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BACKGROUND: In mechanically ventilated patients, diaphragm ultrasound can identify diaphragm weakness and predict weaning failure. We evaluated whether a novel operator-independent ultrasound-based medical device allowing continuous monitoring of the diaphragm (CUSdi) could reliably (1) measure diaphragm excursion (EXdi) and peak contraction velocity (PCVdi), (2) predict weaning outcome, and (3) approximate transdiaphragmatic pressure (Pdi). METHODS: In 49 mechanically ventilated patients, CUSdi was recorded during a 30-min spontaneous breathing trial (SBT), and EXdi and PCVdi were measured. In subgroups of patients, standard ultrasound measurement of EXdi and PCVdi was performed (n = 36), and Pdi derived parameters (peak and pressure time product, n = 30) were measured simultaneously. RESULTS: The agreement bias between standard ultrasound and CUSdi for EXdi was 0.1 cm (95% confidence interval -0.7-0.9 cm). The regression of Passing-Bablok indicated a lack of systematic difference between EXdi measured with standard ultrasound and CUSdi, which were positively correlated (Rho = 0.84, p < 0.001). Weaning failure was observed in 54% of patients. One, two and three minutes after the onset of the SBT, EXdi was higher in the weaning success group than in the failure group. Two minutes after the onset of the SBT, an EXdi < 1.1 cm predicted weaning failure with a sensitivity of 0.83, a specificity of 0.68, a positive predictive value of 0.76, and a negative predictive value of 0.24. There was a weak correlation between EXdi and both peak Pdi (r = 0.22, 95% confidence interval 0.15 - 0.28) and pressure time product (r = 0.13, 95% confidence interval 0.06 - 0.20). Similar results were observed with PCVdi. CONCLUSIONS: Operator-independent continuous diaphragm monitoring quantifies EXdi reliably and can predict weaning failure with an identified cut-off value of 1.1 cm. Trial registration clinicaltrial.gov, NCT04008875 (submitted 12 April 2019, posted 5 July 2019) and NCT03896048 (submitted 27 March 2019, posted 29 March 2019).
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Diafragma , Ultrasonografía , Desconexión del Ventilador , Humanos , Desconexión del Ventilador/métodos , Desconexión del Ventilador/normas , Diafragma/diagnóstico por imagen , Diafragma/fisiopatología , Estudios Prospectivos , Masculino , Femenino , Ultrasonografía/métodos , Ultrasonografía/normas , Persona de Mediana Edad , Anciano , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentación , Respiración Artificial/métodos , Valor Predictivo de las PruebasRESUMEN
Background: There is a lack of bench systems permitting to evaluate ventilation devices in the specific context of cardiac arrest. Objectives: The objective of the study is to assess if a new physiological manikin may permit to evaluate the performances of medical devices dedicated to ventilation during cardiopulmonary resuscitation (CPR). Methods: Specific CPR-related features required to reproduce realistic ventilation were implemented into the SAM (Sarthe Anjou Mayenne) manikin. In the first place, the manikin ability to mimic ventilation during CPR was assessed and compared to real-life tracings of airway pressure, flow and capnogram from three out of hospital cardiac arrest (OHCA) patients. In addition, to illustrate the interest of this manikin, ventilation was evaluated during mechanical continuous chest compressions with two devices dedicated to CPR: the Boussignac cardiac arrest device (B-card - Vygon; Ecouen France) and the Impedance Threshold Device (ITD - Zoll; Chelmsford, MA). Results: The SAM manikin enabled precise replication of ventilation tracings as observed in three OHCA patients during CPR, and it allowed for comparison between two distinct ventilation devices. B-card generated a mean, maximum and minimum intrathoracic pressure of 6.3 (±0.1) cmH2O, 18.9 (±1.1) cmH2O and -0.3 (±0.2) cmH2O respectively; while ITD generated a mean, maximum and minimum intrathoracic pressure of -1.6 (±0.0) cmH2O, 5.7 (±0.1) cmH2O and -4.8 (±0.1) cmH2O respectively during CPR. B-card allowed to increase passive ventilation compared to the ITD which resulted in a dramatic limitation of passive ventilation. Conclusion: The SAM manikin is an innovative model integrating specific physiological features that permit to accurately evaluate and compare ventilation devices during CPR.
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BACKGROUND: Reverse triggering (RT) was described in 2013 as a form of patient-ventilator asynchrony, where patient's respiratory effort follows mechanical insufflation. Diagnosis requires esophageal pressure (Pes) or diaphragmatic electrical activity (EAdi), but RT can also be diagnosed using standard ventilator waveforms. HYPOTHESIS: We wondered (1) how frequently RT would be present but undetected in the figures from literature, especially before 2013; (2) whether it would be more prevalent in the era of small tidal volumes after 2000. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from 1950 to 2017, with key words related to asynchrony to identify papers with figures including ventilator waveforms expected to display RT if present. Experts labelled waveforms. 'Definite' RT was identified when Pes or EAdi were in the tracing, and 'possible' RT when only flow and pressure waveforms were present. Expert assessment was compared to the author's descriptions of waveforms. RESULTS: We found 65 appropriate papers published from 1977 to now, containing 181 ventilator waveforms. 21 cases of 'possible' RT and 25 cases of 'definite' RT were identified by the experts. 18.8% of waveforms prior to 2013 had evidence of RT. Most cases were published after 2000 (1 before vs. 45 after, p = 0.03). 54% of RT cases were attributed to different phenomena. A few cases of identified RT were already described prior to 2013 using different terminology (earliest in 1997). While RT cases attributed to different phenomena decreased after 2013, 60% of 'possible' RT remained missed. CONCLUSION: RT has been present in the literature as early as 1997, but most cases were found after the introduction of low tidal volume ventilation in 2000. Following 2013, the number of undetected cases decreased, but RT are still commonly missed. Reverse Triggering, A Missed Phenomenon in the Literature. Critical Care Canada Forum 2019 Abstracts. Can J Anesth/J Can Anesth 67 (Suppl 1), 1-162 (2020). https://doi-org.myaccess.library.utoronto.ca/ https://doi.org/10.1007/s12630-019-01552-z .
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BACKGROUND: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population. METHODS: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality. RESULTS: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046). CONCLUSIONS: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier # NCT01320384.
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Disnea , Insuficiencia Respiratoria , Humanos , Disnea/etiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Intubación Intratraqueal/estadística & datos numéricos , Intubación Intratraqueal/métodos , Hipoxia/terapia , Hipoxia/fisiopatología , Hipoxia/complicaciones , Unidades de Cuidados Intensivos/estadística & datos numéricos , Unidades de Cuidados Intensivos/organización & administración , Modelos de Riesgos ProporcionalesRESUMEN
Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.
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Enfermedad Crítica , Disnea , Respiración Artificial , Humanos , Masculino , Disnea/mortalidad , Disnea/etiología , Femenino , Estudios Prospectivos , Enfermedad Crítica/mortalidad , Persona de Mediana Edad , Anciano , Francia/epidemiología , Obstrucción de las Vías Aéreas/mortalidad , Obstrucción de las Vías Aéreas/terapia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estudios de CohortesRESUMEN
BACKGROUND: Trained ICU nurses may perform oesophageal pressure measurements which may help facilitate its implementation in the usual patient care to better assess lung and chest wall mechanics and easily detect patient-ventilator asynchronies. AIM AND STUDY DESIGN: We thus conducted a prospective educational study aiming to assess the ability of ICU nurses to perform reliable oesophageal pressure measurements after a short dedicated training program. RESULTS: All the 11 nurses who completed the program succeeded their practical evaluation (nine (82%) at the first evaluation and two (18%) at their second attempt). CONCLUSION: These results show that this training program is feasible and that trained ICU nurses can perform accurate oesophageal pressure measurements in mechanically ventilated patients. RELEVANCE TO CLINICAL PRACTICE: Such training program may help to implement this technique in routine ICU care.
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BACKGROUND: Various Positive End-Expiratory Pressure (PEEP) titration strategies have been proposed to optimize ventilation in patients with acute respiratory distress syndrome (ARDS). We aimed to compare PEEP titration strategies based on electrical impedance tomography (EIT) to methods derived from respiratory system mechanics with or without esophageal pressure measurements, in terms of PEEP levels and association with recruitability. METHODS: Nineteen patients with ARDS were enrolled. Recruitability was assessed by the estimated Recruitment-to-Inflation ratio (R/Iest) between PEEP 15 and 5 cmH2O. Then, a decremental PEEP trial from PEEP 20 to 5 cmH2O was performed. PEEP levels determined by the following strategies were studied: (1) plateau pressure 28-30 cmH2O (Express), (2) minimal positive expiratory transpulmonary pressure (Positive PLe), (3) center of ventilation closest to 0.5 (CoV) and (4) intersection of the EIT-based overdistension and lung collapse curves (Crossing Point). In addition, the PEEP levels determined by the Crossing Point strategy were assessed using different PEEP ranges during the decremental PEEP trial. RESULTS: Express and CoV strategies led to higher PEEP levels than the Positive PLe and Crossing Point ones (17 [14-17], 20 [17-20], 8 [5-11], 10 [8-11] respectively, p < 0.001). For each strategy, there was no significant association between the optimal PEEP level and R/Iest (Crossing Point: r2 = 0.073, p = 0.263; CoV: r2 < 0.001, p = 0.941; Express: r2 < 0.001, p = 0.920; Positive PLe: r2 = 0.037, p = 0.461). The PEEP level obtained with the Crossing Point strategy was impacted by the PEEP range used during the decremental PEEP trial. CONCLUSIONS: CoV and Express strategies led to higher PEEP levels than the Crossing Point and Positive PLe strategies. Optimal PEEP levels proposed by these four methods were not associated with recruitability. Recruitability should be specifically assessed in ARDS patients to optimize PEEP titration.
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Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.
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Síndrome de Dificultad Respiratoria , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/terapia , Oximetría , OxígenoRESUMEN
BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).
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Enfermedad Crítica , Síndrome de Dificultad Respiratoria , Humanos , Peso Corporal , Obesidad/complicaciones , Respiración Artificial , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/terapia , Mecánica RespiratoriaRESUMEN
BACKGROUND: Several noninvasive ventilatory supports rely in their design on high oxygen consumption which may precipitate oxygen shortage, as experienced during the COVID-19 pandemic. In this bench-to-bedside study, we assessed the performance of a new continuous positive airway pressure (CPAP) device integrating a large reservoir ("Bag-CPAP") designed to minimize oxygen consumption, and compared it with other CPAP devices. METHODS: First, a bench study compared the performances of Bag-CPAP and four CPAP devices with an intensive care unit ventilator. Two FiO2 targets (40-60% and 80-100%) at a predefined positive end expiratory pressure (PEEP) level between 5 and 10 cm H2O were tested and fraction of inspired oxygen (FiO2) and oxygen consumption were measured. Device-imposed work of breathing (WOB) was also evaluated. Second, an observational clinical study evaluated the new CPAP in 20 adult patients with acute respiratory failure in two hospitals in France. Actual FiO2, PEEP, peripheral oxygen saturation, respiratory rate, and dyspnea score were assessed. RESULTS: All six systems tested in the bench study reached the minimal FiO2 target of 40% and four reached at least 80% FiO2 while maintaining PEEP in the predefined range. Device-delivered FiO2/consumed oxygen ratio was the highest with the new reservoir-based CPAP irrespective of FiO2 target. WOB induced by the device was higher with Bag-CPAP. In the clinical study, Bag-CPAP was well tolerated and could reach high (> 90%) and moderate (> 50%) FiO2 with an oxygen flow rate of 15 [15-16] and 8 [7-9] L/min, respectively. Dyspnea score improved significantly after introduction of Bag-CPAP, and SpO2 increased. CONCLUSIONS: In vitro, Bag-CPAP exhibited the highest oxygen saving properties albeit had increased WOB. It was well accepted clinically and reduced dyspnea. Bag-CPAP may be useful to treat patients with acute respiratory failure in the field, especially when facing constraints in oxygen delivery.
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COVID-19 , Insuficiencia Respiratoria , Adulto , Humanos , Presión de las Vías Aéreas Positiva Contínua , COVID-19/terapia , Disnea , Oxígeno , Consumo de Oxígeno , Pandemias , Insuficiencia Respiratoria/terapiaRESUMEN
BACKGROUND: Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. OBJECTIVES: To validate the conductive pressure (Pcond) method, which compare the Pcond-defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP-to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. METHODS: The proof-of-concept of the Pcond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the Pcond method was compared with the standard low-flow method. MEASUREMENTS AND MAIN RESULTS: Bench assessments validated the Pcond method proof-of-concept. Sensitivity and specificity of the Pcond method for AOP detection were 93% and 91%, respectively. AOP obtained by Pcond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during Pcond than during standard method (p < 0.001). CONCLUSION: Determination of Pcond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP.
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Insuflación , Humanos , Insuflación/métodos , Pulmón , Fenómenos Fisiológicos Respiratorios , Mecánica Respiratoria , Respiración Artificial/métodosRESUMEN
The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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COVID-19 , Síndrome de Dificultad Respiratoria , Adulto , Humanos , COVID-19/terapia , Respiración Artificial , Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria/terapia , Cuidados CríticosRESUMEN
BACKGROUND: Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. METHODS: Multicentre, retrospective cohort study conducted in France. RESULTS: From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57-72) years, 37 (29-48), and 5 (3-8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1-5.5) days with a median dosage of 10 (7-13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). CONCLUSIONS: Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.
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OBJECTIVE: Prior to the coronavirus disease 2019 (COVID-19) pandemic, influenza was the most frequent cause of viral respiratory pneumonia requiring intensive care unit (ICU) admission. Few studies have compared the characteristics and outcomes of critically ill patients with COVID-19 and influenza. METHODS: This was a French nationwide study comparing COVID-19 (March 1, 2020-June 30, 2021) and influenza patients (January 1, 2014-December 31, 2019) admitted to an ICU during pre-vaccination era. Primary outcome was in-hospital death. Secondary outcome was need for mechanical ventilation. RESULTS: 105,979 COVID-19 patients were compared to 18,763 influenza patients. Critically ill patients with COVID-19 were more likely to be men with more comorbidities. Patients with influenza required more invasive mechanical ventilation (47 vs. 34%, p < 0·001), vasopressors (40% vs. 27, p < 0·001) and renal-replacement therapy (22 vs. 7%, p < 0·001). Hospital mortality was 25% and 21% (p < 0·001) in patients with COVID-19 and influenza, respectively. In the subgroup of patients receiving invasive mechanical ventilation, ICU length of stay was significantly longer in patients with COVID-19 (18 [10-32] vs. 15 [8-26] days, p < 0·001). Adjusting for age, gender, comorbidities, and modified SAPS II score, in-hospital death was higher in COVID-19 patients (adjusted sub-distribution hazard ratio [aSHR]=1.69; 95%CI=1.63-1.75) compared with influenza patients. COVID-19 was also associated with less invasive mechanical ventilation (aSHR=0.87; 95%CI=0.85-0.89) and a higher likelihood of death without invasive mechanical ventilation (aSHR=2.40; 95%CI=2.24-2.57). CONCLUSION: Despite younger age and lower SAPS II score, critically ill COVID-19 patients had a longer hospital stay and higher mortality than patients with influenza.
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COVID-19 , Gripe Humana , Neumonía Viral , Masculino , Humanos , Adulto , Femenino , COVID-19/epidemiología , COVID-19/terapia , SARS-CoV-2 , Mortalidad Hospitalaria , Enfermedad Crítica/terapia , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Unidades de Cuidados Intensivos , Respiración Artificial , Estudios RetrospectivosRESUMEN
Rationale: Extracellular histones, released into the surrounding environment during extensive cell death, promote inflammation and cell death, and these deleterious roles have been well documented in sepsis. Clusterin (CLU) is a ubiquitous extracellular protein that chaperones misfolded proteins and promotes their removal. Objectives: We investigated whether CLU could protect against the deleterious properties of histones. Methods: We assessed CLU and histone expression in patients with sepsis and evaluated the protective role of CLU against histones in in vitro assays and in vivo models of experimental sepsis. Measurements and Main Results: We show that CLU binds to circulating histones and reduces their inflammatory, thrombotic, and cytotoxic properties. We observed that plasma CLU levels decreased in patients with sepsis and that the decrease was greater and more durable in nonsurvivors than in survivors. Accordingly, CLU deficiency was associated with increased mortality in mouse models of sepsis and endotoxemia. Finally, CLU supplementation improved mouse survival in a sepsis model. Conclusions: This study identifies CLU as a central endogenous histone-neutralizing molecule and suggests that, in pathologies with extensive cell death, CLU supplementation may improve disease tolerance and host survival.
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Antineoplásicos , Sepsis , Animales , Ratones , Histonas/metabolismo , Clusterina/metabolismo , Inflamación , Muerte Celular , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: Unique blood culture (UBC) has been proposed to limit the number of venipuncture and to decrease the risk of BC contaminations (BCC) without affecting their yield. We hypothesized that a multi-faceted program based on UBC in the ICU may reduce the rate of contaminants with a similar performance for bloodstream infections (BSI) identification. METHODS: In a before and after design, we compared the proportion of BSI and BCC. A first 3-year period with multi-sampling (MS) strategy followed by a 4-month washout period, where staff received education and training for using UBC, and a 32-month period, where UBC was routinely used, while education and feedback were maintained. During the UBC period, a large volume of blood (40 mL) was sampled through a unique venipuncture with additional BC collections discouraged for 48 h. RESULTS: Of the 4,491 patients included (35% female patients, mean age 62 years) 17,466 BC were collected. The mean volume of blood per bottle collected increased from 2.8 ± 1.8 mL to 8.2 ± 3.9 mL between the MS and UBC periods, P < 0.01. A 59.6% reduction (95% CI 56.7-62.3; P < 0.001) of BC bottles collected per week was observed between the MS and UBC periods. The rate of BCC per patient decreased between the two periods from 11.2% to 3.8% (73.4% reduction; P < 0.001) for the MS and UBC periods, P < 0.001. Meanwhile, the rate of BSI per patient remained stable at 13.2% and 13.2% for the MS and UBC periods, P = 0.98. CONCLUSIONS: In ICU patients, a strategy based on UBC reduces the contamination rate of cultures without affecting their yield.
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BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.
Asunto(s)
Soporte Ventilatorio Interactivo , Respiración Artificial , Humanos , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Soporte Ventilatorio Interactivo/efectos adversos , Desconexión del Ventilador/métodos , Respiración con Presión Positiva/métodos , Respiración , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit. METHODS: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345. FINDINGS: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69). INTERPRETATION: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population. FUNDING: French Ministry of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.