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 H₂O, 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.

Background: In ARDS patients, mechanical ventilation should minimize ventilator-induced lung injury. The mechanical power which is the energy per unit time released to the respiratory system according to the applied tidal volume, PEEP, respiratory rate, and flow should reflect the ventilator-induced lung injury. However, similar levels of mechanical power applied in different lung sizes could be associated to different effects. The aim of this study was to assess the role both of the mechanical power and of the transpulmonary mechanical power, normalized to predicted body weight, respiratory system compliance, lung volume, and amount of aerated tissue on intensive care mortality. Methods: Retrospective analysis of ARDS patients previously enrolled in seven published studies. All patients were sedated, paralyzed, and mechanically ventilated. After 20 min from a recruitment maneuver, partitioned respiratory mechanics measurements and blood gas analyses were performed with a PEEP of 5 cmH₂O while the remaining setting was maintained unchanged from the baseline. A whole lung CT scan at 5 cmH₂O of PEEP was performed to estimate the lung gas volume and the amount of well-inflated tissue. Univariate and multivariable Poisson regression models with robust standard error were used to calculate risk ratios and 95% confidence intervals of ICU mortality. Results: Two hundred twenty-two ARDS patients were included; 88 (40%) died in ICU. Mechanical power was not different between survivors and non-survivors 14.97 [11.51–18.44] vs. 15.46 [12.33–21.45] J/min and did not affect intensive care mortality. The multivariable robust regression models showed that the mechanical power normalized to well-inflated tissue (RR 2.69 [95% CI 1.10–6.56], p = 0.029) and the mechanical power normalized to respiratory system compliance (RR 1.79 [95% CI 1.16–2.76], p = 0.008) were independently associated with intensive care mortality after adjusting for age, SAPS II, and ARDS severity. Also, transpulmonary mechanical power normalized to respiratory system compliance and to well-inflated tissue significantly increased intensive care mortality (RR 1.74 [1.11–2.70], p = 0.015; RR 3.01 [1.15–7.91], p = 0.025). Conclusions: In our ARDS population, there is not a causal relationship between the mechanical power itself and mortality, while mechanical power normalized to the compliance or to the amount of well-aerated tissue is independently associated to the intensive care mortality. Further studies are needed to confirm this data.

Muscular weakness developing from critical illness neuropathy, myopathy and muscle atrophy has been characterized as intensive care unit-acquired weakness (ICUAW). This entity occurs commonly during and after critical care stay. Various causal factors for functional incapacity have been proposed. Among these, individual patient characteristics (such as age, comorbidities and nutritional status), acting in association with sustained bed rest and pharmacological interventions (included the metabolic support approach), seem influential in reducing muscular mass. Long-term outcomes in heterogeneous ICUAW populations include transient disability in 30% of patients and persistent disabilities that may occur even in patients with nearly complete functional recovery. Currently available tools for the assessment of skeletal muscle mass are imprecise and difficult to perform in the ICU setting. A valid alternative to these imaging modalities is muscular ultrasonography, which allows visualization and classification of muscle characteristics by cross-sectional area, muscle layer thickness, echointensity by grayscale and the pennation angle). The aim of this narrative review is to describe the current literature addressing muscular ultrasound for the detection of muscle weakness and its potential impact on treatment and prognosis of critically ill patients when combined with biomarkers of muscle catabolism/anabolism and bioenergetic state. In addition, we suggest a practical flowchart for establishing an early diagnosis.

Modalities of fluid management in patients sustaining the acute respiratory distress syndrome (ARDS) are challenging and controversial. Optimal fluid management should provide adequate oxygen delivery to the body, while avoiding inadvertent increase in lung edema which further impairs gas exchange. In ARDS patients, positive fluid balance has been associated with prolonged mechanical ventilation, longer ICU and hospital stay, and higher mortality. Accordingly, a restrictive strategy has been compared to a more liberal approach in randomized controlled trials conducted in various clinical settings. Restrictive strategies included fluid restriction guided by the monitoring of extravascular lung water, pulmonary capillary wedge or central venous pressure, and furosemide targeted to diuresis and/or albumin replacement in hypoproteinemic patients. Overall, restrictive strategies improved oxygenation significantly and reduced duration of mechanical ventilation, but had no significant effect on mortality. Fluid management may require different approaches depending on the time course of ARDS (i.e., early vs. late period). The effects of fluid strategy management according to ARDS phenotypes remain to be evaluated. Since ARDS is frequently associated with sepsis-induced acute circulatory failure, the prediction of fluid responsiveness is crucial in these patients to avoid hemodynamically inefficient—hence respiratory detrimental—fluid administration. Specific hemodynamic indices of fluid responsiveness or mini-fluid challenges should be preferably used. Since the positive airway pressure contributes to positive fluid balance in ventilated ARDS patients, it should be kept as low as possible. As soon as the hemodynamic status is stabilized, correction of cumulated fluid retention may rely on diuretics administration or renal replacement therapy.

Introduction: Patients with acute respiratory failure requiring respiratory support with invasive mechanical ventilation while awaiting lung transplantation are at a high risk of death. Extracorporeal membrane oxygenation (ECMO) has been proposed as an alternative bridging strategy to mechanical ventilation. The aim of this study was to assess the current evidence regarding how the ECMO bridge influences patients’ survival and length of hospital stay.Methods: We performed a systematic review by searching PubMed, EMBASE and the bibliographies of retrieved articles. Three reviewers independently screened citation titles and abstracts and agreement was reached by consensus. We selected studies enrolling patients who received ECMO with the intention to bridge lung transplant. We included randomized controlled trials (RCTs), case–control studies and case series with ten or more patients. Outcomes of interest included survival and length of hospital stay. Quantitative data summaries were made when feasible.Results: We identified 82 studies, of which 14 were included in the final analysis. All 14 were retrospective studies which enrolled 441 patients in total. Because of the broad heterogeneity among the studies we did not perform a meta-analysis. The mortality rate of patients on ECMO before lung transplant and the one-year survival ranged from 10% to 50% and 50% to 90%, respectively. The intensive care and hospital length of stay ranged between a median of 15 to 47 days and 22 to 47 days, respectively. There was a general paucity of high-quality data and significant heterogeneity among studies in the enrolled patients and technology used, which confounded analysis.Conclusions: In most of the studies, patients on ECMO while awaiting lung transplantation also received invasive mechanical ventilation. Therefore, whether ECMO as an alternative, rather than an adjunction, to invasive mechanical ventilation is a better bridging strategy to lung transplantation still remains an unresolved issue. ECMO support as a bridge for these patients could provide acceptable one-year survival. Future studies are needed to investigate ECMO as part of an algorithm of care for patients with end-stage lung disease.