Severe Hypoxemic Respiratory Failure Research Articles

Alteplase in COVID-19 severe hypoxemic respiratory failure: the TRISTARDS multicenter randomized trial

BackgroundPulmonary intravascular thrombus formation has been widely observed in patients with respiratory failure, for example, in patients with SARS-CoV-2 infection (COVID-19). The aim of this study was to evaluate the efficacy/safety of alteplase thrombolysis in COVID-19 severe hypoxemic respiratory failure. In this multicenter, open-label study, patients were randomized to receive alteplase (low- or high-dose) over 5 days plus standard of care (SOC), or SOC alone. The primary endpoint was time to clinical improvement (≥ 2-point decrease on WHO Clinical Progression Scale, or hospital discharge) up to Day 28. Secondary endpoints included all-cause mortality at Day 28, treatment failure at Day 28 and change in arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) ratio at Day 6 versus baseline.ResultsSixty-nine patients were randomized to alteplase (low- or high-dose) and 35 to SOC; 65% were on high-flow oxygen or non-invasive ventilation at baseline. Median time to clinical improvement was 25 days in the alteplase group and > 28 days (median not reached) in the SOC group. All-cause mortality was 8/69 (12%) versus 10/35 (29%) in the alteplase versus SOC groups, respectively (unadjusted risk difference [RD], − 17% [95% confidence interval (CI) − 34 to 0], p = 0.047; adjusted RD, − 16% [95% CI − 31 to 1], p = 0.058). The PaO2/FiO2 ratio (mean [standard deviation]) increased by + 30 (84) mmHg in the alteplase group and decreased by − 12 (59) mmHg in the SOC group (adjusted mean difference vs. SOC, p = 0.052). Differences were greater in patients receiving high-dose alteplase, and in those not receiving invasive ventilation. Eighteen patients (26.1%) in the alteplase group discontinued treatment due to adverse events. Major bleeding was more frequent with alteplase than with SOC (9 vs. 0 patients); no bleeding was fatal. The study closed early due to insufficient patient recruitment.ConclusionAlteplase was not associated with faster clinical recovery from COVID-19 severe hypoxemic respiratory failure. A numerical difference in survival and PaO2/FiO2 ratio was observed, particularly in patients not receiving invasive ventilation. These exploratory findings merit further investigation in larger patient cohorts that are adequately powered to confirm the hypotheses generated in this study regarding the impact of alteplase on treatment outcomes.Trial registration ClinicalTrials.gov: NCT04640194 (November 23, 2020); https://clinicaltrials.gov/study/NCT04640194 (early discontinuation due to insufficient patient recruitment).

Derivation and validation of generalized sepsis-induced acute respiratory failure phenotypes among critically ill patients: a retrospective study

BackgroundSeptic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis, considering multi-organ dynamics. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes.MethodsWe performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥ 24 h. Data from two different high-volume academic hospital centers were used, where all phenotypes were derived in MICU of Hospital-I (N = 3225). The derived phenotypes were validated in MICU of Hospital-II (N = 848), SICU of Hospital-I (N = 1112), and SICU of Hospital-II (N = 465). Clinical data from 24 h preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts.ResultsFour distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F = 123]), C (mild hypoxia [median P/F = 240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing the MICU of Hospital-II and SICUs from Hospital-I and -II. Kaplan–Meier analysis showed significant difference in 28-day mortality across the phenotypes (p < 0.01) and consistent across MICU and SICU of both Hospital-I and -II. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy.ConclusionThe phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.

Een episode van niet-cardiogeen longoedeem bij een jonge, gezonde atleet

An episode of non-cardiogenic lung edema in a young, healthy athlete This article describes a case of a healthy, active 17-year-old man who underwent an elective endoscopic repair of an inguinal hernia under general anesthesia. After being extubated, he experienced a sudden episode of severe hypoxemic respiratory failure in the recovery room. Eventually, the diagnosis of negative pressure pulmonary edema (NPPE) or post-obstructive pulmonary edema (POPE) was made. This condition involves a non-cardiogenic pulmonary edema which occurs due to the generation of highly negative intrathoracic pressures. The most common cause in the adult population is post-extubation laryngospasm, where significant inspiratory forces are exerted against a closed glottis. Young athletes are at a heightened risk of experiencing this complication because they can develop intensely negative intrathoracic pressures. Given the limited treatment options available, it is crucial to prevent this phenomenon and to promptly identify it if present. Given its rarity and relative obscurity, the authors hope to raise the awareness for this phenomenon. It is a condition that any medical professional (internists, surgeons, anesthesiologists, intensivists) may encounter in his or her practice.

High-flow nasal oxygen in resource-constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic respiratory failure: Comparing outcomes of the first v. third waves at a tertiary centre in South Africa.

High-flow nasal oxygen (HFNO) is an accepted treatment for severe COVID-19-related acute hypoxaemic respiratory failure (AHRF). To determine whether treatment outcomes at Groote Schuur Hospital, Cape Town, South Africa, during the third COVID-19 wave would be affected by increased institutional experience and capacity for HNFO and more restrictive admission criteria for respiratory high-care wards and intensive care units. We included consecutive patients with COVID-19-related AHRF treated with HFNO during the first and third COVID-19 waves. The primary endpoint was comparison of HFNO failure (composite of the need for intubation or death while on HFNO) between waves. A total of 744 patients were included: 343 in the first COVID-19 wave and 401 in the third. Patients treated with HFNO in the first wave were older (median (interquartile range) age 53 (46 - 61) years v. 47 (40 - 56) years; p<0.001), and had higher prevalences of diabetes (46.9% v. 36.9%; p=0.006), hypertension (51.0% v. 35.2%; p<0.001), obesity (33.5% v. 26.2%; p=0.029) and HIV infection (12.5% v. 5.5%; p<0.001). The partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2 /FiO2 ) ratio at HFNO initiation and the ratio of oxygen saturation/FiO2 to respiratory rate within 6 hours (ROX-6 score) after HFNO commencement were lower in the first wave compared with the third (median 57.9 (47.3 - 74.3) mmHg v. 64.3 (51.2 - 79.0) mmHg; p=0.005 and 3.19 (2.37 - 3.77) v. 3.43 (2.93 - 4.00); p<0.001, respectively). The likelihood of HFNO failure (57.1% v. 59.6%; p=0.498) and mortality (46.9% v. 52.1%; p=0.159) did not differ significantly between the first and third waves. Despite differences in patient characteristics, circulating viral variant and institutional experience with HFNO, treatment outcomes were very similar in the first and third COVID-19 waves. We conclude that once AHRF is established in COVID-19 pneumonia, the comorbidity profile and HFNO provider experience do not appear to affect outcome. What the study adds. This study adds to the body of evidence demonstrating the utility of high-flow nasal oxygen (HFNO) in avoiding invasive mechanical ventilation (IMV) in patients with severe COVID-19 hypoxaemic respiratory failure, and shows that this utility remained consistent across different waves of the COVID-19 pandemic.Implications of the study. In resource-constrained settings, HFNO is a feasible non-invasive alternative to IMV and can be employed with favourable and consistent outcomes outside traditional critical care wards. It also confirms that the degree of gas exchange abnormality, and not pre-existing patient-related factors, circulating wave variant or provider experience, is the main predictor of HFNO failure.

Use of inhaled vasodilators in ARDS patients

Abstract:&#x0D; Acute Respiratory Distress Syndrome (ARDS) is a severe lung injury leading to bilateral lung opacities and severe hypoxemic respiratory failure. It results from acute inflammation, endothelial dysfunction, and disruption of the alveolar-capillary membrane. ARDS management encompasses lung-protective supportive care such as lung-protective ventilation strategies. Inhaled pulmonary vasodilators show potential as adjunctive therapies for refractory hypoxemia and hold promise in improving oxygenation and reducing pulmonary vascular resistance in severe ARDS. However, their impact on mortality remains uncertain and current evidence supports their role as rescue therapies. Prudent consideration and assessment of potential benefits and risks are crucial when integrating these agents into clinical practice.

Impact of Center of Admission on Receipt of Extracorporeal Membrane Oxygenation Among Patients With Hypoxemic Respiratory Failure: A Secondary Analysis of the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure and Reseau Europeen de Recherche en Ventilation Artificielle Influenza A(H1N1) Studies

BackgroundGiven the resources and specialized training required to deliver extracorporeal membrane oxygenation (ECMO), the provision of ECMO is often centralized within expert centres. Spurred by recent evidence the use of ECMO has increased dramatically. However, given the centralized nature of ECMO it is possible that inequities in access exist. Research QuestionDoes centre of admission impact the likelihood of receiving ECMO among adults with moderate or severe acute hypoxemic respiratory failure (PaO2/FiO2 ratio ≤ 200mmHg within 48hrs of ventilation). Study Design and MethodsWe performed a retrospective cohort study using data from the LUNG SAFE and REVA influenza A (H1N1) databases. Using modified log-Poisson analysis we estimated the likelihood of receiving ECMO (initiation at the admitting hospital or transfer for initiation), adjusting for disease severity over time. To explore unmeasured confounding, we evaluated the association between centre of admission on three negative controls: neuromuscular blockade, prone positioning, and dialysis. ResultsAmong 1,581 patients (37.7% female, mean age 60.7 years), 76 (4.8%) received ECMO. Longitudinal analysis, adjusted for trends in disease severity, demonstrated that patients admitted to ECMO centres were two-times more likely to receive ECMO than those admitted to non-ECMO centres (RR 2.00; 95% CI 1.17-3.41). Patients at ECMO centres received ECMO two days earlier than those at non-ECMO centres, median (IQR) time to initiation 1 (1-5) vs 3 (2-5) days (p=0.04). Centre of admission was not associated with neuromuscular blockade (RR 1.08; 95% CI 0.90-1.30), prone positioning (RR 0.93; 95% CI 0.68-1.28), or dialysis (RR 1.04; 95% CI 0.84-1.27). InterpretationAdults with hypoxemic respiratory failure admitted to ECMO centres were twice as likely to receive ECMO as those admitted to non-ECMO centres. These finding raise concerns regarding equity in access to care and suggest a potential lower threshold among clinicians at ECMO centres to initiate ECMO.

Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit.

To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency. Prospective, observational, single-center study. Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021. Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included. Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients. Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2-5 mg/L; (normal plasma concentration: > 5 mg/L). Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1-4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10-22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO2/FIO2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients. This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period.

High-Flow Nasal Cannula oxygen therapy in COVID-19: retrospective analysis of clinical outcomes - single center experience.

High-Flow Nasal Cannula (HFNC) oxygen therapy emerged as the therapy of choice in COVID-19-related pneumonia and moderate to severe acute hypoxemic respiratory failure (AHRF). HFNC oxygen therapy in COVID-19 has been recommended based its use to treat AHRF of other etiologies, and studies on assessing outcomes in COVID-19 patients are highly needed. This study aimed to examine outcomes in COVID-19 patients with pneumonia and severe AHRF treated with HFNC. The study included 235 COVID-19 patients with pneumonia treated with HFNC. Data extracted from medical records included demographic characteristics, comorbidities, laboratory parameters, clinical and oxygenation status, clinical complications, as well as the length of hospital stay. Patients were segregated into two groups based on their oxygen therapy needs: HDU group, those who exclusively required HFNC and ICU group, those whose oxygen therapy needed to be escalated at some point of hospital stay. The primary outcome was the need for respiratory support escalation (noninvasive or invasive mechanical ventilation) and the secondary outcome was the in-hospital all-cause mortality. The primary outcome was met in 113 (48%) of patients. The overall mortality was 70%, significantly higher in the ICU group [102 (90.2%) vs. 62 (50.1%), p < 0.001]. The rate of intrahospital infections was significantly higher in the ICU group while there were no significant differences in the length of hospital stay between the groups. The ICU group exhibited significant increases in D-dimer, NLR, and NEWS values, accompanied by a significant decrease in the SaO2/FiO2 ratio. The multivariable COX proportional regression analysis identified malignancy, higher levels of 4C Mortality Score and NEWS2 as significant predictors of mortality. High-Flow Nasal Cannula oxygen therapy is a safe type of respiratory support in patients with COVID-19 pneumonia and acute hypoxemic respiratory failure with significantly less possibility for emergence of intrahospital infections. In 52% of patients, HFNC was successful in treating AHRF in COVID-19 patients. Overall, mortality in COVID-19 pneumonia with AHRF is still very high, especially in patients treated with noninvasive/invasive mechanical ventilation.

Clinical predictors and outcomes of pulmonary infarction in patients with central pulmonary embolism

ABSTRACT Background Given the heterogeneity of predisposing factors associated with pulmonary infarction (PI) and the lack of clinically relevant outcomes among patients with acute pulmonary embolism (PE) complicated by PI, further investigation is required. Methods Retrospective study of patients with central PE in an 11-year period. Data were stratified according to the diagnosis of PI. Multivariable logistic regression analysis was used to analyze factors associated with PI development and determine if PI was associated with severe hypoxemic respiratory failure and mechanical ventilation use. Results Of 645 patients with central PE, 24% (n = 156) had PI. After adjusting for demographics, comorbidities, and clinical features on admission, only age (OR 0.98, CI 0.96–0.99; p = 0.008) was independently associated with PI. Regarding outcomes, 35% (n = 55) had severe hypoxemic respiratory failure, and 19% (n = 29) required mechanical ventilation. After adjusting for demographics, PE severity, and right ventricular dysfunction, PI was independently associated with severe hypoxemic respiratory failure (OR 1.78; CI 1.18–2.69, p = 0.005) and mechanical ventilation (OR 1.92; CI 1.14–3.22, p = 0.013). Conclusions Aging is a protective factor against PI. In acute central PE, subjects with PI had higher odds of developing severe hypoxemic respiratory failure and requiring mechanical ventilation.

Colonic oxygen microbubbles augment systemic oxygenation and CO2 removal in a porcine smoke inhalation model of severe hypoxia

Inhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury. Juvenile female Duroc pigs (n = 6 colonic OMB, n = 6 no treatment) ranging from 39 to 51 kg in weight were exposed to smoke under general anesthesia for 2 h. Animals developed severe hypoxia 48 h after smoke inhalation as reflected by reduction in SpO2 to 66.3 ± 13.1% and PaO2 to 45.3 ± 7.6 mmHg, as well as bilateral diffuse infiltrates demonstrated on chest X-ray. Colonic OMB infusion (75–100 mL/kg dose) resulted in significant improvements in systemic oxygenation as demonstrated by an increase in PaO2 of 13.2 ± 4.7 mmHg and SpO2 of 15.2 ± 10.0% out to 2.5 h, compared to no-treatment control animals that experienced a decline in PaO2 of 8.2 ± 7.9 mmHg and SpO2 of 12.9 ± 18.7% over the same timeframe. Likewise, colonic OMB decreased PaCO2 and PmvCO2 by 19.7 ± 7.6 mmHg and 7.6 ± 6.7 mmHg, respectively, compared to controls that experienced increases in PaCO2 and PmvCO2 of 17.9 ± 11.7 mmHg and 18.3 ± 11.2 mmHg. We conclude that colonic delivery of OMB therapy has potential to treat patients experiencing severe hypoxemic respiratory failure.

Maternal-Fetal Results of COVID-19-Infected Pregnant Women Treated with Extracorporeal Membrane Oxygenation: A Descriptive Report.

COVID-19 infection may produce severe pneumonia, mainly in the adult population. Pregnant women with severe pneumonia are at high risk of developing complications, and conventional therapy sometimes fails to reverse hypoxemia. Therefore, extracorporeal membrane oxygenation (ECMO) is an option in cases with refractory hypoxemic respiratory failure. This study aims to evaluate the maternal-fetal risk factors, clinical characteristics, complications, and outcomes of 11 pregnant or peripartum patients with COVID-19 treated with ECMO. This is a retrospective descriptive study of 11 pregnant women undergoing ECMO therapy during the COVID-19 pandemic. In our cohort, four patients underwent ECMO during pregnancy (36.3%) and 7 during the postpartum period. Initially, they started on venovenous ECMO, and three patients were required to change modality due to clinical conditions. In total, 4/11 pregnant women (36.3%) died. We established two periods that differed in the implementation of a standardized care model for reducing associated morbidities and mortality. Neurological complications were responsible for most deaths. Regarding fetal outcomes at early-stage pregnancies on ECMO (4), we report three stillbirths (75%), and one newborn (twin pregnancy) survived and had a favorable evolution. At later-stage pregnancies, all newborns survived, and we did not identify any vertical infection. ECMO therapy is an alternative for pregnant women with severe hypoxemic respiratory failure due to COVID-19, and may improve maternal and neonatal results. Regarding fetal outcomes, the gestational age played a definitive role. However, the main complications reported in our series and others are neurological. It is essential to develop novel, future interventions to prevent these complications.

THE CRITICAL ROLE OF THE HISTONE MODIFICATION ENZYME SETDB2 IN THE PATHOGENESIS OF ACUTE RESPIRATORY DISTRESS SYNDROME.

Introduction: Acute respiratory distress syndrome (ARDS) is a severe hypoxemic respiratory failure with a high in-hospital mortality. However, the molecular mechanisms underlying ARDS remain unclear. Recent findings have indicated that the onset of severe inflammatory diseases, such as sepsis, is regulated by epigenetic changes. We investigated the role of epigenetic changes in ARDS pathogenesis using mouse models and human samples. Methods: Acute respiratory distress syndrome was induced in a mouse model (C57BL/6 mice, myeloid cell or vascular endothelial cell [VEC]-specific SET domain bifurcated 2 [Setdb2]-deficient mice [Setdb2 ff Lyz2 Cre+ or Setdb2 ff Tie2 Cre+ ], and Cre - littermates) by intratracheal administration of lipopolysaccharide (LPS). Analyses were performed at 6 and 72 h after LPS administration. Sera and lung autopsy specimens from ARDS patients were examined. Results: In the murine ARDS model, we observed high expression of the histone modification enzyme SET domain bifurcated 2 ( Setdb2 ) in the lungs. In situ hybridization examination of the lungs revealed Setdb2 expression in macrophages and VECs. The histological score and albumin level of bronchoalveolar lavage fluid were significantly increased in Setdb2 ff Tie2 Cre+ mice following LPS administration compared with Setdb2 ff Tie2 Cre- mice, whereas there was no significant difference between the control and Setdb2 ff Lyz2 Cre+ mice. Apoptosis of VECs was enhanced in Setdb2 ff Tie2 Cre+ mice. Among the 84 apoptosis-related genes, the expression of TNF receptor superfamily member 10b ( Tnfrsf10b ) was significantly higher in Setdb2 ff Tie2 Cre+ mice than in control mice. Acute respiratory distress syndrome patients' serum showed higher SETDB2 levels than those of healthy volunteers. SETDB2 levels were negatively correlated with the partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen concentration ratio. Conclusion: Acute respiratory distress syndrome elevates Setdb2 , apoptosis of VECs, and vascular permeability. Elevation of histone methyltransferase Setdb2 suggests the possibility to histone change and epigenetic modification. Thus, Setdb2 may be a novel therapeutic target for controlling the pathogenesis of ARDS.

High flow nasal cannula combined with non-invasive ventilation versus high flow nasal cannula alone in patients with acute hypoxemic respiratory failure due to pneumonia: a randomized controlled trial

In this monocentric, open label, randomized controlled trial we aimed to compare the efficacy of combined High Flow Nasal Cannula (HFNC) and Non invasive Ventilation (NIV) versus HFNC alone in acute hypoxemic respiratory failure (hARF) in patients affected by Community Acquired Pneumonia (CAP). We enrolled 49 patients affected by CAP with moderate to severe hypoxemic respiratory failure (P/F &lt; 300). The patients were randomized into two groups: one has been treated with HFNC alone (group A) while the other received NIV alternated to HFNC every 3 hours (group B). The primary outcome was P/F change from baseline to 21 hours. Secondary outcomes included variation of pH and pCO2, need to continue HFNC or NIV/HFNC after 45 hours, orotracheal intubation, mortality rate, and the devices comfort. Not statistical significant differences between the two arms were shown in the P/F change at 21 hours since baseline, in pCO2 and pH variation, mortality at hospital and at follow-up. We emphasize the importance of combined HFNC with NIV as a first step for severe pneumonia treatment whereas HFNC might represent as the first step treatment in less severe patients and during the NIV intervals.

Identification of a pediatric acute hypoxemic respiratory failure signature in peripheral blood leukocytes at 24 hours post-ICU admission with machine learning.

There is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200. We used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked gene lists were selected for pathway analysis. Pathway and network analysis was performed using the Pathway Network Analysis Visualizer (PANEV) and Reactome was used to perform an over-representation gene network analysis of the top-ranked genes common to both cohorts. Changes in metabolic pathways involved in energy balance, fundamental cellular processes such as protein translation, mitochondrial function, oxidative stress, immune signaling, and inflammation are differentially regulated early in pediatric ARDS and sepsis-induced AHRF compared to both healthy controls and to milder acute hypoxemia. Specifically, fundamental pathways related to the severity of hypoxemia emerged and included (1) ribosomal and eukaryotic initiation of factor 2 (eIF2) regulation of protein translation and (2) the nutrient, oxygen, and energy sensing pathway, mTOR, activated via PI3K/AKT signaling. Cellular energetics and metabolic pathways are important mechanisms to consider to further our understanding of the heterogeneity and underlying pathobiology of moderate and severe pediatric acute respiratory distress syndrome. Our findings are hypothesis generating and support the study of metabolic pathways and cellular energetics to understand heterogeneity and underlying pathobiology of moderate and severe acute hypoxemic respiratory failure in children.

Outcomes of a functional rehabilitation protocol in chronic critical disease by COVID-19: A case report

The 2019 novel coronavirus (SARS-CoV-2) is the virus that causes COVID-19. It can cause severe illness, with significant increase in morbidity and mortality rates, requiring the need for hospitalization and mechanical ventilation. This study aims to describe a functional rehabilitation protocol applied to a patient with COVID-19 after 21 days of mechanical ventilation (MV). We report a case of a 56-year-old female patient diagnosed with COVID-19 who presented severe hypoxemic respiratory failure, chronic critical disease, intensive care unit acquired weakness, difficult and prolonged weaning, organ dysfunction, and needed tracheotomy. The patient responded satisfactorily to a late functional rehabilitation protocol showing the importance of well-designed and individualized protocols to achieve maximum functional recovery.

Outcomes Among Mechanically Ventilated Patients With Severe Pneumonia and Acute Hypoxemic Respiratory Failure From SARS-CoV-2 and Other Etiologies

Early observations suggested that COVID-19 pneumonia had a higher mortality rate than other causes of pneumonia. To compare outcomes between mechanically ventilated patients with pneumonia due to COVID-19 (March 2020 to June 2021) and other etiologies (July 2016 to December 2019). This retrospective cohort study was conducted at the Johns Hopkins Healthcare System among adult patients (aged ≥18 years) with pneumonia who required mechanical ventilation in the first 2 weeks of hospitalization. Clinical, laboratory, and mechanical ventilation data were extracted from admission to hospital discharge or death. Pneumonia due to COVID-19. The primary outcome was 90-day in-hospital mortality. Secondary outcomes were time to liberation from mechanical ventilation, hospital length of stay, static respiratory system compliance, and ventilatory ratio. Unadjusted and multivariable-adjusted logistic regression, proportional hazards regression, and doubly robust regression were used in propensity score-matched sets to compare clinical outcomes. Overall, 719 patients (mean [SD] age, 61.8 [15.3] years; 442 [61.5%] were male; 460 [64.0%] belonged to a minoritized racial group and 253 [35.2%] were White) with severe COVID-19 pneumonia and 1127 patients (mean [SD] age, 60.9 [15.8] years; 586 [52.0%] were male; 459 [40.7%] belonged to a minoritized racial group and 655 [58.1%] were White) with severe non-COVID-19 pneumonia. In unadjusted analyses, patients with COVID-19 pneumonia had higher 90-day mortality (odds ratio, 1.21, 95% CI 1.04-1.41), longer time on mechanical ventilation (subdistribution hazard ratio 0.72, 95% CI 0.63-0.81), and lower compliance (32.0 vs 28.4 mL/kg PBW/cm H2O; P < .001) when compared with those with non-COVID-19 pneumonia. In propensity score-matched analyses, patients with COVID-19 pneumonia were equally likely to die within 90 days as those with non-COVID-19 pneumonia (odds ratio, 1.04; 95% CI, 0.81 to 1.35; P = .85), had similar respiratory system compliance (mean difference, 1.82 mL/cm H2O; 95% CI, -1.53 to 5.17 mL/cm H2O; P = .28) and ventilatory ratio (mean difference, -0.05; 95% CI, -0.22 to 0.11; P = .52), but had lower rates of liberation from mechanical ventilation (subdistribution hazard ratio, 0.81; 95% CI, 0.65 to 1.00) when compared with those with non-COVID-19 pneumonia. Patients with COVID-19 pneumonia had somewhat lower rates of being discharged from the hospital alive at 90 days (subdistribution hazard ratio, 0.83; 95% CI, 0.68 to 1.01) than those with non-COVID-19 pneumonia; however, this was not statistically significant. In this study, mechanically ventilated patients with severe COVID-19 pneumonia had similar mortality rates as patients with other causes of severe pneumonia but longer times to liberation from mechanical ventilation. Mechanical ventilation use in COVID-19 pneumonia should follow the same evidence-based guidelines as for any pneumonia.

Pneumoscrotum, a Rare Presentation of Barotrauma Following Noninvasive Positive Pressure Ventilation in Patients with Severe COVID-19 Pneumonia:.

Patients with Coronavirus disease 2019 (COVID-19) pneumonia are at risk of hypoxemic respiratory failure. Hence, many patients may require noninvasive positive pressure ventilation (NIPPV) during their hospital course. Using mechanical ventilation such as bilevel positive airway pressure or a ventilator to provide NIPPV may result in adverse events, including barotrauma. We reported two cases (40- and 43-years-old men) of severe COVID-19 pneumonia and hypoxemic respiratory failure who underwent NIPPV for respiratory support. These cases were complicated with barotrauma in their course of hospital admission that manifested with pneumoscrotum. In the cases of pneumoscrotum, it is crucial to understand its underlying etiology and origin since this clinical finding may be the outcome of life-threatening illnesses requiring urgent treatment.

Snap, Crackle, and Pop: From a Painful Finger to Progressive Dyspnea to Popping Neck Pain

A 40-year-old man was hospitalized with severe hypoxemic respiratory failure. His intolerable breathlessness was preceded by initial discoloration and pain affecting a single digit, which then spread to affect all fingers over a three-month period.

Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation-A Propensity Score-Matched Multicenter Cohort Study.

The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV (“straight intubation”). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the “straight intubation” group and the “NIV” group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.

Systemic thrombolytics as rescue therapy for COVID-19 patients with acute respiratory distress syndrome: A retrospective observational study.

Coronavirus disease 2019 (COVID-19) pneumonia with severe acute respiratory distress syndrome (ARDS) is often associated with a progressive respiratory failure that is refractory to maximal ventilatory support and other ARDS strategies. Studies show evidence of a hypercoagulable state in COVID-19 patients, including capillary thrombosis and alveolar fibrin deposits which impede normal gas exchange. In this context, thrombolysis is considered as a salvage therapy to rescue critically hypoxemic patients. In this retrospective observational study, the efficacy of thrombolysis on outcome of COVID-19 ARDS with respiratory failure was analyzed. Patients with severe ARDS and d-dimer levels of 5 μg/ml or above were initiated on alteplase, as a 25 mg bolus followed by a 25 mg infusion over 22 h. Primary outcome was intensive care unit (ICU) mortality and secondary outcomes were change in PaO2/FiO2 24 h after thrombolysis, avoidance of intubation, ventilator free days (VFD), and ICU and hospital length-of-stay (LOS). Thirteen out of 34 patients with severe COVID ARDS underwent thrombolysis. They had lower ICU mortality than non-thrombolysed patients (23.1% vs. 71.4%, P = 0.006), greater percentage improvement in PaO2/FiO2 (116% vs. 31.5%, P = 0.002), more VFDs (13 days vs. 0 day, P = 0.004), and lesser requirement for intubation (23.1% vs. 76.2%, P = 0.004). ICU and hospital LOS were similar. Thrombolysis can be considered as a rescue therapy for nonintubated COVID-19 ARDS patients with severe hypoxemic respiratory failure, who show evidence of a procoagulant state. Larger studies are needed before inclusion into the regular treatment protocol for COVID-19 patients.