Mechanical ventilation and COPD: from pathophysiology to ventilatory management.

In the chronic obstructive pulmonary disease (COPD), lung and chest-wall morphological alterations determine important and peculiar approaches to mechanical ventilation. Lung emphysema and reduced elastic recoil increase expiratory time, thus worsening dynamic hyperinflation, while airways chronic inflammation rises resistances and can determine distal air-trapping. Muscle wasting and fast fibers prevalence can result in weakness and in an earlier onset of muscle fatigue, prolonging the weaning process. In this narrative review, we explored the connection between altered pathophysiology and necessity for respiratory assistance in COPD, focusing on non-invasive and invasive respiratory management, lung monitoring and weaning difficulties.

Focus on renal blood flow in mechanically ventilated patients with SARS-CoV-2: a prospective pilot study.

Mechanically ventilated patients with ARDS due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seem particularly susceptible to AKI. Our hypothesis was that the renal blood flow could be more compromised in SARS-CoV-2 patients than in patients with "classical" ARDS. We compared the renal resistivity index (RRI) and the renal venous flow (RVF) in ARDS patients with SARS-CoV-2 and in ARDS patients due to other etiologies. Prospective, observational pilot study performed on 30 mechanically ventilated patients (15 with SARS-COV-2 ARDS and 15 with ARDS). Mechanical ventilation settings included constant-flow controlled ventilation, a tidal volume of 6 ml/kg of ideal body weight and the PEEP level titrated to the lowest driving pressure. Ultrasound Doppler measurements of RRI and RVF pattern were performed in each patient. Patients with SARS-COV-2 ARDS had higher RRI than patients with ARDS (0.71[0.67-0.78] vs 0.64[0.60-0.74], p = 0.04). RVF was not-continuous in 9/15 patients (71%) in the SARS-COV-2 ARDS group and in and 5/15 (33%) in the ARDS group (p = 0.27). A linear correlation was found between PEEP and RRI in patients with SARS-COV-2 ARDS (r2 = 0.31; p = 0.03) but not in patients with ARDS. Occurrence of AKI was 53% in patients with SARS-COV-2 ARDS and 33% in patients with ARDS (p = 0.46). We found a more pronounced impairment in renal blood flow in mechanically ventilated patients with SARS-COV-2 ARDS, compared with patients with "classical" ARDS.

Respiratory Drive in Patients with Sepsis and Septic Shock: Modulation by High-flow Nasal Cannula.

BACKGROUND: Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort. METHODS: Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile]. RESULTS: Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = -0.735, P < 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P < 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P < 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases. CONCLUSIONS: Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula.

Calculation of Transpulmonary Pressure From Regional Ventilation Displayed by Electrical Impedance Tomography in Acute Respiratory Distress Syndrome.

Transpulmonary driving pressure (DPL) corresponds to the cyclical stress imposed on the lung parenchyma during tidal breathing and, therefore, can be used to assess the risk of ventilator-induced lung injury (VILI). Its measurement at the bedside requires the use of esophageal pressure (Peso), which is sometimes technically challenging. Recently, it has been demonstrated how in an animal model of ARDS, the transpulmonary pressure (PL) measured with Peso calculated with the absolute values method (PL = Paw-Peso) is equivalent to the transpulmonary pressure directly measured using pleural sensors in the central-dependent part of the lung. We hypothesized that, since the PL derived from Peso reflects the regional behavior of the lung, it could exist a relationship between regional parameters measured by electrical impedance tomography (EIT) and driving PL (DPL). Moreover, we explored if, by integrating airways pressure data and EIT data, it could be possible to estimate non-invasively DPL and consequently lung elastance (EL) and elastance-derived inspiratory PL (PI). We analyzed 59 measurements from 20 patients with ARDS. There was a significant intra-patient correlation between EIT derived regional compliance in regions of interest (ROI1) (r = 0.5, p = 0.001), ROI2 (r = -0.68, p < 0.001), and ROI3 (r = -0.4, p = 0.002), and DPL. A multiple linear regression successfully predicted DPL based on respiratory system elastance (Ers), ideal body weight (IBW), roi1%, roi2%, and roi3% (R 2 = 0.84, p < 0.001). The corresponding Bland-Altmann analysis showed a bias of -1.4e-007 cmH2O and limits of agreement (LoA) of -2.4-2.4 cmH2O. EL and PI calculated using EIT showed good agreement (R 2 = 0.89, p < 0.001 and R 2 = 0.75, p < 0.001) with the esophageal derived correspondent variables. In conclusion, DPL has a good correlation with EIT-derived parameters in the central lung. DPL, PI, and EL can be estimated with good accuracy non-invasively combining information coming from EIT and airway pressure.

Management of Intraoperative Mechanical Ventilation to Prevent Postoperative Complications after General Anesthesia: A Narrative Review.

Mechanical ventilation (MV) is still necessary in many surgical procedures; nonetheless, intraoperative MV is not free from harmful effects. Protective ventilation strategies, which include the combination of low tidal volume and adequate positive end expiratory pressure (PEEP) levels, are usually adopted to minimize the ventilation-induced lung injury and to avoid post-operative pulmonary complications (PPCs). Even so, volutrauma and atelectrauma may co-exist at different levels of tidal volume and PEEP, and therefore, the physiological response to the MV settings should be monitored in each patient. A personalized perioperative approach is gaining relevance in the field of intraoperative MV; in particular, many efforts have been made to individualize PEEP, giving more emphasis on physiological and functional status to the whole body. In this review, we summarized the latest findings about the optimization of PEEP and intraoperative MV in different surgical settings. Starting from a physiological point of view, we described how to approach the individualized MV and monitor the effects of MV on lung function.

Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS.

BACKGROUND: In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO2/FiO2 and compliance. METHODS: Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units. RESULTS: Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27-47]% vs. 21[17-27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07-1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79-0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27-38]% vs. 18 [13-21]%, p < 0.001), while the opposite was true for perfusion (28 [22-38]% vs. 36 [32-44]%, p < 0.001). Higher percentage of only perfused units was correlated with lower dorsal ventilation (r = - 0.486, p < 0.001) and with lower PaO2/FiO2 ratio (r = - 0.293, p = 0.039). CONCLUSIONS: EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.

Quality of life of COVID-19 critically ill survivors after ICU discharge: 90 days follow-up.

PURPOSE: The onset of the coronavirus disease 19 (COVID-19) pandemic in Italy induced a dramatic increase in the need for intensive care unit (ICU) beds for a large proportion of patients affected by COVID-19-related acute respiratory distress syndrome (ARDS). The aim of the present study was to describe the health-related quality of life (HRQoL) at 90 days after ICU discharge in a cohort of COVID-19 patients undergoing invasive mechanical ventilation and to compare it with an age and sex-matched sample from the general Italian and Finnish populations. Moreover, the possible associations between clinical, demographic, social factors, and HRQoL were investigated. METHODS: COVID-19 ARDS survivors from 16 participating ICUs were followed up until 90 days after ICU discharge and the HRQoL was evaluated with the 15D instrument. A parallel cohort of age and sex-matched Italian population from the same geographic areas was interviewed and a third group of matched Finnish population was extracted from the Finnish 2011 National Health survey. A linear regression analysis was performed to evaluate potential associations between the evaluated factors and HRQoL. RESULTS: 205 patients answered to the questionnaire. HRQoL of the COVID-19 ARDS patients was significantly lower than the matched populations in both physical and mental dimensions. Age, sex, number of comorbidities, ARDS class, duration of invasive mechanical ventilation, and occupational status were found to be significant determinants of the 90 days HRQoL. Clinical severity at ICU admission was poorly correlated to HRQoL. CONCLUSION: COVID-19-related ARDS survivors at 90 days after ICU discharge present a significant reduction both on physical and psychological dimensions of HRQoL measured with the 15D instrument. TRIAL REGISTRATION: NCT04411459.

Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study.

BACKGROUND: Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (< median PaO2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation. RESULTS: The median PaO2/FiO2 variation after the first PP cycle was 49 [19-100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP. CONCLUSIONS: Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.

Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients.

BACKGROUND: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. METHODS: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. RESULTS: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). CONCLUSIONS: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.

Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs.

BACKGROUND: A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation.The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. METHODS: This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. RESULTS: Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications.ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. CONCLUSIONS: Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. TRIAL REGISTRATION: NCT04411459.