Flow starvation during square-flow assisted ventilation detected by supervised deep learning techniques.

BACKGROUND: Flow starvation is a type of patient-ventilator asynchrony that occurs when gas delivery does not fully meet the patients' ventilatory demand due to an insufficient airflow and/or a high inspiratory effort, and it is usually identified by visual inspection of airway pressure waveform. Clinical diagnosis is cumbersome and prone to underdiagnosis, being an opportunity for artificial intelligence. Our objective is to develop a supervised artificial intelligence algorithm for identifying airway pressure deformation during square-flow assisted ventilation and patient-triggered breaths. METHODS: Multicenter, observational study. Adult critically ill patients under mechanical ventilation > 24 h on square-flow assisted ventilation were included. As the reference, 5 intensive care experts classified airway pressure deformation severity. Convolutional neural network and recurrent neural network models were trained and evaluated using accuracy, precision, recall and F1 score. In a subgroup of patients with esophageal pressure measurement (ΔPes), we analyzed the association between the intensity of the inspiratory effort and the airway pressure deformation. RESULTS: 6428 breaths from 28 patients were analyzed, 42% were classified as having normal-mild, 23% moderate, and 34% severe airway pressure deformation. The accuracy of recurrent neural network algorithm and convolutional neural network were 87.9% [87.6-88.3], and 86.8% [86.6-87.4], respectively. Double triggering appeared in 8.8% of breaths, always in the presence of severe airway pressure deformation. The subgroup analysis demonstrated that 74.4% of breaths classified as severe airway pressure deformation had a ΔPes > 10 cmH2O and 37.2% a ΔPes > 15 cmH2O. CONCLUSIONS: Recurrent neural network model appears excellent to identify airway pressure deformation due to flow starvation. It could be used as a real-time, 24-h bedside monitoring tool to minimize unrecognized periods of inappropriate patient-ventilator interaction.

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort.

BACKGROUND: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. METHODS: Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. RESULTS: Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. CONCLUSIONS: During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis.

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (ΔCollapse24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Characterization of postintensive care syndrome in a prospective cohort of survivors of COVID-19 critical illness: a 12-month follow-up study.

PURPOSE: Studies integrating an exhaustive longitudinal long-term follow-up of postintensive care syndrome (PICS) in critically ill COVID-19 survivors are scarce. We aimed to 1) describe PICS-related sequelae over a 12-month period after intensive care unit (ICU) discharge, 2) identify relevant demographic and clinical factors related to PICS, and 3) explore how PICS-related sequelae may influence health-related quality of life (HRQoL) in critically ill COVID-19 survivors. METHODS: We conducted a prospective cohort study in adult critically ill survivors of SARS-CoV-2 infection that did or did not need invasive mechanical ventilation (IMV) during the COVID-19 pandemic in Spain (March 2020 to January 2021). We performed a telemedicine follow-up of PICS-related sequelae (physical/functional, cognitive, and mental health) and HRQoL with five data collection points. We retrospectively collected demographic and clinical data. We used multivariable mixed-effects models for data analysis. RESULTS: We included 142 study participants in the final analysis, with a median [interquartile range] age of 61 [53-68] yr; 35% were female and 59% needed IMV. Fatigue/dyspnea, pain, impaired muscle function, psychiatric symptomatology and reduced physical HRQoL were prominent sequelae early after ICU discharge. Over the 12-month follow-up, functionality and fatigue/dyspnea improved progressively, while pain remained stable. We observed slight fluctuations in anxiety symptoms and perception of cognitive deficit, whereas posttraumatic stress disorder (PTSD) and depressive symptoms improved, with a mild rebound at the end of the follow-up. Female sex, younger age, and the need for IMV were risk factors for PICS, while having higher cognitive reserve was a potential protective factor. Physical HRQoL scores showed a general improvement over time, whereas mental HRQoL remained stable. Shorter ICU stay, better functionality, and lower scores for fatigue/dyspnea and pain were associated with better physical HRQoL, while lower scores for anxiety, depression, and PTSD were associated with better mental HRQoL. CONCLUSIONS: Postintensive care syndrome was common in COVID-19 critical illness survivors and persisted in a significant proportion of patients one year after ICU discharge, impacting HRQoL. The presence of risk factors for PICS may identify patients who are more likely to develop the condition and who would benefit from more specific and closer follow-up after ICU admission. STUDY REGISTRATION: ClinicalTrials.gov ( NCT04422444 ); first submitted 9 June 2020.

RéSUMé: OBJECTIF: Les études intégrant un suivi longitudinal exhaustif à long terme des syndromes post-soins intensifs (SPSI) chez les survivant·es gravement malades de la COVID-19 sont rares. Notre objectif était 1) de décrire les séquelles liées au SPSI sur une période de 12 mois après la sortie de l'unité de soins intensifs (USI), 2) d'identifier les facteurs démographiques et cliniques pertinents liés au SPSI, et 3) d'explorer comment les séquelles liées au SPSI peuvent influencer la qualité de vie liée à la santé (QVLS) chez les survivant·es gravement malades de la COVID-19. MéTHODE: Nous avons mené une étude de cohorte prospective chez des adultes gravement malades survivant·es d'une infection par le SRAS-CoV-2 qui ont eu ou non besoin d'une ventilation mécanique invasive (VMI) pendant la pandémie de COVID-19 en Espagne (mars 2020 à janvier 2021). Nous avons effectué un suivi par télémédecine des séquelles liées au SPSI (santé physique/fonctionnelle, cognitive et mentale) et à la QVLS avec cinq points de collecte de données. Nous avons rétrospectivement colligé des données démographiques et cliniques. Des modèles multivariés à effets mixtes ont été utilisés pour l'analyse des données. RéSULTATS: Nous avons inclus 142 participant·es à l'étude dans l'analyse finale, avec un âge médian [intervalle interquartile] de 61 [53-68] ans; 35 % étaient des femmes et 59 % avaient besoin de VMI. La fatigue/dyspnée, la douleur, l'altération de la fonction musculaire, la symptomatologie psychiatrique et la réduction de la QVLS physique étaient des séquelles importantes peu après la sortie de l'USI. Au cours du suivi de 12 mois, la fonctionnalité et la fatigue/dyspnée se sont améliorées progressivement, tandis que la douleur est restée stable. Nous avons observé de légères fluctuations des symptômes d'anxiété et de perception du déficit cognitif, tandis que le trouble de stress post-traumatique (ESPT) et les symptômes dépressifs se sont améliorés, avec un léger rebond à la fin du suivi. Le sexe féminin, un jeune âge et le besoin de VMI étaient des facteurs de risque de SPSI, tandis qu'une réserve cognitive plus élevée était un facteur potentiel de protection. Les scores physiques de la QVLS ont montré une amélioration générale au fil du temps, tandis que la QVLS mentale est restée stable. Un séjour plus court aux soins intensifs, une meilleure fonctionnalité et des scores plus faibles pour la fatigue/dyspnée et la douleur étaient associés à une meilleure QVLS physique, tandis que des scores plus faibles pour l'anxiété, la dépression et le ESPT étaient associés à une meilleure QVLS mentale. CONCLUSION: Le syndrome post-soins intensifs était fréquent chez les survivant·es d'une maladie grave de la COVID-19 et a persisté chez une proportion importante de patient·es un an après leur sortie de l'unité de soins intensifs, ce qui a eu un impact sur la QVLS. La présence de facteurs de risque de SPSI peut identifier les patient·es qui sont plus susceptibles de développer la maladie et qui bénéficieraient d'un suivi plus spécifique et plus étroit après leur admission aux soins intensifs. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT04422444 ); première soumission le 9 juin 2020.

Biomarker Profiles Associated with COVID-19 Severity and Mortality.

INTRODUCTION: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. METHODS: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-É£, MCP-1, MIP-1ß, and TNF-α) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3. RESULTS: At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 (p = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 (p = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC (p = 0.022 and p = 0.024, respectively) and FEV1 (p = 0.012 and p = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, p = 0.001). CONCLUSIONS: Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients.

High-Flow Oxygen with Capping or Suctioning for Tracheostomy Decannulation.

BACKGROUND: When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS: In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS: The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS: Basing the decision to decannulate on suctioning frequency plus continuous high-flow oxygen therapy rather than on 24-hour capping trials plus intermittent high-flow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.).

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis.

BACKGROUND: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes. METHODS: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation. RESULTS: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%; p=0.01), ICU mortality (25.7% versus 36.1%; p=0.007) and 90-day mortality (30.9% versus 40.2%; p=0.02) compared with the early intubation group. Very similar findings were observed when we used a 48-h time-point for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth waves, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (HFNC) (n=294) who were intubated earlier. The subgroup of patients undergoing noninvasive ventilation (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. CONCLUSIONS: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received HFNC.

Prone positioning of nonintubated patients with acute hypoxemic respiratory failure.

PURPOSE OF REVIEW: Since the early pandemic, prone positioning has been broadly utilized for nonintubated patients (so-called 'awake prone positioning, APP') with coronavirus disease 2019 (COVID-19) induced acute hypoxemic respiratory failure (AHRF). RECENT FINDINGS: Numerous clinical studies have been conducted to investigate the effects of APP on oxygenation, intubation, and mortality. However, several questions remain unclear, such as the patient populations who benefit most from APP, the best length of daily duration on APP, how to improve adherence to APP, and the mechanisms of APP efficacy. SUMMARY: APP has been shown to improve oxygenation for patients with COVID-19 induced AHRF and is a safe treatment. However, the benefits of reducing intubation rates are only seen in moderate-to-severe patients who are undergoing HFNC treatment. In these patients, APP should be initiated early and with a target of at least 8 h/day of APP. Pillows under the body and patients-healthcare team collaboration to find the optimal position is essential to enhance patients' adherence. Oxygenation improvement and changes in the lung ultrasound findings may help to identify those patients who are more likely to avoid the need for intubation.

The effects of flow settings during high-flow nasal cannula support for adult subjects: a systematic review.

BACKGROUND: During high-flow nasal cannula (HFNC) therapy, flow plays a crucial role in the physiological effects. However, there is no consensus on the initial flow settings and subsequent titration. Thus, we aimed to systematically synthesize the effects of flows during HFNC treatment. METHODS: In this systematic review, two investigators independently searched PubMed, Embase, Web of Science, Scopus, and Cochrane for in vitro and in vivo studies investigating the effects of flows in HFNC treatment published in English before July 10, 2022. We excluded studies that investigated the pediatric population (< 18 years) or used only one flow. Two investigators independently extracted the data and assessed the risk of bias. The study protocol was prospectively registered with PROSPERO, CRD42022345419. RESULTS: In total, 32,543 studies were identified, and 44 were included. In vitro studies evaluated the effects of flow settings on the fraction of inspired oxygen (FIO2), positive end-expiratory pressure, and carbon dioxide (CO2) washout. These effects are flow-dependent and are maximized when the flow exceeds the patient peak inspiratory flow, which varies between patients and disease conditions. In vivo studies report that higher flows result in improved oxygenation and dead space washout and can reduce work of breathing. Higher flows also lead to alveolar overdistention in non-dependent lung regions and patient discomfort. The impact of flows on different patients is largely heterogeneous. INTERPRETATION: Individualizing flow settings during HFNC treatment is necessary, and titrating flow based on clinical findings like oxygenation, respiratory rates, ROX index, and patient comfort is a pragmatic way forward.

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.

Objective and subjective cognition in survivors of COVID-19 one year after ICU discharge: the role of demographic, clinical, and emotional factors.

BACKGROUND: Intensive Care Unit (ICU) COVID-19 survivors may present long-term cognitive and emotional difficulties after hospital discharge. This study aims to characterize the neuropsychological dysfunction of COVID-19 survivors 12 months after ICU discharge, and to study whether the use of a measure of perceived cognitive deficit allows the detection of objective cognitive impairment. We also explore the relationship between demographic, clinical and emotional factors, and both objective and subjective cognitive deficits. METHODS: Critically ill COVID-19 survivors from two medical ICUs underwent cognitive and emotional assessment one year after discharge. The perception of cognitive deficit and emotional state was screened through self-rated questionnaires (Perceived Deficits Questionnaire, Hospital Anxiety and Depression Scale and Davidson Trauma Scale), and a comprehensive neuropsychological evaluation was carried out. Demographic and clinical data from ICU admission were collected retrospectively. RESULTS: Out of eighty participants included in the final analysis, 31.3% were women, 61.3% received mechanical ventilation and the median age of patients was 60.73 years. Objective cognitive impairment was observed in 30% of COVID-19 survivors. The worst performance was detected in executive functions, processing speed and recognition memory. Almost one in three patients manifested cognitive complaints, and 22.5%, 26.3% and 27.5% reported anxiety, depression and post-traumatic stress disorder (PTSD) symptoms, respectively. No significant differences were found in the perception of cognitive deficit between patients with and without objective cognitive impairment. Gender and PTSD symptomatology were significantly associated with perceived cognitive deficit, and cognitive reserve with objective cognitive impairment. CONCLUSIONS: One-third of COVID-19 survivors suffered objective cognitive impairment with a frontal-subcortical dysfunction 12 months after ICU discharge. Emotional disturbances and perceived cognitive deficits were common. Female gender and PTSD symptoms emerged as predictive factors for perceiving worse cognitive performance. Cognitive reserve emerged as a protective factor for objective cognitive functioning. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422444; June 9, 2021.

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).

BACKGROUND: We 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). METHODS: In 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. RESULTS: Forty-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. CONCLUSIONS: Closed-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 .

Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial.

BACKGROUND: Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. METHODS: In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). RESULTS: Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. CONCLUSION: In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1.

Lung ultrasound response to awake prone positioning predicts the need for intubation in patients with COVID-19 induced acute hypoxemic respiratory failure: an observational study.

BACKGROUND: Awake prone positioning (APP) reduces the intubation rate in COVID-19 patients treated by high-flow nasal cannula (HFNC). However, the lung aeration response to APP has not been addressed. We aimed to explore the lung aeration response to APP by lung ultrasound (LUS). METHODS: This two-center, prospective, observational study enrolled patients with COVID-19-induced acute hypoxemic respiratory failure treated by HFNC and APP. LUS score was recorded 5-10 min before, 1 h after APP, and 5-10 min after supine in the first APP session within the first three days. The primary outcome was LUS score changes in the first three days. Secondary outcomes included changes in SpO2/FiO2 ratio, respiratory rate and ROX index (SpO2/FiO2/respiratory rate) related to APP, and the rate of treatment success (patients who avoided intubation). RESULTS: Seventy-one patients were enrolled. LUS score decreased from 20 (interquartile range [IQR] 19-24) to 19 (18-21) (p < 0.001) after the first APP session, and to 19 (18-21) (p < 0.001) after three days. Compared to patients with treatment failure (n = 20, 28%), LUS score reduction after the first three days in patients with treatment success (n = 51) was greater (- 2.6 [95% confidence intervals - 3.1 to - 2.0] vs 0 [- 1.2 to 1.2], p = 0.001). A decrease in dorsal LUS score > 1 after the first APP session was associated with decreased risk for intubation (Relative risk 0.25 [0.09-0.69]). APP daily duration was correlated with LUS score reduction in patients with treatment success, especially in dorsal lung zones (r = - 0.76; p < 0.001). CONCLUSIONS: In patients with acute hypoxemic respiratory failure due to COVID-19 and treated by HFNC, APP reduced LUS score. The reduction in dorsal LUS scores after APP was associated with treatment success. The longer duration on APP was correlated with greater lung aeration. Trial registration This study was prospectively registered on clinicaltrials.gov on April 22, 2021. Identification number NCT04855162 .

Global lessons learned from COVID-19 mass casualty incidents.

With healthcare systems rapidly becoming overwhelmed and occupied by patients during a pandemic, effective and safe care for patients is easily compromised. During the course of the current pandemic, numerous treatment guidelines have been developed and published that have improved care for patients with COVID-19. Certain lessons have only been learned during the course of the outbreak, from which we can learn for future pandemics. This editorial aims to raise awareness about the importance of timely stockpiling of sufficient amounts of personal protection equipment and medications, adequate oxygen supplies, uninterrupted electricity, and fair locally adapted triage strategies.

Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

To prone or not to prone ARDS patients on ECMO.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy.

Rationale: One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. Objectives: To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/FiO2 to respiratory rate) for determining HFNC outcome (need or not for intubation). Methods: This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Measurements and Main Results: Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264-0.715; P = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182-0.509; P < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161-0.524; P < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/FiO2 had a greater weight than respiratory rate. Conclusions: In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT02845128).

Noninvasive approach for de novo acute hypoxemic respiratory failure: noninvasive ventilation, high-flow nasal cannula, both or none?

PURPOSE OF REVIEW: To summarize the recent evidence regarding the use of noninvasive strategies for de novo acute hypoxemic respiratory failure (AHRF). RECENT FINDINGS: New guidelines for the use of noninvasive ventilation (NIV) in acute respiratory failure have been published. In parallel, high-flow nasal cannula (HFNC) is an emerging noninvasive strategy for AHRF patients. Although some have cautioned against the use of NIV in AHRF, new encouraging data about the use of a helmet interface for NIV in acute respiratory distress syndrome may overcome the limitations of facemask NIV. SUMMARY: In the last two decades, the use of NIV and HFNC in patients with AHRF has considerably expanded, changing the paradigm of management of AHRF. Choice of each technique should be based according to centre experience and patient tolerability. However, when using noninvasive strategies for AHRF, it is crucial to predefine specific criteria for intubation and monitor patients closely for early detection of clinical deterioration to avoid delayed intubation.