Higher levels of IL-1ra, IL-6, IL-8, MCP-1, MIP-3α, MIP-3ß, and fractalkine are associated with 90-day mortality in 132 non-immunomodulated hospitalized patients with COVID-19.

INTRODUCTION: Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. METHODS: Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. RESULTS: A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3ß, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. CONCLUSION: We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.

Interhospital Transfer of Patients With Acute Respiratory Failure in the United States: A Scoping Review.

OBJECTIVES: Interhospital transfer of patients with acute respiratory failure (ARF) is relevant in the current landscape of critical care delivery. However, current transfer practices for patients with ARF are highly variable, poorly formalized, and lack evidence. We aim to synthesize the existing evidence, identify knowledge gaps, and highlight persisting questions related to interhospital transfer of patients with ARF. DATA SOURCES: Ovid Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, CINAHL Plus, and American Psychological Association. STUDY SELECTION: We included studies that evaluated or described hospital transfers of adult (age > 18) patients with ARF between January 2020 and 2024 conducted in the United States. Using predetermined search terms and strategies, a total of 3369 articles were found across all databases. After deduplication, 1748 abstracts were screened by authors with 45 articles that advanced to full-text review. This yielded 16 studies that fit our inclusion criteria. DATA EXTRACTION: The studies were reviewed in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews by three authors. DATA SYNTHESIS: Included studies were mostly retrospective analyses of heterogeneous patients with various etiologies and severity of ARF. Overall, transferred patients were younger, had high severity of illness, and were more likely to have commercial insurance compared with nontransferred cohorts. There is a paucity of data examining why patients get transferred. Studies that retrospectively evaluated outcomes between transferred and nontransferred cohorts found no differences in mortality, although transferred patients have a longer length of stay. There is limited evidence to suggest that patients transferred early in their course have improved outcomes. CONCLUSIONS: Our scoping review highlights the sparse evidence and the urgent need for further research into understanding the complexity behind ARF transfers. Future studies should focus on defining best practices to inform clinical decision-making and improve downstream outcomes.

Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study.

RATIONALE: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting. METHODS: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support. ETHICS AND DISSEMINATION: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693403. PROTOCOL VERSION: 8 September 2023; version 5.

High-flow nasal oxygen therapy compared with conventional oxygen therapy in hospitalised patients with respiratory illness: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal oxygen therapy (HFNO) is used in diverse hospital settings to treat patients with acute respiratory failure (ARF). This systematic review aims to summarise the evidence regarding any benefits HFNO therapy has compared with conventional oxygen therapy (COT) for patients with ARF. METHODS: Three databases (Embase, Medline and CENTRAL) were searched on 22 March 2023 for studies evaluating HFNO compared with COT for the treatment of ARF, with the primary outcome being hospital mortality and secondary outcomes including (but not limited to) escalation to invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV). Risk of bias was assessed using the Cochrane risk-of-bias tool (randomised controlled trials (RCTs)), ROBINS-I (non-randomised trials) or Newcastle-Ottawa Scale (observational studies). RCTs and observational studies were pooled together for primary analyses, and secondary analyses used RCT data only. Treatment effects were pooled using the random effects model. RESULTS: 63 studies (26 RCTs, 13 cross-over and 24 observational studies) were included, with 10 230 participants. There was no significant difference in the primary outcome of hospital mortality (risk ratio, RR 1.08, 95% CI 0.93 to 1.26; p=0.29; 17 studies, n=5887) between HFNO and COT for all causes ARF. However, compared with COT, HFNO significantly reduced the overall need for escalation to IMV (RR 0.85, 95% CI 0.76 to 0.95 p=0.003; 39 studies, n=8932); and overall need for escalation to NIV (RR 0.70, 95% CI 0.50 to 0.98; p=0.04; 16 studies, n=3076). In subgroup analyses, when considering patients by illness types, those with acute-on-chronic respiratory failure who received HFNO compared with COT had a significant reduction in-hospital mortality (RR 0.58, 95% CI 0.37 to 0.91; p=0.02). DISCUSSION: HFNO was superior to COT in reducing the need for escalation to both IMV and NIV but had no impact on the primary outcome of hospital mortality. These findings support recommendations that HFNO may be considered as first-line therapy for ARF. PROSPERO REGISTRATION NUMBER: CRD42021264837.

Nonlinear relationship between platelet count and 30-day in-hospital mortality in ICU acute respiratory failure patients: a multicenter retrospective cohort study.

BACKGROUND: Limited evidence exists regarding the link between platelet count and 30-day in-hospital mortality in acute respiratory failure (ARF) patients. Thus, this study aims to investigate this association among ICU patients experiencing acute respiratory failure. METHODS: We conducted a retrospective cohort study across multiple centers, utilizing data from the US eICU-CRD v2.0 database covering 22,262 patients with ARF in the ICU from 2014 to 2015. Our aim was to investigate the correlation between platelet count and 30-day in-hospital mortality using binary logistic regression, subgroup analyses, and smooth curve fitting. RESULTS: The 30-day in-hospital mortality rate was 19.73% (4393 out of 22,262), with a median platelet count of 213 × 109/L. After adjusting for covariates, our analysis revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.99, 95% CI 0.99, 0.99). Subgroup analyses supported the robustness of these findings. Furthermore, a nonlinear relationship was identified between platelet count and 30-day in-hospital mortality, with the inflection point at 120 × 109/L. Below the inflection point, the effect size (OR) was 0.89 (0.87, 0.91), indicating a significant association. However, beyond this point, the relationship was not statistically significant. CONCLUSION: This study establishes a clear negative association between platelet count and 30-day in-hospital mortality among ICU patients with ARF. Furthermore, we have identified a nonlinear relationship with saturation effects, indicating that among ICU patients with acute respiratory failure, the lowest 30-day in-hospital mortality rate occurs when the baseline platelet count is approximately 120 × 109/L.

What Is the Potential Value of a Randomized Trial of Different Thresholds to Initiate Invasive Ventilation? A Health Economic Analysis.

OBJECTIVES: To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure. PERSPECTIVE: Publicly funded healthcare payer. SETTING: Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice. METHODS: We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year. RESULTS: In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios. CONCLUSIONS: It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival.

One-year mortality and readmission risks following hospitalization for acute exacerbation of chronic obstructive pulmonary disease based on the types of acute respiratory failure: An observational study.

Few studies have examined the risk factors associated with the type of acute respiratory failure (ARF) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). This study evaluated the clinical characteristics and prognosis of patients hospitalized for acute exacerbation of COPD based on the type of ARF. The medical charts of hospitalized patients with acute exacerbation of COPD between 2016 and 2021 were retrospectively reviewed. We classified ARF into 2 types: type 1 ARF with PaO2 < 60 mm Hg in room air or a ratio of arterial partial pressure to fractional inspired oxygen < 300, and type 2 ARF with PaCO2 > 45 mm Hg and arterial pH < 7.35. A total of 435 patients were enrolled in study, including 170 participants without ARF, 165 with type 1 ARF, and 100 with type 2 ARF. Compared with the non-ARF group, the frequency of high-flow nasal cannula, noninvasive ventilation, intensive care unit admissions, and in-hospital deaths was higher in the ARF group compared with the non-ARF group. The ARF group had higher 1-year mortality group (hazard ratio [HR], 2.809; 95% confidence interval [CI], 1.099-7.180; P = .031) and readmission within 1-year rates (HR, 1.561; 95% CI, 1.061-2.295; P = .024) than the non-ARF group. The type 1 ARF group had a higher risk of 1-year mortality (HR, 3.022; 95% CI, 1.041-8.774; P = .042) and hospital readmission within 1-year (HR, 2.053; 95% CI, 1.230-3.428; P = .006) compared with the non-ARF group. There was no difference in mortality and readmission rates between the type 1 and type 2 ARF groups. In conclusion, patients with type 1 ARF rather than type 2 ARF had higher mortality and readmission rates than those without ARF. The prognoses of patients with type 1 and type 2 ARF were similar.

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

High-Flow Nasal Cannula Versus Noninvasive Ventilation as Initial Treatment in Acute Hypoxia: A Propensity Score-Matched Study.

IMPORTANCE: Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used. OBJECTIVES: We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV. MAIN OUTCOMES AND MEASURES: The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio. RESULTS: A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001). CONCLUSIONS AND RELEVANCE: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies.

Dyspnea is severe and associated with a higher intubation rate in de novo acute hypoxemic respiratory failure.

BACKGROUND: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population. METHODS: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality. RESULTS: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046). CONCLUSIONS: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier # NCT01320384.

Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation.

PURPOSE: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. METHODS: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding. RESULTS: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046). CONCLUSION: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

Trophic Nutrition in ICU Patients Undergoing High-Flow Oxygen Therapy and/or Noninvasive Mechanical Ventilation: The Nutri-Trophic Study.

Enteral nutrition (EN) therapy in ICU patients requiring oxygen therapy with high-flow nasal cannula (HFNC) and/or noninvasive mechanical ventilation (NIMV) is controversial. A prospective, cohort, observational, and multicenter study was conducted in 10 ICUs in Spain to analyze the 90-day mortality, tolerance, side effects, and infectious complications of trophic EN in patients requiring HFNC therapy and/or NIVM. A total of 149 patients were enrolled. The mean age, severity scores, tracheobronchitis, bacteremia, and antimicrobial therapy were significantly higher in deceased than in living patients (p < 0.05), and the mortality rate was 14.8%. A total of 110 patients received oral trophic feedings, 36 patients received nasogastric tube feedings (NGFs), and 3 received mixed feedings. Trophic EN was discontinued in only ten (14.9%) patients because of feeding-related complications. The variables selected for the multivariate logistic regression on feeding discontinuation were SOFA upon admission (OR per unit = 1.461) and urea (OR per mg/dL = 1.029). There were no significant differences in the development of new infections according to the route of EN administration. Early trophic feeding administered to patients with acute respiratory failure requiring noninvasive ventilation is safe and feasible, and is associated with few dietary and infectious complications in a mortality, setting comparable to similar studies.

Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Use of CPAP Ventilation in Non-ICU Wards May Influence Outcomes in Patients with Severe Respiratory COVID-19.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Respiratory comorbidities and treatments in Duchenne muscular dystrophy: impact on life expectancy and causes of death.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death. METHODS: All male patients living in Sweden with DMD, born and deceased 1970-2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features. RESULTS: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients. CONCLUSIONS: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia.

Telemedicine critical care availability and outcomes among mechanically ventilated patients.

PURPOSE: Telemedicine Critical Care (TCC) improves adherence to evidence based protocols associated with improved mortality among patients receiving invasive mechanical ventilation (IMV). We sought to evaluate the relationship between hospital availability of TCC and outcomes among patients receiving IMV. MATERIALS AND METHODS: We performed a cross-sectional study of 66,522 adults who received IMV for non-postoperative acute respiratory failure at 318 non-federal hospitals in New York, Massachusetts, Maryland, and Florida in 2018. Hospital-level TCC availability was ascertained from the 2018 American Hospital Association Annual Survey. The primary outcome was in-hospital mortality. Secondary outcomes included the composite of tracheostomy or reintubation and duration of IMV. We used two-level hierarchical multivariable regression models to investigate the association between TCC availability and outcomes. RESULTS: 20,270 (30.5%) patients were admitted into 89 TCC-available hospitals. There was no difference between TCC and non-TCC-available hospitals in mortality (odds ratio [OR] 0.94, 99% confidence interval [CI] 0.84-1.05), composite of tracheostomy or reintubation (OR 0.95 [0.82-1.11], or duration of IMV (OR 0.95 [0.83-1.09]). There was no difference in outcomes among the subgroup of patients with acute respiratory distress syndrome. CONCLUSIONS: Hospital TCC availability was not associated with improved outcomes among patients receiving IMV.

The impact of aggressive and conservative propensity for initiation of neuromuscular blockade in mechanically ventilated patients with hypoxemic respiratory failure.

INTRODUCTION: Neuromuscular blockade (NMB) in ventilated patients may cause benefit or harm. We applied "incremental interventions" to determine the impact of altering NMB initiation aggressiveness. METHODS: Retrospective cohort study of ventilated patients with PaO2/FiO2 ratio < 150 mmHg and PEEP≥ 8cmH2O from the Medical Information Mart of Intensive Care IV database (MIMIC-IV version 1.0) estimating the effect of incremental interventions on in-hospital mortality and ventilator-free days, modifying hourly propensity for NMB initiation to be aggressive or conservative relative to usual care, adjusting for confounding with inverse probability weighting. RESULTS: 5221 patients were included (13.3% initiated on NMB). Incremental interventions estimated a strong effect on NMB usage: 5-fold higher hourly odds of initiation increased usage to 36.5% (CI = [34.3%,38.7%]) and 5-fold lower odds decreased usage to 3.8% (CI = [3.3%,4.3%]). Aggressive and conservative strategies demonstrated a U-shaped mortality relationship. 5-fold higher or lower propensity increased in-hospital mortality by 2.6% (0.95 CI = [1.5%,3.7%]) or 1.3% (0.95 CI = [0.1%,2.5%]) respectively. In secondary analysis of a healthier patient cohort, results were similar, however conservative strategies also improved ventilator-free days. INTERPRETATION: Aggressive or conservative initiation of NMB may worsen mortality. In healthier populations, marginally conservative NMB initiation strategies may lead to increased ventilator free days with minimal impact on mortality.

Analgesia and Sedation Use During Noninvasive Ventilation for Acute Respiratory Failure.

OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.

Pa o2 and Mortality in Neonatal Extracorporeal Membrane Oxygenation: Retrospective Analysis of the Extracorporeal Life Support Organization Registry, 2015-2020.

OBJECTIVES: Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pa o2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020. PATIENTS: Newborns supported by ECMO for respiratory indication were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pa o2 24 hours after ECMO initiation (H24 Pa o2 ) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pa o2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pa o2 < 60 mm Hg) and moderate hyperoxia (Pa o2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045. CONCLUSIONS: Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure.

Hospitalizaciones y eventos por insuficiencia cardiaca sistólica y diastólica en España entre 2016 y 2019. Un estudio de base poblacional / Hospital admissions and outcomes for systolic and diastolic heart failure in Spain between 2016 and 2019: A population-based study

Antecedentes y objetivos: En España carecemos de datos poblacionales de hospitalizaciones por insuficiencia cardiaca (IC) según sea sistólica o diastólica. Analizamos las diferencias clínicas, en mortalidad intrahospitalaria y reingresos de causa cardiovascular a los 30 días entre ambos tipos. Métodos: Estudio observacional retrospectivo de pacientes dados de alta con el diagnóstico principal de IC de los hospitales del Sistema Nacional de Salud entre 2016 y 2019, distinguiendo entre IC sistólica y diastólica. La fuente de datos fue el conjunto mínimo básico de datos del Ministerio de Sanidad. Se calcularon las razones de mortalidad intrahospitalaria y de reingreso a los 30 días estandarizadas por riesgo usando sendos modelos de regresión logística multinivel de ajuste de riesgo. Resultados: Se seleccionaron 190.200 episodios de IC. De ellos, 163.727 (86,1%) fueron por IC diastólica y se caracterizaron por presentar mayor edad, mayor proporción de mujeres, de diabetes y de insuficiencia renal que los de IC sistólica. Según los modelos de ajuste de riesgo la IC diastólica, frente a la sistólica, se comportó como un factor protector de mortalidad intrahospitalaria (odds ratio [OR]: 0,79; intervalo de confianza del 95% [IC 95%]: 0,75-0,83; p<0,001) y de reingreso de causa cardiovascular a los 30 días (OR: 0,93; IC 95%: 0,88-0,97; p0,002). Conclusiones: En España, entre 2016 y 2019, los episodios de hospitalización por IC fueron mayoritariamente por IC diastólica. Según los modelos de ajuste de riesgo la IC diastólica, con respecto a la sistólica, fue un factor protector de mortalidad intrahospitalaria y de reingreso de causa cardiovascular a los 30 días.(AU)

Background and purpose: In Spain there is a lack of population data that specifically compare hospitalization for systolic and diastolic heart failure (HF). We assessed clinical characteristics, in-hospital mortality and 30-day cardiovascular readmission rates differentiating by HF type. Methods: We conducted a retrospective observational study of patients discharged with the principal diagnosis of HF from The National Health System’ acute hospital during 2016-2019, distinguishing between systolic and diastolic HF. The source of the data was the Minimum Basic Data Set. The risk-standardized in-hospital mortality ratio and risk-standardized 30-day cardiovascular readmission ratio were calculated using multilevel risk adjustment models. Results: The 190,200 episodes of HF were selected. Of these, 163,727 (86.1%) were classified as diastolic HF and were characterized by older age, higher proportion of women, diabetes mellitus, dementia and renal failure than those with systolic HF. In the multilevel risk adjustment models, diastolic HF was a protective factor for both in-hospital mortality (odds ratio [OR]: 0.79; 95% confidence interval [CI]: 0.75-0.83; P<.001) and 30-day cardiovascular readmission versus systolic HF (OR: 0.93; 95% CI: 0.88-0.97; P=.002). Conclusions: In Spain, between 2016 and 2019, hospitalization episodes for HF were mostly due to diastolic HF. According to the multilevel risk adjustment models, diastolic HF compared to systolic HF was a protective factor for both in-hospital mortality and 30-day cardiovascular readmission.(AU)