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.

The benefits and drawbacks of home oxygen therapy for COPD: what's next?

INTRODUCTION: Home oxygen therapy is one of the few interventions that can improve survival in patients with chronic obstructive pulmonary disease (COPD) when administered appropriately, although it may cause side effects and be an unnecessary burden for some patients. AREAS COVERED: This narrative review summarizes current literature on assessment of hypoxemia, different types of home oxygen therapy, potential beneficial and adverse effects, and emerging research of home oxygen therapy in COPD. A literature search was performed using MEDLINE and EMBASE up to January 2024, with additional articles being identified through clinical guidelines. EXPERT OPINION: Hypoxemia is common in patients with more severe COPD. Long-term oxygen therapy is established to prolong survival in patients with chronic severe resting hypoxemia. Conversely, in the absence of chronic severe resting hypoxemia, home oxygen therapy has an unclear or conflicting evidence base, including for palliation of breathlessness, and is generally not recommended. However, beneficial effects in some patients cannot be precluded. Evidence is emerging on optimal daily duration of oxygen use, role of high-flow and auto-titrated oxygen therapy, improved informed decision-making, and telemonitoring. Further research is needed to validate novel oxygen delivery systems and monitoring tools, and establish longer-term effects of ambulatory oxygen therapy in COPD.

Perfusion deficits may underlie lung and kidney injury in severe COVID-19 disease: insights from a multicenter international cohort study.

BACKGROUND: Lung perfusion defects, mainly due to endothelial and coagulation activation, are a key contributor to COVID-19 respiratory failure. COVID-19 patients may also develop acute kidney injury (AKI) because of renal perfusion deficit. We aimed to explore AKI-associated factors and the independent prediction of standardized minute ventilation (MV)-a proxy of alveolar dead space-on AKI onset and persistence in COVID-19 mechanically ventilated patients. METHODS: This is a multicenter observational cohort study. We enrolled 157 COVID-19 patients requiring mechanical ventilation and intensive care unit (ICU) admission. We collected clinical information, ventilation, and laboratory data. AKI was defined by the 2012 KDIGO guidelines and classified as transient or persistent according to serum creatinine criteria persistence within 48 h. Ordered univariate and multivariate logistic regression analyses were employed to identify variables associated with AKI onset and persistence. RESULTS: Among 157 COVID-19 patients on mechanical ventilation, 47% developed AKI: 10% had transient AKI, and 37% had persistent AKI. The degree of hypoxia was not associated with differences in AKI severity. Across increasing severity of AKI groups, despite similar levels of paCO2, we observed an increased MV and standardized MV, a robust proxy of alveolar dead space. After adjusting for other clinical and laboratory covariates, standardized MV remained an independent predictor of AKI development and persistence. D-dimer levels were higher in patients with persistent AKI. CONCLUSIONS: In critically ill COVID-19 patients with respiratory failure, increased wasted ventilation is independently associated with a greater risk of persistent AKI. These hypothesis-generating findings may suggest that perfusion derangements may link the pathophysiology of both wasted ventilation and acute kidney injury in our population.

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.

Successful Benralizumab treatment in acute near-fatal asthma with ECMO support: a case report.

INTRODUCTION: Near-fatal asthma (NFA) is a severe condition that can lead to respiratory arrest or high carbon dioxide levels, often requiring mechanical ventilation. Biologics have revolutionized the management of severe asthma, significantly improving symptom severity, reducing the number of exacerbations and hospitalizations, and decreasing the need for oral corticosteroids. However, their effectiveness in acute settings, particularly for ICU patients experiencing severe respiratory failure, is not well-studied. More research is needed to determine if biologics can improve recovery during severe asthma exacerbations. CASE STUDY: We report a case of NFA in a patient with severe allergic eosinophilic asthma, who experienced global respiratory failure necessitating hospitalization, intubation, and veno-venous extracorporeal membrane oxygenation (VV-ECMO). Given the severity of the clinical condition, compassionate administration of Benralizumab, which targets the IL-5 receptor, was attempted. RESULTS: Five days from anti-IL5 receptor treatment start, the patient was extubated and the ECMO stopped. After the stepdown to the respiratory intensive care unit (RICU), the patient was weaned from oxygen therapy and subsequently discharged from hospital. CONCLUSION: Benralizumab demonstrated rapid effectiveness in improving respiratory failure leading to successful weaning from VV-ECMO and subsequent extubation.

A case of testicular tumor and respiratory failure caused by choriocarcinoma syndrome managed through modified chemotherapy and extracorporeal membrane oxygenation.

Introduction: Choriocarcinoma syndrome with multiple lung metastases has a poor prognosis and causes respiratory failure due to alveolar hemorrhage. We encountered a case where the introduction of extracorporeal membrane oxygenation effectively sustained oxygenation until chemotherapy took effect on lung metastases of testicular tumors. Case presentation: A 35-year-old man with dyspnea was referred to our hospital. He showed left testicular tumor with multiple lung metastases. Serum human chorionic gonadotropin level was also elevated. Reduced chemotherapy was initiated and extracorporeal membrane oxygenation was administered because of low oxygen levels on the fourth day. Chemotherapy successfully reduced the size of the lung masses, and extracorporeal membrane oxygenation was discontinued. Respiratory status improved substantially, but the patient died of brain metastases 4 months later. Conclusion: Extracorporeal membrane oxygenation may be a useful option for managing respiratory failure resulting from choriocarcinoma syndrome until the respiratory condition is improved by chemotherapy for testicular tumors.

Flexible fibreoptic bronchoscopy is beneficial in children on extracorporeal membrane oxygenation support.

BACKGROUND: Flexible fibreoptic bronchoscopy (FFB) has the potential to enhance diagnostic capabilities and improve pulmonary function in children on extracorporeal membrane oxygenation (ECMO). OBJECTIVES: The objective of this study was to evaluate the benefits (clinical, radiological, and microbiological) of FFB and assess associated complications in children on ECMO. METHODS: We conducted a single-centre retrospective observational cohort study in a tertiary paediatric intensive care unit. All FFB episodes performed during the study period on children aged 0-18 years on ECMO were included. RESULTS: Out of the 155 children who received ECMO, 36 (23%) underwent a total of 92 episodes of FFB. FFB provided anatomical and pathological information in 53% (19/36) of cases and proved beneficial in clearing the airways in 62% (54/87) of the episodes. Overall, patients exhibited transient increases in ECMO and mechanical ventilation support 1 h post FFB in 14% (13/92) and 9.7% (9/92) episodes, respectively. At 6 h, the mean fraction of inspired oxygen on the mechanical ventilator was lower (0.46 [±0.21] vs 0.53 [±0.21] p < 0.01), with no change in mean airway pressure. Similarly, compared to pre-FFB, the fraction of inspired oxygen on the mechanical ventilator on ECMO was lower at 6 h and 24 h (0.65 [±0.25] vs 0.71 [±0.23] p < 0.01 and 0.006, respectively), with no significant change in the sweep gas flow and ECMO flow. The radiological imaging indicated improved or stable findings in 91% (83/91) of FFB episodes. FFB contributed to the identification of new and previously unknown microbiological information in 75% (27/36) of the patients. The incidence of major complications was 7.6%. Minor self-resolving bleeding occurred in 25% (23/92) episodes, and major bleeding occurred in two episodes, with a total of 10 episodes needing blood product transfusion. CONCLUSIONS: FFB is a valuable adjunct in managing children with severe respiratory failure on ECMO, offering clinical benefits with a low rate of major complications. Further studies should aim to develop a consensus approach encompassing criteria and clinical management around FFB in patients on ECMO.

Acute hypoxic respiratory failure due to Lenalidomide-induced interstitial pneumonitis in a patient with multiple myeloma.

BACKGROUND: Patients with multiple myeloma are immunosuppressed due to both the disease itself and immunosuppressive therapies. Thus, when presenting with respiratory failure and pulmonary opacities, pneumonia must be considered. However, while rare, immunomodulating medications used in the treatment of multiple myeloma can also cause potentially life-threatening respiratory failure, a distinction which has important treatment implications. CASE PRESENTATION: An 80-year-old male with recently diagnosed multiple myeloma undergoing treatment with lenalidomide and daratumumab presented with acute, rapidly progressive hypoxic respiratory failure ultimately requiring intubation and mechanical ventilatory support. Imaging revealed bilateral pulmonary opacities, however infectious workup was negative, and he was ultimately diagnosed with lenalidomide-induced interstitial pneumonitis, a rare but serious adverse effect of this medication. He was treated with drug discontinuation and methylprednisolone, and quickly recovered. CONCLUSION: Lenalidomide is an immunomodulating medication used in the treatment of multiple myeloma, and is associated with rare but serious cases of drug-induced interstitial pneumonitis. Thus, if a patient receiving lenalidomide develops shortness of breath and/or hypoxia, drug-induced pneumonitis must be on the differential. Permanent drug discontinuation with or without corticosteroids is the mainstay of treatment, and patients are often able to fully recover, underscoring the need for early recognition of this condition.

Assessment of echocardiographic interpretation of dual-lumen cannula during venovenous extracorporeal membrane oxygenation use for pediatric respiratory failure.

PURPOSE: Echocardiography is considered essential during cannulation placement and manipulations. Literature evaluating transthoracic echocardiography (TTE) usage during pediatric VV-ECMO is scant. The purpose of this study is to describe the use of echocardiography during VV-ECMO at a large, quaternary children's hospital. METHODS: A retrospective, single-year cohort study was performed of pediatric patients on VV-ECMO via dual-lumen cannula at our institution from January 2019 through December 2019. For each echocardiogram, final cannula component (re-infusion port (ReP), distal tip, proximal port and distal port) positions were evaluated by one echocardiographer. For TTEs with ReP in the right atrium, two echocardiographers independently evaluated ReP direction using 2-point (Yes/No) and 4-point scales, which were semi-quantitative protocols using color Doppler images to estimate ReP jet direction to the tricuspid valve. Cohen's kappa or weighted kappa was used to measure interrater agreement. RESULTS: During study period, 11 patients (64% male) received VV-ECMO with 49 TTEs and one transesophageal echocardiogram performed. The median patient age was 4.3 years [IQR: 1.1-11.5] and median VV-ECMO run time of 192 h [90-349]. The median time between TTEs on VV-ECMO was 34 h [8.3-65]. Most common position for the ReP was the right atrium (n = 33, 67%), and ReP location was not identified in five TTEs (10%). For ReP flow direction, echocardiographers agreed on 82% of TTEs using 2-point evaluation. There was only moderate agreement between echocardiographers on the 2-point and 4-point assessments (k = .54, kw = .46 respectively). CONCLUSIONS: TTE is the predominant cardiac ultrasound modality used during VV-ECMO for pediatric respiratory failure. Subjective evaluation of VV-ECMO ReP jet direction in the right atrium is challenging, regardless of assessment method.

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.

Long-term myocardial effects of noninvasive ventilation in patients with obesity hypoventilation syndrome.

INTRODUCTION: Chronic effects of noninvasive ventilation on myocardial function in patients with obesity hypoventilation syndrome (OHS) are scarcely understood. The aim of the present study was to evaluate the long-term effects of volume-targeted bilevel positive airway pressure ventilation (BiPAP) on cardiac parameters and myocardial biomarkers in patients with OHS. METHODS: Clinically stable patients with OHS referred to the tertiary center for the initiation of long-term BiPAP therapy were consecutively enrolled. At baseline, all participants underwent overnight cardiorespiratory polygraphy. BiPAP therapy using volume-targeted spontaneous/timed mode delivered via an oro-nasal mask was initiated. Beat-to-beat noninvasive monitoring by impedance cardiography was used to assess heart function at baseline and after 3 and 12 months of BiPAP use. Serum troponin 1, N-Terminal Pro-B-Type Natriuretic Peptide (NT-ProBNP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were monitored. RESULTS: Thirteen patients (10 men; mean age, 55.8 ± 9.8 years; mean body mass index of 47.8 ± 5.9 kg/m2) were recruited. From baseline to 3, and to 12 months of BiPAP use, left ventricular stroke volume (SV), ejection time (LVET), and ejection time index significantly increased (P = 0.030; P < 0.001; P = 0.003, respectively), while heart rate and systolic time ratio significantly decreased (P = 0.004; P = 0.034, respectively). Reductions in serum NT-proBNP, IL-6 and TNF-α were observed (P = 0.045; P = 0.018; P = 0.003, respectively). No significant changes in serum troponin were detected throughout the study. CONCLUSIONS: The present findings of increased SV, in association with lengthening of LVET, reductions of NT-proBNP and reductions in circulatory inflammatory markers in patients with stable OHS and chronic moderate-to-severe daytime hypercapnia treated with BiPAP over 1 year support the role of this therapeutic mode in such patients.

Utility of Serum Procalcitonin and Its Clearance in Predicting Outcomes in COVID-19 Patients.

Introduction Identification of coronavirus disease 2019 (COVID-19) patients at risk of worse clinical outcomes is crucial to improving patient care. Various biochemical markers have been used to predict outcomes in such patients. We aimed to evaluate the role of serum PCT (procalcitonin) and the utility of PCT clearance (PCTc) in predicting the outcome of patients with COVID-19 illness. Methods We prospectively included 39 patients with severe or critical COVID-19 illness with an age equal to more than 18 years. In addition to routine baseline investigations, serum PCT was measured at admission (PCT1) and day 5 of hospitalization (PCT2). PCTc was calculated using the formula [Formula: see text]. Results We observed that serum PCT at admission was significantly higher in non-survivors (median: 1.9 ng/ml IQR: 0.51-4.23) compared to survivors (median 0.35 (IQR: 0.1-1.2), p 0.002). On serial serum-PCT estimation, non-survivors had persistently elevated serum-PCT (median PCT1:1.9 ng/ml (IQR: 0.51-4.23) to median PCT2: 1.9ng/ml (IQR: 0.83-2.72), p 0.51) than survivors (median PCT1:0.35ng/ml (IQR: 0.1-1.19) to median PCT2: 0.15ng/ml (IQR: 0.05-0.29), p 0.01). However, no difference in serum PCTc was observed between the two groups (median: 35.3% (IQR: 12.5-84.9) in survivors vs. 71.7% (33.3-91.7) in non-survivors, p = 0.165). Conclusion Serum PCT is a potential biochemical marker that could predict outcomes in COVID-19 patients. Measurement of serial serum PCT and estimation of PCT clearance may serve as better predictors than a single value; however, well-designed studies are required to identify the definite role of serum PCT in COVID-19 patients of varying severity.

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.

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.

An Unusual Case of Bicuspid Aortic Valve With Prolapse Masquerading as Cusp Perforation.

We present a unique clinical scenario of a 58-year-old male with a past medical history of hypertension who initially presented with chest pain and was ruled in for non-ST elevation myocardial infarction (NSTEMI) but rapidly developed respiratory failure secondary to aortic insufficiency complicated by cardiogenic shock (CS), attributed to aortic valve prolapse. Intriguingly, the patient had a normal ECG on presentation, underscoring the dynamic nature of valvular pathology. The development of CS highlights the importance of early recognition, prompt diagnosis, and interdisciplinary management in such complex cases.

Advanced waveform analysis of diaphragm surface EMG allows for continuous non-invasive assessment of respiratory effort in critically ill patients at different PEEP levels.

BACKGROUND: Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm (sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi. METHODS: NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi. RESULTS: 593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (Ntolerant = 155, 37%, Nstrict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (Ntolerant = 145, 35%, Nstrict = 145, 31%), and high sEAdi area under the baseline (Ntolerant = 94, 23%, Nstrict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH2O. CONCLUSION: Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.

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.

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.

Hypophosphatemia in Chronic Obstructive Pulmonary Disease Patients Requiring Mechanical Ventilation and Its Impact on Weaning in an Intensive Care Unit of a Tertiary Care Hospital in Eastern India.

Background Hypophosphatemia, defined as a serum phosphate level less than 2.5 mg/dL, is a frequent finding in patients with chronic obstructive pulmonary disease (COPD) and has been speculated to negatively affect weaning outcomes. This study aimed to determine the incidence of hypophosphatemia in COPD patients requiring mechanical ventilation and evaluate the predictive role of hypophosphatemia as an indicator of successful weaning from mechanical ventilation in such patients admitted to the intensive care unit (ICU) in a tertiary care hospital in eastern India. Methodology This prospective observational study included 60 adult patients aged 18 to 75 years with acute exacerbations of COPD on mechanical ventilation in the ICU who were planned to undergo a weaning trial. Serum phosphate levels were assessed at the time of admission and before each weaning attempt. Weaning outcomes at each attempt, length of ventilator and ICU stay, and mortality were recorded. Data collection was initiated after approval of the Institutional Ethics Committee. Receiver operating curve (ROC) analysis was done to identify the cut-off value of serum phosphate which predicted successful weaning. Results Of 60 participants, hypophosphatemia on admission was present in 15 (25%) patients. Despite the correction, 13 (21.7%) patients had hypophosphatemia before the first weaning attempt. Only 22 patients out of 60 were successfully weaned off from mechanical ventilation in the first trial, accounting for a success rate of 36.7%, of whom 20 were normophosphatemic (90.9%). In the second and third weaning trials, hypophosphatemia was significantly associated with weaning failure. Overall differences in mean serum phosphate levels among those who failed to wean in each weaning trial and the successful attempt were statistically significant (p < 0.001). On ROC analysis of serum phosphate level before the first weaning trial, a cut-off value of ≥3.0 mg/dL was identified to have 86.4% sensitivity, 55.3% specificity, 52.8% positive predictive value, 87.5% negative predictive value, and 66.7% diagnostic accuracy in predicting weaning success. Five patients died, accounting for a mortality rate of 8.3%. Lower mean serum phosphate levels before the first weaning trial, higher mean age, and longer ventilator and ICU days were significantly associated with mortality among our study participants (p < 0.05). Conclusions Our findings suggest that maintaining normal serum phosphate levels is critical to successfully weaning off patients with COPD from ventilator support.