Clinical outcomes and complications of S53P4 bioactive glass in chronic osteomyelitis and septic non-unions: a retrospective single-center study.

INTRODUCTION: Dead space management following debridement surgery in chronic osteomyelitis or septic non-unions is one of the most crucial and discussed steps for the success of the surgical treatment of these conditions. In this retrospective clinical study, we described the efficacy and safety profile of surgical debridement and local application of S53P4 bioactive glass (S53P4 BAG) in the treatment of bone infections. METHODS: A consecutive single-center series of 38 patients with chronic osteomyelitis (24) and septic non-unions (14), treated with bioactive glass S53P4 as dead space management following surgical debridement between May 2015 and November 2020, were identified and evaluated retrospectively. RESULTS: Infection eradication was reached in 22 out of 24 patients (91.7%) with chronic osteomyelitis. Eleven out of 14 patients (78.6%) with septic non-union achieved both fracture healing and infection healing in 9.1 ± 4.9 months. Three patients (7.9%) developed prolonged serous discharge with wound dehiscence but healed within 2 months with no further surgical intervention. Average patient follow-up time was 19.8 months ± 7.6 months. CONCLUSION: S53P4 bioactive glass is an effective and safe therapeutic option in the treatment of chronic osteomyelitis and septic non-unions because of its unique antibacterial properties, but also for its ability to generate a growth response in the remaining healthy bone at the bone-glass interface.

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.

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

OBJECTIVE: Our 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. METHODS: In 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. RESULTS: Fifteen 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. CONCLUSIONS: During 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.

Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis.

BACKGROUND: Adjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters. METHODS: The PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. INTERVENTIONS: Changes in trunk inclination. MEASUREMENTS: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency. RESULTS: After searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change. CONCLUSION: In patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Progressive changes in pulmonary gas exchange during invasive respiratory support for COVID-19 associated acute respiratory failure: A retrospective study of the association with 90-day mortality.

BACKGROUND: Ratio of arterial pressure of oxygen and fraction of inspired oxygen (P/F ratio) together with the fractional dead space (Vd/Vt) provides a global assessment of pulmonary gas exchange. The aim of this study was to assess the potential value of these variables to prognosticate 90-day survival in patients with COVID-19 associated ARDS admitted to the Intensive Care Unit (ICU) for invasive ventilatory support. METHODS: In this single-center observational, retrospective study, P/F ratios and Vd/Vt were assessed up to 4 weeks after ICU-admission. Measurements from the first 2 weeks were used to evaluate the predictive value of P/F ratio and Vd/Vt for 90-day mortality and reported by the adjusted hazard ratio (HR) and 95% confidence intervals [95%CI] by Cox proportional hazard regression. RESULTS: Almost 20,000 blood gases in 130 patients were analyzed. The overall 90-day mortality was 30% and using the data from the first ICU week, the HR was 0.85 [0.77-0.94] for every 10 mmHg increase in P/F ratio and 1.61 [1.20-2.16] for every 0.1 increase in Vd/Vt. In the second week, the HR for 90-day mortality was 0.82 [0.75-0.89] for every 10 mmHg increase in P/F ratio and 1.97 [1.42-2.73] for every 0.1 increase in Vd/Vt. CONCLUSION: The progressive changes in P/F ratio and Vd/Vt in the first 2 weeks of invasive ventilatory support for COVID-19 ARDS were significant predictors for 90-day mortality.

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

INTRODUCTION: COVID-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. METHODS: we 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). RESULTS: there 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). CONCLUSION: prone position did not change DSF in C-ARDS.

Individualized estimation of arterial carbon dioxide partial pressure using machine learning in children receiving mechanical ventilation.

BACKGROUND: Measuring arterial partial pressure of carbon dioxide (PaCO2) is crucial for proper mechanical ventilation, but the current sampling method is invasive. End-tidal carbon dioxide (EtCO2) has been used as a surrogate, which can be measured non-invasively, but its limited accuracy is due to ventilation-perfusion mismatch. This study aimed to develop a non-invasive PaCO2 estimation model using machine learning. METHODS: This retrospective observational study included pediatric patients (< 18 years) admitted to the pediatric intensive care unit of a tertiary children's hospital and received mechanical ventilation between January 2021 and June 2022. Clinical information, including mechanical ventilation parameters and laboratory test results, was used for machine learning. Linear regression, multilayer perceptron, and extreme gradient boosting were implemented. The dataset was divided into 7:3 ratios for training and testing. Model performance was assessed using the R2 value. RESULTS: We analyzed total 2,427 measurements from 32 patients. The median (interquartile range) age was 16 (12-19.5) months, and 74.1% were female. The PaCO2 and EtCO2 were 63 (50-83) mmHg and 43 (35-54) mmHg, respectively. A significant discrepancy of 19 (12-31) mmHg existed between EtCO2 and the measured PaCO2. The R2 coefficient of determination for the developed models was 0.799 for the linear regression model, 0.851 for the multilayer perceptron model, and 0.877 for the extreme gradient boosting model. The correlations with PaCO2 were higher in all three models compared to EtCO2. CONCLUSIONS: We developed machine learning models to non-invasively estimate PaCO2 in pediatric patients receiving mechanical ventilation, demonstrating acceptable performance. Further research is needed to improve reliability and external validation.

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.

Eureka: objective assessment of the empty pelvis syndrome to measure volumetric changes in pelvic dead space following pelvic exenteration.

BACKGROUND: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS. METHODS: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle. RESULTS: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%. CONCLUSIONS: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes.

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.

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.

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.

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

INTRODUCTION: Electrical 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. METHODS: Pixel-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. RESULTS: Among 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. CONCLUSION: Neglecting 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.

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.

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.

Arterial to end-tidal carbon dioxide gap and its characterization in mechanically ventilated adults in the emergency department.

PURPOSE: To evaluate early measurement of the arterial to end-tidal carbon dioxide (PaCO2-PetCO2) gap, a surrogate for physiologic dead space, and its association with clinical outcomes in intubated adults in the emergency department (ED). MATERIALS AND METHODS: Observational cohort study of invasively mechanically ventilated adults in an academic medical center (years 2009 to 2016). The association of the PaCO2-PetCO2 gap was evaluated with respect to clinical outcomes; the primary outcome was in-hospital mortality. RESULTS: 519 patients were included. 325 (63%) patients had an elevated (>5 mmHg) PaCO2-PetCO2. Patients with an elevated PaCO2-PetCO2 were significantly older, had higher APACHE II scores, more frequently had chronic obstructive pulmonary disease (COPD), had lower arterial oxygen to fraction of inspired oxygen (P:F) ratios, and were more likely to be intubated for exacerbation of COPD or sepsis. There was no difference in mortality for patients with an elevated PaCO2-PetCO2 (25% vs 26%) in unadjusted analysis (p = 0.829) or adjusted analysis (aOR = 0.81 [95% CI: 0.53-1.26]), as compared to a non-elevated PaCO2-PetCO2. CONCLUSIONS: An elevated PaCO2-PetCO2 gap is common in the post-intubation period in the ED, but not significantly associated with clinical outcomes.

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.

Arterial to end-tidal CO2 gradients during isocapnic hyperventilation.

Isocapnic hyperventilation (ICHV) is occasionally used to maintain the end-expired CO2 partial pressure (PETCO2) when the inspired CO2 (PICO2) rises. Whether maintaining PETCO2 with ICHV during an increase of the PICO2 also maintains arterial PCO2 (PaCO2) remains poorly documented. 12 ASA PS I-II subjects undergoing a robot-assisted radical prostatectomy (RARP) (n = 11) or cystectomy (n = 1) under general endotracheal anesthesia with sevoflurane in O2/air (40% inspired O2) were enrolled. PICO2 was sequentially increased from 0 to 0.5, 1.0, 1.5 and 2% by adding CO2 to the inspiratory limb of the circle system, while increasing ventilation to a target PETCO2 of 4.7-4.9% by adjusting respiratory rate during controlled mechanical ventilation. Pa-ETCO2 gradients were determined after a 15 min equilibration period at each PICO2 level and compared using ANOVA. Mean (standard deviation) age, height, and weight were 66 (6) years, 171 (6) cm, and 75 (8) kg, respectively. Capnograms were normal and hemodynamic parameters remained stable. PETCO2 could be maintained within 4.7-4.9% in all subjects at all times except in 1 subject with 1.5% PICO2 and 5 subjects with 2.0% PICO2; data from the one subject in whom both 1.5 and 2.0% PICO2 resulted in PETCO2 > 5.1% were excluded from analysis. Pa-ETCO2 gradients did not change when PICO2 increased. The effect of a modest rise of PICO2 up to 1.5% on PETCO2 during RARP can be readily overcome by increasing ventilation without altering the Pa-ETCO2 gradients. At higher PICO2, airway pressures may become a limiting factor, which requires further study.

Model analysis of multiple breath nitrogen washout data: robustness to variations in breathing pattern.

We recently developed a model-based method for analyzing multiple breath nitrogen washout data that does not require identification of Phase-III. In the present study, we assessed the effect of irregular breathing patterns on the intra-subject variabilities of the model parameters. Nitrogen fraction at the mouth was measured in 18 healthy and 20 asthmatic subjects during triplicate performances of multiple breath nitrogen washout, during controlled (target tidal volume 1 L at 8-12 breaths per minute) and free (unrestricted) breathing. The parameters Scond, Sacin and functional residual capacity (FRC) were obtained by conventional analysis of the slope of Phase-III. Fitting the model to the washout data provided functional residual capacity (FRCM), dead space volume (VD), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of Sacin (Sacin-M). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRCM < 5.2%, VD < 5.4%, [Formula: see text] < 9.0%, and Sacin-M < 45.6% for controlled breathing, and FRCM < 4.6%, VD < 5.3%, [Formula: see text] < 13.2%, and Sacin-M < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with Scond < 73.6% and Sacin < 49.2% for controlled breathing and Scond < 35.0% and Sacin < 74.4% for free breathing. The model-fitting approach to multiple breath nitrogen washout analysis provides a measure of regional ventilation heterogeneity in [Formula: see text] that is less affected by irregularities in the breathing pattern than its corresponding Phase-III slope analysis parameter Scond.

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.