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.

COVID-19: dealing with ventilator shortage.

PURPOSE OF REVIEW: To describe different strategies adopted during coronavirus disease 2019 pandemic to cope with the shortage of mechanical ventilators. RECENT FINDINGS: Short-term interventions aimed to increase ventilator supply and decrease demand. They included: redistributing and centralizing patients, repurposing operating rooms into intensive care units (ICUs) and boosting ventilator production and using stocks and back-ups; support by the critical care outreach team to optimize treatment of patients in the ward and permit early discharge from the ICU, ethical allocation of mechanical ventilators to patients who could benefit more from intensive treatment and short term ICU trials for selected patients with uncertain prognosis, respectively. Long-term strategies included education and training of non-ICU physicians and nurses to the care of critically-ill patients and measures to decrease viral spread among the population and the progression from mild to severe disease. SUMMARY: The experience and evidence gained during the current pandemic is of paramount importance for physicians and law-makers to plan in advance an appropriate response to any future similar crisis. Intensive care unit, hospital, national and international policies can all be improved to build systems capable of treating an unexpectedly large number of patients, while keeping a high standard of safety.

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.

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.

Short-term Physiologic Consequences of Regional Pulmonary Vascular Occlusion in Pigs.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: After pulmonary artery occlusion (mimicking a pulmonary embolism), perfusion is redistributed to the rest of the lung tissue, but the distribution of ventilation is uncertain. WHAT THIS ARTICLE TELLS US THAT IS NEW: Data from anesthetized pigs (uninjured lungs) indicate that the perfusion is redistributed as suspected. Similarly, ventilation is redistributed from nonperfused to perfused lung tissue. This limits the increase in dead space and is accompanied by less density in the occluded lung. BACKGROUND: Acute unilateral pulmonary arterial occlusion causes ventilation-perfusion mismatch of the affected lung area. A diversion of ventilation from nonperfused to perfused lung areas, limiting the increase in dead space, has been described. The hypothesis was that the occlusion of a distal branch of the pulmonary artery would cause local redistribution of ventilation and changes in regional lung densitometry as assessed with quantitative computed tomography. METHODS: In eight healthy, anesthetized pigs (18.5 ± 3.8 kg) ventilated with constant ventilatory settings, respiratory mechanics, arterial blood gases, and quantitative computed tomography scans were recorded at baseline and 30 min after the inflation of the balloon of a pulmonary artery catheter. Regional (left vs. right lung and perfused vs. nonperfused area) quantitative computed tomography was performed. RESULTS: The balloon always occluded a branch of the left pulmonary artery perfusing approximately 30% of lung tissue. Physiologic dead space increased (0.37 ± 0.17 vs. 0.43 ± 0.17, P = 0.005), causing an increase in PaCO2 (39.8 [35.2 to 43.0] vs. 41.8 [37.5 to 47.1] mmHg, P = 0.008) and reduction in pH (7.46 [7.42 to 7.50] vs. 7.42 [7.38 to 7.47], P = 0.008). Respiratory system compliance was reduced (24.4 ± 4.2 vs. 22.8 ± 4.8 ml · cm H2O, P = 0.028), and the reduction was more pronounced in the left hemithorax. Quantitative analysis of the nonperfused lung area revealed a significant reduction in lung density (-436 [-490 to -401] vs. -478 [-543 to -474] Hounsfield units, P = 0.016), due to a reduction in lung tissue (90 ± 23 vs. 81 ± 22 g, P < 0.001) and an increase in air volume (70 ± 22 vs. 82 ± 26 ml, P = 0.022). CONCLUSIONS: Regional pulmonary vascular occlusion is associated with a diversion of ventilation from nonperfused to perfused lung areas. This compensatory mechanism effectively limits ventilation perfusion mismatch. Quantitative computed tomography documented acute changes in lung densitometry after pulmonary vascular occlusion. In particular, the nonperfused lung area showed an increase in air volume and reduction in tissue mass, resulting in a decreased lung density.

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.

Role of Strain Rate in the Pathogenesis of Ventilator-Induced Lung Edema.

OBJECTIVE: Lungs behave as viscoelastic polymers. Harms of mechanical ventilation could then depend on not only amplitude (strain) but also velocity (strain rate) of lung deformation. Herein, we tested this hypothesis. DESIGN: Laboratory investigation. SETTING: Animal unit. SUBJECTS: Thirty healthy piglets. INTERVENTIONS: Two groups of animals were ventilated for 54 hours with matched lung strains (ratio between tidal volume and functional residual capacity) but different lung strain rates (ratio between strain and inspiratory time). Individual strains ranged between 0.6 and 3.5 in both groups. Piglets ventilated with low strain rates had an inspiratory-to-expiratory time ratio of 1:2-1:3. Those ventilated with high strain rates had much lower inspiratory-to-expiratory time ratios (down to 1:9). Respiratory rate was always 15 breaths/min. Lung viscoelastic behavior, with ventilator setting required per protocol, was "quantified" as dynamic respiratory system hysteresis (pressure-volume loop [in Joules]) and stress relaxation (airway pressure drop during an end-inspiratory pause [in cm H2O]). Primary outcome was the occurrence of pulmonary edema within 54 hours. MEASUREMENTS AND MAIN RESULTS: On average, the two study groups were ventilated with well-matched strains (2.1 ± 0.9 vs 2.1 ± 0.9; p = 0.864) but different strain rates (1.8 ± 0.8 vs 4.6 ± 1.5 s; p < 0.001), dynamic respiratory system hysteresis (0.6 ± 0.3 vs 1.4 ± 0.8 J; p = 0.001), and stress relaxation (3.1 ± 0.9 vs 5.0 ± 2.3 cm H2O; p = 0.008). The prevalence of pulmonary edema was 20% among piglets ventilated with low strain rates and 73% among those ventilated with high strain rates (p = 0.010). CONCLUSIONS: High strain rate is a risk factor for ventilator-induced pulmonary edema, possibly because it amplifies lung viscoelastic behavior.

"Awake" extracorporeal membrane oxygenation (ECMO): pathophysiology, technical considerations, and clinical pioneering.

Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.e., as an alternative to invasive mechanical ventilation in awake, non-intubated, spontaneously breathing patients with respiratory failure ("awake" ECMO). There is a strong rationale for this type of respiratory support as it avoids several side effects related to sedation, intubation, and mechanical ventilation. However, the complexity of the patient-ECMO interactions, the difficulties related to respiratory monitoring, and the management of an awake patient on extracorporeal support together pose a major challenge for the intensive care unit staff. Here, we review the use of vv-ECMO in awake, spontaneously breathing patients with respiratory failure, highlighting the pros and cons of this approach, analyzing the pathophysiology of patient-ECMO interactions, detailing some of the technical aspects, and summarizing the initial clinical experience gained over the past years.

Physiology versus evidence-based guidance for critical care practice.

Evidence based medicine is an attempt to optimize the medical decision process through methods primarily based on evidence coming from meta-analyses, systematic reviews, and randomized controlled trials ("evidence-based medicine"), rather than on "clinical judgment" alone. The randomized trials are the cornerstones of this process. However, the randomized trials are just a method to prove or disprove a given hypothesis, which, in turn, derives from a general observation of the reality (premises or theories). In this paper we will examine some of the most recent randomized trials performed in Intensive Care, analyzing their premises, hypothesis and outcome. It is quite evident that when the premises are wrong or too vague the unavoidable consequences will be a negative outcome. We should pay when designing the trial an equal attention in defining premises and hypothesis that we pay for the trial conduction.

Estimation of normal lung weight index in healthy female domestic pigs.

INTRODUCTION: Lung weight is an important study endpoint to assess lung edema in porcine experiments on acute respiratory distress syndrome and ventilatory induced lung injury. Evidence on the relationship between lung-body weight relationship is lacking in the literature. The aim of this work is to provide a reference equation between normal lung and body weight in female domestic piglets. MATERIALS AND METHODS: 177 healthy female domestic piglets from previous studies were included in the analysis. Lung weight was assessed either via a CT-scan before any experimental injury or with a scale after autopsy. The animals were randomly divided in a training (n = 141) and a validation population (n = 36). The relation between body weight and lung weight index (lung weight/body weight, g/kg) was described by an exponential function on the training population. The equation was tested on the validation population. A Bland-Altman analysis was performed to compare the lung weight index in the validation population and its theoretical value calculated with the reference equation. RESULTS: A good fit was found between the validation population and the exponential equation extracted from the training population (RMSE = 0.060). The equation to determine lung weight index from body weight was: [Formula: see text] At the Bland and Altman analyses, the mean bias between the real and the expected lung weight index was - 0.26 g/kg (95% CI - 0.96-0.43), upper LOA 3.80 g/kg [95% CI 2.59-5.01], lower LOA - 4.33 g/kg [95% CI = - 5.54-(- 3.12)]. CONCLUSIONS: This exponential function might be a valuable tool to assess lung edema in experiments involving 16-50 kg female domestic piglets. The error that can be made due to the 95% confidence intervals of the formula is smaller than the one made considering the lung to body weight as a linear relationship.

The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).

Lung stress and strain during mechanical ventilation: any difference between statics and dynamics?

OBJECTIVE: Tidal volume (VT) and volume of gas caused by positive end-expiratory pressure (VPEEP) generate dynamic and static lung strains, respectively. Our aim was to clarify whether different combinations of dynamic and static strains, resulting in the same large global strain, constantly produce lung edema. DESIGN: Laboratory investigation. SETTING: Animal unit. SUBJECTS: Twenty-eight healthy pigs. INTERVENTIONS: After lung computed tomography, 20 animals were ventilated for 54 hours at a global strain of 2.5, either entirely dynamic (VT 100% and VPEEP 0%), partly dynamic and partly static (VT 75-50% and VPEEP 25-50%), or mainly static (VT 25% and VPEEP 75%) and then killed. In eight other pigs (VT 25% and VPEEP 75%), VPEEP was abruptly zeroed after 36-54 hours and ventilation continued for 3 hours. MEASUREMENTS AND MAIN RESULTS: Edema was diagnosed when final lung weight (balance) exceeded the initial weight (computed tomography). Mortality, lung mechanics, gas exchange, pulmonary histology, and inflammation were evaluated. All animals ventilated with entirely dynamic strain (VT 825±424 mL) developed pulmonary edema (lung weight from 334±38 to 658±99 g, p<0.01), whereas none of those ventilated with mainly static strain (VT 237±21 mL and VPEEP 906±114 mL, corresponding to 19±1 cm H2O of positive end-expiratory pressure) did (from 314±55 to 277±46 g, p=0.65). Animals ventilated with intermediate combinations finally had normal or largely increased lung weight. Smaller dynamic and larger static strains lowered mortality (p<0.01), derangement of lung mechanics (p<0.01), and arterial oxygenation (p<0.01), histological injury score (p=0.03), and bronchoalveolar interleukin-6 concentration (p<0.01). Removal of positive end-expiratory pressure did not result in abrupt increase in lung weight (from 336±36 to 351±77 g, p=0.51). CONCLUSIONS: Lung edema forms (possibly as an all-or-none response) depending not only on global strain but also on its components. Large static are less harmful than large dynamic strains, but not because the former merely counteracts fluid extravasation.

Pathophysiology of hypoxemia in mechanically-ventilated patients with COVID-19: A computed tomography study.

The pathogenesis of hypoxemia during acute respiratory distress syndrome caused by SARS-CoV-2 infection (C-ARDS) is debated. Some observations led to hypothesize ventilation to perfusion mismatch, rather than anatomical shunt, as the main determinant of hypoxemia. In this observational study 24 C-ARDS patients were studied 1 (0-1) days after intubation. Patients underwent a CT scan analysis to estimate anatomical shunt and a clinical test to measure venous admixture at two fractions of inspired oxygen (FiO2), to eliminate oxygen-responsive mechanisms of hypoxemia (ventilation to perfusion mismatch and diffusion limitation). In 10 out of 24 patients venous admixture was higher than anatomical shunt both at clinical (≈50 %) and 100 % FiO2. These patients were ventilated with a higher PEEP and had lower amount of anatomical shunt compared with patients with venous admixture equal/lower than anatomical shunt. In a subset of C-ARDS patients early after endotracheal intubation, hypoxemia might be explained by an abnormally high perfusion of a relatively low anatomical shunt.

Lung stress and strain during mechanical ventilation: any safe threshold?

RATIONALE: Unphysiologic strain (the ratio between tidal volume and functional residual capacity) and stress (the transpulmonary pressure) can cause ventilator-induced lung damage. OBJECTIVES: To identify a strain-stress threshold (if any) above which ventilator-induced lung damage can occur. METHODS: Twenty-nine healthy pigs were mechanically ventilated for 54 hours with a tidal volume producing a strain between 0.45 and 3.30. Ventilator-induced lung damage was defined as net increase in lung weight. MEASUREMENTS AND MAIN RESULTS: Initial lung weight and functional residual capacity were measured with computed tomography. Final lung weight was measured using a balance. After setting tidal volume, data collection included respiratory system mechanics, gas exchange and hemodynamics (every 6 h); cytokine levels in serum (every 12 h) and bronchoalveolar lavage fluid (end of the experiment); and blood laboratory examination (start and end of the experiment). Two clusters of animals could be clearly identified: animals that increased their lung weight (n = 14) and those that did not (n = 15). Tidal volume was 38 ± 9 ml/kg in the former and 22 ± 8 ml/kg in the latter group, corresponding to a strain of 2.16 ± 0.58 and 1.29 ± 0.57 and a stress of 13 ± 5 and 8 ± 3 cm H(2)O, respectively. Lung weight gain was associated with deterioration in respiratory system mechanics, gas exchange, and hemodynamics, pulmonary and systemic inflammation and multiple organ dysfunction. CONCLUSIONS: In healthy pigs, ventilator-induced lung damage develops only when a strain greater than 1.5-2 is reached or overcome. Because of differences in intrinsic lung properties, caution is warranted in translating these findings to humans.

Lung Response to a Higher Positive End-Expiratory Pressure in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: International guidelines suggest using a higher (> 10 cm H2O) positive end-expiratory pressure (PEEP) in patients with moderate-to-severe ARDS due to COVID-19. However, even if oxygenation generally improves with a higher PEEP, compliance, and Paco2 frequently do not, as if recruitment was small. RESEARCH QUESTION: Is the potential for lung recruitment small in patients with early ARDS due to COVID-19? STUDY DESIGN AND METHODS: Forty patients with ARDS due to COVID-19 were studied in the supine position within 3 days of endotracheal intubation. They all underwent a PEEP trial, in which oxygenation, compliance, and Paco2 were measured with 5, 10, and 15 cm H2O of PEEP, and all other ventilatory settings unchanged. Twenty underwent a whole-lung static CT scan at 5 and 45 cm H2O, and the other 20 at 5 and 15 cm H2O of airway pressure. Recruitment and hyperinflation were defined as a decrease in the volume of the non-aerated (density above -100 HU) and an increase in the volume of the over-aerated (density below -900 HU) lung compartments, respectively. RESULTS: From 5 to 15 cm H2O, oxygenation improved in 36 (90%) patients but compliance only in 11 (28%) and Paco2 only in 14 (35%). From 5 to 45 cm H2O, recruitment was 351 (161-462) mL and hyperinflation 465 (220-681) mL. From 5 to 15 cm H2O, recruitment was 168 (110-202) mL and hyperinflation 121 (63-270) mL. Hyperinflation variably developed in all patients and exceeded recruitment in more than half of them. INTERPRETATION: Patients with early ARDS due to COVID-19, ventilated in the supine position, present with a large potential for lung recruitment. Even so, their compliance and Paco2 do not generally improve with a higher PEEP, possibly because of hyperinflation.

Management of chronic musculoskeletal pain in veterans: a systematic review.

BACKGROUND AND AIM OF THE WORK: Veterans are military with health problems due to military conditions. The improved body armor and operational conditions has reduced the number of deaths, but increased the number of veterans with severe injuries, affected by musculoskeletal pain and associated syndromes, such as post-traumatic stress disorder. Multimodal approaches are considered in USA the gold standard for the treatment of these problems, while in Europe and Italy the data are unknown. The aim of this review was to describe and summarize multimodal therapeutic approaches that apply to the veteran population for chronic musculoskeletal pain and relate syndromes management. METHODS: A comprehensive systematic review of the literature on Cochrane Library, PubMed, CINAHL e PsycINFO databases was conducted, from 2001 to 2020. RESULTS: 228 papers have been found, 134 were selected after the first screening. 24 quantitative studies were included in the review, all from USA. Different multimodal interventions with different kind of treatment types emerged. The analyzed studies' sample size was 11 million (mean age = 57.67 years; SD=±11.94). The multimodal approaches showed a significant improvement in all outcomes (pain reduction and control, opioid therapy reduction, psychosocial outcomes) compared to traditional therapy. CONCLUSIONS: Multimodal therapeutic approaches seem to guarantee a good management chronic musculoskeletal pain and related mental disorders, and the reduction and control to opioid use. Military nurses emerged as professionals who have a central role in this approach. European and Italian authorities should consider veterans, in order to assess their expected increase in the future.

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.

Barotrauma in mechanically ventilated patients with Coronavirus disease 2019: a survey of 38 hospitals in Lombardy, Italy.

BACKGROUND: The aim was to describe the incidence and risk factors of barotrauma in patients with the Coronavirus disease 2019 (COVID-19) on invasive mechanical ventilation, during the outbreak in our region (Lombardy, Italy). METHODS: The study was an electronic survey open from March 27th to May 2nd, 2020. Patients with COVID-19 who developed barotrauma while on invasive mechanical ventilation from 61 hospitals of the COVID-19 Lombardy Intensive Care Unit network were involved. RESULTS: The response rate was 38/61 (62%). The incidence of barotrauma was 145/2041 (7.1%; 95%-CI: 6.1-8.3%). Only a few cases occurred with ventilatory settings that may be considered non-protective such as a plateau airway pressure >35 cmH2O (2/113 [2%]), a driving airway pressure >15 cmH2O (30/113 [27%]), or a tidal volume >8 mL/kg of ideal body weight and a plateau airway pressure >30 cmH2O (12/134 [9%]). CONCLUSIONS: Within the limits of a survey, patients with COVID-19 might be at high risk for barotrauma during invasive (and allegedly lung-protective) mechanical ventilation.