Absolute values of regional ventilation-perfusion mismatch in patients with ARDS monitored by electrical impedance tomography and the role of dead space and shunt compensation.

BACKGROUND: Assessment of regional ventilation/perfusion (V'/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V'/Q mismatch. METHODS: We enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V'/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V'/Q-ABS), left unadjusted (V'/Q-REL), or corrected by MV/CO ratio derived from EIT data (V'/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units ( V D ' /QSHUNT) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (QND/ V DS ' ) was calculated as an index of hypocapnic pneumoconstriction. RESULTS: Our calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V'/Q-ABS, V'/Q-REL maps overestimated ventilation (p = 0.013) and perfusion (p = 0.002) to low V'/Q units and underestimated ventilation (p = 0.011) and perfusion (p = 0.008) to high V'/Q units. The heterogeneity of ventilation and perfusion reaching different V'/Q compartments was underestimated. V'/Q-CORR maps eliminated all these differences with V'/Q-ABS (p > 0.05). Higher V D ' / Q SHUNT correlated with higher PaO2/FiO2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ = - 0.59, p = 0.005). Higher Q ND / V DS ' correlated with lower PEEP (ρ = - 0.62, p = 0.003) and plateau pressure (ρ = - 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days (p = 0.05 and p = 0.03, respectively). CONCLUSIONS: Regional V'/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes.

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

OBJECTIVES: 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)]). DESIGN: Retrospective cohort data, 2017-2023. SETTING: Quaternary PICU. PATIENTS: One hundred thirty-one children with acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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 .

Monitoring CO2 kinetics as a marker of cardiopulmonary efficiency.

PURPOSE OF REVIEW: To describe current and near future developments and applications of CO2 kinetics in clinical respiratory and cardiovascular monitoring. RECENT FINDINGS: In the last years, we have witnessed a renewed interest in CO2 kinetics in relation with a better understanding of volumetric capnography and its derived parameters. This together with technological advances and improved measurement systems have expanded the monitoring potential of CO2 kinetics including breath by breath continuous end-expiratory lung volume and continuous noninvasive cardiac output. Dead space has slowly been gaining relevance in clinical monitoring and prognostic evaluation. Easy to measure dead space surrogates such as the ventilatory ratio have demonstrated a strong prognostic value in patients with acute respiratory failure. SUMMARY: The kinetics of carbon dioxide describe many relevant physiological processes. The clinical introduction of new ways of assessing respiratory and circulatory efficiency based on advanced analysis of CO2 kinetics are paving the road to a long-desired goal in clinical monitoring of critically ill patients: the integration of respiratory and circulatory monitoring during mechanical ventilation.

Large animal ventilator-integrated volumetric capnography generates clinically acceptable values of physiologic dead space in anesthetized healthy adult horses.

OBJECTIVE: To evaluate the agreement between the Tafonius large animal ventilator-integrated volumetric capnography (vCap) software and the Respironics NICO noninvasive cardiac output monitor reference system. ANIMALS: Data were collected from 56 healthy adult horses undergoing general anesthesia. METHODS: Animals were placed under general anesthesia and connected to the Tafonius large animal ventilator circle system. A flow partitioning device with CO2 and flow sensors was utilized to couple the endotracheal tube to the NICO monitor. Tafonius CO2 and flow sensors are incorporated into the Y-piece of the breathing circuit. Arterial blood samples were collected to determine the partial pressure of arterial carbon dioxide (PaCO2) immediately before data collection. The PaCO2 was input into the Tafonius and NICO monitor, and dead space ventilation (%Vd), end-tidal CO2 partial pressure (ETco2), mixed-expired CO2 partial pressure (Peco2), and expired tidal volume (Vt) were calculated over a single breath. Multiple measurements were completed for each patient, with a total of 200 paired data points collected for analysis. Data were assessed for normality, and Bland-Altman analysis was performed. Bias and 95% limits of agreement were calculated. RESULTS: The limits of agreement for %Vd of the ventilator-derived measurements fell within ± 10% of the NICO monitor reference method. CLINICAL RELEVANCE: Our results indicate that, when compared to the NICO monitor method, the Tafonius-integrated vCap software provides clinically acceptable values of Peco2, Vt, and %Vd in healthy adult horses.

Effect of additional dead space using end-tidal CO2 measurement on ventilating preterm infants: An experimental study.

BACKGROUND: Dead space is the part of the airway where no gas exchange takes place. Any increase in dead space volume has a proportional effect on the required tidal volume and thus on the risk of ventilation-induced lung injury. Inserts that increase dead space are therefore not used in small preterm infants. This includes end-tidal CO2 measurement. OBJECTIVE: The aim of this study was to investigate the effect of the end-tidal CO2 measurement adapter on ventilation. METHODS: In an experimental setup, an end-tidal CO2 measurement adapter, three different pneumotachographs (PNT-A, PNT-B, PNT-Neo), and a closed suction adapter were combined in varying set-ups. The time required for CO2 elimination by a CO2-flooded preterm infant test lung was measured. RESULTS: PNT-A prolonged CO2 elimination time by 0.9 s (+3.3%), Neo-PNT by 3.2 s (+11.6%) and PNT-B by 9.0 s (+32.7%). The end-tidal CO2 measurement adapter prolonged the elimination time by an additional second without the pneumotachograph (+3.6%) and in combination with PNT-A (+3.1%) and PNT-Neo (+3.1%). In conjunction with PNT-B, the end-tidal CO2 measurement adapter reduced the elimination time by 0.3 seconds (-1%). The use of a closed suction adaptor increased the CO2 elimination time by a further second with PNT-Neo (+3.1%) and by an additional two seconds with no flow sensor (+6.9%), with PNT-A (+6.4%) and with PNT-B (+5.5%). CONCLUSION: The flow sensor had the greatest influence on ventilatory effort, while end-tidal CO2 measurement had only a moderate effect. The increased ventilatory effort levied by the CO2 measurement was dependent on the flow sensor selected. The use of closed suctioning more negatively impacted ventilatory effort than did end-tidal CO2 measurement.

SAMAY S24: a novel wireless 'online' device for real-time monitoring and analysis of volumetric capnography.

Volumetric capnography (VCap) provides information about CO2 exhaled per breath (VCO2br) and physiologic dead space (VDphys). A novel wireless device with a high response time CO2 mainstream sensor coupled with a digital flowmeter was designed to monitor all VCap parameters online in rabbits (SAMAY S24).Ten New Zealand rabbits were anesthetized and mechanically ventilated. VCO2br corresponds to the area under the VCap curve. We used the modified Langley method to assess the airway VD (VDaw) and the alveolar CO2 pressure. VDphys was estimated using Bohr's formula, and the alveolar VD was calculated by subtracting VDaw from VDphys. We compared (Bland-Altman) the critical VCap parameters obtained by SAMAY S24 (Langley) with the Functional Approximation based on the Levenberg-Marquardt Algorithm (FA-LMA) approach during closed and opened chest conditions.SAMAY S24 could assess dead space volumes and VCap shape in real time with similar accuracy and precision compared to the 'offline' FA-LMA approach. The opened chest condition impaired CO2 kinetics, decreasing the phase II slope, which was correlated with the volume of CO2 exhaled per minute.

Increased intrapulmonary shunt and alveolar dead space post-COVID-19.

Increased intrapulmonary shunt (QS/Qt) and alveolar dead space (VD/VT) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients recovering from severe critical acute illness (NIH category 3-5) would have greater and longer lasting increased QS/Qt and VD/VT than patients with mild-moderate acute illness (NIH 1-2). Fifty-nine unvaccinated patients (33 males, aged 52 [38-61] yr, body mass index [BMI] 28.8 [25.3-33.6] kg/m2; median [IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease) were studied 15-403 days postacute severe acute respiratory syndrome coronavirus infection. Breathing ambient air, steady-state mean alveolar Pco2, and Po2 were recorded simultaneously with arterial Po2/Pco2 yielding aAPco2, AaPo2, and from these, QS/Qt%, VD/VT%, and relative alveolar ventilation (40 mmHg/[Formula: see text], VArel) were calculated. Median [Formula: see text] was 39.4 [35.6-41.1] mmHg, [Formula: see text] 92.3 [87.1-98.2] mmHg; [Formula: see text] 32.8 [28.6-35.3] mmHg, [Formula: see text] 112.9 [109.4-117.0] mmHg, AaPo2 18.8 [12.6-26.8] mmHg, aAPco2 5.9 [4.3-8.0] mmHg, QS/Qt 4.3 [2.1-5.9] %, and VD/VT16.6 [12.6-24.4]%. Only 14% of patients had normal QS/Qt and VD/VT; 1% increased QS/Qt but normal VD/VT; 49% normal QS/Qt and elevated VD/VT; 36% both abnormal QS/Qt and VD/VT. Previous severe critical COVID-19 predicted increased QS/Qt (2.69 [0.82-4.57]% per category severity [95% CI], P < 0.01), but not VD/VT. Increasing age weakly predicted increased VD/VT (1.6 [0.1-3.2]% per decade, P < 0.04). Time since infection, BMI, and comorbidities were not predictors (all P > 0.11). VArel was increased in most patients. In our population, recovery from COVID-19 was associated with increased QS/Qt in 37% of patients, increased VD/VT in 86%, and increased alveolar ventilation up to ∼13 mo postinfection. NIH severity predicted QS/Qt but not elevated VD/VT. Increased VD/VT suggests pulmonary microvascular pathology persists post-COVID-19 in most patients.NEW & NOTEWORTHY Using novel methodology quantifying intrapulmonary shunt and alveolar dead space in COVID-19 patients up to 403 days after acute illness, 37% had increased intrapulmonary shunt and 86% had elevated alveolar dead space likely due to independent pathology. Elevated shunt was partially related to severe acute illness, and increased alveolar dead space was weakly related to increasing age. Ventilation was increased in the majority of patients regardless of previous disease severity. These results demonstrate persisting gas exchange abnormalities after recovery.

A coupled model for the dynamics of gas exchanges in the human lung with Haldane and Bohr's effects.

We propose an integrated dynamical model for oxygen and carbon dioxide transfer from the lung into the blood, coupled with a lumped mechanical model for the ventilation process, for healthy patients as well as in pathological cases. In particular, we take into account the nonlinear interaction between oxygen and carbon dioxide in the blood volume, referred to as the Bohr and Haldane effects. We also propose a definition of the physiological dead space volume (the lung volume that does not contribute to gas exchange) which depends on the pathological state and the breathing scenario. This coupled ventilation-gas diffusion model is driven by the sole action of the respiratory muscles. We analyse its sensitivity with respect to characteristic parameters: the resistance of the bronchial tree, the elastance of the lung tissue and the oxygen and carbon dioxide diffusion coefficients of the alveolo-capillary membrane. Idealized pathological situations are also numerically investigated. We obtain realistic qualitative tendencies, which represent a first step towards classification of the pathological behaviours with respect to the considered input parameters.

Effects of apparatus dead space on volumetric capnograms in neonates with healthy lungs: a simulation study.

BACKGROUND: Volumetric capnography in healthy ventilated neonates showed deformed waveforms, which are supposedly due to technological limitations of flow and carbon dioxide sensors. AIMS: This bench study analyzed the role of apparatus dead space on the shape of capnograms in simulated neonates with healthy lungs. METHODS: We simulated mechanical breaths in neonates of 2, 2.5, and 3 kg of body weight using a neonatal volumetric capnography simulator. The simulator was fed by a fixed amount of carbon dioxide of 6 mL/kg/min. Such simulator was ventilated in a volume control mode using fixed ventilatory settings with a tidal volume of 8 mL/kg and respiratory rates of 40, 35, and 30 breaths per minute for the 2, 2.5 and 3 kg neonates, respectively. We tested the above baseline ventilation with and without an additional apparatus dead space of 4 mL. RESULTS: Simulations showed that adding the apparatus dead space to baseline ventilation increased the amount of re-inhaled carbon dioxide in all neonates: 0.16 ± 0.01 to 0.32 ± 0.03 mL (2 kg), 0.14 ± 0.02 to 0.39 ± 0.05 mL (2.5 kg), and 0.13 ± 0.01 to 0.36 ± 0.05 mL (3 kg); (p < .001). Apparatus dead space was computed as part of the airway dead space, and therefore, the ratio of airway dead space to tidal volume increased from 0.51 ± 0.04 to 0.68 ± 0.06, from 0.43 ± 0.04 to 0.62 ± 0.01 and from 0.38 ± 0.01 to 0.60 ± 0.02 in the 2, 2.5 and 3 kg simulated neonates, respectively (p < .001). Compared to baseline ventilation, adding apparatus dead space decreased the ratio of the volume of phase III to VT size from 31% to 11% (2 kg), from 40% to 16% (2.5 kg) and from 50% to 18% (3 kg); (p < .001). CONCLUSIONS: The addition of a small apparatus dead space artificially deformed the volumetric capnograms in simulated neonates with healthy lungs.

Association Between Dead Space to Tidal Volume Ratio and Duration of Respiratory Support After Extubation in Critically Ill Children.

BACKGROUND: The dead-space-to-tidal-volume ratio (VD/VT) has been used to successfully predict extubation failure in children who are critically ill. However, a singular reliable measure to predict the level and duration of respiratory support after liberation from invasive mechanical ventilation has remained elusive. The objective of this study was to evaluate the association between VD/VT and the duration of postextubation respiratory support. METHODS: This was a retrospective cohort study of subjects who were mechanically ventilated and admitted to a single-center pediatric ICU between March 2019 and July 2021, and who had been extubated with a recorded VD/VT. A cutoff of 0.30 was chosen a priori, with subjects divided into 2 groups, VD/VT < 0.30 and VD/VT ≥ 0.30, and postextubation respiratory support was recorded at specified time intervals (24 h, 48 h, 72 h, 7 d, and 14 d). RESULTS: We studied 54 subjects. Those with VD/VT ≥ 0.30 had a significantly longer median (interquartile range) duration of respiratory support after extubation (6 [3-14] d vs 2 [0-4] d; P = .001) and longer median (interquartile range) ICU stay (14 [12-19] d vs 8 [5-22] d; P = .046) versus the subjects with VD/VT < 0.30. The distribution of respiratory support did not differ significantly between VD/VT at the time of extubation (P = .13) or at 14 d after extubation (P = .21) but was significantly different during the intervening time points after extubation (24 h [P = .01], 48 h [P < .001], 72 h [P < .001], and 7 d [P = .02]). CONCLUSIONS: VD/VT was associated with the duration and level of respiratory support needed after extubation. Prospective studies are needed to establish if VD/VT can successfully predict the level of respiratory support after extubation.

Effect of external dead space removal on CO2 homeostasis in mechanically ventilated adult Covid-19 patients.

BACKGROUND: Patients with Covid-19 respiratory failure present with hypoxemia, often in combination with hypercapnia. In this prospective, observational study we examined the effect of removing external dead space (DS) on CO2 -homeostasis in mechanically ventilated Covid-19 patients. In addition, volumetric capnography was validated for its ability to estimate external DS volume using in vitro measured DS volumes as reference. METHODS: In total, 10 patients with acute respiratory distress syndrome from Covid-19 were included. Volumetric capnography, mechanical ventilation, and arterial blood gas data were analyzed before and after removal of external DS and analyzed for potentially significant changes in response to DS removal. Measurements of external DS were obtained in circuit using volumetric capnography and compared to actual measured DS volumes off the circuit. RESULTS: After the removal of external DS, the alveolar minute ventilation and CO2 elimination improved, notwithstanding unchanged respiratory rate and tidal volumes. The increase in CO2 elimination was associated with a decrease in arterial CO2 partial pressure (PaCO2 ). The volumetric capnography method for assessment of external DS showed a low bias of -9 mL (lower limit of agreement -40, 95% CI -60 to -20 mL, upper limit of agreement 21 mL, 95% CI: 1-40 mL) and a percentage error of 48% compared to absolute values measured in vitro. CONCLUSION: Removal of external DS increased alveolar minute ventilation and CO2 elimination in Covid-19 patients with respiratory failure in the current study. This was associated with a decrease in PaCO2 . This may indicate a decreased CO2 production due to decreased work of breathing and more effective gas-exchange in response to DS removal. In addition, volumetric capnography appears to be a clinically feasible method for continuous measurement of external DS in the current study and may be of value in optimizing ventilator treatment.

Alveolar target ventilation and dead space in children under anaesthesia: The proventiped cohort study.

INTRODUCTION: Ventilator settings in children under anaesthesia remain difficult because of the changes in the physiology and the high dead space. OBJECTIVE: To determine the alveolar minute-volume to sustain normocapnia in children under mechanical ventilation. DESIGN: A prospective observational study. SETTINGS: This study was performed between May and October 2019 in a tertiary care children's hospital. PATIENTS: Children between 2 months and 12 years, weighing between 5 and 40 kg, admitted for general anaesthesia. INTERVENTION: Volumetric capnography was used to estimate the alveolar and dead space volume (Vd). MAIN OUTCOME MEASURES: Total and alveolar minute ventilation in (ml kg -1  min -1 ) over 100 breaths. RESULTS: Sixty patients were included comprising 20 per group: 5 to 10 kg (group 1), 10 to 20 kg (group 2), 20 to 40 kg (group 3). Seven patients were excluded for aberrant capnographic curves. After normalisation to weight, the median [IQR] tidal volume per kilogram was similar between the three groups: 6.5 ml kg -1 [6.0 to 7.5 ml kg -1 ], 6.4  ml kg -1 [5.7 to 7.3  ml kg -1 ], 6.4  ml kg -1 [5.3 to 6.8  ml kg -1 ]; P  = 0.3. Total Vd (in ml kg -1 ) was negatively correlated to weight ( r  = -0.62, 95% confidence interval -0.41 to -0.76, P  < 0.001). The total normalised minute ventilation (ml kg -1  min -1 ) to obtain normocapnia was higher in group 1 than in group 2 and in group 3; 203  ml kg -1  min -1 [175 to 219 ml kg -1  min -1 ], 150  ml kg -1  min -1 [139 to 181  ml kg -1  min -1 ] and 128  ml kg -1  min -1 [107 to 157  ml kg -1  min -1 ]; P  < 0.001 (mean ± SD), but (mean ± SD) alveolar minute ventilation was similar between the three groups; 68 ±â€Š21  ml kg -1  min -1 . CONCLUSION: Total dead space volume (including apparatus dead space) represents a major component of tidal volume in children less than 30 kg, when using large heat and moisture exchanger filters. The total minute ventilation necessary to achieve normocapnia decreased with increasing weight, while the alveolar minute ventilation remained constant. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03901599.

Dead space ventilation-related indices: bedside tools to evaluate the ventilation and perfusion relationship in patients with acute respiratory distress syndrome.

Cumulative evidence has demonstrated that the ventilatory ratio closely correlates with mortality in acute respiratory distress syndrome (ARDS), and a primary feature in coronavirus disease 2019 (COVID-19)-ARDS is increased dead space that has been reported recently. Thus, new attention has been given to this group of dead space ventilation-related indices, such as physiological dead space fraction, ventilatory ratio, and end-tidal-to-arterial PCO2 ratio, which, albeit distinctive, are all global indices with which to assess the relationship between ventilation and perfusion. These parameters have already been applied to positive end expiratory pressure titration, prediction of responses to the prone position and the field of extracorporeal life support for patients suffering from ARDS. Dead space ventilation-related indices remain hampered by several deflects; notwithstanding, for this catastrophic syndrome, they may facilitate better stratifications and identifications of subphenotypes, thereby providing therapy tailored to individual needs.

The end-tidal alveolar dead space fraction for risk stratification during the first week of invasive mechanical ventilation: an observational cohort study.

BACKGROUND: The end-tidal alveolar dead space fraction (AVDSf = [PaCO2-PETCO2]/PaCO2) is a metric used to estimate alveolar dead space. Higher AVDSf on the first day of mechanical ventilation is associated with mortality and fewer ventilator-free days. It is not clear if AVDSf is associated with length of ventilation in survivors, how AVDSf performs for risk stratification beyond the first day of ventilation, or whether AVDSf adds predictive value to oxygenation (oxygenation index [OI]) or severity of illness (Pediatric Risk of Mortality [PRISM III]) markers. METHODS: Retrospective single-center observational cohort study of children and young adults receiving invasive mechanical ventilation. In those with arterial or capillary blood gases, AVDSf was calculated at the time of every blood gas for the first week of mechanical ventilation. RESULTS: There were 2335 children and young adults (median age 5.8 years [IQR 1.2, 13.2]) enrolled with 8004 analyzed AVDSf values. Higher AVDSf was associated with mortality and longer length of ventilation in survivors throughout the first week of ventilation after controlling for OI and PRISM III. Higher OI was not associated with increased mortality until ≥ 48 h of ventilation after controlling for AVDSf and PRISM III. When using standardized variables, AVDSf effect estimates were generally higher than OI for mortality, whereas OI effect estimates were generally higher than AVDSf for the length of ventilation in survivors. An AVDSf > 0.3 was associated with a higher mortality than an AVDSf < 0.2 within each pediatric acute respiratory distress syndrome severity category. The maximum AVDSf within 12 h of intensive care unit admission demonstrated good risk stratification for mortality (AUC 0.768 [95% CI 0.732, 0.803]). AVDSf did not improve mortality risk stratification when added to PRISM III but did improve mortality risk stratification when added to the gas exchange components of PRISM III (minimum 12-h PaO2 and maximum 12-h PCO2) (p < 0.00001). CONCLUSIONS: AVDSf is associated with mortality and length of ventilation in survivors throughout the first week of invasive mechanical ventilation. Some analyses suggest AVDSf may better stratify mortality risk than OI, whereas OI may better stratify risk for prolonged ventilation in survivors than AVDSf.

Instrumental dead space: A glass ceiling for extremely low birth weight preterm infants? A dead space washout bench study.

BACKGROUND: When ventilating extremely low birth weight infants, clinicians face the problem of instrumental dead space, which is often larger than tidal volume. Hence, aggressive ventilation is necessary to achieve CO2 removal. Continuous tracheal gas insufflation can wash out CO2 from dead space and might also have an impact on O2 and water vapor transport. The objective of this bench study is to test the impact of instrumental dead space on the transport of CO2 , O2 , and water vapor and the ability of continuous tracheal gas insufflation to remedy this problem during small tidal volume ventilation. METHODS: A test-lung located in an incubator at 37°C was ventilated with pressure levels needed to reach different tidal volumes from 1.5 to 5 mL. End-tidal CO2 at the test-lung exit, O2 concentration, and relative humidity in the test-lung were measured for each tidal volume with and without a 0.2 L/min continuous tracheal gas insufflation flow. RESULTS: CO2 clearance was improved by continuous tracheal gas insufflation allowing a 28%-44% of tidal volume reduction. With continuous tracheal gas insufflation, time to reach desired O2 concentration was reduced from 20% to 80% and relative humidity was restored. These results are inversely related to tidal volume and are particularly critical below 3 mL. CONCLUSION: For the smallest tidal volumes, reduction of instrumental dead space seems mandatory for CO2 , O2 , and water vapor transfer. Continuous tracheal gas insufflation improved CO2 clearance, time to reach desired O2 concentration and humidification of airways and, thus, may be an option to protect lung development.

Ventilatory ratio, dead space, and venous admixture in patients with acute respiratory distress syndrome.

BACKGROUND: Ventilatory ratio (VR) has been proposed as an alternative approach to estimate physiological dead space. However, the absolute value of VR, at constant dead space, might be affected by venous admixture and CO2 volume expired per minute (VCO2). METHODS: This was a retrospective, observational study of mechanically ventilated patients with acute respiratory distress syndrome (ARDS) in the UK and Italy. Venous admixture was either directly measured or estimated using the surrogate measure PaO2/FiO2 ratio. VCO2 was estimated through the resting energy expenditure derived from the Harris-Benedict formula. RESULTS: A total of 641 mechanically ventilated patients with mild (n=65), moderate (n=363), or severe (n=213) ARDS were studied. Venous admixture was measured (n=153 patients) or estimated using the PaO2/FiO2 ratio (n=448). The VR increased exponentially as a function of the dead space, and the absolute values of this relationship were a function of VCO2. At a physiological dead space of 0.6, VR was 1.1, 1.4, and 1.7 in patients with VCO2 equal to 200, 250, and 300, respectively. VR was independently associated with mortality (odds ratio [OR]=2.5; 95% confidence interval [CI], 1.8-3.5), but was not associated when adjusted for VD/VTphys, VCO2, PaO2/FiO2 (ORadj=1.2; 95% CI, 0.7-2.1). These three variables remained independent predictors of ICU mortality (VD/VTphys [ORadj=17.9; 95% CI, 1.8-185; P<0.05]; VCO2 [ORadj=0.99; 95% CI, 0.99-1.00; P<0.001]; and PaO2/FiO2 (ORadj=0.99; 95% CI, 0.99-1.00; P<0.001]). CONCLUSIONS: VR is a useful aggregate variable associated with outcome, but variables not associated with ventilation (VCO2 and venous admixture) strongly contribute to the high values of VR seen in patients with severe illness.

Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery.

BACKGROUND: Pathological evidence suggests that coronavirus disease 2019 (COVID-19) pulmonary infection involves both alveolar damage (causing shunt) and diffuse microvascular thrombus formation (causing alveolar dead space). We propose that measuring respiratory gas exchange enables detection and quantification of these abnormalities. We aimed to measure shunt and alveolar dead space in moderate COVID-19 during acute illness and recovery. METHODS: We studied 30 patients (22 males; mean±sd age 49.9±13.5 years) 3-15 days from symptom onset and again during recovery, 55±10 days later (n=17). Arterial blood (breathing ambient air) was collected while exhaled oxygen and carbon dioxide concentrations were measured, yielding alveolar-arterial differences for each gas (P A-aO2 and P a-ACO2 , respectively) from which shunt and alveolar dead space were computed. RESULTS: For acute COVID-19 patients, group mean (range) for P A-aO2 was 41.4 (-3.5-69.3) mmHg and for P a-ACO2 was 6.0 (-2.3-13.4) mmHg. Both shunt (% cardiac output) at 10.4% (0-22.0%) and alveolar dead space (% tidal volume) at 14.9% (0-32.3%) were elevated (normal: <5% and <10%, respectively), but not correlated (p=0.27). At recovery, shunt was 2.4% (0-6.1%) and alveolar dead space was 8.5% (0-22.4%) (both p<0.05 versus acute). Shunt was marginally elevated for two patients; however, five patients (30%) had elevated alveolar dead space. CONCLUSIONS: We speculate impaired pulmonary gas exchange in early COVID-19 pneumonitis arises from two concurrent, independent and variable processes (alveolar filling and pulmonary vascular obstruction). For most patients these resolve within weeks; however, high alveolar dead space in ∼30% of recovered patients suggests persistent pulmonary vascular pathology.