Plasma Volume Expansion Research Articles

Sub-clinical injury in AKI prior to pregnancy induces renal inflammation, renal fibrosis and suppresses the renin-angiotensin aldosterone system (RAAS) in female rats

Acute kidney injury (AKI), a sudden loss of kidney function, is responsible for 1 in 5 US hospitalizations. Although women are considered to be protected from AKI, they make up 40% of AKI patients. Recent clinical data report a 3-5-fold increase in adverse pregnancy outcomes among women with a history of AKI, despite apparent clinical recovery of renal function before pregnancy. These women have increased odds for developing preeclampsia and fetal growth restriction, via mechanisms unknown. To address this clinical issue, we developed a rat model of pregnancy post-AKI. We show that female Sprague-Dawley (SD) rats recover renal function as measured by creatinine clearance 30 days post-AKI. These rats exhibit decreased creatinine clearance, increased blood pressure, reduced plasma volume expansion and fetal growth restriction during pregnancy compared to sham rats. This study tested the hypothesis that AKI prior to pregnancy induces renal inflammation, fibrosis and dysregulates the renin-angiotensin aldosterone system (RAAS). Female SD rats were randomized to 45-minute warm sham or bilateral renal ischemia reperfusion (N=6/grp) and mated 30 days post sham/AKI surgery. Gestational day 1 (GD1) was identified through vaginal smear. Rats were placed in metabolic cages on GD19 for urine collection and euthanized on GD20. Urinary volume/day (30±5 vs 19±2 ml/day, P=0.08) and water intake (55±5 ml vs 41±1 ml, *P<0.05) increased in post-AKI pregnant rats compared to sham. In addition, urinary aldosterone levels measured by ELISA decreased in post-AKI pregnant rats compared to sham (188±34 pg/ml/day vs 312±35, *P<0.05). These data suggest disruption of fluid homeostasis and RAAS by pre-pregnancy AKI. Kidney injury marker-1 (KIM-1) measured via ELISA trended to increase in pre-pregnant AKI rats compared to sham at 30 days post AKI (580±169 pg/ml vs 257±17, P=0.09) and in pregnancy (283±28 vs 216±12 pg/ml, P=0.06), suggesting a lingering kidney injury despite creatinine clearance returning to sham levels. Mason Trichrome renal staining at GD20 revealed increases in both glomerular fibrosis (0.93±0.08 vs 0.04±0.04 score, *P<0.05) and tubular fibrosis (1.7±0.19 vs 0.0±0.0 score, *P<0.05) in post-AKI pregnant rats compared to sham. T regulatory immune (Tregs) cell populations in blood and kidney were measured via flow cytometry on GD20. Blood Tregs (16195±2935 cells/ml vs 26740±2508, *P<0.05) as well as renal Tregs (1811±364 cells/gram kidney vs 3241±405.6, *P<0.05) decreased in post-AKI pregnant rats compared to sham, suggesting AKI prior to pregnancy increases renal inflammation. Taken together, these data suggest that history of AKI predisposes to pregnancy induced dysregulation of fluid hemodynamics, renal inflammation, renal fibrosis and sustained renal injury mediating adverse fetal and maternal outcomes. R00 HL146948-03 to DM; AHA CDA858380 to JLF; AHA DIVSUP0224732 to DM This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hepatorenal Syndrome: Current Concepts and Future Perspectives.

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis (ATN). The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Biochemical Profile of African American Women During Three Trimesters of Pregnancy and at Delivery

The data presented are the results from a prospective observational study which was conducted to investigate the effects of nutrition and other related factors on the outcome of pregnancy in nulliparous African American women 16-35 years old. Fasting blood samples were collected from the women during the first, second and third trimesters of pregnancy. At delivery, both maternal and cord samples were collected. Biochemical variables such as, serum folate, vitamin B12, ascorbic acid, vitamin E, ferritin, selected minerals as well as complete blood count (CBC) and red cell folate were analyzed in the blood samples. The concentrations of hematocrit, hemoglobin, white blood cells, red blood cells and vitamin B12 were below the reference non-pregnant ranges throughout gestation. Maternal concentrations of folate and vitamin E increased sequentially with increased gestational age. Serum ferritin, during the third trimester, declined to 58% of the first trimester concentration. Maternal levels of ferritin at delivery were one third of the values found in the infant (cord) sample. Cord levels of folate, ascorbic acid and vitamin B12 were higher than the concentrations in the maternal delivery samples. The data suggest that among this group of pregnant women, major physiological changes, such as plasma volume expansion which alters blood chemistry and maternal to fetal transfer of nutrients, were similar to the findings of other investigators. In this population however, the findings for serum and whole blood folate are contrary to those reported by other researchers, and the sequential increase in the maternal concentration of the vitamin during pregnancy could be attributed to the use of vitamin supplements.

Temporal changes in the systemic concentrations of retinoids in pregnant and postpartum women.

Retinoids and vitamin A are essential for multiple biological functions, including vision and immune responses, as well as the development of an embryo during pregnancy. Despite its importance, alterations in retinoid homeostasis during normal human pregnancy are incompletely understood. We aimed to characterize the temporal changes in the systemic retinoid concentrations across pregnancy and postpartum period. Monthly blood samples were collected from twenty healthy pregnant women, and plasma concentrations of retinol, all-trans-retinoic acid (atRA), 13-cis-retinoic acid (13cisRA), and 4-oxo-retinoic acids were measured using liquid chromatography-tandem mass spectrometry. Significant decreases in 13cisRA concentrations over the pregnancy were observed, with rebound increases in retinol and 13cisRA levels after delivery. Of note, atRA concentrations exhibited a unique temporal pattern with levels peaking at mid-pregnancy. While the 4-oxo-atRA concentration was below the limit of quantification, 4-oxo-13cisRA was readily detectable, and its temporal change mimicked that of 13cisRA. The time profiles of atRA and 13cisRA remained similar after correction by albumin levels for plasma volume expansion adjustment. Together, the comprehensive profiling of systemic retinoid concentrations over the course of pregnancy provides insights into pregnancy-mediated changes in retinoid disposition to maintain its homeostasis.

The influence of exercise volume and posture on exercise-induced plasma volume expansion.

Acute high-intensity interval exercise is known to expand plasma volume 24 h after exercise. Upright exercise posture plays a role in expanding plasma volume by influencing lymphatic outflow and redistributing albumin while supine exercise does not. We examined if further upright and weight-bearing exercises could further promote plasma volume expansion. We also tested the volume of intervals needed to induce plasma volume expansion. To test the first hypothesis, 10 subjects performed intermittent high-intensity exercise (4min at 85% V̇O2max , 5min at 40% V̇O2max repeated 8 times) on separate days on the treadmill and cycle ergometer. For the second study, 10 subjects performed four, six, and eight intervals of the same interval protocol on separate days. Changes in plasma volume were calculated from changes in hematocrit and hemoglobin. Transthoracic impedance (Z0 ) and plasma albumin were assessed while seated before and postexercise. Plasma volume increased 7.3% ± 4.4% and 6.3% ± 3.5% following treadmill and cycle ergometer exercise, respectively. For four, six, and eight intervals, plasma volume increased by 6.6% ± 4.0%, 4.7% ± 2.6%, and 4.2% ± 5.6%, respectively. The increases in plasma volume were similar for both exercise modes and all three exercise volumes. There were no differences in Z0 or plasma albumin content between trials. In conclusion, rapid plasma volume expansion following eight bouts of high-intensity intervals appears to be independent of upright exercise posture (treadmill versus cycle ergometer). Meanwhile, plasma volume expansion was similar after four, six, and eight intervals of cycle ergometry.

Differences in red blood cell mass profiles impact intravascular volume and outcome risk in chronic heart failure.

To identify different red blood cell mass (RBCM) profiles, separate from haemoglobin concentrations, and their impact on blood volume expansion and clinical outcomes in chronic heart failure. RBCM was measured at hospital discharge using standardized nuclear medicine indicator-dilution methodology in patients following diuretic treatment for clinical congestion. Individual RBCM phenotypes were prospectively identified and analysed for heart failure-related mortality or first rehospitalization over 1year. Of 132 patients, 42 (32%) demonstrated normal RBCM, 36 (27%) RBCM deficit (true anaemia), and 54 (41%) RBCM excess (erythrocythemia). Dilutional 'anaemia' defined by haemoglobin <12g/dL with normal or an excess in RBCM with plasma volume expansion was identified in 37 (28%) patients. There were 61 composite outcome events, which included 38 deaths (29% of cohort) occurring over the 1year follow-up period [14/36 (39%) in RBCM deficit, 12/42 (29%) in normal RBCM, and 12/54 (22%) in RBCM excess subgroups]. By Kaplan-Meier and multivariate analyses, RBCM excess was independently associated with the best event-free survival while RBCM deficit (true anaemia) the poorest outcomes; both compared with normal RBCM (P<0.001). Dilutional 'anaemia' demonstrated a lower risk compared with true anaemia (P=0.03). Markedly different RBCM profiles are identifiable among comparably compensated heart failure patients, and this variability carries significant implications for post-hospital outcomes. Novel to this analysis and in contrast to RBCM deficit is the independent association of RBCM excess with better event-free survival compared with normal RBCM. The distinction of RBCM profiles to guide risk stratification and individualized patient management strategies warrants further study.

Gerakan “ATIKA” Makanan Ibu Hamil di Puskesmas Tungkal II Kabupaten Tanjung Jabung Barat

Lack of hemoglobin levels in pregnant women is one of the health problems that are prone to occur during pregnancy and can increase the risk of low birth weight babies (LBW), the risk of bleeding before and during delivery, and can even cause the death of mothers and babies if the pregnant woman suffering from severe anemia. Anemia that is often experienced by pregnant women is due to iron deficiency because in pregnant women there is a twofold increase in iron due to an increase in blood volume without plasma volume expansion to meet the needs of the mother and fetal growth. One of the factors that can affect hemoglobin levels is the type of food consumed. Types of foods that are rarely consumed but are very beneficial for pregnant women are liver, eggs, and fish which can be abbreviated as "ATIKA". Emodemo is a method that can be used to convey information in the form of demonstrations that are attractive and fun for the target audience, because what is being done is not material but role-play and discussion. The result that the target understood the material presented and was able to practice measuring the amount of food consumption of iron sources. It is suggested that the Community Health Centre Tungkal II can increase the activities of education that interactive and interesting related nutritional problems that occur in pregnant women

Abstract 11787: Impact of Estimated Plasma Volume Status on Clinical Outcomes in Lower Extremity Artery Disease Patients Who Underwent Endovascular Therapy

Introduction: Lower extremity artery disease (LEAD) is an arterial occlusive disease associated with high morbidity and mortality. Estimated plasma volume status (ePVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular disease. However, it remains undetermined the impact of ePVS on clinical outcome in patients with LEAD. Methods: We calculated two ePVS using Kaplan-Hakim and Duarte formula in 288 LEAD patients who underwent first endovascular therapy and retrospectively followed during a median follow-up period of 617 days. The primary and secondary endpoints were composite events including all-cause death and major adverse limb events (Death/MALE) and major adverse cardiovascular events (MACE), respectively. Results: ePVS significantly increased with advancing Fontaine class. All patients were divided into two groups based on the median ePVS value. Kaplan-Meier analysis demonstrated high ePVS group had higher incidence of composite events and MACE compared to low ePVS group. A multivariate Cox proportional hazard analysis revealed that ePVS was an independent predictor of Death/MALE and MACE after adjustment for confounding risk factors. Prognostic ability for Death/MALE was significantly improved by addition of ePVS to the basic predictors. These results are consistent with each formula. Conclusions: ePVS was associated with severity of LEAD and clinical outcome, suggesting ePVS could be an additional risk factor for Death/MALE and MACE in LEAD patients who underwent endovascular therapy.

Terapie innovative per il diabete: effetti sul rischio di scompenso cardiovascolare nel paziente non diabetico

Most of the glucose is reabsorbed in the kidney by the sodium-glucose cotransporters 2 (SGLT2): SGLT2i inhibitors significantly reduce the renal glucose threshold in the patient with and in the patient without diabetes. This effect explains the consistent drop in blood sugar in the patient with diabetes and a decrease (5-10 mg/dl) in the non-diabetic person. Notably, SGLT2i inhibit sodium reabsorption leading to a reduction in the expansion of plasma volume and blood pressure. At the cardiovascular level, SGLT2i reduce preload and post-load, improves cardiac metabolism and bioenergetics, inhibits the sodium hydrogen antiport, and reduce the adrenergic system’s activation. Glucagon-like peptide 1 receptor agonists (GLP-1RA) enhance endothelial function, stabilize atherosclerotic plaque and increase angiogenesis. Similar to SGLT2i, GLP-1RAs reduce arterial stiffness and low-grade inflammation. A peculiar action of GLP-1 is the inhibition of platelet aggregation, most likely linked to the ability of these drugs to stimulate nitric oxide synthesis in platelets. They also increase sodium excretion with a consequent drop in blood pressure and significantly reduce fatty liver disease, an important cardiovascular risk factor. The clinical characteristics of these two classes of drugs are described, and their benefits on the cardiovascular system in patients without diabetes are discussed.

Mutagenesis of the cleavage site of (pro)renin receptor abrogates aldosterone-salt-induced hypertension and renal injury in mice.

Soluble (pro)renin receptor (sPRR), the extracellular domain of (pro)renin receptor (PRR), is primarily generated by site-1 protease and furin. It has been reported that sPRR functions as an important regulator of intrarenal renin contributing to angiotensin II (ANG II)-induced hypertension. Relatively, less is known for the function of sPRR in ANG II-independent hypertension such as mineralocorticoid excess. In the present study, we used a novel mouse model with mutagenesis of the cleavage site in PRR (termed as PRRR279V/L282V or mutant) to examine the phenotype during aldosterone (Aldo)-salt treatment. The hypertensive response of mutant mice to Aldo-salt treatment was blunted in parallel with the attenuated response of plasma volume expansion and renal medullary α-epithelial Na+ channel expression. Moreover, Aldo-salt-induced hypertrophy in the heart and kidney as well as proteinuria were improved, accompanied by blunted polydipsia and polyuria. Together, these results represent strong evidence favoring endogenous sPRR as a mediator of Aldo-salt-induced hypertension and renal injury.NEW & NOTEWORTHY We used a novel mouse model with mutagenesis of the cleavage site of PRR to support soluble PRR as an essential mediator of aldosterone-salt-induced hypertension and also as a potential therapeutic target for patients with mineralocorticoid excess. We firstly report that soluble PRR-dependent pathway medicates the Na+-retaining action of aldosterone in the distal nephron, which opens up a new area for a better understanding of the molecular basis of renal handling of Na+ balance and blood pressure.

MPN-541 Estimated Plasma Volume Status in Patients With Primary Myelofibrosis and Associated Thrombotic and Mortality Risks.

Blood plasma experiences substantial changes in both volume and composition in patients with chronic myeloproliferative neoplasms (MPN) and represents a large reservoir of cytokines and other mediators of inflammation. Higher estimated plasma volume status (ePVS) has recently been shown to correlate with increased thrombotic risk in polycythemia vera patients. To estimate clinical and prognostic associations of ePVS in patients with myelofibrosis. Retrospective cohort study. 6 hematology centers. 238 myelofibrosis patients, 168 with PMF, 34 with post-PV SMF and 36 with post-ET SMF. ePVS was calculated using the Strauss derived Duarte formula: (100-hematocrit (%)/hemoglobin (g/dL) and expressed as dl/g. Overall survival (OS) and time to thrombosis (TTT). Median ePVS was 5.8 dl/g and it did not significantly differ between PMF and SMF patients. Among other associations, higher ePVS was significantly associated with higher degree of bone-marrow fibrosis, absence of JAK2-mutation, lower white blood cells (WBC), platelets and hemoglobin, presence of circulatory blasts, higher C-reactive protein, higher lactate dehydrogenase, lower albumin and higher Charlson comorbidity index in an overall cohort, as well as with more pronounced splenomegaly and higher Dynamic International Prognostic Scoring System (DIPSS) risk in primary myelofibrosis (PMF) and higher Mysec-PM risk in secondary myelofibrosis (SMF) patients (P<0.05 for all analyses). Higher ePVS (>5.6 dl/g) was associated with shorter overall-survival (OS) in PMF (HR=2.8, P<0.001) and SMF (HR=2.55, P=0.025) and with shorter time-to-thrombosis in PMF (>7 dl/g, HR=4.1, P=0.009) patients. Associations with overall survival diminished in multivariate analyses after adjustments for DIPSS and Mysec-PM, respectively. Association with TTT remained significant independently of JAK2, WBC and chronic kidney disease. Myelofibrosis patients with more advanced disease features and more pronounced inflammation have higher ePVS, indicative of expanded plasma volume. Higher ePVS is associated with impaired survival in PMF and SMF and higher thrombotic risk in PMF patients.

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

The kinetics of isotonic and hypertonic resuscitation fluids is dependent on the sizes of the body fluid volumes.

The extracellular and intracellular fluid volumes (ECV and ICV) vary not only with age, gender, and body weight but also with the habitual intake of water. The present study examines whether the baseline variations in the ECV and ICV change the distribution and elimination of subsequently given infusion fluids. Twenty healthy male volunteers underwent 50 infusion experiments with crystalloid fluid for which the fluid volume kinetics was calculated based on frequent measurements of the hemodilution using mixed-effects modeling software. The results were compared with the ECV and ICV measured with multifrequency bioimpedance analysis before each infusion started. The fluids were given over 30 minutes and comprised 25 mL/kg Ringer's acetate (N = 20), Ringer's lactate, 5 mL/kg 7.5% saline, and 3 mL/kg 7.5% saline in 6% dextran 70 (these fluids, N = 10). A large ICV was associated with a small extravascular accumulation of infused fluid, which increased the plasma volume expansion and the urinary excretion. With hypertonic fluid, a large ECV greatly accelerated urinary excretion. The body weight did not serve as a covariate in the kinetic models. Albumin was recruited to the plasma during infusion of both types of fluid. The hypertonic fluids served as diuretics. The infused excess sodium and osmolality were distributed over a 35% larger space than the sum of the ECV and ICV. A large ICV reduced the rate of distribution of Ringer's solution, whereas a large ECV accelerated the excretion of hypertonic saline.

Abstract 031: Mutagenesis Of The Cleavage Site Of (pro)renin Receptor Abrogates Aldosterone-salt-induced Hypertension And Renal Injury In Mice

Soluble (pro)renin receptor (sPRR), the extracellular domain of (pro)renin receptor (PRR), is primarily generated by site-1 protease (S1P) and furin. It has been reported that sPRR functions as an important regulator of intrarenal renin contributing to angiotensin II (Ang II)-induced hypertension. Relatively, less is known for the function of sPRR in Ang II-independent hypertension such as mineralocorticoid excess. In the present study, we employed a novel mouse model with mutagenesis of the cleavage site in PRR (termed as Mutant mice) to examine the phenotype during aldosterone (Aldo)-salt treatment. The hypertensive response of Mutant mice to Aldo-salt treatment was blunted (day 12, delta MAP: WT/Aldo-salt 22.4±4.1 mm Hg vs. Mutant/Aldo-salt 11.7±2.5 mm Hg, n=6, p&lt;0.05), in parallel with attenuated response of plasma volume expansion and sodium-water retention. Renal cortical and inner medullary mRNA and protein expression of α-, β-, and γ-subunits of epithelial sodium channel (ENaC) were all increased in WT mice after Aldo-salt treatment but only the increase of α-ENaC in inner medulla was blunted in Mutant mice. The plasma sPRR was increased 1.5-fold after Aldo-salt treatment, which was reduced by 57% in Mutant mice. Moreover, Aldo-salt-induced hypertrophy in the heart and kidney, which were improved in Mutant mice (Heart Weight/Body Weight: WT/Aldo-salt 5.8±0.4 mg/g vs. Mutant/Aldo-salt 4.2±0.3 mg/g; Kidney Weight/Body Weight: WT/Aldo-salt 9.9±0.4 mg/g vs. Mutant/Aldo-salt 7.3±0.4 mg/g, n=6, p&lt;0.01), accompanied with blunted polydipsia and polyuria in Mutant mice. Furthermore, the urinary albumin was increased 8.3-fold after Aldo-salt treatment, which was reduced by 32% in Mutant mice. The mRNA levels of Fibronectin, α-SMA, IL-6, MCP-1 and TGF-β were increased in Aldo-salt/WT mice, which were prevented almost 60% in Aldo-salt/Mutant mice. Together, these results represent strong evidence favoring endogenous sPRR as a mediator of Aldo-salt-induced hypertension and renal injury. Here, we firstly report that sPRR-dependent pathway medicates the Na + -retaining action of Aldo in the distal nephron, which opens up a new area for a better understanding of the molecular basis of renal handling of Na + balance and blood pressure.

Plasma volume expansion reveals hidden metabolic acidosis in patients with diabetic ketoacidosis

BackgroundHyperchloremic metabolic acidosis that develops during the treatment of diabetic ketoacidosis is usually attributed to the chloride content of resuscitation fluids. We explored an alternative explanation, namely that fluid-induced plasma volume expansion alters the absolute differences in the concentrations of sodium and chloride (the Na–Cl gap) enough to affect the acid–base balance. We analyzed data from a prospective single-center cohort study of 14 patients treated for diabetic ketoacidosis. All patients received 1 L of 0.9% saline over 30 min on two consecutive days. Blood gases were sampled before and after the infusions.ResultsThe initial plasma volume was estimated to be 25 ± 13% (mean ± SD) below normal on admission to the intensive care unit. At that time, most patients had an increased actual Na–Cl gap, which counteracts acidosis. However, the correction of the plasma volume deficit revealed that these patients would have had a decreased Na–Cl gap upon admission if they had been normovolemic at that time; the estimated “virtual Na–Cl gap” of 29 ± 5 mmol/L was significantly lower than the uncorrected value, which was 39 ± 5 mmol/L (P < 0.001). On Day 2, most patients had a decreased actual Na–Cl gap (33 ± 5 mmol/L), approaching the corrected value on Day 1.ConclusionsThe hyperchloremic acidosis commonly seen in diabetic ketoacidosis may not be primarily caused by the chloride content of resuscitation fluids but, rather, by the restoration of plasma volume, which reveals the hidden metabolic acidosis caused by a decreased Na–Cl gap.Trial registration Clinical Trials Identifier NCT02172092, registered June 24, 2014, https://www.clinicaltrials.gov/NCT02172092

Impact of Estimated Plasma Volume Status on Mortality in Right Heart Failure Patients: A Retrospective Cohort Study in Indonesia.

Background:Plasma volume (PV) expansion hallmarks the syndrome of heart failure (HF) but is difficult to be quantified noninvasively. Estimated plasma volume status (ePVS) has marked prognostic utility in the failing left heart, however its use in right heart failure (RHF) remains unknown. This study aims to investigate the prognostic value of ePVS among isolated RHF patients.Methods:We retrospectively collected 208 patients admitted for RHF in our hospital from the electronic database from 2017 to 2019. ePVS was calculated using the Hakim formula. Patients were divided into low and high groups based on their PV value. Logistic regression was used to compare the odds of in-hospital mortality between these groups.Results:The overall in-hospital mortality was 12.5%, tripled from the low group to the high group (6.7% vs. 18.3%), within a median of 6 (3–19) days. High ePVS significantly predicted mortality in RHF, even after being adjusted for demographic, hemodynamic, chemistry, and medication variables (adjusted OR: 5.83, 95% CI: 1.62–20.95, p < 0.01).Conclusion:ePVS is associated with in-hospital mortality among isolated RHF patients. Given not only the wide accessibility of hemogram but also the low cost and the rapid quantification of relative PV, this simple tool can potentially aid in optimizing RHF management, especially in rural area, although further evaluation is warranted.

Clinically unrecognized plasma volume expansion predicts long-term all-cause-mortality in chronic heart failure.

IntroductionChronic heart failure (CHF) is associated with elevated total blood volume (BV) and distinct phenotypes of total red cell volume (RCV) and plasma volume (PV) elevations. Especially PV expansion during clinical decompensation is linked with adverse clinical outcomes. The role of PV expansion in compensated CHF patients is less clear. Aim of the present study is to investigate the impact of BV parameters on long‐term mortality in CHF patients investigated at a compensated state.Methods and ResultsBV, PV and RCV were determined in 44 (9 female) compensated CHF patients using an abbreviated carbon monoxide method, who were followed up for 6.0 years, (range: 3.7–6.5 years) for all‐cause mortality. In univariate analysis PV expansion but not BV and RCV predicted all‐cause mortality (p = .021). A cutoff of 1800 ml PV/m² body‐surface area allows stratification for all‐cause mortality (p = .044). PV expansion but not RCV reduction explains the significantly lower hematocrit values of nonsurvivors.DiscussionIn this pilot study, PV expansion, which was unnoticed from a clinician's perspective, but is indicated by significantly lower hematocrit, appears to be a relevant predictor of long‐term all‐cause mortality. Whether PV expansion constitutes an adverse CHF phenotype and can be targeted by diuretic therapy is currently unclear.

Fast versus slow infusion of 20% albumin: a randomized controlled cross-over trial in volunteers

BackgroundWe investigated whether plasma volume (PV) expansion of 20% albumin is larger when the fluid is administered rapidly compared with a slow infusion.MethodsIn this open-labeled randomized interventional controlled trial, 12 volunteers (mean age, 28 years) received 3 mL/kg of 20% albumin (approximately 225 mL) over 30 min (fast) and 120 min (slow) in a cross-over fashion. Blood hemoglobin and plasma albumin were measured on 15 occasions during 6 h to estimate the PV expansion and the capillary leakage of albumin and fluid.ResultsThe largest PV expansion was 16.1% ± 6.5% (mean ± SD) for fast infusion and 12.8% ± 4.0% for slow infusion (p = 0.52). The median area under the curve for the PV expansion was 69% larger for the fast infusion during the first 2 h (p = 0.034), but was then similar for both infusions. The half-life of the PV expansion did not differ significantly (median, 5.6 h versus 5.4 h, p = 0.345), whereas the intravascular half-life of the excess albumin was 8.0 h for fast infusion and 6.3 h for slow infusion (p = 0.028). The measured urine output was almost three times larger than the infused volume. The plasma concentration of atrial natriuretic peptide (MR-proANP) accelerated the capillary leakage of albumin and the urine flow.ConclusionsThe intravascular persistence of albumin was longer, but the fluid kinetics was the same, when 20% albumin was infused over 30 min compared with 120 min. We found no disadvantages of administering the albumin at the higher rate.Trial registration EU Clinical Trials Register, EudraCT2017-003687-12, registered September 22, 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-003687-12/SE

Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction.

This narrative review summarizes current evidence on the association between maternal low volume circulation and poor fetal growth. Though much work has been devoted to the study of cardiac output and peripheral vascular resistance, a low intravascular volume may explain why high vascular resistance causes hypertension in women with preeclampsia (PE) that is associated with fetal growth restriction (FGR) and, at the same time, presents with normotension in FGR itself. Normotensive women with small for gestational age babies show normal gestational blood volume expansion superimposed upon a constitutionally low intravascular volume. Early onset preeclampsia (EPE; occurring before 32 weeks) is commonly associated with FGR, and poor plasma volume expandability may already be present before conception, thus preceding gestational volume expansion. Experimentally induced low plasma volume in rodents predisposes to poor fetal growth and interventions that enhance plasma volume expansion in FGR have shown beneficial effects on intrauterine fetal condition, prolongation of gestation and birth weight. This review makes the case for elevating the maternal intravascular volume with physical exercise with or without Nitric Oxide Donors in FGR and EPE, and evaluating its role as a potential target for prevention and/or management of these conditions.

Kinetics of 5% and 20% albumin: A controlled crossover trial in volunteers.

BackgroundAlbumin for intravenous infusion is marketed in two concentrations, 20% and 5%, but how they compare with regard to plasma volume expansion over time is unclear.MethodsIn a prospective crossover study, 12 volunteers received 3 ml kg−1 of 20% albumin and, on another occasion, 12 ml kg−1 of 5% albumin over 30 min. Hence, equivalent amounts of albumin were given. Blood was collected on 15 occasions over 6 h. Mass balance and volume kinetics were used to estimate the plasma volume expansion and the capillary leakage of albumin and fluid based on measurements of blood hemoglobin, plasma albumin, and the colloid osmotic pressure.ResultsThe greatest plasma volume expansion was 16.0 ± 6.4% (mean ± SD) with 20% albumin and 19.0 ± 5.2% with 5% albumin (p < .03). The volume expansion with 20% albumin corresponded to twice the infused volume. One third of the 5% albumin volume quickly leaked out of the plasma, probably because of the higher colloid osmotic pressure of the volunteer plasma (mean, 24.5 mmHg) than the albumin solution (19.1 mmHg). At 6 h, the capillary leakage amounted to 42 ± 15% and 47 ± 11% of the administered albumin with the 20% and 5% preparations, respectively (p = .28). The corresponding urine outputs were 547 (316–780) ml and 687 (626–1080) ml (median and interquartile range; p = .24).ConclusionThe most important difference between the fluids was a dehydrating effect of 20% albumin when the same albumin mass was administered.