Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

A simple and novel equation to estimate the degree of bleeding in haemorrhagic shock: mathematical derivation and preliminary in vivo validation.

Determining blood loss [100% - RBV (%)] is challenging in the management of haemorrhagic shock. We derived an equation estimating RBV (%) via serial haematocrits (Hct1, Hct2) by fixing infused crystalloid fluid volume (N) as [0.015 × body weight (g)]. Then, we validated it in vivo. Mathematically, the following estimation equation was derived: RBV (%) = 24k / [(Hct1 / Hct2) - 1]. For validation, nonongoing haemorrhagic shock was induced in Sprague-Dawley rats by withdrawing 20.0%-60.0% of their total blood volume (TBV) in 5.0% intervals (n = 9). Hct1 was checked after 10 min and normal saline N cc was infused over 10 min. Hct2 was checked five minutes later. We applied a linear equation to explain RBV (%) with 1 / [(Hct1 / Hct2) - 1]. Seven rats losing 30.0%-60.0% of their TBV suffered shock persistently. For them, RBV (%) was updated as 5.67 / [(Hct1 / Hct2) - 1] + 32.8 (95% confidence interval [CI] of the slope: 3.14-8.21, p = 0.002, R2 = 0.87). On a Bland-Altman plot, the difference between the estimated and actual RBV was 0.00 ± 4.03%; the 95% CIs of the limits of agreements were included within the pre-determined criterion of validation (< 20%). For rats suffering from persistent, non-ongoing haemorrhagic shock, we derived and validated a simple equation estimating RBV (%). This enables the calculation of blood loss via information on serial haematocrits under a fixed N. Clinical validation is required before utilisation for emergency care of haemorrhagic shock.

Applying the Optimized CO Rebreathing Method for Measuring Blood Volumes and Hemoglobin Mass in Heart Failure Patients.

Introduction: Determination of blood volume, red cell volume, and plasma volume contributes to the understanding of the pathophysiology in heart failure, especially concerning anemia and volume load. The optimized carbon monoxide (CO)-rebreathing method (oCORM) is used to determine these parameters and hemoglobin mass (Hbmass) in exercise physiology. The applicability of oCORM to determine the intravascular volumes and Hbmass in heart failure patients is currently undetermined because assumptions concerning CO kinetics with oCORM rely on healthy subjects with a normal ejection fraction. Therefore, the aim of the present study is to determine the applicability and the systematic error of oCORM arising from a reduced EF when oCORM is used for measurement of intravascular volumes and Hbmass in heart failure patients. Methods: oCORM was performed in 21 patients with heart failure and a reduced ejection fraction (EF) of < 30% (EFsev) and 25 controls (CONT). CO kinetics in capillary blood was studied 3-15 min after commencement of CO rebreathing. Differences in CO kinetics between the groups were assessed using a generalized linear model. The systematic error for determination of Hbmass with oCORM arising from differences in CO kinetics was assessed using the Monte Carlo method. Results: The CO kinetics was significantly different between EFsev and CONT. In both groups, exposure to CO led to a COHb increase to 6.0 ± 1.0% 3 min after CO rebreathing. There were no CO related side effects or any clinical symptoms. Monte Carlo simulation quantifies the systematic error for determination of Hbmass arising from an impaired ejection fraction to be -0.88%. Conclusion: Our results indicate an impaired vascular mixing of CO when EF is severely reduced. When Hbmass is determined using the original oCORM protocol in heart failure patients with a reduced EF, the systematic underestimation of about 1% should be considered. However, the error arising from this impaired vascular mixing appears small and clinically negligible. Furthermore, application of oCORM was safe and not related to any side effects resulting from CO exposure. In conclusion, oCORM can be used for assessing intravascular volumes and Hbmass in patients with a reduced EF.

Evaluation of end-tidal carbon dioxide gradient as a predictor of volume responsiveness in spontaneously breathing healthy adults.

BACKGROUND: Methods to guide fluid therapy in spontaneously breathing patients are scarce. No studies have reported the accuracy of end-tidal CO2 (ET-CO2) to predict volume responsiveness in these patients. We sought to evaluate the ET-CO2 gradient (ΔET-CO2) after a passive leg rise (PLR) maneuver to predict volume responsiveness in spontaneously breathing healthy adults. METHODS: We conducted a prospective study in healthy adult human volunteers. A PLR maneuver was performed and cardiac output (CO) was measured by transthoracic echocardiography. ET-CO2 was measured with non-invasive capnographs. Volume responsiveness was defined as an increase in cardiac output (CO) > 12% at 90 s after PLR. RESULTS: Of the 50 volunteers, 32% were classified as volume responders. In this group, the left ventricle outflow tract velocity time integral (VTILVOT) increased from 17.9 ± 3.0 to 20.4 ± 3.4 (p = 0.0004), CO increased from 4.4 ± 1.5 to 5.5 ± 1.6 (p = 0.0), and ET-CO2 rose from 32 ± 4.84 to 33 ± 5.07 (p = 0.135). Within the entire population, PLR-induced percentage ∆CO was not correlated with percentage ∆ET-CO2 (R2 = 0.13; p = 0.36). The area under the receiver operating curve for the ability of ET-CO2 to discriminate responders from non-responders was of 0.67 ± 0.09 (95% CI 0.498-0.853). A ΔET-CO2 ≥ 2 mmHg had a sensitivity of 50%, specificity of 97.06%, positive likelihood ratio of 17.00, negative likelihood ratio of 0.51, positive predictive value of 88.9%, and negative predictive value of 80.5% for the prediction of fluid responsiveness. CONCLUSIONS: ΔET-CO2 after a PLR has limited utility to discriminate responders from non-responders among healthy spontaneously breathing adults.

Calculation of the Residual Blood Volume after Acute, Non-Ongoing Hemorrhage Using Serial Hematocrit Measurements and the Volume of Isotonic Fluid Infused: Theoretical Hypothesis Generating Study.

Fluid resuscitation, hemostasis, and transfusion is essential in care of hemorrhagic shock. Although estimation of the residual blood volume is crucial, the standard measuring methods are impractical or unsafe. Vital signs, central venous or pulmonary artery pressures are inaccurate. We hypothesized that the residual blood volume for acute, non-ongoing hemorrhage was calculable using serial hematocrit measurements and the volume of isotonic solution infused. Blood volume is the sum of volumes of red blood cells and plasma. For acute, non-ongoing hemorrhage, red blood cell volume would not change. A certain portion of the isotonic fluid would increase plasma volume. Mathematically, we suggest that the residual blood volume after acute, non-ongoing hemorrhage might be calculated as 0·25N/[(Hct1/Hct2)-1], where Hct1 and Hct2 are the initial and subsequent hematocrits, respectively, and N is the volume of isotonic solution infused. In vivo validation and modification is needed before clinical application of this model.

Prospective analysis of cardiac collapsibility of inferior vena cava using ultrasonography.

PURPOSE: The inferior vena cava (IVC) diameter and its respiratory change (respiratory variation) reportedly correlate well with the central venous pressure and response to fluid. However, changes in the IVC diameter are related to the cardiac rhythm (cardiac variation), which can be useful as an indicator for intravascular volume but can affect respiratory variation. We conducted a prospective analysis of this cardiac variation in adult emergency department patients. METHODS: Ultrasonographic IVC images from 190 consecutive adult emergency department patients were collected prospectively. The IVC diameters 2 cm caudal from the middle hepatic vein were tracked automatically and measured. The IVC diameter changes were analyzed using a software program that tracks 2-dimensional motion in B-mode images. Cardiac and respiratory variations were calculated and analyzed. RESULTS: The average IVC cardiac variation was 11.0% (95% confidence interval, 9.8%-12.3%) in these patients, which affects the respiratory variation resulting in 1.68-fold higher overestimation of respiratory variation. The coefficient of correlation between IVC cardiac variations and respiratory variations was 0.34 (P < .05). CONCLUSIONS: The IVC cardiac variation affects our interpretation of ultrasonography IVC imaging. The IVC cardiac variation provides several advantages over other parameters of intravascular volume. Therefore, it can be a novel tool to assess the intravascular volume of the patients.

Pulmonary blood volume measured by contrast enhanced ultrasound: a comparison with transpulmonary thermodilution.

BACKGROUND: Blood volume quantification is essential for haemodynamic evaluation guiding fluid management in anaesthesia and intensive care practice. Ultrasound contrast agent (UCA)-dilution measured by contrast enhanced ultrasound (CEUS) can provide the UCA mean transit time (MTT) between the right and left heart, enabling the assessment of the intrathoracic blood volume (ITBV(UCA)). The purpose of the present study was to investigate the agreement between UCA-dilution using CEUS and transpulmonary thermodilution (TPTD) in vitro and in vivo. METHODS: In an in vitro setup, with variable flows and volumes, we injected a double indicator, ice-cold saline with SonoVue(®), and performed volume measurements using transesophageal echo and thermodilution by PiCCO(®). In a pilot study, we assigned 17 patients undergoing elective cardiac surgery for pulmonary blood volume (PBV) measurement using TPTD by PiCCO(®) and ITBV by UCA-dilution. Correlation coefficients and Bland-Altman analysis were performed for all volume measurements. RESULTS: In vitro, 73 experimental MTT's were obtained using PiCCO(®) and UCA-dilution. The volumes by PiCCO(®) and UCA-dilution correlated with true volumes; r(s)=0.96 (95% CI, 0.93-0.97; P<0.0001) and r(s)=0.97 (95% CI, 0.95-0.98; P<0.0001), respectively. The bias of PBV by PiCCO(®) and ITBV(UCA) were -380 ml and -42 ml, respectively. In 16 patients, 86 measurements were performed. The correlation between PBV by PiCCO(®) and ITBV(UCA) was r(s)=0.69 (95% CI 0.55-0.79; P<0.0001). Bland-Altman analysis revealed a bias of -323 ml. CONCLUSIONS: ITBV assessment with CEUS seems a promising technique for blood volume measurement, which is minimally-invasive and bedside applicable. CLINICAL TRIAL REGISTRATION: ISRCTN90330260.

A Theoretical Mathematical Model to Estimate Blood Volume in Clinical Practice.

Perioperative intravenous (IV) fluid management is controversial. Fluid therapy is guided by inaccurate algorithms and changes in the patient's vital signs that are nonspecific for changes to the patient's blood volume (BV). Anesthetic agents, patient comorbidities, and surgical techniques interact and further confound clinical assessment of volume status. Through adaptation of existing acute normovolemic hemodilution algorithms, it may be possible to predict patient's BV by measuring hematocrit (HcT) before and after hemodilution. Our proposed mathematical model requires the following four data points to estimate a patient's total BV: ideal BV, baseline HcT, a known fluid bolus (FB), and a second HcT following the FB. To test our method, we obtained 10 ideal and 10 actual subject BV data measures from 9 unique subjects derived from a commercially used Food and Drug Administration-approved, semi-automated, BV analyzer. With these data, we calculated the theoretical BV change following a FB. Using the four required data points, we predicted BVs (BVp) and compared our predictions with the actual BV (BVa) measures provided by the data set. The BVp calculated using our model highly correlated with the BVa provided by the BV analyzer data set (df = 8, r = .99). Our calculations suggest that, with accurate HcT measurement, this method shows promise for the identification of abnormal BV states such as hyper- and hypovolemia and may prove to be a reliable method for titrating IV fluid.

RBC volume deficiency in patients with excessive orthostatic decrease in cerebral blood flow velocity.

BACKGROUND: Orthostatic intolerance (OI) is common but heterogeneous. There is a subgroup of OI patients who have excessive decrease in cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries (MCAs) during head-up tilt without systemic blood pressure change. This study evaluated the role of blood volume reduction in such patients. METHODS: Patients with idiopathic OI who had excessive orthostatic decrease (>20% of the supine level) in mean CBFV of bilateral MCAs and who also received blood volume determination were collected. The chromium (5¹Cr) dilution method was used for red blood cell (RBC) volume determination in these patients. The blood volume was expressed as a percentage of the expected volume. These patients were further divided into two groups, those with postural tachycardia syndrome (POTS group) and those without (non-POTS group). The data of RBC volume were compared between the two groups. Besides, we used multivariate linear regression to evaluate the factors that predict RBC volume. RESULTS: Twenty-five patients (13 females, median age = 28 years) were enrolled in this study. Nine of these patients had POTS (5 females, median age = 26 years) and 16 did not (8 females, median age = 29.5 years). Compared with the expected volume, the RBC volume was significantly reduced in all patients (median = 82% of the expected volume). Moreover, the RBC volume was significantly lower in the POTS group than that in the non-POTS group (78% vs. 85% of the expected volume, p = 0.013). The orthostatic decrease of MCA flow velocity was 28.3% in the POTS group and 32.5% in the non-POTS group (p = 0.140). The orthostatic pulsatility index increment was 15.4% in the POTS group and 20.5% in the non-POTS group (p = 0.438). Moreover, basic demography and hemoglobin levels were not different between the two groups. After multivariate linear regression (dependent variables including age, sex, body surface, and groups), only the presence of POTS significantly predicted the RBC volume (p = 0.006). CONCLUSION: The results of our study indicated that low RBC volume may play an important role in the pathophysiology of OI in this group of patients. Moreover, its role seems even more relevant in patients with POTS than in those without. Further studies for mechanistic evaluation are needed in the future.

Radioisotope blood volume measurement in hemodialysis patients.

Accurate assessment of blood volume (BV) may be helpful for prescribing hemodialysis (HD) and for reducing complications related to hypovolemia and volume overload. Monitoring changes in relative BV (RBV) using hematocrit, e.g., Crit-Line Monitor (CLM-III), an indirect method, cannot be used to determine absolute BV. We report the first study of BV measurement for assessing volume status in HD patients using the indicator dilutional method. Ten adult HD patients were enrolled in this prospective observational study. BV measurement was performed before and after HD using BV analysis (BVA)-100 (Daxor Corporation, New York, NY, USA). BVA-100 calculates BV using radiolabeled albumin (Iodine-131) followed by serial measures of the radioisotope. Fluid loss from the extravascular space was calculated by subtracting the change in BV from total weight loss. Intradialytic changes in RBV were measured by CLM-III. Eight out of 10 cases had significant hypervolemia, two cases were normovolemic. The range of BV variation from predicted normal was 156 to 1990 mL. Significant inter-individual differences in extravascular space fluid loss ranged from 54% to 99% of total weight loss. Spearman correlation showed a good correlation in the measurement of RBV by BVA-100 and CLM-III in 8 out of 10 patients (r(2) = 0.64). BV measurement using BVA-100 is useful to determine absolute BV as well as changes in BV and correlates reasonably well with CLM-III measurements. Individual refilling ability can be determined as well. This may prove useful in prescribing and monitoring ultrafiltration rates, establishment of optimal BV in HD patients and reducing morbidity and mortality associated with chronic HD.

Avaliação da responsividade a volume em pacientes sob ventilação espontânea: [revisão] / Assessment of fluid responsiveness in patients under spontaneous breathing activity~: [review]

A avaliação da responsividade a volume no paciente em ventilação espontânea representa um desafio para o intensivista. A maior parte dos conhecimentos adquiridos sobre interação coração-pulmão e o cálculo de índices dinâmicos de responsividade a fluidos podem não ser adequados para essa avaliação. Historicamente, as variáveis mais frequentemente utilizadas para guiar a responsividade a volume têm sido as medidas estáticas de pré-carga. Mais recentemente, índices dinâmicos obtidos por dispositivos menos invasivos têm sido mais usados, apesar de sua eficácia para esse fim em pacientes em ventilação espontânea ainda não ter sido adequadamente estabelecida. O objetivo deste estudo foi revisar as principais evidências sobre a avaliação da responsividade a volume nos pacientes em ventilação espontânea. A pesquisa na literatura demonstrou escassez nas evidências para utilização de medidas estáticas da volemia como as pressões de enchimento e o volume diastólico final dos ventrículos. Medidas dinâmicas como variação da pressão de pulso e outros índices também não foram adequadamente testados durante a ventilação espontânea. Resultados favoráveis foram obtidos com a variação dinâmica da pressão venosa central e com parâmetros dinâmicos que utilizam o ecocardiograma transtorácico ou doppler esofágico associado à elevação passiva dos membros inferiores. Conclui-se que embora a variação da pressão venosa central e variáveis obtidas com o ecocardiograma transtorácico ou doppler esofágico possam ser úteis na avaliação da responsividade a volume em pacientes sob ventilação espontânea, definitivamente são necessários mais estudos neste grupo de pacientes.

To assess fluid responsiveness in patients under spontaneous breathing activity ventilation remains a challenge for intensive care physicians. Much of the knowledge on heart-lung interactions and dynamic indexes of fluid responsiveness may not be useful for these patients. Historically, the most frequently used variables to guide fluid responsiveness on this population have been the static preload indexes. However, more recently, dynamic indexes from less invasive devices are being often used, even though their usefulness on spontaneously-breathing subjects remains controversial. The purpose of this article was to review evidences on the assessment of fluid responsiveness in patients under spontaneous ventilation. A search in literature showed poor evidence for use of static variables, such as filling pressures and ventricular end-diastolic volumes. Dynamic indexes, such as pulse pressure variation and other indexes had not been appropriately tested during spontaneous ventilation. Favorable results were found with central venous pressure variation and with transthoracic echocardiography or transesophageal Doppler dynamic indexes, especially when associated to passive lower limb elevation. We conclude that although central venous pressure variation and echocardiography variables could aid bedside clinicians in assessing fluid responsiveness during spontaneous ventilation, more studies on this subject are definitely required.