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Purpose: Growing evidence shows the complex interaction between lung and kidney in critically ill patients. The renal resistive index (RRI) is a bedside measurement of the resistance of the renal blood flow and it is correlated with kidney injury. The positive end-expiratory pressure (PEEP) level could affect the resistance of renal blood flow, so we assumed that RRI could help to monitoring the changes in renal hemodynamics at different PEEP levels. Our hypothesis was that the RRI at ICU admission could predict the risk of acute kidney injury in mechanical ventilated critically ill patients., Methods: We performed a prospective study including 92 patients requiring mechanical ventilation for ≥ 48 h. A RRI ≥ 0.70, was deemed as pathological. RRI was measured within 24 h from ICU admission while applying 5,10 and 15 cmH 2 O of PEEP in random order (PEEP trial)., Results: Overall, RRI increased from 0.62 ± 0.09 at PEEP 5 to 0.66 ± 0.09 at PEEP 15 (p < 0.001). The mean RRI value during the PEEP trial was able to predict the occurrence of AKI with AUROC = 0.834 [95%CI 0.742-0.927]. Patients exhibiting a RRI ≥ 0.70 were 17/92(18%) at PEEP 5, 28/92(30%) at PEEP 10, 38/92(41%) at PEEP 15, respectively. Thirty-eight patients (41%) exhibited RRI ≥ 0.70 at least once during the PEEP trial. In these patients, AKI occurred in 55% of the cases, versus 13% remaining patients, p < 0.001., Conclusions: RRI seems able to predict the risk of AKI in mechanical ventilated patients; further, RRI values are influenced by the PEEP level applied., Trial Registration: Clinical gov NCT03969914 Registered 31 May 2019., (© 2024. The Author(s).)

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 (P 0.1 ), diaphragm electrical activity (EAdi), inspiratory effort derived from EAdi (∆Pmus EAdi ) and from occlusion of airway pressure (∆Pocc) (Pmus ΔPocc ), and dynamic transpulmonary driving pressure (ΔP L,dyn ) were measured at the first transition to assisted spontaneous breathing. Results : A total of 4171 breaths were analyzed in 48 patients. P 0.1 was >3.5 cmH 2 O in 10%, EAdi PEAK > 15 µV in 29%, ∆Pmus EAdi > 15 cmH 2 O in 28%, and ΔP L,dyn > 15 cmH 2 O 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.

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 cmH 2 O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH 2 O). 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 cmH 2 O [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., (© 2024. The Author(s).)

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 PaO 2 /FiO 2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH 2 O = PEEP LOW , and titrated to achieve positive end-expiratory transpulmonary pressure P L,EE  = PEEP TITRATED ) were used for measurements., Results: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median P L,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH 2 O and lung elastance (E L ) 44 [40-51] cmH 2 O/L. At PEEP LOW , P L,EE remained negative and E L did not change (p = 0.995) versus ZEEP. At PEEP TITRATED , P L,EE increased to 0.8 [0.3-1.5] cmH 2 O and E L to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEP LOW , respectively). ΔP L decreased at PEEP LOW (p = 0.018) and increased at PEEP TITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive P L,EE did not result in significant changes in E L and ΔP L ., Conclusions: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive P L,EE significantly worsened lung mechanics., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

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.

Background: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial)., Methods: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO 2 /FiO 2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH 2 O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH 2 O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH 2 O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH 2 O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment., Discussion: The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS., Trial Registration: ClinicalTrials.gov NCT04012073 . Registered 9 July 2019., (© 2022. The Author(s).)

Background: Patients with acute respiratory failure (ARF) may need mechanical ventilation (MV), which can lead to diaphragmatic dysfunction and muscle wasting, thus making difficult the weaning from the ventilator. Currently, there are no biomarkers specific for respiratory muscle and their function can only be assessed trough ultrasound or other invasive methods. Previously, the fast and slow isoform of the skeletal troponin I (fsTnI and ssTnI, respectively) have shown to be specific markers of muscle damage in healthy volunteers. We aimed therefore at describing the trend of skeletal troponin in mixed population of ICU patients undergoing weaning from mechanical ventilation and compared the value of fsTnI and ssTnI with diaphragmatic ultrasound derived parameters. Methods: In this prospective observational study we enrolled consecutive patients recovering from acute hypoxemic respiratory failure (AHRF) within 24 h from the start of weaning. Every day an arterial blood sample was collected to measure fsTnI, ssTnI, and global markers of muscle damage, such as ALT, AST, and CPK. Moreover, thickening fraction (TF) and diaphragmatic displacement (DE) were assessed by diaphragmatic ultrasound. The trend of fsTnI and ssTnI was evaluated during the first 3 days of weaning. Results: We enrolled 62 consecutive patients in the study, with a mean age of 67 ± 13 years and 43 of them (69%) were male. We did not find significant variations in the ssTnI trend ( p = 0.623), but fsTnI significantly decreased over time by 30% from Day 1 to Day 2 and by 20% from Day 2 to Day 3 ( p < 0.05). There was a significant interaction effect between baseline ssTnI and DE [ F (2) = 4.396, p = 0.015], with high basal levels of ssTnI being associated to a higher decrease in DE. On the contrary, the high basal levels of fsTnI at day 1 were characterized by significant higher DE at each time point. Conclusions: Skeletal muscle proteins have a distinctive pattern of variation during weaning from mechanical ventilation. At day 1, a high basal value of ssTnI were associated to a higher decrease over time of diaphragmatic function while high values of fsTnI were associated to a higher displacement at each time point., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Spadaro, Dalla Corte, Scaramuzzo, Grasso, Cinnella, Rosta, Chiavieri, Alvisi, Di Mussi, Volta, Bellini and Trentini.)

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 (P 0.1 ) 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 (P musc ) greater than 10 cmH 2 O while breaths with low inspiratory effort were defined by a P musc lower than 5 cmH 2 O. The areas under the receiver operating characteristic curves of Flow Index and respiratory rate, tidal volume,respiratory rate over tidal volume and P 0.1 were analyzed and compared to identify breaths with low or high inspiratory effort., Results: P musc , P 0.1 , Pressure Time Product and Flow Index differed between breaths with high, low and intermediate inspiratory effort, while RR, RR/V T and V T /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., (© 2021. The Author(s).)

During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (∆P) could reduce postoperative pulmonary complications. However, it is unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEP INCREMENTAL ) or by stepwise decrease after a lung recruiting manoeuvre (PEEP DECREMENTAL ). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEP INCREMENTAL or PEEP DECREMENTAL strategy to match the lowest ∆P. In the PEEP INCREMENTAL group, PEEP was stepwise titrated from ZEEP up to 16 cm H 2 O, whereas in the PEEP DECREMENTAL group PEEP was decrementally titrated, starting from 16 cm H 2 O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 [39-55]% to 35 [28-42]% in the PEEP INCREMENTAL and from 45 [37-58]% to 33 [25-45]% in the PEEP DECREMENTAL group (both p < 0.001 vs baseline). The resulting ∆P, however, was lower in the PEEP DECREMENTAL than in the PEEP INCREMENTAL group (8 [7-11] vs 10 [9-11] cm H 2 O; p = 0.03). In the PEEP DECREMENTAL group the PaO 2 / FIO 2 ratio increased significantly after intervention (from 140 [99-176] to 186 [152-243], p < 0.001). Both the PEEP INCREMENTAL and the PEEP DECREMENTAL strategies were able to decrease intraoperative shunt, but only PEEP DECREMENTAL improved oxygenation and lowered intraoperative ΔP.Clinical trial number NCT03635281; August 2018; "retrospectively registered"., (© 2020. Springer Nature B.V.)

Background: Patient-ventilator asynchronies are challenging during pediatric mechanical ventilation. We hypothesized that monitoring the electrical activity of the diaphragm (EAdi) together with the "standard" airway opening pressure (Pao) and flow-time waveforms during pressure support ventilation would improve the ability of a cohort of critical care physicians to detect asynchronies in ventilated children., Methods: We recorded the flow, Pao and EAdi waveforms in ten consecutive patients. The recordings were split in periods of 15 s, each reproducing a ventilator screenshot. From this pool, a team of four experts selected the most representative screenshots including at least one of the three most common asynchronies (missed efforts, auto-triggering and double triggering) and split them into two versions, respectively showing or not the EAdi waveforms. The screenshots were shown in random order in a questionnaire to sixty experienced pediatric intensivists that were asked to identify any episode of patient-ventilator asynchrony., Results: Among the ten patients included in the study, only eight had EAdi tracings without artifacts and were analyzed. When the Eadi waveform was shown, the auto-triggering detection improved from 13% to 67% (P<0.0001) and the missed efforts detection improved from 43% to 95% (P<0.0001). The detection of double triggering, instead, did not improve (85% with the EAdi vs. 78% without the EAdi waveform; P=0.52)., Conclusions: This single center study suggests that the EAdi waveform may improve the ability of pediatric intensivists to detect missed efforts and auto-triggering asynchronies. Further studies are required to determine the clinical implications of these findings.

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.

Introduction: Pressure support ventilation (PSV) should allow spontaneous breathing with a "normal" neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of "Low" and/or "High" neuro-ventilatory drive during clinical application of PSV., Method: In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdi PEAK ), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTP DI/b and PTP DI/min , respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with "Normal" (EAdi PEAK 5-15 μV), "Low" (EAdi PEAK  < 5 μV) and "High" (EAdi PEAK  > 15 μV) neuro-ventilatory drive., Results: Within all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdi PEAK , was "Low" in 50.116 breath (28%), "Normal" in 88.419 breaths (50%) and "High" in 38.582 breaths (22%). The average times spent in "Low", "Normal" and "High" class were 1.37, 3.67 and 0.55 h, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the "Low" neuro-ventilatory drive class for more than 1 h, median 6.1 [3.9-8.5] h and 6 in the "High" neuro-ventilatory drive class, median 3.4 [2.2-7.8] h. The asynchrony index was significantly higher in the "Low" neuro-ventilatory class, mainly because of a higher number of missed efforts., Conclusions: We observed wide variations in EAdi amplitude and unevenly distributed "Low" and "High" neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings.

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.

Purpose: High-flow oxygen therapy delivered through nasal cannulae improves oxygenation and decreases work of breathing in critically ill patients. Little is known of the physiological effects of high-flow oxygen therapy applied to the tracheostomy cannula (T-HF). In this study, we compared the effects of T-HF or conventional low-flow oxygen therapy (conventional O 2 ) on neuro-ventilatory drive, work of breathing, respiratory rate (RR) and gas exchange, in a mixed population of tracheostomized patients at high risk of weaning failure., Methods: This was a single-center, unblinded, cross-over study on fourteen patients. After disconnection from the ventilator, each patient received two 1-h periods of T-HF (T-HF1 and T-HF2) alternated with 1 h of conventional O 2 . The inspiratory oxygen fraction was titrated to achieve an arterial O 2 saturation target of 94-98% (88-92% in COPD patients). We recorded neuro-ventilatory drive (electrical diaphragmatic activity, EAdi), work of breathing (inspiratory muscular pressure-time product per breath and per minute, PTP musc/b and PTP musc/min , respectively) respiratory rate and arterial blood gases., Results: The EAdi peak remained unchanged (mean ± SD) in the T-HF1, conventional O 2 and T-HF2 study periods (8.8 ± 4.3 μV vs 8.9 ± 4.8 μV vs 9.0 ± 4.1 μV, respectively, p = 0.99). Similarly, PTP musc/b and PTP musc/min , RR and gas exchange remained unchanged., Conclusions: In tracheostomized patients at high risk of weaning failure from mechanical ventilation, T-HF did not improve neuro-ventilatory drive, work of breathing, respiratory rate and gas exchange compared with conventional O 2 after disconnection from the ventilator. The present findings might suggest that physiological effects of high-flow therapy through tracheostomy substantially differ from nasal high flow.

Background: The physiological effects of high-flow nasal cannula O 2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure. In this study, we compared the effects of HFNC and conventional low-flow O 2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure., Methods: This was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies. After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O 2 therapy via a face mask. The inspiratory fraction of oxygen was titrated to achieve an arterial O 2 saturation target of 88-92%. Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTP DI/min )) were recorded., Results: EAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 μV switching from HFNC1 to conventional O 2 , and then returned to 15.2 ± 6.4 μV during HFNC2 (conventional O 2 : p < 0.05 versus HFNC1 and HFNC2). Similarly, the PTP DI/min increased from 135 ± 60 to 211 ± 70 cmH 2 O/s/min, and then decreased again during HFNC2 to 132 ± 56 (conventional O 2 : p < 0.05 versus HFNC1 and HFNC2)., Conclusions: In patients with COPD, the application of HFNC postextubation significantly decreased the neuroventilatory drive and work of breathing compared with conventional O 2 therapy.

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.

Background: Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency., Method: Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours., Results: In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/μV at baseline to 62 ± 30 ml/μV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH2O/μV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38- 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78- 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04)., Conclusion: After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not., Trial Registration: ClinicalTrials.gov study registration: NCT02473172, 06/11/2015.