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.

Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI).

Rationale: Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. Objectives: To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. Methods: In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. Measurements and Main Results: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.79; P = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06-3.42; P = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01-2.28; P = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85-2.27; P = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. Conclusions: In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

High-volume hemofiltration does not protect human kidney endothelial and tubular epithelial cells from septic plasma-induced injury.

High volume hemofiltration (HVHF) could remove from plasma inflammatory mediators involved in sepsis-associated acute kidney injury (SA-AKI). The IVOIRE trial did not show improvements of outcome and organ dysfunction using HVHF. The aim of this study was to evaluate in vitro the biological effects of plasma of patients treated by HVHF or standard volume hemofiltration (SVHF). We evaluated leukocyte adhesion, apoptosis and functional alterations of endothelial cells (EC) and tubular epithelial cells (TEC). In vitro data were correlated with plasma levels of TNF-α, Fas-Ligand (FasL), CD40-Ligand (CD40L), von Willebrand Factor (vWF) and endothelial-derived microparticles. An experimental model of in vitro hemofiltration using LPS-activated blood was established to assess cytokine mass adsorption during HVHF or SVHF. Plasma concentrations of TNF-ɑ, FasL, CD40L and von Willebrand Factor (vWF) were elevated at the start (d1h0) of both HVHF and SVHF, significantly decreased after 6 h (d1h6), remained stable after 12 h (d1h12) and then newly increased at 48 h (d3h0). Plasma levels of all these molecules were similar between HVHF- and SVHF-treated patients at all time points considered. In addition, the levels of endothelial microparticles remained always elevated, suggesting the presence of a persistent microvascular injury. Plasma from septic patients induced leukocyte adhesion on EC and TEC through up-regulation of adhesion receptors. Moreover, on EC, septic plasma induced a cytotoxic and anti-angiogenic effect. On TEC, septic plasma exerted a direct pro-apoptotic effect via Fas up-regulation and caspase activation, loss of polarity, altered expression of megalin and tight junction molecules with an impaired ability to internalize albumin. The inhibition of plasma-induced cell injury was concomitant to the decrease of TNF-α, Fas-Ligand and CD40-Ligand levels. The protective effect of both HVHF and SVHF was time-limited, since a further increase of circulating mediators and plasma-induced cell injury was observed after 48 h (d3h0). No significant difference of EC/TEC damage were observed using HVHF- or SVHF-treated plasma. The in vitro hemofiltration model confirmed the absence of a significant modulation of cytokine adsorption between HVHF and SVHF. In comparison to SVHF, HVHF did not increase inflammatory cytokine clearance and did not reverse the detrimental effects of septic plasma-induced EC and TEC injury. Further studies using adsorptive membranes are needed to evaluate the potential role of high dose convective therapies in the limitation of the harmful activity of plasma soluble factors involved in SA-AKI.Trial registration IVOIRE randomized clinical trial; ClinicalTrials.gov (NCT00241228) (18/10/2005).

Orthostatic Ex-Vivo Lung Perfusion (EVLP): A Proof of Concept.

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position.

Outcomes and Impact of Pre-ECMO Clinical Course in Severe COVID-19-Related ARDS Treated with VV-ECMO: Data from an Italian Referral ECMO Center.

Background: The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. Methods: We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. Results: The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, p = 0.018 and 73.2% vs. 28.6%, p = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06-4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10-24) and the hospital stay (32 days, IQR: 24-47). Static lung compliance was lower in non-survivors (p = 0.031) and differed over time (p = 0.049), decreasing by 48% compared to initial values in non-survivors. Conclusions: Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker.

Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study.

BACKGROUND: The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. MATERIAL AND METHODS: We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). RESULTS: We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7-11 vs. 10, IQR: 8-13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. CONCLUSION: COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.

Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Electromyographic signature of isometric squat in the highest refuge in Europe.

Reports of electromyography during hypoxic exercise are contrasting, due to protocol and muscle diversity. This work aimed to investigate alterations in muscle activation and myoelectrical fatigue during exercise at high-altitude in those muscles primarily involved in trekking. Twelve young adults balanced by gender and age were tested at low (1,667 m) and high (4,554 m, "Capanna Margherita", Italy) altitude, during an isometric squat lasting 60 seconds. High-density surface electromyography was performed from the quadriceps of right limb. The root mean square (RMS), median frequency with its slope, and muscle fiber conduction velocity (MFCV) were computed. Neither males nor females showed changes in median frequency (Med: 36.13 vs 35.63 Hz) and its slope (Med: -9 vs -12 degree) in response to high-altitude trekking, despite a great inter-individual heterogeneity, nor differences were found for MFCV. RMS was not significantly equivalent, with greater values at low altitude (0.385 ± 0.104 mV) than high altitude (0.346 ± 0.090 mV). Unexpected results can be due either to a postural compensation of the whole body compensating for a relatively greater effort or to the inability to support muscle activation after repeated physical efforts.  Interesting results may emerge by measuring simultaneously electromyography, muscle oxygenation and kinematics comparing trekking at normoxia vs hypoxia.

Cytokines Removal During Ex-Vivo Lung Perfusion: Initial Clinical Experience.

Ex Vivo Lung Perfusion (EVLP) can be potentially used to manipulate organs and to achieve a proper reconditioning process. During EVLP pro-inflammatory cytokines have been shown to accumulate in perfusate over time and their production is correlated with poor outcomes of the graft. Aim of the present study is to investigate the feasibility and safety of cytokine adsorption during EVLP. From July 2011 to March 2020, 54 EVLP procedures have been carried out, 21 grafts treated with an adsorption system and 33 without. Comparing the grafts perfused during EVLP with or without cytokine adsorption, the use of a filter significantly decreased the levels of IL10 and GCSFat the end of the procedure. Among the 38 transplanted patients, the adsorption group experienced a significant decreased IL6, IL10, MCP1 and GCSF concentrations and deltas compared to the no-adsorption group, with a lower in-hospital mortality (p = 0.03) and 1-year death rate (p = 0.01). This interventional study is the first human experience suggesting the safety and efficacy of a porous polymer beads adsorption device in reducing the level of inflammatory mediators during EVLP. Clinical impact of cytokines reduction during EVLP must be evaluated in further studies.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission.

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field.

Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission.

Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid-base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required.Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient's bleeding risk.Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail.

Feature Selection Based on a Genetic Algorithm for Optimizing Weaning Success.

Finding the right time for weaning from ventilator is a difficult clinical decision. Several systems based on machine or deep learning are reported in literature. However, the results of these applications are not completely satisfactory and may be improved. An important aspect is represented by the features used as input of these systems. In this paper we present the results of the application of genetic algorithms to perform feature selection on a dataset containing 13688 patients under mechanical ventilation characterizing by 58 variables, extracted from the MIMIC III database. The results show that all features are important, but four of them are essential: 'Sedation_days', 'Mean_Airway_Pressure', 'PaO2', and 'Chloride'. This is only the initial step to obtain a tool to be added to the other clinical indices for minimize the risk of extubation failure.

Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study.

Background: Mid-regional pro-adrenomedullin (MR-proADM), an endothelium-related peptide, is a predictor of death and multi-organ failure in respiratory infections and sepsis and seems to be effective in identifying COVID-19 severe forms. The study aims to evaluate the effectiveness of MR-proADM in comparison to routine inflammatory biomarkers, lymphocyte subpopulations, and immunoglobulin (Ig) at an intensive care unit (ICU) admission and over time in predicting mortality in patients with severe COVID-19. Methods: All adult patients with COVID-19 pneumonia admitted between March 2020 and June 2021 in the ICUs of a university hospital in Italy were enrolled. MR-proADM, lymphocyte subpopulations, Ig, and routine laboratory tests were measured within 48 h and on days 3 and 7. The log-rank test was used to compare survival curves with MR-proADM cutoff value of >1.5 nmol/L. Predictive ability was compared using the area under the curve (AUC) and 95% confidence interval (CI) of different receiver-operating characteristic curves. Results: A total of 209 patients, with high clinical severity [SOFA 7, IQR 4-9; SAPS II 52, IQR 41-59; median viral pneumonia mortality score (MuLBSTA)-11, IQR 9-13] were enrolled. ICU and overall mortality were 55.5 and 60.8%, respectively. Procalcitonin, lactate dehydrogenase, D-dimer, the N-terminal prohormone of brain natriuretic peptide, myoglobin, troponin, neutrophil count, lymphocyte count, and natural killer lymphocyte count were significantly different between survivors and non-survivors, while lymphocyte subpopulations and Ig were not different in the two groups. MR-proADM was significantly higher in non-survivors (1.17 ± 0.73 vs. 2.31 ± 2.63, p < 0.0001). A value of >1.5 nmol/L was an independent risk factor for mortality at day 28 [odds ratio of 1.9 (95% CI: 1.220-3.060)] after adjusting for age, lactate at admission, SOFA, MuLBSTA, superinfections, cardiovascular disease, and respiratory disease. On days 3 and 7 of the ICU stay, the MR-proADM trend evaluated within 48 h of admission maintained a correlation with mortality (p < 0.0001). Compared to all other biomarkers considered, the MR-proADM value within 48 h had the best accuracy in predicting mortality at day 28 [AUC = 0.695 (95% CI: 0.624-0.759)]. Conclusion: MR-proADM seems to be the best biomarker for the stratification of mortality risk in critically ill patients with COVID-19. The Ig levels and lymphocyte subpopulations (except for natural killers) seem not to be correlated with mortality. Larger, multicentric studies are needed to confirm these findings.

Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study.

BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

Clinical performance of lung ultrasound in predicting time-dependent changes in lung aeration in ARDS patients.

To evaluate whether lung ultrasound is reliable bedside tool to monitor changes of lung aeration at the early and late stages of ARDS. LUS was performed in ARDS patients that underwent at least two consecutive CT scan at ICU admission and at least 1 week after admission. Twelve fields were evaluated and graded from 0 (normal) to 3 (consolidation). Changes of LUS score in twelve fields (ΔLUStot) and in four ventral (ΔLUSV), intermediate (ΔLUSI) and dorsal (ΔLUSD) zones were calculated at each time points. Three categories were described: Improve (ΔLUS < 0), Equal (ΔLUS = 0) or Worse (ΔLUS > 0). LUS scores were correlated with total changes in lung CT aeration (ΔCTair) and with normally, poorly and not aerated regions (ΔCTnorm, ΔCTpoor and ΔCTnot, respectively). Eleven patients were enrolled. ΔLUStot had significant correlation with ΔCTair (r = - 0.74, p < 0.01). ΔLUSV, ΔLUSI and ΔLUSD showed significant correlations with ΔCTair (r = - 0.66, r = - 0.69, r = - 0.63, respectively; p < 0.05). Compared to Equal, Improve and Worse categories had significantly higher (p < 0.01) and lower (p < 0.05) ΔCTair values, respectively. Compared to Equal, Improve and Worse categories had lower (p < 0.01) and higher (p < 0.01) ΔCTnot values, respectively. LUS score had a good correlation with lung CT in detecting changes of lung aeration.

Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome.

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.