Comparison of mathematically arterialised venous blood gas sampling with arterial, capillary, and venous sampling in adult patients with hypercapnic respiratory failure: a single-centre longitudinal cohort study.

BACKGROUND: Accurate arterial blood gas (ABG) analysis is essential in the management of patients with hypercapnic respiratory failure, but repeated sampling requires technical expertise and is painful. Missed sampling is common and has a negative impact on patient care. A newer venous to arterial conversion method (v-TAC, Roche) uses mathematical models of acid-base chemistry, a venous blood gas sample and peripheral blood oxygen saturation to calculate arterial acid-base status. It has the potential to replace routine ABG sampling for selected patient cohorts. The aim of this study was to compare v-TAC with ABG, capillary and venous sampling in a patient cohort referred to start non-invasive ventilation (NIV). METHODS: Recruited patients underwent near simultaneous ABG, capillary blood gas (CBG) and venous blood gas (VBG) sampling at day 0, and up to two further occasions (day 1 NIV and discharge). The primary outcome was the reliability of v-TAC sampling compared with ABG, via Bland-Altman analysis, to identify respiratory failure (via PaCO2) and to detect changes in PaCO2 in response to NIV. Secondary outcomes included agreements with pH, sampling success rates and pain. RESULTS: The agreement between ABG and v-TAC/venous PaCO2 was assessed for 119 matched sampling episodes and 105 between ABG and CBG. Close agreement was shown for v-TAC (mean difference (SD) 0.01 (0.5) kPa), but not for CBG (-0.75 (0.69) kPa) or VBG (+1.00 (0.90) kPa). Longitudinal data for 32 patients started on NIV showed the closest agreement for ABG and v-TAC (R2=0.61). v-TAC sampling had the highest first-time success rate (88%) and was less painful than arterial (p<0.0001). CONCLUSION: Mathematical arterialisation of venous samples was easier to obtain and less painful than ABG sampling. Results showed close agreement for PaCO2 and pH and tracked well longitudinally such that the v-TAC method could replace routine ABG testing to recognise and monitor patients with hypercapnic respiratory failure. TRIAL REGISTRATION NUMBER: NCT04072848; www. CLINICALTRIALS: gov.

Mathematically arterialised venous blood is a stable representation of patient acid-base status at steady state following acute transient changes in ventilation.

Hyper- or hypoventilation are commonly occurring stress responses to arterial puncture around the time of blood sampling and have been shown to rapidly alter arterial blood acid-base parameters. This study aimed to evaluate a physiology-based mathematical method to transform peripheral venous blood acid-base values into mathematically arterialised equivalents following acute, transient changes in ventilation. Data from thirty patients scheduled for elective surgery were analysed using the physiology-based method. These data described ventilator changes simulating 'hyper-' or 'hypoventilation' at arterial puncture and included acid-base status from simultaneously drawn blood samples from arterial and peripheral venous catheters at baseline and following ventilatory change. Venous blood was used to calculate mathematically arterialised equivalents using the physiology-based method; baseline values were analysed using Bland-Altman plots. When compared to baseline, measured arterial and calculated arterialised values at each time point within limits of pH: ± 0.03 and PCO2: ± 0.5 kPa, were considered 'not different from baseline'. Percentage of values considered not different from baseline were calculated at each sampling timepoint following hyper- and hypoventilation. For the physiological method, bias and limits of agreement for pH and PCO2 were -0.001 (-0.022 to 0.020) and -0.02 (-0.37 to 0.33) kPa at baseline, respectively. 60 s following a change in ventilation, 100% of the mathematically arterialised values of pH and PCO2 were not different from baseline, compared to less than 40% of the measured arterial values at the same timepoint. In clinical situations where transient breath-holding or hyperventilation may compromise the accuracy of arterial blood samples, arterialised venous blood is a stable representative of steady state arterial blood.

Changes in central venous to arterial carbon dioxide gap (PCO2 gap) in response to acute changes in ventilation.

BACKGROUND: Early diagnosis of shock is a predetermining factor for a good prognosis in intensive care. An elevated central venous to arterial PCO2 difference (∆PCO2) over 0.8 kPa (6 mm Hg) is indicative of low blood flow states. Disturbances around the time of blood sampling could result in inaccurate calculations of ∆PCO2, thereby misrepresenting the patient status. This study aimed to determine the influences of acute changes in ventilation on ∆PCO2 and understand its clinical implications. METHODS: To investigate the isolated effects of changes in ventilation on ∆PCO2, eight pigs were studied in a prospective observational cohort. Arterial and central venous catheters were inserted following anaesthetisation. Baseline ventilator settings were titrated to achieve an EtCO2 of 5±0.5 kPa (VT = 8 mL/kg, Freq = 14 ± 2/min). Blood was sampled simultaneously from both catheters at baseline and 30, 60, 90, 120, 180 and 240 s after a change in ventilation. Pigs were subjected to both hyperventilation and hypoventilation, wherein the respiratory frequency was doubled or halved from baseline. ∆PCO2 changes from baseline were analysed using repeated measures ANOVA with post-hoc analysis using Bonferroni's correction. RESULTS: ∆PCO2 at baseline for all pigs was 0.76±0.29 kPa (5.7±2.2 mm Hg). Following hyperventilation, there was a rapid increase in the ∆PCO2, increasing maximally to 1.35±0.29 kPa (10.1±2.2 mm Hg). A corresponding decrease in the ∆PCO2 was seen following hypoventilation, decreasing maximally to 0.23±0.31 kPa (1.7±2.3 mm Hg). These changes were statistically significant from baseline 30 s after the change in ventilation. CONCLUSION: Disturbances around the time of blood sampling can rapidly affect the PCO2, leading to inaccurate calculations of the ∆PCO2, resulting in misinterpretation of patient status. Care should be taken when interpreting blood gases, if there is doubt as to the presence of acute and transient changes in ventilation.

Comparison of two methods for converting central venous values of acid-base status to arterial values in critically ill patients.

BACKGROUND: Assessment of the critically ill patient requires arterial acid-base status. Venous blood could provide a surrogate, with methods transforming venous values to arterial, improving their utility. This manuscript compares two of these methods, a statistical and a physiological method. Where these methods are inadequate to describe critically ill patients, physiological mechanisms are explored to explain discrepancies. METHODS: 1109 paired arterial and central-venous blood samples, from patients diagnosed with acute circulatory failure, were available for retrospective analysis. Of these, 386 samples were used previously to validate the statistical model. The statistical method of Boulain et al. 2016 and the physiological method of Rees et al. 2006 were applied to the 386 sample pairs, and compared using Bland-Altman analysis. A subset of the 1109 samples, where the physiological method could not accurately calculate arterial values, were analysed further to assess the necessary addition of CO2 or strong acid at the tissues to account for arterio-venous differences. RESULTS: Bias (LoA) for comparison of calculated and measured arterial values (n = 386) were similar for the statistical method (pH: -0.003 (-0.051 to 0.045), PCO2: -0.02 (-1.33 to 1.29 kPa)) and physiological method (pH: 0.009 (-0.033 to 0.052), PCO2: -0.08 (-1.20 to 1.03 kPa)). In the 381 cases (of the 1109 sample pairs) defined as not accurately described, addition of a median CO2 concentration of 0.72 mmol/l in excess of aerobic metabolism, explained this for 333 cases, with the remainder requiring simultaneous strong acid transport. CONCLUSION: Both methods appear equal in their ability to transform central-venous values to arterial, albeit warranting caution when using either in a critically ill population. The physiological approach was able to describe arterio-venous differences not explained by aerobic metabolism alone.

Evaluation of Mathematical Arterialization of Venous Blood in Intensive Care and Pulmonary Ward Patients.

BACKGROUND: Arterial blood gases are important when assessing acute or critically ill patients. Capillary blood and mathematical arterialization of venous blood have been proposed as alternative methods, eliminating pain and complications of arterial puncture. OBJECTIVES: This study compares the arterial samples, arterialized venous samples, and capillary samples in ICU and pulmonary ward patients. METHOD: Ninety-one adult patients with respiratory failure were included in the analysis. Arterial, peripheral venous, and mathematically arterialized venous samples were compared in all patients using Bland-Altman analysis, with capillary samples included in 36 patients. RESULTS: Overall for pH and PCO2, arterialized venous values, and in the subset of 36 patients, capillary values, compared well to arterial values and were within the pre-defined clinically acceptable differences (pH ± 0.05 and PCO2 ± 0.88 kPa). For PO2, arterialized or capillary values describe arterial with similar precision (PO2 arterialized -0.03, LoA -1.48 to 1.42 kPa and PO2 capillary 0.82, LoA -1.36 to 3 kPa), with capillary values underestimating arterial. CONCLUSIONS: Mathematical arterialization functions well in a range of patients in an ICU and ward outside the country of development of the method. Furthermore, accuracy and precision are similar to capillary blood samples. When considering a replacement for arterial sampling in ward patients, using capillary sampling or mathematical arterialization should depend on logistic ease of implementation and use rather than improved measurements of using either technique.

Arterial and transcutaneous variability and agreement between multiple successive measurements of carbon dioxide in patients with chronic obstructive lung disease.

PURPOSE: This study evaluates agreement between carbon dioxide measured arterial (PaCO2) and transcutaneous (PtcCO2) over time, by repeated successive measures, taking into consideration the inherent variability of arterial measurements. METHODS AND RESULTS: 11 patients receiving LTOT, with severe to very severe COPD in a stable phase were studied. Repeated arterial blood samples were drawn and PtcCO2 measured simultaneously at the ear lobe. Bland-Altman analysis was used to evaluate 95 % limits of agreement (LoA). 194 paired samples were analysed. Following correction for bias, the difference between PaCO2 and PtCO2 during dynamic conditions was 0.02 kPa and LoA 0.94 to -0.90 kPa while 29 % of PtCO2 measurements were outside the range of variability for arterial measurements. CONCLUSION: PtcCO2 corrected for intra-patient bias provide reasonable description of PaCO2 values within but not outside steady state conditions. Our results suggest that PtcCO2 is a valuable method for monitoring in chronic rather than acute conditions when bias can be removed.

Reliability of, and Agreement Between, two Breath-by-Breath Indirect Calorimeters at Varying Levels of Inspiratory Oxygen.

BACKGROUND: Indirect calorimetry (IC) is considered the accurate way of measuring energy expenditure (EE). IC devices often apply the Haldane transformation, introducing errors at inspiratory oxygen fraction (FiO2 ) >60%. The aim was to assess measurement reliability and agreement between an unevaluated IC (device 2) (Beacon Caresystem, Mermaid Care A/S, Noerresundby, Denmark) not using Haldane transformation and an IC that does (device 1) (Ecovx, GE, Helsinki, Finland) at varying FiO2 . METHODS: Twenty healthy male subjects participated, with 16 completing the study (33 ± 9 years, 83.3 ± 16 kg, 1.83 ± 0.08 m). Subjects were mechanically ventilated in pressure support (3cmH2 O; positive end-expiratory pressure: 3cmH2 O) at FiO2 of 21%, 50%, 85%, and 21% for 15 minutes at each FiO2 . Mean EE, oxygen consumption (VO2 ), and CO2 production (VCO2 ) were compared within and between devices across FiO2 levels. RESULTS: Device 2 showed within-device EE significant differences at 21% vs 50% FiO2 and device 1 for VCO2 at 50% vs. 85% FiO2 . For all variables, both devices showed reliable measurements at 21% and 50% FiO2 , but at 85%, FiO2 bias and limits of agreement increased. Between devices, there were significant differences for EE at both 21% and 85% FiO2 for VO2 and for VCO2 at 85% FiO2 . CONCLUSION: Both systems measured EE, VO2 , and VCO2 at 21%-85% FiO2 reliably but with bias at 85% FiO2 . The devices were in agreement at 21% and 50% FiO2 , but further studies need to confirm accuracy at high FiO2 .

Diffusion capacity of the lung for carbon monoxide - A potential marker of impaired gas exchange or of systemic deconditioning in chronic obstructive lung disease?

Gas exchange impairment is primarily caused by ventilation-perfusion mismatch in chronic obstructive pulmonary disease (COPD), where diffusing capacity of the lungs for carbon monoxide (DLCO) remains the clinical measure. This study investigates whether DLCO: (1) can predict respiratory impairment in COPD, that is, changes in oxygen and carbon dioxide (CO2); (2) is associated with combined risk assessment score for COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) score); and (3) is associated with blood glucose and body mass index (BMI). Fifty patients were included retrospectively. DLCO; arterial blood gas at inspired oxygen (FiO2) = 0.21; oxygen saturation (SpO2) at FiO2 = 0.21 (SpO2 (21)) and FiO2 = 0.15 (SpO2 (15)) were registered. Difference between arterial and end-tidal CO2 (ΔCO2) was calculated. COPD severity was stratified according to GOLD score. The association between DLCO, SpO2, ΔCO2, GOLD score, blood glucose, and BMI was investigated. Multiple regression showed association between DLCO and GOLD score, BMI, and glucose level (R (2) = 0.6, p < 0.0001). Linear and multiple regression showed an association between DLCO and SpO2 (21) (R (2) = 0.3, p = 0.001 and p = 0.03, respectively) without contribution from SpO2 (15) or ΔCO2. A stronger association between DLCO and GOLD score than between DLCO and SpO2 could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed. A weaker association is seen between DLCO and SpO2 (21) without contribution from SpO2 (15) and ΔCO2. This could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed.

The effect of comorbidities on COPD assessment: a pilot study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from comorbidities. COPD severity may be evaluated by the Global initiative for chronic Obstructive Lung Disease (GOLD) combined risk assessment score (GOLD score). Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HR-CT) measure lung function and elucidate pulmonary pathology. This study assesses associations between GOLD score and measurements of lung function in COPD patients with and without (≤1) comorbidities. It evaluates whether the presence of comorbidities influences evaluation by GOLD score of COPD severity, and questions whether GOLD score describes morbidity rather than COPD severity. METHODS: In this prospective study, 106 patients with stable COPD were included. Patients treated for lung cancer were excluded. Demographics, oxygen saturation (SpO2), modified Medical Research Council Dyspnea Scale, COPD exacerbations, and comorbidities were recorded. Body plethysmography and DLCO were measured, and HR-CT performed and evaluated for emphysema and airways disease. COPD severity was stratified by the GOLD score. Correlation analyses: 1) GOLD score, 2) emphysema grade, and 3) airways disease and lung function parameters, described by: forced expiratory volume in the first second in percent of expected value (FEV1%), inspiratory capacity (IC%), total lung volume (TLC%), IC/TLC, and SpO2. Correlation analyses between subgroups and hierarchical cluster analysis were performed. RESULTS: Significant associations were found between GOLD score and both emphysema grade (correlation coefficients [cc]: -0.2, P=0.03) and lung function parameters (cc: -0.5 to -0.7, P-values all <0.001) weakened in patients with >1 comorbidity (cc: -0.4 to -0.5, P-values all 0.001). Significant differences between subgroups were found in GOLD score and both FEV1% (cc: -0.2, P=0.02) and IC/TLC (cc: -0.2, P=0.02). Comorbidities were associated with GOLD score and composite measures in hierarchical cluster analysis. CONCLUSION: The presence of comorbidities influences the relationship between GOLD score and lung function measurements. GOLD score may be more representative of morbidity than of COPD severity.

Electrical activity of the diaphragm during progressive cycling exercise in endurance-trained men.

The study aimed to investigate diaphragm respiratory drive modulation through electrical activity of the diaphragm (EADi) during progressive cycling in endurance-trained men (N=7) and to test day-to-day measurement reliability. Normalized EADi increased at exercise intensities from 40% workload (WL) to 70% and 85%WL but plateaued from 70% to 85% (p<0.05). V˙O2, V˙CO2, V˙E, increased at all exercise intensities, where Vt and BF increased from 40% to 55% WL and from 70% to 85% and RER increased at 70% and 85% (p<0.05). Bland-Altman plots of normalized EADi showed bias of 0.9% and -6.4% and limits of agreement of ±36.0% and ±30.4% for absolute measurements and relative changes from 40% WL, respectively. Within-day variability appeared constant indicating that measurements within a trial are reliable. Results suggest that diaphragm respiratory drive increases at moderate exercise intensities, but plateaus at high intensities where other respiratory muscles might contribute significantly to the breathing effort, perhaps to "protect" against diaphragm fatigue.

Hemoglobin variant (hemoglobin Aalborg) mimicking interstitial pulmonary disease.

Hemoglobin Aalborg is a moderately unstable hemoglobin variant with no affiliation to serious hematological abnormality or major clinical symptoms under normal circumstances. Our index person was a healthy woman of 58, not previously diagnosed with hemoglobinopathy Aalborg, who developed acute respiratory failure after a routine cholecystectomy. Initially she was suspected of idiopathic interstitial lung disease, yet a series of tests uncovered various abnormal physiological parameters and set the diagnosis of hemoglobinopathy Aalborg. This led us to examine a group of the index person's relatives known with hemoglobinopathy Aalborg in order to study whether the same physiological abnormalities would be reencountered. They were all subjected to spirometry and body plethysmography, six-minute walking test, pulse oximetry, and arterial blood gas samples before and after the walking test. The entire study population presented the same physiological anomalies: reduction in diffusion capacity, and abnormalities in P(a)O2 and p50 values; the latter could not be presented by the arterial blood gas analyzer; furthermore there was concordance between pulse oximetry and arterial blood gas samples regarding saturation. These data suggest that, based upon the above mentioned anomalies in physiological parameters, the diagnosis of hemoglobinopathy Aalborg should be considered.