Subphenotypes in patients with acute respiratory distress syndrome treated with high-flow oxygen.

BACKGROUND: Acute respiratory distress syndrome (ARDS) subphenotypes differ in outcomes and treatment responses. Subphenotypes in high-flow nasal oxygen (HFNO)-treated ARDS patients have not been investigated. OBJECTIVES: To identify biological subphenotypes in HFNO-treated ARDS patients. METHODS: Secondary analysis of a prospective multicenter observational study including ARDS patients supported with HFNO. Plasma inflammation markers (interleukin [IL]-6, IL-8, and IL-33 and soluble suppression of tumorigenicity-2 [sST2]) and lung epithelial (receptor for advanced glycation end products [RAGE] and surfactant protein D [SP-D]) and endothelial (angiopoietin-2 [Ang-2]) injury were measured. These biomarkers and bicarbonate were used in K-means cluster analysis to identify subphenotypes. Logistic regression was performed on biomarker combinations to predict clustering. We chose the model with the best AUROC and the lowest number of variables. This model was used to describe the HAIS (High-flow ARDS Inflammatory Subphenotype) score. RESULTS: Among 41 HFNO patients, two subphenotypes were identified. Hyperinflammatory subphenotype (n = 17) showed higher biomarker levels than hypoinflammatory (n = 24). Despite similar baseline characteristics, the hyperinflammatory subphenotype had higher 60-day mortality (47 vs 8.3% p = 0.014) and longer ICU length of stay (22.0 days [18.0-30.0] vs 39.5 [25.5-60.0], p = 0.034). The HAIS score, based on IL-8 and sST2, accurately distinguished subphenotypes (AUROC 0.96 [95%CI: 0.90-1.00]). A HAIS score ≥ 7.45 was predictor of hyperinflammatory subphenotype. CONCLUSION: ARDS patients treated with HFNO exhibit two biological subphenotypes that have similar clinical characteristics, but hyperinflammatory patients have worse outcomes. The HAIS score may identify patients with hyperinflammatory subphenotype and might be used for enrichment strategies in future clinical trials.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

A Machine Learning decision-making tool for extubation in Intensive Care Unit patients.

BACKGROUND AND OBJECTIVE: To increase the success rate of invasive mechanical ventilation weaning in critically ill patients using Machine Learning models capable of accurately predicting the outcome of programmed extubations. METHODS: The study population was adult patients admitted to the Intensive Care Unit. Target events were programmed extubations, both successful and failed. The working dataset is assembled by combining heterogeneous data including time series from Clinical Information Systems, patient demographics, medical records and respiratory event logs. Three classification learners have been compared: Logistic Discriminant Analysis, Gradient Boosting Method and Support Vector Machines. Standard methodologies have been used for preprocessing, hyperparameter tuning and resampling. RESULTS: The Support Vector Machine classifier is found to correctly predict the outcome of an extubation with a 94.6% accuracy. Contrary to current decision-making criteria for extubation based on Spontaneous Breathing Trials, the classifier predictors only require monitor data, medical entry records and patient demographics. CONCLUSIONS: Machine Learning-based tools have been found to accurately predict the extubation outcome in critical patients with invasive mechanical ventilation. The use of this important predictive capability to assess the extubation decision could potentially reduce the rate of extubation failure, currently at 9%. With about 40% of critically ill patients eventually receiving invasive mechanical ventilation during their stay and given the serious potential complications associated to reintubation, the excellent predictive ability of the model presented here suggests that Machine Learning techniques could significantly improve the clinical outcomes of critical patients.

Safety incidents in airway and mechanical ventilation in Spanish ICUs: The IVeMVA study.

PURPOSE: To assess incidence, related factors and characteristics of safety incidents associated with the whole process of airway management and mechanical ventilation (MV) in Spanish ICUs. MATERIALS AND METHODS: Observational, prospective, 7 days cross-sectional multicenter study. Airway and MV related incidents were reported using structured questionnaire. Type, characteristics, severity, avoidability and contributing factors of the incidents were assessed. RESULTS: Participant ICUs: 104. Inclusion of 1267 patients; 745 (59%) suffered one or more incidents. Incidents reported: 2492 (59% non-harm-events, 41% adverse events). Individual risk of suffering at least one incident: 66.6%. Incidence ratio (median) of incidents: 2 per 100 patient-hours. 73.7% of incidents were related to MV process, 9.5% to tracheostomy, 6.2% to non-invasive MV, 5.4% to weaning/extubation, 4.4% to intubation and 0.8% to prone position. Temporary damage was produced in 12% incidents, while 0.8% was related to permanent injuries, risk to the patient's life or contributed to death. Incidents were considered avoidable in 73.5% of cases. 98% of all incidents had 1 or more contributing factors. CONCLUSIONS: MV is a risk process in critical patients. Although most incidents did not harm patients, some caused damage and a few were related to the patient's death or permanent damage. Preventability is high.

Reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial.

BACKGROUND: Spontaneous breathing trials (SBT) can be exhausting, but the preventive role of rest has never been studied. This study aimed to evaluate whether reconnection to mechanical ventilation (MV) for 1 h after the effort of a successful SBT could reduce the need for reintubation in critically ill patients. METHODS: Randomized multicenter trial conducted in 17 Spanish medical-surgical intensive care units (Oct 2013-Jan 2015). Patients under MV for longer than 12 h who fulfilled criteria for planned extubation were randomly allocated after a successful SBT to direct extubation (control group) or reconnection to the ventilator for a 1-h rest before extubation (rest group). The primary outcome was reintubation within 48 h. Analysis was by intention to treat. RESULTS: We recruited 243 patients randomized to the control group and 227 to the rest group. Median time from intubation to SBT did not differ between groups [5.5 (2.7, 9.6) days in the control group vs. 5.7 (2.7, 10.6) in the rest group; p = 0.85]. Reintubation within 48 h after extubation was more common in the control than in the rest group [35 (14%) vs. 12 (5%) patients; OR 0.33; 95% CI 0.16-0.65; p < 0.001]. A multivariable regression model demonstrated that the variables independently associated with reintubation were rest [OR 0.34 (95%CI 0.17-0.68)], APACHE II [OR 1.04 (1.002-1.077)], and days of MV before SBT [OR 1.04 (1.001-1.073)], whereas age, reason for admission, and type and duration of SBT were not. CONCLUSION: One-hour rest after a successful SBT reduced the rates of reintubation within 48 h after extubation in critically ill patients. Trial registration Clinicaltrials.gov identifier NCT01915563.

Hypoxemic Patients With Bilateral Infiltrates Treated With High-Flow Nasal Cannula Present a Similar Pattern of Biomarkers of Inflammation and Injury to Acute Respiratory Distress Syndrome Patients.

OBJECTIVE: To examine whether patients with acute hypoxemia and bilateral opacities treated with high-flow nasal cannula and acute respiratory distress syndrome patients who were directly mechanically ventilated are similar in terms of lung epithelial, endothelial, and inflammatory biomarkers. DESIGN: Prospective, multicenter study. SETTING: ICUs at three university tertiary hospitals. PATIENTS: Intubated and nonintubated patients admitted to the ICU with acute hypoxemia (PaO2/FIO2 ≤ 300) and bilateral opacities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Either high-flow nasal cannula or mechanical ventilation was initiated, at the discretion of the attending physician. We measured plasma biomarkers of lung epithelial injury (receptor for advanced glycation end products and surfactant protein D) and endothelial injury (angiopoietin-2) and inflammation (interleukin-6, interleukin-8, and interleukin-33 and soluble suppression of tumorigenicity-2) within 24 hours of acute respiratory distress syndrome onset. Propensity score matching was performed using six different variables (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, PaO2/FIO2, origin of acute respiratory distress syndrome, steroids, renal failure and need for vasopressors). Nonhypoxemic mechanically ventilated critically ill patients and healthy volunteers served as controls. Of the 170 patients enrolled, 127 (74.7%) were intubated and 43 (25.3%) were treated with high-flow nasal cannula at acute respiratory distress syndrome onset. After propensity score matching (39 high-flow nasal cannula patients vs 39 mechanical ventilation patients), no significant differences were observed in receptor for advanced glycation end products, surfactant protein D, angiopoietin-2, interleukin-6, interleukin-8, interleukin-33, and soluble suppression of tumorigenicity-2 between matched patients who were treated with high-flow nasal cannula and those who were intubated at acute respiratory distress syndrome onset. After matching, no differences in mortality or length of stay were observed. All biomarkers (with the exception of interleukin-33) were higher in both groups of matched acute respiratory distress syndrome patients than in both control groups. CONCLUSIONS: Acute hypoxemic patients with bilateral infiltrates treated with high-flow nasal cannula presented a similar pattern of biomarkers of inflammation and injury to acute respiratory distress syndrome patients undergoing direct mechanical ventilation. The results suggest that these high-flow nasal cannula patients should be considered as acute respiratory distress syndrome patients.

Risk Factors for Noninvasive Ventilation Failure in Critically Ill Subjects With Confirmed Influenza Infection.

BACKGROUND: Despite wide use of noninvasive ventilation (NIV) in several clinical settings, the beneficial effects of NIV in patients with hypoxemic acute respiratory failure (ARF) due to influenza infection remain controversial. The aim of this study was to identify the profile of patients with risk factors for NIV failure using chi-square automatic interaction detection (CHAID) analysis and to determine whether NIV failure is associated with ICU mortality. METHODS: This work was a secondary analysis from prospective and observational multi-center analysis in critically ill subjects admitted to the ICU with ARF due to influenza infection requiring mechanical ventilation. Three groups of subjects were compared: (1) subjects who received NIV immediately after ICU admission for ARF and then failed (NIV failure group); (2) subjects who received NIV immediately after ICU admission for ARF and then succeeded (NIV success group); and (3) subjects who received invasive mechanical ventilation immediately after ICU admission for ARF (invasive mechanical ventilation group). Profiles of subjects with risk factors for NIV failure were obtained using CHAID analysis. RESULTS: Of 1,898 subjects, 806 underwent NIV, and 56.8% of them failed. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, infiltrates in chest radiograph, and ICU mortality (38.4% vs 6.3%) were higher (P < .001) in the NIV failure than in the NIV success group. SOFA score was the variable most associated with NIV failure, and 2 cutoffs were determined. Subjects with SOFA ≥ 5 had a higher risk of NIV failure (odds ratio = 3.3, 95% CI 2.4-4.5). ICU mortality was higher in subjects with NIV failure (38.4%) compared with invasive mechanical ventilation subjects (31.3%, P = .018), and NIV failure was associated with increased ICU mortality (odds ratio = 11.4, 95% CI 6.5-20.1). CONCLUSIONS: An automatic and non-subjective algorithm based on CHAID decision-tree analysis can help to define the profile of patients with different risks of NIV failure, which might be a promising tool to assist in clinical decision making to avoid the possible complications associated with NIV failure.

The prognostic value of muscle regional oxygen saturation index in severe community-acquired pneumonia: a prospective observational study.

BACKGROUND: Community-acquired pneumonia (CAP) mortality exceeds 20 % in critical care patients despite appropriate antibiotic therapy. Regional tissue oxygen saturation index (rSO2) measured with near-infrared spectroscopy (NIRS) might facilitate early detection for patients at risk of serious complications. Our objectives were to determine the relationship between early determination of rSO2 and mortality and to compare discrimination power for mortality of rSO2 and other resuscitation variables in critically ill CAP patients. METHODS: This is a prospective observational study. Patients with CAP were enrolled within 6 h to intensive care admission. Demographics and clinical variables were recorded. rSO2 was determined using NIRS in brachioradialis muscle. All variables were determined at baseline and 24 h after admission. RESULTS: Forty patients were enrolled. Fourteen patients (35 %) had a baseline rSO2 < 60 % and 7 of them died (50 %). Only 1 of 26 (3.8 %) patients with rSO2 ≥ 60 % died (p = 0.007). The area under ROC curve (AUROC) showed consistent mortality discrimination at baseline (0.84, p = 0.03) and at 24 h (0.86, p = 0.006) for rSO2 values. Cox regression analysis showed that "low" rSO2 at ICU admission (hazard ratio (HR) = 8.99; 95 % confidence interval (CI) 1.05-76.8; p = 0.045) and "low" rSO2 at 24 h (HR = 13.18; 95 % CI 1.52-113.6; p = 0.019) were variables independently associated with mortality. In contrast, other variables such as Acute Physiology and Chronic Health Evaluation (APACHE II) score (HR = 1.09; 95 % CI 0.99-1.19; p = 0.052) were not associated with mortality. CONCLUSIONS: Our findings suggest that forearm skeletal muscle rSO2 differs in patients with severe CAP according to outcome and might be an early prognosis tool.

Corticosteroid therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza.

OBJECTIVE: During the first pandemic, some patients with pandemic (H1N1) 2009 influenza were treated with corticosteroids. The objective of this study was to assess the effect on survival of corticosteroid therapy in patients with pandemic (H1N1) 2009 influenza. METHODS: Prospective, observational, multicenter study performed in 148 ICU. Data were recorded in the GTEI/SEMICYUC registry. Adult patients with pandemic (H1N1) 2009 influenza confirmed by rt-PCR were included in the analysis. Database records specified corticosteroid type and reason for corticosteroid treatment. RESULTS: 372 patients with the diagnosis of primary viral pneumonia and completed outcomes treated in an ICU were included in the database. Mechanical ventilation was used in 70.2% of the patients. 136 (36.6%) patients received corticosteroids after a diagnosis of primary viral pneumonia. Obesity (35.6% vs 47.8% p = 0.021) and asthma (7.6% vs 15.4% p = 0.018), were more frequent in the group treated with corticosteroids. A Cox regression analysis adjusted for severity and potential confounding factors found that the use of corticosteroid therapy was not significantly associated with mortality (HR = 1.06, 95% CI 0.626-1.801; p = 0.825). CONCLUSIONS: Corticosteroid therapy in a selected group of patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza does not improve survival.

Bacteremia is an independent risk factor for mortality in nosocomial pneumonia: a prospective and observational multicenter study.

INTRODUCTION: Since positive blood cultures are uncommon in patients with nosocomial pneumonia (NP), the responsible pathogens are usually isolated from respiratory samples. Studies on bacteremia associated with hospital-acquired pneumonia (HAP) have reported fatality rates of up to 50%. The purpose of the study is to compare risk factors, pathogens and outcomes between bacteremic nosocomial pneumonia (B-NP) and nonbacteremic nosocomial pneumonia (NB-NP) episodes. METHODS: This is a prospective, observational and multicenter study (27 intensive care units in nine European countries). Consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of pneumonia or on mechanical ventilation for > 48 hours irrespective of admission diagnosis were recruited. RESULTS: A total of 2,436 patients were evaluated; 689 intubated patients presented with NP, 224 of them developed HAP and 465 developed ventilation-acquired pneumonia. Blood samples were extracted in 479 (69.5%) patients, 70 (14.6%) being positive. B-NP patients had higher Simplified Acute Physiology Score (SAPS) II score (51.5 ± 19.8 vs. 46.6 ± 17.5, P = 0.03) and were more frequently medical patients (77.1% vs. 60.4%, P = 0.01). Mortality in the intensive care unit was higher in B-NP patients compared with NB-NP patients (57.1% vs. 33%, P < 0.001). B-NP patients had a more prolonged mean intensive care unit length of stay after pneumonia onset than NB-NP patients (28.5 ± 30.6 vs. 20.5 ± 17.1 days, P = 0.03). Logistic regression analysis confirmed that medical patients (odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.93 to 16.99, P = 0.002), methicillin-resistant Staphylococcus aureus (MRSA) etiology (OR = 3.42, 95% CI = 1.57 to 5.81, P = 0.01), Acinetobacter baumannii etiology (OR = 4.78, 95% CI = 2.46 to 9.29, P < 0.001) and days of mechanical ventilation (OR = 1.02, 95% CI = 1.01 to 1.03, P < 0.001) were independently associated with B-NP episodes. Bacteremia (OR = 2.01, 95% CI = 1.22 to 3.55, P = 0.008), diagnostic category (medical patients (OR = 3.71, 95% CI = 2.01 to 6.95, P = 0.02) and surgical patients (OR = 2.32, 95% CI = 1.10 to 4.97, P = 0.03)) and higher SAPS II score (OR = 1.02, 95% CI = 1.01 to 1.03, P = 0.008) were independent risk factors for mortality. CONCLUSIONS: B-NP episodes are more frequent in patients with medical admission, MRSA and A. baumannii etiology and prolonged mechanical ventilation, and are independently associated with higher mortality rates.

Severe 2009 A/H1N1v influenza in pregnant women in Spain.

OBJECTIVES: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units. DESIGN AND PATIENTS: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units. MAIN RESULTS: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women. CONCLUSIONS: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

A randomized trial of dental brushing for preventing ventilator-associated pneumonia.

BACKGROUND: Poor oral hygiene is associated with respiratory pathogen colonization and secondary lung infection. The impact of adding electric toothbrushing to oral care in order to reduce ventilator-associated pneumonia (VAP) incidence is unknown. METHODS: The study design was a prospective, simple-blind, randomized trial of adult patients intubated for > 48 h. Controlling for exposure to antibiotic treatment, patients were randomized to oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group). VAP was documented by quantitative respiratory cultures. Mechanical ventilation (MV) duration, hospital ICU length of stay (LOS), antibiotic use, and hospital ICU mortality were secondary end points. RESULTS: The study was terminated after randomizing 147 patients (74 toothbrush group) in a scheduled interim analysis. The two groups were comparable at baseline. The toothbrush group and standard group had similar rates of suspected VAP (20.3% vs 24.7%; p = 0.55). After adjustment for severity of illness and admission diagnosis, the incidence of microbiologically documented VAP was also similar in the two groups (hazard ratio, 0.84; 95% confidence interval, 0.41 to 1.73). The groups did not differ significantly in mortality, antibiotic-free days, duration of MV, or hospital ICU LOS. CONCLUSIONS: Our findings suggest that the addition of electric toothbrushing to standard oral care with 0.12% chlorhexidine digluconate is not effective for the prevention of VAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00842478.