Importance
The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated.


Objectives
To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC).


Design, Setting, and Participants
This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021.


Interventions
Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2.


Main Outcomes and Measures
The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs).


Results
Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant.


Conclusions and Relevance
In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement.


Trial Registration
ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.

/pdf/high-dose-dexamethasone-and-oxygen-support-strategies-in-2ifev1qr.pdf

High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure: The COVIDICUS Randomized Clinical Trial.

Patients with severe lung injury usually have a high respiratory drive, resulting in intense inspiratory effort that may even worsen lung damage by several mechanisms gathered under the name "patient-self inflicted lung injury" (P-SILI). Even though no clinical study has yet demonstrated that a ventilatory strategy to limit the risk of P-SILI can improve the outcome, the concept of P-SILI relies on sound physiological reasoning, an accumulation of clinical observations and some consistent experimental data. In this review, we detail the main pathophysiological mechanisms by which the patient's respiratory effort could become deleterious: excessive transpulmonary pressure resulting in over-distension; inhomogeneous distribution of transpulmonary pressure variations across the lung leading to cyclic opening/closing of nondependent regions and pendelluft phenomenon; increase in the transvascular pressure favoring the aggravation of pulmonary edema. We also describe potentially harmful patient-ventilator interactions. Finally, we discuss in a practical way how to detect in the clinical setting situations at risk for P-SILI and to what extent this recognition can help personalize the treatment strategy.

Patient-Self Inflicted Lung Injury: A Practical Review

Non-invasive respiratory support in the management of acute COVID-19 pneumonia: considerations for clinical practice and priorities for research

Non-invasive respiratory support in the management of acute COVID-19 pneumonia: considerations for clinical practice and priorities for research.

Noninvasive respiratory support can be useful for cardiogenic pulmonary edema and COPD exacerbations. For other conditions, its benefits need to be balanced against the potential harms of delaying intubation. 

Noninvasive Respiratory Support for Adults with Acute Respiratory Failure

We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter (“Filter Frugal CPAP”, FF-CPAP) in and out the ICU. (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient’s work of breathing (6–34%) needed to sustain the tidal volume, depending on the filter’s resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test). Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.

/pdf/continuous-positive-airway-pressure-for-respiratory-support-29j5r85aaj.pdf

Manuella Pons

Papers

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside