Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Capnodynamic end-expiratory lung volume assessment in anesthetized healthy children.

BACKGROUND: Capnodynamic lung function monitoring generates variables that may be useful for pediatric perioperative ventilation. AIMS: Establish normal values for end-expiratory lung volume CO2 in healthy children undergoing anesthesia and to compare these values to previously published values obtained with alternative end-expiratory lung volume methods. The secondary aim was to investigate the ability of end-expiratory lung volume CO2 to react to positive end-expiratory pressure-induced changes in end-expiratory lung volume. In addition, normal values for associated volumetric capnography lung function variables were examined. METHODS: Fifteen pediatric patients with healthy lungs (median age 8 months, range 1-36 months) undergoing general anesthesia were examined before start of surgery. Tested variables were recorded at baseline positive end-expiratory pressure 3 cmH2 O, 1 and 3 min after positive end-expiratory pressure 10 cmH2 O and 3 min after returning to baseline positive end-expiratory pressure 3 cmH2 O. RESULTS: Baseline end-expiratory lung volume CO2 was 32 mL kg-1 (95% CI 29-34 mL kg-1 ) which increased to 39 mL kg-1 (95% CI 35-43 mL kg-1 , p < .0001) and 37 mL kg-1 (95% CI 34-41 mL kg-1 , p = .0003) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively. End-expiratory lung volume CO2 returned to baseline, 33 mL kg-1 (95% CI 29-37 mL kg-1 , p = .72) 3 min after re-establishing positive end-expiratory pressure 3 cmH2 O. Airway dead space increased from 1.1 mL kg-1 (95% CI 0.9-1.4 mL kg-1 ) to 1.4 (95% CI 1.1-1.8 mL kg-1 , p = .003) and 1.5 (95% CI 1.1-1.8 mL kg-1 , p < .0001) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively, and 1.2 mL kg-1 (95% CI 0.9-1.4 mL kg-1 , p = .08) after 3 min of positive end-expiratory pressure 3 cmH2 O. Additional volumetric capnography and lung function variables showed no major changes in response to positive end-expiratory pressure variations. CONCLUSIONS: Capnodynamic noninvasive and continuous end-expiratory lung volume CO2 values assessed during anesthesia in children were in close agreement with previously reported end-expiratory lung volume values generated by alternative methods. Furthermore, positive end-expiratory pressure changes resulted in physiologically expected end-expiratory lung volume CO2 responses in a timely manner, suggesting that it can be used to trend end-expiratory lung volume changes during anesthesia.

Dead space volumes in cats and dogs with small body mass ventilated with a fixed tidal volume.

OBJECTIVE: To compare the portion of tidal volume (VT) ventilating dead space volumes in nonbrachycephalic cats and dogs with small body mass receiving volume-controlled ventilation (VCV) with a fixed VT. STUDY DESIGN: Prospective, experimental study. ANIMALS: A group of eight healthy adult cats and dogs [ideal body weight (IBW): 3.0 ± 0.5 and 3.8 ± 1.1 kg, respectively]. METHODS: Anesthetized cats and dogs received VCV with a 12 mL kg-1 VT (inspiratory pause ≥ 0.5 seconds). Respiratory rate (fR) was adjusted to maintain normocapnia. Airway dead space (VDaw) and alveolar tidal volume (VTalv) were measured by volumetric capnography. Physiological dead space (VDphys) and VDphys/VT ratio were calculated using the Bohr-Enghoff method. Data recorded before surgery were compared by an unpaired t-test or Mann-Whitney U test (p < 0.05 considered significant). RESULTS: The IBW (p = 0.07), PaCO2 (p = 0.40) and expired VT [VT(exp)] (p = 0.77) did not differ significantly between species. The VDaw (mL kg-1) was lower in cats (3.7 ± 0.4) than in dogs (7.7 ± 0.9) (p < 0.0001). The VTalv (mL kg-1) was larger in cats (8.3 ± 0.7) than in dogs (4.3 ± 0.7) (p < 0.0001). Cats presented a smaller VDphys/VT ratio (0.33 ± 0.03) and VDphys (4.0 ± 0.3 mL kg-1) than dogs (VDphys/VT: 0.60 ± 0.09; VDphys: 7.2 ± 1.4 mL kg-1) (p < 0.0001). The fR and minute ventilation (VT(exp) × fR) were lower in cats than in dogs (p = 0.048 and p = 0.038, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: A fixed VT results in more effective ventilation in cats than in dogs with small body mass because of species-specific differences in and VDaw and VDphys. Because of the smaller VDaw and VDphys in cats than in dogs, a lower fR is required to maintain normocapnia in cats.

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.

Effect of end-inspiratory pause on airway and physiological dead space in anesthetized horses.

OBJECTIVE: To evaluate the impact of a 30% end-inspiratory pause (EIP) on alveolar tidal volume (VTalv), airway (VDaw) and physiological (VDphys) dead spaces in mechanically ventilated horses using volumetric capnography, and to evaluate the effect of EIP on carbon dioxide (CO2) elimination per breath (Vco2br-1), PaCO2, and the ratio of PaO2-to-fractional inspired oxygen (PaO2:FiO2). STUDY DESIGN: Prospective research study. ANIMALS: A group of eight healthy research horses undergoing laparotomy. METHODS: Anesthetized horses were mechanically ventilated as follows: 6 breaths minute-1, tidal volume (VT) 13 mL kg-1, inspiratory-to-expiratory time ratio 1:2, positive end-expiratory pressure 5 cmH2O and EIP 0%. Vco2br-1 and expired tidal volume (VTE) of 10 consecutive breaths were recorded 30 minutes after induction, after adding 30% EIP and upon EIP removal to construct volumetric capnograms. A stabilization period of 15 minutes was allowed between phases. Data were analyzed using a mixed-effect linear model. Significance was set at p < 0.05. RESULTS: The EIP decreased VDaw from 6.6 (6.1-6.7) to 5.5 (5.3-6.1) mL kg-1 (p < 0.001) and increased VTalv from 7.7 ± 0.7 to 8.6 ± 0.6 mL kg-1 (p = 0.002) without changing the VTE. The VDphys to VTE ratio decreased from 51.0% to 45.5% (p < 0.001) with EIP. The EIP also increased PaO2:FiO2 from 393.3 ± 160.7 to 450.5 ± 182.5 mmHg (52.5 ± 21.4 to 60.0 ± 24.3 kPa; p < 0.001) and Vco2br-1 from 0.49 (0.45-0.50) to 0.59 (0.45-0.61) mL kg-1 (p = 0.008) without reducing PaCO2. CONCLUSIONS AND CLINICAL RELEVANCE: The EIP improved oxygenation and reduced VDaw and VDphys, without reductions in PaCO2. Future studies should evaluate the impact of different EIP in healthy and pathological equine populations under anesthesia.

Effects of PEEP on the relationship between tidal volume and total impedance change measured via electrical impedance tomography (EIT).

Electrical impedance tomography (EIT) is used in lung physiology monitoring. There is evidence that EIT is linearly associated with global tidal volume (VT) in clinically healthy patients where no positive end-expiratory pressure (PEEP) is applied. This linearity has not been challenged by altering lung conditions. The aim of this study was to determine the effect of PEEP on VT estimation, using EIT technology and spirometry, and observe the stability of the relationship under changing lung conditions. Twelve male castrated cattle (Steer), mean age 7.8 months (SD ± 1.7) were premedicated with xylazine followed by anaesthesia induction with ketamine and maintenance with halothane in oxygen via an endotracheal tube. An EIT belt was applied around the thorax at the level of the fifth intercostal space. Volume controlled ventilation was used. PEEP was increased in a stepwise manner from 0 to 5, 10 and 15 cmH2O. At each PEEP, the VT was increased stepwise from 5 to 10 and 15 mL kg-1. After a minute of stabilisation, total impedance change (VTEIT), using EIT and VT measured by a spirometer connected to a flow-partitioning device (VTSpiro) was recorded for the following minute before changing ventilator settings. Data was analysed using linear regression and multi variable analysis. There was a linear relationship between VTEIT and VTSpiro at all levels of PEEP with an R2 of 0.71, 0.68, 0.63 and 0.63 at 0, 5, 10 and 15 cmH2O, respectively. The variance in VTEIT was best described by peak inspiratory pressure (PIP) and PEEP (adjusted R2 0.82) while variance in VTSpiro was best described by PIP and airway deadspace (adjusted R2 0.76). The relationship between VTEIT and VTSpiro remains linear with changes in tidal volume, and stable across altered lung conditions. This may have application for monitoring and assessment in vivo.

Assessment of a new volumetric capnography-derived parameter to reflect compression quality and to predict return of spontaneous circulation during cardiopulmonary resuscitation in a porcine model.

We aimed to evaluate a volumetric capnography (Vcap)-derived parameter, the volume of CO2 eliminated per minute and per kg body weight (VCO2/kg), as an indicator of the quality of chest compression (CC) and to predict the return to spontaneous circulation (ROSC) under stable ventilation status. Twelve male domestic pigs were utilized for the randomized crossover study. After 4 min of untreated ventricular fibrillation (VF), mechanical cardiopulmonary resuscitation and ventilation were administered. Following 5-min washout periods, each animal underwent two sessions of experiments: three types of CC quality for 5 min stages in the first session, followed by advanced life support, consecutively in two sessions. Different CC quality had a significant effect on the partial pressure of end-tidal carbon dioxide (PetCO2), VCO2/kg, aortic pressure (mean), aortic systolic pressure, aortic diastolic pressure, right atrial pressure (mean), and carotid blood flow (P < 0.05). With the improvement in CC quality, the values of PetCO2 and VCO2/kg also increased, and the difference between the groups was statistically significant (P < 0.05). The Spearman rank test revealed a significant correlation between the Vcap-derived parameters and hemodynamics. PetCO2 and VCO2/kg have similar capabilities for discriminating survivors from non-survivors, and the area under the curve for both was 0.97. VCO2/kg had similar performance as PetCO2 in reflecting the quality of CC and prediction of achieving ROSC under stable ventilation status in a porcine model of VF-related cardiac arrest. However, VCO2/kg requires a longer time to achieve a stable state after adjusting for quality of CC than PetCO2.

Reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates with respiratory distress.

Hypercapnia occurs in ventilated infants even if tidal volume (VT) and minute ventilation (VE) are maintained. We hypothesised that increased physiological dead space (Vd,phys) caused decreased minute alveolar ventilation (VA; alveolar ventilation (VA) × respiratory rate) in well-ventilated infants with hypercapnia. We investigated the relationship between dead space and partial pressure of carbon dioxide (PaCO2) and assessed VA. Intubated infants (n = 33; mean birth weight, 2257 ± 641 g; mean gestational age, 35.0 ± 3.3 weeks) were enrolled. We performed volumetric capnography (Vcap), and calculated Vd,phys and VA when arterial blood sampling was necessary. PaCO2 was positively correlated with alveolar dead space (Vd,alv) (r = 0.54, p < 0.001) and Vd,phys (r = 0.48, p < 0.001), but not Fowler dead space (r = 0.14, p = 0.12). Normocapnia (82 measurements; 35 mmHg ≤ PaCO2 < 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg ≤ PaCO2) were classified. The hypercapnia group had higher Vd,phys (median 0.57 (IQR, 0.44-0.67)) than the normocapnia group (median Vd,phys/VT = 0.46 (IQR, 0.37-0.58)], with no difference in VT. The hypercapnia group had lower VA (123 (IQR, 87-166) ml/kg/min) than the normocapnia group (151 (IQR, 115-180) ml/kg/min), with no difference in VE.Conclusion: Reduction of VA in well-ventilated neonates induces hypercapnia, caused by an increase in Vd,phys. What is Known: • Volumetric capnography based on ventilator graphics and capnograms is a useful tool in determining physiological dead space of ventilated infants and investigating the cause of hypercapnia. What is New: • This study adds evidence that reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates.

Clinical use of volumetric capnography in mechanically ventilated patients.

Capnography is a first line monitoring system in mechanically ventilated patients. Volumetric capnography supports noninvasive and breath-by-breath information at the bedside using mainstream CO2 and flow sensors placed at the airways opening. This volume-based capnography provides information of important body functions related to the kinetics of carbon dioxide. Volumetric capnography goes one step forward standard respiratory mechanics and provides a new dimension for monitoring of mechanical ventilation. The article discusses the role of volumetric capnography for the clinical monitoring of mechanical ventilation.

Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study.

BACKGROUND: Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO2D) for determination of PEEPi is evaluated. METHODS: In 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7 cmH2O; mean 8.45 ± 0.32 cmH2O) were studied. The etCO2D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. RESULTS: The etCO2D method detected PEEPi step changes of 0.2 cmH2O. Reference and etCO2D PEEPi presented a good correlation (R2 0.80, P < 0.0001) and good agreement, bias - 0.26, and limits of agreement ± 1.96 SD (2.23, - 2.74) (P < 0.0001). CONCLUSIONS: The etCO2D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.

Evaluation of three tidal volumes (10, 12 and 15 mL kg-1) in dogs for controlled mechanical ventilation assessed by volumetric capnography: a randomized clinical trial.

OBJECTIVE: To evaluate three routinely used tidal volumes (VT; 10, 12 and 15 mL kg-1) for controlled mechanical ventilation (CMV) in lung-healthy anaesthetized dogs by assessing alveolar ventilation (VTalv) and dead space (DS). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 36 client-owned dogs. METHODS: Dogs were randomly allocated to a VT of 10 (G10), 12 (G12) or 15 (G15) mL kg-1. After induction CMV was started. End-tidal carbon dioxide tension was maintained at 4.7-5.3 kPa by changing the respiratory frequency (fR; 630. VTalv kg-1 (p=0.001) increased and VDBohr (p=0.002) decreased with greater VT. VTCO2,br (p=0.017) increased and VDaw/VT (p=0.006), VDBE (p=0.008) and fR (p=0.002) decreased between G10 and G15. PIP (p=0.013) was significantly higher in G15 compared with that in G10 and G12. No changes were observed in MawP. CONCLUSIONS AND CLINICAL RELEVANCE: A VT of 15 mL kg-1 is most appropriate for CMV in lung-healthy dogs (as evaluated by respiratory mechanics and VCap) and does not impair cardiovascular variables.

Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: Physiological dead space (VD/VT) represents the fraction of ventilation not participating in gas exchange. In patients with acute respiratory distress syndrome (ARDS), VD/VT has prognostic value and can be used to guide ventilator settings. However, VD/VT is rarely calculated in clinical practice, because its measurement is perceived as challenging. Recently, a novel technique to calculate partial pressure of carbon dioxide in alveolar air (PACO2) using volumetric capnography (VCap) was validated. The purpose of the present study was to evaluate how VCap and other available techniques to measure PACO2 and partial pressure of carbon dioxide in mixed expired air (PeCO2) affect calculated VD/VT. METHODS: In a prospective, observational study, 15 post-cardiac surgery patients and 15 patients with ARDS were included. PACO2 was measured using VCap to calculate Bohr dead space or substituted with partial pressure of carbon dioxide in arterial blood (PaCO2) to calculate the Enghoff modification. PeCO2 was measured in expired air using three techniques: Douglas bag (DBag), indirect calorimetry (InCal), and VCap. Subsequently, VD/VT was calculated using four methods: Enghoff-DBag, Enghoff-InCal, Enghoff-VCap, and Bohr-VCap. RESULTS: PaCO2 was higher than PACO2, particularly in patients with ARDS (post-cardiac surgery PACO2 = 4.3 ± 0.6 kPa vs. PaCO2 = 5.2 ± 0.5 kPa, P < 0.05; ARDS PACO2 = 3.9 ± 0.8 kPa vs. PaCO2 = 6.9 ± 1.7 kPa, P < 0.05). There was good agreement in PeCO2 calculated with DBag vs. VCap (post-cardiac surgery bias = 0.04 ± 0.19 kPa; ARDS bias = 0.03 ± 0.27 kPa) and relatively low agreement with DBag vs. InCal (post-cardiac surgery bias = -1.17 ± 0.50 kPa; ARDS mean bias = -0.15 ± 0.53 kPa). These differences strongly affected calculated VD/VT. For example, in patients with ARDS, VD/VTcalculated with Enghoff-InCal was much higher than Bohr-VCap (VD/VT Enghoff-InCal = 66 ± 10 % vs. VD/VT Bohr-VCap = 45 ± 7 %; P < 0.05). CONCLUSIONS: Different techniques to measure PACO2 and PeCO2 result in clinically relevant mean and individual differences in calculated VD/VT, particularly in patients with ARDS. Volumetric capnography is a promising technique to calculate true Bohr dead space. Our results demonstrate the challenges clinicians face in interpreting an apparently simple measurement such as VD/VT.

A Novel Approach for the Detection and Severity Grading of Chronic Obstructive Pulmonary Disease Based on Transformed Volumetric Capnography.

Chronic Obstructive Pulmonary Disease (COPD), as the third leading cause of death worldwide, is a major global health issue. The early detection and grading of COPD are pivotal for effective treatment. Traditional spirometry tests, requiring considerable physical effort and strict adherence to quality standards, pose challenges in COPD diagnosis. Volumetric capnography (VCap), which can be performed during natural breathing without requiring additional compliance, presents a promising alternative tool. In this study, the dataset comprised 279 subjects with normal pulmonary function and 148 patients diagnosed with COPD. We introduced a novel quantitative analysis method for VCap. Volumetric capnograms were converted into two-dimensional grayscale images through the application of Gramian Angular Field (GAF) transformation. Subsequently, a multi-scale convolutional neural network, CapnoNet, was conducted to extract features and facilitate classification. To improve CapnoNet's performance, two data augmentation techniques were implemented. The proposed model exhibited a detection accuracy for COPD of 95.83%, with precision, recall, and F1 measures of 95.21%, 95.70%, and 95.45%, respectively. In the task of grading the severity of COPD, the model attained an accuracy of 96.36%, complemented by precision, recall, and F1 scores of 88.49%, 89.99%, and 89.15%, respectively. This work provides a new perspective for the quantitative analysis of volumetric capnography and demonstrates the strong performance of the proposed CapnoNet in the diagnosis and grading of COPD. It offers direction and an effective solution for the clinical application of capnography.

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.

Pathophysiology of gas exchange impairment in extreme prematurity: Insights from combining volumetric capnography and measurements of ventilation/perfusion ratio.

Background: Infants born extremely preterm often suffer from respiratory disease and are invasively ventilated. We aimed to test the hypothesis that gas exchange in ventilated extremely preterm infants occurs both at the level of the alveoli and via mixing of fresh deadspace gas in the airways. Methods: We measured the normalised slopes of phase II and phase III of volumetric capnography and related them with non-invasive measurements of ventilation to perfusion ratio (VA/Q) and right-to-left shunt in ventilated extremely preterm infants studied at one week of life. Cardiac right-to-left shunt was excluded by concurrent echocardiography. Results: We studied 25 infants (15 male) with a median (range) gestational age of 26.0 (22.9-27.9) weeks and birth weight of 795 (515-1,165) grams. The median (IQR) VA/Q was 0.52 (0.46-0.56) and shunt was 8 (2-13) %. The median (IQR) normalised slope of phase II was 99.6 (82.7-116.1) mmHg and of phase III was 24.6 (16.9-35.0) mmHg. The VA/Q was significantly related to the normalised slope of phase III (ρ = -0.573, p = 0.016) but not to the slope of phase II (ρ = 0.045, p = 0.770). The right-to-left shunt was not independently associated with either the slope of phase II or the slope of phase III after adjusting for confounding parameters. Conclusions: Abnormal gas exchange in ventilated extremely preterm infants was associated with lung disease at the alveolar level. Abnormal gas exchange at the level of the airways was not associated with quantified indices of gas exchange impairment.

Increased respiratory dead space could associate with coagulation activation and poor outcomes in COVID-19 ARDS.

PURPOSE: To determine whether VDPhys/VT is associated with coagulation activation and outcomes. MATERIALS AND METHODS: We enrolled patients with COVID-19 pneumonia who were supported by invasive mechanical ventilation and were monitored using volumetric capnography. Measurements were performed during the first 24 h of mechanical ventilation. The primary endpoint was the likelihood of being discharge alive on day 28. RESULTS: Sixty patients were enrolled, of which 25 (42%) had high VDPhys/VT (>57%). Patients with high vs. low VDPhys/VT had higher APACHE II (10[8-13] vs. 8[6-9] points, p = 0.002), lower static compliance of the respiratory system (35[24-46] mL/cmH2O vs. 42[37-45] mL/cmH2O, p = 0.005), and higher D-dimer levels (1246[1050-1594] ng FEU/mL vs. 792[538-1159] ng FEU/mL, p = 0.001), without differences in P/F ratio (157[112-226] vs. 168[136-226], p = 0.719). Additionally, D-dimer levels correlated with VDPhys/VT (r = 0.530, p < 0.001), but not with the P/F ratio (r = -0.103, p = 0.433). Patients with high VDPhys/VT were less likely to be discharged alive on day 28 (32% vs. 71%, aHR = 3.393[1.161-9.915], p = 0.026). CONCLUSIONS: In critically ill COVID-19 patients, increased VDPhys/VT was associated with high D-dimer levels and a lower likelihood of being discharged alive. Dichotomic VDPhys/VT could help identify a high-risk subgroup of patients neglected by the P/F ratio.

Determination of tidal volume by electrical impedance tomography (EIT) after indirect two-point calibration.

Objective. A linear relationship between impedance change (ΔZ) measured by thoracic electrical impedance tomography (EIT) and tidal volume (VT) has been demonstrated. This study evaluated the agreement between the displayed VT calculated by the EIT software (VTEIT) and spirometry (VTSPIRO) after an indirect two-point calibration.Approach.The EIT software was programmed to execute a bedside two-point calibration from the subject-specific, linear equation defining the relationship between ΔZand VTSPIROand displaying VTEITbreath-by-breath in 20 neutered male, juvenile pigs. After EIT calibration VTs of 8, 12, 16 and 20 ml kg-1were applied to the lungs. VTEITand VTSPIROwere recorded and analysed using Bland-Altman plot for multiple subject measurements. Volumetric capnography (VCap) and spirometry data were explored as components of variance using multiple regression.Main results.A mean relative difference (bias) of 0.7% with 95% confidence interval (CI) of -10.4% to 10.7% were found between VTEITand VTSPIROfor the analysed data set. The variance in VTEITcould not be explained by any of the measured VCap or spirometry variables.Significance.The narrow CI estimated in this study allows the conclusion that EIT and its software can be used to measure and accurately convert ΔZinto mililitre VT at the bedside after applying an indirect two-point calibration.

Bronchiectasis associated with severe COPD: Clinical, functional, microbiological and tomographic features.

Background: Bronchiectasis is frequently identified in patients with COPD, especially in severe patients, but the relevance of this finding remains unclear. We aimed to investigate the factors that would increase the chance of having bronchiectasis in patients with severe COPD. Methods: This is an analytical, observational, cross-sectional study. Patients with severe COPD with (BC group) and without bronchiectasis (NBC group) were clinically evaluated and performed spirometry, 6-minute walk test (6MWT), volumetric capnography (VCap) and high resolution computed tomography (CT). CT was scored for the findings, and multiple linear regression was performed to identify variables related to the score's severity and logistic regression in order to identify factors that could be associated with the presence of bronchiectasis. Results: There was no significant difference between BC and NBC groups regarding clinical variables, except in the smoking load, which was lower in the BC group. In functional evaluation, NBC patients walked shorter distances in 6MWT (P < 0.005). In the BC group the distribution of CT findings was mostly bilateral and in lower lobes. Using the multiple linear regression analysis within the BC group, we found that the higher the bronchiectasis score, the higher ΔSpO2 during the 6MWT and the lower the FVC. The chance of having bronchiectasis was 4.78 times higher in the presence of positive isolates (sputum) (CI 1.35-16.865; P = 0.023). The higher the distance covered (6MWT) and Slp3 (VCap), (OR 1.01, CI 1.004; 1.0202, P = 0.0036; OR 1.04, CI 1.003; 1.077; P = 0.036), the greater are likelihood of bronchiectasis. Conclusions: In patients with COPD and bronchiectasis, higher CT scores were associated with worse lung function and a greater drop in oxygenation during exercise.

Effects of volume-targeted pressure-controlled inverse ratio ventilation on functional residual capacity and dead space in obese patients undergoing robot-assisted laparoscopic radical prostatectomy.

Background: The effect of inverse inspiration:expiration (I:E) ratio on functional residual capacity (FRC) during pneumoperitoneum is unclear. We hypothesised that volume-targeted pressure-controlled inverse ratio ventilation (vtPC-IRV) would increase FRC by increasing the level of auto-PEEP in low respiratory compliance situations. Methods: During robot-assisted laparoscopic radical prostatectomy, 20 obese patients were sequentially ventilated with four different settings for 30 min in each setting: (1) control, I:E ratio of 1:2 and baseline airway pressure (BAP) of 5 cm H2O; (2) IRV2, I:E ratio of 2:1 and BAP off; (3) IRV3, I:E ratio of 3:1 and BAP off; and (4) IRV4, I:E ratio of 4:1 and BAP off. The changes in FRC were identified and compared among these settings. Results: The FRC significantly increased as the I:E ratio increased. The FRC values expressed as median (inter-quartile range) during control, IRV2, IRV3, and IRV4 were 1149 (898-1386), 1485 (1018-1717), 1602 (1209-1775), and 1757 (1337-1955) ml, respectively. Auto-PEEP increased significantly as the I:E ratio increased and correlated with FRC (rho=0.303; P=0.006). Shunt and physiological dead space were significantly lower in all IRV groups than in the control group; however, there were no significant differences among the IRV groups. Conclusions: vtPC-IRV with shortened expiratory time and increased auto-PEEP effectively increases FRC during robot-assisted laparoscopic radical prostatectomy in obese patients. FRC increases progressively as the I:E ratio increases from 1:2 to 4:1; however, an I:E ratio higher than 2:1 does not further improve the dead space. Clinical trial registration: UMIN000038989.