Factors associated with decreased compliance after on-site extracorporeal membrane oxygenation cannulation for acute respiratory distress syndrome: A retrospective, observational cohort study.

Background: 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. Methods: 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. Results: CRS decreased within the first 3 h after ECMO cannulation (-28.3%, 95% confidence interval [CI]: -38.8 to -17.9, P<0.001), 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. Conclusions: 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.

Physiologic Effects of Reconnection to the Ventilator for 1 Hour Following a Successful Spontaneous Breathing Trial.

BACKGROUND: Reconnection to the ventilator for 1 h following a successful spontaneous breathing trial (SBT) may reduce reintubation rates compared with direct extubation. However, the physiologic mechanisms leading to this effect are unclear. RESEARCH QUESTION: Does reconnection to the ventilator for 1 h reverse alveolar derecruitment induced by SBT, and is alveolar derecruitment more pronounced with a T-piece than with pressure-support ventilation (PSV)? STUDY DESIGN AND METHODS: This is an ancillary study of a randomized clinical trial comparing SBT performed with a T-piece or with PSV. Alveolar recruitment was assessed by using measurement of end-expiratory lung volume (EELV). RESULTS: Of the 25 patients analyzed following successful SBT, 11 underwent SBT with a T-piece and 14 with PSV. At the end of the SBT, EELV decreased by -30% (95% CI, -37 to -23) compared with baseline prior to the SBT. This reduction was greater with a T-piece than with PSV: -43% (95% CI, -51 to -35) vs -20% (95% CI, -26 to -13); P < .001. Following reconnection to the ventilator for 1 h, EELV accounted for 96% (95% CI, 92 to 101) of baseline EELV and did not significantly differ from prior to the SBT (P = .104). Following 10 min of reconnection to the ventilator, EELV wasted at the end of the SBT was completely recovered using PSV (P = .574), whereas it remained lower than prior to the SBT using a T-piece (P = .010). INTERPRETATION: Significant alveolar derecruitment was observed at the end of an SBT and was markedly more pronounced with a T-piece than with PSV. Reconnection to the ventilator for 1 h allowed complete recovery of alveolar derecruitment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04227639; URL: www. CLINICALTRIALS: gov.

Sex difference in the risk of extubation failure in ICUs.

BACKGROUND: Little attention has been paid to potential differences in prognosis between mechanically ventilated males and females in intensive care units (ICUs). We hypothesized that a sex gap in the risk of extubation failure in ICUs may exist. METHODS: Post hoc analysis of a large-scale clinical trial including patients at high risk of extubation failure in ICUs, with the aim of assessing the risk of extubation failure according to sex. The primary outcome was reintubation within the 7 days following extubation. RESULTS: Out of 641 patients, 425 (66%) were males and 216 (34%) were females. Males were more likely to be admitted for cardiac arrest and to have underlying ischemic heart disease whereas females were more likely to be admitted for coma and to have obesity. Whereas the rate of reintubation at 48 h was significantly higher in males than in females (11.0% vs. 6.0%; difference, + 5.0 [95% CI, 0.2 to 9.2]; P = 0.038), the rate of reintubation at day 7 did not significantly differ between males and females (16.7% vs. 11.1%; difference, + 5.6% [95%CI, - 0.3 to 10.8], P = 0.059). Using multivariable logistic regression analysis, male sex was independently associated with reintubation within the 7 days following extubation (adjusted OR 1.70 [95% CI, 1.01 to 2.89]; P = 0.048), even after adjustment on reason for admission, body-mass index, severity score, respiratory rate before extubation, and noninvasive ventilation after extubation. CONCLUSION: In this post hoc analysis of a clinical trial including a homogeneous subset of patients at high risk of extubation failure, sex was independently associated with reintubation. The role of sex on outcomes should be systematically examined in future studies of critically ill patients.

High-flow nasal cannula oxygen versus conventional oxygen therapy for acute respiratory failure due to COVID-19: a systematic review and meta-analysis.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).

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.

Evolution of respiratory system compliance and potential for lung recruitment in COVID-19-induced acute respiratory distress syndrome.

Background: Coronavirus disease 2019 (COVID-19) has been frequently complicated by severe acute respiratory distress syndrome (ARDS) with prolonged invasive ventilation. While respiratory system compliance and lung recruitability have been described within the first days after ICU admission, data about their longitudinal changes are still limited. Therefore, we conducted this study to assess the evolution of respiratory system compliance and lung recruitability in patients with COVID-19-related ARDS. Method: We conducted a prospective single-center study in patients admitted for COVID-19-related ARDS during the first wave of the pandemic, from March 16, 2020 to April 10, 2020. Respiratory system compliance was calculated daily at clinical positive end-expiratory pressure (PEEP) during passive breathing. The potential for lung recruitment was assessed by measuring the volume derecruited between PEEP 15 cmH2O and 5 cmH2O, and using the calculation of the recruitment-to-inflation ratio (R/I ratio). Recruitable lung was considered when the R/I ratio was at least 0.5. The primary outcome was the evolution of respiratory mechanics over time. The secondary outcome was the evolution of lung recruitability over time. Results: Thirty-two patients were included in this study. The respiratory mechanics were assessed 222 times (7 ± 5 times per patient). Respiratory system compliance at clinical PEEP was 29.1 mL/cmH2O (interquartile range [IQR]: 24.1-33.9 mL/cmH2O) and decreased significantly over time (P <0.0001). Lung recruitability was assessed in 22 out of the 32 patients (60 assessments). The median volume derecruited between PEEP 15 cmH2O and 5 cmH2O was 246.8 mL (IQR: 180.8-352.2 mL) and the median R/I ratio was 0.56 (IQR: 0.39-0.73). Neither changed significantly over time. The proportion of patients with recruitable lung was 50.0% (6/12) within the first 3 days after intubation, 69.2% (9/13) between day 4 and day 7, and 66.7% (8/12) after day 7 (P=0.7934). Conclusions: In our cohort, respiratory system compliance was low and decreased over time. The potential for lung recruitment was high and persisted despite prolonged mechanical ventilation, suggesting that maintaining high PEEP levels in the later course of COVID-19 could be adequate.

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.

Corticosteroids alter alveolar macrophage control of Lichtheimia corymbifera spores in an ex vivo mouse model.

Alveolar macrophages (AM) are the first-line lung defense against Mucorales in pulmonary mucormycosis. Since corticosteroid use is a known risk factor for mucormycosis, the aim of this study was to describe the role of corticosteroids on AM capacities to control Lichtheimia corymbifera spore growth using a new ex vivo model. An in vivo mouse model was developed to determine the acetate cortisone dose able to trigger pulmonary invasive infection. Then, in the ex vivo model, male BALB/c mice were pretreated with the corticosteroid regimen triggering invasive infection, before AM collection through bronchoalveolar lavage. AMs from corticosteroid-treated mice and untreated control AMs were then exposed to L. corymbifera spores in vitro (ratio 1:5). AM control of fungal growth, adherence/phagocytosis, and oxidative burst were assessed using optical densities by spectrophotometer, flow cytometry, and 2', 7'-dichlorofluoresceine diacetate fluorescence, respectively. Cortisone acetate at 500 mg/kg, at D-3 and at D0, led to pulmonary invasive infection at D3. Co-incubated spores and AMs from corticosteroid-treated mice had significantly higher absorbance (fungal growth) than co-incubated spores and control AMs, at 24 h (P = .025), 36 h (P = .004), and 48 h (P = .001). Colocalization of spores with AMs from corticosteroid-treated mice was significantly lower than for control AMs (7.6 ± 1.9% vs 22.3 ± 5.8%; P = .003), reflecting spore adherence and phagocytosis inhibition. Finally, oxidative burst was significantly increased when control AMs were incubated with spores (P = 0.029), while corticosteroids hampered oxidative burst from treated AMs (P = 0.321). Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease in our ex vivo model. LAY SUMMARY: The aim of this study was to describe the impact of corticosteroids on alveolar macrophage (AM) capacities to control Mucorales growth in a new murine ex vivo model. Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease.