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Background Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. Research Question Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study Design and Methods We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. Results Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, –7%; 95% CI, –18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. Interpretation Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. Trial Registry ClinicalTrials.gov ; No.: NCT03201263 ; URL: www.clinicaltrials.gov

Rationale: Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS). To date, no evidence supports the use of prone positioning (PP) during venovenous extracorporeal oxygenation (ECMO). Objectives: The aim of the study was to assess the feasibility, safety, and effect on oxygenation and lung mechanics of PP during ECMO. As a secondary exploratory aim, we assessed the association between PP and hospital mortality. Methods: We performed a multicenter retrospective cohort study in six Italian ECMO centers, including patients managed with PP during ECMO support (prone group; four centers) and patients managed in the supine position (control group; two centers). Physiological variables were analyzed at four time points (supine before PP, start of PP, end of PP, and supine after PP). The association between PP and hospital mortality was assessed by multivariate analysis and propensity score–matching. Results: A total of 240 patients were included, with 107 in the prone group and 133 in the supine group. The median duration of the 326 pronation cycles was 15 (12–18) hours. Minor reversible complications were reported in 6% of PP maneuvers. PP improved oxygenation and reduced intrapulmonary shunt. Unadjusted hospital mortality was lower in the prone group (34 vs. 50%; P = 0.017). After adjusting for covariates, PP remained significantly associated with a reduction of hospital mortality (odds ratio, 0.50; 95% confidence interval, 0.29–0.87). Sixty-six propensity score–matched patients were identified in each group. In this matched sample, patients who underwent pronation had higher ECMO duration (16 vs. 10 d; P = 0.0344) but lower hospital mortality (30% vs. 53%; P = 0.0241). Conclusions: PP during ECMO improved oxygenation and was associated with a reduction of hospital mortality.

Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p

Objectives Supplementation of antithrombin might decrease the amount of heparin needed to achieve a given anticoagulation target during extracorporeal membrane oxygenation. However, exogenous antithrombin itself may increase the risk of bleeding. We conceived a study to evaluate the effect of antithrombin supplementation in adult patients requiring venovenous extracorporeal membrane oxygenation for respiratory failure on heparin dose, adequacy of anticoagulation, and safety. Design Prospective randomized controlled trial. Setting ICUs of two Italian referral extracorporeal membrane oxygenation centers. Patients Adult patients requiring venovenous extracorporeal membrane oxygenation for severe respiratory failure and unfractionated heparin for systemic anticoagulation. Interventions Before extracorporeal membrane oxygenation start, patients were randomized to either receive antithrombin concentrate to maintain a plasmatic level 80-120% (treatment) or not (control) during the extracorporeal membrane oxygenation course. Measurements and main results The primary outcome was the total amount of heparin required to maintain activated partial thromboplastin time ratio 1.5-2. Secondary outcomes were anti-factor Xa, the incidence of hemorrhagic and thrombotic events, and the amount of blood products transfused. Twenty-four patients in the treatment group and 24 in the control group were included in the intention-to-treat analysis. Antithrombin was 109.5% (93.0-123.0%) in the treatment group and 84.0% (68.5-98.0%) in the control group (p = 0.001). Supplementation of antithrombin did not decrease heparin dose (13.5 international units/kg/hr [9.6-17.9 international units/kg/hr] vs 15.1 international units/kg/hr [10.7-18.3 international units/kg/hr] in the treatment and control group, respectively; p = 0.33) and anti-Factor Xa levels (0.4 international units/mL [0.3-0.5 international units/mL] vs 0.3 international units/mL [0.2-0.5 international units/mL] in the treatment group and control group respectively; p = 0.65). Bleeding, blood product transfusions, and thrombosis were not different in the two groups. Conclusions Antithrombin supplementation may not decrease heparin requirement nor diminish the incidence of bleeding and/or thrombosis in adult patients on venovenous extracorporeal membrane oxygenation.

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

Background We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. Methods The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome). The response to the carbon dioxide removal was evaluated in terms of respiratory rate and esophageal pressure swings by increasing (“relief” threshold) and decreasing (“distress” threshold) the extracorporeal membrane oxygenation gas flow, starting from baseline condition. Results Considering all 48 patients, spontaneous breathing extracorporeal membrane oxygenation was performed in 100% bridge to lung transplant (9 of 9 extubated), 86% COPD (5 of 6 extubated), but 27% acute respiratory distress syndrome patients (6 of 8 extubated; P < 0.001) and was maintained for 92, 69, and 38% of the extracorporeal membrane oxygenation days (P = 0.021), respectively. In all the 23 patients enrolled in the study, gas flow increase (from 2.3 ± 2.2 to 9.2 ± 3.2 l/min) determined a decrease of both respiratory rate (from 29 ± 6 to 8 ± 9 breaths/min) and esophageal pressure swings (from 20 ± 9 to 4 ± 4 cm H2O; P < 0.001 for all). All COPD and bridge to lung transplant patients were responders (reached the relief threshold), while 50% of acute respiratory distress syndrome patients were nonresponders. Conclusions Carbon dioxide removal through extracorporeal membrane oxygenation relieves work of breathing and permits extubation in many patients, mainly bridge to lung transplant and COPD. Only few patients with acute respiratory distress syndrome were able to perform the spontaneous breathing trial, and in about 50% of these, removal of large amount of patient’s carbon dioxide production was not sufficient to prevent potentially harmful spontaneous respiratory effort.

To the Editors: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is commonly treated with different kinds of noninvasive positive pressure devices, ranging from helmet or face-mask continuous positive airway pressure (CPAP) to noninvasive pressure support ventilation (NPPV), or Bi-PAP [1]. The use of positive end-expiratory pressure (PEEP) and NPPV often results in the successful treatment of COPD patients with respiratory distress [1, 2]. If, despite maximal medical management, respiratory distress and gas exchange deteriorate with increasing tachypnoea and acidosis, and with altered level of consciousness, then tracheal intubation and mechanical ventilation (MV) become mandatory [3]. However, tracheal intubation and MV have several detrimental side-effects that may concur to determine the high morbidity and mortality reported in COPD patients requiring them [3, 4]. Indeed, the increase in airway resistance, the prolonged time required for lung emptying and the resulting dynamic hyperinflation, named auto-PEEP [4], are the most important physiological alterations during COPD exacerbation. In this condition, the application of MV could increase lung hyperinflation and lead to barotrauma and circulatory failure [4, 5]. Furthermore, tracheal intubation is usually associated with the need for sedation. The side-effects of intubation, sedation and MV may initiate a vicious circle, often resulting in a very difficult or impossible weaning. In this report, we describe a patient with severe exacerbation of COPD, in whom after failure of noninvasive ventilation, we decided to treat the respiratory acidosis, tachypnoea and ventilatory fatigue by removing CO2 with an artificial lung. This avoided the need for tracheal intubation and MV, leaving the patient in spontaneous breathing. In September 2010, a 72-yr-old, female heavy …

To investigate the possibility of artificially decreasing intra-abdominal pressure (IAP) by applying continuous negative pressure around the abdomen. We investigated the effects of negative extra-abdominal pressure (NEXAP) on IAP and central venous pressure (CVP) in 30 patients admitted to our intensive care unit (age 57±17 years, BMI 26.1±4.0 kg/m2, SAPS II 41.8±17.0). Patients with severe hemodynamic instability and/or those admitted following a laparotomy were not studied. Measurements included bladder pressure as an estimate of IAP, CVP, invasive mean arterial pressure (MAP) and heart rate (HR). In five patients extensive hemodynamic measurements were also taken using a Swan-Ganz catheter. Following measurements at baseline (Basal), NEXAP (Life Care – Nev 100, Respironics) was applied on the abdomen, in random order, at a pressure equal to IAP (NEXAP0), 5 cmH2O (NEXAP-5) or 10 cmH2O (NEXAP-10) more negative than NEXAP0. Basal IAP ranged from 4 to 22 mmHg. NEXAP decreased IAP from 8.7±4.3 mmHg to 6±4.2 (Basal vs NEXAP0 p

On November 2009, the Italian health authorities set up a network of selected intensive care unit (ICU) centers (ECMOnet) to prepare for the treatment of the sickest patients of influenza A (H1N1) by means of extracorporeal membrane oxygenation (ECMO). To quickly and efficaciously train all the physicians working in the ICUs of the ECMOnet on ECMO use, we decided to take advantages of the opportunity provided by simulation technology. Simulation proved efficacious in providing adequate training and education to participants as confirmed by the survival results obtained by the group of ICUs of the ECMOnet. Our experience supports the use of simulation as a valuable alternative to animal laboratory sessions proposed by traditional ECMO training programs providing participants with cognitive, technical, and behavioral skills and allowing a proficient transfer of those skills to the real medical domain. Copyright © 2012 Society for Simulation in Healthcare.

Acid-base balance may be defined as a status in which, at steady state, the acid-base input in the system equals the acid-base output.

Pelosi, P., M. Croci, I. Ravagnan, M. Cerisara, P. Vicardi, A. Lissoni, and L. Gattinoni. Respiratory system mechanics in sedated, paralyzed, morbidly obese patients J. Appl. Physiol. 82(3): 811–818, 1997.—The effects of inspiratory flow and inflation volume on the mechanical properties of the respiratory system in eight sedated and paralyzed postoperative morbidly obese patients (aged 37.6 ± 11.8 yr who had never smoked and had normal preoperative seated spirometry) were investigated by using the technique of rapid airway occlusion during constant-flow inflation. With the patients in the supine position, we measured the interrupter resistance (Rint,rs), which in humans probably reflects airway resistance, the “additional” resistance (ΔRrs) due to viscoelastic pressure dissipation and time-constant inequalities, and static respiratory elastance (Est,rs). Intra-abdominal pressure (IAP) was measured by using a bladder catheter, and functional residual capacity was measured by the helium-dilution technique. The results were compared with a previous study on 16 normal anesthetized paralyzed humans. Compared with normal persons, we found that in obese subjects: 1) functional residual capacity was markedly lower (0.645 ± 0.208 liter) and IAP was higher (24 ± 2.2 cmH2O); 2) alveolar-arterial oxygenation gradient was increased (178 ± 59 mmHg); 3) the volume-pressure curve of the respiratory system was curvilinear with an “inflection” point; 4) Est,rs, Rint,rs, and ΔRrs were higher than normal (29.3 ± 5.04 cmH2O/l, 5.9 ± 2.4 cmH2O ⋅ l−1 ⋅ s, and 6.4 ± 1.6 cmH2O ⋅ l−1 ⋅ s, respectively); 5) Rint,rs increased with increasing inspiratory flow, Est,rs did not change, and ΔRrs decreased progressively; and 6) with increasing inflation volume, Rint,rs and Est,rs decreased, whereas ΔRrs rose progressively. Overall, our data suggest that obese subjects during sedation and paralysis are characterized by hypoxemia and marked alterations of the mechanical properties of the respiratory system, largely explained by a reduction in lung volume due to the excessive unopposed IAP.

Objective. - To assess the clinical consequences of duration of adult respiratory distress syndrome (ARDS) on lung structure and function. Design. - Retrospective analysis. Setting. - A university hospital referral center for extracorporeal support. Patients. - A total of 84 patients with severe ARDS (Murray score >2.5) recruited from 48 intensive care units (1979 to 1992), who suffered ARDS and underwent mechanical ventilation for up to 1 week (37 patients with early ARDS), between 1 and 2 weeks (24 patients with intermediate ARDS), or more than 2 weeks (23 patients with late ARDS) and subsequently underwent extracorporeal support. Main Outcome Measures. - Before beginning extracorporeal support, we measured gas exchange, pulmonary mechanics, hemodynamics, oxygen transport and delivery, incidence of barotrauma (presence of one or more thoracic tubes for pneumothorax drainage), and organ dysfunctions. In a subgroup of 16 patients, we studied lung structure by computed tomographic scan, scoring the densities and quantifying the emphysemalike lesions (bullae). Results. - Late ARDS showed lower respiratory compliance, higher dead space, higher PaCO2, lower venous admixture, and lower positive end-expiratory pressure requirement compared with early ARDS (P

Mechanical ventilation with plateau pressure lower than 35 cm H2O and high positive end-expiratory pressure (PEEP) has been recommended as lung protective strategy. Ten patients with ARDS (five from pulmonary [p] and five from extrapulmonary [exp] origin), underwent 2 h of lung protective strategy, 1 h of lung protective strategy with three consecutive sighs/min at 45 cm H2O plateau pressure, and 1 h of lung protective strategy. Total minute ventilation, PEEP (14.0 +/- 2.2 cm H2O), inspiratory oxygen fraction, and mean airway pressure were kept constant. After 1 h of sigh we found that: (1) PaO2 increased (from 92.8 +/- 18.6 to 137.6 +/- 23.9 mm Hg, p0.01), venous admixture and PaCO2 decreased (from 38 +/- 12 to 28 +/- 14%, p0.01; and from 52.7 +/- 19.4 to 49.1 +/- 18.4 mm Hg, p0.05, respectively); (2) end-expiratory lung volume increased (from 1.49 +/- 0.58 to 1.91 +/- 0.67 L, p0.01), and was significantly correlated with the oxygenation (r = 0.82, p0.01) and lung elastance (r = 0.76, p0.01) improvement. Sigh was more effective in ARDSexp than in ARDSp. After 1 h of sigh interruption, all the physiologic variables returned to baseline. The derecruitment was correlated with PaCO2 (r = 0.86, p0.01). We conclude that: (1) lung protective strategy alone at the PEEP level used in this study may not provide full lung recruitment and best oxygenation; (2) application of sigh during lung protective strategy may improve recruitment and oxygenation.