The Predictive Validity of the Berlin Definition of Acute Respiratory Distress Syndrome for Patients With COVID-19-Related Respiratory Failure Treated With High-Flow Nasal Oxygen: A Multicenter, Prospective Cohort Study.

OBJECTIVES: The Berlin definition of acute respiratory distress syndrome (ARDS) was constructed for patients receiving invasive mechanical ventilation (IMV) with consideration given to issues related to reliability, feasibility, and validity. Notwithstanding, patients with acute respiratory failure (ARF) may be treated with high-flow nasal oxygen (HFNO) and may not fall within the scope of the original definition. We aimed to evaluate the predictive validity of the Berlin definition in HFNO-treated patients with COVID-19-related respiratory failure who otherwise met ARDS criteria. DESIGN: Multicenter, prospective cohort study. SETTING: Five ICUs of five centers in Argentina from March 2020 to September 2021. PATIENTS: We consecutively included HFNO-treated patients older than 18 years with confirmed COVID-19-related ARF, a Pa o2 /F io2 of less than 300 mm Hg, bilateral infiltrates on imaging, and worsening respiratory symptoms for less than 1 week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the predictive validity of mortality at day 28 using the area under the receiver operating characteristics curve (AUC), compared the predictive validity across subgroups, and characterized relevant clinical outcomes. We screened 1,231 patients and included 696 ARDS patients [30 (4%) mild, 380 (55%) moderate, and 286 (41%) severe]. For the study cohort, the AUC for mortality at day 28 was 0.606 (95% CI, 0.561-0.651) with the AUC for subgroups being similar to that of the overall cohort. Two hundred fifty-six patients (37%) received IMV. By day 28, 142 patients (21%) had died, of whom 81 (57%) had severe ARDS. Mortality occurred primarily in patients who were transitioned to IMV. CONCLUSIONS: The predictive validity of the Berlin ARDS definition was similar for HFNO-treated patients as compared with the original population of invasively ventilated patients. Our findings support the extension of the Berlin definition to HFNO-treated patients with ARDS.

A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial.

BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901.

Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary edema.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been widely used to alleviate signs and symptoms of respiratory distress due to cardiogenic pulmonary edema. NPPV prevents alveolar collapse and helps redistribute intra-alveolar fluid, improving pulmonary compliance and reducing the pressure of breathing. OBJECTIVES: To determine the effectiveness and safety of NPPV in the treatment of adult patients with cardiogenic pulmonary edema. SEARCH STRATEGY: We undertook a comprehensive search of the following databases in April 2005: CENTRAL, MEDLINE, EMBASE, CINAHL, DARE and LILACS. We also reviewed reference lists of included studies and contacted experts, equipment manufacturers, and the Cochrane Heart Group. We did not apply language restrictions. SELECTION CRITERIA: We selected blinded or unblinded randomized or quasi-randomized clinical trials, reporting on adult patients with acute or acute-on-chronic cardiogenic pulmonary edema and where NPPV (continuous positive airway pressure (CPAP)) and/or bilevel NPPV plus standard medical care was compared with standard medical care alone. DATA COLLECTION AND ANALYSIS: Two authors independently selected articles and abstracted data using a standardized data collection form. We evaluated study quality with emphasis on allocation concealment, adherence to the intention-to-treat principle and losses to follow-up. MAIN RESULTS: We included 21 studies involving 1,071 participants. Compared to standard medical care, NPPV significantly reduced hospital mortality (RR 0.6, 95% CI 0.45 to 0.84) and endotracheal intubation (RR 0.53, 95% CI 0.34 to 0.83) with numbers needed to treat of 13 and 8, respectively. We found no difference in hospital length of stay with NPPV, however, intensive care unit stay was reduced by 1 day (WMD -1.07 days, 95% CI -1.60 to -0.53). Compared to standard medical care, we did not observe significant increases in the incidence of acute myocardial infarction with NPPV during (RR 1.24, 95% CI 0.79 to 1.95) or after (RR 0.82, 95% CI 0.09 to 7.54) its application. AUTHORS' CONCLUSIONS: NPPV, especially CPAP, in addition to standard medical care is an effective and safe intervention for the treatment of adult patients with acute cardiogenic pulmonary edema.