severely low Hct (10%) ANH was associated with renal injury as indicated by increased NGAL levels. Changes in renal microcirculatory flow (CEUS and LSI) followed those seen in the sublingual microcirculation measured with HVM.

Assessment of Abnormal Skeletal Muscle Perfusion by Contrast-Enhanced Ultrasound With Parametric Imaging in Rats After Severe Injury, Hemorrhagic Shock, and Whole Blood Resuscitation

“…The injury is followed by a whole blood transfusion. This is consistent with current resuscitation practices and avoids the hemodilution that impairs hemostasis and does not play a causal role in MBF derangement (32). The model produces a loss of coherence between macrohemodynamics and microhemodynamics, which is consistent with clinical observations and can be difficult to capture with other methods of measuring MBF (33).…”

Intra-renal microcirculatory alterations on non-traumatic hemorrhagic shock induced acute kidney injury in pigs

“…In this study, we showed that aggressive fluid resuscitation could improve the systemic hemodynamic parameters such as MAP, CVP, and cardiac output following non-traumatic hemorrhagic shock, despite low systemic vascular resistance (SVR) and consistent tissue hypoxia shown by plasma lactate and serum creatinine levels. Similar to our previous study in stepwise hemodilution in pigs [26], it is shown that the correction of systemic hemodynamic variables was not accompanied with the improvement of renal cortical perfusion, intra-renal blood volume, renal damage, and systemic microcirculation following 1 h of fluid resuscitation. Lastly, we suggest that, regardless of fluid type, fluids need to be administered to patients with caution, and the measurement of renal injury biomarkers and microcirculatory assessments can be used for guiding the optimization of therapies.…”

“…Interestingly, despite RVR was normalized probably due to renal autoregulation, SVR was still depleted throughout the experiment because of the low blood viscosity. In our previous study, we demonstrated that high RBC velocity could persist during hemodilution with HES, which resulted in renal damage without the association of hyperlactatemia despite sustained or, in some part, improved systemic and renal hemodynamics [26]. However, in the present study, we found that the sublingual RBC velocity was not influenced after normalization of systemic hemodynamics by crystalloid resuscitation, but there were less capillaries than…”