The Association Between Ventilatory Ratio and Mortality of Adult Patients with ARDS: Systematic Review and Meta-Analysis

Background: Ventilatory ratio is a simple bedside index of impaired efficiency of ventilation and correlates well with physiological dead space fraction in patients with ARDS. So it was regarded as a dead-space marker associated with mortality in mechanically ventilated adults with ARDS. However, the association between VR and outcome of patients with ARDS remains largely unknown. Methods: We searched articles in three electronic databases including PubMed, EMBASE and Web of Science. All the English publications up to 1 st Oct. 2021 will be searched without any restriction of countries. All the observational study that investigated the association between ventilatory ratio and the mortality of ARDS patients were identified in this meta-analysis. The main outcome was mortality. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes with accompanying 95% confidence interval (CI) were expressed. Results: A total of 9 trials enrolling 5638 patients were finally included in this meta-analysis. The results revealed that the use of ventilatory ratio could be significantly related to the mortality in adult ARDS (OR=1.27; 95% CI 1.10 to 1.47; P=0.001). Ventilatory ratio may have the capability of predicting the mortality of NON- COVID-related patients (OR 1.39, 95% CI 1.12 to 1.73 P = 0.003) while it has no predictable significance in patients with COVID (OR 1.18, 95% CI 0.94 to 1.48 P = 0.16). Importantly, the dynamic changes of VR adds more predictable value (OR 1.21 vs 1.19). Conclusion: Our study suggests that ventilatory ratio can be regarded as a valuable marker to predict the mortality of adult patients with ARDS. Compared to patients with COVID, ventilatory ratio is more predictable in patients with NON-COVID. What’s more, the dynamic changes of VR may have the potential to improve the prognostic value.

Changes in dead space components during pressure-controlled inverse ratio ventilation: A secondary analysis of a randomized trial

Background We previously reported that there were no differences between the lung-protective actions of pressure-controlled inverse ratio ventilation and volume control ventilation based on the changes in serum cytokine levels. Dead space represents a ventilation-perfusion mismatch, and can enable us to understand the heterogeneity and elapsed time changes in ventilation-perfusion mismatch. Methods This study was a secondary analysis of a randomized controlled trial of patients who underwent robot-assisted laparoscopic radical prostatectomy. The inspiratory to expiratory ratio was adjusted individually by observing the expiratory flow-time wave in the pressure-controlled inverse ratio ventilation group (n = 14) and was set to 1:2 in the volume-control ventilation group (n = 13). Using volumetric capnography, the physiological dead space was divided into three dead space components: airway, alveolar, and shunt dead space. The influence of pressure-controlled inverse ratio ventilation and time factor on the changes in each dead space component rate was analyzed using the Mann-Whitney U test and Wilcoxon’s signed rank test. Results The physiological dead space and shunt dead space rate were decreased in the pressure-controlled inverse ratio ventilation group compared with those in the volume control ventilation group (p < 0.001 and p = 0.003, respectively), and both dead space rates increased with time in both groups. The airway dead space rate increased with time, but the difference between the groups was not significant. There were no significant changes in the alveolar dead space rate. Conclusions Pressure-controlled inverse ratio ventilation reduced the physiological dead space rate, suggesting an improvement in the total ventilation/perfusion mismatch due to improved inflation of the alveoli affected by heterogeneous expansion disorder without hyperinflation of the normal alveoli. However, the shunt dead space rate increased with time, suggesting that atelectasis developed with time in both groups.

Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications

There is well established evidence that the minute ventilation (V′E)/carbon dioxide output (V′CO2) relationship is relevant to a number of patient-related outcomes in COPD. In most circumstances, an increased V′E/V′CO2 reflects an enlarged physiological dead space (“wasted” ventilation), although alveolar hyperventilation (largely due to increased chemosensitivity) may play an adjunct role, particularly in patients with coexistent cardiovascular disease. The V′E/V′CO2 nadir, in particular, has been found to be an important predictor of dyspnoea and poor exercise tolerance, even in patients with largely preserved forced expiratory volume in 1 s. As the disease progresses, a high nadir might help to unravel the cause of disproportionate breathlessness. When analysed in association with measurements of dynamic inspiratory constraints, a high V′E/V′CO2 is valuable to ascertain a role for the “lungs” in limiting dyspnoeic patients. Regardless of disease severity, cardiocirculatory (heart failure and pulmonary hypertension) and respiratory (lung fibrosis) comorbidities can further increase V′E/V′CO2. A high V′E/V′CO2 is a predictor of poor outcome in lung resection surgery, adding value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of disease severity. Considering its potential usefulness, the V′E/V′CO2 should be valued in the clinical management of patients with COPD.

Usefulness of Respiratory Mechanics and Laboratory Parameter Trends as Markers of Early Treatment Success in Mechanically Ventilated Severe Coronavirus Disease: A Single-Center Pilot Study

Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients’ median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5–95) versus 2.5 (0–22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin–antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting.

End-tidal to arterial PCO2 ratio: a bedside meter of the overall gas exchanger performance

Background The physiological dead space is a strong indicator of severity and outcome of acute respiratory distress syndrome (ARDS). The “ideal” alveolar PCO2, in equilibrium with pulmonary capillary PCO2, is a central concept in the physiological dead space measurement. As it cannot be measured, it is surrogated by arterial PCO2 which, unfortunately, may be far higher than ideal alveolar PCO2, when the right-to-left venous admixture is present. The “ideal” alveolar PCO2 equals the end-tidal PCO2 (PETCO2) only in absence of alveolar dead space. Therefore, in the perfect gas exchanger (alveolar dead space = 0, venous admixture = 0), the PETCO2/PaCO2 is 1, as PETCO2, PACO2 and PaCO2 are equal. Our aim is to investigate if and at which extent the PETCO2/PaCO2, a comprehensive meter of the “gas exchanger” performance, is related to the anatomo physiological characteristics in ARDS. Results We retrospectively studied 200 patients with ARDS. The source was a database in which we collected since 2003 all the patients enrolled in different CT scan studies. The PETCO2/PaCO2, measured at 5 cmH2O airway pressure, significantly decreased from mild to mild–moderate moderate–severe and severe ARDS. The overall populations was divided into four groups (~ 50 patients each) according to the quartiles of the PETCO2/PaCO2 (lowest ratio, the worst = group 1, highest ratio, the best = group 4). The progressive increase PETCO2/PaCO2 from quartile 1 to 4 (i.e., the progressive approach to the “perfect” gas exchanger value of 1.0) was associated with a significant decrease of non-aerated tissue, inohomogeneity index and increase of well-aerated tissue. The respiratory system elastance significantly improved from quartile 1 to 4, as well as the PaO2/FiO2 and PaCO2. The improvement of PETCO2/PaCO2 was also associated with a significant decrease of physiological dead space and venous admixture. When PEEP was increased from 5 to 15 cmH2O, the greatest improvement of non-aerated tissue, PaO2 and venous admixture were observed in quartile 1 of PETCO2/PaCO2 and the worst deterioration of dead space in quartile 4. Conclusion The ratio PETCO2/PaCO2 is highly correlated with CT scan, physiological and clinical variables. It appears as an excellent measure of the overall “gas exchanger” status.

Ventilation/carbon dioxide output relationships during exercise in health

“Ventilatory efficiency” is widely used in cardiopulmonary exercise testing to make inferences regarding the normality (or otherwise) of the arterial CO2 tension (PaCO2) and physiological dead-space fraction of the breath (VD/VT) responses to rapid-incremental (or ramp) exercise. It is quantified as: 1) the slope of the linear region of the relationship between ventilation (V′E) and pulmonary CO2 output (V′CO2); and/or 2) the ventilatory equivalent for CO2 at the lactate threshold (V′E/V′CO2) or its minimum value (V′E/V′CO2min), which occurs soon after but before respiratory compensation. Although these indices are normally numerically similar, they are not equally robust. That is, high values for V′E/V′CO2 and V′E/V′CO2min provide a rigorous index of an elevated VD/VT when PaCO2 is known (or can be assumed) to be regulated. In contrast, a high V′E–V′CO2 slope on its own does not, as account has also to be taken of the associated normally positive and small V′E intercept. Interpretation is complicated by factors such as: the extent to which PaCO2 is actually regulated during rapid-incremental exercise (as is the case for steady-state moderate exercise); and whether V′E/V′CO2 or V′E/V′CO2min provide accurate reflections of the true asymptotic value of V′E/V′CO2, to which the V′E–V′CO2 slope approximates at very high work rates.

Physiological Effects of Exercising at Different Intensities Wearing TNT or Double-layer Cotton Facemasks Compared to Not Wearing a Mask

We compared the physiological differences between exercising wearing a TNT or a double-layer-cotton (DLC) facemask (FM) and not wearing a mask (NM). Sixteen volunteers underwent 4 sets (S) of 2 sequential bouts (B). B1 and B2 corresponded to light and moderate intensity cycling, respectively. FMs were used as follows: S1: NM; S2: TNT or DLC; S3: DLC or TNT; and S4: NM. Metabolic, pulmonary, and perceptual variables were collected. The main results are expressed as effect sizes and confidence intervals (ES [95%CI]) for TNT and DLC unless otherwise indicated. Compared to NM, FM increased the duty cycle (B1=1.11[0.58-1.61] and 1.53[0.81-2.18]; B2=1.27[0.63-1.84] and 1.93[0.97-2.68]) and decreased breath frequency (B1=0.59[0.23-0.94] and 1.43[0.79-2.07], B2=0.39[0.05-0.71] and 1.33[0.71-1.94]). Only B1 tidal volume increased (0.33[0.09-0.56] and 0.62[0.18-1.05]) enough to avoid a ventilation reduction with TNT but not with DLC (B1=0.52[0.23-0.79]; B2=0.84[0.44-1.22]). Both FMs reduced oxygen saturation in B1 (0.56 [0.07-1.03] and 0.69 [0.09-1.28]) but only DLC did so in B2 (0.66 [0.11-1.13]). Both end tidal CO2 (B1=0.23[0.05-0.4] and 0.71[0.38-1.02]; B2=0.56[0.2-0.9] and 1.20[0.65-1.68]) and mixed-expired-CO2 (B1=0.74[0.38-1.08] 1.71[1.03-2.37], B2=0.94[0.45-1.38] and 1.78[0.97-2.42]) increased with FMs. Ventilatory adaptations imposed during FM exercising influenced blood-lung gas exchange. Larger ESs were seen with DLC. No adverse changes to human health were observed. Novelty Bullets Facemasks affect the breathing pattern by changing the frequency and amplitude of pulmonary ventilation. The augmented ventilatory work increases VO2, VCO2, and RPE and promotes non-concerning drops in SpO2 and CO2 retention. Increased inspiratory and expiratory pressure can account for the reduction in pulmonary physiological dead space.

Lung-protective properties of expiratory flow-initiated pressure-controlled inverse ratio ventilation: A randomised controlled trial

Background Expiratory flow-initiated pressure-controlled inverse ratio ventilation (EF-initiated PC-IRV) reduces physiological dead space. We hypothesised that EF-initiated PC-IRV would be lung protective compared with volume-controlled ventilation (VCV). Methods Twenty-eight men undergoing robot-assisted laparoscopic radical prostatectomy were enrolled in this randomised controlled trial. The EF-initiated PC-IRV group (n = 14) used pressure-controlled ventilation with the volume guaranteed mode. The inspiratory to expiratory (I:E) ratio was individually adjusted by observing the expiratory flow-time wave. The VCV group (n = 14) used the volume control mode with a 1:2 I:E ratio. The Mann–Whitney U test was used to compare differences in the serum cytokine levels. Results There were no significant differences in serum IL-6 between the EF-initiated PC-IRV (median 34 pg ml-1 (IQR 20.5 to 63.5)) and VCV (31 pg ml-1 (24.5 to 59)) groups (P = 0.84). The physiological dead space rate (physiological dead space/expired tidal volume) was significantly reduced in the EF-initiated PC-IRV group as compared with that in the VCV group (0.31 ± 0.06 vs 0.4 ± 0.07; P<0.001). The physiological dead space rate was negatively correlated with the forced vital capacity (% predicted) in the VCV group (r = -0.85, P<0.001), but not in the EF-initiated PC-IRV group (r = 0.15, P = 0.62). Two patients in the VCV group had permissive hypercapnia with low forced vital capacity (% predicted). Conclusions There were no differences in the lung-protective properties between the two ventilatory strategies. However, EF-initiated PC-IRV reduced physiological dead space rate; thus, it may be useful for reducing the ventilatory volume that is necessary to maintain normocapnia in patients with low forced vital capacity (% predicted) during robot-assisted laparoscopic radical prostatectomy.