Integral assessment of gas exchange during veno-arterial ECMO: accuracy and precision of a modified Fick principle in a porcine model.

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (V̇co2) or oxygen uptake (V̇o2) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (V̇/Q̇) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement -542 to 741 mL/min) with blood content V̇o2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias -395, limits of agreement -1,290 to 500 mL/min). Bias and trending further depended on the gas (O2, CO2) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA -1,357 to 1,863 mL/min] for expired V̇o2 bias 482 [LoA -760 to 1,724 mL/min] for expired V̇co2) and could be improved by correction of V̇/Q̇ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.

Cardiopulmonary exercise testing for treatment effect assessment in chronic thromboembolic pulmonary hypertension patients.

Aim      To determine possibilities of the cardiopulmonary stress test (CPST) as an unbiassed, noninvasive method for evaluation of the effect of managing patients with chronic thromboembolic pulmonary hypertension (CTEPH).Material and methods  This study included 37 patients with CTEPH, 24 men (mean age, 53±15 years) and 13 women (mean age, 58±8.5 years). The diagnosis was verified and theCoperability was assessed according to 2015 European Society of Cardiology Clinical Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension (PH). The surgical treatment was used in 65 % (n=24) of CTEPH patients: the group with pulmonary thromboendarterectomy constituted 35 % (n=13); the group with balloon pulmonary angioplasty 30% (n=11); and the conservative tactics was used in 27 % (n=10) of patients.Results Baseline CPST parameters significantly correlated with parameters of right heart catheterization (RHC): mixed venous oxygen saturation (SvO2) significantly positively correlated with V´O2peak (r=0.640, p<0.05), V´O2 / heart rate (HR) (r=0.557; p<0.001), PETCO2 peak (r=0.598, p<0.05), and V´E / V´CO2 (r=0.587; p<0.001); cardiac output (CO) correlated with V´O2 / HR (r=0.555, p<0.001), PETCO2peak (r= -0.476; p<0.05 and r=0.555, p<0.001 for ´E / V´CO2). In repeated testing, the physical working capacity (V´O2peak) increased only in patients after the surgical treatment of CTEPH. Importantly in this process, significant correlations remained between a number of CPST and RHC parameters: SvO2 correlated with V´O2peak (r=0.743; p<0.05), V´O2 /HR (r=0.627; p<0.001), PETCO2peak (r=0.538; p<0.05), and V´E / V´CO2 (r=0.597; p<0.001); V´O2 / HR, PETCO2peak, and V´E / V´CO2 significantly correlated with CO (r=0.645, p<0.001; r= -0.516, p<0.001, and r=0.555, p<0.001, respectively.Conclusion      CPST can be used as a noninvasive instrument for evaluation of the effect of CTEPH treatment, particularly in the absence of echocardiographic data for residual PH.

High-intensity resistance exercise is not as effective as traditional high-intensity interval exercise for increasing the cardiorespiratory response and energy expenditure in recreationally active subjects.

PURPOSE: Traditional high-intensity interval exercise (HIIE) highly stimulates the cardiorespiratory system and increases energy expenditure (EE) during exercise. High-intensity resistance exercise (HIRE) has become more popular in recreationally active subjects. The physiological responses to HIRE performed with light or moderate load is currently largely unknown. Here, we examined the effect of the type of interval exercise [HIRE at 40% (HIRE40) and 60% (HIRE60) 1-RM vs. traditional HIIE] on the cardiorespiratory response and EE during and after exercise. METHODS: Fifteen recreationally active adults randomly completed traditional HIIE on an ergocyle, HIRE40 and HIRE60. The sessions consisted of two sets of ten 30-s intervals (power at 100% VO2max during HIIE; maximal number of repetitions for 10 different free-weight exercises during HIRE40 and HIRE60) separated by 30-s active recovery periods. Gas exchange, heart rate (HR) and EE were assessed during and after exercise. RESULTS: VO2mean, VO2peak, HRmean, the time spent above 90% VO2max and HRmax, and aerobic EE were lower in both HIRE sessions compared with HIIE (P < 0.05). Anaerobic glycolytic contribution to total exercise EE was higher in HIRE40 and HIRE60 compared with HIIE (P < 0.001). EE from excess post-exercise oxygen consumption (EPOC) was similar after the three sessions. Overall, similar cardiorespiratory responses and EE were found in HIRE40 and HIRE60. CONCLUSIONS: HIRE is not as effective as HIIE for increasing the cardiorespiratory response and EE during exercise, while EPOC remains similar in HIRE and HIIE. These parameters are not substantially different between HIRE40 and HIRE60.

Degradation of energy cost with fatigue induced by trail running: effect of distance.

PURPOSE: The effect of trail running competitions on cost of running (Cr) remains unclear and no study has directly examined the effect of distances in similar conditions on Cr. Accordingly, the aims of this study were to (i) assess the effect of trail running races of 40-170 km on Cr and (ii) to assess whether the incline at which Cr is measured influences changes in Cr. METHODS: Twenty trail runners completed races of < 100 km (SHORT) and 26 trail runners completed races of > 100 km (LONG) on similar courses and environmental conditions. Oxygen uptake, respiratory exchange ratio, ventilation, and blood lactate were measured before and after the events on a treadmill with 0% (FLAT) and 15% incline (UH) and Cr was calculated. RESULTS: Cr increased significantly after SHORT but not LONG races. There was no clear relationship between changes in Cr and changes in ventilation or blood lactate. There was a significant correlation (r = 0.75, p < 0.01) between changes in FLAT and UH Cr, and the change in Cr was not affected by the incline at which Cr was measured. CONCLUSION: The distance of the trail running race, but not the slope at which it is measured, influence the changes in Cr with fatigue. The mechanism by which Cr increases only in SHORT is not related to increased cost of breathing.

Simplified bedside assessment of pulmonary gas exchange in very preterm infants at 36 weeks' postmenstrual age.

INTRODUCTION: We aimed to develop and validate a prediction table for a simplified measure of rightward shift of the fetal oxyhaemoglobin saturation (SpO2) versus inspired oxygen pressure (PIO2) curve as an objective marker of lung disease severity in very preterm infants, independent of unit altitude or oxygen prescribing policies. METHODS: Very preterm infants (n=219) had an oxygen reduction test at median (IQR) test age of 354 (345-360) weeks' postmenstrual age (PMA). Shift was derived from at least three paired SpO2 versus PIO2 measurements using a computer algorithm, using the fetal oxyhaemoglobin dissociation curve as the reference. Linear regression of resultant shift values enabled construction of a table to predict shift using a single paired SpO2 versus PIO2 measurement, validated subsequently in a separate infant cohort using Bland-Altman analysis. Receiver operating curve analysis provided threshold values equating to a clinical diagnosis of mild bronchopulmonary dysplasia (BPD) or moderate to severe BPD. RESULTS: The median (IQR) age of 63 infants in the validation cohort was 360 (356-362) weeks' PMA. Mean difference (95% CI) between predicted and measured shift was 2.1 (-0.8% to 4.9%) with wide limits of agreement (-20.7% to 24.8%). Predicted shift >10.1 kPa identified mild BPD with 71% sensitivity and 88% specificity while values>13.0 kPa identified moderate to severe BPD with 81% sensitivity and 100% specificity. DISCUSSION: Shift predicted from a single paired SpO2 versus PIO2 measurement using our validated table enables objective bedside screening of lung disease severity in very preterm infant cohorts at 36 weeks' PMA.

First in vivo assessment of RAS-Q technology as lung support device for pulmonary hypertension.

OBJECTIVES: To assess the in vivo hemodynamic effects on the pressure overloaded right ventricle of RAS-Q® technology, the world's first gas exchanger with a fully integrated compliance. METHODS: In six acute in vivo trials RAS-Q was implanted in sheep between the pulmonary artery and left atrium. Right ventricular pressure overload was induced by pulmonary artery banding. Pressures and flows were recorded in baseline, moderate and severe pulmonary hypertension conditions. In one trial, RAS-Q was benchmarked against the pediatric Quadrox-i®. RESULTS: With 1.00 and 1.17 L/min, RAS-Q delivered 31% and 39% of the total cardiac output in moderate and severe pulmonary hypertension, respectively. Pulmonary artery pressures and mean pulmonary artery pressure/mean arterial blood pressure ratio successfully decreased, implying a successful right ventricular unloading. Cardiac output was restored to normal levels in both pulmonary hypertension conditions. With both devices in parallel, RAS-Q provided three times higher flow rates and a 10 times higher pressure relief, compared to the pediatric Quadrox-i. CONCLUSION: A gas exchanger with a fully integrated compliance better unloads the right ventricle compared to a non-compliant gas exchanger and it can restore cardiac output to normal levels in cases of severe pulmonary hypertension.

Validation of a Noninvasive Assessment of Pulmonary Gas Exchange During Exercise in Hypoxia.

BACKGROUND: Pulmonary gas exchange efficiency, determined by the alveolar-to-arterial Po2 difference (A-aDo2), progressively worsens during exercise at sea-level; this response is further elevated during exercise in hypoxia. Traditionally, pulmonary gas exchange efficiency is assessed through measurements of ventilation and end-tidal gases paired with direct arterial blood gas (ABG) sampling. Because these measures have a number of caveats, particularly invasive blood sampling, the development of new approaches for the noninvasive assessment of pulmonary gas exchange is needed. RESEARCH QUESTION: Is a noninvasive method of assessing pulmonary gas exchange valid during rest and exercise in acute hypoxia? STUDY DESIGN AND METHODS: Twenty-five healthy participants (10 female) completed a staged maximal exercise test on a cycle ergometer in a hypoxic chamber (Fio2 = 0.11). Simultaneous ABGs via a radial arterial catheter and noninvasive gas-exchange measurements (AGM100) were obtained in 2-minute intervals. Noninvasive gas exchange, termed the O2 deficit, was calculated from the difference between the end-tidal and the calculated Pao2 (via pulse oximetry and corrected for the Bohr effect by using the end-tidal Pco2). Noninvasive O2 deficit was compared with the traditional alveolar to arterial oxygen difference (A-aDo2), using the traditional Riley analysis. RESULTS: Under conditions of rest at room air, hypoxic rest, and hypoxic exercise, strong correlations between the calculated gPao2 and directly measured Pao2 (R2 = 0.97; P < .001; mean bias = 1.70 mm Hg) were observed. At hypoxic rest and exercise, strong relationships between the estimated and directly measured Pao2 (R2 = 0.68; P < .001; mean bias = 1.01 mm Hg) and O2 deficit with the traditional A-aDo2 (R2 = 0.70; P < .001; mean bias = 5.24 mm Hg) remained. INTERPRETATIONS: Our findings support the use of a noninvasive measure of gas exchange during acute hypoxic exercise in heathy humans. Further studies are required to determine whether this approach can be used clinically as a tool during normoxic exercise in patients with preexisting impairments in gas exchange efficiency.

Cellular Ex Vivo Lung Perfusion Beyond 1 Hour May Improve Marginal Donor Lung Assessment.

BACKGROUND: Ex vivo lung perfusion (EVLP) permits extended evaluation of donor lungs for transplant. However, the optimal EVLP duration of Lund protocol is unclear. Using human lungs rejected for clinical transplant, we sought to compare the results of 1 versus 2 h of EVLP using the Lund protocol. METHODS: Twenty-five pairs of human lungs rejected for clinical transplant were perfused with the Lund EVLP protocol. Blood gas analysis, lung compliance, bronchoscopy assessment, and perfusate cytokine analysis were performed at both 1 and 2 h. Recruitment was performed at both time points. Donor lung transplant suitability was determined at both time points. RESULTS: All cases were divided into four groups based on transplant suitability assessment at 1 h and 2 h of EVLP. In group A (n = 10), lungs were judged suitable for transplant at both 1 and 2 h of EVLP. In group B (n = 6), lungs were suitable at 1 h but nonsuitable at 2 h. In group C (n = 2), lungs were nonsuitable at 1 h but suitable at 2 h. Finally, in group D (n = 7), lungs were nonsuitable for transplant at both time points. In both groups B and C (n = 8), the transplant suitability assessment changed between 1 and 2 h of EVLP. CONCLUSIONS: In human lungs rejected for transplant, transplant suitability differed at 1 versus 2 h of EVLP in 32% of lungs studied. Evaluation of lungs with Lund protocol EVLP beyond 1 h may improve donor organ assessment.

The Anthropometry of Economical Running.

The influence of anthropometry and body composition on running economy is unclear, with previous investigations involving small relatively homogeneous groups of runners and limited anthropometric/composition measurements. PURPOSE: To comprehensively investigate the relationships of anthropometry and body composition with running economy within a large heterogeneous sample of runners. METHODS: Eighty-five runners (males [M], n = 45; females [F], n = 40), of diverse competitive standard, performed a discontinuous protocol of incremental treadmill running (4-min stages, 1 km·h increments) to establish locomotory energy cost (LEc) of running at submaximal speeds (averaged across 10-12 km·h; the highest common speed < lactate turnpoint). Measurements of anthropometry, including segment lengths, perimeters, masses and moments of inertia, and body composition were obtained using tape-based measurements and dual-energy x-ray absorptiometry. RESULTS: Absolute LEc (ABSLEc, kcal·km) was positively correlated with 21 (of 27) absolute anthropometric variables in both male and female cohorts. Multiple-regression analyses revealed that one variable (mean perimeter z score) explained 49.4% (M) and 68.9% (F) of the variance in ABSLEc. Relative LEc (RELLEc, kcal·kg·km) was also correlated with five (M) and seven (F) normalized anthropometric variables, and regression analyses explained 31.6% (M; percentage bone mass and normalized hip perimeter) and 33.3% (F, normalized forearm perimeter) of the variance in RELLEc. CONCLUSIONS: These findings provide novel and robust evidence that anthropometry and body composition variables, predominantly indicative of relative slenderness, explain a considerable proportion of the variance in running economy (i.e., more slender, lower energy cost). We, therefore, recommend that runners and coaches are attentive to relative slenderness in selecting and training athletes with the aim of enhancing running economy, and improving distance running performance.

Biomechanical factors affecting energy cost during running utilising different slopes.

This study aimed to examine the characteristics of electromyography (EMG) and kinematics of the supporting leg affecting energy cost while running at incline, level, and decline slopes. Twelve male Japanese middle- and long-distance runners volunteered for this study. The subjects were asked to run at 13.5 km·h-1 on a treadmill under three slope conditions. Sagittal plane kinematics and the EMG of the lower limb muscles, respiratory gases were recorded. Energy cost differed significantly between slopes, being the lowest in decline slope and the greatest in incline slope. Integrated EMG (iEMG) of leg extensor muscles was greater in the incline slope than in the decline slope, and iEMG of the gastrocnemius and soleus muscles correlated positively with energy cost. The knee and ankle joint kinematics were associated with energy cost during running. In incline slope, the knee and ankle joints were more extended (plantarflexed) to lift the body. These movements may disturb the coordination between the ankle and knee joints. The gastrocnemius muscle would do greater mechanical work to plantarflex the ankle joint rather than transfer mechanical energy as well as greater mechanical work of mono-articular muscles. These muscular activities would increase energy cost.

Accuracy of Impedance Cardiography for Hemodynamic Assessment During Rest and Exercise in Wheelchair Rugby Players.

Purpose: The aim of the study was to analyze the accuracy of impedance cardiography (ICG) for hemodynamic assessment in wheelchair rugby players during rest and exercise. Method: The study included 21 players (mean age 33.0 ± 5.4, 86% male) with posttraumatic tetraplegia. ECG, echocardiography, and gas exchange analysis during rest and exercise were used to obtain heart rate (HR), stroke volume (SV), and cardiac output (CO) for comparison with PhysioFlow®. Results: There was a good correlation between reference methods and ICG for HR, SV, CO at rest and CO at peak exercise (r = 0.69-0.77, p < .001) and a very good correlation for peak HR (r = 0.91, p < .0001). ICG overestimated SV at rest, CO at rest, and peak CO, which resulted in low intraclass correlation coefficients (ICC = 0.250 and 0.570). Conclusions: ICG can serve as a good estimate of basic hemodynamic parameters during rest and exercise in wheelchair rugby players but overestimates stroke volume and cardiac output.

The "independent breath" algorithm: assessment of oxygen uptake during exercise.

PURPOSE: Reduction of noise of breath-by-breath gas-exchange data is crucial to improve measurements. A recently described algorithm ("independent breath"), that neglects the contiguity in time of breaths, was tested. METHODS: Oxygen, carbon dioxide fractions, and ventilatory flow were recorded continuously over 26 min in 20 healthy volunteers at rest, during unloaded and moderate intensity cycling and subsequent recovery; oxygen uptake ([Formula: see text]) was calculated with the "independent breath" algorithm (IND) and, for comparison, with three other "classical" algorithms. Average [Formula: see text] and standard deviations were calculated for steady-state conditions; non-linear regression was run throughout the [Formula: see text] data of the transient phases (ON and OFF), using a mono-exponential function. RESULTS: Comparisons of the different algorithms showed that they yielded similar average [Formula: see text] at steady state (p = NS). The standard deviations were significantly lower for IND (post hoc contrasts, p < 0.001), with the slope of the relationship with the corresponding data obtained from "classical" algorithms being < 0.69. For both transients, the overall kinetics (evaluated as time delay + time constant) was significantly faster for IND (post hoc contrasts, p < 0.001). For the ON transient, the asymptotic standard errors of the kinetic parameters were significantly lower for IND, with the slope of the regression line with the corresponding values obtained from the "classical" algorithms being < 0.60. CONCLUSION: The "independent breath" algorithm provided consistent average O2 uptake values while reducing the overall noise of about 30%, which might result in the halving of the required number of repeated trials needed to assess the kinetic parameters of the ON transient.

Hyperpolarised xenon magnetic resonance spectroscopy for the longitudinal assessment of changes in gas diffusion in IPF.

Prognosticating idiopathic pulmonary fibrosis (IPF) is challenging, in part due to a lack of sensitive biomarkers. A recent article in Thorax described how hyperpolarised xenon magnetic resonance spectroscopy may quantify regional gas exchange in IPF lungs. In a population of patients with IPF, we find that the xenon signal from red blood cells diminishes relative to the tissue/plasma signal over a 12-month time period, even when the diffusion factor for carbon monoxide is static over the same time period. We conclude that hyperpolarised 129Xe MR spectroscopy may be sensitive to short-term changes in interstitial gas diffusion in IPF.

Assessment of Lung Aeration and Recruitment by CT Scan and Ultrasound in Acute Respiratory Distress Syndrome Patients.

OBJECTIVES: Lung ultrasound is commonly used to evaluate lung morphology in patients with acute respiratory distress syndrome. Aim of this study was to determine lung ultrasound reliability in assessing lung aeration and positive end-expiratory pressure-induced recruitment compared with CT. DESIGN: Randomized crossover study. SETTING: University hospital ICU. PATIENTS: Twenty sedated paralyzed acute respiratory distress syndrome patients: age 56 years (43-72 yr), body mass index 25 kg/m (22-27 kg/m), and PaO2/FIO2 160 (113-218). INTERVENTIONS: Lung CT and lung ultrasound examination were performed at positive end-expiratory pressure 5 and 15 cm H2O. MEASUREMENTS AND MAIN RESULTS: Global and regional Lung Ultrasound scores were compared with CT quantitative analysis. Lung recruitment (i.e., decrease in not aerated tissue as assessed with CT) was compared with global Lung Ultrasound score variations. Global Lung Ultrasound score was strongly associated with average lung tissue density at positive end-expiratory pressure 5 (R = 0.78; p < 0.0001) and positive end-expiratory pressure 15 (R = 0.62; p < 0.0001). Regional Lung Ultrasound score strongly correlated with tissue density at positive end-expiratory pressure 5 (rs = 0.79; p < 0.0001) and positive end-expiratory pressure 15 (rs = 0.79; p < 0.0001). Each step increase of regional Lung Ultrasound score was associated with significant increase of tissue density (p < 0.005). A substantial agreement was found between regional Lung Ultrasound score and CT classification at positive end-expiratory pressure 5 (k = 0.69 [0.63-0.75]) and at positive end-expiratory pressure 15 (k = 0.70 [0.64-0.75]). At positive end-expiratory pressure 15, both global Lung Ultrasound score (22 [16-27] vs 26 [21-29]; p < 0.0001) and not aerated tissue (42% [25-57%] vs 52% [39-67%]; p < 0.0001) decreased. However, Lung Ultrasound score variations were not associated with lung recruitment (R = 0.01; p = 0.67). CONCLUSIONS: Lung Ultrasound score is a valid tool to assess regional and global lung aeration. Global Lung Ultrasound score variations should not be used for bedside assessment of positive end-expiratory pressure-induced recruitment.

Is There an Optimal Speed for Economical Running?

The influence of running speed and sex on running economy is unclear and may have been confounded by measurements of oxygen cost that do not account for known differences in substrate metabolism, across a limited range of speeds, and differences in performance standard. Therefore, this study assessed the energy cost of running over a wide range of speeds in high-level and recreational runners to investigate the effect of speed (in absolute and relative terms) and sex (men vs women of equivalent performance standard) on running economy. To determine the energy cost (kcal · kg-1 · km-1) of submaximal running, speed at lactate turn point (sLTP), and maximal rate of oxygen uptake, 92 healthy runners (high-level men, n = 14; high-level women, n = 10; recreational men, n = 35; recreational women, n = 33) completed a discontinuous incremental treadmill test. There were no sex-specific differences in the energy cost of running for the recreational or high-level runners when compared at absolute or relative running speeds (P > .05). The absolute and relative speed-energy cost relationships for the high-level runners demonstrated a curvilinear U shape with a nadir reflecting the most economical speed at 13 km/h or 70% sLTP. The high-level runners were more economical than the recreational runners at all absolute and relative running speeds (P < .05). These findings demonstrate that there is an optimal speed for economical running, there is no sex-specific difference, and high-level endurance runners exhibit better running economy than recreational endurance runners.

Acute Metabolic Response, Energy Expenditure, and EMG Activity in Sitting and Standing.

PURPOSE: While merely standing up interrupts sedentary behavior, it is important to study acute metabolic responses during single bouts of sitting and standing to understand the physiological processes affecting the health of office workers. METHODS: Eighteen healthy middle-age women 49.4 ± 7.9 yr old (range: 40-64) with a body mass index of 23.4 ± 2.8 kg·m volunteered for this laboratory-based randomized crossover trial where they performed 2 h desk work in either sitting or standing postures after overnight fasting. Muscle activity (normalized to walking at 5 km·h), respiratory gas exchange, and blood samples were assessed after glucose loading (75 g). RESULTS: Compared with seated work, continuous standing resulted in greater activity in the thigh muscles (mean of biceps femoris and vastus lateralis: 17% ± 8% vs 7% ± 2%, P < 0.001) and leg muscles (mean of tibialis anterior, gastrocnemius medialis, and soleus: 16% ± 6% vs 7% ± 3%, P < 0.001), but no increases in back muscle activity (thoracic erector spinae, lumbar erector spinae, and multifidus). Concomitant with 9% higher energy expenditure (EE) (P = 0.002), standing resulted in higher fat oxidation (48% ± 9% EE vs 39% ± 7% EE, P = 0.008) and lower carbohydrate oxidation (52% ± 9% EE vs 61% ± 7% EE, P = 0.008) than sitting. Glucose total and net incremental area under the curve were approximately 10% (P = 0.026) and 42% (P = 0.017) higher during standing than sitting, respectively. Insulin concentration did not differ between conditions. CONCLUSION: Compared with sitting, 2 h of standing increased muscle activity, fat oxidation, and circulating glucose level. These results suggest fuel switching in favor of fat oxidation during standing despite extra carbohydrate availability.

Data collection, handling, and fitting strategies to optimize accuracy and precision of oxygen uptake kinetics estimation from breath-by-breath measurements.

Phase 2 pulmonary oxygen uptake kinetics (ϕ2 τV̇o2P) reflect muscle oxygen consumption dynamics and are sensitive to changes in state of training or health. This study identified an unbiased method for data collection, handling, and fitting to optimize V̇o2P kinetics estimation. A validated computational model of V̇o2P kinetics and a Monte Carlo approach simulated 2 × 105 moderate-intensity transitions using a distribution of metabolic and circulatory parameters spanning normal health. Effects of averaging (interpolation, binning, stacking, or separate fitting of up to 10 transitions) and fitting procedures (biexponential fitting, or ϕ2 isolation by time removal, statistical, or derivative methods followed by monoexponential fitting) on accuracy and precision of V̇o2P kinetics estimation were assessed. The optimal strategy to maximize accuracy and precision of τV̇o2P estimation was 1-s interpolation of 4 bouts, ensemble averaged, with the first 20 s of exercise data removed. Contradictory to previous advice, we found optimal fitting procedures removed no more than 20 s of ϕ1 data. Averaging method was less critical: interpolation, binning, and stacking gave similar results, each with greater accuracy compared with analyzing repeated bouts separately. The optimal procedure resulted in ϕ2 τV̇o2P estimates for transitions from an unloaded or loaded baseline that averaged 1.97 ± 2.08 and 1.04 ± 2.30 s from true, but were within 2 s of true in only 47-62% of simulations. Optimized 95% confidence intervals for τV̇o2P ranged from 4.08 to 4.51 s, suggesting a minimally important difference of ~5 s to determine significant changes in τV̇o2P during interventional and comparative studies.NEW & NOTEWORTHY We identified an unbiased method to maximize accuracy and precision of oxygen uptake kinetics (τV̇o2P) estimation. The optimum number of bouts to average was four; interpolation, bin, and stacking averaging methods gave similar results. Contradictory to previous advice, we found that optimal fitting procedures removed no more than 20 s of phase 1 data. Our data suggest a minimally important difference of ~5 s to determine significant changes in τV̇o2P during interventional and comparative studies.

Can calculation of energy expenditure based on CO2 measurements replace indirect calorimetry?

BACKGROUND: Methods to calculate energy expenditure (EE) based on CO2 measurements (EEVCO2) have been proposed as a surrogate to indirect calorimetry. This study aimed at evaluating whether EEVCO2 could be considered as an alternative to EE measured by indirect calorimetry. METHODS: Indirect calorimetry measurements conducted for clinical purposes on 278 mechanically ventilated ICU patients were retrospectively analyzed. EEVCO2 was calculated by a converted Weir's equation using CO2 consumption (VCO2) measured by indirect calorimetry and assumed respiratory quotients (RQ): 0.85 (EEVCO2_0.85) and food quotient (FQ; EEVCO2_FQ). Mean calculated EEVCO2 and measured EE were compared by paired t test. Accuracy of EEVCO2 was evaluated according to the clinically relevant standard of 5% accuracy rate to the measured EE, and the more general standard of 10% accuracy rate. The effects of the timing of measurement (before or after the 7th ICU day) and energy provision rates (<90 or ≥90% of EE) on 5% accuracy rates were also analyzed (chi-square tests). RESULTS: Mean biases for EEVCO2_0.85 and EEVCO2_FQ were -21 and -48 kcal/d (p = 0.04 and 0.00, respectively), and 10% accuracy rates were 77.7 and 77.3%, respectively. However, 5% accuracy rates were 46.0 and 46.4%, respectively. Accuracy rates were not affected by the timing of the measurement, or the energy provision rates at the time of measurements. CONCLUSIONS: Calculated EE based on CO2 measurement was not sufficiently accurate to consider the results as an alternative to measured EE by indirect calorimetry. Therefore, EE measured by indirect calorimetry remains as the gold standard to guide nutrition therapy.

Evaluating Pulmonary Function: An Assessment of PaO2/FIO2.

OBJECTIVES: PaO2/FIO2 is used commonly for diagnosis of lung injury (acute respiratory distress syndrome and transfusion-related acute lung injury), for assessment of pulmonary disease course and therapy, and in pulmonary transplantation for evaluation of donor lungs and clinical outcome. It was developed for convenience, without formal mathematical and graphic assessment to validate its suitability for these purposes. DESIGN: We examined, mathematically and graphically, the relationship of PaO2/FIO2 to FIO2 at constant normal and several degrees of increased intrapulmonary shunting (QS/QT), assessing the impact of intra- and extrapulmonary factors on the relationship and thus the reliability of PaO2/FIO2. MEASUREMENTS AND MAIN RESULTS: The relationship of PaO2/FIO2 varies at all shunt fractions but most with QS/QT from 0.1 to 0.3 with FIO2 approximately greater than 0.4. At higher QS/QT, the relationship is more constant and changes less with FIO2 more than 0.4. Hemoglobin concentration and arterial-venous oxygen content difference have large effects that can confound interpretation of PaO2/FIO2. Barometric pressure has a substantial effect; PCO2, base excess, and respiratory quotient have small effects. CONCLUSIONS: At high QS/QT with FIO2 more than 0.4, the relationship of PaO2/FIO2 to FIO2 is relatively constant. However, with QS/QT of 0.1-0.3, PaO2/FIO2 changes substantially with FIO2. Understanding the important effects of nonpulmonary factors (especially hemoglobin concentration and arterial-venous oxygen content difference) should enhance appropriate clinical use, interpretation of PaO2/FIO2, and interpretation of previous publications and future studies (especially those seeking to assess effects of anemia or transfusion on lung function). The ratio of PaO2/FIO2 is a good tool for some, but not many clinical circumstances, and is insufficiently robust for most research applications.