Hypoxaemic respiratory failure and awake prone ventilation (HYPER-AP) - Protocol for randomized, controlled clinical trial.

BACKGROUND: Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure. METHODS: This is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation. CONCLUSION: The Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.

Persistent Peril: Recurrent Deep Vein Thrombosis and Pulmonary Embolism in a Patient With Protein S Deficiency Despite Optimal Anticoagulation Therapies.

The clotting system has evolved as an adaptive mechanism to prevent blood loss during vascular damage. However, the intricate nature of the clotting cascade and the complexities of human life can sometimes lead to the unnatural activation of this delicate cascade. This can result in blood clot formation within the cardiovascular system, contributing to a wide range of pathological conditions. Abnormal intravascular coagulation most commonly occurs in the deep veins of the lower extremities, and can emboli to other organs, hence, it is termed "venous thromboembolism" (VTE). In this report, we introduce a challenging case of VTE that poses a dilemma for current medical management. The patient with possible protein S deficiency underwent various guideline-directed medical treatments, yet experienced recurrent VTE episodes, including deep vein thrombosis (DVT) and pulmonary embolism (PE), leading to hospital readmissions. This case report sheds light on our challenges in effectively treating VTE.

ROX Index Variation as a Predictor of Outcomes in COVID-19 Patients.

Background: During the COVID-19 pandemic, emergency departments were overcrowded with critically ill patients, and many providers were confronted with ethical dilemmas in assigning respiratory support to them due to scarce resources. Quick tools for evaluating patients upon admission were necessary, as many existing scores proved inaccurate in predicting outcomes. The ROX Index (RI), a rapid and straightforward scoring system reflecting respiratory status in acute respiratory failure patients, has shown promise in predicting outcomes for COVID-19 patients. The 24 h difference in the RI accurately gauges mortality and the need for invasive mechanical ventilation (IMV) among patients with COVID-19. Methods: Study design: Prospective cohort study. A total of 204 patients were admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The RI was calculated at admission and 24 h later, and the difference was used to predict the association with mortality and the need for IMV, a logistic regression model was used to adjust for age, sex, presence of comorbidities, and disease severity. Finally, the data were analyzed using ROC. Results: The difference in respiratory RI between admission and 24 h is a good predictor for death (AUC 0.92) and for mechanic ventilation (AUC: 0.75). Each one-unit decrease in the RI difference at 24 h was associated with an odds ratio of 1.48 for the risk of death (95%CI: 1.31-1.67) and an odds ratio of 1.16 for IMV (95% IC: 1.1-1.23). Conclusions: The 24 h variation of RI is a good prediction tool to allow healthcare professionals to identify the patients who will benefit from invasive treatment, especially in low-resource settings.

Case series of dogs with blastomycosis managed with high-flow nasal oxygen therapy (2019-2023): 19 cases.

Objective: To describe the clinical presentation, progression, treatment, and outcome of dogs with blastomycosis treated with high-flow nasal oxygen therapy (HFNOT). Design: Retrospective case review. Setting: University veterinary teaching hospital. Animals: Nineteen client-owned dogs with strongly suspected or confirmed blastomycosis treated with HFNOT. Measurements and main results: The medical records of dogs with strongly suspected or confirmed blastomycosis between October 2019 and May 2023 that received HFNOT were evaluated. Nineteen dogs were included. Nine dogs were started directly on high-flow nasal oxygen therapy. The remaining 10 dogs first received traditional oxygen therapy and were then transitioned to HFNOT 3-142 h later. Of the 19 dogs, 1 survived to discharge from hospital, 12 were euthanized due to progression of disease, and 6 died during the hospitalization period. Conclusions and clinical importance: The prognosis for survival of dogs with severe blastomycosis requiring therapy beyond traditional oxygen methods was poor to grave in this population. This is the first known documented report of HFNOT use in dogs with confirmed or suspected blastomycosis.

Basing intubation of acutely hypoxemic patients on physiologic principles.

The decision to intubate a patient with acute hypoxemic respiratory failure who is not in apparent respiratory distress is one of the most difficult clinical decisions faced by intensivists. A conservative approach exposes patients to the dangers of hypoxemia, while a liberal approach exposes them to the dangers of inserting an endotracheal tube and invasive mechanical ventilation. To assist intensivists in this decision, investigators have used various thresholds of peripheral or arterial oxygen saturation, partial pressure of oxygen, partial pressure of oxygen-to-fraction of inspired oxygen ratio, and arterial oxygen content. In this review we will discuss how each of these oxygenation indices provides inaccurate information about the volume of oxygen transported in the arterial blood (convective oxygen delivery) or the pressure gradient driving oxygen from the capillaries to the cells (diffusive oxygen delivery). The decision to intubate hypoxemic patients is further complicated by our nescience of the critical point below which global and cerebral oxygen supply become delivery-dependent in the individual patient. Accordingly, intubation requires a nuanced understanding of oxygenation indexes. In this review, we will also discuss our approach to intubation based on clinical observations and physiologic principles. Specifically, we consider intubation when hypoxemic patients, who are neither in apparent respiratory distress nor in shock, become cognitively impaired suggesting emergent cerebral hypoxia. When deciding to intubate, we also consider additional factors including estimates of cardiac function, peripheral perfusion, arterial oxygen content and its determinants. It is not possible, however, to pick an oxygenation breakpoint below which the benefits of mechanical ventilation decidedly outweigh its hazards. It is futile to imagine that decision making about instituting mechanical ventilation in an individual patient can be condensed into an algorithm with absolute numbers at each nodal point. In sum, an algorithm cannot replace the presence of a physician well skilled in the art of clinical evaluation who has a deep understanding of pathophysiologic principles.

Designing a Bayesian adaptive clinical trial to evaluate novel mechanical ventilation strategies in acute respiratory failure using integrated nested Laplace approximations.

BACKGROUND: Adaptive trials usually require simulations to determine values for design parameters, demonstrate error rates, and establish the sample size. We designed a Bayesian adaptive trial comparing ventilation strategies for patients with acute hypoxemic respiratory failure using simulations. The complexity of the analysis would usually require computationally expensive Markov Chain Monte Carlo methods but this barrier to simulation was overcome using the Integrated Nested Laplace Approximations (INLA) algorithm to provide fast, approximate Bayesian inference. METHODS: We simulated two-arm Bayesian adaptive trials with equal randomization that stratified participants into two disease severity states. The analysis used a proportional odds model, fit using INLA. Trials were stopped based on pre-specified posterior probability thresholds for superiority or futility, separately for each state. We calculated the type I error and power across 64 scenarios that varied the probability thresholds and the initial minimum sample size before commencing adaptive analyses. Two designs that maintained a type I error below 5%, a power above 80%, and a feasible mean sample size were evaluated further to determine the optimal design. RESULTS: Power generally increased as the initial sample size and the futility threshold increased. The chosen design had an initial recruitment of 500 and a superiority threshold of 0.9925, and futility threshold of 0.95. It maintained high power and was likely to reach a conclusion before exceeding a feasible sample size. CONCLUSIONS: We designed a Bayesian adaptive trial to evaluate novel strategies for ventilation using the INLA algorithm to efficiently evaluate a wide range of designs through simulation.

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.

PaCO2 is nonlinearly associated with NIV failure in patients with hypoxemic respiratory failure.

OBJECTIVE: To explore the association between PaCO2 and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure. METHODS: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened. We enrolled the patients with hypoxemic respiratory failure. However, patients who used NIV due to acute-on-chronic respiratory failure or heart failure were excluded. Data before the use of NIV were collected. Requirement of intubation was defined as NIV failure. RESULTS: A total of 1029 patients were enrolled in final analysis. The rate of NIV failure was 45% (461/1029). A nonlinear relationship between PaCO2 and NIV failure was found by restricted cubic splines (p = 0.03). The inflection point was 32 mmHg. The rate of NIV failure was 42% (224/535) in patients with PaCO2 >32 mmHg. However, it increased to 48% (237/494) in those with PaCO2 ≤ 32 mmHg. The crude and adjusted hazard ratio (HR) for NIV failure was 1.36 (95%CI:1.13-1.64) and 1.23(1.01-1.49), respectively, if the patients with PaCO2 >32 mmHg were set as reference. In patients with PaCO2 ≤ 32 mmHg, one unit increment of PaCO2 was associated with 5% reduction of NIV failure. However, it did not associate with NIV failure in patients with PaCO2 >32 mmHg. CONCLUSIONS: PaCO2 and NIV failure was nonlinear relationship. The inflection point was 32 mmHg. Below the inflection point, lower PaCO2 was associated with higher NIV failure. However, it did not associate with NIV failure above this point.

Severe pulmonary hypertension and circulatory failure associated with Congenital syphilis. Case report.

BACKGROUND: Congenital syphilis is a vertical infection caused by Treponema pallidum. Despite the implementation of preventive strategies during pregnancy, its incidence is increasing, and it constitutes an important public health problem. Most patients with congenital syphilis are asymptomatic; however, a small group may develop severe disease at birth with the need of advanced resuscitation in the delivery room, acute hypoxemic respiratory failure, and hemodynamic instability. Therefore, awareness is needed. METHODS AND RESULTS: This series describes the clinical course of two late preterm infants with congenital syphilis who developed acute hypoxemic respiratory failure, pulmonary hypertension, and circulatory collapse early after birth. Integrated hemodynamic evaluation with neonatologist-performed echocardiography (NPE) and therapeutic management is provided. CONCLUSIONS: A comprehensive hemodynamic evaluation including early and serial functional echocardiography in these patients is needed to address the underlying complex pathophysiology and to help to establish accurate treatment.

Chronic obstructive pulmonary disease (COPD) and COPD-like phenotypes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Historically, two COPD phenotypes have been described: chronic bronchitis and emphysema. Although these phenotypes may provide additional characterization of the pathophysiology of the disease, they are not extensive enough to reflect the heterogeneity of COPD and do not provide granular categorization that indicates specific treatment, perhaps with the exception of adding inhaled glucocorticoids (ICS) in patients with chronic bronchitis. In this review, we describe COPD phenotypes that provide prognostication and/or indicate specific treatment. We also describe COPD-like phenotypes that do not necessarily meet the current diagnostic criteria for COPD but provide additional prognostication and may be the targets for future clinical trials.

Oxygenation saturation index in neonatal hypoxemic respiratory failure.

BACKGROUND: This study aimed to assess the validity of the oxygenation saturation index (OSI) and the ratio of oxygen saturation to the fraction of inspired oxygen (FIO2) (S/F ratio) with percutaneous oxygen saturation (OSISpO2 and the Sp/F ratio) and to evaluate the correlation between these values and the oxygen index (OI). It also determined their cut-off values for predicting OI in accordance with neonatal hypoxic respiratory failure severity. METHODS: We reviewed the data of 77 neonates (gestational age 31.7 ± 6.1 weeks; birthweight, 1768 ± 983 g) requiring invasive mechanical ventilation between 2013 and 2020, 1233 arterial blood gas samples in total. We calculated the OI, OSISpO2, OSI with arterial oxygen saturation (SaO2) (OSISaO2), Sp/F ratio, and the ratio of SaO2 to FIO2 (Sa/F ratio). RESULTS: The regression and Bland-Altman analysis showed good agreement between OSISpO2 or the Sp/F ratio and OSISaO2 or the Sa/F ratio. Although a significant positive correlation was found between OSISpO2 and OI, OSISpO2 was overestimated in SpO2 > 98% with a higher slope of the fitted regression line than that below 98% of SpO2. Furthermore, receiver-operating characteristic curve analysis using only SpO2 ≤ 98% samples showed that the optimal cut-off points of OSISpO2 and the Sp/F ratio for predicting OI were: OI 5, 3.0 and 332; OI 10, 5.3 and 231; OI 15, 7.7 and 108; OI 20, 11.0 and 149; and OI 25, 17.1 and 103, respectively. CONCLUSION: The cut-off OSISpO2 and Sp/F ratio values could allow continuous monitoring for oxygenation changes in neonates with the potential for wider clinical applications.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

BACKGROUND: The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

Switches in non-invasive respiratory support strategies during acute hypoxemic respiratory failure: Need to monitoring from a retrospective observational study

Objective To explore combined non-invasive-respiratory-support (NIRS) patterns, reasons for NIRS switching, and their potential impact on clinical outcomes in acute-hypoxemic-respiratory-failure (AHRF) patients. Design Retrospective, single-center observational study. Setting Intensive Care Medicine. Patients AHRF patients (cardiac origin and respiratory acidosis excluded) underwent combined NIRS therapies such as non-invasive-ventilation (NIV) and High-Flow-Nasal-Cannula (HFNC). Interventions Patients were classified based on the first NIRS switch performed (HFNC-to-NIV or NIV-to-HFNC), and further specific NIRS switching strategies (NIV trial-like vs. Non-NIV trial-like and single vs. multiples switches) were independently evaluated. Main variables of interest Reasons for switching, NIRS failure and mortality rates. Results A total of 63 patients with AHRF were included, receiving combined NIRS, 58.7% classified in the HFNC-to-NIV group and 41.3% in the NIV-to-HFNC group. Reason for switching from HFNC to NIV was AHRF worsening (100%), while from NIV to HFNC was respiratory improvement (76.9%). NIRS failure rates were higher in the HFNC-to-NIV than in NIV-to-HFNC group (81% vs. 35%, p < 0.001). Among HFNC-to-NIV patients, there was no difference in the failure rate between the NIV trial-like and non-NIV trial-like groups (86% vs. 78%, p = 0.575) but the mortality rate was significantly lower in NIV trial-like group (14% vs. 52%, p = 0.02). Among NIV to HFNC patients, NIV failure was lower in the single switch group compared to the multiple switches group (15% vs. 53%, p = 0.039), with a shorter length of stay (5 [2–8] vs. 12 [8–30] days, p = 0.001). Conclusions NIRS combination is used in real life and both switches’ strategies, HFNC to NIV and NIV to HFNC, are common in AHRF management. Transitioning from HFNC to NIV is suggested as a therapeutic escalation and in this context performance of a NIV-trial could be beneficial. ... (AU)

Objetivo Explorar los patrones combinados de soporte-respiratorio-no-invasivo (SRNI), las razones para cambiar de SRNI y su potencial impacto en los resultados clínicos en pacientes con insuficiencia-respiratoria-aguda-hipoxémica (IRAH). Diseño Estudio observacional retrospectivo unicéntrico. Ámbito Cuidados Intensivos. Pacientes Pacientes con IRAH (excluyendo causa cardíaca y acidosis respiratoria) que recibieron tanto ventilación-no-invasiva (VNI) como cánula-nasal-de-alto-flujo (CNAF). Intervenciones Se categorizó a los pacientes según el primer cambio de SRNI realizado (CNAF-to-VNI o VNI-to-CNAF) y se evaluaron estrategias específicas de SRNI (VNI trial-like vs. Non-VNI trial-like y cambio único vs. múltiples cambios de NIRS) de manera independiente. Variables de interés principales Razones para el cambio, así como las tasas de fracaso de SRNI y la mortalidad. Resultados Un total de 63 pacientes recibieron SRNI combinado, 58,7% clasificados en el grupo CNAF-to-VNI y 41,3% en el grupo VNI-to-CNAF. Los cambios de CNAF a VNI ocurrieron por empeoramiento de la IRHA (100%) y de VNI a CNAF por mejora respiratoria (76.9%). Las tasas de fracaso de SRNI fueron mayores de CNAF a VNI que de VNI a CNAF (81% vs. 35%, p < 0.001). Dentro de los pacientes de CNAF a VNI, no hubo diferencia en las tasas de fracaso entre los grupos VNI trial-like y no-VNI trial-like (86% vs. 78%, p = 0.575), pero la mortalidad fue menor en el grupo VNI trial-like (14% vs. 52%, p = 0.02). Dentro de los pacientes de VNI a CNAF, el fracaso de VNI fue menor en grupo de cambio único vs. múltiple (15% vs. 53%, p = 0.039). Conclusiones Los cambios de estrategia de SRNI son comunes en el manejo clínico diario de la IRHA. El cambio de CNAF a VNI impresiona de ser una escalada terapéutica y en este contexto la realización de un VNI-trial puede ser beneficioso. Al contrario, cambiar de VNI a CNAF impresiona de ser una desescalada terapéutica y parece segura si no hay fracaso ... (AU)

Diagnosis and Epidemiology of Acute Respiratory Failure.

Acute respiratory failure is a common clinical finding caused by insufficient oxygenation (hypoxemia) or ventilation (hypocapnia). Understanding the pathophysiology of acute respiratory failure can help to facilitate recognition, diagnosis, and treatment. The cause of acute respiratory failure can be identified through utilization of physical examination findings, laboratory analysis, and chest imaging.

Association between the ROX index and mortality in patients with acute hypoxemic respiratory failure: a retrospective cohort study.

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.

A Prospective Observational Study Comparing Oxygen Saturation/Fraction of Inspired Oxygen Ratio with Partial Pressure of Oxygen in Arterial Blood/Fraction of Inspired Oxygen Ratio among Critically Ill Patients Requiring Different Modes of Oxygen Supplementation in Intensive Care Unit.

Background: Intensive care unit (ICU) patients face a significant rise in mortality rates due to acute hypoxemic respiratory failure (AHRF). The diagnosis of AHRF is based on the PF ratio, but it has limitations in resource-constrained settings. Instead, the Kigali modification suggests using the oxygen saturation/fraction of inspired oxygen (SF) ratio. This study aims to correlate SF ratio and arterial oxygen pressure (PF) ratio in critically ill adults with hypoxemic respiratory failure, who required O2 therapy through different modes of oxygen supplementation. Materials and methods: In an ICU, a prospective observational study included 125 adult AHRF patients receiving oxygen therapy, with data collected on FiO2, PaO2, and SpO2. The SF ratio and PF ratio were calculated, and their correlation was assessed using statistical analysis. The receiver operator characteristics (ROC) curve analysis was conducted to assess the diagnostic precision of the SF ratio in identifying AHRF. Results: Data from a total of 250 samples were collected. The study showed a positive correlation (r = 0.622) between the SF ratio and the PF ratio. The SF threshold values of 252 and 321 were established for PF values of 200 and 300, respectively, featuring a sensitivity of 69% and specificity of 95%. Furthermore, it is worth noting that the PF ratio and SF ratio are interchangeable, regardless of the type of oxygen therapy, as the median values of both the PF ratio and SF ratio displayed statistical significance (p < 0.01) in both acidosis and alkalosis conditions. Conclusion: For patients with AHRF, the noninvasive SF ratio can effectively serve as a substitute for the invasive PF ratio across all oxygen supplementation modes. How to cite this article: Alur TR, Iyer SS, Shah JN, Kulkarni S, Jedge P, Patil V. A Prospective Observational Study Comparing Oxygen Saturation/Fraction of Inspired Oxygen Ratio with Partial Pressure of Oxygen in Arterial Blood/Fraction of Inspired Oxygen Ratio among Critically Ill Patients Requiring Different Modes of Oxygen Supplementation in Intensive Care Unit. Indian J Crit Care Med 2024; 28(3):251-255.

Inhaled Nitric Oxide in Neonatal Pulmonary Hypertension.

Pivotal trials investigating the use of inhaled nitric oxide (iNO) in the 1990s led to approval by the Food and Drug Administration in 1999. Inhaled nitric oxide is the only approved pulmonary vasodilator for persistent pulmonary hypertension of the newborn (PPHN). Selective pulmonary vasodilation with iNO in near-term and term neonates with PPHN is safe, and targeted use of iNO in less mature neonates with pulmonary hypertension (PH) can be beneficial. This review addresses a brief history of iNO, clinical features of neonatal PH, and the clinical application of iNO.

Novel subtypes of severe COVID-19 respiratory failure based on biological heterogeneity: a secondary analysis of a randomized controlled trial.

BACKGROUND: Despite evidence associating inflammatory biomarkers with worse outcomes in hospitalized adults with COVID-19, trials of immunomodulatory therapies have met with mixed results, likely due in part to biological heterogeneity of participants. Latent class analysis (LCA) of clinical and protein biomarker data has identified two subtypes of non-COVID acute respiratory distress syndrome (ARDS) with different clinical outcomes and treatment responses. We studied biological heterogeneity and clinical outcomes in a multi-institutional platform randomized controlled trial of adults with severe COVID-19 hypoxemic respiratory failure (I-SPY COVID). METHODS: Clinical and plasma protein biomarker data were analyzed from 400 trial participants enrolled from September 2020 until October 2021 with severe COVID-19 requiring ≥ 6 L/min supplemental oxygen. Seventeen hypothesis-directed protein biomarkers were measured at enrollment using multiplex Luminex panels or single analyte enzyme linked immunoassay methods (ELISA). Biomarkers and clinical variables were used to test for latent subtypes and longitudinal biomarker changes by subtype were explored. A validated parsimonious model using interleukin-8, bicarbonate, and protein C was used for comparison with non-COVID hyper- and hypo-inflammatory ARDS subtypes. RESULTS: Average participant age was 60 ± 14 years; 67% were male, and 28-day mortality was 25%. At trial enrollment, 85% of participants required high flow oxygen or non-invasive ventilation, and 97% were receiving dexamethasone. Several biomarkers of inflammation (IL-6, IL-8, IL-10, sTNFR-1, TREM-1), epithelial injury (sRAGE), and endothelial injury (Ang-1, thrombomodulin) were associated with 28- and 60-day mortality. Two latent subtypes were identified. Subtype 2 (27% of participants) was characterized by persistent derangements in biomarkers of inflammation, endothelial and epithelial injury, and disordered coagulation and had twice the mortality rate compared with Subtype 1. Only one person was classified as hyper-inflammatory using the previously validated non-COVID ARDS model. CONCLUSIONS: We discovered evidence of two novel biological subtypes of severe COVID-19 with significantly different clinical outcomes. These subtypes differed from previously established hyper- and hypo-inflammatory non-COVID subtypes of ARDS. Biological heterogeneity may explain inconsistent findings from trials of hospitalized patients with COVID-19 and guide treatment approaches.

Optimal timing for awake prone positioning in Covid-19 patients: Insights from an observational study from two centers.

BACKGROUND: The widespread application and interest in awake prone positioning stems from its ease and availability and its ability to enhance patients' oxygenation. Nevertheless, due to the absence of consensus over the regimen of awake prone positioning, the efficacy of awake prone positioning remains uncertain. OBJECTIVE: To explore the optimal regimen for awake prone positioning, including the timing of initiation, ideal daily duration, and strategies for improving patient comfort and encouraging adherence. DESIGN: Retrospective observational study. SETTING(S): Two university-affiliated hospitals in Shanghai. PARTICIPANTS: Between December 2022 and February 2023, a total of 475 patients with COVID-19-related pneumonia who received awake prone positioning were observed. METHODS: The data were collected from the hospital's electronic medical record system. The differentiation efficiency of peripheral blood oxygen saturation [SpO2]:fractional oxygen concentration in inspired air [FiO2] ratio at first awake prone positioning for different outcomes was tested by the area under the receiver operating characteristic curve. The Cox proportional hazard regression model was used to analyze the relationship between time to occurrence of 28-day outcomes and collected variables. Kaplan-Meier curves were plotted with the percentage of 28-day outcomes according to the SpO2:FiO2 ratio at first awake prone positioning after controlling covariates through Cox regression. RESULTS: The best efficiency in predicting patient outcomes was achieved when the cutoff SpO2:FiO2 ratio at first awake prone positioning was 200. Patients with a reduced SpO2:FiO2 ratio (≤200) experienced more adverse respiratory outcomes (RR = 5.42, 95%CI [3.35, 8.76], p < 0·001) and higher mortality (RR = 16.64, 95%CI [5.53, 50.13], p < 0.001). Patients with a SpO2:FiO2 ratio of ≥200 at first awake prone positioning, longer duration between first awake prone positioning and admission, more awake prone positioning days, and better awake prone positioning completion were significantly protected from 28-day adverse respiratory outcomes and mortality. CONCLUSIONS: Initiating awake prone positioning with a SpO2:FiO2 ratio exceeding 200, increasing the number of awake prone positioning days, prolonging the time between first awake prone positioning and admission, and achieving better completion of awake prone positioning were found to be significantly associated with reduced adverse respiratory outcomes and mortality. REGISTRATION: ClinicalTrials.gov; No.: NCT05795751; URL: www. CLINICALTRIALS: gov.