Limited Effect of Dehydrating via Active vs. Passive Heat Stress on Plasma Volume or Osmolality, Relative to the Effect of These Stressors per Se.

The physiological, perceptual, and functional effects of dehydration may depend on how it is incurred (e.g., intense exercise releases endogenous water via glycogenolysis) but this basic notion has rarely been examined. We investigated the effects of active (exercise) heat- vs. passive heat-induced dehydration, and the kinetics of ad libitum rehydration following each method. Twelve fit participants (five females and seven males) completed four trials in randomised order: DEHydration to -3% change in body mass (∆BM) under passive or active heat stress, and EUHydration to prevent ∆BM under passive or active heat stress. In all trials, participants then sat in a temperate-controlled environment, ate a standard snack and had free access to water and sports drink during their two-hour recovery. During mild dehydration (≤2% ∆BM), active and passive heating caused comparable increases in plasma osmolality (Posm: ~4 mOsmol/kg, interaction: p = 0.138) and reductions in plasma volume (PV: ~10%, interaction: p = 0.718), but heat stress per se was the main driver of hypovolaemia. Thirst in DEHydration was comparably stimulated by active than passive heat stress (p < 0.161) and shared the same relation to Posm (r ≥ 0.744) and ∆BM (r ≥ 0.882). Following heat exposures, at 3% gross ∆BM, PV reduction was approximately twice as large from passive versus active heating (p = 0.003), whereas Posm perturbations were approximately twice as large from EUHydration versus DEHydration (p < 0.001). Rehydrating ad libitum resulted in a similar net fluid balance between passive versus active heat stress and restored PV despite the incomplete replacement of ∆BM. In conclusion, dehydrating by 2% ∆BM via passive heat stress generally did not cause larger changes to PV or Posm than via active heat stress. The heat stressors themselves caused a greater reduction in PV than dehydration did, whereas ingesting water to maintain euhydration produced large reductions in Posm in recovery and therefore appears to be of more physiological significance.

The Effects of Exercise Training on Plasma Volume Variations: A Systematic Review.

The aim of this systematic review was to summarize the evidence on the acute and long-term effects of exercise training on PV, in both trained and untrained individuals and to examine associations between changes in %PVV and change in physical/physiological performance. Despite the status of participants and the exercise duration or intensity, all the acute studies reported a significant decrease of PV (effect size: 0.85

High versus low ultrafiltration rates during experimental peritoneal dialysis in rats: Acute effects on plasma volume and systemic haemodynamics.

INTRODUCTION: Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates. METHODS: Experiments were conducted in two groups of healthy Sprague-Dawley rats: one group with a high ultrafiltration rate (N = 7) induced by 8.5% glucose and a low UF group (N = 6; 1.5% glucose), with an initial assessment of the extracellular fluid volume, followed by 30 min PD with plasma volume measurements at baseline, 5, 10, 15 and 30 min. Mean arterial pressure, central venous pressure and heart rate were continuously monitored during the experiment. RESULTS: No significant changes over time in plasma volume, mean arterial pressure or central venous pressure were detected during the course of the experiments, despite an ultrafiltration (UF) rate of 56 mL/h/kg in the high UF group. In the high UF group, a decrease in extracellular fluid volume of -7 mL (-10.7% (95% confidence interval: -13.8% to -7.6%)) was observed, in line with the average UF volume of 8.0 mL (standard deviation: 0.5 mL). CONCLUSION: Despite high UF rates, we found that plasma volumes were remarkably preserved in the present experiments, indicating effective refilling of the plasma compartment from interstitial tissues. Further studies should clarify which mechanisms preserve the plasma volume during high UF rates in PD.

New Classification for the Combined Assessment of the Fractional Excretion of Urea Nitrogen and Estimated Plasma Volume Status in Acute Heart Failure.

Background The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long-term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all-cause death. Secondary end points were (1) the composite of all-cause death and HF readmission, and (2) HF readmission in a time-to-event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, <35%) and ePVS (>5.5%, ≤5.5%) values at discharge: high-FEUN/low-ePVS, high-FEUN/high-ePVS, low-FEUN/low-ePVS, and low-FEUN/high-ePVS groups. During a median follow-up period of 28.1 months, there were 173 all-cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan-Meier curve analysis showed that the high-FEUN/low-ePVS group had a better prognosis than the other groups (log-rank test, P<0.001). In the multivariable Cox regression analysis, the low-FEUN/high-ePVS group had a higher mortality than the high-FEUN/low-ePVS group (hazard ratio, 2.92 [95% CIs, 1.73-4.92; P<0.001]). Conclusions The new classification of the 4 hemodynamic profiles using the FEUN and ePVS values may play an important role in improving outcomes in patients with stable acute decompensated HF.

Hypoxia briefly increases diuresis but reduces plasma volume by fluid redistribution in women.

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

Mechanistic insights into chloride-related heart failure progression according to the plasma volume status.

AIMS: Two types of heart failure (HF) progression were recently proposed on the basis of an increased vs. non-increased serum chloride concentration. The applicability of this concept to real-world HF pathophysiology requires further investigation. The present study evaluated the mechanisms of HF progression to a different type according to changes in the estimated plasma volume status (ePVS). METHODS AND RESULTS: Data from 47 patients (32% men; 78.2 ± 9.7 years of age) with stable to worsening HF (37.5 ± 16 days) were analysed. Physical examination, standard blood tests, and b-type natriuretic peptide (BNP) measurements were conducted. The ePVS was calculated as follows: ePVS (dL/g) = [100 - haematocrit (%)]/[haemoglobin (g/dL)]. For the study subjects as a whole (n = 47), changes in the ePVS correlated positively with changes in the serum chloride concentration from stable to worsening HF (r = 0.398, P = 0.0056). When divided into two groups of worsening HF with an increased (n = 31) vs. non-increased serum chloride concentration (n = 16), no significant baseline differences in body weight, serum logBNP, or ePVS were detected between groups. Under worsening HF, the increase in body weight (2.34 ± 1.12 vs. 2.59 ± 1.56 kg, P = 0.57) and logBNP (0.39 ± 0.30 vs. 0.54 ± 0.31 pg/mL, P = 0.13) did not differ between groups, but the increase in the ePVS was smaller in the group with a non-increased serum chloride concentration compared with that with an increased serum chloride concentration (0.292 ± 0.49 vs. 0.653 ± 0.60 dL/g, P = 0.044). An increase in the %change in ePVS ≥ 10% was less common in patients with a non-increased chloride concentration (37% vs. 71%, P = 0.03). Patients with a non-increased serum chloride concentration had more HF signs (3.31 ± 0.79 vs. 2.65 ± 0.71, P = 0.005) and a higher incidence of pulmonary rales (63% vs. 16%, P = 0.0024) than those with an increased serum chloride concentration. CONCLUSIONS: According to the changes in the ePVS, HF progression may result from a difference between two HF types (i.e. increased vs. non-increased serum chloride concentration) in the cardiac reserve in response to a given cardiac burden by modulating plasma volume status via the possible tonicity potential of chloride.

Hemodynamic pathways of gestational hypertension and preeclampsia.

Gestational hypertension and preeclampsia are the 2 main types of hypertensive disorders in pregnancy. Noninvasive maternal cardiovascular function assessment, which helps obtain information from all the components of circulation, has shown that venous hemodynamic dysfunction is a feature of preeclampsia but not of gestational hypertension. Venous congestion is a known cause of organ dysfunction, but its potential role in the pathophysiology of preeclampsia is currently poorly investigated. Body water volume expansion occurs in both gestational hypertension and preeclampsia, and this is associated with the common feature of new-onset hypertension after 20 weeks of gestation. Blood pressure, by definition, is the product of intravascular volume load and vascular resistance (Ohm's law). Fundamentally, hypertension may present as a spectrum of cardiovascular states varying between 2 extremes: one with a predominance of raised cardiac output and the other with a predominance of increased total peripheral resistance. In clinical practice, however, this bipolar nature of hypertension is rarely considered, despite the important implications for screening, prevention, management, and monitoring of disease. This review summarizes the evidence of type-specific hemodynamic profiles in the latent and clinical stages of hypertensive disorders in pregnancy. Gestational volume expansion superimposed on an early gestational closed circulatory circuit in a pressure- or volume-overloaded condition predisposes a patient to the gradual deterioration of overall circulatory function, finally presenting as gestational hypertension or preeclampsia-the latter when venous dysfunction is involved. The eventual phenotype of hypertensive disorder is already predictable from early gestation onward, on the condition of including information from all the major components of circulation into the maternal cardiovascular assessment: the heart, central and peripheral arteries, conductive and capacitance veins, and body water content. The relevance of this approach, outlined in this review, openly invites for more in-depth research into the fundamental hemodynamics of gestational hypertensive disorders, not only from the perspective of the physiologist or the scientist, but also in assistance of clinicians toward understanding and managing effectively these severe complications of pregnancy.

One-year change in plasma volume and mortality in the Japanese general population: An observational cohort study.

BACKGROUND: Changes in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population. METHODS AND RESULTS: We used a nationwide database of 134,291 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss-Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan-Meier analysis demonstrated that the highest 5th quintile had the greatest risk among the five groups. Multivariate Cox proportional hazard regression analysis demonstrated that a 1-year change in plasma volume was an independent risk factor for all-cause, cardiovascular, non-cardiovascular, and cancer deaths. The addition of a 1-year change in plasma volume to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes. CONCLUSIONS: Here, we have demonstrated for the first time that a 1-year change in plasma volume could be an additional risk factor for all-cause, cardiovascular, and non-cardiovascular (mainly cancer) mortality in the general population.

Interval-induced metabolic perturbation determines tissue fluid shifts into skeletal muscle.

Intense interval exercise has proven to be as effective as traditional endurance exercise in improving maximal oxygen uptake. Shared by these two exercise regimes is an acute reduction in plasma volume, which is a suggested stimulus behind exercise-induced increases in blood volume and maximal oxygen uptake. This study aimed to link exercise-induced metabolic perturbation with volume shifts into skeletal muscle tissue. Ten healthy subjects (mean age 33 ± 8 years, 5 males and 5 females) performed three 30 s all-out sprints on a cycle ergometer. Upon cessation of exercise magnetic resonance imaging, 31 Phosphorus magnetic resonance spectroscopy and blood samples were used to measure changes in muscle volume, intramuscular energy metabolites and plasma volume. Compared to pre-exercise, muscle volume increased from 1147.1 ± 35.6 ml to 1283.3 ± 11.0 ml 8 min post-exercise. At 30 min post-exercise, muscle volume was still higher than pre-exercise (1147.1 ± 35.6 vs. 1222.2 ± 6.8 ml). Plasma volume decreased by 16 ± 3% immediately post-exercise and recovered back to - 5 ± 6% after 30 min. Principal component analysis of exercise performance, muscle and plasma volume changes as well as changes in intramuscular energy metabolites showed generally strong correlations between metabolic and physiological variables. The strongest predictor for the volume shifts of muscle and plasma was the magnitude of glucose-6-phosphate accumulation post-exercise. Interval training leads to large metabolic and hemodynamic perturbations with accumulation of glucose-6-phosphate as a possible key event in the fluid flux between the vascular compartment and muscle tissue.

Plasma volume treated with double filtration plasmapheresis and outcomes of acute antibody-mediated rejection in kidney transplant recipients: A retrospective cohort study.

A retrospective cohort study was conducted to evaluate the association between the plasma volume treated by double filtration plasmapheresis and allograft outcomes for the treatment of acute antibody-mediated rejection in kidney transplant recipients. Patients were divided into two groups: group 1, plasma volume treated between 1 and <1.3 total plasma volume and group 2, plasma volume treated ≥1.3 total plasma volume. Primary outcome was ≥50% reduction of serum creatinine rising from baseline value at 1 month. A total of 32 courses (146 sessions) of double filtration plasmapheresis were performed; 17 and 15 courses in group 1 and group 2, respectively. Primary outcome occurred in 41% of group 1 and 40% of group 2 (adjusted risk ratio 1.15 [95%CI, 0.48-2.76]). Graft loss at 1 year did not differ between the two groups (adjusted hazard ratio 0.65 [95%CI, 0.23-1.87]). Infection tendency seemed to be higher in group 2 (40% vs 18%, P = .243).

Calculated plasma volume status predicts outcomes after transcatheter aortic valve implantation.

OBJECTIVES: Congestion can worsen outcomes after transcatheter aortic valve implantation (TAVI), but can be difficult to quantify non-invasively. We hypothesised that preprocedural plasma volume status (PVS), estimated using a validated formula that enumerates percentage change from ideal PV, would provide prognostic utility post-TAVI. METHODS: This retrospective cohort study identified patients who underwent TAVI (2007-2017) from a prospectively collected database. Actual ([1-haematocrit] × [a + (b × weight (Kg))] and ideal (c × weight (Kg)) PV were quantified from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual - ideal PV)/ideal PV]). RESULTS: In 564 patients (mean age 82±7 years, 49% male), mean PVS was -2.7±10.2%, with PV expansion (PVS >0%) evident in 39%. Only logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) independently predicted a PVS >0% (OR 1.85, p=0.002). On Cox analyses, a PVS >0% was associated with greater mortality at 3 (HR 2.29, 95% CI 1.11 to 4.74, p=0.03) and 12 months (HR 2.00, 95% CI 1.23 to 3.26, p=0.006) after TAVI, independently of, and incremental to, the EuroSCORE and New York Heart Association class. A PVS >0% was also independently associated with more days in intensive care (coefficient: 0.41, 95% CI 0.04 to 0.78, p=0.03) and in hospital (coefficient: 1.95, 95% CI 0.48 to 3.41, p=0.009). CONCLUSION: Higher PVS values, calculated simply from weight and haematocrit, are associated with greater mortality and longer hospitalisation post-TAVI. PVS could help refine risk stratification and further investigations into the utility of PVS-guided management in TAVI patients is warranted.

Low Plasma Volume and Increased Pressure Load Relate to Concentric Left Ventricular Remodeling After Preeclampsia: A Longitudinal Study.

Background During uncomplicated pregnancy, left ventricular remodeling occurs in an eccentric way. In contrast, during preeclamptic gestation, the left ventricle hypertrophies concentrically, concurrent with loss in circulatory volume and increased blood pressure. Concentric cardiac structure persists in a substantial proportion of women and may be associated with pressure and volume load after preeclampsia. We hypothesize that low volume load, as indicated by plasma volume (PV) after preeclampsia and increased pressure load, is associated with remote concentric remodeling. Methods and Results In this longitudinal cohort study, we included 100 formerly preeclamptic women. Two visits were performed: at 0.8 years postpartum and at 4.8 years postpartum. During visit 1, we measured blood pressure and PV (I125 dilution technique, low PV ≤48 mL/kg lean body mass). During the second visit, we assessed cardiac geometry by cardiac ultrasound. Concentric remodeling was defined as relative wall thickness >0.42 and left ventricular mass index ≤95 g/m2. We adjusted multivariable analysis for primiparity, systolic blood pressure, PV mL/kg lean body mass, and antihypertensive medication at visit 1. Low PV is associated with remote concentric remodeling (odds ratio [OR], 4.37; 95% CI, 1.06-17.40; and adjusted OR, 4.67; 95% CI, 1.02-21.42). Arterial pressure load (systolic, diastolic, and mean arterial pressure) is also associated with development of concentric remodeling (OR, 1.15 [95% CI, 0.99-1.35]; OR, 1.24 [95% CI, 0.98-1.58]; and OR, 1.20 [95% CI, 0.98-1.47], respectively). Conclusions In former preeclamptic women, development toward left ventricular concentric remodeling is associated with low volume load and increased pressure load.

A multi-parametric approach to remove the influence of plasma volume on the athlete biological passport during a Union Cycliste Internationale cycling stage race.

Fluctuations in plasma volume (PV) present potential confounders within the concentration-based markers of the haematological athlete biological passport (ABP). Here, a multi-parametric approach involving a simple blood test is applied to the current ABP adaptive model in an attempt to remove the influence of PV expansion, induced by a cycling stage race. Blood samples were obtained from 29 professional cyclists (14 male, 15 female) before, during and after 4-5 consecutive days of racing. Whole blood was analysed in accordance with the World Anti-Doping Agency ABP guidelines for haemoglobin ([Hb]) concentration and platelets. Serum and plasma were analysed for transferrin, albumin, calcium, creatinine, total protein and low-density lipoprotein. PV variation (Z-scores) was estimated using a multi-parametric model (consisting of the biomarkers mentioned earlier) and compared against calculated variations in PV (measured via CO-rebreathing). Significant reductions in [Hb] and the OFF-score were observed in female cyclists after 3 and 4 days of racing, with accompanying increases in PV, which returned to baseline values 4 days post competition. Similarly, a significant increase in PV was observed in male cyclists after 3 and 5 days of racing. When individual estimations of PV variance were applied to the adaptive model, the upper and lower reference predictions for [Hb] and the OFF-score were refined such that all outliers consistent with racing-induced PV changes were removed. The PV model appears capable of reducing the influence of PV on concentration-dependent markers during competition. This is an important step towards the inclusion of the PV correction in the ABP haematological module.

Effects of recreational scuba diving on erythropoiesis-"normobaric oxygen paradox" or "plasma volume regulation" as a trigger for erythropoietin?

PURPOSE: Previous studies have shown an increase in erythrocyte lipid peroxidation and a decrease in red blood cell (RBC) count, hemoglobin, and hematocrit after only one recreational scuba diving session. The aim of this study was to examine the effect of repetitive scuba diving on RBC parameters and erythropoiesis. METHODS: Divers (N = 14) conducted one dive per week over 5 weeks at a depth of 20-30 m for 30 min. For measuring RBC parameters, erythropoietin, iron, and ferritin, blood samples were collected before and after the first, third, and fifth dive. RESULTS: Between pre- and post-dive results, a statistically significant increase in RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), RBC distribution width (RDW), iron, and ferritin was observed. Analysis of the results between the first, third, and fifth dive showed that the erythropoietin increase at the third (pre-dive p = 0.009; post-dive p = 0.004) and fifth dive (pre-dive p < 0.001; post-dive p = 0.003) was not accompanied by changes in RBC count, hemoglobin, iron, and ferritin. In parallel, a continuous increase in hematocrit, MCV, and RDW was observed, whereas mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) decreased. CONCLUSIONS: Changes in RBC indices and EPO elevation indicate that the occasional switch from hyperoxia to normoxia or mechanisms for plasma volume regulation may be a step in the maintenance of erythropoiesis.

Fluctuations in hematological athlete biological passport biomarkers in relation to the menstrual cycle.

The interpretation of athlete biological passport (ABP) is strengthened by understanding the natural fluctuations in its biological parameters. Here we have assessed the influence of the menstrual cycle on the hematological module of the ABP. Seventeen women with regular menses were included. Blood samples were collected once a week for two consecutive cycles and analyzed for hematological parameters. Menstrual phases were hormonally determined. The intra-individual variation in the hematological parameters was similar between the two cycles. Reticulocyte percentage was significantly lower in the follicle phase (median 0.95%) than in the ovulatory (median 1.10%) and luteal phases (median 1.16%), P = 0.006, whereas no differences were found in hemoglobin concentration, hematocrit, red blood cell count, or red blood cell indices. When the values were entered into the ABP model, findings outside the program-calculated individual thresholds were identified in two participants. One woman showed an atypical low OFF-score in the last sample collected, mainly because of increased reticulocyte percentage. This was likely a response to treated insufficient iron stores. One woman displayed an atypical hemoglobin value at the lower limit 2 weeks after ovulation, which was likely due to fluctuations in plasma volume. In conclusion, the ABP parameters in general are stable throughout the menstrual cycle. Significant differences between the menstrual phases were found in reticulocytes; however, the variation was not related to findings outside the individual thresholds, except in one individual. Moreover, our results highlight the importance of having information about iron supplementation available when evaluating hematological passports.

Understanding and extending the Starling principle.

The Starling Principle states that fluid movements between blood and tissues are determined by differences in hydrostatic and colloid osmotic (oncotic) pressures between plasma inside microvessels and fluid outside them. The Revised Starling Principle recognizes that, because microvessels are permeable to macromolecules, a balance of pressures cannot halt fluid exchange. In most tissues, steady oncotic pressure differences between plasma and interstitial fluid depend on low levels of steady filtration from plasma to tissues for which the Revised Principle provides the theory. Plasma volume is normally maintained by fluid losses from filtration being matched by fluid gains from lymph. Steady state fluid uptake into plasma only occurs in tissues such as intestinal mucosa and renal peri-tubular capillaries where a protein-free secretion of adjacent epithelia contributes significantly to interstitial fluid volume and keeps interstitial oncotic pressure low. Steady filtration rates in different tissues are disturbed locally by reflex changes in capillary pressure and perfusion. The rapid overall decline in capillary pressure after acute blood loss initiates rapid fluid uptake from tissue to plasma, that is, autotransfusion. Fluid uptake is transient, being rapid at first then attenuating but low levels may continue for more than an hour. The Revised Principle highlights the role of oncotic pressure of small volumes of interstitial fluid within a sub-compartment surrounding the microvessels rather than the tissue's mean interstitial fluid oncotic pressure. This maximizes oncotic pressure differences when capillary pressure are high and enhances initial absorption rates when pressures are low, accelerating short-term regulation of plasma volume.

Volume kinetic analysis of fluid retention after induction of general anesthesia.

BACKGROUND: Induction of general anesthesia increases the hemodilution resulting from infusion of crystalloid fluid, which is believed to be due to slower distribution caused by arterial hypotension. When normal distribution returns is not known. METHODS: An intravenous infusion of 25 mL kg- 1 of Ringer's lactate was infused over 30 min to 25 volunteers just after induction of general anesthesia for open abdominal hysterectomy. A two-volume model was fitted to the repeated measurements of the blood hemoglobin concentration and the urinary excretion using mixed-effects modelling software. Individual-specific covariates were added in sequence. RESULTS: Distribution of infused fluid was interrupted during the first 20 min of the infusions. During this time 16.6 mL kg- 1 of lactated Ringer's had been infused, of which virtually all remained in the circulating blood. Thereafter, the fluid kinetics was similar to that previously been found in awake volunteers except for the elimination rate constant (k10), which remained to be very low (0.86 × 10- 3 min- 1). Redistribution of infused fluid from the interstitium to the plasma occurred faster (higher k21) when the arterial pressure was low. No covariance was found between the fixed parameters and preoperatively concentrated urine, the use of sevoflurane or propofol to maintain the anesthesia, or the plasma concentrations of two degradation products of the endothelial glycocalyx, syndecan-1 and heparan sulfate. CONCLUSIONS: Induction of general anesthesia interrupted the distribution of lactated Ringer's solution up to when 16.6 mL kg- 1 of crystalloid fluid had been infused. Plasma volume expansion during this period of time was pronounced. TRIAL REGISTRATION: Controlled-trials.com (ISRCTN81005631) on May 17, 2016 (retrospectively registered).

Drugs in pregnancy: Pharmacologic and physiologic changes that affect clinical care.

Pharmacologic interventions play a major role in obstetrical care throughout pregnancy, labor and delivery and the postpartum. Traditionally, obstetrical providers have utilized standard dosing regimens developed for non-obstetrical indications based on pharmacokinetic knowledge from studies in men or non-pregnant women. With the recognition of pregnancy as a special pharmacokinetic population in the late 1990s, investigators have begun to study drug disposition in this unique patient dyad. Many of the basic physiologic changes that occur during pregnancy have significant impact on drug absorption, distribution and clearance. Activity of Phase I and Phase II drug metabolizing enzymes are differentially altered by pregnancy, resulting in drug concentrations sufficiently different for some medications that efficacy or toxicity is affected. Placental transporters play a major dynamic role in determining fetal drug exposure. In the past two decades, we have begun to expand our understanding of obstetrical pharmacology; however, to truly optimize pharmacologic care of our pregnant patients and their developing fetus, additional research is critically needed.

Intravascular volumes evaluated by a carbon monoxide rebreathing method in patients undergoing chronic hemodialysis.

INTRODUCTION: Treatment of fluid overload and anemia remains a challenge in patients undergoing hemodialysis. Hypervolemia can be evaluated using a carbon monoxide (CO) rebreathing method by which blood volume (BV), plasma volume (PV), and red blood cell volumes (RBCV) can be determined. We hypothesized that recurrent hypervolemia would cause hemoglobin (Hb) levels to be in the anemic range without a concurrent reduction in RBCV in patients undergoing hemodialysis. METHODS: BV, PV, and RBCV were determined by a CO rebreathing test in 19 patients with type 2 diabetes undergoing chronic hemodialysis. The tests were performed 20 minutes before initiating dialysis, and the measured intravascular volumes were compared with predicted normal intravascular volumes according to Nadler's equation. Before initiating dialysis, Hb and blood pressure were measured, and edema severity was graded. FINDINGS: Measured BV was higher in 17 out of the 19 patients with a median of 71.1 (62.4-76.9) mL/kg and higher than the predicted BV of 58.3 (53.5-59.9) mL/kg (P < 0.001). The measured PV was found to be higher in all patients. RBCV was measured as 25.2 (23.4-28.2) mL/kg with a predicted volume of 25.9 (22.4-26.7) mL/kg (P = 0.56). Eighteen patients were anemic as determined by Hb concentrations (defined as Hb < 13 g/dL for men and <12 g/dL for women), and nine were anemic according to RBCV. DISCUSSION: The CO rebreathing test is a new approach to measuring intravascular volumes in hemodialysis patients. Compared with predicted intravascular volumes, the predialysis BV was expanded in the majority with elevated PV as the main cause. No overall difference in RBCV was found between the measured and predicted volumes. According to predialysis Hb levels, all but one patient was anemic, but according to the measured RBCV, only nine were in the anemic range, indicating dilution of Hb.

Estimated plasma volume and mortality: analysis from NHANES 1999-2014.

BACKGROUND: While estimated plasma volume (ePV) has been studied in some diseases, such as heart failure, the relationship between ePV and all-cause or cause-specific mortality remains unexplored. Therefore, we investigated the association between ePV and all-cause, cardiovascular (CV), and cancer-related mortality among adults in the US. METHOD: We used the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and included participants older than 18 years. Mortality data were obtained from the National Death Index and matched to the NHANES participants. ePV was derived using Strauss formula. Cox proportional hazard models were fit to estimate hazard ratios for all-cause and cause-specific mortality without and with adjustment for potential confounders. RESULTS: Of the 42,705 participants, 5194 died (1121 CV deaths) during mean follow-up of 8.0 (range 0-16.7) years. Mean ± SD age and ePV of the participants were 47.2 ± 19.4 years and 4.2 ± 0.84, respectively. In unadjusted models, 1 unit increase in ePV was associated with 29%, 32%, and 16% increased risk in all-cause (HR 1.29; 95% CI 1.24, 1.35), CV (HR 1.32; 95% CI 1.22, 1.43), and cancer-related (HR 1.16; 95% CI 1.05, 1.27) mortality. Risk remained high in adjusted models (all-cause HR 1.24; 95% CI 1.18, 1.30; CV HR 1.22; 95% CI 1.11, 1.34; cancer-specific HR 1.24; 95% CI 1.10, 1.39). When comparing the highest and lowest ePV quartiles, similar results were noted (adjusted all-cause HR 1.64; 95% CI 1.45, 1.86; CV HR 1.52; 95% CI 1.19, 1.93; cancer HR 1.85; 95% CI 1.38, 2.49). CONCLUSION: An increase in ePV was associated with increased all-cause and cause-specific mortality. Further studies are needed to explore the mechanism of this relationship and translation into a better outcome.