Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

BACKGROUND: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. METHODS: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements. RESULTS: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH2O and lung elastance (EL) 44 [40-51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3-1.5] cmH2O and EL to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL. CONCLUSIONS: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Flow Index accurately identifies breaths with low or high inspiratory effort during pressure support ventilation.

BACKGROUND: Flow Index, a numerical expression of the shape of the inspiratory flow-time waveform recorded during pressure support ventilation, is associated with patient inspiratory effort. The aim of this study was to assess the accuracy of Flow Index in detecting high or low inspiratory effort during pressure support ventilation and to establish cutoff values for the Flow index to identify these conditions. The secondary aim was to compare the performance of Flow index,of breathing pattern parameters and of airway occlusion pressure (P0.1) in detecting high or low inspiratory effort during pressure support ventilation. METHODS: Data from 24 subjects was included in the analysis, accounting for a total of 702 breaths. Breaths with high inspiratory effort were defined by a pressure developed by inspiratory muscles (Pmusc) greater than 10 cmH2O while breaths with low inspiratory effort were defined by a Pmusc lower than 5 cmH2O. The areas under the receiver operating characteristic curves of Flow Index and respiratory rate, tidal volume,respiratory rate over tidal volume and P0.1 were analyzed and compared to identify breaths with low or high inspiratory effort. RESULTS: Pmusc, P0.1, Pressure Time Product and Flow Index differed between breaths with high, low and intermediate inspiratory effort, while RR, RR/VT and VT/kg of IBW did not differ in a statistically significant way. A Flow index higher than 4.5 identified breaths with high inspiratory effort [AUC 0.89 (CI 95% 0.85-0.93)], a Flow Index lower than 2.6 identified breaths with low inspiratory effort [AUC 0.80 (CI 95% 0.76-0.83)]. CONCLUSIONS: Flow Index is accurate in detecting high and low spontaneous inspiratory effort during pressure support ventilation.

Effects of Positive End-Expiratory Pressure in "High Compliance" Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome.

OBJECTIVES: Clinical observation suggests that early acute respiratory distress syndrome induced by the severe acute respiratory syndrome coronavirus 2 may be "atypical" due to a discrepancy between a relatively unaffected static respiratory system compliance and a significant hypoxemia. This would imply an "atypical" response to the positive end-expiratory pressure. DESIGN: Single-center, unblinded, crossover study. SETTING: ICU of Bari Policlinico Academic Hospital (Italy), dedicated to care patients with confirmed diagnosis of novel coronavirus disease 2019. PATIENTS: Eight patients with early severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and static respiratory compliance higher than or equal to 50 mL/cm H2O. INTERVENTIONS: We compared a "lower" and a "higher" positive end-expiratory pressure approach, respectively, according to the intervention arms of the acute respiratory distress syndrome network and the positive end-expiratory pressure setting in adults with acute respiratory distress syndrome studies. MEASUREMENTS AND MAIN RESULTS: Patients were ventilated with the acute respiratory distress syndrome network and, subsequently, with the ExPress protocol. After 1 hour of ventilation, for each protocol, we recorded arterial blood gas, respiratory mechanics, alveolar recruitment, and hemodynamic variables. Comparisons were performed with analysis of variance for repeated measures or Friedman test as appropriate. Positive end-expiratory pressure was increased from 9 ± 3.5 to 17.7 ± 1.7 cm H2O (p < 0.01). Alveolar recruitment was 450 ± 111 mL. Static respiratory system compliance decreased from 58.3 ± 7.6 mL/cm H2O to 47.4 ± 14.5 mL/cm H2O (p = 0.018) and the "stress index" increased from 0.97 ± 0.03 to 1.22 ± 0.07 (p < 0.001). The PaO2/FIO2 ratio increased from 131 ± 22 to 207 ± 41 (p < 0.001), and the PaCO2 increased from 45.9 ± 12.7 to 49.8 ± 13.2 mm Hg (p < 0.001). The cardiac index went from 3.6 ± 0.4 to 2.9 ± 0.6 L/min/m (p = 0.01). CONCLUSIONS: Our data suggest that the "higher" positive end-expiratory pressure approach in patients with severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and high compliance improves oxygenation and lung aeration but may result in alveolar hyperinflation and hemodynamic alterations.

Lung Recruitability in Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Quantification of potential for lung recruitment may guide the ventilatory strategy in acute respiratory distress syndrome. However, there are no quantitative data on recruitability in patients with severe acute respiratory distress syndrome who require extracorporeal membrane oxygenation. We sought to quantify potential for lung recruitment and its relationship with outcomes in this cohort of patients. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center in a university hospital in the United Kingdom. PATIENTS: Forty-seven adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe acute respiratory distress syndrome-mainly of pulmonary origin (86%)-the potential for lung recruitment and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue were assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were categorized as high or low potential for lung recruitment based on the median potential for lung recruitment value of the study population. The median potential for lung recruitment was 24.3% (interquartile range = 11.4-37%) ranging from -2% to 76.3% of the total lung weight. Patients with potential for lung recruitment above the median had significantly shorter extracorporeal membrane oxygenation duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), but mortality was not statistically different (24% vs 46%; p = 0.159). CONCLUSIONS: We observed significant variability in potential for lung recruitment in patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Patients with high potential for lung recruitment had a shorter ICU stay and shorter extracorporeal membrane oxygenation duration.

Can diaphragmatic ultrasonography performed during the T-tube trial predict weaning failure? The role of diaphragmatic rapid shallow breathing index.

BACKGROUND: The rapid shallow breathing index (RSBI), which is the ratio between respiratory rate (RR) and tidal volume (VT), is one of the most widely used indices to predict weaning outcome. Whereas the diaphragm plays a fundamental role in generating VT, in the case of diaphragmatic dysfunction the inspiratory accessory muscles may contribute. If this occurs during a weaning trial, delayed weaning failure is likely since the accessory muscles are more fatigable than the diaphragm. Hence, we hypothesised that the traditional RSBI could be implemented by substituting VT with the ultrasonographic evaluation of diaphragmatic displacement (DD). We named the new index the diaphragmatic-RSBI (D-RSBI). The aim of this study was to compare the ability of the traditional RSBI and D-RSBI to predict weaning failure in ready-to-wean patients. METHODS: We performed a prospective observational study. During a T-tube spontaneous breathing trial (SBT) we simultaneously evaluated right hemidiaphragm displacement (i.e., DD) by using M-mode ultrasonography as well as the RSBI. Outcome of the weaning attempt, length of mechanical ventilation, length of intensive care unit and hospital stay, and hospital mortality were recorded. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic accuracy of D-RSBI and RSBI. RESULTS: We enrolled 51 patients requiring mechanical ventilation for more than 48 h who were ready to perform a SBT. Most of the patients, 34 (66 %), were successfully weaned from mechanical ventilation. When considering the 17 patients that failed the weaning attempt, 11 (64 %) had to be reconnected to the ventilator during the SBT, three (18 %) had to be re-intubated within 48 h of extubation, and three (18 %) required non-invasive ventilation support within 48 h of extubation. The areas under the ROC curves for D-RSBI and RSBI were 0.89 and 0.72, respectively (P = 0.006). CONCLUSIONS: D-RSBI (RR/DD) was more accurate than traditional RSBI (RR/VT) in predicting the weaning outcome. TRIAL REGISTRATION: Our clinical trial was retrospectively registered with ClinicalTrials.gov (identifier: NCT02696018 ). ClinicalTrials.gov processed our record on 25 February 2016.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Respiratory Drive, Effort, and Lung-Distending Pressure during Transitioning from Controlled to Spontaneous Assisted Ventilation in Patients with ARDS: A Multicenter Prospective Cohort Study.

Objectives: To investigate the impact of patient characteristics and treatment factors on excessive respiratory drive, effort, and lung-distending pressure during transitioning from controlled to spontaneous assisted ventilation in patients with acute respiratory distress syndrome (ARDS). Methods: Multicenter cohort observational study of patients with ARDS at four academic intensive care units. Respiratory drive (P0.1), diaphragm electrical activity (EAdi), inspiratory effort derived from EAdi (∆PmusEAdi) and from occlusion of airway pressure (∆Pocc) (PmusΔPocc), and dynamic transpulmonary driving pressure (ΔPL,dyn) were measured at the first transition to assisted spontaneous breathing. Results: A total of 4171 breaths were analyzed in 48 patients. P0.1 was >3.5 cmH2O in 10%, EAdiPEAK > 15 µV in 29%, ∆PmusEAdi > 15 cmH2O in 28%, and ΔPL,dyn > 15 cmH2O in 60% of the studied breaths. COVID-19 etiology of ARDS was the strongest independent risk factor for a higher proportion of breaths with excessive respiratory drive (RR 3.00 [2.43-3.71], p < 0.0001), inspiratory effort (RR 1.84 [1.58-2.15], p < 0.0001), and transpulmonary driving pressure (RR 1.48 [1.36-1.62], p < 0.0001). The P/F ratio at ICU admission, days of deep sedation, and dose of steroids were additional risk factors for vigorous inspiratory effort. Age and dose of steroids were risk factors for high transpulmonary driving pressure. Days of deep sedation (aHR 1.15 [1.07-1.24], p = 0.0002) and COVID-19 diagnosis (aHR 6.96 [1-48.5], p = 0.05) of ARDS were independently associated with composite outcome of transitioning from light to deep sedation (RASS from 0/-3 to -4/-5) or return to controlled ventilation within 48 h of spontaneous assisted breathing. Conclusions: This study identified that specific patient characteristics, including age, COVID-19-related ARDS, and P/F ratio, along with treatment factors such as the duration of deep sedation and the dosage of steroids, are independently associated with an increased likelihood of assisted breaths reaching potentially harmful thresholds of drive, effort, and lung-distending pressure during the initial transition to spontaneous assisted breathing. It is noteworthy that patients who were subjected to prolonged deep sedation under controlled mechanical ventilation, as well as those with COVID-19, were more susceptible to failing the transition from controlled to assisted breathing.

Adverse Maternal Outcomes in Pregnant Women Affected by Severe-Critical COVID-19 Illness: Correlation with Vaccination Status in the Time of Different Viral Strains' Dominancy.

This is a monocentric and cross-sectional study conducted at the COVID-19 Division of the Obstetrical and Gynecological Unit and Intensive Care Units (ICUs) of Policlinico di Bari, in Bari, Italy, between September 2020 and April 2022. This study aimed to identify the prevalence of severe-critical COVID-19 illness requiring access to the Intensive Care Unit (ICU) among 287 pregnant patients, and possible correlations between the SARS-CoV-2 variants, the specific pandemic wave (dominated by wild, Alpha, Delta, and Omicron strains), and severe-critical adverse maternal outcomes. The prevalence of severe-critical COVID-19 illness was 2.8% (8/287), reaching 4.9% (8/163) excluding the 4th wave (Omicron dominant). The Delta variant determined the highest risk ratio and odds for access to the ICU due to severe-critical COVID-19-related symptoms compared to the other variants (wild, Alpha, Omicron). During the third wave (Delta), the ICU cases underwent a higher rate of hyperimmune plasma infusion (75%), antibiotic therapy (75%), and remdesivir (33%); all of the patients were intubated. During the Omicron wave, the patients were asymptomatic or with few symptoms: most of them (70%) were vaccinated with a median of two doses. The maternal outcome worsened in the case of Alpha and, especially, Delta variants for severe-critical COVID-19-related symptoms and ICU access.