Acute Hypoxemic Respiratory Failure Patients Research Articles

Respiratory rate-oxygenation index on the 3rd day is the best predictor of treatment failure in COVID-19 patients.

Predictors of outcomes are essential to identifying severe COVID-19 cases and optimizing treatment and care settings. The respiratory rate-oxygenation (ROX) index, originally introduced for predicting the failure of non-invasive support in acute hypoxemic respiratory failure (AHRF), has not been extensively studied over time during hospitalization. This multicenter prospective observational study analyzed COVID-19-related AHRF patients admitted to eight Italian hospitals during the second pandemic wave. The study assessed the ROX index using receiver operator characteristic curves and areas under the curve with 95% confidence intervals to predict treatment failure, defined as endotracheal intubation (ETI) or death. A total of 227 patients (69.2% males) were enrolled, with a median arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at admission of 248 (interquartile range: 170-295). Nearly one-third (29.5%) required ETI or died during hospitalization. Those who experienced treatment failure were older (median age 70 versus 61 years, p<0.001), more likely to be current or former smokers (8.5% versus 6.4% and 42.4% versus 25.5%, p=0.039), had a higher prevalence of cardiovascular diseases (74.6% versus 46.3%, p<0.001), and had a lower PaO2/FiO2 ratio at presentation (median 229 versus 254, p=0.014). Gender, body mass index, and other comorbidities showed no significant differences. In patients who failed treatment, the ROX index was higher at presentation and worsened sharply by days 3 and 4. Conversely, in patients who survived without requiring ETI, the ROX index remained stable and reduced after 5-6 days. The ROX index's predictive ability improved notably by the third day of hospitalization, with the best cut-off value identified at 8.53 (sensitivity 75%, specificity 68%). Kaplan-Meier curves indicated that a ROX index of 8.53 or lower on days 1, 2, or 3 was associated with a higher risk of treatment failure. Thus, a single ROX index assessment on day 3 is more informative than its variability over time, with values of 8.53 or lower predicting non-invasive respiratory support failure in hospitalized COVID-19 patients.

Digital Twins of Acute Hypoxemic Respiratory Failure Patients Suggest a Mechanistic Basis for Success and Failure of Noninvasive Ventilation.

To clarify the mechanistic basis for the success or failure of noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF). We created digital twins based on mechanistic computational models of individual patients with AHRF. Interdisciplinary Collaboration in Systems Medicine Research Network. We used individual patient data from 30 moderate-to-severe AHRF patients who had failed high-flow nasal cannula (HFNC) therapy and subsequently underwent a trial of NIV. Using the digital twins, we evaluated lung mechanics, quantified the separate contributions of external support and patient respiratory effort to lung injury indices, and investigated their relative impact on NIV success or failure. In digital twins of patients who successfully completed/failed NIV, after 2 hours of the trial the mean (sd) of the change in total lung stress was -10.9 (6.2)/-0.35 (3.38) cm H2O, mechanical power -13.4 (12.2)/-1.0 (5.4) J/min, and total lung strain 0.02 (0.24)/0.16 (0.30). In the digital twins, positive end-expiratory pressure (PEEP) produced by HFNC was similar to that set during NIV. In digital twins of patients who failed NIV vs. those who succeeded, intrinsic PEEP was 3.5 (0.6) vs. 2.3 (0.8) cm H2O, inspiratory pressure support was 8.3 (5.9) vs. 22.3 (7.2) cm H2O, and tidal volume was 10.9 (1.2) vs. 9.4 (1.8) mL/kg. In digital twins, successful NIV increased respiratory system compliance +25.0 (16.4) mL/cm H2O, lowered inspiratory muscle pressure -9.7 (9.6) cm H2O, and reduced the contribution of patient spontaneous breathing to total driving pressure by 57.0%. In digital twins of AHRF patients, successful NIV improved lung mechanics, lowering respiratory effort and indices associated with lung injury. NIV failed in patients for whom only low levels of positive inspiratory pressure support could be applied without risking patient self-inflicted lung injury due to excessive tidal volumes.

Dysregulated Coagulation and Fibrinolysis Are Present in Patients Admitted to the Emergency Department with Acute Hypoxemic Respiratory Failure: A Prospective Study.

Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting a connection between dysregulated coagulant and fibrinolytic pathways in ARDS progression, it is plausible that this dysregulation also exists in AHRF. The aim of this study was to explore whether levels of soluble endothelial protein C receptor (sEPCR) and plasminogen differentiate patients admitted to the emergency department (ED) with AHRF. sEPCR and plasminogen levels were measured in 130 AHRF patients upon ED presentation by ELISA. Our results demonstrated that patients presenting to the ED with AHRF had elevated levels of sEPCR and plasminogen. It seems that dysregulation of coagulation and fibrinolysis occur in the early stages of respiratory failure requiring hospitalisation. Further research is needed to fully comprehend the contribution of sEPCR and plasminogen in AHRF.

Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure

BackgroundIn this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19).MethodsWe comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation.ResultsCompared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1β were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1β (202), IL-31 (169), MCP-1 (81), MIP-1β (55), and TNF-α (47) were lower.ConclusionsThe ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1β were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

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.

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. 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. 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. For patients with AHRF, the noninvasive SF ratio can effectively serve as a substitute for the invasive PF ratio across all oxygen supplementation modes. 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.

Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial

BackgroundHigh-flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position (APP) has been proven to increase oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, the APP is poorly tolerated in patients, and its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Therefore, it is worth exploring whether the lateral position is better for awake patients with AHRF.MethodsThis is a protocol for a three-arm parallel-group multicentre randomised controlled open-label exploratory trial. A total of 583 patients from two hospitals in Chongqing, China, will be randomised to take the semi-recumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19 pneumonia or lung infection and receiving HFNO therapy. The primary outcome is ventilator-free days in 28 days. The secondary outcomes are the 28-day intubation rate, 28-day all-cause mortality, total position change time, the incidence of adverse events, number of hours using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen (PaO2/FiO2) ratio (> 200 mmHg or ≤ 200 mmHg), time from admission to intervention implementation (< 24 h or ≥ 24 h), position changing time, and different diagnoses.DiscussionThis trial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19AHRF and compare the differences between them. To provide evidence for clinical decision-making and further research on position management.Trial registrationThis trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822. Registered on January 20, 2022.

Application of 24-h respiratory rate and oxygenation index variation to predict the outcome of high-flow nasal cannula therapy in patients with acute hypoxemic respiratory failure in arespiratory intensive care unit.

Background: An evaluation system is urgently needed to describe early predictors of the outcome of high-flow nasal cannula (HFNC) oxygen therapy in acute hypoxemic respiratory failure (AHRF) patients. Methods: All consecutive AHRF patients in aRespiratory Intensive Care Unit(RICU) receiving HFNC therapy between January 2019 and December 2021 were enrolled. Results: Of the 106 enrolled AHRF subjects, 57 (53.8%) succeeded in HFNC therapy and 49 (46.2%) failed. Being male (p = 0.006), initial respiratory rate oxygenation (ROX) index (p = 0.011), Acute Physiology and Chronic Health Evaluation II score (p = 0.007) and 24-h ROX index variation rate (p = 0.004) were independent factors of HFNC outcome; among these, 24-h ROX index variation rate (area under the curve =0.825) was the best evaluation indicator. Conclusion: 24-h ROX index variation rate, introduced by our study, has shown the best potential to predict HFNC outcome in AHRF patients.

Comparison of the efficacy and comfort of high-flow nasal cannula with different initial flow settings in patients with acute hypoxemic respiratory failure: a systematic review and network meta-analysis

BackgroundHigh-flow nasal cannula (HFNC) has been proven effective in improving patients with acute hypoxemic respiratory failure (AHRF), but a discussion of its use for initial flow settings still need to be provided. We aimed to compare the effectiveness and comfort evaluation of HFNC with different initial flow settings in patients with AHRF.MethodsStudies published by October 10, 2022, were searched exhaustively in PubMed, Embase, Web of Science, Cochrane Library (CENTRAL), and the China National Knowledge Infrastructure (CNKI) database. Network meta-analysis (NMA) was performed with STATA 17.0 and R software (version 4.2.1). A Bayesian framework was applied for this NMA. Comparisons of competing models based on the deviance information criterion (DIC) were used to select the best model for NMA. The primary outcome is the intubation at day 28. Secondary outcomes included short-term and long-term mortality, comfort score, length of ICU or hospital stay, and 24-h PaO2/FiO2.ResultsThis NMA included 23 randomized controlled trials (RCTs) with 5774 patients. With NIV as the control, the HFNC_high group was significantly associated with lower intubation rates (odds ratio [OR] 0.72 95% credible interval [CrI] 0.56 to 0.93; moderate quality evidence) and short-term mortality (OR 0.81 95% CrI 0.69 to 0.96; moderate quality evidence). Using HFNC_Moderate (Mod) group (mean difference [MD] − 1.98 95% CrI -3.98 to 0.01; very low quality evidence) as a comparator, the HFNC_Low group had a slight advantage in comfort scores but no statistically significant difference. Of all possible interventions, the HFNC_High group had the highest probability of being the best in reducing intubation rates (73.04%), short-term (82.74%) and long-term mortality (67.08%). While surface under the cumulative ranking curve value (SUCRA) indicated that the HFNC_Low group had the highest probability of being the best in terms of comfort scores.ConclusionsThe high initial flow settings (50–60 L/min) performed better in decreasing the occurrence of intubation and mortality, albeit with poor comfort scores. Treatment of HFNC for AHRF patients ought to be initiated from moderate flow rates (30–40 L/min), and individualized flow settings can make HFNC more sensible in clinical practice.

An observational study on the timing of intubation and outcome in COVID-19 ARDS patients who were treated with high flow nasal oxygen prior to invasive mechanical ventilation: A time series analysis (InOutHFNO trial).

Prolonged high flow nasal oxygen (HFNO) application might delay intubation and increase mortality in acute hypoxemic respiratory failure (AHRF) patients. Intubation in coronavirus disease 2019 (COVID-19) AHRF (CAHRF) patients 24 to 48 hours after HFNO initiation has been associated with increased mortality in previous studies. This cut-off period is variable in previous studies. A time series analysis could reflect more robust data on outcome in relation to HFNO duration before intubation in CAHRF. A retrospective study was conducted at 30-bedded ICU of a tertiary care teaching hospital from July 2020 to August 2021. The study cohort comprised 116 patients who required HFNO and were subsequently intubated following HFNO failure. A time series analysis of patient outcomes on each day of HFNO application prior to invasive mechanical ventilation (IMV) was done. ICU and hospital mortality was 67.2%. Beyond day 4 of HFNO application, there was a trend towards increased risk-adjusted ICU and hospital mortality for each day delay in intubation of CAHRF patients on HFNO [OR 2.718; 95% CI 0.957-7.721; P 0.061]. This trend was maintained till day 8 of HFNO application, after which there was 100% mortality. Taking day four as a cut-off in the timeline of HFNO application, we have observed an absolute mortality benefit of 15% with early intubation despite a higher APACHE-IV score than the late intubation group. IMV beyond the 4th day of HFNO initiation in CAHRF patients increases mortality.

ROX index versus HACOR scale in predicting success and failure of high-flow nasal cannula in the emergency department for patients with acute hypoxemic respiratory failure: a prospective observational study

BackgroundHigh-flow nasal cannula has been a promising initial respiratory support measure for patients with acute hypoxemic respiratory failure (AHRF) in the emergency department (ED). However, delayed detection of HFNC failure is associated with increased mortality. The ROX index is a tool that can help predict HFNC success. Nonetheless, its utility in ED patients is limited, and no studies have compared it with the HACOR scale, another tool that may be as accurate in predicting HFNC failure. Therefore, we aimed to compare the prognostic utility of the ROX index and the HACOR scale in emergency AHRF patients.MethodsThis prospective observational study was conducted at the ED of Siriraj Hospital, Thailand, between August 2018 and February 2020. Adult patients with AHRF requiring HFNC in the ED were included. The ROX index and the HACOR scale were measured at 1, 2, and 6 h after HFNC initiation. The primary outcome was HFNC success, defined as no intolerance or escalation towards mechanical ventilation or non-invasive ventilation within 48 h.ResultsA total of 75 patients were enrolled; 52 (69.3%) had a successful treatment. The ROX index was higher in the success group, while the HACOR scale was lower at all timepoints. The ROX index yielded generally higher discrimination capacity based on the area under the receiver operating characteristic curve (AUROC) than the HACOR scale [AUROC at 1, 2, and 6 h = 0.815, 0.784, 0.853 for ROX in predicting HFNC success and 0.733, 0.690, and 0.764 for HACOR in predicting HFNC failure]. The ROX index measured at 6 h at the cut-point of 4.88 had 92.98% sensitivity, 61.11% specificity, 88.33% positive predictive value, and 73.33% negative predictive value with a diagnostic accuracy of 85.33%.ConclusionThe ROX index had superior prognostic utility in predicting HFNC outcome (success/failure) compared to the HACOR scale in patients with AHRF in the ED setting. Moreover, it is less complex and more efficient to be employed at bedside. Therefore, the ROX index is a more appropriate tool to guide further management and potential escalation therapy for AHRF patients with HFNC therapy initiated in the ED.

Predictors of Noninvasive Respiratory Support Failure in COVID-19 Patients: A Prospective Observational Study.

Background and Objective: Respiratory assistance tactic that is best for COVID-19-associated acute hypoxemic respiratory failure (AHRF) individuals has yet to be determined. Patients with AHRF may benefit from the use of a high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The goals of this prospective observational research were to estimate predictive factors for HFNC and NIV failure in COVID-19-related AHRF subjects. Materials and Methods: The research enlisted the participation of 124 patients. A stepwise treatment approach was used. HFNC and NIV were used on 124 (100%) and 64 (51.6%) patients, respectively. Thirty (24.2%) of 124 patients were intubated and received invasive mechanical ventilation. Results: 85 (68.5%) patients were managed successfully. Patients who required NIV exhibited a higher prevalence of treatment failure (70.3% vs. 51.6%, p = 0.019) and had higher mortality (59.4% vs. 31.5%, p = 0.001) than patients who received HFNC. Using logistic regression, the respiratory rate oxygenation (ROX) index at 24 h (odds ratio (OR) = 0.74, p = 0.018) and the Charlson Comorbidity Index (CCI) (OR = 1.60, p = 0.003) were found to be predictors of HFNC efficacy. It was the ROX index at 24 h and the CCI optimum cut-off values for HFNC outcome that were 6.1 (area under the curve (AUC) = 0.73) and 2.5 (AUC = 0.68), respectively. Serum ferritin level (OR = 0.23, p = 0.041) and lymphocyte count (OR = 1.03, p = 0.01) were confirmed as predictors of NIV failure. Serum ferritin level at a cut-off value of 456.2 ng/mL (AUC = 0.67) and lymphocyte count lower than 0.70 per mm3, (AUC = 0.70) were associated with NIV failure with 70.5% sensitivity, 68.7% specificity and sensitivity of 84.1%, specificity of 56.2%, respectively. Conclusion: The ROX index at 24 h, CCI, as well as serum ferritin level, and lymphocyte count can be used as markers for HFNC and NIV failure, respectively, in SARS-CoV-2-induced AHRF patients.

Midline peripheral catheters inserted in the superficial femoral vein at mid-thigh: Wise choice in COVID-19 acute hypoxemic respiratory failure patients with helmet continuous positive airway pressure.

During coronavirus disease 2019 (COVID-19) pandemic, Helmet Continuous Positive Airway Pressure (h-CPAP) has been widely used to treat Acute Hypoxemic Respiratory Failure (AHRF). In COVID-19 patients undergoing h-CPAP a simple short peripheral catheter could be insufficient. According to the European Recommendations for Proper Indication and Use of Peripheral venous access consensus, a stable peripheral Vascular Access Device is indicated for intravenous treatment compatible with the peripheral route scheduled for more than 1 week. The aim of this prospective study was to evaluate the performance and the potential complications of superficial femoral midline catheters (SFMC) inserted in the Superficial Femoral Vein by direct Seldinger technique with peripheral tip (Arrow®, Teleflex; 20 cm length four FR single lumen and seven FR dual lumen) in AHRF COVID-19 patient. Complications were divided in early (accidental puncture of superficial femoral artery (APSFA); accidental saphenous nerve puncture (ASNP); bleeding) and late (Catheter Related Thrombosis (CRT); Catheter-Related Bloodstream Infections (CRBSI); Accidental Removal (AR); persistent withdrawal occlusion (PWO)). From 1st October 2020 to 30th June 2021 we conducted a prospective observational study in COVID-19 sub-intensive wards at Luigi Sacco Hospital (Milan). Hundred seventy five SFMC (mean dwell time 11.1 ± 9.8 days) were implanted in COVID-19 patients, 107 (61.1%) during h-CPAP treatment (10.5 ± 8.9 days), the remaining 68 (38.9%) in patients with severe disease. We recorded two minor immediate/early complications (APSFA without sequelae) and no major complications.The long-term follow-up registered four CRBSI (2.3%-2.5/1000 catheters days (CD)), five CRT (2.9%: 2.6/1000 CD), 22 AR (12.6%; 11.4/1000 CD), 38 PWO (36.5%), 34 of which occurred due to fibroblastic sleeve (32.7%). SFMC proved to be safe, easy and time-saving. It could be implemented, after a careful benefits and risks evaluation, in particular settings such as h-CPAP, delirium, bleeding risk factors and palliative care patients.

Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

BackgroundDelaying intubation in patients who fail high-flow nasal cannula (HFNC) may result in increased mortality. The ROX index has been validated to predict HFNC failure among pneumonia patients with acute hypoxemic respiratory failure (AHRF), but little information is available for non-pneumonia causes. In this study, we validate the ROX index among AHRF patients due to both pneumonia or non-pneumonia causes, focusing on early prediction.MethodsThis was a retrospective observational study in eight Singapore intensive care units from 1 January 2015 to 30 September 2017. All patients >18 years who were treated with HFNC for AHRF were eligible and recruited. Clinical parameters and arterial blood gas values at HFNC initiation and one hour were recorded. HFNC failure was defined as requiring intubation post-HFNC initiation.ResultsHFNC was used in 483 patients with 185 (38.3%) failing HFNC. Among pneumonia patients, the ROX index was most discriminatory in pneumonia patients one hour after HFNC initiation [AUC 0.71 (95% CI 0.64–0.79)], with a threshold value of <6.06 at one hour predicting HFNC failure (sensitivity 51%, specificity 80%, positive predictive value 61%, negative predictive value 73%). The discriminatory power remained moderate among pneumonia patients upon HFNC initiation [AUC 0.65 (95% CI 0.57–0.72)], non-pneumonia patients at HFNC initiation [AUC 0.62 (95% CI 0.55–0.69)] and one hour later [AUC 0.63 (95% CI 0.56–0.70)].ConclusionThe ROX index demonstrated moderate discriminatory power among patients with either pneumonia or non-pneumonia-related AHRF at HFNC initiation and one hour later.

Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study)

BackgroundWe aimed to assess the efficacy of a closed-loop oxygen control in critically ill patients with moderate to severe acute hypoxemic respiratory failure (AHRF) treated with high flow nasal oxygen (HFNO).MethodsIn this single-centre, single-blinded, randomized crossover study, adult patients with moderate to severe AHRF who were treated with HFNO (flow rate ≥ 40 L/min with FiO2 ≥ 0.30) were randomly assigned to start with a 4-h period of closed-loop oxygen control or 4-h period of manual oxygen titration, after which each patient was switched to the alternate therapy. The primary outcome was the percentage of time spent in the individualized optimal SpO2 range.ResultsForty-five patients were included. Patients spent more time in the optimal SpO2 range with closed-loop oxygen control compared with manual titrations of oxygen (96.5 [93.5 to 98.9] % vs. 89 [77.4 to 95.9] %; p < 0.0001) (difference estimate, 10.4 (95% confidence interval 5.2 to 17.2). Patients spent less time in the suboptimal range during closed-loop oxygen control, both above and below the cut-offs of the optimal SpO2 range, and less time above the suboptimal range. Fewer number of manual adjustments per hour were needed with closed-loop oxygen control. The number of events of SpO2 < 88% and < 85% were not significantly different between groups.ConclusionsClosed-loop oxygen control improves oxygen administration in patients with moderate-to-severe AHRF treated with HFNO, increasing the percentage of time in the optimal oxygenation range and decreasing the workload of healthcare personnel. These results are especially relevant in a context of limited oxygen supply and high medical demand, such as the COVID-19 pandemic.Trial registration The HILOOP study was registered at www.clinicaltrials.gov under the identifier NCT04965844.

Extracorporeal membrane oxygenation (ECMO) support for acute hypoxemic respiratory failure patients: outcomes and predictive factors.

BackgroundExtracorporeal membrane oxygenation (ECMO) is an important rescue therapy for patients with refractory respiratory or circulatory failure. High cost and associated complications warrant careful case selection. The aim of this study was to investigate the outcomes and factors associated with mortality in acute hypoxemic respiratory failure patients who received ECMO support, and to externally validate preexisting ECMO survival prediction scoring systems.MethodsThis retrospective study enrolled acute hypoxemic respiratory failure patients who received veno-venous (VV) or veno-arterial (VA) ECMO support at Siriraj Hospital (Bangkok, Thailand) from 2010 to 2020. All relevant baseline patient characteristics including ECMO survival prediction scores were recorded. The primary outcome was in-hospital mortality. Multivariate logistic regression analysis was employed to identify independent predictors of in-hospital mortality.ResultsOf a total of 65 patients, 34 (52%) were male, the median (IQR) age was 61 years (49–70 years), the median body mass index (BMI) was 22.6 kg/m2 (20.6–28 kg/m2), and the median Sequential Organ Failure Assessment (SOFA) score was 13 [11–16]. Forty-three patients (66%) received VV-ECMO, and 22 (34%) received VA-ECMO support. In-hospital mortality was 69%. Multivariate analysis identified a SOFA score >14, hospitalized >72 hours before ECMO initiation, PaO2/FiO2 ratio <60, and pH <7.2 as independent predictors of in-hospital mortality. These four parameters were combined to create the SHOP (S: SOFA >14, H: hospitalize >72 hours, O: PF ratio <60, and P: pH <7.2) score. Compared with three different preexisting ECMO survival prediction scoring systems, the SHOP score had the highest area under the curve (AUC) for predicting in-hospital mortality (overall: 0.873, VV-EMCO: 0.866, and VA-EMCO: 0.891).ConclusionsIn-hospital mortality among ECMO-supported patients was high at 69%. SOFA score >14, hospitalized >72 hours, PaO2/FiO2 ratio <60, and pH <7.2 were found to be independent predictors of in-hospital mortality. A SHOP score of 2 or higher significantly predicts in-hospital mortality in EMCO-supported patients.Trial Registrationwww.clinicaltrials.gov (reg. No. NCT 04031794).

Helmet and face mask for non-invasive respiratory support in patients with acute hypoxemic respiratory failure: A retrospective study.

Non-invasive respiratory support could reduce the incidence of intubation in patients with Acute Hypoxemic Respiratory Failure (AHRF). The optimal interface or modality of non-invasive respiratory support is debated. We sought to evaluate the differences between patients who succeeded or failed non-invasive respiratory support, with a specific focus on the type of non-invasive respiratory support (i.e. helmet CPAP versus face mask NIV). In a single-center observational retrospective study, we investigated baseline, clinical characteristics and AHRF management by non-invasive respiratory support between January 2015 to December 2016. Data on gas exchange and respiratory mechanics, non-invasive respiratory support duration, ICU length of stay and mortality were collected. 110 patients with AHRF were included of which 41 patients (37%) were intubated. The use of helmet CPAP (p = 0.016) and a lower fluid balance (p = 0.038) were independently associated with a decreased rate of intubation after adjustment for confounders. Face mask NIV patients trended to a higher respiratory frequency at 1 h after treatment [28 (22-36) versus 24 (18-29) hours, p = 0.067], and showed a longer ICU stay (p = 0.009) compared to patients treated with helmet CPAP. Helmet CPAP and a lower fluid balance were independent predictors of a lower intubation rate in AHRF patients in ICU. Prospective studies aimed at identifying the optimal interface and modality of non-invasive respiratory support in AHRF patients are needed.

Factors affecting the outcome of the usage of high-flow nasal cannula on severe or critically ill COVID-19 patients: a multicentric study from a developing nation

In resource-constrained settings, High-Flow Nasal Cannula (HFNC) can reduce the burden on mechanical ventilation in COVID-19 induced Acute Hypoxemic Respiratory Failure (AHRF). The aim was to observe the factors those might affect the outcome of the usage of HFNC on severe/critically ill COVID-19 patients. This is a multicentric prospective observational study. We observed rRT-PCR positive severe/critically ill ICU patients requiring HFNC for more than six hours. Statistical analysis was done to correlate between factors and outcome. Weaning from HFNC was successful in 47.5% of patients. The death rate was higher in ≥ 50 years older (56.50%), and patients with asthma (60.57%), COPD (60.00%), and CKD (68.42%). Fever (91.67%), cough (72.5%), and dyspnea (67.5%) were the most common symptoms. Mortality rates were higher for patients with raised blood sugar, creatinine levels. Severely systemic inflammatory response was seen very high for the expired patients. On HFNC, percent saturation of oxygen (SpO2) and partial pressure of oxygen (PaO2) progression was significantly high for the surviving patients requiring less inspired fraction of oxygen (FiO2%). The survival rate was higher for the patients using both HFNC and non-rebreather mask (NRM) concomitantly. While after HFNC- SpO2% and FiO2% were significantly related with outcome of the HFNC only treated patients, duration of hospital stay and on HFNC- FiO2% affected the HFNC + NRM treated patients’ outcome. HFNC could save more lives of critically ill AHRF patients who otherwise might need invasive or noninvasive ventilation. Some biochemical tests were observed to have association with the prognosis of the disease though HFNC was given to all. Survival benefit of dual HFNC and NRM therapy needs future study. Asian J. Med. Biol. Res. 2021, 7 (3), 260-272

Identification of persistent and resolving subphenotypes of acute hypoxemic respiratory failure in two independent cohorts

BackgroundAcute hypoxemic respiratory failure (HRF) is associated with high morbidity and mortality, but its heterogeneity challenges the identification of effective therapies. Defining subphenotypes with distinct prognoses or biologic features can improve therapeutic trials, but prior work has focused on ARDS, which excludes many acute HRF patients. We aimed to characterize persistent and resolving subphenotypes in the broader HRF population.MethodsIn this secondary analysis of 2 independent prospective ICU cohorts, we included adults with acute HRF, defined by invasive mechanical ventilation and PaO2-to-FIO2 ratio ≤ 300 on cohort enrollment (n = 768 in the discovery cohort and n = 1715 in the validation cohort). We classified patients as persistent HRF if still requiring mechanical ventilation with PaO2-to-FIO2 ratio ≤ 300 on day 3 following ICU admission, or resolving HRF if otherwise. We estimated relative risk of 28-day hospital mortality associated with persistent HRF, compared to resolving HRF, using generalized linear models. We also estimated fold difference in circulating biomarkers of inflammation and endothelial activation on cohort enrollment among persistent HRF compared to resolving HRF. Finally, we stratified our analyses by ARDS to understand whether this was driving differences between persistent and resolving HRF.ResultsOver 50% developed persistent HRF in both the discovery (n = 386) and validation (n = 1032) cohorts. Persistent HRF was associated with higher risk of death relative to resolving HRF in both the discovery (1.68-fold, 95% CI 1.11, 2.54) and validation cohorts (1.93-fold, 95% CI 1.50, 2.47), after adjustment for age, sex, chronic respiratory illness, and acute illness severity on enrollment (APACHE-III in discovery, APACHE-II in validation). Patients with persistent HRF displayed higher biomarkers of inflammation (interleukin-6, interleukin-8) and endothelial dysfunction (angiopoietin-2) than resolving HRF after adjustment. Only half of persistent HRF patients had ARDS, yet exhibited higher mortality and biomarkers than resolving HRF regardless of whether they qualified for ARDS.ConclusionPatients with persistent HRF are common and have higher mortality and elevated circulating markers of lung injury compared to resolving HRF, and yet only a subset are captured by ARDS definitions. Persistent HRF may represent a clinically important, inclusive target for future therapeutic trials in HRF.

Utility of SpO2/FiO2 ratio for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Acute hypoxemic respiratory failure (AHRF) with bilateral opacities causes fatalities in the intensive care unit (ICU). It is often difficult to identify the causes of AHRF at the time of admission. The SpO2 to FiO2 (S/F) ratio has been recently used as a non-invasive and alternative marker of the PaO2/FiO2 (P/F) ratio in acute respiratory failure. This retrospective cohort study was conducted from October 2010 to March 2019 at the Showa University Hospital, Tokyo, Japan. We enrolled 94 AHRF patients who had bilateral opacities and received mechanical ventilation in ICU to investigate their prognostic markers including S/F ratio. Significant differences were observed for APACHE II, S/F ratio, PaO2/FiO2 (P/F) ratio, and ventilator-free-days at day 28 for ICU mortality, and for age, S/F ratio, P/F ratio, duration of mechanical ventilation, and ventilator-free days at day 28 for hospital mortality. Multivariate logistic regression analysis showed that the S/F ratio was significantly and independently associated with the risk of death during in ICU (p = 0.003) and hospitalization (p = 0.002). The area under the receiver operating characteristic curves (AUC) based on the S/F ratio were significantly greater than those based on simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) for ICU mortality (0.785 in S/F ratio vs. 0.575 in SAPS II, p = 0.012; 0.785 in S/F ratio vs 0.594 in SOFA, p = 0.021) and for hospital mortality (0.701 in S/F ratio vs. 0.502 in SAPS II, p = 0.012; 0.701 in S/F ratio vs. 0.503 in SOFA, p = 0.005). In the subanalysis for bacterial pneumonia and interstitial lung disease groups, the AUC based on the S/F ratio was the greatest among all prognostic markers, including APACHE II, SAPS II, and SOFA. The S/F ratio may be a useful and noninvasive predictive prognostic marker for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Oral anticoagulation and clinical outcomes in COVID-19: An Italian multicenter experience

BackgroundSince the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients. MethodIn this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled. Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated. The primary outcome was mortality. ResultsA total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization. Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p < 0.001). At overall multivariate logistical regression, use of heparin (n = 394, 46.6%) was associated with a better chance of survival to hospital discharge (OR 0.60 [0.38–0.94], p < 0.001), in particular in patients with AHRF, with no association found with the use of OACs. In a sub-analysis, the highest mortality rate was found for AHRF patients when heparin was not administered. ConclusionIn our cohort, OACs appeared to be ineffective in reducing mortality rate, while heparin resulted to be a useful treatment when lung disease was sufficiently severe, potentially suggesting a crucial role of microthrombosis in severe COVID-19. Due to the relatively small number of COVID-19 patients treated with OACs included in our analysis and their higher number of comorbidities, larger studies are needed in order to confirm our findings.