Alveolar Dead Space Research Articles

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. NCT03266016; August 23, 2017.

Invasive ventilation at the boundary of viability: A respiratory pathophysiology study of infants born between 22 and 24 weeks of gestation

BackgroundInvasive ventilation of infants born before 24 weeks of gestation is critical for survival and long-term respiratory outcomes, but currently there is a lack of evidence to guide respiratory management. We aimed to compare respiratory mechanics and gas exchange in ventilated extremely preterm infants born before and after 24 weeks of gestation. MethodsSecondary analysis of two prospective observational cohort studies, comparing respiratory mechanics and indices of gas exchange in ventilated infants born at 22–24 weeks of gestation (N=14) compared to infants born at 25–27 weeks (N=37). The ventilation/perfusion ratio (VA/Q), intrapulmonary shunt, alveolar dead space (VDalv) and adjusted alveolar surface area (SA) were measured in infants born at the Neonatal Unit of King’s College Hospital NHS Foundation Trust, London, UK. ResultsCompared to infants of 25–27 weeks, infants of 22–24 weeks had higher median (IQR) intrapulmonary shunt [18 (4 - 29) % vs 8 (2 – 12) %, p=0.044] and higher VDalv [0.9 (0.6 – 1.4) vs 0.6 (0.5 – 0.7) ml/kg, p=0.036], but did not differ in VA/Q. Compared to infants of 25–27 weeks, the infants of 22–24 weeks had a lower adjusted SA [509 (322- 687) vs 706 (564 - 800) cm2, p=0.044]. The infants in the two groups did not differ in any of the indices of respiratory mechanics. ConclusionVentilated infants born before 24 completed weeks of gestation exhibit abnormal gas exchange, with higher alveolar dead space and intrapulmonary shunt and a decreased alveolar surface area compared to extreme preterms born after 24 weeks of gestation.

Flow-controlled expiration ventilation using a piston ventilator: effects of expiration time and speed on respiratory and pulmonary mechanics with focus on hysteresis and compliance in healthy horses.

To investigate the effects of FLow-controlled EXpiration (FLEX) ventilation expiration time and speed on respiratory and pulmonary mechanics in anesthetized horses in dorsal recumbency. 6 healthy adult research horses. In this randomized crossover experimental study, horses were anesthetized 3 times and were ventilated each time for 60 minutes using conventional volume-controlled ventilation (VCV), linear emptying of the lung over 50% of the expiratory time (FLEX50), or linear emptying of the lung over 100% of the expiratory time (FLEX100) in a randomized order. The primary outcome variables were dynamic compliance (Cdyn), hysteresis, and alveolar dead space. The data was analyzed using two-factor ANOVA. Significance was set to P < .05. Horses ventilated using FLEX50 and FLEX100 showed significantly higher Cdyn and significantly lower hysteresis values compared to horses ventilated using VCV. Horses ventilated using FLEX50 had significantly lower alveolar dead space compared to horses ventilated using FLEX100 or VCV. Horses ventilated using FLEX100 had significantly lower alveolar dead space compared to VCV horses. Our results demonstrate improved Cdyn, hysteresis, and alveolar dead space in horses ventilated with either FLEX50 or FLEX100 relative to traditional VCV. The use of FLEX with a faster exhalation speed (FLEX50) offers additional respiratory advantages.

Cardiopulmonary effects of apneustic anesthesia ventilation in anesthetized pigs: a new mode of ventilation for anesthetized veterinary species

ObjectiveTo compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new mode of ventilation for anesthetized veterinary species.Study designRandomized, crossover design without washout.AnimalsTwelve healthy, female white Landrace pigs.MethodsFollowing ketamine-midazolam premedication and anesthetic induction with propofol, the trachea was intubated, and each pig was positioned in dorsal recumbency. Anesthesia was maintained with propofol and sufentanil infusions. Pigs were instrumented and their lungs were sequentially ventilated with each mode, in random order, for 1 h according to predefined criteria [fraction of inspired oxygen (FiO2) = 0.21, 10 mL kg−1 tidal volume (VT), and arterial carbon dioxide tension (PaCO2) within 40–45 mmHg]. Cardiopulmonary data were collected at baseline, 30 and 60 min. In 8 pigs, thoracic computed tomography (CT) was performed following the 60 min time point for each mode of ventilation and images were analyzed to quantify lung aeration. The effects of ventilation mode, time, and order were analyzed using repeated measures ANOVA. Paired t-tests were used to compare lung aeration between modes. Significance was defined as p &amp;lt; 0.05.ResultsData from 12 pigs were analyzed. A significant effect of mode was found for heart rate, mean arterial pressure (MAP), pulmonary artery occlusion pressure, cardiac index (CI), stroke volume index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery index (DO2I), oxygen extraction ratio (O2ER), VT, arterial oxygen tension, arterial hemoglobin saturation, PaCO2, end-tidal carbon dioxide tension, alveolar dead space (VDalv/VTalv), venous admixture (Q.s/Q.t), mean airway pressure, and dynamic compliance index (CRSI). Order effects were also observed for some cardiovascular and respiratory variables. For the eight pigs that underwent thoracic CT, AAV resulted in significantly larger proportions of normally and hyperaerated lung while CMV resulted in larger proportions of hypoaerated and atelectatic lung.ConclusionsIn dorsally recumbent anesthetized pigs, ventilated with FiO2 = 0.21, both modes of ventilation supported adequate oxygenation while AAV resulted in higher CRSI, and lower VDalv/VTalv and Q.s/Q.t, compared with CMV. AAV was also associated with lower MAP, CI, and DO2I and higher O2ER compared with CMV. Further investigation of AAV in anesthetized animals is warranted.

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

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

Apneustic anesthesia ventilation improves pulmonary function in anesthetized bottlenose dolphins (Tursiops truncatus).

Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.

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

BackgroundPulmonary 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.MethodsAnesthetized 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.ResultsIn 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.ConclusionsOur 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.

Improved oxygenation in prone positioning of mechanically ventilated patients with COVID-19 acute respiratory distress syndrome is associated with decreased pulmonary shunt fraction: a prospective multicenter study

BackgroundProne position is used in acute respiratory distress syndrome and in coronavirus disease 2019 (Covid-19) acute respiratory distress syndrome (ARDS). However, physiological mechanisms remain unclear. The aim of this study was to determine whether improved oxygenation was related to pulmonary shunt fraction (Q’s/Q’t), alveolar dead space (Vd/Vtalv) and ventilation/perfusion mismatch (V’A/Q’).MethodsThis was an international, prospective, observational, multicenter, cohort study, including six intensive care units in Sweden and Poland and 71 mechanically ventilated adult patients.ResultsProne position increased PaO2:FiO2 after 30 min, by 78% (83–148 mm Hg). The effect persisted 120 min after return to supine (p < 0.001). The oxygenation index decreased 30 min after prone positioning by 43% (21–12 units). Q’s/Q’t decreased already after 30 min in the prone position by 17% (0.41–0.34). The effect persisted 120 min after return to supine (p < 0.005). Q’s/Q’t and PaO2:FiO2 were correlated both in prone (Beta -137) (p < 0.001) and in the supine position (Beta -270) (p < 0.001). V’A/Q’ was unaffected and did not correlate to PaO2:FiO2 (p = 0.8). Vd/Vtalv increased at 120 min by 11% (0.55–0.61) (p < 0.05) and did not correlate to PaO2:FiO2 (p = 0.3). The ventilatory ratio increased after 30 min in the prone position by 58% (1.9–3.0) (p < 0.001). PaO2:FiO2 at baseline predicted PaO2:FiO2 at 30 min after proning (Beta 1.3) (p < 0.001).ConclusionsImproved oxygenation by prone positioning in COVID-19 ARDS patients was primarily associated with a decrease in pulmonary shunt fraction. Dead space remained high and the global V’A/Q’ measure could not explain the differences in gas exchange.

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

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

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

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

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.

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

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

A modal definition of ideal alveolar oxygen.

In the three-compartment model of lung ventilation-perfusion heterogeneity (VA/Q scatter), both Bohr dead space and shunt equations require values for central "ideal" compartment O2 and CO2 partial pressures. However, the ideal alveolar gas equation most accurately calculates mixed (ideal and alveolar dead space) PAO2 . A novel "modal" definition has been validated for ideal alveolar CO2 partial pressure, at the VA/Q ratio in a lung distribution where CO2 elimination is maximal. A multicompartment computer model of physiological, lognormal distributions of VA and Q was used to identify modal "ideal" PAO2 , and find a modification of the alveolar gas equation to estimate it across a wide range of severity of VA/Q heterogeneity and FIO2 . This was then validated in vivo using data from a study of 36 anesthetized, ventilated patients with FIO2 0.35-80. Substitution in the alveolar gas equation of respiratory exchange ratio R with achieved excellent agreement (r2 = 0.999) between the calculated ideal PAO2 and the alveolar-capillary Pc'O2 at the modal VO2 point ("modal" Pc'O2 ), across a range of log standard deviation of VA 0.25-1.75, true shunt 0%-20%, overall VA/Q 0.4-1.6, and FIO2 0.18-1.0, where the modeled PaO2 was over 50 mm Hg. Modal ideal PAO2 can be reliably estimated using routine blood gas measurements.

Cardiac output affects the response to pulsed inhaled nitric oxide in mechanically ventilated anesthetized ponies determined by CT angiography of the lung.

To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arterial pressure < 70 mmHg) was treated using dobutamine after 30 minutes of PiNO delivery. Following the discontinuation of PiNO, dobutamine administration was discontinued in 3 ponies and was continued in 3 ponies. The lung was imaged at 30, 60, and 105 minutes. Anesthetic 2: hypotension persisted throughout anesthesia. The lung was imaged at 30, 60, and 90 minutes. At all time points, arterial and mixed venous blood samples were analyzed and cardiac output (Q˙t) was measured. Pulmonary perfusion was calculated from CT image analysis. During PiNO delivery, perfusion to well-ventilated lungs increased if ponies were normotensive, leading to increased arterial oxygenation, reduced alveolar dead space, and reduced alveolar to arterial oxygen tension gradient. When PiNO was stopped and dobutamine administration continued, alveolar dead space and venous admixture increased, in contrast to when dobutamine and PiNO were both discontinued. If PiNO is administered to mechanically ventilated, anesthetized ponies with concurrent hypotension and low Q˙t, this must be supported to achieve favorable redistribution of pulmonary perfusion to improve pulmonary gas exchange.

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

Ventilator settings in children under anaesthesia remain difficult because of the changes in the physiology and the high dead space. To determine the alveolar minute-volume to sustain normocapnia in children under mechanical ventilation. A prospective observational study. This study was performed between May and October 2019 in a tertiary care children's hospital. Children between 2 months and 12 years, weighing between 5 and 40 kg, admitted for general anaesthesia. Volumetric capnography was used to estimate the alveolar and dead space volume (Vd). Total and alveolar minute ventilation in (ml kg-1 min-1) over 100 breaths. 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 ± 21 ml kg-1 min-1. 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. ClinicalTrials.gov, identifier: NCT03901599.

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for [formula omitted] Mismatch

The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vdalv; Enghoff modification of the Bohr equation) and the alveolar-arterial Po2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙e)/CO2 elimination (V˙co2) slope was also calculated as the slope of the V˙e and V˙co2 relationship, which reflects ventilatory efficiency. Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vsNTG: 4.03 ± 2.18; P= .009) despite a clear decrease in pulmonary capillary wedge pressure at 20W (PLC: 19.7 ± 8.2 vsNTG: 15.9 ± 7.4mmHg; P< .001). Moreover, Vdalv (PLC: 0.28 ± 0.07 vsNTG: 0.31 ± 0.08 L/breath; P= .01), A-aDO2 (PLC: 19.6 ± 6.7 vsNTG: 21.1 ± 6.7; P= .04), and V˙e/V˙co2 slope (PLC: 37.6 ± 5.7 vsNTG: 40.2 ± 6.5; P< .001) all increased at 20W after a decrease in pulmonary capillary wedge pressure. These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.

The Effects of Positive End Expiratory Pressure and Lung Volume on Diaphragm Thickness and Thickening

Introduction: Diaphragm dysfunction is common in patients undergoing mechanical ventilation. The application of positive end-expiratory pressure (PEEP) and the varying end-expiratory lung volume cause changes in diaphragm geometry. We aimed to assess the impact of the level of PEEP and lung inflation on diaphragm thickness, thickening fraction and displacement. Methods: An observational study in a mixed medical and surgical ICU was conducted. The patients underwent a PEEP-titration trial with the application of three random levels of PEEP: 0 cmH2O (PEEP0), 8 cmH2O (PEEP8) and 15 cmH2O (PEEP15). At each step, the indices of respiratory effort were assessed, together with arterial blood and diaphragm ultrasound; end-expiratory lung volume was measured. Results: 14 patients were enrolled. The tidal volume, diaphragm displacement and thickening fraction were significantly lower with higher levels of PEEP, while both the expiratory and inspiratory thickness increased with higher PEEP levels. The inspiratory effort, as evaluated by the esophageal pressure swing, was unchanged. Both the diaphragm thickening fraction and displacement were significantly correlated with inspiratory effort in the whole dataset. For both measurements, the correlation was stronger at lower levels of PEEP. The difference in the diaphragm thickening fraction during tidal breathing between PEEP 15 and PEEP 0 was negatively related to the change in the functional residual capacity and the change in alveolar dead space. Conclusions: Different levels of PEEP significantly modified the diaphragmatic thickness and thickening fraction, showing a PEEP-induced decrease in the diaphragm contractile efficiency. When using ultrasound to assess diaphragm size and function, the potential effect of lung inflation should be taken into account.

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

BackgroundThe 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.MethodsRetrospective 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.ResultsThere 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).ConclusionsAVDSf 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.

965: THE ASSOCIATION BETWEEN VENTILATORY EFFICIENCY, A NONINVASIVE DEAD SPACE METRIC, AND MORTALITY

Introduction: Higher dead space is associated with increased mortality and prolonged mechanical ventilation in children and adults with acute respiratory distress syndrome (ARDS). Dead space assessment typically requires measurement of PCO2. Ventilatory efficiency (minute ventilation/VCO2) may be a useful non-invasive continuous dead space surrogate with prognostic value. Methods: Prospective observational cohort study. Mechanically ventilated children with ARDS were monitored with volumetric capnography. The first simultaneous measurements of ventilatory efficiency, physiologic dead space (VD/VT=[PCO2-PeCO2]/PCO2), the end-tidal alveolar dead space fraction (AVDSf=[PCO2-PETCO2]/PCO2), and oxygenation index (OI) within the first 72h of mechanical ventilation were used in the analysis. Results: There were 80 enrolled children. Median VD/VT was 0.46 (IQR 0.38, 0.58) and OI was 7.5 (IQR 4.6, 14.2). Mortality was 19%. The correlation between VD/VT and ventilatory efficiency (rs=0.68, p< 0.001) and VD/VT and AVDSf (rs=0.74, p< 0.001) were high. The correlation between AVDSf and ventilatory efficiency was lower (rs=0.48, p< 0.001). After controlling for OI and severity of illness (PRISM III) in separate multivariable models, higher VD/VT (per 0.1 increase, OR 1.66 [95% CI 1.04, 2.64], p=0.035), ventilatory efficiency (per 0.01, OR 1.69 [95% CI 1.10, 2.59], p=0.017), and AVDSf (per 0.1, OR 1.88 (95% CI 1.05, 3.38), p=0.035) were all associated with increased mortality. However, VD/VT, ventilatory efficiency, and AVDSf were not independently associated with fewer 28-day ventilator free days (VFD) or longer length of mechanical ventilation in survivors (LMV) after controlling for OI and PRISM III. OI was not associated with mortality after controlling for any of the dead space terms (all p>0.15) and PRISM III, but was independently associated with fewer 28-day VFDs (all p< 0.03) and longer LMV (all p< 0.01). Conclusions: Higher ventilatory efficiency, a continuous non-invasive measure of dead space that does not rely on blood gas measurement, is highly correlated with VD/VT and is independently associated with increased mortality in children with acute hypoxemic respiratory failure. Dead space metrics appear more strongly associated with mortality while OI appears more strongly associated with length of ventilation.

Alveolar dead space fraction is not associated with early RV systolic dysfunction in pediatric ARDS.

We hypothesized that higher alveolar dead space fraction (AVDSf) at pediatric acute respiratory distress syndrome (PARDS) onset would be associated with right ventricular (RV) systolic dysfunction within the first 24 h of PARDS. We performed a retrospective single-center cohort study of PARDS patients with clinically obtained echocardiograms within 24 h. Primary exposure was AVDSf at PARDS onset. Primary outcome was RV systolic dysfunction as defined by RV global longitudinal strain (GLS) (>-18%). Secondary outcomes included pulmonary hypertension (PH) and RV systolic dysfunction as defined by other echocardiogram parameters, and measures of oxygenation. Unadjusted and adjusted logistic and linear regression were used to investigate AVDSf associations with outcomes. Ninety-one patients were included: median age 6.2 years, 46% female, and 65% with moderate or severe PARDS. Median AVDSf was 0.2 (interquartile range [IQR] 0.0-0.3), 33% had RV dysfunction, and 21% had PH. Unadjusted and adjusted logistic regression showed no association between AVDSf and RV systolic dysfunction or PH by any echocardiographic measure, but unadjusted and adjusted linear regression did show an association between AVDSf and PaO2 /FiO2 . AVDSf at PARDS onset was not associated with RV systolic dysfunction or PH within 24 h but was associated with PaO2 /FiO2 ratio and may be more reflective of pulmonary causes of ventilation-perfusion mismatch. Future investigations should focus on clarifying the clinical utility of AVDSf in relation to existing metrics throughout the course of PARDS.