Automated detection and quantification of reverse triggering effort under mechanical ventilation

Reverse triggering (RT) is a dyssynchrony defined by a respiratory muscle contraction following a passive mechanical insufflation. It is potentially harmful for the lung and the diaphragm, but its detection is challenging. Magnitude of effort generated by RT is currently unknown. Our objective was to validate supervised methods for automatic detection of RT using only airway pressure (Paw) and flow. A secondary objective was to describe the magnitude of the efforts generated during RT. We developed algorithms for detection of RT using Paw and flow waveforms. Experts having Paw, flow and esophageal pressure (Pes) assessed automatic detection accuracy by comparison against visual assessment. Muscular pressure (Pmus) was measured from Pes during RT, triggered breaths and ineffective efforts. Tracings from 20 hypoxemic patients were used (mean age 65 ± 12 years, 65% male, ICU survival 75%). RT was present in 24% of the breaths ranging from 0 (patients paralyzed or in pressure support ventilation) to 93.3%. Automatic detection accuracy was 95.5%: sensitivity 83.1%, specificity 99.4%, positive predictive value 97.6%, negative predictive value 95.0% and kappa index of 0.87. Pmus of RT ranged from 1.3 to 36.8 cmH0, with a median of 8.7 cmH0. RT with breath stacking had the highest levels of Pmus, and RTs with no breath stacking were of similar magnitude than pressure support breaths. An automated detection tool using airway pressure and flow can diagnose reverse triggering with excellent accuracy. RT generates a median Pmus of 9 cmHO with important variability between and within patients. BEARDS, NCT03447288

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Stratégies d'oxygénation non invasives dans l'insuffisance respiratoire aiguë hypoxémique des patients immunodéprimés

Acute respiratory failure is the leading cause of intensive care unit admission in immunocompromised patients. Despite therapeutic progresses, their mortality rate remains intolerably high when invasive mechanical ventilation is needed. Noninvasive ventilation (NIV) is currently recommended as first-line treatment in this setting given the mortality reduction reported in old randomized trials. Recently, benefits of NIV have been challenged by large sample sized trials. However, NIV settings may have been suboptimal in these studies and consequently dampened its efficacy. Moreover, high-flow nasal cannula oxygen therapy (HFOT), a more recent oxygenation technique, was associated with promising results in various clinical settings. This project aims at conducting a randomized multicenter controlled trial comparing optimized NIV with HFOT in critically ill immunocompromised patients with acute respiratory failure. First, we validated the research hypothesis, the primary outcome, the sample size calculation and the recruitment rate of the project by means of a pilot retrospective study. Then, the NIV protocol was built based on a systematic review of literature comparing the efficacy of previously published NIV protocols. Afterwards, we identified factors independently associated with NIV failure in hypoxemic patients to identify respiratory parameters to monitor during NIV. Next, we determined mechanisms leading to physiological effects of HFOT in a bench study and a study on healthy volunteers. Last, we chose the most reliable method to estimate inspired oxygen fraction under oxygen mask in a study comparing the different existing methods in order to refine inclusion criteria of the project. All in all, these five above-mentioned preliminary studies enabled to conduct a prospective multicenter randomized trial in 30 centers in France and in Italy aiming at comparing effects of HFOT alone at 60 L/min to its association with optimized NIV (applied at least 12 hours a day with a positive end-expiratory pressure of at least 8 cmH2O and an expired tidal volume lower than 8 ml/kg of predicted body weight) on mortality at day 28 in 300 immunocompromised patients admitted to the ICU for acute respiratory failure.L’insuffisance respiratoire aiguë est la première cause d’admission en Réanimation des patients immunodéprimés. Malgré les progrès thérapeutiques, leur mortalité reste très élevée en cas de recours à la ventilation mécanique invasive. La ventilation non invasive (VNI) est recommandée comme traitement de première ligne en raison de la diminution de mortalité rapportée dans les études randomisées anciennes. Récemment, ces bénéfices ont été remis en cause par des essais de plus grande ampleur. Toutefois, il est possible que les réglages de la VNI n’aient pas été optimaux dans ces études, diminuant ainsi son efficacité. Par ailleurs, l’oxygénothérapie nasale à haut débit (OHD) est une technique d’oxygénation récente avec des résultats prometteurs dans de nombreuses situations cliniques. L’objectif final de ce projet était de conduire une étude prospective randomisée multicentrique comparant la VNI avec des réglages optimisés à l’OHD chez les patients immunodéprimés admis en Réanimation pour une insuffisance respiratoire aiguë. Nous avons tout d’abord validé l’hypothèse de recherche du projet, son objectif principal, les calculs d’effectif et le taux de recrutement au moyen d’une étude pilote rétrospective. Puis nous avons élaboré le protocole de VNI à partir d’une revue systématique de la littérature comparant l’efficacité des différents protocoles de VNI publiés. Ensuite, nous avons analysé les facteurs de risque d’échec de la VNI chez les patients hypoxémiques afin d’identifier les paramètres physiologiques respiratoires à surveiller chez les patients traités par VNI. En outre, nous avons identifié les mécanismes responsables des effets physiologiques de l’OHD au moyen d’une étude sur banc puis chez des volontaires sains. Enfin, nous avons sélectionné la méthode d’estimation de la fraction inspirée en dioxygène mesurée au masque la plus fiable en comparant les différentes méthodes existantes dans le but d’affiner les critères d’inclusion du projet. Ces cinq études préliminaires nous ont permis de conduire une étude prospective randomisée dans 30 centres en France et en Italie dans le but de comparer les effets de l’OHD seule délivrée à 60 L/min à son association à la VNI intensive (administrée au moins 12 heures par jour avec une pression expiratoire positive d’au moins 8 cmH2O et un volume courant expiré inférieur à 8 ml/kg de poids prédit) sur la mortalité à 28 jours chez 300 patients immunodéprimés admis en Réanimation pour une insuffisance respiratoire aiguë

Noninvasive oxgenation strategies in immunocompromised patients with acute hypoxemic respiratory failure.

L’insuffisance respiratoire aiguë est la première cause d’admission en Réanimation des patients immunodéprimés. Malgré les progrès thérapeutiques, leur mortalité reste très élevée en cas de recours à la ventilation mécanique invasive. La ventilation non invasive (VNI) est recommandée comme traitement de première ligne en raison de la diminution de mortalité rapportée dans les études randomisées anciennes. Récemment, ces bénéfices ont été remis en cause par des essais de plus grande ampleur. Toutefois, il est possible que les réglages de la VNI n’aient pas été optimaux dans ces études, diminuant ainsi son efficacité. Par ailleurs, l’oxygénothérapie nasale à haut débit (OHD) est une technique d’oxygénation récente avec des résultats prometteurs dans de nombreuses situations cliniques. L’objectif final de ce projet était de conduire une étude prospective randomisée multicentrique comparant la VNI avec des réglages optimisés à l’OHD chez les patients immunodéprimés admis en Réanimation pour une insuffisance respiratoire aiguë. Nous avons tout d’abord validé l’hypothèse de recherche du projet, son objectif principal, les calculs d’effectif et le taux de recrutement au moyen d’une étude pilote rétrospective. Puis nous avons élaboré le protocole de VNI à partir d’une revue systématique de la littérature comparant l’efficacité des différents protocoles de VNI publiés. Ensuite, nous avons analysé les facteurs de risque d’échec de la VNI chez les patients hypoxémiques afin d’identifier les paramètres physiologiques respiratoires à surveiller chez les patients traités par VNI. En outre, nous avons identifié les mécanismes responsables des effets physiologiques de l’OHD au moyen d’une étude sur banc puis chez des volontaires sains. Enfin, nous avons sélectionné la méthode d’estimation de la fraction inspirée en dioxygène mesurée au masque la plus fiable en comparant les différentes méthodes existantes dans le but d’affiner les critères d’inclusion du projet. Ces cinq études préliminaires nous ont permis de conduire une étude prospective randomisée dans 30 centres en France et en Italie dans le but de comparer les effets de l’OHD seule délivrée à 60 L/min à son association à la VNI intensive (administrée au moins 12 heures par jour avec une pression expiratoire positive d’au moins 8 cmH2O et un volume courant expiré inférieur à 8 ml/kg de poids prédit) sur la mortalité à 28 jours chez 300 patients immunodéprimés admis en Réanimation pour une insuffisance respiratoire aiguë.Acute respiratory failure is the leading cause of intensive care unit admission in immunocompromised patients. Despite therapeutic progresses, their mortality rate remains intolerably high when invasive mechanical ventilation is needed. Noninvasive ventilation (NIV) is currently recommended as first-line treatment in this setting given the mortality reduction reported in old randomized trials. Recently, benefits of NIV have been challenged by large sample sized trials. However, NIV settings may have been suboptimal in these studies and consequently dampened its efficacy. Moreover, high-flow nasal cannula oxygen therapy (HFOT), a more recent oxygenation technique, was associated with promising results in various clinical settings. This project aims at conducting a randomized multicenter controlled trial comparing optimized NIV with HFOT in critically ill immunocompromised patients with acute respiratory failure. First, we validated the research hypothesis, the primary outcome, the sample size calculation and the recruitment rate of the project by means of a pilot retrospective study. Then, the NIV protocol was built based on a systematic review of literature comparing the efficacy of previously published NIV protocols. Afterwards, we identified factors independently associated with NIV failure in hypoxemic patients to identify respiratory parameters to monitor during NIV. Next, we determined mechanisms leading to physiological effects of HFOT in a bench study and a study on healthy volunteers. Last, we chose the most reliable method to estimate inspired oxygen fraction under oxygen mask in a study comparing the different existing methods in order to refine inclusion criteria of the project. All in all, these five above-mentioned preliminary studies enabled to conduct a prospective multicenter randomized trial in 30 centers in France and in Italy aiming at comparing effects of HFOT alone at 60 L/min to its association with optimized NIV (applied at least 12 hours a day with a positive end-expiratory pressure of at least 8 cmH2O and an expired tidal volume lower than 8 ml/kg of predicted body weight) on mortality at day 28 in 300 immunocompromised patients admitted to the ICU for acute respiratory failure

Early Identification and Diagnostic Approach in Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is a life-threatening condition defined by the acute onset of severe hypoxemia with bilateral pulmonary infiltrates, in the absence of a predominant cardiac involvement. Whereas the current Berlin definition was proposed in 2012 and mainly focused on intubated patients under invasive mechanical ventilation, the recent COVID-19 pandemic has highlighted the need for a more comprehensive definition of ARDS including patients treated with noninvasive oxygenation strategies, especially high-flow nasal oxygen therapy, and fulfilling all other diagnostic criteria. Early identification of ARDS in patients breathing spontaneously may allow assessment of earlier initiation of pharmacological and non-pharmacological treatments. In the same way, accurate identification of the ARDS etiology is obviously of paramount importance for early initiation of adequate treatment. The precise underlying etiological diagnostic (bacterial, viral, fungal, immune, malignant, drug-induced, etc.) as well as the diagnostic approach have been understudied in the literature. To date, no clinical practice guidelines have recommended structured diagnostic work-up in ARDS patients. In addition to lung-protective ventilation with the aim of preventing worsening lung injury, specific treatment of the underlying cause has a central role to improve outcomes. In this review, we discuss early identification of ARDS in non-intubated patients breathing spontaneously and propose a structured diagnosis work-up

High-flow nasal cannula oxygen therapy in acute hypoxemic respiratory failure and COVID-19-related respiratory failure

Although standard oxygen face masks are first-line therapy for patients with acute hypoxemic respiratory failure, high-flow nasal cannula oxygen therapy has gained major popularity in intensive care units. The physiological effects of high-flow oxygen counterbalance the physiological consequences of acute hypoxemic respiratory failure by lessening the deleterious effects of intense and prolonged inspiratory efforts generated by patients. Its simplicity of application for physicians and nurses and its comfort for patients are other arguments for its use in this setting. Although clinical studies have reported a decreased risk of intubation with high-flow oxygen compared with standard oxygen, its survival benefit is uncertain. A more precise definition of acute hypoxemic respiratory failure, including a classification of severity based on oxygenation levels, is needed to better compare the efficiencies of different non-invasive oxygenation support methods (standard oxygen, high-flow oxygen, and non-invasive ventilation). Additionally, the respective role of each non-invasive oxygenation support method needs to be established through further clinical trials in acute hypoxemic respiratory failure, especially in severe forms