Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

Early Hospital Discharge on Day Two Post Robotic Lobectomy with Telehealth Home Monitoring: A Pilot Study.

Despite the adoption of enhanced recovery programs, the reported postoperative length of stay after robotic surgery is 4 days even in highly specialized centers. We report preliminary results of a pilot study for a new protocol of early discharge (on day 2) with telehealth home monitoring after robotic lobectomy for lung cancer. All patients with a caregiver were discharged on postoperative day 2 with a telemonitoring device if they satisfied specific discharge criteria. Teleconsultations were scheduled once in the afternoon of post-operative day 2, twice on postoperative day 3, and then once a day until the chest tube removal. Post-discharge vital signs were recorded by patients at least four times daily through the device and were available for consultation by two surgeons through phone application. In case of sudden variation of vital signs or occurrence of adverse events, a direct telephone line was available for patients as well as a protected re-hospitalization path. Primary outcome was the safety evaluated by the occurrence of post-discharge complications and readmissions. Secondary outcome was the evaluation of resources optimization (hospitalization days) maintaining the standard of care. During the study period, twelve patients satisfied all preoperative clinical criteria to be enrolled in our protocol. Two of twelve enrolled patients were successively excluded because they did not satisfy discharge criteria on postoperative day 2. During telehealth home monitoring a total of 27/427 vital-sign measurements violated the threshold in seven patients. Among the threshold violations, only 1 out of 27 was a critical violation and was managed at home. No postoperative complication occurred neither readmission was needed. A mean number of three hospitalization days was avoided and an estimated economic benefit of about EUR 500 for a single patient was obtained if compared with patients submitted to VATS lobectomy in the same period. These preliminary results confirm that adoption of telemonitoring allows, in selected patients, a safe discharge on postoperative day 2 after robotic surgery for early-stage NSCLC. A potential economic benefit could derive from this protocol if this data will be confirmed in larger sample.

Lung response to prone positioning in mechanically-ventilated patients with COVID-19.

BACKGROUND: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population. METHODS: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity. RESULTS: By the time of the study, PEEP was 12 (10-14) cmH2O and the PaO2:FiO2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001). CONCLUSIONS: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.

Transparent decision support for mechanical ventilation using visualization of clinical preferences.

BACKGROUND: Systems aiding in selecting the correct settings for mechanical ventilation should visualize patient information at an appropriate level of complexity, so as to reduce information overload and to make reasoning behind advice transparent. Metaphor graphics have been applied to this effect, but these have largely been used to display diagnostic and physiologic information, rather than the clinical decision at hand. This paper describes how the conflicting goals of mechanical ventilation can be visualized and applied in making decisions. Data from previous studies are analyzed to assess whether visual patterns exist which may be of use to the clinical decision maker. MATERIALS AND METHODS: The structure and screen visualizations of a commercial clinical decision support system (CDSS) are described, including the visualization of the conflicting goals of mechanical ventilation represented as a hexagon. Retrospective analysis is performed on 95 patients from 2 previous clinical studies applying the CDSS, to identify repeated patterns of hexagon symbols. RESULTS: Visual patterns were identified describing optimal ventilation, over and under ventilation and pressure support, and over oxygenation, with these patterns identified for both control and support modes of mechanical ventilation. Numerous clinical examples are presented for these patterns illustrating their potential interpretation at the bedside. CONCLUSIONS: Visual patterns can be identified which describe the trade-offs required in mechanical ventilation. These may have potential to reduce information overload and help in simple and rapid identification of sub-optimal settings.

Associations Between Expiratory Flow Limitation and Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery.

OBJECTIVES: To determine whether driving pressure and expiratory flow limitation are associated with the development of postoperative pulmonary complications (PPCs) in cardiac surgery patients. DESIGN: Prospective cohort study. SETTING: University Hospital San Raffaele, Milan, Italy. PARTICIPANTS: Patients undergoing elective cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the occurrence of a predefined composite of PPCs. The authors determined the association among PPCs and intraoperative ventilation parameters, mechanical power and energy load, and occurrence of expiratory flow limitation (EFL) assessed with the positive end-expiratory pressure test. Two hundred patients were enrolled, of whom 78 (39%) developed one or more PPCs. Patients with PPCs, compared with those without PPCs, had similar driving pressure (mean difference [MD] -0.1 [95% confidence interval (CI), -1.0 to 0.7] cmH2O, p = 0.561), mechanical power (MD 0.5 [95% CI, -0.3 to 1.1] J/m, p = 0.364), and total energy load (MD 95 [95% CI, -78 to 263] J, p = 0.293), but they had a higher incidence of EFL (51% v 38%, p = 0.005). Only EFL was associated independently with the development of PPCs (odds ratio 2.46 [95% CI, 1.28-4.80], p = 0.007). CONCLUSIONS: PPCs occurred frequently in this patient population undergoing cardiac surgery. PPCs were associated independently with the presence of EFL but not with driving pressure, total energy load, or mechanical power.

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.

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units.

PURPOSE: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). METHODS: In this retrospective-prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. RESULTS: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55-69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89-175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil-lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. CONCLUSION: Daily values or trends over time of parameters associated with acute organ dysfunction, acid-base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.

Short-term health-related quality of life, physical function and psychological consequences of severe COVID-19.

BACKGROUND: Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU. METHODS: Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months. RESULTS: 47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2-3]. The median distance walked in 6 min was 470 [406-516] m, 83 [67-99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70-90] out of 100 at early follow-up with a slight improvement to 85 [77.5-90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents. CONCLUSIONS: Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.

Return to Work After Coronavirus Disease 2019 Acute Respiratory Distress Syndrome and Intensive Care Admission: Prospective, Case Series at 6 Months From Hospital Discharge.

OBJECTIVES: Joblessness is common in survivors from critical care. Our aim was to describe rates of return to work versus unemployment following coronavirus disease 2019 acute respiratory distress syndrome requiring intensive care admission. DESIGN: Single-center, prospective case series. SETTING: Critical Care Follow-Up Clinic, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. PATIENTS: One hundred and one consecutive laboratory-confirmed coronavirus disease 2019 patients were discharged from our hospital following an ICU stay between March 1, 2020, and June 30, 2020. Twenty-five died in the ICU. Seventy-six were discharged alive from hospital. Two patients refused participation, while three were unreachable. The remaining 71 were alive at 6 months and interviewed. INTERVENTIONS: Baseline and outcome healthcare data were extracted from the electronic patient records. Employment data were collected using a previously published structured interview instrument that included current and previous employment status, hours worked per week, and timing of return to work. Health-related quality of life status was assessed using the Italian EQ-5D-5L questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 71 interviewed patients, 45 (63%) were employed prior to coronavirus disease 2019, of which 40 (89%) of them worked full-time. Thirty-three (73%) of the previously employed survivors had returned to work by 6 months, 10 (22%) were unemployed, and 2 (5%) were newly retired. Among those who returned to work, 20 (85%) of them reported reduced effectiveness at work. Those who did not return to work were either still on sick leave or lost their job as a consequence of coronavirus disease 2019. Reported quality of life of survivors not returning to work was worse than of those returning to work. CONCLUSIONS: The majority of coronavirus disease 2019 survivors following ICU in our cohort had returned to work by 6 months of follow-up. However, most of them reported reduced work effectiveness. Prolonged sick leave and unemployment were common findings in those not returning.

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

BACKGROUND: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. METHODS: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. RESULTS: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). CONCLUSIONS: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. TRIAL REGISTRATION: clinicaltrials.gov number: NCT04388670.

Circulating Skeletal Troponin During Weaning From Mechanical Ventilation and Their Association to Diaphragmatic Function: A Pilot Study.

Background: Patients with acute respiratory failure (ARF) may need mechanical ventilation (MV), which can lead to diaphragmatic dysfunction and muscle wasting, thus making difficult the weaning from the ventilator. Currently, there are no biomarkers specific for respiratory muscle and their function can only be assessed trough ultrasound or other invasive methods. Previously, the fast and slow isoform of the skeletal troponin I (fsTnI and ssTnI, respectively) have shown to be specific markers of muscle damage in healthy volunteers. We aimed therefore at describing the trend of skeletal troponin in mixed population of ICU patients undergoing weaning from mechanical ventilation and compared the value of fsTnI and ssTnI with diaphragmatic ultrasound derived parameters. Methods: In this prospective observational study we enrolled consecutive patients recovering from acute hypoxemic respiratory failure (AHRF) within 24 h from the start of weaning. Every day an arterial blood sample was collected to measure fsTnI, ssTnI, and global markers of muscle damage, such as ALT, AST, and CPK. Moreover, thickening fraction (TF) and diaphragmatic displacement (DE) were assessed by diaphragmatic ultrasound. The trend of fsTnI and ssTnI was evaluated during the first 3 days of weaning. Results: We enrolled 62 consecutive patients in the study, with a mean age of 67 ± 13 years and 43 of them (69%) were male. We did not find significant variations in the ssTnI trend (p = 0.623), but fsTnI significantly decreased over time by 30% from Day 1 to Day 2 and by 20% from Day 2 to Day 3 (p < 0.05). There was a significant interaction effect between baseline ssTnI and DE [F (2) = 4.396, p = 0.015], with high basal levels of ssTnI being associated to a higher decrease in DE. On the contrary, the high basal levels of fsTnI at day 1 were characterized by significant higher DE at each time point. Conclusions: Skeletal muscle proteins have a distinctive pattern of variation during weaning from mechanical ventilation. At day 1, a high basal value of ssTnI were associated to a higher decrease over time of diaphragmatic function while high values of fsTnI were associated to a higher displacement at each time point.

Nasal high flow higher than 60 L/min in patients with acute hypoxemic respiratory failure: a physiological study.

BACKGROUND: Nasal high flow delivered at flow rates higher than 60 L/min in patients with acute hypoxemic respiratory failure might be associated with improved physiological effects. However, poor comfort might limit feasibility of its clinical use. METHODS: We performed a prospective randomized cross-over physiological study on 12 ICU patients with acute hypoxemic respiratory failure. Patients underwent three steps at the following gas flow: 0.5 L/kg PBW/min, 1 L/kg PBW/min, and 1.5 L/kg PBW/min in random order for 20 min. Temperature and FiO2 remained unchanged. Toward the end of each phase, we collected arterial blood gases, lung volumes, and regional distribution of ventilation assessed by electrical impedance tomography (EIT), and comfort. RESULTS: In five patients, the etiology was pulmonary; infective disease characterized seven patients; median PaO2/FiO2 at enrollment was 213 [IQR 136-232]. The range of flow rate during NHF 1.5 was 75-120 L/min. PaO2/FiO2 increased with flow, albeit non significantly (p = 0.064), PaCO2 and arterial pH remained stable (p = 0.108 and p = 0.105). Respiratory rate decreased at higher flow rates (p = 0.014). Inhomogeneity of ventilation decreased significantly at higher flows (p = 0.004) and lung volume at end-expiration significantly increased (p = 0.007), but mostly in the non-dependent regions. Comfort was significantly poorer during the step performed at the highest flow (p < 0.001). CONCLUSIONS: NHF delivered at rates higher than 60 L/min in critically ill patients with acute hypoxemic respiratory failure is associated with reduced respiratory rate, increased lung homogeneity, and additional positive pressure effect, but also with worse comfort.

Gravitational distribution of regional opening and closing pressures, hysteresis and atelectrauma in ARDS evaluated by electrical impedance tomography.

BACKGROUND: The physiological behavior of lungs affected by the acute respiratory distress syndrome (ARDS) differs between inspiration and expiration and presents heterogeneous gravity-dependent distribution. This phenomenon, highlighted by the different distribution of opening/closing pressure and by the hysteresis of the pressure-volume curve, can be studied by CT scan, but the technique expose the patient to radiations, cannot track changes during time and is not feasible at the bedside. Electrical impedance tomography (EIT) could help in assessing at the bedside regional inspiratory and expiratory mechanical properties. We evaluated regional opening/closing pressures, hysteresis and atelectrauma during inspiratory and expiratory low-flow pressure-volume curves in ARDS using electrical impedance tomography. METHODS: Pixel-level inspiratory and expiratory PV curves (PVpixel) between 5 and 40 cmH2O were constructed integrating EIT images and airway opening pressure signal from 8 ARDS patients. The lower inflection point in the inspiratory and expiratory PVpixel were used to find opening (OPpixel) and closing (CPpixel) pressures. A novel atelectrauma index (AtI) was calculated as the percentage of pixels opening during the inspiratory and closing during the expiratory PV curves. The maximal hysteresis (HysMax) was calculated as the maximal difference between normalized expiratory and inspiratory PV curves. Analyses were conducted in the global, dependent and non-dependent lung regions. RESULTS: Gaussian distribution was confirmed for both global OPpixel (r2 = 0.90) and global CPpixel (r2 = 0.94). The two distributions were significantly different with higher values for OPpixel (p < 0.0001). Regional OPpixel and CPpixel distributions were Gaussian, and in the dependent lung regions, both were significantly higher than in the non-dependent ones (p < 0.001). Both AtI and the HysMax were significantly higher in the dependent regions compared to the non-dependent ones (p < 0.05 for both). CONCLUSIONS: Gravity impacts the regional distribution of opening and closing pressure, hysteresis and atelectrauma, with higher values in the dorsal lung. Regional differences between inspiratory and expiratory lung physiology are detectable at the bedside using EIT and could allow in-depth characterization of ARDS phenotypes and guide personalized ventilation settings.

Personalized Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome: Comparison Between Optimal Distribution of Regional Ventilation and Positive Transpulmonary Pressure.

OBJECTIVES: Different techniques exist to select personalized positive end-expiratory pressure in patients affected by the acute respiratory distress syndrome. The positive end-expiratory transpulmonary pressure strategy aims to counteract dorsal lung collapse, whereas electrical impedance tomography could guide positive end-expiratory pressure selection based on optimal homogeneity of ventilation distribution. We compared the physiologic effects of positive end-expiratory pressure guided by electrical impedance tomography versus transpulmonary pressure in patients affected by acute respiratory distress syndrome. DESIGN: Cross-over prospective physiologic study. SETTING: Two academic ICUs. PATIENTS: Twenty ICU patients affected by acute respiratory distress syndrome undergoing mechanical ventilation. INTERVENTION: Patients monitored by an esophageal catheter and a 32-electrode electrical impedance tomography monitor underwent two positive end-expiratory pressure titration trials by randomized cross-over design to find the level of positive end-expiratory pressure associated with: 1) positive end-expiratory transpulmonary pressure (PEEPPL) and 2) proportion of poorly or nonventilated lung units (Silent Spaces) less than or equal to 15% (PEEPEIT). Each positive end-expiratory pressure level was maintained for 20 minutes, and afterward, lung mechanics, gas exchange, and electrical impedance tomography data were collected. MEASUREMENTS AND MAIN RESULTS: PEEPEIT and PEEPPL differed in all patients, and there was no correlation between the levels identified by the two methods (Rs = 0.25; p = 0.29). PEEPEIT determined a more homogeneous distribution of ventilation with a lower percentage of dependent Silent Spaces (p = 0.02), whereas PEEPPL was characterized by lower airway-but not transpulmonary-driving pressure (p = 0.04). PEEPEIT was significantly higher than PEEPPL in subjects with extrapulmonary acute respiratory distress syndrome (p = 0.006), whereas the opposite was true for pulmonary acute respiratory distress syndrome (p = 0.03). CONCLUSIONS: Personalized positive end-expiratory pressure levels selected by electrical impedance tomography- and transpulmonary pressure-based methods are not correlated at the individual patient level. PEEPPL is associated with lower dynamic stress, whereas PEEPEIT may help to optimize lung recruitment and homogeneity of ventilation. The underlying etiology of acute respiratory distress syndrome could deeply influence results from each method.

Dynamic bedside assessment of the physiologic effects of prone position in acute respiratory distress syndrome patients by electrical impedance tomography.

BACKGROUND: Prone position (PP) improves acute respiratory distress syndrome (ARDS) survival by reducing the risk of ventilation-induced lung injury. However, inter-individual variability is a hallmark of ARDS and lung protection by PP might not be optimal in all patients. In the present study, we dynamically assessed physiologic effects of PP by electrical impedance tomography (EIT) and identified predictors of improved lung protection by PP in ARDS patients. METHODS: Prospective physiologic study on 16 intubated, sedated and paralyzed patients with ARDS undergoing PP as per clinical decision. EIT data were recorded during two consecutive steps: 1) baseline supine position before and after a recruitment maneuver (RM); 2) prone position before and after a RM. "Improved lung protection" by PP was defined in the presence of simultaneous improvement of ventilation homogeneity (Hom), alveolar overdistension and collapse (ODCL) and amount of recruitable lung volume by RM in comparison to supine. RESULTS: PP versus supine increased the tidal volume distending the dependent regions (Vtdep), resulting in improved Hom (1.1±0.9 vs. 1.7±0.9, P=0.021). PP also reduced ODCL (19±9% vs. 28±8%, P=0.005) and increased the recruitable lung volume (80 [71-157] vs. 59 [1-110] mL, P=0.025). "Improved lung protection" by PP was predicted by lower Vtdep, higher Vtndep and poorer Hom measured during baseline supine position (P<0.05). CONCLUSIONS: EIT enables dynamic bedside assessment of the physiologic effects of PP and might support early recognition of ARDS patients more likely to benefit from PP.

Expiratory flow limitation in intensive care: prevalence and risk factors.

BACKGROUND: Expiratory flow limitation (EFL) is characterised by a markedly reduced expiratory flow insensitive to the expiratory driving pressure. The presence of EFL can influence the respiratory and cardiovascular function and damage the small airways; its occurrence has been demonstrated in different diseases, such as COPD, asthma, obesity, cardiac failure, ARDS, and cystic fibrosis. Our aim was to evaluate the prevalence of EFL in patients requiring mechanical ventilation for acute respiratory failure and to determine the main clinical characteristics, the risk factors and clinical outcome associated with the presence of EFL. METHODS: Patients admitted to the intensive care unit (ICU) with an expected length of mechanical ventilation of 72 h were enrolled in this prospective, observational study. Patients were evaluated, within 24 h from ICU admission and for at least 72 h, in terms of respiratory mechanics, presence of EFL through the PEEP test, daily fluid balance and followed for outcome measurements. RESULTS: Among the 121 patients enrolled, 37 (31%) exhibited EFL upon admission. Flow-limited patients had higher BMI, history of pulmonary or heart disease, worse respiratory dyspnoea score, higher intrinsic positive end-expiratory pressure, flow and additional resistance. Over the course of the initial 72 h of mechanical ventilation, additional 21 patients (17%) developed EFL. New onset EFL was associated with a more positive cumulative fluid balance at day 3 (103.3 ml/kg) compared to that of patients without EFL (65.8 ml/kg). Flow-limited patients had longer duration of mechanical ventilation, longer ICU length of stay and higher in-ICU mortality. CONCLUSIONS: EFL is common among ICU patients and correlates with adverse outcomes. The major determinant for developing EFL in patients during the first 3 days of their ICU stay is a positive fluid balance. Further studies are needed to assess if a restrictive fluid therapy might be associated with a lower incidence of EFL.

Effects of inspiratory flow on lung stress, pendelluft, and ventilation heterogeneity in ARDS: a physiological study.

BACKGROUND: High inspiratory flow might damage the lungs by mechanisms not fully understood yet. We hypothesized that increasing inspiratory flow would increase lung stress, ventilation heterogeneity, and pendelluft in ARDS patients undergoing volume-controlled ventilation with constant tidal volume and that higher PEEP levels would reduce this phenomenon. METHODS: Ten ARDS patients were studied during protective volume-controlled ventilation. Three inspiratory flows (400, 800, and 1200 ml/s) and two PEEP levels (5 and 15 cmH2O) were applied in random order to each patient. Airway and esophageal pressures were recorded, end-inspiratory and end-expiratory holds were performed, and ventilation distribution was measured with electrical impedance tomography. Peak and plateau airway and transpulmonary pressures were recorded, together with the airway and transpulmonary pressure corresponding to the first point of zero end-inspiratory flow (P1). Ventilation heterogeneity was measured by the EIT-based global inhomogeneity (GI) index. Pendelluft was measured as the absolute difference between pixel-level inflation measured at plateau pressure minus P1. RESULTS: Plateau airway and transpulmonary pressure was not affected by inspiratory flow, while P1 increased at increasing inspiratory flow. The difference between P1 and plateau pressure was higher at higher flows at both PEEP levels (p < 0.001). While higher PEEP reduced heterogeneity of ventilation, higher inspiratory flow increased GI (p = 0.05), irrespective of the PEEP level. Finally, gas volume undergoing pendelluft was larger at higher inspiratory flow (p < 0.001), while PEEP had no effect. CONCLUSIONS: The present exploratory analysis suggests that higher inspiratory flow increases additional inspiratory pressure, heterogeneity of ventilation, and pendelluft while PEEP has negligible effects on these flow-dependent phenomena. The clinical significance of these findings needs to be further clarified.

Noninvasive assessment of airflows by electrical impedance tomography in intubated hypoxemic patients: an exploratory study.

BACKGROUND: Noninvasive monitoring of maximal inspiratory and expiratory flows (MIF and MEF, respectively) by electrical impedance tomography (EIT) might enable early recognition of changes in the mechanical properties of the respiratory system due to new conditions or in response to treatments. We aimed to validate EIT-based measures of MIF and MEF against spirometry in intubated hypoxemic patients during controlled ventilation and spontaneous breathing. Moreover, regional distribution of maximal airflows might interact with lung pathology and increase the risk of additional ventilation injury. Thus, we also aimed to describe the effects of mechanical ventilation settings on regional MIF and MEF. METHODS: We performed a new analysis of data from two prospective, randomized, crossover studies. We included intubated patients admitted to the intensive care unit with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) undergoing pressure support ventilation (PSV, n = 10) and volume-controlled ventilation (VCV, n = 20). We measured MIF and MEF by spirometry and EIT during six different combinations of ventilation settings: higher vs. lower support during PSV and higher vs. lower positive end-expiratory pressure (PEEP) during both PSV and VCV. Regional airflows were assessed by EIT in dependent and non-dependent lung regions, too. RESULTS: MIF and MEF measured by EIT were tightly correlated with those measured by spirometry during all conditions (range of R2 0.629-0.776 and R2 0.606-0.772, respectively, p < 0.05 for all), with clinically acceptable limits of agreement. Higher PEEP significantly improved homogeneity in the regional distribution of MIF and MEF during volume-controlled ventilation, by increasing airflows in the dependent lung regions and lowering them in the non-dependent ones. CONCLUSIONS: EIT provides accurate noninvasive monitoring of MIF and MEF. The present study also generates the hypothesis that EIT could guide PSV and PEEP settings aimed to increase homogeneity of distending and deflating regional airflows.

Nasal high flow: physiology, efficacy and safety in the acute care setting, a narrative review.

Nasal high flow (NHF) is a promising novel oxygen delivery device, whose mechanisms of action offer some beneficial effects over conventional oxygen systems. It is considered to have a number of physiological effects: it improves oxygenation, dynamic lung compliance, homogeneity and end expiratory lung volume; it decreases anatomical dead space and generates a positive airway pressure that can reduce respiratory rate, the work of breathing, and enhance patient comfort. NHF has been used as a prophylactic tool or as a treatment device mostly in patients with acute hypoxemic respiratory failure such as pre-oxygenation before intubation, immunocompromised patients and acute heart failure. Moreover, there is some evidence that NHF could be used during procedural sedation. Finally, NHF was deemed to be effective in chronic obstructive pulmonary disease patients with its positive end expiratory pressure effects and dead-space washout. However, careful monitoring is crucial to maximize NHF settings aimed at maximizing patient comfort while limiting the risk of delayed intubation. The present review presents the most updated evidence for NHF use in the adult acute care setting with the goal of providing clinicians with useful insights on the physiologic effects, main clinical indications, and safety issues of NHF treatment.

Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study.

The ROX (Respiratory rate-OXygenation) index is an early predictor of failure of nasal high flow (NHF), with lower values indicating higher risk of intubation. We measured the ROX index at set flow rate of 30 and 60 l/min in 57 hypoxemic patients on NHF. Patients with increased ROX index values at higher flow (n = 40) showed worse baseline oxygenation, higher respiratory rate and lower ROX index in comparison to patients with unchanged or decreased ROX index values (n = 17). The ROX index variation between flows was correlated with the change in end expiratory lung volume. Set flow rate during NHF might impact the ROX index value.