To evaluate whether the shape of the airway pressure-time (Paw-t) curve during constant flow inflation corresponds to radiologic evidence of tidal recruitment or tidal hyperinflation in an experimental model of acute lung injury. Prospective randomized laboratory animal investigation. Department of Clinical Physiology, University of Uppsala, Sweden. Anesthetized, paralyzed, and mechanically ventilated pigs. Acute lung injury was induced by lung lavage. During constant inspiratory flow, the Paw-t curve was fitted to a power equation: airway pressure =a · timeb+c,where coefficient b (stress index) describes the shape of the curve:b = 1, straight curve; b < 1, progressive increase in slope; and b > 1, progressive decrease in slope. Tidal volume (Vt) was 6 mL/kg, and positive end-expiratory pressure was set to obtain a b value between 0.9 and 1.1 before (b = 1) and after (b = 1 after recruiting maneuver) application of a recruiting maneuver. Positive end-expiratory pressure was decreased and Vt increased to obtain 0.9 >b > 0.8 and 0.8 >b > 0.6, whereas positive end-expiratory pressure and Vt were both increased to obtain 1.3 >b > 1.1 and 1.5 >b > 1.3. Experimental conditions sequence was random. Pulmonary computed tomography was obtained during end-expiratory and end-inspiratory occlusions. Tidal recruitment was quantified as nonaerated (between −100 and +100 Hounsfield units) lung area at end-expiration minus end-inspiration. Tidal hyperinflation was quantified as hyperinflated (between −900 and −1000 Hounsfield units) lung area at end-inspiration minus end-expiration. Computed tomography images showed that tidal recruitment and tidal hyperinflation corresponded to b < 1 and b > 1, respectively. Stress index values and tidal recruitment and tidal hyperinflation values were significantly correlated (R2 = .917 and R2 = .911, p < .0001, respectively). Shape of the Paw-t curve detects tidal recruitment and tidal hyperinflation.

Background: Mechanical ventilation with a tidal volume (V_T) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (P_plat) lower than 30 cmH₂O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low V_T combined with extracorporeal carbon dioxide removal (ECCO₂R). Methods: In fifteen patients with moderate ARDS, V_T was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure – (P_plat) between 23 and 25 cmH₂O. Low-flow ECCO₂R was initiated when respiratory acidosis developed (pH < 7.25, PaCO₂ > 60 mmHg). Ventilation parameters (V_T, respiratory rate, PEEP), respiratory compliance (C_RS), driving pressure (DeltaP = V_T/C_RS), arterial blood gases, and ECCO₂R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO₂R when PaO₂/FiO₂ was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO₂R were also collected. Results: During the 2 h run in phase, V_T reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO₂R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO₂ to within 10 % of baseline values. PEEP values tended to increase at V_T of 4 mL/kg from 12.2 to 14.5 cmH₂O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH₂O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). Conclusions: The low-flow ECCO₂R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. Matched cohort study with historical control. Two academic Italian ICUs. Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ≤ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

Acute respiratory distress syndrome: new definition, current and future therapeutic options

A recent study by the Acute Respiratory Distress Syndrome Network compared the traditional lower end-expiratory pressure strategy with a higher end-expiratory pressure strategy in patients with the acute respiratory distress syndrome ventilated with low tidal volumes. Clinical outcomes were similar whether lower or higher positive end-expiratory pressure (PEEP) levels were used. We applied both the lower (9 ± 2 cm H2O) and higher (16 ± 1 cm H2O) PEEP strategy in 19 patients. In nine recruiters, the higher end-expiratory pressure strategy resulted in significant alveolar recruitment (587 ± 158 ml), improvement in arterial oxygen partial pressure/inspired oxygen fraction ratio (from 150 ± 36 to 396 ± 138), and reduction in static lung elastance (from 23 ± 3 to 20 ± 2 cm H2O/L). In 10 nonrecruiters, alveolar recruitment was minimal, oxygenation did not improve, and static lung elastance significantly increased (from 26 ± 5 to 28 ± 6 cm H2O/L). The increase in oxygenation, the reduction in static lung elastance, and the shape of the volume–pressure curve during the lower PEEP strategy were independently associated with alveolar recruitment. In conclusion, the protocol proposed by the Acute Respiratory Distress Syndrome Network, lacking solid physiologic basis, frequently fails to induce alveolar recruitment and may increase the risk of alveolar overinflation.

Acute respiratory distress syndrome (ARDS) was first described in 1967, and since then there have been a large number of studies addressing its pathogenesis and therapies. Despite intense research efforts, very few therapies for ARDS have been shown to be effective other than the use of lung protection strategies. The scarcity of therapeutic choices is related to the intricate pathogenesis of the syndrome and to insensitive and aspecific criteria to diagnose this profound acute respiratory failure. The aim of this paper is to summarize advances of new ARDS definitions and provide an overview of new relevant signaling pathways that mediate acute lung injury.