The effectiveness of high-flow nasal cannula oxygen therapy (HFNC) in patients with acute respiratory failure due to COVID-19 remains uncertain. We aimed at assessing whether HFNC is associated with reduced risk of intubation or mortality in patients with acute respiratory failure due to COVID-19 compared with conventional oxygen therapy (COT).In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, and CENTRAL databases for randomized controlled trials (RCTs) and observational studies comparing HFNC vs. COT in patients with acute respiratory failure due to COVID-19, published in English from inception to December 2022. Pediatric studies, studies that compared HFNC with a noninvasive respiratory support other than COT and those in which intubation or mortality were not reported were excluded. Two authors independently screened and selected articles for inclusion, extracted data, and assessed the risk of bias. Fixed-effects or random-effects meta-analysis were performed according to statistical heterogeneity. Primary outcomes were risk of intubation and mortality across RCTs. Effect estimates were calculated as risk ratios and 95% confidence interval (RR; 95% CI). Observational studies were used for sensitivity analyses.Twenty studies were analyzed, accounting for 8383 patients, including 6 RCTs (2509 patients) and 14 observational studies (5874 patients). By pooling the 6 RCTs, HFNC compared with COT significantly reduced the risk of intubation (RR 0.89, 95% CI 0.80 to 0.98; p = 0.02) and reduced length of stay in hospital. HFNC did not significantly reduce the risk of mortality (RR 0.93, 95% CI 0.77 to 1.11; p = 0.40).In patients with acute respiratory failure due to COVID-19, HFNC reduced the need for intubation and shortened length of stay in hospital without significant decreased risk of mortality. Trial registration The study was registered on the International prospective register of systematic reviews (PROSPERO) at https://www.crd.york.ac.uk/prospero/ with the trial registration number CRD42022340035 (06/20/2022).
Extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) is systematically associated with decreased respiratory system compliance (CRS). It remains unclear whether transportation to the referral ECMO center, changes in ventilatory mode or settings to achieve ultra-protective ventilation, or the natural evolution of ARDS drives this change in respiratory mechanics. Herein, we assessed the precise moment when CRS decreases after ECMO cannulation and identified factors associated with decreased CRS. To rule out the effect of transportation and the different modes of ventilation on CRS, we conducted a retrospective, single-center, observational cohort study from January 2013 to May 2020, on 22 patients with severe ARDS requiring on-site ECMO and ventilated in pressure-controlled mode to achieve ultra-protective ventilation. CRS was assessed at different time points ranging from 12 h before ECMO cannulation to 72 h after ECMO cannulation. The primary outcome was the relative change in CRS between 3 h before and 3 h after ECMO cannulation. The secondary outcomes included variables associated with the relative changes in CRS within the first 3 h after ECMO cannulation and the relative changes in CRS at each time point. CRS decreased within the first 3 h after ECMO cannulation (−28.3%, 95% confidence interval [CI]: −38.8 to −17.9), while the decrease was mild before and after these first 3 h after ECMO cannulation. To achieve ultra-protective ventilation, respiratory rate decreased in the mean by –13 breaths/min (95% CI: −15 to −11) and driving pressure by −8.3 cmH2O (95% CI: −11.2 to −5.3), resulting in decreased tidal volume by −3.3 mL/kg of predicted body weight (95% CI: −3.9 to −2.6) as compared to before ECMO cannulation (P <0.001 for all). Plateau pressure reduction, driving pressure reduction, and tidal volume reduction were significantly associated with decreased CRS after ECMO cannulation, whereas neither respiratory rate, positive end-expiratory pressure, inspired fraction of oxygen, fluid balance, nor mean airway pressure was associated with decreased CRS. Decreased driving pressure resulting in lower tidal volume to achieve ultra-protective ventilation after ECMO cannulation was associated with a marked decrease in CRS in ARDS patients with on-site ECMO cannulation.
In a recent issue of the Journal of American Medical Association , Patel and colleagues compared two different interfaces to carry out noninvasive ventilation (NIV) in patients admitted to ICU for acute hypoxemic respiratory failure (1). Among them, only those who met the criteria for acute respiratory distress syndrome (ARDS) according to the Berlin definition (2) could be included, i.e., those having had worsening of respiratory symptoms within the previous week, a PaO 2 /FiO 2 ≤300 mmHg with positive end-expiratory pressure (PEEP) at least 5 cmH 2 O, and bilateral pulmonary infiltrates, after excluding those with cardiogenic pulmonary edema. However, patients were included after at least 8 hours of NIV as first-line therapy with a standard face mask.
Abstract Background Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. Methods Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m −2 ) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO 2 /FiO 2 < 300 mm Hg). The primary outcome was the occurrence of severe hypoxemia (pulse oximetry < 80%) during the intubation procedure. Results Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m −2 . Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI − 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77–93] with noninvasive ventilation and 86% [78–92] with high-flow nasal oxygen ( P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission. Conclusions Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov )
Rationale: Whether patients with coronavirus disease (COVID-19) 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 versus 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 versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results: A total of 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 on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0–9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, −2%; 95% confidence interval, −10 to 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 IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of 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 regions with ECMO capacities specifically organized to handle high demand.
Abstract: High-flow nasal cannula (HFNC) oxygen therapy is a recent technique delivering a high flow of heated and humidified gas. HFNC is simpler to use and apply than noninvasive ventilation (NIV) and appears to be a good alternative treatment for hypoxemic acute respiratory failure (ARF). HFNC is better tolerated than NIV, delivers high fraction of inspired oxygen (FiO2), generates a low level of positive pressure and provides washout of dead space in the upper airways, thereby improving mechanical pulmonary properties and unloading inspiratory muscles during ARF. A recent multicenter randomized controlled trial showed benefits of HFNC concerning mortality and intubation in severe patients with hypoxemic ARF. In management of patients with hypoxemic ARF, NIV results have been conflicting. Despite improved oxygenation, NIV delivered with face mask may generate high tidal volumes and subsequent ventilator-induced lung injury. An approach applying NIV with a helmet, high levels of positive end-expiratory pressure (PEEP) and low pressure support (PS) levels seems to open new opportunities in patients with hypoxemic ARF. However, a large-scale randomized controlled study is needed to assess and compare this approach with HFNC.
Background In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. Methods We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. Results Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference −0.6%, 95% CI −16.8– +15.6%; OR 0.98, 95% CI 0.50–1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168–476 days) versus 177 days (64–288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. Conclusions In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.
Abstract Background Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19. Methods All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgium and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. Results Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay and 491 (23%) during the first 24 h following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO 2 /FiO 2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% versus 39.3% in the early PP group ( p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies was more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two study groups (HR 1.34 [0.96–1.68], p = 0.09 and HR 1.19 [0.998–1.412], p = 0.053 in complete case analysis or in multiple imputation analysis, respectively). Conclusions In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, our data failed to show a survival benefit associated with early PP started within 24 h after ICU admission compared to PP after day-1 for all COVID-19 patients requiring invasive mechanical ventilation regardless of their severity.
