Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support.

OBJECTIVE: To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence. METHODS: Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence. RESULTS: Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7-13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5-7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8-10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short- and prolonged-antimicrobial treatment. CONCLUSIONS: In patients with severe Covid-19-ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.

Antiphospholipid Patients Admitted in the Intensive Care Unit: What Must The Rheumatologist Know?

PURPOSE OF THE REVIEW: Antiphospholipid syndrome (APS) is a rare systemic autoimmune disorder that can escalate into a 'thrombotic storm' called the catastrophic antiphospholipid syndrome (CAPS), frequently requiring ICU admission for multiple organ failure. This review aims to offer insight and recent evidence on critically-ill APS patients. RECENT FINDINGS: The CAPS classification criteria define this condition as the involvement of at least three organs/systems/tissues within less than a week, caused by small vessel thrombosis, in patients with elevated antiphospholipid antibodies levels. These criteria do not encompass the full spectrum of critically-ill thrombotic APS patients and they need to be cautiously used for the bedside diagnosis of CAPS. Thrombocytopenia is the laboratory hallmark of CAPS, sometimes dropping below 20G/L, but a complete thrombotic microangiopathy pattern is infrequent. Anticoagulation is the pivotal treatment for APS and CAPS, associated with improved outcome. Triple therapy - the combination of anticoagulation, high-dose corticosteroids, and either plasma exchange or intravenous immunoglobulins - remains the standard treatment for CAPS patients. Eculizumab, an anti-C5 monoclonal antibody, may be useful in refractory patients. Despite significant progress, CAPS mortality rate remains high. Its diagnosis and management are complex, requiring a close multidisciplinary cross talk between APS specialists and intensivists.

Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R.

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Head-to-toe bedside ultrasound for adult patients on extracorporeal membrane oxygenation.

Bedside ultrasound represents a well-suited diagnostic and monitoring tool for patients on extracorporeal membrane oxygenation (ECMO) who may be too unstable for transport to other hospital areas for diagnostic tests. The role of ultrasound, however, starts even before ECMO initiation. Every patient considered for ECMO should have a thorough ultrasonographic assessment of cardiac and valvular function, as well as vascular anatomy without delaying ECMO cannulation. The role of pre-ECMO ultrasound is to confirm the indication for ECMO, identify clinical situations for which ECMO is not indicated, rule out contraindications, and inform the choice of ECMO configuration. During ECMO cannulation, the use of vascular and cardiac ultrasound reduces the risk of complications and ensures adequate cannula positioning. Ultrasound remains key for monitoring during ECMO support and troubleshooting ECMO complications. For instance, ultrasound is helpful in the assessment of drainage insufficiency, hemodynamic instability, biventricular function, persistent hypoxemia, and recirculation on venovenous (VV) ECMO. Lung ultrasound can be used to monitor signs of recovery on VV ECMO. Brain ultrasound provides valuable diagnostic and prognostic information on ECMO. Echocardiography is essential in the assessment of readiness for liberation from venoarterial (VA) ECMO. Lastly, post decannulation ultrasound mainly aims at identifying post decannulation thrombosis and vascular complications. This review will cover the role of head-to-toe ultrasound for the management of adult ECMO patients from decision to initiate ECMO to the post decannulation phase.

Increasing sweep gas flow reduces respiratory drive and dyspnea in non-intubated veno-arterial ECMO patients - a pilot study.

BACKGROUND.: Data on assessment and management of dyspnea in patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are lacking. We hypothesized that increasing sweep gas flow through the VA-ECMO oxygenator may decrease dyspnea in non-intubated VA-ECMO patients exhibiting clinically significant dyspnea, with a parallel reduction in respiratory drive. METHODS.: Non-intubated, spontaneously breathing, supine patients on VA-ECMO for cardiogenic shock who presented with a visual analog dyspnea scale (dyspnea-VAS) ≥ 40/100 mm were included. Sweep gas flow was increased up to +6 L/min by three steps of +2 L/min each. Dyspnea was assessed with dyspnea-VAS and Multidimensional Dyspnea Profile. The respiratory drive was assessed by the electromyographic activity of the alae nasi and parasternal muscles. RESULTS.: We included 21 patients. On inclusion, median dyspnea-VAS was 50 ([interquartile range] 45-60) mm and sweep gas flow was 1.0 L/min (0.5-2.0). An increase in sweep gas flow significantly decreased dyspnea-VAS (50[45-60] at baseline vs 20[10-30] at 6L/min; p<0.001). The decrease in dyspnea was greater for the sensory component of dyspnea (-50%[43-75]) than for the affective and emotional components (-17%[0-25] and -12%[0-17], p<0.001). An increase in sweep gas flow significantly decreased electromyographic activity of the alae nasi and parasternal muscles (-23%[36-10] and -20[41-0], p<0.001). There was a significant correlation between the sweep gas flow and the dyspnea-VAS (r=-0.91 95%CI[-0.94, -0.87]), between the respiratory drive and the sensory component of dyspnea (r=0.29 95%CI[0.13, 0.44]), between the respiratory drive and the affective component of dyspnea (r=0.29 95%CI[0.02, 0.54]) and between the sweep gas flow and the alae nasi and parasternal (r=-0.31 95%CI[-0.44, -0.22] and r=-0.25 95%CI[-0.44, -0.16]). CONCLUSION.: In critically ill patients with VA-ECMO, an increase in sweep gas flow through the oxygenation membrane decreases dyspnea, possibly mediated by a decrease in respiratory drive.

Bleeding complications, coagulation disorders, and their management in acute myocardial infarction-related cardiogenic shock rescued by veno-arterial ECMO: A retrospective cohort study.

PURPOSE: Management of dual antiplatelet therapy (DAPT) in patients on venoarterial-extracorporeal membrane (VA-ECMO) after acute myocardial infarction (AMI) is challenging. Our objective was to describe the frequency, management and outcomes of severe bleeding complications and determine their occurrence risk factors. MATERIAL AND METHODS: We conducted a retrospective observational cohort study including post-AMI cardiogenic shock patients requiring VA-ECMO. Severe bleeding was defined based on the Bleeding Academic Research Consortium classification. We calculated multivariable Fine-Gray models to assess factors associated with risk of severe bleeding. RESULTS: From January 2015 to July 2019, 176 patients received VA-ECMO after AMI and 132 patients were included. Sixty-five (49%) patients died. Severe bleeding occurred in 39% of cases. Severe thrombocytopenia (< 50 G/L) and hypofibrinogenemia (<1,5 g/L) occurred in respectively 31% and 19% of patients. DAPT was stopped in 32% of patients with a 6% rate of stent thrombosis. Anticoagulation was stopped in 39% of patients. Using a multivariate competing risk model, female sex, time on ECMO, troponin at admission and Impella® implantation were independently associated with severe bleeding. CONCLUSIONS: Bleeding complications and coagulation disorders were frequent and severe in patients on VA-ECMO after AMI, leading of antiplatelet therapy withdrawal in one third of patients.

Ceftazidime/avibactam serum concentration in patients on ECMO.

OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing. METHODS: Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8 mg/L for ceftazidime and 4 mg/L for avibactam, and explored factors associated with underdosing. RESULTS: Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8 mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4 mg/L. Increased renal clearance (creatinine clearance > 130 mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition. CONCLUSIONS: In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing.

Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence?

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes.

Venoarterial extracorporeal membrane oxygenation in immunocompromised patients with cardiogenic shock: a cohort study and propensity-weighted analysis.

PURPOSE: The outcomes of immunocompromised patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are seldom documented, making ECMO candidacy decisions challenging. This study aims (1) to report outcomes of immunocompromised patients treated with VA-ECMO, (2) to identify pre-ECMO predictors of 90-day mortality, (3) to assess the impact of immunodepression on 90-day mortality, and (4) to describe the main ECMO-related complications. METHODS: This is a retrospective, propensity-weighted study conducted in two French experienced ECMO centers. RESULTS: From January 2006 to January 2022, 177 critically ill immunocompromised patients (median (interquartile range, IQR) age 49 (32-60) years) received VA-ECMO. The main causes of immunosuppression were long-term corticosteroids/immunosuppressant treatment (29%), hematological malignancy (26%), solid organ transplant (20%), and solid tumor (13%). Overall 90-day and 1-year mortality were 70% (95% confidence interval (CI) 63-77%) and 75% (95% CI 65-79%), respectively. Older age and higher pre-ECMO lactate were independently associated with 90-day mortality. Across immunodepression causes, 1-year mortality ranged from 58% for patients with infection by human immunodeficiency virus (HIV) or asplenia, to 89% for solid organ transplant recipients. Hemorrhagic and infectious complications affected 39% and 54% of patients, while more than half the stay in intensive care unit (ICU) was spent on antibiotics. In a propensity score-weighted model comparing the 177 patients with 942 non-immunocompromised patients experiencing cardiogenic shock on VA-ECMO, immunocompromised status was independently associated with a higher 90-day mortality (odds ratio 2.53, 95% CI 1.72-3.79). CONCLUSION: Immunocompromised patients undergoing VA-ECMO treatment face an unfavorable prognosis, with higher 90-day mortality compared to non-immunocompromised patients. This underscores the necessity for thorough evaluation and careful selection of ECMO candidates within this frail population.

Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial.

BACKGROUND: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock. METHODS: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 µg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209). FINDINGS: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction). INTERPRETATION: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004.

Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial.

PURPOSE: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI. METHODS: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization. RESULTS: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results. CONCLUSION: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.

Mechanical circulatory support for cardiogenic shock: a network meta-analysis of randomized controlled trials and propensity score-matched studies.

PURPOSE: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. METHODS: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. RESULTS: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66). CONCLUSION: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.

Use of the Win Ratio Analysis in Critical Care Trials.

Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.

Noninvasive Ventilation Before Intubation and Mortality in Patients Receiving Extracorporeal Membrane Oxygenation for COVID-19: An Analysis of the Extracorporeal Life Support Organization Registry.

Bilevel-positive airway pressure (BiPAP) is a noninvasive respiratory support modality which reduces effort in patients with respiratory failure. However, it may increase tidal ventilation and transpulmonary pressure, potentially aggravating lung injury. We aimed to assess if the use of BiPAP before intubation was associated with increased mortality in adult patients with coronavirus disease 2019 (COVID-19) who received venovenous extracorporeal membrane oxygenation (ECMO). We used the Extracorporeal Life Support Organization Registry to analyze adult patients with COVID-19 supported with venovenous ECMO from January 1, 2020, to December 31, 2021. Patients treated with BiPAP were compared with patients who received other modalities of respiratory support or no respiratory support. A total of 9,819 patients from 421 centers were included. A total of 3,882 of them (39.5%) were treated with BiPAP before endotracheal intubation. Patients supported with BiPAP were intubated later (4.3 vs. 3.3 days, p < 0.001) and showed higher unadjusted hospital mortality (51.7% vs. 44.9%, p < 0.001). The use of BiPAP before intubation and time from hospital admission to intubation resulted as independently associated with increased hospital mortality (odds ratio [OR], 1.32 [95% confidence interval {CI}, 1.08-1.61] and 1.03 [1-1.06] per day increase). In ECMO patients with severe acute respiratory failure due to COVID-19, the extended use of BiPAP before intubation should be regarded as a risk factor for mortality.

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.

A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.