Search

Purpose High-flow nasal cannula (HFNC) oxygen therapy was noninferior to noninvasive ventilation (NIV) for preventing reintubation in a heterogeneous population at high-risk for extubation failure. However, outcomes might differ in certain subgroups of patients. Thus, we aimed to determine whether NIV with active humidification is superior to HFNC in preventing reintubation in patients with ≥ 4 risk factors (very high risk for extubation failure). Methods Randomized controlled trial in two intensive care units in Spain (June 2020‒June 2021). Patients ready for planned extubation with ≥ 4 of the following risk factors for reintubation were included: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 on extubation day, body mass index > 30, inadequate secretions management, difficult or prolonged weaning, ≥ 2 comorbidities, acute heart failure indicating mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation, or hypercapnia on finishing the spontaneous breathing trial. Patients were randomized to undergo NIV with active humidification or HFNC for 48 h after extubation. The primary outcome was reintubation rate within 7 days after extubation. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, length of stay, mortality, adverse events, and time to reintubation. Results Of 182 patients (mean age, 60 [standard deviation (SD), 15] years; 117 [64%] men), 92 received NIV and 90 HFNC. Reintubation was required in 21 (23.3%) patients receiving NIV vs 35 (38.8%) of those receiving HFNC (difference −15.5%; 95% confidence interval (CI) −28.3 to −1%). Hospital length of stay was lower in those patients treated with NIV (20 [12‒36.7] days vs 26.5 [15‒45] days, difference 6.5 [95%CI 0.5–21.1]). No additional differences in the other secondary outcomes were observed. Conclusions Among adult critically ill patients at very high-risk for extubation failure, NIV with active humidification was superior to HFNC for preventing reintubation. post-print 1227 KB

Objectives To measure the impact of clusters of double triggering on clinical outcomes. Design Prospective cohort study. Setting Respiratory ICU in Brazil. Patients Adult patients under recent mechanical ventilation and with expectation of mechanical ventilation for more than 24 hours after enrollment. Interventions None. Measurements and main results We used a dedicated software to analyze ventilator waveforms throughout the entire period of mechanical ventilation and detect double triggering. We defined a cluster of double triggering as a period of time containing at least six double triggering events in a 3-minute period. Patients were followed until hospital discharge. We addressed the association between the presence and the duration of clusters with clinical outcomes. A total of 103 patients were enrolled in the study and 90 (87%) had at least one cluster of double triggering. The median number of clusters per patient was 19 (interquartile range, 6-41), with a median duration of 8 minutes (6-12 min). Compared with patients who had no clusters, patients with at least one cluster had longer duration of mechanical ventilation (7 d [4-11 d] vs 2 d [2-3 d]) and ICU length of stay (9 d [7-16 d] vs 13 d [2-8 d]). Thirty-three patients had high cumulative duration of clusters of double triggering (≥ 12 hr), and it was associated with longer duration of mechanical ventilation, fewer ventilator-free days, and longer ICU length of stay. Adjusted by duration of mechanical ventilation and severity of illness, high cumulative duration of clusters was associated with shorter survival at 28 days (hazard ratio, 2.09 d; 95% CI, 1.04-4.19 d). Conclusions Clusters of double triggering are common and were associated with worse clinical outcomes. Patients who had a high cumulative duration of clusters had fewer ventilator-free days, longer duration of mechanical ventilation, longer ICU length of stay, and shorter survival than patients with low cumulative duration of cluster.

BackgroundIt is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation related complications.Design and MethodsThe PRONELIFE study is an investigator–initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all–cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning.DiscussionThe PRONELIFE study is amongst the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation––patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible––however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study has the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure.Trial registrationISRCTN, ISRCTN11536318. Registered 17 September 2021, https://www.isrctn.com/ISRCTN11536318The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients’ cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the “treatment as usual” (TAU, n = 38) or the “early neurocognitive stimulation” (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At onemonth follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group–time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ¿p2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Sepsis is a serious, heterogeneous clinical entity produced by a severe and systemic host inflammatory response to infection. Methotrexate (MTX) is a folate-antagonist that induces the generation of adenosine and also inhibits JAK/STAT pathway, MTX it is widely used as an anti-inflammatory drug to control the immune system. Objective: The aim of this study was to assess the beneficial effects of a single and low dose of MTX in the systemic response and acute lung injury (ALI) induced by sepsis. As in the clinics, we treated our animals with antibiotics and fluids and performed the source control to mimic the current clinic treatment. Methods and main results: Sepsis was induced in rats by a cecal ligation puncture (CLP) procedure. Six hours after induction of sepsis, we proceeded to the source control, fluids and antibiotics were administered at 6 h and 24 h after CLP. MTX (2.5 mg/Kg) was administered 6 h after the first surgery in one CLP experimental group and to one Sham group. A protective effect of MTX was observed through a significant reduction of pro-inflammatory cytokines and a decrease infiltration of inflammatory cells in the lung. In addition, we found a regulation in adenosine receptor A2aR and the metalloproteinases by MTX. Conclusion: A single, low dose of MTX attenuates sepsis lung-associated damage by decreasing pro-inflammatory response, infiltration of pro-inflammatory cells and avoiding defective tissue lung remodeling.

RationaleOutcomes in patients with severe SARS-CoV-2 infection (COVID-19) are conditioned by virus clearance and regulation of inflammation. Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections.ObjectiveTo characterize the impact of IFIH1 rs199076 variants on host response and outcomes after severe COVID-19.MethodsPatients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modelled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials.Measurements and Main Results227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to a MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids (N=14) survived their ICU stay (HR 2.49, 95% confidence interval 1.29–4.79). Patients with a TT variant treated with dexamethasone (N=50) showed an increased hospital mortality (HR 2.19, 95% confidence interval 1.01–4.87) and serum IL-6. In-silico clinical trials supported these findings.ConclusionsCOVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype.

In this study we aimed to determine the effect of the exosomes derived from Mesenchymal stromal cells (MSC) on cell proliferation, and to study how pre-conditioning the MSCs to a septic environment, changes their exosomes’ content and consequently, their regenerative capacity. MSC were isolated from male rats’ femora and tibiae and cultured in non pre-stimulated and pre-stimulated (with LPS) conditions. The secreted exosomes were obtained via standard ultracentrifugation protocol. Cell proliferation experiments were conducted by treating an epithelial cell line with exosomes from non pre-stimulated MSC (Control exosomes) and pre-stimulated MSC (LPS exosomes) through an in vitro scratch assay. Exosomal protein profile was analyzed by a liquid chromatography-mass spectrometry analysis. The treatment of epithelial cells with LPS exosomes increases a 10% its capacity to proliferate and to heal the wound in comparison with the cells treated with Control exosomes (Fig.1a). The analysis of the protein content of both types of exosomes confirmed that pre-conditioning MSCs to a septic environment modifies the protein cargo of its exosomes (Fig. 1b), resulting in the appearance proteins related to cell cycle regulation and cell proliferation. In conclusion, pre-stimulating MSC with LPS enhances their paracrine activity and improves the reparative capacity of their secreted exosomes.

INTRODUCTION Surrogates for impaired ventilation such as estimated dead-space fractions and the ventilatory ratio are independently associated with an increased risk of mortality in the acute respiratory distress syndrome (ARDS) and small case series of COVID-19 related ARDS. METHODS This study aimed to quantify the dynamics and determine the prognostic value of surrogate markers of impaired ventilation in patients with COVID-19 related ARDS. The present study is a secondary analysis of the PRactice Of VENTilation in COVID-19 patients (PROVENT-COVID) in 22 intensive care unit hospitals in the Netherlands. Surrogates of impaired ventilation such as the estimated dead space fraction (by Harris-Benedict-VD/VT HB and direct method-VD/VT DIR), ventilatory ratio (VR), and end-tidal-to-arterial PCO2 ratio (PETCO2/PaCO2) were used. RESULTS 927 consecutive patients admitted with COVID-19 related ARDS were included in this study. Surrogates of impaired ventilation were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p

Mechanical ventilation induces a number of systemic responses for which the brain plays an essential role. During the last decade, substantial evidence has emerged showing that the brain modifies pulmonary responses to physical and biological stimuli by various mechanisms, including the modulation of neuroinflammatory reflexes and the onset of abnormal breathing patterns. Afferent signals and circulating factors from injured peripheral tissues, including the lung, can induce neuronal reprogramming, potentially contributing to neurocognitive dysfunction and psychological alterations seen in critically ill patients. These impairments are ubiquitous in the presence of positive pressure ventilation. This narrative review summarises current evidence of lung-brain crosstalk in patients receiving mechanical ventilation and describes the clinical implications of this crosstalk. Further, it proposes directions for future research ranging from identifying mechanisms of multiorgan failure to mitigating long-term sequelae after critical illness.

The ideal moment to withdraw respiratory supply of patients under Mechanical Ventilation at Intensive Care Units (ICU), is not easy to be determined for clinicians. Although the Spontaneous Breathing Trial (SBT) provides a measure of the patients' readiness, there is still around 15-20% of predictive failure rate. This work is a proof of concept focused on adding new value to the prediction of the weaning outcome. Heart Rate Variability (HRV) and Cardiopulmonary Coupling (CPC) methods are evaluated as new complementary estimates to assess weaning readiness. The CPC is related to how the mechanisms regulating respiration and cardiac pumping are working simultaneously, and it is defined from HRV in combination with respiratory information. Three different techniques are used to estimate the CPC, including Time-Frequency Coherence, Dynamic Mutual Information and Orthogonal Subspace Projections. The cohort study includes 22 patients in pressure support ventilation, ready to undergo the SBT, analysed in the 24 h previous to the SBT. Of these, 13 had a successful weaning and 9 failed the SBT or needed reintubation -being both considered as failed weaning. Results illustrate that traditional variables such as heart rate, respiratory frequency, and the parameters derived from HRV do not differ in patients with successful or failed weaning. Results revealed that HRV parameters can vary considerably depending on the time at which they are measured. This fact could be attributed to circadian rhythms, having a strong influence on HRV values. On the contrary, significant statistical differences are found in the proposed CPC parameters when comparing the values of the two groups, and throughout the whole recordings. In addition, differences are greater at night, probably because patients with failed weaning might be experiencing more respiratory episodes, e.g. apneas during the night, which is directly related to a reduced respiratory sinus arrhythmia. Therefore, results suggest that the traditional measures could be used in combination with the proposed CPC biomarkers to improve weaning readiness. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Background: Recent evidence suggests the beneficial effects of cell therapies and nebulized anticoagulants for acute respiratory distress syndrome (ARDS). Aim: Determine the therapeutic benefit of a combined cell therapy (alveolar type II cells (ATII), mesenchymal stem cells (MSC), supernatant (SN) ATII, SN MSC) with antithrombin in vitro in a coculture of ATII and alveolar macrophages injured with lipopolysaccharide (LPS). Methods: Cocultured ATII and alveolar macrophages isolated from rat lungs were injured with LPS (10 ng/ml). Two hours after the injury a combined cell therapy (ATII, MSC, SN ATII, SN MSC) with antithrombin (0.1 ng/ml) was administered. Proinflammatory mediators and coagulant factors were analyzed via qRT-PCR at 18 h. Data are expressed as mean±SEM. Statistical analysis was performed using One-Way-ANOVA and Bonferroni post-hoc test (statistical significance p≤0.05). Results: Proinflammatory mediators and coagulant factors were significantly increased after LPS administration. After administering the different treatments compared the expression of IL1β, IL6, TF PAI-1 and Plasminogen was not as high as in the LPS group. Conclusions: The results indicate that combined cell therapy with antithrombin are able to attenuate inflammation and coagulation in vitro in a coculture of ATII and macrophages. Both treatments together are able to face different processes involved in lung injury.

Patient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm’s performance was compared versus the gold standard (the ventilator’s waveform recordings for CP-VI were scored visually by three experts; Fleiss’ kappa = 0.90 (0.87–0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient’s own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78–0.86) and 0.78 (0.78–0.85), and accuracies of 0.93 (0.89–0.93) and 0.89 (0.89–0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.

Objective: To determine whether adalimumab administration before mechanical ventilation reduces ventilator- -induced lung injury (VILI). Methods: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/ kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. Results: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). Conclusion: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage., Facultad de Ciencias Médicas

Background To cope with shortages of equipment during the COVID-19 pandemic, we established a nonprofit end-to-end system to identify, validate, regulate, manufacture, and distribute 3D-printed medical equipment. Here we describe the local and global impact of this system. Methods Together with critical care experts, we identified potentially lacking medical equipment and proposed solutions based on 3D printing. Validation was based on the ISO 13485 quality standard for the manufacturing of customized medical devices. We posted the design files for each device on our website together with their technical and printing specifications and created a supply chain so that hospitals from our region could request them. We analyzed the number/type of items, petitioners, manufacturers, and catalogue views. Results Among 33 devices analyzed, 26 (78·8%) were validated. Of these, 23 (88·5%) were airway consumables and 3 (11·5%) were personal protective equipment. Orders came from 19 (76%) hospitals and 6 (24%) other healthcare institutions. Peak production was reached 10 days after the catalogue was published. A total of 22,135 items were manufactured by 59 companies in 18 sectors; 19,212 items were distributed to requesting sites during the busiest days of the pandemic. Our online catalogue was also viewed by 27,861 individuals from 113 countries. Conclusions 3D printing helped mitigate shortages of medical devices due to problems in the global supply chain.

Background The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. Aim To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Materials and methods Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. Results At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Conclusions Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI.

Background ICU patients undergoing invasive mechanical ventilation experience cognitive decline associated with their critical illness and its management. The early detection of different cognitive phenotypes might reveal the involvement of diverse pathophysiological mechanisms and help to clarify the role of the precipitating and predisposing factors. Our main objective is to identify cognitive phenotypes in critically ill survivors 1 month after ICU discharge using an unsupervised machine learning method, and to contrast them with the classical approach of cognitive impairment assessment. For descriptive purposes, precipitating and predisposing factors for cognitive impairment were explored. Methods A total of 156 mechanically ventilated critically ill patients from two medical/surgical ICUs were prospectively studied. Patients with previous cognitive impairment, neurological or psychiatric diagnosis were excluded. Clinical variables were registered during ICU stay, and 100 patients were cognitively assessed 1 month after ICU discharge. The unsupervised machine learning K-means clustering algorithm was applied to detect cognitive phenotypes. Exploratory analyses were used to study precipitating and predisposing factors for cognitive impairment. Results K-means testing identified three clusters (K) of patients with different cognitive phenotypes: K1 (n = 13), severe cognitive impairment in speed of processing (92%) and executive function (85%); K2 (n = 33), moderate-to-severe deficits in learning-memory (55%), memory retrieval (67%), speed of processing (36.4%) and executive function (33.3%); and K3 (n = 46), normal cognitive profile in 89% of patients. Using the classical approach, moderate-to-severe cognitive decline was recorded in 47% of patients, while the K-means method accurately classified 85.9%. The descriptive analysis showed significant differences in days (p = 0.016) and doses (p = 0.039) with opioid treatment in K1 vs. K2 and K3. In K2, there were more women, patients were older and had more comorbidities (p = 0.001) than in K1 or K3. Cognitive reserve was significantly (p = 0.001) higher in K3 than in K1 or K2. Conclusion One month after ICU discharge, three groups of patients with different cognitive phenotypes were identified through an unsupervised machine learning method. This novel approach improved the classical classification of cognitive impairment in ICU survivors. In the exploratory analysis, gender, age and the level of cognitive reserve emerged as relevant predisposing factors for cognitive impairment in ICU patients. Trial registration ClinicalTrials.gov Identifier:NCT02390024; March 17,2015.

RESUMO Objetivo: Determinar se a administracao de adalimumabe previamente a ventilacao mecânica reduz a lesao pulmonar induzida por ventilacao mecânica. Metodos: Randomizaram-se 18 ratos em tres grupos submetidos a ventilacao mecânica por 3 horas com uma fracao inspirada de oxigenio de 0,40%. Os tres grupos foram assim caracterizados: um grupo com baixo volume corrente (n = 6), no qual se utilizaram volume corrente de 8mL/kg e pressao expiratoria final positiva de 5cmH2O; um grupo com alto volume corrente (n = 6), no qual se utilizaram volume corrente de 35mL/kg e pressao expiratoria final positiva de zero; e um grupo pre-tratado com alto volume corrente (n = 6), no qual se administraram adalimumabe (100µg/kg) por via intraperitoneal 24 horas antes do inicio da ventilacao mecânica, volume corrente de 35mL/kg e pressao expiratoria final positiva de zero. Realizou-se ANOVA para comparacao de dano histologico (com utilizacao de escores segundo o ATS 2010 Lung Injury Scoring System), edema pulmonar, complacencia pulmonar, pressao parcial de oxigenio arterial e pressao arterial media entre os grupos. Resultados: Apos 3 horas de ventilacao, o escore medio de lesao histologica pulmonar foi mais elevado no grupo com alto volume corrente do que no grupo com baixo volume corrente (0,030 versus 0,0051; p = 0,003). O grupo com alto volume corrente demonstrou complacencia pulmonar diminuida apos 3 horas (p = 0,04) e hipoxemia (p = 0,018 versus controle). O grupo alto volume corrente tratado previamente teve melhora do escore histologico, principalmente devido a reducao significante da infiltracao leucocitaria (p = 0,003). Conclusao: O exame histologico apos 3 horas de ventilacao lesiva revelou lesao pulmonar induzida por ventilacao mecânica na ausencia de modificacoes mensuraveis na mecânica pulmonar e na oxigenacao; a administracao de adalimumabe antes da ventilacao mecânica diminuiu o edema pulmonar e o dano histologico.

Ineffective effort during expiration (IEE) occurs when there is a mismatch between the demand of a mechanically ventilated patient and the support delivered by a Mechanical ventilator during the expiration. This work presents a pressure–flow characterization for respiratory asynchronies and validates a machine-learning method, based on the presented characterization, to identify IEEs. 1500 breaths produced by 8 mechanically-ventilated patients were considered: 500 of them were included into the training set and the remaining 1000 into the test set. Each of them was evaluated by 3 experts and classified as either normal, artefact, or containing inspiratory, expiratory, or cycling-off asynchronies. A software implementing the proposed method was trained by using the experts’ evaluations of the training set and used to identify IEEs in the test set. The outcomes were compared with a consensus of three expert evaluations. The software classified IEEs with sensitivity 0.904, specificity 0.995, accuracy 0.983, positive and negative predictive value 0.963 and 0.986, respectively. The Cohen’s kappa is 0.983 (with 95% confidence interval (CI): [0.884, 0.962]). The pressure–flow characterization of respiratory cycles and the monitoring technique proposed in this work automatically identified IEEs in real-time in close agreement with the experts.

Background Big data analytics promise insights into healthcare processes and management, improving outcomes while reducing costs. However, data quality is a major challenge for reliable results. Business process discovery techniques and an associated data model were used to develop data management tool, ICU-DaMa, for extracting variables essential for overseeing the quality of care in the intensive care unit (ICU). Objective To determine the feasibility of using ICU-DaMa to automatically extract variables for the minimum dataset and ICU quality indicators from the clinical information system (CIS). Methods The Wilcoxon signed-rank test and Fisher’s exact test were used to compare the values extracted from the CIS with ICU-DaMa for 25 variables from all patients attended in a polyvalent ICU during a two-month period against the gold standard of values manually extracted by two trained physicians. Discrepancies with the gold standard were classified into plausibility, conformance, and completeness errors. Results Data from 149 patients were included. Although there were no significant differences between the automatic method and the manual method, we detected differences in values for five variables, including one plausibility error and two conformance and completeness errors. Plausibility: 1) Sex, ICU-DaMa incorrectly classified one male patient as female (error generated by the Hospital’s Admissions Department). Conformance: 2) Reason for isolation, ICU-DaMa failed to detect a human error in which a professional misclassified a patient’s isolation. 3) Brain death, ICU-DaMa failed to detect another human error in which a professional likely entered two mutually exclusive values related to the death of the patient (brain death and controlled donation after circulatory death). Completeness: 4) Destination at ICU discharge, ICU-DaMa incorrectly classified two patients due to a professional failing to fill out the patient discharge form when thepatients died. 5) Length of continuous renal replacement therapy, data were missing for one patient because the CRRT device was not connected to the CIS. Conclusions Automatic generation of minimum dataset and ICU quality indicators using ICU-DaMa is feasible. The discrepancies were identified and can be corrected by improving CIS ergonomics, training healthcare professionals in the culture of the quality of information, and using tools for detecting and correcting data errors.

Patient-ventilator asynchrony exists when the phases of breath delivered by the ventilator do not match those of the patient. Asynchronies occur throughout mechanical ventilation and negatively affect patient comfort, duration of mechanical ventilation, length of ICU stays, and mortality. Identifying asynchronies requires careful attention to patients and their ventilator waveforms. This review discusses the different types of asynchronies, how they are generated, and their impact on patient comfort and outcome. Moreover, it discusses practical approaches for detecting, correcting, and preventing asynchronies. Current evidence suggests that the best approach to managing asynchronies is by adjusting ventilator settings. Proportional modes improve patient-ventilator coupling, resulting in greater comfort and less dyspnea, but not in improved outcomes with respect to the duration of mechanical ventilation, delirium, or cognitive impairment. Advanced computational technologies will allow smart alerts, and models based on time series of asynchronies will be able to predict and prevent asynchronies, making it possible to tailor mechanical ventilation to meet each patient's needs throughout the course of mechanical ventilation.

Mechanical ventilation is a common procedure of life support in intensive care. Patient-ventilator asynchronies (PVAs) occur when the timing of the ventilator cycle is not simultaneous with the timing of the patient respiratory cycle. The association between severity markers and the events death or alive discharge has been acknowledged before, however, little is known about the addition of PVAs data to the analyses. We used an index of asynchronies (AI) to measure PVAs and the SOFA (sequential organ failure assessment) score to assess overall severity. To investigate the added value of including the AI, we propose a Bayesian joint model of bivariate longitudinal and competing risks data. The longitudinal process includes a mixed effects model for the SOFA score and a mixed effects beta regression model for the AI. The survival process is defined in terms of a cause-specific hazards model for the competing risks death or alive discharge. Our model indicates that the SOFA score is strongly related to vital status. PVAs are positively associated with alive discharge but there is not enough evidence that PVAs provide a more accurate indication of death prognosis than the SOFA score alone.

Ineffective effort during expiration (IEE) occurs when there is a mismatch between the demand of a mechanically ventilated patient and the support delivered by a Mechanical ventilator during the expiration. This work presents a pressure-flow characterization for respiratory asynchronies and validates a machine-learning method, based on the presented characterization, to identify IEEs. 1500 breaths produced by 8 mechanically-ventilated patients were considered: 500 of them were included into the training set and the remaining 1000 into the test set. Each of them was evaluated by 3 experts and classified as either normal, artefact, or containing inspiratory, expiratory, or cycling-off asynchronies. A software implementing the proposed method was trained by using the experts' evaluations of the training set and used to identify IEEs in the test set. The outcomes were compared with a consensus of three expert evaluations. The software classified IEEs with sensitivity 0.904, specificity 0.995, accuracy 0.983, positive and negative predictive value 0.963 and 0.986, respectively. The Cohen's kappa is 0.983 (with 95% confidence interval (CI): [0.884, 0.962]). The pressure-flow characterization of respiratory cycles and the monitoring technique proposed in this work automatically identified IEEs in real-time in close agreement with the experts.

Background During acute respiratory distress syndrome, proinflammatory mediators inhibit natural anticoagulant factors, which alter the normal balance between coagulation and fibrinolysis leading to a procoagulant state. We hypothesize that pulmonary administration of anticoagulants might be beneficial to treat acute respiratory distress syndrome for their anticoagulant and antiinflammatory effects and reduce the risk of systemic bleeding. Objectives Our aim is to study the effects of nebulized antithrombin (AT) and combined AT and heparin in an animal model of acute lung injury. Methods Acute lung injury was induced in rats by the intratracheal administration of hydrochloric acid and lipopolysaccharide. AT alone (500 IU/kg body weight) or combined with heparin (1000 IU/kg body weight) were nebulized after the injury. Control groups received saline instead. Blood, lung tissue, bronchoalveolar lavage, and alveolar macrophages (AM) isolated from bronchoalveolar lavage were collected after 48 hours and analyzed. Results Nebulized anticoagulant treatments reduced protein concentration in the lungs and decreased injury-mediated coagulation factors (tissue factor, plasminogen activator inhibitor-1, plasminogen, and fibrinogen degradation product) and inflammation (tumor necrosis factor α and interleukin 1β) in the alveolar space without affecting systemic coagulation and no bleeding. AT alone reduced fibrin deposition and edema in the lungs. Heparin did not potentiate AT coagulant effect but promoted the reduction of macrophages infiltration into the alveolar compartment. Anticoagulants reduced nuclear factor-kB downstream effectors in AM. Conclusions Nebulized AT and heparin attenuate lung injury through decreasing coagulation and inflammation without altering systemic coagulation and no bleeding. However, combined AT and heparin did not produce a synergistic effect.

Background Mechanical ventilation is common in critically ill patients. This life-saving treatment can cause complications and is also associated with long-term sequelae. Patient-ventilator asynchronies are frequent but underdiagnosed, and they have been associated with worse outcomes. Main body Asynchronies occur when ventilator assistance does not match the patient’s demand. Ventilatory overassistance or underassistance translates to different types of asynchronies with different effects on patients. Underassistance can result in an excessive load on respiratory muscles, air hunger, or lung injury due to excessive tidal volumes. Overassistance can result in lower patient inspiratory drive and can lead to reverse triggering, which can also worsen lung injury. Identifying the type of asynchrony and its causes is crucial for effective treatment. Mechanical ventilation and asynchronies can affect hemodynamics. An increase in intrathoracic pressure during ventilation modifies ventricular preload and afterload of ventricles, thereby affecting cardiac output and hemodynamic status. Ineffective efforts can decrease intrathoracic pressure, but double cycling can increase it. Thus, asynchronies can lower the predictive accuracy of some hemodynamic parameters of fluid responsiveness. New research is also exploring the psychological effects of asynchronies. Anxiety and depression are common in survivors of critical illness long after discharge. Patients on mechanical ventilation feel anxiety, fear, agony, and insecurity, which can worsen in the presence of asynchronies. Asynchronies have been associated with worse overall prognosis, but the direct causal relation between poor patient-ventilator interaction and worse outcomes has yet to be clearly demonstrated. Critical care patients generate huge volumes of data that are vastly underexploited. New monitoring systems can analyze waveforms together with other inputs, helping us to detect, analyze, and even predict asynchronies. Big data approaches promise to help us understand asynchronies better and improve their diagnosis and management. Conclusions Although our understanding of asynchronies has increased in recent years, many questions remain to be answered. Evolving concepts in asynchronies, lung crosstalk with other organs, and the difficulties of data management make more efforts necessary in this field.

IntroductionPatient-ventilator asynchrony is common during the entire period of invasive mechanical ventilation (MV) and is associated with worse clinical outcomes. However, risk factors associated with asynchrony are not completely understood. The main objectives of this study are to estimate the incidence of asynchrony during invasive MV and its association with respiratory mechanics and other baseline patient characteristics.Methods and analysisWe designed a prospective cohort study of patients admitted to the intensive care unit (ICU) of a university hospital. Inclusion criteria are adult patients under invasive MV initiated for less than 72 hours, and with expectation of remaining under MV for more than 24 hours. Exclusion criteria are high flow bronchopleural fistula, inability to measure respiratory mechanics and previous tracheostomy. Baseline assessment includes clinical characteristics of patients at ICU admission, including severity of illness, reason for initiation of MV, and measurement of static mechanics of the respiratory system. We will capture ventilator waveforms during the entire MV period that will be analysed with dedicated software (Better Care, Barcelona, Spain), which automatically identifies several types of asynchrony and calculates the asynchrony index (AI). We will use a linear regression model to identify risk factors associated with AI. To assess the relationship between survival and AI we will use Kaplan-Meier curves, log rank tests and Cox regression. The calculated sample size is 103 patients. The statistical analysis will be performed by the software R Programming (www.R-project.org) and will be considered statistically significant if the p value is less than 0.05.Ethics and disseminationThe study was approved by the Ethics Committee of Instituto do Coração, School of Medicine, University of São Paulo, Brazil, and informed consent was waived due to the observational nature of the study. We aim to disseminate the study findings through peer-reviewed publications and national and international conference presentations.Trial registration numberNCT02687802; Pre-results.

BACKGROUND: In critically ill patients, poor patient-ventilator interaction may worsen outcomes. Although sedatives are often administered to improve comfort and facilitate ventilation, they can be deleterious. Whether opioids improve asynchronies with fewer negative effects is unknown. We hypothesized that opioids alone would improve asynchronies and result in more wakeful patients than sedatives alone or sedatives-plus-opioids. METHODS: This prospective multicenter observational trial enrolled critically ill adults mechanically ventilated (MV) > 24 h. We compared asynchronies and sedation depth in patients receiving sedatives, opioids, or both. We recorded sedation level and doses of sedatives and opioids. BetterCare™ software continuously registered ineffective inspiratory efforts during expiration (IEE), double cycling (DC), and asynchrony index (AI) as well as MV modes. All variables were averaged per day. We used linear mixed-effects models to analyze the relationships between asynchronies, sedation level, and sedative and opioid doses. RESULTS: In 79 patients, 14,166,469 breaths were recorded during 579 days of MV. Overall asynchronies were not significantly different in days classified as sedatives-only, opioids-only, and sedatives-plus-opioids and were more prevalent in days classified as no-drugs than in those classified as sedatives-plus-opioids, irrespective of the ventilatory mode. Sedative doses were associated with sedation level and with reduced DC (p

In mechanical ventilation, it is paramount to ensure the patient’s ventilatory demand is met while minimizing asynchronies. We aimed to develop a model to predict the likelihood of asynchronies occurring. We analyzed 10,409,357 breaths from 51 critically ill patients who underwent mechanical ventilation >24 h. Patients were continuously monitored and common asynchronies were identified and regularly indexed. Based on discrete time-series data representing the total count of asynchronies, we defined four states or levels of risk of asynchronies, z1 (very-low-risk) – z4 (very-high-risk). A Poisson hidden Markov model was used to predict the probability of each level of risk occurring in the next period. Long periods with very few asynchronous events, and consequently very-low-risk, were more likely than periods with many events (state z4). States were persistent; large shifts of states were uncommon and most switches were to neighbouring states. Thus, patients entering states with a high number of asynchronies were very likely to continue in that state, which may have serious implications. This novel approach to dealing with patient-ventilator asynchrony is a first step in developing smart alarms to alert professionals to patients entering high-risk states so they can consider actions to improve patient-ventilator interaction.

End-of-life care in the intensive care unit (ICU) was identified as an objective in a series of Task Forces developed by the World Federation of Societies of Intensive and Critical Care Medicine Council in 2014. The objective was to develop a generic statement about current knowledge and to identify challenges relevant to the global community that may inform regional and local initiatives. An updated summary of published statements on end-of-life care in the ICU from national Societies is presented, highlighting commonalities and differences within and between international regions. The complexity of end-of-life care in the ICU, particularly relating to withholding and withdrawing life-sustaining treatment while ensuring the alleviation of suffering, within different ethical and cultural environments is recognized. Although no single statement can therefore be regarded as a criterion standard applicable to all countries and societies, the World Federation of Societies of Intensive and Critical Care Medicine endorses and encourages the role of Member Societies to lead the debate regarding end-of-life care in the ICU within each country and to take a leading role in developing national guidelines and recommendations within each country.