Dead Space Fraction Research Articles

Relationships between capnogram parameters by mainstream and sidestream techniques at different breathing frequencies

Capnography, routinely used in operating rooms and intensive care units, reveals essential information on lung ventilation and ventilation–perfusion matching. Mainstream capnography directly measures CO2 in the breathing circuit for accurate analysis and is considered a reference technique. Sidestream capnography, however, analyzes gas away from the patient leading to potentially less accurate measures. While these methodological differences impact the capnogram indices in mechanically ventilated patients, such assessments during spontaneous breathing are essentially lacking. Accordingly, we aimed to compare mainstream and sidestream capnography in spontaneously breathing subjects, focusing on differences in capnogram shape and dead space indices at various respiratory rates. Simultaneous mainstream and sidestream time and volumetric capnography were performed on spontaneously breathing adults (n = 35). Measurements were performed during controlled low (10/min), medium (12/min), and high (20/min) breathing rates as a challenge. Correlation and Bland–Altman analyses were used to assess trends and agreements between time and volumetric capnography indices obtained by the mainstream and sidestream techniques, including end-tidal CO2 (ETCO2), shape factors reflecting the slopes of phases 2 and 3, and anatomical and physiological dead space fractions. ETCO2 and physiological dead space measured by mainstream and sidestream techniques showed excellent correlations (r > 0.90, p < 0.001 for all breathing rates) and agreements. While strong correlations and moderate agreements were evidenced in the parameters reflecting the late phase of expiration (phase 3 slope and exhaled CO2 volume), these relationships were weaker for indices related to the early phase of expiration (phase 2 slope, anatomical dead space). Changing breathing frequency caused significant alterations in all capnography parameters, which were detectable by both mainstream and sidestream techniques. Sidestream capnography cannot substitute the more accurate mainstream technique for measuring the absolute values of shape factors and ventilation dead space fractions. However, sidestream capnography is also able to detect and track changes in uneven alveolar emptying, ventilation–perfusion matching and ventilation dead space fraction in spontaneously breathing subjects.

Increased physiologic dead space fraction is associated with mortality after comprehensive stage 2 operation.

Our objective was to assess the predictive value of physiologic dead space fraction for mortality in patients undergoing the comprehensive stage 2 operation. This was a single-centre retrospective observational study conducted at a quaternary free-standing children's hospital specialising in hybrid palliation of single ventricle cardiac disease. 180 patients underwent the comprehensive stage 2 operation. 76 patients (42%) underwent early extubation, 59 (33%) standard extubation, and 45 (25%) delayed extubation. We measured time to extubation, post-operative outcomes, length of stay and utilised Fine gray models, Youden's J statistic, cumulative incidence function, and logistic regression to analyse outcomes. Delayed extubation group suffered significantly higher rates of mortality (31.1% vs. 6.8%), cardiac arrest (40.0% vs. 10.2%), stroke (37.8% vs. 11.9%), and need for catheter (28.9% vs. 5.1%) and surgical intervention (24.4% vs. 8.5%) (P < 0.001). Physiologic dead space fraction was significantly higher in the delayed extubation group and in non-survivors with a value of 0.3, which was found to be the discriminatory point by Youden's J statistic. For a 0.1 unit increase in physiologic dead space fraction on post-operative day 1, the odds of a patient expiring increase by a factor of 2.26 (95% CI 1.41-3.97, p < 0.001) and by a factor of 3.79 (95% CI 1.65-11.7, p 0.01) on post-operative day 3. Delayed extubation impacts morbidity and mortality in patients undergoing the comprehensive stage 2 operation. Increased physiologic dead space fraction in the first 60 hours after arrival to the ICU is associated with higher mortality.

Nonideal mixing effect based on Cholette’s model on Van de Vusse reaction selectivity dynamics in an isothermal continuous stirred-tank reactor

Abstract The nonideal mixing effect on the Van de Vusse reaction dynamic in a continuous stirred-tank reactor (CSTR) has rarely been studied in literature. This work presents the mixing operation condition and kinetic reaction constant effects on the Van de Vusse reaction selectivity dynamic in an isothermal CSTR based on Cholette’s model. The mixing condition effect is defined using the parameter μ = n/m, where n is the flow fraction to the reactor and m is the dead space fraction in the reactor. In Cholette’s model, μ = 1 and μ ≠ 1 represent, respectively, the ideal and nonideal mixing operations. Herein, the final desired product yield steady state in the phase plane is first constructed under reaction constant and mixing condition combinations, indicating that the larger the μ values, the higher the desired product steady-state yield. In the selectivity dynamic simulations, the phase plane is divided into transient extreme yield region and region of monotonic variation in yield. It is found for the first time that a higher μ value leads to a decrease in the transient maximum selectivity region area and an increase in the transient minimum selectivity region area in the phase plane. Moreover, the trajectory from the start up to the final steady state will be changed due to nonideal mixing. These results have not been published and have direct applications in real reactor design and operation. Since a CSTR with ideal mixing is hardly attainable in practice, our results benefit the real reactor design and startup policy development in the desired product transient maximum yield.

Effects of different VV ECMO blood flow rates on lung perfusion assessment by hypertonic saline bolus-based electrical impedance tomography

ObjectiveOur study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO.MethodsIn this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared.ResultsFifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93–42.16)% to 41.29 (35.32–43.75)%, p = 0.003, and 48.86 (45.53–58.96)% to 54.12 (45.07–61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42–9.78)% to 6.08 (5.27–9.34)%, p = 0.049, and 51.14 (41.04–54.47)% to 45.88 (38.84–54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt.ConclusionsDuring VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.

Association of dead space fraction to mortality in patients with COVID-19-related ARDS: A historical cohort observational study

ObjectiveTo assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DesignObservational study of a historical cohort. SettingUniversity hospital in Medellin, Colombia. ParticipantsPatients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation. InterventionsMeasurement of VD/VT, CMV, and VR in COVID-19 patients. Main variables of interestVD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters. ResultsDuring the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003–1.525; p = 0.046), age (HR 1.024; 95%CI 1.014–1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001–1.07; p = 0.017). ConclusionsVD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

Asociación de fracción de espacio muerto con la mortalidad en pacientes con síndrome de dificultad respiratoria aguda por COVID-19: Un estudio observacional de una cohorte histórica

ObjectiveTo assess the association between dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV), and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DesignObservational study of a historical cohort in an university hospital in Medellin, Colombia. ParticipantsPatients aged 15 and above with confirmed COVID-19 diagnosis admitted to the ICU requiring mechanical ventilation; interventions: measurement of VD/VT, CMV, and VR in COVID-19 patients. Main variables of interestVD/VT, CMV, VR, demographic data, oxygenation index, and ventilatory parameters. ResultsDuring the study period, 1,047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. Multivariate analysis revealed independent associations with in-hospital mortality, higher VD/VT (HR: 1.24; 95% CI: 1.003-1.525; P=0.046), age (HR: 1.024; 95% CI: 1.014-1.034; P<0.001), and SOFA score at onset (HR: 1.036; 95% CI: 1.001-1.07; P=0.017). ConclusionsVD/VT demonstrated an association with mortality in COVID-19 ARDS patients on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

Noninvasive Surrogate for Physiologic Dead Space Using the Carbon Dioxide Ventilatory Equivalent: Testing in a Single-Center Cohort, 2017-2023.

We sought to evaluate the association between the carbon dioxide ( co2 ) ventilatory equivalent (VEq co2 = minute ventilation/volume of co2 produced per min), a marker of dead space that does not require a blood gas measurement, and mortality risk. We compared the strength of this association to that of physiologic dead space fraction (V D /V t = [Pa co2 -mixed-expired P co2 ]/Pa co2 ) as well as to other commonly used markers of dead space (i.e., the end-tidal alveolar dead space fraction [AVDSf = (Pa co2 -end-tidal P co2 )/Pa co2 ], and ventilatory ratio [VR = (minute ventilation × Pa co2 )/(age-adjusted predicted minute ventilation × 37.5)]). Retrospective cohort data, 2017-2023. Quaternary PICU. One hundred thirty-one children with acute respiratory distress syndrome. None. All dead space markers were calculated at the same 1-minute timepoint for each patient within the first 72 hours of using invasive mechanical ventilation. The 131 children had a median (interquartile range, IQR) age of 5.8 (IQR 1.4, 12.6) years, oxygenation index (OI) of 7.5 (IQR 4.6, 14.3), V D /V t of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEq co2 ( p = 0.003), V D /V t ( p = 0.002), and VR ( p = 0.013) were all associated with greater odds of mortality in multivariable models adjusting for OI, immunosuppressive comorbidity, and overall severity of illness. We failed to identify an association between AVDSf and mortality in the multivariable modeling. Similarly, we also failed to identify an association between OI and mortality after controlling for any dead space marker in the modeling. For the 28-day ventilator-free days outcome, we failed to identify an association between V D /V t and the dead space markers in multivariable modeling, although OI was significant. VEq co2 performs similarly to V D /V t and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for V D /V t .

Management of Respiratory Failure in Hemorrhagic Shock.

Hemorrhagic shock results in acute respiratory failure due to respiratory muscle fatigue and inadequate pulmonary blood flow. Because positive pressure ventilation can reduce venous return and cardiac output, clinicians should use the minimum possible mean airway pressure during assisted or mechanical ventilation, particularly during episodes of severe hypovolemia. Hypoperfusion also worsens dead space fraction. Therefore, clinicians should monitor capnography during mechanical ventilation and recognize that hypercapnia may be treated with fluid resuscitation rather than increasing minute ventilation.

Impact of prone position on dead-space fraction in COVID-19 related acute respiratory distress syndrome

IntroductionCOVID-19 Related Acute Respiratory Syndrome (C-ARDS) is characterized by a mismatch between respiratory mechanics and hypoxemia, suggesting increased dead-space fraction (DSF). Prone position is a cornerstone treatment of ARDS under invasive mechanical ventilation reducing mortality. We sought to investigate the impact of prone position on DSF in C-ARDS in a cohort of patients receiving invasive mechanical ventilation.Methodswe retrospectively analysed data from 85 invasively mechanically ventilated patients with C-ARDS in supine and in prone positions, hospitalized in Intensive Care Unit (Reims University Hospital), between November, 1st 2020 and November, 1st 2022. DSF was estimated via 3 formulas usable at patients’ bedside, based on partial pressure of carbon dioxide (PaCO2) and end-tidal carbon dioxide (EtCO2).Resultsthere was no difference of DSF between supine and prone position, using the 3 formulas. According to Enghoff, Frankenfield and Gattinoni equations, DSF in supine vs. prone position was in median respectively [IQR]: 0.29 [0.13–0.45] vs. 0.31 [0.19–0.51] (p = 0.37), 0.5 [0.48–0.52] vs. 0.51 [0.49–0.53] (p = 0.43), and 0.71 [0.55–0.87] vs. 0.69 [0.57–0.81], (p = 0.32).Conclusionprone position did not change DSF in C-ARDS.

Increased body condition score has a detrimental effect on arterial oxygen tension and increases the risk of hypoxaemia in anaesthetised horses

SummaryBackgroundImpaired oxygenation during anaesthesia can be detrimental. Bodyweight and body shape influence arterial oxygen tension (PaO2) but the effect of body condition score (BCS) has not been investigated.ObjectivesTo examine the effect of BCS on respiratory indices.Study designRetrospective.MethodsIn total, 524 anaesthetic records were reviewed. Records from healthy adult horses under isoflurane anaesthesia in dorsal recumbency, receiving controlled mechanical ventilation, with complete ventilation and arterial blood gas data and BCS assessment by one person (KL) were included in data analysis. Data were analysed using student's t‐test, Mann–Whitney U test, chi‐squared analysis and logistic regression.ResultsIn total, 135 records for 85 horses with BCS &lt;6/9 (Group N) and 50 horses with BCS ≥6/9 (Group O) met the inclusion criteria. Overall, there was a strong negative correlation between BCS and PaO2 (Spearman's r = 0.72, p &lt; 0.001). Group O had significantly lower PaO2 (112 [50–546 mmHg]) compared to Group N (380 [65–658 mmHg], p &lt; 0.001) which remained when horses were further categorised by bodyweight &gt;500 kg (118 mmHg vs. 390 mmHg, p &lt; 0.001) and &lt;500 kg (160 mmHg vs. 451 mmHg, p &lt; 0.04). Group O were 34 times more likely to be hypoxaemic (PaO2 &lt; 100 mmHg) compared to Group N (χ2 = 34.39, p = 0.03). Alveolar dead space fraction was greater in Group O (0.27 [0.10–0.41]) versus Group N (0.24 [0.12–0.35]), p &lt; 0.001. Multivariate logistic regression analysis identified a significant association between PaO2 and bodyweight (p = 0.01), alveolar dead space fraction (p = 0.005) and BCS (p &lt; 0.001).Main limitationsRetrospective design.ConclusionsBody condition score ≥6/9 has a detrimental effect on PaO2, alveolar dead space fraction and is a risk factor for hypoxaemia in healthy anaesthetised horses in dorsal recumbency.

Early time-course of respiratory mechanics, mechanical power and gas exchange in ARDS patients

PurposeTo describe the clinical course of ARDS during the first three days of mechanical ventilation, to compare ventilatory setting, respiratory mechanics and gas exchange variables collected during the first three days of mechanical ventilation between patients who survived and died during intensive care unit (ICU) stay and to investigate the variables associated with mortality at ICU admission and throughout the first three days of mechanical ventilation. Materials and methodsProspective observational study. Mechanically ventilated ARDS patients were studied at ICU admission and for the following three days. Univariate logistic regression models were performed for PaO2/FiO2 ratio, driving pressure and alveolar dead space fraction and for mechanical power and mechanical power ratio. ResultsMechanical power ratio was higher in non survivors at ICU admission and over time; PaO2/FiO2 ratio was higher in survivors with a similar behavior over time in the two groups while alveolar dead space fraction was similar at ICU admission and over time between groups. Mechanical power ratio was the only physiological variable which remained consistently associated with ICU mortality throughout the study. ConclusionsThe alteration in oxygenation, dead space, and mechanical power ratio should be assessed not at intensive care admission, but during the first days of mechanical ventilation to better predict outcome.

Prognostic value of time-varying dead space estimates in mechanically ventilated patients with acute respiratory distress syndrome

BackgroundThe dead space fraction (VD/VT) has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome (ARDS). However, its measurement relies on expired carbon dioxide, limiting its widespread application in clinical practice. Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT. In this study, we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation. MethodsThis retrospective observational study was conducted using data from the Chinese database in intensive care (CDIC). Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021. We collected data during the first 7 days of ventilation to calculate various dead space estimates, including ventilatory ratio (VR), corrected minute ventilation (V˙Ecorr), VD/VT (Harris–Benedict), VD/VT (Siddiki estimate), and VD/VT (Penn State estimate) longitudinally. A time-dependent Cox model was used to handle these time-varying estimates. ResultsA total of 392 patients (median age 66 [interquartile range: 55–77] years, median SOFA score 9 [interquartile range: 7–12]) were finally included in our analysis, among whom 132 (33.7%) patients died within 28 days of admission. VR (hazard ratio [HR]=1.04 per 0.1 increase, 95% confidence interval [CI]: 1.01 to 1.06; P=0.013), V˙Ecorr (HR=1.08 per 1 increase, 95% CI: 1.04 to 1.12; P < 0.001), VD/VT (Harris–Benedict) (HR=1.25 per 0.1 increase, 95% CI: 1.06 to 1.47; P=0.006), and VD/VT (Penn State estimate) (HR=1.22 per 0.1 increase, 95% CI: 1.04 to 1.44; P=0.017) remained significant after adjustment, while VD/VT (Siddiki estimate) (HR=1.10 per 0.1 increase, 95% CI: 1.00 to 1.20; P=0.058) did not. Given a large number of negative values, VD/VT (Siddiki estimate) and VD/VT (Penn State estimate) were not recommended as reliable substitutes. Long-term exposure to VR >1.3, V˙Ecorr >7.53, and VD/VT (Harris–Benedict) >0.59 was independently associated with an increased risk of mortality in ARDS patients. These findings were validated in the fluid and catheter treatment trial (FACTT) database. ConclusionsIn cases where VD/VT cannot be measured directly, early time-varying estimates of VD/VT such as VR, V˙Ecorr, and VD/VT (Harris–Benedict) can be considered for predicting mortality in ARDS patients, offering a rapid bedside application.

Capnometry after an inspiratory breath hold, PLAT CO2 , as a surrogate for in mild to moderate pediatric acute respiratory distress syndrome: A feasibility study.

Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end-tidal measured immediately after a 3-s inspiratory-hold (PLAT CO2 ) by capnometry and measured by arterial blood gases (ABG) in PARDS. Prospective cohort study. Seven-bed Pediatric Intensive Care Unit, Hospital El Carmen de Maipú, Chile. Thirteen mechanically ventilated patients aged ≤15 years old undergoing neuromuscular blockade as part of management for PARDS. None. All patients were in volume-controlled ventilation mode. The regular end-tidal (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory-hold of 3 s was performed for lung mechanics measurements, recording in the breath following the inspiratory-hold. (PLAT CO2 ). End-tidal alveolar dead space fraction (AVDSf) was calculated as and its surrogate (S)AVDSf as . Measurements of were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland-Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2-11) months. Tidal volume was 5.8 (5.7-6.3) mL/kg, PEEP 8 (6-8), driving pressure 10 (8-11), and plateau pressure 17 (17-19) cm H2 O. Forty-one paired measurements were analyzed. was higher than (52 mmHg [48-54] vs. 42 mmHg [38-45], p < 0.01), and there were no significant differences with PLAT CO2 (50 mmHg [46-55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between and PLAT CO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67-0.90]; and rho = 0.80, p < 0.001.), and for were weak and strong (ρc = 0.27 [95% CI: 0.15-0.38]; and rho = 0.63, p < 0.01). The bias between PLAT CO2 and was -0.4 ± 3.5 mmHg (LoA -7.2 to 6.4), and between and was -8.5 ± 4.1 mmHg (LoA -16.6 to -0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was -0.5 ± 5.6% (LoA -11.5 to 10.5). This pilot study showed the feasibility of measuring end-tidal CO2 after a 3-s end-inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.

Hypoxaemia in patients with heart failure and preserved ejection fraction.

It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO2 ), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO2 , and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7-5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01-3.96; p = 0.046). Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.

Gas volume corrections in intensive care unit: needed or pointless?

The conditions of temperature, pressure, and saturation in which respiratory gas volumes are expressed [standard temperature and pressure, dry (STPD), ambient temperature and pressure, saturated (ATPS), or body temperature and pressure, saturated (BTPS)] are physiologically relevant, but often ignored or unknown in clinical practice. In this study, we aimed to investigate whether and at which extent the gas volume corrections, either in natural or artificial lung, may alter key respiratory and metabolic variables and the possible clinical consequences. We primarily referred to the effects of gas volume corrections on three physiological variables: physiological dead space, venous admixture, and total CO2 production (V̇co2) during extracorporeal support. We used three physiological models in which calculations of these variables have been performed with and without correction of gas volumes, both in a theoretical model and in 448 patients. The lack of gas volume correction leads to an error in the computation of physiological dead space fraction between 0.05 and 0.15, both in the theoretical model and in the patient population. The venous admixture was minimally affected by the absence of correction (0.01-0.04 error). During extracorporeal support, if the V̇co2 of natural and membrane lung is expressed in different conditions, potentially large errors (0%-18.4%) may occur in the computation of total V̇co2 (V̇co2tot = V̇co2ML + V̇co2NL). This may lead to inappropriate settings of mechanical ventilation with higher plateau pressure. As the dead space and the CO2 sharing between natural and artificial lung are relevant both as prognostic index and as a guide for appropriate mechanical ventilation, their inappropriate computation may lead to erroneous categorization of the patients and inappropriate mechanical treatment.NEW & NOTEWORTHY Gas volume conditions are often ignored or unknown in the clinical practice. However, they could have relevance for the calculation of some key variables in ICU setting. This study shows that gas volume corrections are mostly relevant when assessing CO2 clearance, both in mechanical ventilation and during extracorporeal support, whereas irrelevant for oxygenation assessment of patients. Knowing when the appropriate corrections are needed allows to better understand patients' clinical conditions and to tailor the treatment.

Dead-Space Ventilation Indices and Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Acute respiratory distress syndrome (ARDS) is associated with high ventilation-perfusion heterogeneity and dead-space ventilation. However, whether the degree of dead-space ventilation is associated with outcomes is uncertain. In this systematic review and meta-analysis, we evaluated the ability of dead-space ventilation measures to predict mortality in patients with ARDS. MEDLINE, CENTRAL, and Google Scholar from inception to November 2022. Studies including adults with ARDS reporting a dead-space ventilation index and mortality. Two reviewers independently identified eligible studies and extracted data. We calculated pooled effect estimates using a random effects model for both adjusted and unadjusted results. The quality and strength of evidence were assessed using the Quality in Prognostic Studies and Grading of Recommendations, Assessment, Development, and Evaluation, respectively. We included 28 studies in our review, 21 of which were included in our meta-analysis. All studies had a low risk of bias. A high pulmonary dead-space fraction was associated with increased mortality (odds ratio [OR], 3.52; 95% CI, 2.22-5.58; p < 0.001; I2 = 84%). After adjusting for other confounding variables, every 0.05 increase in pulmonary-dead space fraction was associated with an increased odds of death (OR, 1.23; 95% CI, 1.13-1.34; p < 0.001; I2 = 57%). A high ventilatory ratio was also associated with increased mortality (OR, 1.55; 95% CI, 1.33-1.80; p < 0.001; I2 = 48%). This association was independent of common confounding variables (OR, 1.33; 95% CI, 1.12-1.58; p = 0.001; I2 = 66%). Dead-space ventilation indices were independently associated with mortality in adults with ARDS. These indices could be incorporated into clinical trials and used to identify patients who could benefit from early institution of adjunctive therapies. The cut-offs identified in this study should be prospectively validated.

Impact of cardiac output and alveolar ventilation in estimating ventilation/perfusion mismatch in ARDS using electrical impedance tomography

IntroductionElectrical impedance tomography (EIT) can be used to assess ventilation/perfusion (V/Q) mismatch within the lungs. Several methods have been proposed, some of them neglecting the absolute value of alveolar ventilation (VA) and cardiac output (QC). Whether this omission results in acceptable bias is unknown.MethodsPixel-level V/Q maps of 25 ARDS patients were computed once considering (absolute V/Q map) and once neglecting (relative V/Q map) the value of QC and VA. Previously published indices of V/Q mismatch were computed using absolute V/Q maps and relative V/Q maps. Indices computed with relative V/Q maps were compared to their counterparts computed using absolute V/Q maps.ResultsAmong 21 patients with ratio of alveolar ventilation to cardiac output (VA/QC) > 1, relative shunt fraction was significantly higher than absolute shunt fraction [37% (24–66) vs 19% (11–46), respectively, p < 0.001], while relative dead space fraction was significantly lower than absolute dead space fraction [40% (22–49) vs 58% (46–84), respectively, p < 0.001]. Relative wasted ventilation was significantly lower than the absolute wasted ventilation [16% (11–27) vs 29% (19–35), respectively, p < 0.001], while relative wasted perfusion was significantly higher than absolute wasted perfusion [18% (11–23) vs 11% (7–19), respectively, p < 0.001]. The opposite findings were retrieved in the four patients with VA/QC < 1.ConclusionNeglecting cardiac output and alveolar ventilation when assessing V/Q mismatch indices using EIT in ARDS patients results in significant bias, whose direction depends on the VA/QC ratio value.

Relationship between D-dimers and dead-space on disease severity and mortality in COVID-19 acute respiratory distress syndrome: A retrospective observational cohort study

BackgroundDespite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices, markers of inflammation, immunothrombosis, severity and intensive care unit (ICU) mortality. ResultsRetrospective data including demographics, gas exchange, ventilatory parameters, and respiratory mechanics in the first 24 h of invasive ventilation. Plasma concentrations of D-dimers and ferritin were not significantly different across C-ARDS severity categories. Weak relationships were found between D-dimers and VR (r = 0.07, p = 0.13), PETCO2/PaCO2 (r = −0.1, p = 0.02), or estimated dead space fraction (r = 0.019, p = 0.68). Age, PaO2/FiO2, pH, PETCO2/PaCO2 and ferritin, were independently associated with ICU mortality. We found no association between D-dimers or ferritin and any dead-space indices adjusting for PaO2/FiO2, days of ventilation, tidal volume, and respiratory system compliance. ConclusionsWe report no association between dead space and inflammatory markers in mechanically ventilated patients with C-ARDS. Our results support theories suggesting that multiple mechanisms, in addition to immunothrombosis, play a role in the pathophysiology of respiratory failure and degree of dead space in C-ARDS.

Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation.

Post-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation. This prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd 90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis. 87 patients were evaluated; mean±sd peak oxygen consumption was 19.5±5.0 mL·kg-1·min-1, and the tertiles were ≤17.0, 17.1-22.2 and ≥22.3 mL·kg-1·min-1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg-1·min-1 reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg-1·min-1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption. Exercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.