Identification of persistent and resolving subphenotypes of acute hypoxemic respiratory failure in two independent cohorts

Abstract Background Acute hypoxemic respiratory failure (HRF) is associated with high morbidity and mortality, but its heterogeneity challenges the identification of effective therapies. Defining subphenotypes with distinct prognoses or biologic features can improve therapeutic trials, but prior work has focused on ARDS, which excludes many acute HRF patients. We aimed to characterize persistent and resolving subphenotypes in the broader HRF population. Methods In this secondary analysis of 2 independent prospective ICU cohorts, we included adults with acute HRF, defined by invasive mechanical ventilation and PaO2-to-FIO2 ratio ≤ 300 on cohort enrollment (n = 768 in the discovery cohort and n = 1715 in the validation cohort). We classified patients as persistent HRF if still requiring mechanical ventilation with PaO2-to-FIO2 ratio ≤ 300 on day 3 following ICU admission, or resolving HRF if otherwise. We estimated relative risk of 28-day hospital mortality associated with persistent HRF, compared to resolving HRF, using generalized linear models. We also estimated fold difference in circulating biomarkers of inflammation and endothelial activation on cohort enrollment among persistent HRF compared to resolving HRF. Finally, we stratified our analyses by ARDS to understand whether this was driving differences between persistent and resolving HRF. Results Over 50% developed persistent HRF in both the discovery (n = 386) and validation (n = 1032) cohorts. Persistent HRF was associated with higher risk of death relative to resolving HRF in both the discovery (1.68-fold, 95% CI 1.11, 2.54) and validation cohorts (1.93-fold, 95% CI 1.50, 2.47), after adjustment for age, sex, chronic respiratory illness, and acute illness severity on enrollment (APACHE-III in discovery, APACHE-II in validation). Patients with persistent HRF displayed higher biomarkers of inflammation (interleukin-6, interleukin-8) and endothelial dysfunction (angiopoietin-2) than resolving HRF after adjustment. Only half of persistent HRF patients had ARDS, yet exhibited higher mortality and biomarkers than resolving HRF regardless of whether they qualified for ARDS. Conclusion Patients with persistent HRF are common and have higher mortality and elevated circulating markers of lung injury compared to resolving HRF, and yet only a subset are captured by ARDS definitions. Persistent HRF may represent a clinically important, inclusive target for future therapeutic trials in HRF.

Download Full-text

Non-Invasive Oxygenation Strategies in Adult Patients with Acute Respiratory Failure: A Protocol for a Systematic Review and Network Meta-analysis

10.21203/rs.2.23684/v1 ◽

2020 ◽

Author(s):

Bruno Leonel Ferreyro ◽

Federico Angriman ◽

Laveena Munshi ◽

Lorenzo del Sorbo ◽

Niall D Ferguson ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Acute Respiratory Failure ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Risk Of Bias ◽

Adult Patients ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Non Invasive

Abstract Background: Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and associated with high mortality. Non-invasive oxygenation strategies such as high flow nasal cannula, standard oxygen therapy and non-invasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of non-invasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Methods: We will search key databases for randomized controlled trials assessing the effect of non-invasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology. Discussion : This study will help to guide clinical decision making when caring for adult patients with AHRF and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure.

Download Full-text

High-flow nasal cannula versus noninvasive ventilation in the prevention of escalation to invasive mechanical ventilation in patients with acute hypoxemic respiratory failure

Egyptian Journal of Chest Diseases and Tuberculosis ◽

10.4103/ecdt.ecdt_12_20 ◽

2022 ◽

Vol 71 (1) ◽

pp. 81

Author(s):

ManalA Mahmoud ◽

Gamal Agmy ◽

Mohamed Adam ◽

EntsarH.M Hsanen

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Noninvasive Ventilation ◽

Invasive Mechanical Ventilation ◽

High Flow ◽

Nasal Cannula ◽

High Flow Nasal Cannula ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure

Download Full-text

Association Between Early Invasive Mechanical Ventilation and Day-60 Mortality in Acute Hypoxemic Respiratory Failure Related to Coronavirus Disease-2019 Pneumonia

Critical Care Explorations ◽

10.1097/cce.0000000000000329 ◽

2021 ◽

Vol 3 (1) ◽

pp. e0329

Author(s):

Claire Dupuis ◽

Lila Bouadma ◽

Etienne de Montmollin ◽

Dany Goldgran-Toledano ◽

Carole Schwebel ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Invasive Mechanical Ventilation ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure

Download Full-text

Utility of SpO2/FiO2 ratio for acute hypoxemic respiratory failure with bilateral opacities in the ICU

PLoS ONE ◽

10.1371/journal.pone.0245927 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245927

Author(s):

Yosuke Fukuda ◽

Akihiko Tanaka ◽

Tetsuya Homma ◽

Keisuke Kaneko ◽

Tomoki Uno ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Hospital Mortality ◽

Prognostic Markers ◽

Apache Ii ◽

Icu Mortality ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Risk Of Death ◽

Saps Ii

Acute hypoxemic respiratory failure (AHRF) with bilateral opacities causes fatalities in the intensive care unit (ICU). It is often difficult to identify the causes of AHRF at the time of admission. The SpO2 to FiO2 (S/F) ratio has been recently used as a non-invasive and alternative marker of the PaO2/FiO2 (P/F) ratio in acute respiratory failure. This retrospective cohort study was conducted from October 2010 to March 2019 at the Showa University Hospital, Tokyo, Japan. We enrolled 94 AHRF patients who had bilateral opacities and received mechanical ventilation in ICU to investigate their prognostic markers including S/F ratio. Significant differences were observed for APACHE II, S/F ratio, PaO2/FiO2 (P/F) ratio, and ventilator−free-days at day 28 for ICU mortality, and for age, S/F ratio, P/F ratio, duration of mechanical ventilation, and ventilator−free days at day 28 for hospital mortality. Multivariate logistic regression analysis showed that the S/F ratio was significantly and independently associated with the risk of death during in ICU (p = 0.003) and hospitalization (p = 0.002). The area under the receiver operating characteristic curves (AUC) based on the S/F ratio were significantly greater than those based on simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) for ICU mortality (0.785 in S/F ratio vs. 0.575 in SAPS II, p = 0.012; 0.785 in S/F ratio vs 0.594 in SOFA, p = 0.021) and for hospital mortality (0.701 in S/F ratio vs. 0.502 in SAPS II, p = 0.012; 0.701 in S/F ratio vs. 0.503 in SOFA, p = 0.005). In the subanalysis for bacterial pneumonia and interstitial lung disease groups, the AUC based on the S/F ratio was the greatest among all prognostic markers, including APACHE II, SAPS II, and SOFA. The S/F ratio may be a useful and noninvasive predictive prognostic marker for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Download Full-text

Effect of Early vs. Delayed or No Intubation on Clinical Outcomes of Patients With COVID-19: An Observational Study

Frontiers in Medicine ◽

10.3389/fmed.2020.614152 ◽

2020 ◽

Vol 7 ◽

Author(s):

Ilias I. Siempos ◽

Eleni Xourgia ◽

Theodora K. Ntaidou ◽

Dimitris Zervakis ◽

Eleni E. Magira ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Observational Study ◽

Clinical Outcomes ◽

Controlled Trial ◽

Invasive Mechanical Ventilation ◽

Optimal Timing ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Early Intubation

Background: Optimal timing of initiation of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 is unknown. Thanks to early flattening of the epidemiological curve, ventilator demand in Greece was kept lower than supply throughout the pandemic, allowing for unbiased comparison of the outcomes of patients undergoing early intubation vs. delayed or no intubation.Methods: We conducted an observational study including all adult patients with laboratory-confirmed COVID-19 consecutively admitted in Evangelismos Hospital, Athens, Greece between March 11, 2020 and April 15, 2020. Patients subsequently admitted in the intensive care unit (ICU) were categorized into the “early intubation” vs. the “delayed or no intubation” group. The “delayed or no intubation” group included patients receiving non-rebreather mask for equal to or more than 24 h or high-flow nasal oxygen for any period of time or non-invasive mechanical ventilation for any period of time in an attempt to avoid intubation. The remaining intubated patients comprised the “early intubation” group.Results: During the study period, a total of 101 patients (37% female, median age 65 years) were admitted in the hospital. Fifty-nine patients (58% of the entire cohort) were exclusively hospitalized in general wards with a mortality of 3% and median length of stay of 7 days. Forty-two patients (19% female, median age 65 years) were admitted in the ICU; all with acute hypoxemic respiratory failure. Of those admitted in the ICU, 62% had at least one comorbidity and 14% were never intubated. Early intubation was not associated with higher ICU-mortality (21 vs. 33%), fewer ventilator-free days (3 vs. 2 days) or fewer ICU-free days than delayed or no intubation.Conclusions: A strategy of early intubation was not associated with worse clinical outcomes compared to delayed or no intubation. Given that early intubation may presumably reduce virus aerosolization, these results may justify further research with a randomized controlled trial.

Download Full-text

High flow nasal cannula oxygen and non-invasive mechanical ventilation in management of COVID-19 patients with acute respiratory failure: a retrospective observational study

Egyptian Journal of Bronchology ◽

10.1186/s43168-021-00063-0 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Amr Mounir Shoukri

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Mortality Rate ◽

Endotracheal Intubation ◽

Invasive Mechanical Ventilation ◽

High Flow ◽

Nasal Cannula ◽

High Flow Nasal Cannula ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure

Abstract Background High flow nasal cannula oxygen (HFNCO) is a relatively new technique used to deliver oxygen in respiratory failure patients. This retrospective study is aiming to assess the role and benefits of using HFNCO compared to non-invasive ventilation (NIV) in management of patients with acute hypoxemic respiratory failure associated with coronavirus disease 2019 (COVID-19). Results A retrospective analysis of the files of 63 patients with COVID-19 and acute hypoxemic respiratory failure admitted to the intensive care unit (ICU), 37 patients received HFNCO as initial therapy, and 26 patients were primarily treated with NIV. There was no significant difference between the 2 groups in terms of baseline characteristics, laboratory tests, arterial blood gases, PaO2/FiO2 values, and vital signs. Re-assessment after 24 h of starting treatment with either HFNCO or NIV showed significant improvement (P<0.01) in the respiratory rate, heart rate, and oxygenation parameters. The magnitude of improvement of the vital signs and oxygenation was not significantly different between patients using HFNCO or NIV. Success rate of HFNCO was 86.4%, endotracheal intubation with invasive mechanical ventilation was required in 10.81% of patients, and mortality rate was 2.7%. Success rate of NIV was 84.6%, endotracheal intubation rate was 11.53%, and mortality rate was 3.8%. No significant difference (P>0.05) between the 2 groups as regards the duration of treatment, rate of endotracheal intubation with invasive mechanical ventilation, and mortality rate. Conclusion High flow nasal cannula oxygen (HFNCO) is effective in the management of acute hypoxemic respiratory failure associated with COVID-19. Its efficacy is similar to NIV, with no difference in the duration of treatment, endotracheal intubation rate, or mortality rate.

Download Full-text

Noninvasive Oxygenation Strategies in Adult Patients with Acute Respiratory Failure: A Protocol for a Systematic Review and Network Meta-analysis

10.21203/rs.2.23684/v2 ◽

2020 ◽

Author(s):

Bruno Leonel Ferreyro ◽

Federico Angriman ◽

Laveena Munshi ◽

Lorenzo del Sorbo ◽

Niall D Ferguson ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Acute Respiratory Failure ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Risk Of Bias ◽

Adult Patients ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Non Invasive

Download Full-text

Acute Hypoxemic Respiratory Failure in Children at the Start of COVID-19 Outbreak: A Nationwide Experience

Journal of Clinical Medicine ◽

10.3390/jcm10194301 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4301

Author(s):

Yolanda M. López-Fernández ◽

Amelia Martínez-de-Azagra ◽

José M. González-Gómez ◽

César Pérez-Caballero Macarrón ◽

María García-González ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Distress Syndrome ◽

Invasive Mechanical Ventilation ◽

Oxygenation Index ◽

Pediatric Intensive Care ◽

Inclusion Criteria ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Respiratory Management

Study design: This is a prospective, multicenter, and observational study with the aim of describing physiological characteristics, respiratory management, and outcomes of children with acute hypoxemic respiratory failure (AHRF) from different etiologies receiving invasive mechanical ventilation (IMV) compared with those affected by SARS-CoV-2. Methods and Main Results: Twenty-eight patients met the inclusion criteria: 9 patients with coronavirus disease 2019 (COVID-19) and 19 patients without COVID-19. Non-COVID-19 patients had more pre-existing comorbidities (78.9% vs. 44.4%) than COVID-19 patients. At AHRF onset, non-COVID-19 patients had worse oxygenation (PaO2/FiO2 = 95 mmHg (65.5–133) vs. 150 mmHg (105–220), p = 0.04), oxygenation index = 15.9 (11–28.4) vs. 9.3 (6.7–10.6), p = 0.01), and higher PaCO2 (48 mmHg (46.5–63) vs. 41 mmHg (40–45), p = 0.07, that remained higher at 48 h: 54 mmHg (43–58.7) vs. 41 (38.5–45.5), p = 0.03). In 12 patients (5 COVID-19 and 7 non-COVID-19), AHRF evolved to pediatric acute respiratory distress syndrome (PARDS). All non-COVID-19 patients had severe PARDS, while 3 out of 5 patients in the COVID-19 group had mild or moderate PARDS. Overall Pediatric Intensive Care Medicine (PICU) mortality was 14.3%. Conclusions: Children with AHRF due to SARS-CoV2 infection had fewer comorbidities and better oxygenation than patients with non-COVID-19 AHRF. In this study, progression to severe PARDS was rarely observed in children with COVID-19.

Download Full-text

Effect of early versus delayed or no intubation on clinical outcomes of patients with COVID-19

10.21203/rs.3.rs-52647/v1 ◽

2020 ◽

Author(s):

Ilias Siempos ◽

Elena Xourgia ◽

Theodora K. Ntaidou ◽

Dimitris Zervakis ◽

Eleni E. Magira ◽

...

Keyword(s):

Respiratory Failure ◽

Clinical Outcomes ◽

Controlled Trial ◽

Invasive Mechanical Ventilation ◽

Optimal Timing ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Entire Cohort ◽

Early Intubation ◽

General Wards

Abstract Background: Optimal timing of initiation of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 is unknown. Thanks to early flattening of the epidemiological curve, ventilator demand in Greece was kept lower than supply throughout the pandemic, allowing for unbiased comparison of the outcomes of patients undergoing early intubation versus delayed or no intubation.Methods: We conducted an observational study including all adult patients with laboratory-confirmed COVID-19 consecutively admitted in Evangelismos Hospital, Athens, Greece between March 11, 2020 and April 15, 2020. Patients subsequently admitted in the intensive care unit (ICU) were categorized into the “early intubation” versus the “delayed or no intubation” group.Results: During the study period, a total of 101 patients (37% female, median age 65 years) were admitted in the hospital. Fifty-nine patients (58% of the entire cohort) were exclusively hospitalized in general wards with a mortality of 3% and median length of stay of 7 days. Forty-two patients (19% female, median age 65 years, 62% with at least one comorbidity, 14% never intubated) were admitted in the ICU; all with acute hypoxemic respiratory failure. Early intubation was not associated with higher ICU-mortality (21% versus 33%), fewer ventilator-free days (3 versus 2 days) or fewer ICU-free days than delayed or no intubation.Conclusions: A strategy of early intubation was not associated with worse clinical outcomes compared to delayed or no intubation. Given that early intubation may presumably reduce virus aerosolization, these results may justify further research with a randomized controlled trial.

Download Full-text

Noninvasive Oxygenation Strategies in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials

Journal of Intensive Care Medicine ◽

10.1177/0885066619844713 ◽

2019 ◽

Vol 35 (11) ◽

pp. 1216-1225 ◽

Cited By ~ 2

Author(s):

Yazan Zayed ◽

Momen Banifadel ◽

Mahmoud Barbarawi ◽

Babikir Kheiri ◽

Adam Chahine ◽

...

Keyword(s):

Mechanical Ventilation ◽

Oxygen Therapy ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Controlled Trials ◽

Immunocompromised Patients ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Randomized Controlled

Introduction: Acute hypoxemic respiratory failure (AHRF) is a leading cause of intensive care unit (ICU) admission among immunocompromised patients. Invasive mechanical ventilation is associated with increased morbidity and mortality. Objective: To evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in immunocompromised patients with AHRF. Methods: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to December 2018. We included all randomized controlled trials (RCTs) comparing different modalities of initial oxygenation strategies in immunocompromised patients with AHRF. Our primary outcome was the need for intubation and invasive mechanical ventilation while secondary outcomes were ICU acquired infections and short- and long-term mortality. Data were extracted separately and independently by 2 reviewers. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrIs). Results: Nine RCTs were included (1570 patients, mean age 61.1 ± 13.8 years with 64% male). Noninvasive ventilation was associated with a significantly reduced intubation rate compared with standard oxygen therapy (OR: 0.53; 95% CrI: 0.26-0.91). There were no significant reductions of intubation between NIV versus HFNC (OR: 0.83; 95% CrI: 0.35-2.11) or HFNC versus standard oxygen therapy (OR: 0.65; 95% CrI: 0.26-1.24). There were no significant differences between all groups regarding short-term (28-day or ICU) mortality or long-term (90-day or hospital) mortality or ICU-acquired infections ( P > 0.05). Conclusion: Among immunocompromised patients with AHRF, NIV was associated with a significant reduction of intubation compared with standard oxygen therapy. There were no significant differences among all oxygenation strategies regarding mortality and ICU-acquired infections.

Download Full-text