Factors associated with mortality in acute respiratory failure patients without acute respiratory distress syndrome.

Background: Excess tidal volume and driving pressure were associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). Still, the appropriate mechanical ventilation strategy for patients who do not have ARDS needs to be understood. This study aimed to identify risk factors for mortality in acute respiratory failure patients without ARDS. Methods: We included all mechanically ventilated patients who did not meet the criteria for ARDS and were admitted to the medical intensive care unit (ICU) from October 2017 to September 2018. Patients who had tracheostomy before admission, were intubated for more than 24 hours before transfer to ICU, or underwent extracorporeal membrane oxygenation within 24 hours of ICU admission were excluded. Clinical and physiologic data were recorded and compared between survived and non-survived patients. Results: Of 289 patients with acute respiratory failure, 134 patients without ARDS were included; 69 (51%) died within 28 days. Demographics, principal diagnosis, and lung injury score on the first day of admission were not significantly different between survived and non-survived patients. In multivariate analysis, higher peak inspiratory pressure (PIP) during the first 3 days of admission [odds ratio (OR) 1.11, 95% confidence interval (CI): 1.01-1.22, P=0.04], higher sequential organ failure assessment score (OR 1.15, 95% CI: 1.04-1.28, P=0.008) and underlying cerebrovascular diseases (OR 7.09, 95% CI: 1.78-28.28, P=0.006) were independently associated with mortality in these patients, whereas dynamic lung compliance (Cdyn) and respiratory rate were not associated with mortality in the multivariate model. Conclusions: Mortality was high in mechanically ventilated patients without ARDS. Higher PIP is a potentially modifiable risk factor for mortality in these patients, independent of the baseline Cdyn. Underlying cerebrovascular diseases and increased disease severity are also independent factors associated with 28-day mortality.

Age, comorbidity burden and late presentation are significant predictors of hospitalization length and acute respiratory failure in patients with influenza.

Influenza viruses are responsible for a high number of infections and hospitalizations every year. In this study, we aimed to identify clinical and host-specific factors that influence the duration of hospitalization and the progression to acute respiratory failure (ARF) in influenza. We performed an analysis of data from a prospective active influenza surveillance study that was conducted over five seasons (2018/19 to 2022/23). A total of 1402 patients with influenza were included in the analysis, the majority of which (64.5%) were children (under 18 years), and 9.1% were elderly. At least one chronic condition was present in 29.2% of patients, and 9.9% of patients developed ARF. The median hospital stay was 4 days (IQR: 3, 6 days). The most important predictors of prolonged hospital stay and development of ARF were extremes of age (infants and elderly), presence of chronic diseases, particularly the cumulus of at least 3 chronic diseases, and late presentation to hospital. Among the chronic diseases, chronic obstructive pulmonary disease, cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease were strongly associated with a longer duration of hospitalization and occurrence of ARF. In this context, interventions aimed at chronic disease management, promoting influenza vaccination, and improving awareness and access to health services may contribute to reducing the impact of influenza not only in Romania but globally. In addition, continued monitoring of the circulation of influenza viruses is essential to limit their spread among vulnerable populations.

Racial Differences in Accuracy of Predictive Models for High-Flow Nasal Cannula Failure in COVID-19.

OBJECTIVES: To develop and validate machine learning (ML) models to predict high-flow nasal cannula (HFNC) failure in COVID-19, compare their performance to the respiratory rate-oxygenation (ROX) index, and evaluate model accuracy by self-reported race. DESIGN: Retrospective cohort study. SETTING: Four Emory University Hospitals in Atlanta, GA. PATIENTS: Adult patients hospitalized with COVID-19 between March 2020 and April 2022 who received HFNC therapy within 24 hours of ICU admission were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four types of supervised ML models were developed for predicting HFNC failure (defined as intubation or death within 7 d of HFNC initiation), using routine clinical variables from the first 24 hours of ICU admission. Models were trained on the first 60% (n = 594) of admissions and validated on the latter 40% (n = 390) of admissions to simulate prospective implementation. Among 984 patients included, 317 patients (32.2%) developed HFNC failure. eXtreme Gradient Boosting (XGB) model had the highest area under the receiver-operator characteristic curve (AUROC) for predicting HFNC failure (0.707), and was the only model with significantly better performance than the ROX index (AUROC 0.616). XGB model had significantly worse performance in Black patients compared with White patients (AUROC 0.663 vs. 0.808, p = 0.02). Racial differences in the XGB model were reduced and no longer statistically significant when restricted to patients with nonmissing arterial blood gas data, and when XGB model was developed to predict mortality (rather than the composite outcome of failure, which could be influenced by biased clinical decisions for intubation). CONCLUSIONS: Our XGB model had better discrimination for predicting HFNC failure in COVID-19 than the ROX index, but had racial differences in accuracy of predictions. Further studies are needed to understand and mitigate potential sources of biases in clinical ML models and to improve their equitability.

High-flow nasal cannula oxygen therapy for mild-moderate acute respiratory failure in patients with blunt chest trauma: An exploratory descriptive study.

OBJECTIVE: The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute respiratory failure (ARF). However, limited evidence exists regarding the effectiveness of HFNC for hypoxemic ARF in patients with blunt chest trauma (BCT). METHODS: This retrospective analysis focused on BCT patients with mild-moderate hypoxemic ARF who were treated with either HFNC or non-invasive ventilation (NIV) in the emergency medicine department from January 2021 to December 2022. The primary endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa). RESULTS: A total of 157 patients with BCT (72 in the HFNC group and 85 in the NIV group) were included in this study. The treatment failure rate in the HFNC group was 11.1% and 16.5% in the NIV group - risk difference of 5.36% (95% CI, -5.94-16.10%; P = 0.366). The most common cause of failure in the HFNC group was aggravation of respiratory distress. While in the NIV group, the most common reason for failure was treatment intolerance. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (1.4% vs 9.4%, 95% CI 0.40-16.18; P = 0.039). Univariate logistic regression analysis showed that chronic respiratory disease, abbreviated injury scale score (chest) (≥3), Acute Physiology and Chronic Health Evaluation II score (≥15), partial arterial oxygen tension /fraction of inspired oxygen (≤200) at 1 h of treatment and respiratory rate (≥32 /min) at 1 h of treatment were risk factors associated with HFNC failure. CONCLUSION: In BCT patients with mild-moderate hypoxemic ARF, the usage of HFNC did not lead to higher rate of treatment failure when compared to NIV. HFNC was found to offer better comfort and tolerance than NIV, suggesting it may be a promising new respiratory support therapy for BCT patients with mild-moderate ARF.

Performance of continuous glucose monitoring in patients with acute respiratory failure: a prospective, single-center observational study.

OBJECTIVE: Continuous glucose monitoring (CGM) may have benefits in achieving glycemic control in critically ill patients. The aim of this study was to assess the accuracy of the Freestyle Libre H (professional version of the Libre Pro). in patients with acute respiratory failure (ARF) in the intensive care unit (ICU). METHODS: 52 adult patients with ARF were selected. The performance of CGM was evaluated using arterial blood glucose (aBG) and point-of-care (POC) glucose as reference values. Numerical accuracy was evaluated by the mean absolute relative difference (MARD), Bland-Altman analysis, and %15/15(the percentage of CGM values within 15 mg/dL or 15% of reference values <100 mg/dL or >100mg/dL, respectively), %20/20 and %30/30; Clinical accuracy was assessed by Clarke error grid analysis. RESULTS: 519 and 1504 pairs of aBG/CGM and POC/CGM glucose values were analyzed. The MARD values were 13.8% and 14.7%, respectively. The mean deviation of the Bland‒Altman analysis was 0.82 mmol/L and 0.81 mmol/L. %15/15, %20/20 and %30/30 of aBG values were 62.6%, 75.5%, and 92.4%, respectively; %15/15, %20/20 and %30/30 of POC values were 57.1%, 72.9%, and 88.7%, respectively. The Clarke error grid analysis showed that 97.8% and 99.3% of the values located in the (A+B) zone. Additionally, accuracy of CGM is not affected by general patient factors. CONCLUSION: This study demonstrated that the accuracy of CGM in patients with ARF is lower than that in most outpatients, and it is not affected by general patient factors. Whether CGM is beneficial to glucose management in ICU needs further evaluation.

[High-flow nasal oxygen therapy and hypercapnic acute respiratory failure]. / Oxygénothérapie nasale à haut débit et insuffisance respiratoire aiguë hypercapnique.

Humidified high-flow nasal oxygen therapy (HFNO) has, in recent years, come to assume a key role in the management of hypoxemic acute respiratory failure (ARF). While non-invasive ventilation (NIV) currently represents the first-line ventilatory strategy in patients exhibiting hypercapnic ARF, the operating principles and physiological effects of HFNO could be interesting and useful in the initial management of hypercapnic ARF and/or after extubation, particularly in acute exacerbations of chronic obstructive pulmonary disease. Under these conditions, HFNO could be used either alone continuously or in combination with NIV during breaks in spontaneous breathing, depending on the severity and etiology of the underlying hypercapnic ARF.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024.

BACKGROUND: A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients. METHODS: The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI). RESULTS: During the study period (November 2022-January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21). CONCLUSIONS: Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.

Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation.

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Acute Respiratory Failure Resulting From Lambert-Eaton Myasthenic Syndrome: A Case Report and Literature Review.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder due to auto-antibodies against presynaptic voltage-gated calcium channels (VGCC). The typical manifestation of LEMS is proximal muscle weakness, autonomic dysfunction, and areflexia; however, an atypical manifestation of LEMS is weakness of respiratory muscles, leading to acute respiratory failure. Herein, we describe a case of acute respiratory failure resulting from LEMS. Our patient was a 63-year-old woman with a past medical history of metastatic small cell lung cancer (SCLC) who presented with ambulatory dysfunction, dysarthria, and progressive dyspnea. She was intubated because of hypoxia and developed acute respiratory failure without a clear pulmonary etiology, raising the suspicion of a neuromuscular junction disorder. She was diagnosed with LEMS with a positive paraneoplastic panel for VGCC antibodies, confirmed by electromyography and nerve conduction study (EMG/NCS), and treated with intravenous immunoglobulin (IVIg). The patient's hospital stay was complicated by pneumonia, and comfort care was ultimately pursued. Our case highlights the importance of considering LEMS in patients presenting with isolated respiratory muscle weakness without focal neurological deficits. To our knowledge, this is the first report to review all reported cases of LEMS with resultant respiratory failure. We aim to establish the association of LEMS with respiratory failure so that appropriate treatment is initiated as early as possible.

Severity and mortality of acute respiratory failure in pediatrics: A prospective multicenter cohort in Bogotá, Colombia.

Background and Aims: Acute respiratory failure (ARF) is the most frequent cause of cardiorespiratory arrest and subsequent death in children worldwide. There have been limited studies regarding ARF in high altitude settings. The aim of this study was to calculate mortality and describe associated factors for severity and mortality in children with ARF. Methods: The study was conducted within a prospective multicentric cohort that evaluated the natural history of pediatric ARF. For this analysis three primary outcomes were studied: mortality, invasive mechanical ventilation, and pediatric intensive care unit (PICU) length of stay. Eligible patients were children older than 1 month and younger than 18 years of age with respiratory difficulty at the time of admission. Patients who developed ARF were followed at the time of ARF, 48 h later, at the time of discharge, and at 30 and 60 days after discharge. It was conducted in the pediatric emergency, in-hospital, and critical-care services in three hospitals in Bogotá, Colombia, from April 2020 to June 2021. Results: Out of a total of 685 eligible patients, 296 developed ARF for a calculated incidence of ARF of 43.2%. Of the ARF group, 90 patients (30.4%) needed orotracheal intubation, for a mean of 9.57 days of ventilation (interquartile range = 3.00-11.5). Incidence of mortality was 6.1% (n = 18). The associated factors for mortality in ARF were a history of a neurologic comorbidity and a higher fraction of inspired oxygen at ARF diagnosis. For PICU length of stay, the associated factors were age between 2 and 5 years of age, exposure to smokers, and respiratory comorbidity. Finally, for mechanical ventilation, the risk factors were obesity and being unstable at admission. Conclusions: ARF is a common cause of morbidity and mortality in children. Understanding the factors associated with greater mortality and severity of ARF might allow earlier recognition and initiation of prompt treatment strategies.

Pediatric pulmonology year in review-Pediatric pulmonary critical care.

Pediatric pulmonary critical care literature has continued to grow in recent years. Our aim in this review is to narrowly focus on publications providing clinically-relevant advances in pediatric pulmonary critical care in 2023.

Failure Prediction of High-Flow Nasal Cannula at the Conventional Oxygen Therapy Phase in the Emergency Department.

INTRODUCTION: The use of high-flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure has been increasing in the emergency department (ED). However, studies are lacking on the prediction of HFNC failure before therapy initiation in the ED. We investigated whether the existing indices, such as the ratio of pulse oximetry oxygen saturation/fraction of inspired oxygen to respiratory rate (ROX) and ratio of ROX index to heart rate (ROX-HR), can accurately predict HFNC failure at the conventional oxygen therapy phase in the ED. METHODS: This retrospective single-center study included patients treated with HFNC in the ED. The ROX and ROX-HR indices were calculated before initiating HFNC. An estimated fraction of inspired oxygen was used for conventional oxygen therapy. We plotted each index's receiver operating characteristics curve and calculated the area under the curve (AUC) for diagnostic capacity. The optimal cutoff values were assessed using the Youden index. The primary outcome was HFNC failure, defined as intubation in the ED. RESULTS: Among the 97 included patients, 25 (25.8%) failed HFNC therapy in the ED. The ROX and ROX-HR indices measured before initiating HFNC showed AUCs of 0.709 and 0.754, respectively. A ROX index of <5.614 and a ROX-HR index of <6.152 were associated with a high risk of intubation, even after correcting for confounding variables. CONCLUSION: The ROX and ROX-HR indices measured before initiating HFNC provide a relatively fair predictive value of HFNC failure in the ED.

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.

Implementing High-Flow Nasal Oxygen Therapy in Medical Wards: A Scoping Review to Understand Hospital Protocols and Procedures.

Acute hypoxemic respiratory failure (ARF) is a common cause for hospital admission. High-flow nasal oxygen (HFNO) is increasingly used as a first-line treatment for patients with ARF, including in medical wards. Clinical guidance is crucial when providing HFNO, and health services use local health guidance documents (LHGDs) to achieve this. It is unknown what hospital LHGDs recommend regarding ward administration of HFNO. This study examined Australian hospitals' LHGDs regarding ward-based HFNO administration to determine content that may affect safe delivery. A scoping review was undertaken on 2 May 2022 and updated on 29 January 2024 to identify public hospitals' LHGDs regarding delivery of HFNO to adults with ARF in medical wards in two Australian states. Data were extracted and analysed regarding HFNO initiation, monitoring, maintenance and weaning, and management of clinical deterioration. Of the twenty-six included LHGDs, five documents referenced Australian Oxygen Guidelines. Twenty LHGDs did not define a threshold level of hypoxaemia where HFNO use was recommended over conventional oxygen therapy. Thirteen did not provide target oxygen saturation ranges whilst utilising HFNO. Recommendations varied regarding maximal levels of inspired oxygen and flow rates in the medical ward. Eight LHGDs did not specify any system to identify and manage deteriorating patients. Five LHGDs did not provide guidance for weaning patients from HFNO. There was substantial variation in the LHGDs regarding HFNO care for adult patients with ARF in Australian hospitals. These findings have implications for the delivery of high-quality, safe clinical care in hospitals.

Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure.

Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.

Advanced Respiratory Monitoring during Extracorporeal Membrane Oxygenation.

Advanced respiratory monitoring encompasses a diverse range of mini- or noninvasive tools used to evaluate various aspects of respiratory function in patients experiencing acute respiratory failure, including those requiring extracorporeal membrane oxygenation (ECMO) support. Among these techniques, key modalities include esophageal pressure measurement (including derived pressures), lung and respiratory muscle ultrasounds, electrical impedance tomography, the monitoring of diaphragm electrical activity, and assessment of flow index. These tools play a critical role in assessing essential parameters such as lung recruitment and overdistention, lung aeration and morphology, ventilation/perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient-ventilator synchrony. In contrast to conventional methods, advanced respiratory monitoring offers a deeper understanding of pathological changes in lung aeration caused by underlying diseases. Moreover, it allows for meticulous tracking of responses to therapeutic interventions, aiding in the development of personalized respiratory support strategies aimed at preserving lung function and respiratory muscle integrity. The integration of advanced respiratory monitoring represents a significant advancement in the clinical management of acute respiratory failure. It serves as a cornerstone in scenarios where treatment strategies rely on tailored approaches, empowering clinicians to make informed decisions about intervention selection and adjustment. By enabling real-time assessment and modification of respiratory support, advanced monitoring not only optimizes care for patients with acute respiratory distress syndrome but also contributes to improved outcomes and enhanced patient safety.

A non-invasive method to monitor respiratory muscle effort during mechanical ventilation.

PURPOSE: This study introduces a method to non-invasively and automatically quantify respiratory muscle effort (Pmus) during mechanical ventilation (MV). The methodology hinges on numerically solving the respiratory system's equation of motion, utilizing measurements of airway pressure (Paw) and airflow (Faw). To evaluate the technique's effectiveness, Pmus was correlated with expected physiological responses. In volume-control (VC) mode, where tidal volume (VT) is pre-determined, Pmus is expected to be linked to Paw fluctuations. In contrast, during pressure-control (PC) mode, where Paw is held constant, Pmus should correlate with VT variations. METHODS: The study utilized data from 250 patients on invasive MV. The data included detailed recordings of Paw and Faw, sampled at 31.25 Hz and saved in 131.1-second epochs, each covering 34 to 41 breaths. The algorithm identified 51,268 epochs containing breaths on either VC or PC mode exclusively. In these epochs, Pmus and its pressure-time product (PmusPTP) were computed and correlated with Paw's pressure-time product (PawPTP) and VT, respectively. RESULTS: There was a strong correlation of PmusPTP with PawPTP in VC mode (R² = 0.91 [0.76, 0.96]; n = 17,648 epochs) and with VT in PC mode (R² = 0.88 [0.74, 0.94]; n = 33,620 epochs), confirming the hypothesis. As expected, negligible correlations were observed between PmusPTP and VT in VC mode (R² = 0.03) and between PmusPTP and PawPTP in PC mode (R² = 0.06). CONCLUSION: The study supports the feasibility of assessing respiratory effort during MV non-invasively through airway signal analysis. Further research is warranted to validate this method and investigate its clinical applications.

SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure.

BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.