An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Association Between Hospital Type and Resilience During COVID-19 Caseload Stress : A Retrospective Cohort Study.

BACKGROUND: Imbalances between hospital caseload and care resources that strained U.S. hospitals during the pandemic have persisted after the pandemic amid ongoing staff shortages. Understanding which hospital types were more resilient to pandemic overcrowding-related excess deaths may prioritize patient safety during future crises. OBJECTIVE: To determine whether hospital type classified by capabilities and resources (that is, extracorporeal membrane oxygenation [ECMO] capability, multiplicity of intensive care unit [ICU] types, and large or small hospital) influenced COVID-19 volume-outcome relationships during Delta wave surges. DESIGN: Retrospective cohort study. SETTING: 620 U.S. hospitals in the PINC AI Healthcare Database. PARTICIPANTS: Adult inpatients with COVID-19 admitted July to November 2021. MEASUREMENTS: Hospital-months were ranked by previously validated surge index (severity-weighted COVID-19 inpatient caseload relative to hospital bed capacity) percentiles. Hierarchical models were used to evaluate the effect of log-transformed surge index on the marginally adjusted probability of in-hospital mortality or discharge to hospice. Effect modification was assessed for by 4 mutually exclusive hospital types. RESULTS: Among 620 hospitals recording 223 380 inpatients with COVID-19 during the Delta wave, there were 208 ECMO-capable, 216 multi-ICU, 36 large (≥200 beds) single-ICU, and 160 small (<200 beds) single-ICU hospitals. Overall, 50 752 (23%) patients required admission to the ICU, and 34 274 (15.3%) died. The marginally adjusted probability for mortality was 5.51% (95% CI, 4.53% to 6.50%) per unit increase in the log surge index (strain attributable mortality = 7375 [CI, 5936 to 8813] or 1 in 5 COVID-19 deaths). The test for interaction showed no difference (P = 0.32) in log surge index-mortality relationship across 4 hospital types. Results were consistent after excluding transferred patients, restricting to patients with acute respiratory failure and mechanical ventilation, and using alternative strain metrics. LIMITATION: Residual confounding. CONCLUSION: Comparably detrimental relationships between COVID-19 caseload and survival were seen across all hospital types, including highly advanced centers, and well beyond the pandemic's learning curve. These lessons from the pandemic heighten the need to minimize caseload surges and their effects across all hospital types during public health and staffing crises. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center.

Standardized Definitions for Cardiogenic Shock Research and Mechanical Circulatory Support Devices: Scientific Expert Panel From the Shock Academic Research Consortium (SHARC).

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety.

The Roles of Venopulmonary Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Concise definitive review of the use of venopulmonary arterial extracorporeal membrane oxygenation (V-PA ECMO) support in patients with cardiopulmonary failure. DATA SOURCES: Original investigations identified through a PubMed search with search terms "percutaneous right ventricular assist device," "oxy-RVAD," "V-PA ECMO," and "veno-pulmonary arterial ECMO" were reviewed and evaluated for relevance. STUDY SELECTION: Studies that included more than three patients supported with V-PA ECMO were included. DATA EXTRACTION: Clinically relevant data from included studies, including patient-important outcomes, were summarized and discussed. DATA SYNTHESIS: We identified four groups of patients where V-PA ECMO has been studied: acute respiratory distress syndrome, right ventricular dysfunction after left ventricular assist device placement, bridge to lung transplantation, and pulmonary embolism. Most identified works are small, single center, and retrospective in nature, precluding definitive conclusions regarding the efficacy of V-PA ECMO. There have been no clinical trials evaluating the efficacy of V-PA ECMO for any indication. CONCLUSIONS: V-PA ECMO is a promising form of extracorporeal support for patients with right ventricular dysfunction. Future work should focus on identifying the optimal timing and populations for the use of V-PA ECMO.

Association Between Inability to Stand at ICU Discharge and Readmission: A Historical Cohort Study.

OBJECTIVES: The aim of this study was to determine if being unable to stand at ICU discharge was associated with an increased probability of ICU readmission. DESIGN: A multicenter retrospective cohort study was conducted using the Toronto Intensive Care Observational Registry (iCORE) project. SETTING: Nine tertiary academic ICUs in Toronto, Canada, affiliated with the University of Toronto. PATIENTS: All patients admitted to ICUs participating in iCORE from September 2014 to January 2020 were included. Patients had to be mechanically ventilated for more than 4 hours to be included in iCORE. Exclusion criteria were death during the initial ICU stay, transfer to another institution not included in iCORE at ICU discharge, and a short ICU stay defined as less than 2 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure in this study was the inability of the patient to stand at ICU discharge, documented daily in the database within the ICU Mobility Scale. The primary outcome of this study was readmission to the ICU. After adjusting for potential confounders, being unable to stand at ICU discharge was associated with increased odds of readmission (odds ratio, 1.85; 95% CI, 1.31-2.62; p < 0.001). CONCLUSIONS: In patients with an ICU stay of 2 days or more, being unable to stand at ICU discharge is associated with increased odds of readmission to the ICU.

Epidemiology, ventilation management and outcomes of COVID-19 ARDS patients versus patients with ARDS due to pneumonia in the Pre-COVID era.

BACKGROUND: Ventilation management may differ between COVID-19 ARDS (COVID-ARDS) patients and patients with pre-COVID ARDS (CLASSIC-ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC-ARDS also exist in COVID-ARDS. METHODS: Individual patient data analysis of COVID-ARDS and CLASSIC-ARDS patients in six observational studies of ventilation, four in the COVID-19 pandemic and two pre-pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator-free days and alive (VFD-60) at day 60. RESULTS: This analysis included 6702 COVID-ARDS patients and 1415 CLASSIC-ARDS patients. COVID-ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60-day mortality and less VFD-60 in both groups. Higher PEEP had an association with less VFD-60, but only in COVID-ARDS patients. CONCLUSIONS: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID-ARDS and CLASSIC-ARDS. TRIAL REGISTRATION: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.

Echocardiographic Findings in Critically Ill COVID-19 Patients Treated With and Without Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe echocardiographic findings among mechanically ventilated patients with COVID-19 acute respiratory distress syndrome, comparing those with and without venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Single-center, retrospective cohort study. SETTING: Intensive care unit (ICU) of a quaternary academic center. PARTICIPANTS: Patients with COVID-19 admitted between March 2020 and June 2021 receiving mechanical ventilation, with an echocardiogram within 72 hours of admission. INTERVENTIONS: Admission and follow-up echocardiograms during ICU stay. MEASUREMENTS: Patient characteristics and echocardiographic findings were analyzed. Mortality odds ratio (OR) for right ventricular (RV) systolic dysfunction and acute cor pulmonale (ACP) was calculated. MAIN RESULTS: Among 242 patients, 145 (60%) received VV ECMO. Median (IQR) PaO2/FiO2 was 76 (65-95) and 98 (85-140) in ECMO and non-ECMO patients, respectively (p ≤ 0.001). Initial echocardiograms showed no significant differences in left ventricular systolic dysfunction (10% v 15 %, p = 0.31) and RV systolic dysfunction (38% v. 27%, p = 0.27) between ECMO and non-ECMO patients. ACP was more frequent in the ECMO group at baseline (41% v. 26 %, p = 0.02). During the ICU stay, patients on ECMO exhibited a higher prevalence of RV systolic dysfunction (55% v 34%, p = 0.001) and ACP (51% v 26%, p = 0.002). RV systolic dysfunction (OR 1.99; 95% CI 1.09-3.63) and ACP (OR 2.95; 95% CI 1.55-5.62) on the follow-up echocardiograms were associated with higher odds of ICU mortality. CONCLUSIONS: The prevalence of echocardiographic abnormalities, in particular RV dysfunction, was frequent among patients with COVID-19 receiving VV ECMO support and was associated with worse clinical outcomes.

Estimating the attributable fraction of mortality from acute respiratory distress syndrome to inform enrichment in future randomised clinical trials.

BACKGROUND: Efficiency of randomised clinical trials of acute respiratory distress syndrome (ARDS) depends on the fraction of deaths attributable to ARDS (AFARDS) to which interventions are targeted. Estimates of AFARDS in subpopulations of ARDS could improve design of ARDS trials. METHODS: We performed a matched case-control study using the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE cohort. Primary outcome was intensive care unit mortality. We used nearest neighbour propensity score matching without replacement to match ARDS to non-ARDS populations. We derived two separate AFARDS estimates by matching patients with ARDS to patients with non-acute hypoxaemic respiratory failure (non-AHRF) and to patients with AHRF with unilateral infiltrates only (AHRF-UL). We also estimated AFARDS in subgroups based on severity of hypoxaemia, number of lung quadrants involved and hyperinflammatory versus hypoinflammatory phenotypes. Additionally, we derived AFAHRF estimates by matching patients with AHRF to non-AHRF controls, and AFAHRF-UL estimates by matching patients with AHRF-UL to non-AHRF controls. RESULTS: Estimated AFARDS was 20.9% (95% CI 10.5% to 31.4%) when compared with AHRF-UL controls and 38.0% (95% CI 34.4% to 41.6%) compared with non-AHRF controls. Within subgroups, estimates for AFARDS compared with AHRF-UL controls were highest in patients with severe hypoxaemia (41.1% (95% CI 25.2% to 57.1%)), in those with four quadrant involvement on chest radiography (28.9% (95% CI 13.4% to 44.3%)) and in the hyperinflammatory subphenotype (26.8% (95% CI 6.9% to 46.7%)). Estimated AFAHRF was 33.8% (95% CI 30.5% to 37.1%) compared with non-AHRF controls. Estimated AFAHRF-UL was 21.3% (95% CI 312.8% to 29.7%) compared with non-AHRF controls. CONCLUSIONS: Overall AFARDS mean values were between 20.9% and 38.0%, with higher AFARDS seen with severe hypoxaemia, four quadrant involvement on chest radiography and hyperinflammatory ARDS.

Limiting Dynamic Driving Pressure in Patients Requiring Mechanical Ventilation.

OBJECTIVES: Previous studies reported an association between higher driving pressure (∆P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on ∆P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic ∆P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation. DESIGN: For this comparative effectiveness study, we emulated pragmatic clinical trials using data from the Toronto Intensive Care Observational Registry recorded between April 2014 and August 2021. The per-protocol effect of the interventions was estimated using the parametric g-formula, a method that controls for baseline and time-varying confounding, as well as for competing events in the analysis of longitudinal exposures. SETTING: Nine ICUs from seven University of Toronto-affiliated hospitals. PATIENTS: Adult patients (≥18 yr) requiring greater than or equal to 24 hours of mechanical ventilation. INTERVENTIONS: Receipt of a ventilation strategy that limited either daily static or dynamic ∆P less than or equal to 15 cm H 2 O compared with usual care. MEASUREMENTS AND MAIN RESULTS: Among the 12,865 eligible patients, 4,468 of (35%) were ventilated with dynamic ∆P greater than 15 cm H 2 O at baseline. Mortality under usual care was 20.1% (95% CI, 19.4-20.9%). Limiting daily dynamic ∆P less than or equal to 15 cm H 2 O in addition to traditional lung-protective ventilation reduced adherence-adjusted mortality to 18.1% (95% CI, 17.5-18.9%) (risk ratio, 0.90; 95% CI, 0.89-0.92). In further analyses, this effect was most pronounced for early and sustained interventions. Static ∆P at baseline were recorded in only 2,473 patients but similar effects were observed. Conversely, strict interventions on tidal volumes or peak inspiratory pressures, irrespective of ∆P, did not reduce mortality compared with usual care. CONCLUSIONS: Limiting either static or dynamic ∆P can further reduce the mortality of patients requiring mechanical ventilation.

Patients with fulminant myocarditis supported with veno-arterial extracorporeal membrane oxygenation: a systematic review and meta-analysis of short-term mortality and impact of risk factors.

Fulminant myocarditis (FM) may lead to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Results of effectiveness studies of VA-ECMO have been contradictory. We evaluated the aggregate short-term mortality after VA-ECMO and predictive factors in patients with FM. We systematically searched in electronic databases (February 2022) to identify studies evaluating short-term mortality (defined as mortality at 30 days or in-hospital) after VA-ECMO support for FM. We included studies with 5 or more patients published after 2009. We assessed the quality of the evidence using the QUIPS and GRADE tools. Mortality was pooled using random effect models. We performed meta-regression to explore heterogeneity based on a priori defined factors. We included 54 observational studies encompassing 2388 FM patients supported with VA-ECMO. Median age was 41 years (25th to 75th percentile 37-47), and 50% were female. The pooled short-term mortality was 35% (95% CI 29-40%, I2 = 69%; moderate certainty). By meta-regression, studies with younger populations showed lower mortality. Female sex, receiving a biopsy, cardiac arrest, left ventricular unloading, and earlier recruitment time frame, did not explain heterogeneity. These results remained consistent regardless of continent and the risk of bias category. In individual studies, low pH value, high lactate, absence of functional cardiac recovery on ECMO, increased burden of malignant arrhythmia, high peak coronary markers, and IVIG use were identified as independent predictors of mortality. When conventional therapies have failed, especially in younger patients, cardiopulmonary support with VA-ECMO should be considered in the treatment of severe FM.

Early Changes in Arterial Partial Pressure of Carbon Dioxide and Blood Pressure After Starting Extracorporeal Membrane Oxygenation in Children: Extracorporeal Life Support Organization Database Study of Neurologic Complications.

OBJECTIVE: Neurologic complications in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) are common and lead to morbidity and mortality; however, few modifiable factors are known. DESIGN: Retrospective study of the Extracorporeal Life Support Organization registry (2010-2019). SETTING: Multicenter international database. PATIENTS: Pediatric patients receiving ECMO (2010-2019) for all indications and any mode of support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We investigated if early relative change in Pa co2 or mean arterial blood pressure (MAP) soon after starting ECMO was associated with neurologic complications. The primary outcome of neurologic complications was defined as a report of seizures, central nervous system infarction or hemorrhage, or brain death. All-cause mortality (including brain death) was used as a secondary outcome.Out of 7,270 patients, 15.6% had neurologic complications. Neurologic complications increased when the relative Pa co2 decreased by greater than 50% (18.4%) or 30-50% (16.5%) versus those who had a minimal change (13.9%, p < 0.01 and p = 0.046). When the relative MAP increased greater than 50%, the rate of neurologic complications was 16.9% versus 13.1% those with minimal change ( p = 0.007). In a multivariable model adjusting for confounders, a relative decrease in Pa co2 greater than 30% was independently associated with greater odds of neurologic complication (odds ratio [OR], 1.25; 95% CI, 1.07-1.46; p = 0.005). Within this group, with a relative decrease in Pa co2 greater than 30%, the effects of increased relative MAP increased neurologic complications (0.05% per BP Percentile; 95% CI, 0.001-0.11; p = 0.05). CONCLUSIONS: In pediatric patients, a large decrease in Pa co2 and increase in MAP following ECMO initiation are both associated with neurologic complications. Future research focusing on managing these issues carefully soon after ECMO deployment can potentially help to reduce neurologic complications.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation: a prospective observational study.

PURPOSE: Descriptive information on referral patterns and short-term outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation (ECMO) is lacking. METHODS: We conducted a prospective single-centre observational cohort study of ECMO referrals to Toronto General Hospital (receiving hospital) for severe respiratory failure (COVID-19 and non-COVID-19), between 1 December 2019 and 30 November 2020. Data related to the referral, the referral decision, and reasons for refusal were collected. Reasons for refusal were grouped into three mutually exclusive categories selected a priori: "too sick now," "too sick before," and "not sick enough." In declined referrals, referring physicians were surveyed to collect patient outcome on day 7 after the referral. The primary study endpoints were referral outcome (accepted/declined) and patient outcome (alive/deceased). RESULTS: A total of 193 referrals were included; 73% were declined for transfer. Referral outcome was influenced by age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95 to 0.96; P < 0.01) and involvement of other members of the ECMO team in the discussion (OR, 4.42; 95% CI, 1.28 to 15.2; P < 0.01). Patient outcomes were missing in 46 (24%) referrals (inability to locate the referring physician or the referring physician being unable to recall the outcome). Using available data (95 declined and 52 accepted referrals; n = 147), survival to day 7 was 49% for declined referrals (35% for patients deemed "too sick now," 53% for "too sick before," 100% for "not sick enough," and 50% for reason for refusal not reported) and 98% for transferred patients. Sensitivity analysis setting missing outcomes to directional extreme values retained robustness of survival probabilities. CONCLUSION: Nearly half of the patients declined for ECMO consideration were alive on day 7. More information on patient trajectory and long-term outcomes in declined referrals is needed to refine selection criteria.

RéSUMé: OBJECTIF: On manque d'informations descriptives sur les schémas de références et les devenirs à court terme des patient·es atteint·es d'insuffisance respiratoire n'ayant pas pu recevoir une oxygénation par membrane extracorporelle (ECMO). MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective monocentrique sur les références vers l'ECMO à l'Hôpital général de Toronto (hôpital d'accueil) pour insuffisance respiratoire grave (COVID-19 et non-COVID-19), entre le 1er décembre 2019 et le 30 novembre 2020. Les données relatives à la référence, à la décision de référence et aux motifs du refus ont été recueillies. Les motifs de refus ont été regroupés en trois catégories mutuellement exclusives sélectionnées a priori : « Trop malade maintenant ¼, « Trop malade avant ¼ et « Pas assez malade ¼. En ce qui concerne les références refusées, un sondage envoyé aux médecins traitant·es avait pour objectif de recueillir les devenirs des patient·es le jour 7 suivant la référence. Les critères d'évaluation principaux de l'étude étaient le résultat de la référence (accepté/refusé) et le devenir des patient·es (vivant·e/décédé·e). RéSULTATS: Au total, 193 références ont été incluses; le transfert a été refusé dans 73 % des cas. L'acceptation ou le refus de la référence était influencé par l'âge (rapport de cotes [RC], 0,97; intervalle de confiance [IC] à 95 %, 0,95 à 0,96; P < 0,01) et la participation d'autres membres de l'équipe ECMO à la discussion (RC, 4,42; IC 95 %, 1,28 à 15,2; P < 0,01). Les devenirs des patient·es étaient manquants pour 46 (24 %) des personnes référées (incapacité de localiser les médecins traitant·es ou incapacité des médecins de se souvenir du devenir). À l'aide des données disponibles (95 références refusées et 52 références acceptées; n = 147), la survie jusqu'au jour 7 était de 49 % pour les références refusées (35 % pour la patientèle jugée « trop malade maintenant ¼, 53 % pour celle « trop malade avant ¼, 100 % pour celle « pas assez malade ¼ et 50 % pour les cas où la raison du refus n'était pas déclarée) et 98 % pour les patient·es transféré·es. L'analyse de sensibilité établissant les résultats manquants à des valeurs extrêmes directionnelles a conservé la robustesse des probabilités de survie. CONCLUSION: Près de la moitié des patient·es pour lesquel·les un traitement sous ECMO a été refusé étaient en vie au jour 7. Davantage d'informations concernant la trajectoire et les devenirs à long terme des patient·es refusé·es sont nécessaires pour parfaire les critères de sélection.

The care of critically ill adults with COVID-19 in Ontario pediatric intensive care units.

PURPOSE: To describe and review the experience of two pediatric intensive care units (PICUs) in Ontario, Canada, adapting and providing care to critically ill adults during the COVID-19 pandemic. CLINICAL FEATURES: At a time of extreme pressure to adult intensive care unit (ICU) capacity, two PICUs provided care to critically ill adults with COVID-19 pneumonia. Substantial yet rapid planning was required to facilitate safe delivery of critical care to adult patients while maintaining PICU services, including thoughtful development of care pathways and patient selection. To prepare clinical staff, several communication strategies, knowledge translation, skill consolidation, and system-adaptation mechanisms were developed. There was iterative adaptation of operational processes, including staffing models, specialist consultation, and the pharmacy. Care provided by the interprofessional teams was reoriented as appropriate to the needs of critically ill adults in close collaboration with adult ICU teams. Forty-one adults were admitted to the two PICUs over a 12-week period. In total, 36 patients (88%) received invasive ventilation, eight patients (20%) were supported with venovenous extracorporeal membrane oxygenation, and six patients (15%) received continuous renal replacement therapy. Four died in the PICU during this period. Feedback from staff included anxiety around reorienting practice to the care of critically ill adults, physical exhaustion, and psychological distress. Importantly, staff also reported a renewed sense of purpose with participation in the program. CONCLUSION: Though challenging, the experience has provided opportunity to enhance collaboration with partner institutions and improve the care of older children and adolescents in the PICU.

RéSUMé: OBJECTIF: Nous avions pour objectif de décrire et examiner l'expérience de deux unités de soins intensifs pédiatriques (USIP) en Ontario, au Canada, qui se sont adaptées et ont fourni des soins aux adultes gravement malades pendant la pandémie de COVID-19. CARACTéRISTIQUES CLINIQUES: À l'époque où la capacité des unités de soins intensifs (USI) pour adultes était extrêmement sollicitée, deux USIP ont prodigué des soins à des adultes gravement malades souffrant de pneumonie liée à la COVID-19. Une planification substantielle mais rapide a été nécessaire pour faciliter la prestation sécuritaire de soins intensifs à une patientèle adulte tout en maintenant les services de l'USIP, y compris l'élaboration réfléchie des trajectoires de soins et la sélection de la patientèle. Pour préparer le personnel clinique, plusieurs stratégies de communication, d'application des connaissances, de consolidation des compétences et de mécanismes d'adaptation du système ont été élaborées. Il y a eu une adaptation progressive des processus opérationnels, y compris des modèles de dotation, des consultations de spécialistes et de la pharmacie. Les soins fournis par les équipes interprofessionnelles ont été réorientés en fonction des besoins des adultes gravement malades en étroite collaboration avec les équipes adultes de soins intensifs. Quarante et une personnes adultes ont été admises dans les deux unités de soins intensifs pédiatriques sur une période de 12 semaines. Au total, 36 adultes (88 %) ont bénéficié d'une ventilation invasive, huit personnes (20 %) ont reçu une oxygénation par membrane extracorporelle veino-veineuse, et six (15 %) ont reçu un traitement substitutif de l'insuffisance rénale en continu. Quatre personnes sont décédées à l'USIP au cours de cette période. Les commentaires du personnel comprenaient de l'anxiété liée à la réorientation de leur pratique vers des soins à des adultes gravement malades, l'épuisement physique et la détresse psychologique. Fait important, le personnel a également signalé un regain de motivation lié à la participation de leur USIP à ce programme. CONCLUSION: Bien que difficile, l'expérience a permis d'améliorer la collaboration avec les établissements partenaires et d'améliorer les soins aux enfants plus âgé·es et aux adolescent·es de l'USIP.

Extracorporeal membrane oxygenation for COVID-19: evolving outcomes from the international Extracorporeal Life Support Organization Registry.

BACKGROUND: Over the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date. METHODS: We retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres-ie, those using ECMO support for COVID-19 throughout 2020-we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups. FINDINGS: In 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1-39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0-53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4-62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70-0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17-1·73]). INTERPRETATION: Mortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers. FUNDING: None.

Prognostic factors for development of acute respiratory distress syndrome following traumatic injury: a systematic review and meta-analysis.

BACKGROUND: Our purpose was to summarise the prognostic associations between various clinical risk factors and development of acute respiratory distress syndrome (ARDS) following traumatic injury. METHODS: We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with development of post-traumatic ARDS, as defined by either the American-European Consensus Conference or Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS (Quality in Prognosis Studies) tool and certainty of findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. RESULTS: We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with development of post-traumatic ARDS (adjusted OR 1.19, 95% CI 1.15-1.24 for each additional litre of crystalloid administered within the first 6 h after injury; high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic White race, blunt mechanism of injury, presence of head injury, pulmonary contusion or rib fracture and increasing chest injury severity. CONCLUSIONS: We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform development of risk stratification tools.

Complications Associated With Venovenous Extracorporeal Membrane Oxygenation-What Can Go Wrong?

OBJECTIVES: Despite increasing use and promising outcomes, venovenous extracorporeal membrane oxygenation (V-V ECMO) introduces the risk of a number of complications across the spectrum of ECMO care. This narrative review describes the variety of short- and long-term complications that can occur during treatment with ECMO and how patient selection and management decisions may influence the risk of these complications. DATA SOURCES: English language articles were identified in PubMed using phrases related to V-V ECMO, acute respiratory distress syndrome, severe respiratory failure, and complications. STUDY SELECTION: Original research, review articles, commentaries, and published guidelines from the Extracorporeal Life support Organization were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: Selecting patients for V-V ECMO exposes the patient to a number of complications. Adequate knowledge of these risks is needed to weigh them against the anticipated benefit of treatment. Timing of ECMO initiation and transfer to centers capable of providing ECMO affect patient outcomes. Choosing a configuration that insufficiently addresses the patient's physiologic deficit leads to consequences of inadequate physiologic support. Suboptimal mechanical ventilator management during ECMO may lead to worsening lung injury, delayed lung recovery, or ventilator-associated pneumonia. Premature decannulation from ECMO as lungs recover can lead to clinical worsening, and delayed decannulation can prolong exposure to complications unnecessarily. Short-term complications include bleeding, thrombosis, and hemolysis, renal and neurologic injury, concomitant infections, and technical and mechanical problems. Long-term complications reflect the physical, functional, and neurologic sequelae of critical illness. ECMO can introduce ethical and emotional challenges, particularly when bridging strategies fail. CONCLUSIONS: V-V ECMO is associated with a number of complications. ECMO selection, timing of initiation, and management decisions impact the presence and severity of these potential harms.

Monitoring during extracorporeal membrane oxygenation.

PURPOSE OF REVIEW: Extracorporeal membrane oxygenation (ECMO) offers advanced mechanical support to patients with severe acute respiratory and/or cardiac failure. Ensuring an adequate therapeutic approach as well as prevention of ECMO-associated complications, by means of timely liberation, forms an essential part of standard ECMO care and is only achievable through continuous monitoring and evaluation. This review focus on the cardiorespiratory monitoring tools that can be used to assess and titrate adequacy of ECMO therapy; as well as methods to assess readiness to wean and/or discontinue ECMO support. RECENT FINDINGS: Surrogates of tissue perfusion and near infrared spectroscopy are not standards of care but may provide useful information in select patients. Echocardiography allows to determine cannulas position, evaluate cardiac structures, and function, and diagnose complications. Respiratory monitoring is mandatory to achieve lung protective ventilation and identify early lung recovery, surrogate measurements of respiratory effort and ECMO derived parameters are invaluable in optimally managing ECMO patients. SUMMARY: Novel applications of existing monitoring modalities alongside evolving technological advances enable the advanced monitoring required for safe delivery of ECMO. Liberation trials are necessary to minimize time sensitive ECMO related complications; however, these have yet to be standardized.

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. METHODS: We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. RESULTS: Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8-52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. CONCLUSIONS: The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial.

BACKGROUND: Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF. METHODS: In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort. RESULTS: Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets. CONCLUSION: Respiratory effort is frequently absent  under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy. TRIAL REGISTRATION: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).