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Objective: We routinely calculate the pulmonary to systemic (Qp/Qs) ratio to avoid missing any left-to-right shunts in patients with precapillary pulmonary hypertension (PH). However, the pulmonary artery oxygen saturation (SpaO(2)) was lower than the mixed venous oxygen saturation (SmvO(2)) calculated using the formula; hence, the Qp/Qs ratio was calculated as less than "1" in some patients despite the absence of any detectable shunt. We hypothesized that this observation might have prognostic significance; however, to the best of our knowledge, it has not been investigated yet. Therefore, we aimed to examine the prognostic value of the Qp/Qs ratio in precapillary PH without left-to-right shunts.

When exercising with a small muscle mass, the mass-specific O2 delivery exceeds the muscle oxidative capacity resulting in a lower O2 extraction compared with whole-body exercise. We elevated the muscle oxidative capacity and tested its impact on O2 extraction during small muscle mass exercise. Nine individuals conducted six weeks of one-legged knee extension (1L-KE) endurance training. After training, the trained leg (TL) displayed 45% higher citrate synthase and COX-IV protein content in vastus lateralis and 15%-22% higher pulmonary oxygen uptake ( V˙O2peak ) and peak power output ( W˙peak ) during 1L-KE than the control leg (CON; all P

Direct Fick method is considered a standard reference method for estimation of cardiac output. It relies on indirect calorimetry to measure oxygen consumption. This is important as only a minor measurement error in oxygen consumption can result in false estimation of cardiac output. A number of studies have shown that indirect calorimetry overestimates oxygen consumption in adults. The aim of this prospective single center observational method comparison study was to compare the determination of oxygen consumption by indirect calorimetry and reverse Fick method in pediatric patients. Forty-two children mean age 352 days (range 30 to 1303 days) and mean weight 7.1 kg (range 2.7–13.6 kg) undergoing corrective cardiac surgery were included in the study. The mean (standard deviation) oxygen consumption by reverse Fick method was 43.5 (16.2) ml/min and by indirect calorimetry 49.9 (18.8) ml/min (p

Background There is continuing interest among clinicians in the potential for advanced hemodynamic monitoring and “goal directed” intravenous fluid administration guided by minimally-invasive cardiac output measurement to reduce complication rates in high risk patients undergoing major surgery. However, the adoption of the available technologies has been limited, due to cost, complexity and reliability of measurements provided. We review progress in the development of new generation methods for continuous non-invasive monitoring of cardiac output from measurement of carbon dioxide elimination in ventilated patients using the Differential Fick method. Main text The history and underlying theoretical basis are described, and its recent further development and implementation using modern generation anesthesia monitoring and delivery systems by two separate but parallel methods, termed “Capnotracking” and “Capnodynamics”. Both methods generate breath-by-breath hands-free cardiac output monitoring from changes in carbon dioxide elimination produced by automatic computerized modulation of respiratory rate delivered by an electronic ventilator. Extensive preclinical validation in animal models of hemodynamic instability, with implanted ultrasonic flow probes for gold standard reference measurements, shows this approach delivers reliable, continuous cardiac output measurement in real time. The accuracy and precision of measurement by the Capnodynamic method were maintained under a wide range of both hemodynamic and respiratory conditions, including inotropic stimulation, vasodilatation, hemorrhage, caval compression, alveolar lavage, changes in tidal volume and positive end-expiratory pressure, and hypercapnia, with only brief derangement observed in a model of lower body ischemia involving release of prolonged aortic occlusion by an intra-aortic balloon. Phase 2 testing of a Capnotracking system in patients undergoing cardiac surgery and liver transplantation has achieved a percentage error of agreement with thermodilution of +/− 38.7% across a wide range of hemodynamic states. Conclusions Progress in development of these technologies suggest that a robust, automated and reliable method of non-invasive cardiac output monitoring from capnography is close at hand for use in major surgery and critical care. The great advantage of this approach is that it can be fully integrated into the anesthesia machine and ventilator, using components that are already standard in modern anesthesia and intensive care workstations, and should be virtually hands-free and automatic.

BackgroundObjective markers of cardiac function are limited in the outpatient setting and may be beneficial for monitoring patients with chronic cardiac conditions.ObjectiveWe assess the accuracy of a scale, with the ability to capture ballistocardiography, electrocardiography, and impedance plethysmography signals from a patient’s feet while standing on the scale, in measuring stroke volume and cardiac output compared to the gold-standard direct Fick method.MethodsThirty-two patients with unexplained dyspnea undergoing level 3 invasive cardiopulmonary exercise test at a tertiary medical center were included in the final analysis. We obtained scale and direct Fick measurements of stroke volume and cardiac output before and immediately after invasive cardiopulmonary exercise test.ResultsStroke volume and cardiac output from a cardiac scale and the direct Fick method correlated with r = 0.81 and r = 0.85, respectively (P < 0.001 each). The mean absolute error of the scale estimated stroke volume was -1.58 mL, with a 95% limits of agreement (LOA) of -21.97 mL to 18.81 mL. The mean error for the scale estimated cardiac output was -0.31 L/min, with a 95% LOA of -2.62 L/min to 2.00 L/min. The change in stroke volume and cardiac output before and after exercise were 78.9% and 96.7% concordant, respectively between the two measuring methods.ConclusionsThis novel scale with cardiac monitoring abilities may allow for non-invasive, longitudinal measures of cardiac function. Using the widely accepted form factor of a bathroom scale, this method of monitoring can be easily integrated into a patient’s lifestyle.

Background Early rehabilitation can reduce ventilation duration and improve functional outcomes in critically ill patients. Upper limb strength is associated with ventilator weaning. Passive muscle loading may preserve muscle fibre function, help recover peripheral muscle strength and improve longer term, post-hospital discharge function capacity. The physiological effects of initiating rehabilitation soon after physiological stabilisation of these patients can be concerning for clinicians. This study investigated the feasibility of measuring metabolic demand and the safety and feasibility of early upper limb passive ergometry. An additional comparison of results, achieved from simultaneous application of the methods, is reported. Methods This was an observational feasibility study undertaken in an acute teaching hospital’s General Intensive Care Unit in the United Kingdom. Twelve haemodynamically stable, mechanically ventilated patients underwent 30 minutes of arm ergometry. Cardiovascular and respiratory parameters were monitored. A Friedman test identified changes in physiological parameters. A metabolic cart was attached to the ventilator to measure oxygen uptake. Oxygen uptake was concurrently calculated by the reverse Fick method, utilising cardiac output from the LiDCO™ and paired mixed venous and arterial samples. A comparison of the two methods was made. Data collection began 10 minutes before ergometry and continued to recovery. Paired mixed venous and arterial samples were taken every 10 minutes. Results Twelve patients were studied; 9 male, median age 55 years, range (27–82), median APACHE score 18.5, range (7–31), median fraction inspired oxygen 42.5%, range (28–60). Eight patients were receiving noradrenaline. Mean dose was 0.07 mcg/kg/min, range (0.01–0.15). Early ergometry was well tolerated. There were no clinically significant changes in respiratory, haemodynamic or metabolic variables pre ergometry to end recovery. There was no significant difference between the two methods of calculating VO2 (p = 0.70). Conclusions We report the feasibility of using the reverse Fick method and indirect calorimetry to measure metabolic demand during early physical rehabilitation of critically ill patients. More research is needed to ascertain the most reliable method. Minimal change in metabolic demand supports the safety and feasibility of upper limb ergometry. These results will inform future study designs for further research into exercise response in critically ill patients. Trial Registration Clinicaltrials.gov No. NCT04383171. Registered on 06 May 2020 - Retrospectively registered. http://www.clinicaltrials.gov.

This chapter examines a cornerstone of critical care medicine: the measurement and monitoring of cardiac output (CO). A key focus is placed on the relevance of CO and clinical decision-making in intensive care setting. The concepts of normalization of CO to body size and fundamentals such as the Fick principle are discussed. Expanding upon these core concepts, indicator dilution methods and thermodilution techniques with their general concepts and sources of variability are explored and applied to clinical practice. The indirect Fick method is then outlined and its clinical applications. With the evolution of critical care medicine, emphasis has been placed on ability to measure CO by using a minimally invasive approach. Pulse contour analysis and the technology available to monitor CO such as Vigileo-FloTrac system, LiDCO plus system, and PiCCO system are reviewed; their clinical relevance is outlined. Echocardiographic techniques (transesophageal and transthoracic) of estimating CO have been described. The chapter concludes with analysis of methods to assess changes in thoracic volume and their relation to CO: thoracic bioimpedance and thoracocardiography.

We analysed the importance of systemic and peripheral arteriovenous O2 difference ( a - v ¯ O 2 difference and a-vf O2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake ( V ˙ O 2max ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with V ˙ O 2max . Articles (n = 17) publishing individual data (n = 154) on V ˙ O 2max , maximal cardiac output ( Q ˙ max ; indicator-dilution or the Fick method), a - v ¯ O 2 difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group-mean data (articles: n = 27; subjects: n = 234) on leg blood flow (LBF; thermodilution), a-vf O2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Q ˙ max and two-LBF increased linearly by 4.9-6.0 L · min-1 per 1 L · min-1 increase in V ˙ O 2max (R2 = .73 and R2 = .67, respectively; both P a - v ¯ O 2 difference increased from 118-168 mL · L-1 from a V ˙ O 2max of 2-4.5 L · min-1 followed by a reduction (second-order polynomial: R2 = .27). After accounting for a hypoxemia-induced decrease in arterial O2 content with increasing V ˙ O 2max (R2 = .17; P V ˙ O 2max : 4.5 L · min-1 ) with no further change (exponential decay model: R2 = .42). Likewise, leg O2 extraction fraction increased with V ˙ O 2max to approach a maximal value of ~90-95% (R2 = .83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with V ˙ O 2max (R2 = .77 and R2 = .31, respectively; both P V ˙ O 2max , enhanced O2 extraction fraction (≥90%) contributes to the remarkably high V ˙ O 2max in endurance-trained individuals.

To compare the accuracy and trending ability of the cardiac index (CI) measured by FloTrac/Vigileo™ (CIFT) or derived by the Fick equation (CIFick) using E-CAiOVX (enables continuous monitoring of oxygen consumption) with that measured by thermodilution (CITD) in patients with off-pump coronary artery bypass surgery. Twenty-two patients undergoing elective off-pump coronary artery bypass surgery were included. CIFT and CIFick were determined simultaneously at six time-points during off-pump coronary artery bypass surgery. At each time-point, phenylephrine (50 µg) was administered to increase systematic vascular resistance, with CI measured before and after administration (CITD used as reference method). Agreement of each method was evaluated by Bland–Altman analysis, while trending ability was evaluated by four-quadrant plot analysis and polar plot analysis. By Bland–Altman analysis, CIFT and CIFick showed percentage errors of 49.5% and 78.6%, respectively, compared with CITD. Subgroup analysis showed a percentage error between COFT and COTD of 28.9% in patients with a CI ≥ 2.4 L/min/m2, and 78.1% in patients with a CI ≥ 2.4 L/min/m2. The concordance rate of four-quadrant plot analysis was 93.3% for CIFT and 66.7% for CIFick in datasets where CITD ≥ 2.4 L/min/m2 before and after phenylephrine administration were included. CIFT and CIFick had wide limits of agreement with CITD, and were below acceptable limits for tracking phenylephrine-induced CI changes. However, subgroup analysis showed improved accuracy and trending ability of CIFT when only points where CITD ≥ 2.4 L/min/m2 were included, while there was no improvement in CIFick accuracy or trending ability.

Background Novel quantification of stroke volume according to mitral inflow and aortic outflow using automated real-time 3-dimensional volume colour flow Doppler echocardiography (3D-RT-VCFDE) is more accurate than 2-dimensional echocardiography and has excellent correlation with cardiac magnetic resonance imaging-based flows in adults. This technology is applied for the first time to the right heart and in children. Methods 3D-RT-VCFDE was performed in 61 image sets of flow through the aortic (AV), mitral (MV), pulmonary (PV), and tricuspid (TV) valves of 34 children. These were compared with stroke volumes of the right (RV) and left (LV) ventricles and ratio of pulmonary to systemic blood flow determined using the Fick method in 31 children with atrial shunts. Results The mean age was 8.0 ± 3.3 years, and the mean weight was 27.8 ± 10.0 kg. The mean temporal resolution for flow analyses was ≥ 22 volumes per second. In conditions with no shunt, the correlations were: AV with MV flows ( r = 0.98), PV with TV flows ( r = 0.96), RV stroke volume with PV flow ( r = 0.95), and with TV flow ( r = 0.93), LV stroke volume with AV flow ( r = 0.87), and with MV flow ( r = 0.89). Fick ratio of pulmonary to systemic blood flow correlations were: PV/AV ratio ( r = 0.84), TV/MV ratio ( r = 0.87), and RV/LV ratio ( r = 0.70). Conclusions Stroke volume determined using automated 3D-RT-VCFDE is feasible in children and in the right side of the heart. This technique potentially provides a noninvasive alternative to historically invasively acquired hemodynamic data and to cardiac magnetic resonance imaging.

Background: There is an increased interest in methods of objective cardiac output measurement in pediatric cardiac surgery. Several techniques are available, but have limitations, among the new technologies pressure recording analytical method with MostCare (MostCare-PRAM), a minimally invasive hemodynamic monitoring system, represents a novel arterial pulse contour method that does not require calibration. For this reason, we compared the MostCare-PRAM vs the Fick method for estimation of cardiac output. Methods: We studied prospectively 13 pediatric patients who underwent cardiac surgery and compared intraoperatively Cardiac Index (CI) measured with the MostCare-PRAM with the CI measured with the Fick method. We also measured Cardiac Cycle Efficiency (CCE) and maximal arterial pressure/time ratio (dp/dt max) and compared with Fick method. Results: The data showed good agreement between CI Fick and CI MostCare-PRAM (r = 0.93 and R2= 0.86; p < 0.0001) and also between CCE (r = 0.82 and R2 = 0.67; p < 0.001) and dp/dt (r = 0.84; R2 = 0.81; p < 0.001) with CI measured with Fick method. Conclusion: In pediatric patients submitted to cardiac surgery, the MostCare-PRAM seems to estimate CI with a good level of agreement with the Fick method measurements.

Both cardiac magnetic resonance (CMR) and cardiac catheterization (cath) may assess patients with single ventricle physiology prior to stage II or Fontan palliation. However, development of significant aortopulmonary collaterals may invalidate assumptions of the Fick method. We compared CMR and cath flow measurements and evaluated the relation to collateral flow. This single-center study included all pre-stage II and pre-Fontan patients between 2010 and 2017 with CMR and cath within 1 month. Pulmonary (Qp) and systemic flow (Qs) by cath were calculated by Fick method. CMR Qp was calculated by total pulmonary venous flow, and Qs by total vena caval flow. Collateral flow by CMR was the difference of pulmonary vein and pulmonary artery flow. In 26 studies (16 pre-stage II and 10 pre-Fontan) in 21 patients, collateral flow was higher in pre-Fontan patients (1.8 ± 0.6 vs 0.9 ± 0.8 L/min/m2, p = 0.01). Overall, CMR and cath had good agreement for Qs and Qp:Qs, with moderate correlation (r = 0.44, p = 0.02 for Qs, r = 0.48, p = 0.02 for Qp:Qs). In pre-Fontan but not in pre-stage II patients, CMR had higher Qp (mean difference − 1.71 L/min/m2) and Qp:Qs (mean difference − 0.36). The underestimation of cath Qp correlated with amount of collateral flow (r = − 0.47, p = 0.02). Neither cath nor CMR flow measurements correlated with outcomes in this small cohort. In conclusion, collaterals lead to systematically higher Qp and Qp:Qs measurements by CMR vs cath in single ventricle patients. Measurements may not be used interchangeably, with potential clinical significance in estimating pulmonary vascular resistance. Further study is necessary to evaluate possible relation to clinical outcomes.

Cardiac output during cardiac catheterization is often estimated using the modified Fick method (COFick). In this proof-of-concept, prospective non-randomized study carried out in a single academic healthcare centre, we examined whether replacing COFick in the Gorlin formula with Cheetah-NICOM monitor cardiac output (COCheetah) could produce an accurate and precise estimate of aortic valve area in patients with severe aortic stenosis. In twenty-six subjects, COFick and COCheetah were obtained concurrently. A spot and 3-minute running average of COCheetah was used. Bland and Altman analysis was used to derive bias, 95% limits of agreement (LOA) and confidence intervals (CI). The mean difference (bias) between AVACheetah (average) and AVAFick was 0.11 cm2 and the 95% LOA were ±0.42 cm2. The 95% CI of the bias was 0.02–0.2 cm2. The bias and 95% LOA of AVACheetah (spot value) were 0.14 ± 0.42cm2, with a 95% CI of 0.06–0.23 cm2. No proportional bias was present. AVACheetah thus appears to be a reasonably accurate measure of AVA in patients with severe aortic stenosis compared to AVAFick measured using a modified Fick CO. However, the limits of agreement were not narrow enough to consider AVACheetah and AVAFick interchangeable.

The need to quantify blood flow through the heart has led to the development of different techniques for its measurement. The 3 main approaches are the Fick method, dye dilution, and thermodilution techniques. The latter 2 are based on the use of indicators that indirectly quantify blood flow. These have slowly been developed over centuries, from the concept of measuring blood flow, to a technique, and its clinical utility. Thermodilution is the most popular dilution method used for measuring cardiac output (CO) in the clinical setting. The information obtained during this procedure is relevant in the process of clinical decision making in patients with critical illness, valvular heart disease, and congestive heart failure. The technique increased in popularity in the early 1970's after Swan and Ganz invented the pulmonary artery catheter that simplified thermodilution enough to utilize it as a bedside procedure. This was only possible with simple yet clever engineering methods that are not commonly known in the medical community. Despite these advancements, the concept of measuring CO by dilution techniques is one where its optimal use in the clinical setting continues to be an area of investigation. The thermodilution concept and the mechanism of measuring CO will be discussed in the following review.

Purpose Direct Fick is the gold standard for measuring cardiac output (CO). Due to direct Fick complexity, indirect Fick (iFICK) and Thermodilution (TD) are most commonly used to assess CO during right heart catheterization (RHC). However, a small previous study found a 45% discordance in CO estimations when comparing TD with iFick in LVAD patients. This study aimed to compare TD and iFick estimations to direct Fick in order to compare which common method was most accurate. Methods We included 16 LVAD patients referred for clinically indicated RHC. Concomitant with obtaining mixed venous oxygen saturation, resting oxygen consumption was obtained via the MGC diagnostics calorimeter system. Three common formulae were used to calculate iFick for comparison - Lafarge, Dehmer, and Bergstra. Thermodilution was measured in triplicate and averaged with removal of outliers. Correlation between each method and direct Fick was assessed with linear regression. Bias between each method and direct Fick was compared using Bland-Altman Plot analysis. Greater than 25% percent error was used a priori as clinically unacceptable. Results Moderate correlation was present between all methods and direct Fick (TD: R=0.45; Lafarge: R=0.61; Dehmer: R=0.51; Bergstra: R=0.4). However, while absolute bias was lowest between TD and direct Fick (+14.5 ± 30%), all methods tended to overestimate CO compared to direct Fick and had poor overall agreement (Figure). By any method, more than 30% of measurements carried significant discrepancy (>25%) compared to direct Fick. Conclusion Though TD CO carried the least bias, both it and all methods of iFick calculation tend to overestimate CO and have poor agreement when compared to the direct Fick method. These imprecise CO measurements could lead to poor clinical decisions in VAD patients and misjudgment of transplant candidacy due to inaccurate calculation of pulmonary vascular resistance. Where possible, direct Fick should be used to measure CO in LVAD patients.

Purpose The thermodilution (Td) method is routinely used for measurement of cardiac output although its accuracy in low-output states remains uncertain. Criteria for designating heart transplant listing status in the contemporary allocation system is incumbent on meeting strict cardiac index (CI) cutoffs. We aimed to assess the agreement between Td and direct Fick (dFick) CI in patients with low CI. Methods In this retrospective analysis of 535 patients who underwent right heart catheterization with dFick CI measurement as part of clinically indicated hemodynamic evaluation using the gold-standard Douglas bag technique, 253 patients had both Td/dFick CI measurements. Three saline injections were typically used and averaged in Td CI measurements. We included 118 patients who specifically had a CI of Results Among the 118 patients included (Mean [SD] age 60 [12.2] years, 42.3% female), Median (interquartile range, IQR) overall dFick and Td CI values differed significantly (1.86 [1.65, 2.1] and 2.03 [1.78, 2.31] L/min/m2, respectively; P 25% in 33.1% of patients. Conclusion The agreement of Td with the gold-standard dFick CI measurements in patients with low CI was suboptimal. These data are important consider in in clinical scenarios such as heart transplant listing status where strict hemodynamic cutoffs guide urgency.

Monitoring of cardiac index (CI) by uncalibrated pulse contour (PC) methods has been shown to be inaccurate in critically ill patients. We tested accuracy and trending of a new pulse contour method and a modified Fick method using central venous oxygen saturation. We studied 21 critically ill and mechanically ventilated patients (age 20–86 years) monitored by PC (PulsioFlex®) and transpulmonary thermodilution (TPTD, PiCCO2®) as reference. At baseline, reference and PC–derived CI (CIPC) were recorded and CI obtained by Fick's method (FM, CIFICK). After four hours, measurements were performed analogously for trending analysis. CI are given in l/min/m2as mean ± standard deviation. At baseline CITPTDwas 3.7 ± 0.7, CIPC3.8 ± 0.7 and CIFICK5.2 ± 1.8. After 4 hours, CITPTDwas 3.5 ± 0.6, CIPC3.8 ± 1.2 and CIFICK4.8 ± 1.7. Mean bias for PC at baseline was −0.1 (limits of agreement [LOA] −1.4 to 1.2) and −0.4 (LOA −2.6 to 1.9) after four hours. Percentage errors (PE) were 34% and 60% respectively. FM revealed a bias of −1.5 (LOA −4.8 to 1.8, PE 74%) at baseline and −1.5 (LOA −4.5 to 1.4, PE 68%) at four hours. With an exclusion window of 10% of mean cardiac index, trending analysis by polar plots showed an angular bias of 5° (radial LOA ± 57°) for PC and 16° (radial LOA ± 51°) for FM. Although PC values at baseline were marginally acceptable, both methods fail to yield clinically acceptable absolute values. Likewise, trending ability is not adequate for both methods to be used in critically ill patients.

Background Effective pulmonary blood flow (COEPBF) has recently been validated for its ability to measure cardiac output (CO) in children and animals. This study compared COEPBF with the Fick method (COFick) and CO measurements using an invasive pulmonary artery flow probe (COTS). The aim of the study was to validate COEPBF against these reference methods in a porcine model of hypoxia-induced selective pulmonary hypertension. Methods Ten anaesthetised mechanically ventilated piglets (median weight 23.9 kg) were exposed to a hypoxic gas mixture inducing selective pulmonary hypertension. Pulmonary hypertension was subsequently reversed with inhaled nitric oxide. Simultaneous recordings of COEPBF, COFick, and COTS were performed throughout the protocol and examined for agreement and trending ability. Results Overall bias (Bland-Altman) between COEPBF and COTS was 0.2 L min−1 (limits of agreement −0.5 and +0.9 L min−1) with a mean percentage error of 25%. Overall bias between COEPBF and COFick was −0.1 L min−1 (limits of agreement −0.9 and +0.6 L min−1) and a mean percentage error of 25%. The concordance rate was 86% for COEPBF when compared with COTS using a 10% exclusion zone. Conclusions Estimation of CO with COEPBF results in values very close to the gold standard reference methods COFick and COTS. COEPBF appears to be an accurate tool for monitoring absolute values and changes in CO during hypoxia-induced pulmonary hypertension and inhaled nitric oxide treatment.

Cardiovascular-safety studies assessing glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have provided inconsistent data on the risk for developing heart failure. Animal studies have shown that GLP-1 is a vasodilator; if confirmed in humans, this may ameliorate heart failure symptoms.In a single-center, observational pilot study, we recruited 10 patients with advanced heart failure undergoing right heart catheterization, and we recorded pulmonary hemodynamic measures, including cardiac output calculated by thermodilution and the indirect Fick method before and after a 15-minute continuous infusion of native GLP-1 (7-36) NHThere was a neutral effect of GLP-1 on all pressure and hemodynamics indices as derived by cardiac output calculated by thermodilution. However, there was a small but consistent reduction in cardiac output as calculated by the indirect Fick method after GLP-1 infusion (baseline, 4.0 [1.1] L/min vs GLP-1, 3.6 [0.9] L/min; P = 0.003), driven by a consistent reduction in mixed venous oxygen saturation after GLP-1 infusion (baseline, 62.2% [7.0%] vs GLP-1, 59.3% [6.8%]; P 0.001), whereas arterial saturation remained constant (baseline, 96.8% [3.3%] vs GLP-1, 97.0% [3.2%]; P = 0.34). This resulted in an increase in systemic vascular resistance by Fick (baseline, 1285 [228] dyn · s/cmAcute infusion of GLP-1 has a neutral hemodynamic effect, when assessed by thermodilution, in patients with heart failure. However, GLP-1 reduces mixed venous oxygen saturation. ClinicalTrials.gov identifier: NCT02129179.

The paper reviews the existing methods for hemodynamic parameters measurement, namely the Fick method, the thermodilution technique and the Cardiocode technology. Comparative analysis of the above methods is presented. Strong and weak points in each method and their informative values are identified. Distinctive features of the Cardiocode method, as the only noninvasive one, are described.

Pharmacokinetic modeling has a long history that originates from tracers or indicators that were injected into the bloodstream and needed direct contact with a sensor to be detected. Examples of these approaches are provided by the Fick method [1], requiring blood sampling to assess the oxygen saturation, or thermodilution [2, 3], where a catheter is inserted in the central circulation to measure the blood temperature. Pharmacokinetic modeling has a long history that originates from tracers or indicators that were injected into the bloodstream and needed direct contact with a sensor to be detected. Examples of these approaches are provided by the Fick method [1], requiring blood sampling to assess the oxygen saturation, or thermodilution [2, 3], where a catheter is inserted in the central circulation to measure the blood temperature. Modeling was adopted to deal with noisy data and to provide a physiological interpretation of the measurements. Since the introduction of the first indicators, accuracy and complexity of the adopted models have shown terrific development, supported by increasing computing capabilities. Model fitting computations that only few decades ago could take several days, today can be solved in a split of a second. This chapter introduces the fundamental knowledge on pharmacokinetic modeling, establishing the basis for the modern developments applied to contrast-enhanced imaging.

Purpose: The aim of the present study is to find clinical and hemodynamic factors influencing the difference between the direct Fick method ("gold standard") and both - the indirect Fick method and thermodilution. Materials and methods: Twenty three patients were enrolled in our study with mean age 46 ±13 years and mean pulmonary arterial pressure 47±14 mmHg. Twelve of them had a diagnosis of chronic thromboembolic pulmonary hypertension, and others had idiopathic pulmonary hypertension. All patients went through right heart catheterization where cardiac output (CO) was calculated. Three methods were used: the direct Fick method, the indirect Fick method, thermodilution. For the direct Fick method we used Vo2. It was measured at rest by a spirometer right before catheterization. To find significant factors influencing the difference between methods statistical research was performed among clinical and echocardiographic parameters. Results: The significant difference (p Our research showed that significant and highest divergence between two methods and the “gold standard” was in patients with low tricuspid regurgitation (1st -2d degree), high FC (1-2 according to WHO) and with 6MWT > 429m, p Conclusion: To make considerations about diagnosis accurately and define treatment strategy in patients with severe pulmonary hypertension the direct Fick cardiac output measurement method should be preferable.

AIM We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER). METHODS Seven individuals performed 2 incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and 2 on a 1-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibres and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery. RESULTS The ex vivo p50mito increased from 0.06 ± 0.02 to 0.17 ± 0.04 kPa with varying substrate supply and O2 flux rates from 9.84 ± 2.91 to 16.34 ± 4.07 pmol O2 ·s-1 ·μg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time. CONCLUSION O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise.

Background: Cardiac output (CO) is a prognostic factor in pulmonary hypertension (PH). Right heart catheterisation using the direct Fick method or thermodilution (TD) is the reference technique for CO measurement. Impedance cardiography (IPc) is a known non-invasive method of measuring CO. Objectives: In our study, we assume that the measurement of CO by IPc using the PHYSIOFLOW® system is as accurate as TD or using the direct Fick method in patients with PH in group 1 or group 4. Methods: A total of 75 patients were enrolled in a prospective study carried out at the hypertension reference centre of Toulouse University Hospital. Right heart catheterisation was performed for the diagnosis or follow-up of the disease. CO was measured using the Fick method, TD, and IPc simultaneously. A Bland-Altman analysis was plotted. Results: CO was 5.7 ± 1.9 L/min as measured by the Fick method, 5.4 ± 1.5 L/min by TD, and 5.5 ± 1.7 L/min by IPc. The bias between CO measurements by IPc and the direct Fick method was 0.149 L/min (95% CI, –0.298 to 0.596). The bias between CO measurements by IPc and the TD method was –0.153 L/min (95% CI, –0.450 to 0.153). The correlation decreased with the more extreme CO values (< 3 L/min or > 7 L/min). A few factors changed the agreement between measurements (BMI or membership in group 4). Conclusion: To conclude, this study shows that the measurement of CO by IPc in PH patients is reliable compared to the direct Fick method and TD obtained by right heart catheterisation. This accuracy decreases for extreme CO values.

Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2 = 12%). While all four methods reported a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0.001] and hypoxia (7.2 ± 0.7, 4.9 ± 0.5, 6.4 ± 0.8 and 5.1 ± 0.4 L/min per L/min; P = 0.04). In hypoxia, the increase in the Q/VO2 slope was not detected by Nexfin. In normoxia, Q increases by 5-6 L/min per L/min increase in VO2, which is within the 95% confidence interval of the Q/VO2 slopes determined by the modified Fick method, Physioflow, and Nexfin apparatus while Innocor provided a lower value, potentially reflecting recirculation of the test gas into the pulmonary circulation. Thus, determination of Q during exercise depends significantly on the applied method.

AIM: It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low-intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low-intensity exercise training alters regional muscle VO2 .METHODS: In nine healthy volunteers (seven males, two females), haemodynamic and metabolic responses to incremental arm cycling were measured by the Fick method and biopsy of the deltoid and triceps muscles before and after 42 days of skiing for 6 h day(-1) at 60% max heart rate.RESULTS: Peak pulmonary VO2 during arm crank was unchanged after training (2.38 ± 0.19 vs. 2.18 ± 0.2 L min(-1) pre-training) yet arm VO2 (1.04 ± 0.08 vs. 0.83 ± 0.1 L min(1) , P < 0.05) and power output (137 ± 9 vs. 114 ± 10 Watts) were increased along with a higher arm blood flow (7.9 ± 0.5 vs. 6.8 ± 0.6 L min(-1) , P < 0.05) and expanded muscle capillary volume (76 ± 7 vs. 62 ± 4 mL, P < 0.05). Muscle O2 diffusion capacity (16.2 ± 1 vs. 12.5 ± 0.9 mL min(-1) mHg(-1) , P < 0.05) and O2 extraction (68 ± 1 vs. 62 ± 1%, P < 0.05) were enhanced at a similar mean capillary transit time (569 ± 43 vs. 564 ± 31 ms) and P50 (35.8 ± 0.7 vs. 35 ± 0.8), whereas mitochondrial O2 flux capacity was unchanged (147 ± 6 mL kg min(-1) vs. 146 ± 8 mL kg min(-1) ).CONCLUSION: The mechanisms underlying the increase in peak arm VO2 with prolonged low-intensity training in previously untrained subjects are an increased convective O2 delivery specifically to the muscles of the arm combined with a larger capillary-muscle surface area that enhance diffusional O2 conductance, with no apparent role of mitochondrial respiratory capacity.

The aim was to assess if computed tomography is able to measure pulmonary artery pulsatility in patients affected by chronic obstructive pulmonary disease and to ascertain whether pulsatility is different in patients with and without pulmonary hypertension and whether it is related to haemodynamics. We selected two groups of patients, the first one with pulmonary hypertension and the second one without. In patient with hypertension, pulmonary artery pressure and resistance were increased with the increased diameters (transverse 36 ± 5 mm and axial 38 ± 4 mm versus 22 ± 3 and 25 ± 5, resp.), the increased cross-sectional area (10 ± 08 versus 4 ± 1 cm2), and the reduced pulsatility (21 ± 7 versus 10% ± 5%). Arterial stretching was decreased in patients with hypertension (10 ± 5 versus 21% ± 7%) and significantly related to pulmonary vascular resistances and pressure. Cardiac output measured by tomography was significantly related to that obtained by Fick method and was not different in the two groups. The diameters allow to identify patients with PH, assuming a cut-off of 28 mm and assuming a pulsatility of right branch of 26% as well. These preliminary observations indicate tomography as a suitable technique, being able to measure the pulsatility and the dimensions of the arteries and the right ventricular functional parameters.

Background: Right heart catheterization (RHC) is the gold standard for the diagnosis of pu lmonary hypertension (PH) and a useful tool for monitoring PH . However, there are some disadvantages in the regular use of RHC because it is invasive . Noninvasive methods for monitoring hemodynamics are needed to manage patients with PH. In this study, we aimed to evaluate the reliability of noninvasive hemodynamic assessment with whole-body impedance cardiography (Non-Invasive Cardiac System [NICaS]) for PH. Methods and Results: We investigated 55 consecutive patients undergoing RHC. Two- thirds of them had pulmo­ nary arterial hypertension and one-third had chronic thromboembolic PH ; 25% of the patients were receiving medi­ cal therapy. Cardiac output (CO) was estimated by NICaS (NI-CO), thermodilution (TO-CO), and the Fick method (Fick-CO). There was a strong correlation between NI-CO and TO-CO (r=O.715. P

Background and aims Pulmonary hypertension (PH) is increasingly recognised in patients with diffuse lung disease, and is associated with increased mortality. Cardiac output (CO) is a prognostic marker in PH. Non-invasive assessment of pulmonary blood flow (PBF INNOCOR ) with the inert gas rebreathing Innocor device has been validated against CO in PH, but not in PH associated with parenchymal lung disease. PBF INNOCOR may be less accurate in patients with lung disease because of intrapulmonary shunting and/or incomplete gas mixing. Our aim was to determine the variability of PBF INNOCOR in normal subjects, before evaluating PBF INNOCOR in diffuse lung disease against CO measured by the indirect Fick method (CO FICK ) at right heart catheterisation (RHC). Methods and results 23 normal subjects had lung volume measurements by a constant-volume body plethysmograph and three consecutive PBF INNOCOR measurements on the same day. 20 subjects returned for repeat assessment. PBF INNOCOR had good intrasession repeatability (coefficient of variation (CV)=6.57%) and intersession reproducibility (mean CO difference=0.13; single determinant SD=0.49; CV=9.7%). 28 consecutive patients with lung fibrosis referred for RHC had PBF INNOCOR measured within 24 h of RHC. There was good agreement between CO FICK and PBF INNOCOR , with no evidence of systematic bias (mean CO FICK 4.3±1.0; PBF INNOCOR 4.0±1.2l/ min; p=0.07). Bland–Altman analysis revealed a mean difference of −0.32 and limits of agreement of −2.10 to +1.45. Conclusion Non-invasive PBF measured by the inert gas rebreathing Innocor device has good intrasession repeatability and intersession reproducibility. In diffuse lung disease, CO can be accurately and non-invasively measured by the Innocor device.

Background: It remains a great challenge to measure systemic blood flow in critically ill newborns. In a former study we validated the modified carbon dioxide Fick (mCO2F) method for measurement of cardiac output in a newborn lamb model. In this new study we studied the influence of a left-to-right shunt on the accuracy of the mCO2F method. Objective: To analyze the influence of a left-to-right shunt on the agreement between cardiac output measurement with the mCO2F method and ultrasonic transit time pulmonary blood flow in a lamb model. Methods: The study was approved by the Ethical Committee on Animal Research of the Radboud University Nijmegen and performed in 8 random-bred lambs. A Gore-Tex® shunt was placed between the left pulmonary artery and the descending aorta. This aortopulmonary shunt was intermittently opened and closed, while cardiac output was manipulated by creating hemorrhagic hypotension. Cardiac output measurement with the mCO2F method (QmCO2F) was compared with pulmonary blood flow obtained by a transit time ultrasonic flow probe positioned around the common pulmonary artery (QAPC). Results: Bias, defined as QmCO2F – QAPC, was calculated for each measurement. With an open shunt there was a significant left-to-right shunt (mean Qp/Qs ratio 2.26; range 1.56–3.69). Mean bias (SD) was –12.3 (50.4) ml·kg–1·min–1 and –12.3 (42.7) ml·kg–1·min–1 for measurements with a closed and open shunt, respectively (no statistical significant difference). Conclusions: Cardiac output measurement with the mCO2F method is reliable and easily applicable in ventilated newborn lambs, also in the presence of a significant left-to-right shunt.

Ten adult patients with mitral disc valve implants have been examined on the catheterization table. Non-invasive ultrasound Doppler data, pulmonary artery wedge pressure and left ventricular pressure were recorded simultaneously. The cardiac output was determined with the direct Fick method. The effective valve area was taken as a measure of the flow obstruction in the disc valve implants. This area was calculated from the ultrasound data and the cardiac output as well as from the manometric data and the cardiac output. The resulting two sets of areas demonstrated a linear correlation coefficient of 0.86. The effective valve areas calculated from the ultrasound data were reasonable when compared with the results of in vitro studies of disc valve performance and demonstrated good agreement with the findings of other investigators.