Number Of Ventilator-free Days Research Articles

Effects of mechanical insufflation-exsufflation on ventilator-free days in intensive care unit subjects with sputum retention; a randomized clinical trial.

Mechanical insufflation-exsufflation (MI-E) facilitates extubation. However, its potential to reduce the duration of ventilator use remains unclear. Therefore, the present study investigated whether the use of MI-E shortened the duration of mechanical ventilation in patients with high sputum retention. A randomized open-label trial was conducted at a single intensive care unit (ICU) in Japan between November 2017 and June 2019. Ventilated subjects requiring suctioning at least once every hour due to sputum retention were randomly assigned to the MI-E group or conventional care group. The primary endpoint was the number of ventilator-free days on day 28. Secondary endpoints were ventilator days in surviving subjects, the length of ICU stay, and mortality and tracheostomy rates among survivors. Forty-eight subjects (81% males) with a median age of 72 years (interquartile range [IQR], 65-85 years) were enrolled. There were 27 subjects in the MI-E group and 21 in the control group. The median number of ventilator-free days was 21 (IQR, 13-24) and 18, respectively (IQR, 0-23) (P = .38). No significant differences were observed in the ICU length of stay (median, 10 days (IQR, 7-12) vs 12 days (IQR, 6-15); P = .31), mortality rate (19% vs 15%; odds ratio [OR], 1.36 [0.28-6.50]; P = .69), or tracheostomy rate among survivors (14% vs 28%; OR, 0.40 [0.08-1.91]; P = .25). In ventilated subjects in the ICU with high sputum retention, the use of MI-E did not significantly increase the number of ventilator-free days over that with conventional care.

Association of antibiotic duration and all-cause mortality in a prospective study of patients with ventilator-associated pneumonia in a tertiary-level critical care unit in Southern India

ObjectivesTo estimate all-cause mortality in ventilator-associated pneumonia (VAP) and determine whether antibiotic duration beyond 8 days is associated with reduction in all-cause mortality in patients admitted with VAP in the...

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial

IntroductionLung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite...

Early Mobilization Using a Mobile Patient Lift in the ICU: A Randomized Controlled Trial.

To ascertain whether a mobile patient lift facilitates early mobilization in ventilated ICU patients. A single-center, open-label, randomized controlled trial. An academic ICU in Tokyo. Eighty patients were admitted to ICU and expected ventilation for at least 48 hours. In the intervention group, in addition to the rehabilitation protocol received by the control group, patients were assisted in sitting, standing, transfers, and walking using the mobile patient lift. The intervention group predominantly stood faster than the control group (1.0 vs. 3.0 d, p < 0.01). The Intervention group also had significantly higher Functional Status Score-ICU scores at ICU discharge. However, the Medical Research Council score and Barthel index at discharge, length of ICU stay, and number of ventilator-free days did not differ between the two groups. The use of mobile patient lifts facilitates the earlier standing of patients on ventilators. This may contribute to patients improved physical function in the ICU. The study protocol was registered with the University Hospital Medical Information Network (UMIN) under the registration number UMIN000044965. Registered July 30, 2021.

Efficacy and Safety of Glucocorticoid in the Treatment of Acute Respiratory Distress Syndrome caused by Covid-19: A Systematic Review and Meta-Analysis.

Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of glucocorticoids in the treatment of ARDS caused by COVID-19 are still controversial; therefore, we conducted this meta-analysis of the literature on this topic. Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from the establishment of the databases to August 16, 2023. Randomized controlled trials (RCTs) and cohort studies that compared glucocorticoid versus standard treatment for ARDS caused by COVID-19 were included. The Newcastle-Ottawa Scale (NOS) checklist and the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias. Review Manager 5.4 software and STATA 17.0 were used for meta-analy-sis, and the relative risk (RR), mean difference, and 95% confidence intervals (CIs) were then determined. Results: A total of 17 studies involving 8592 patients were evaluated, including 14 retrospective studies and 3 RCTs. Sixteen studies reported data on all-cause mortality. The results of the meta-analysis showed that glucocorticoids did not reduce all-cause (RR, 0.96; 95% CI 0.82-1.13, P = .62) or 28-day (RR, 1.01; 95% CI 0.78-1.32, P = .93) mortality. Subgroup analysis showed that only methylprednisolone reduced all-cause mortality. No matter whether glucocorticoid use was early or delayed, high-dose or low-dose, long-term or short-term, no regimen reduced all-cause mortality. Furthermore, there were no significant differences in length of intensive care unit (ICU) stay, length of hospital stay, hyperglycemia, and ventilator-associated pneumonia (VAP); how-ever, glucocorticoids increased the number of ventilator-free days. Although methylprednisolone may reduce all-cause mortality from ARDS caused by COVID-19, this effect was not found with other types of glucocorticoids. At the same time, glucocorticoid use was associ-ated with more ventilator-free days, without increasing the incidence of hyperglycemic events or VAP. Con-sidering that almost all of the included studies were retrospective cohort studies, more RCTs are needed to confirm these findings.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial

PurposeEvaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). Materials and methodsRandomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90). ResultsEighty-three patients were randomized and received infusions (Cx611: n = 42]; placebo: n = 41]. The mean age was similar (Cx611: 61.1 [11.2] years; placebo: 63.4 [10.4] years). The number of AEs and treatment-emergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611: n = 9; placebo: n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611: 86.7%; placebo: 93.8%), mean number of ventilator-free days (Cx611: 12.2 [10.29] days; placebo: 15.4 [10.75] days), and overall survival (Cx611: 71.5%; placebo: 77.0%) did not differ between study arms. ConclusionCx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation. Trial registrationNCT03158727 (retrospectively registered: May 09, 2017).Full study protocol: https://clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf

Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy–controlled, phase 2 multicenter study (ONE-BRIDGE)

BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow–derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated.MethodsA randomized, open-label, standard therapy–controlled, phase 2 study (January 2019–September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 2:1 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30–60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates.ResultsMedian (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0–24.0] vs 11.0 [0.0–14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)]: invimestrocel group, 11.6 [6.9–16.3]; standard group, 6.2 [− 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [− 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel.ConclusionsIn Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated.Trial registration: ClinicalTrials.gov, Identifier: NCT03807804; January 8, 2019; https://clinicaltrials.gov/ct2/show/NCT03807804.

Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial

BackgroundFindings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis.MethodsA multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30.ResultsBetween June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15–30] and 30 days [18–30], respectively; median absolute difference of − 0.0 days, 95% CI − 3.3 to 3.3; p = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5–28] versus 6 days [2–13], p = 0.02).ConclusionsIn a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation.Trial registration: ClinicalTrials.gov registration number NCT02126332, April 30, 2014.

Positive End-Expiratory Pressure Levels in Adult Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome

Positive End-Expiratory Pressure Levels in Adult Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome

Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial

BackgroundPatients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders.Methods and analysisThis study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.

Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial

BackgroundFluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28.MethodsThe “effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients” (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician’s discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1–7 after randomisation and on days 1–7 after start of LUS examination; mean serum lactate on days 1–7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28.DiscussionThe CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable.Trial registrationClinicalTrials.gov NCT05188092. Registered since January 12, 2022

Identification and development of a five-gene signature to improve the prediction of mechanical ventilator-free days for patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe COVID-19 infection causes complications in the respiratory tract, which results in pulmonary failure, thus requiring prolonged mechanical ventilation (MV). An increase in the number of patients with COVID-19 poses numerous challenges to the healthcare system, including the shortage of MV facilities. Despite continued efforts to improve COVID-19 diagnosis and treatment, no study has established a reliable predictive model for the risk assessment of deteriorating COVID-19 cases. We extracted the expression profiles and clinical data of the GSE157103, GSE116560 and GSE21802 cohorts from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified as the intersection of the resulting differential genes as analysed via limma, edgeR and DESeq2 R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the R package 'clusterProfiler'. Variables closely related to MV were examined using univariate Cox regression analysis, and significant variables were subjected to least absolute shrinkage and selection operator regression (LASSO) analysis for the construction of a risk model. Kaplan-Meier analysis and receiver operating characteristic (ROC) curves were generated to verify the predictive values of the risk model. We identified 198 unigenes that were differentially expressed in COVID-19 samples. Moreover, a five-gene signature (BTN3A1, GPR35, HAAO, SLC2A6 and TEX2) was constructed to predict the ventilator-free days of patients with COVID-19. In our study, we used the five-gene signature to calculate the risk score (MV score) for each patient. The results revealed a statistical correlation between the MV score and the scores of the Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment of patients with COVID-19. Kaplan-Meier analysis revealed that the number of ventilator-free days was significantly reduced in the low-MVscore group compared to the high-MVscore group. The ROC curves revealed that our model had a good performance, and the areas under the ROC curve were 0.93 (3-week ROC) and 0.97 (4-week ROC). The 'Limma' package analysis revealed 71 upregulated genes and 59 downregulated genes in the high-MV score group compared to the low-MV score group. These DEGs were mainly enriched in cytokine signalling in immune system and cellular response to cytokine stimulus. This study identified a five-gene signature that can predict the length of ventilator-free days for patients with COVID-19.

Early Light Sedation Increased the Duration of Mechanical Ventilation in Patients With Severe Lung Injury.

The international guidelines recommend light sedation management for patients receiving mechanical ventilation. One of the benefits of light sedation management during mechanical ventilation is the preservation of spontaneous breathing, which leads to improved gas-exchange and patient outcomes. Conversely, recent experimental animal studies have suggested that strong spontaneous breathing effort may cause worsening of lung injury, especially in severe lung injury cases. The association between depth of sedation and patient outcomes may depend on the severity of lung injury. This study aimed to describe the patients' clinical outcomes under deep or light sedation during the first 48 h of mechanical ventilation and investigate the association of light sedation on patient outcomes for each severity of lung injury. The researchers performed a retrospective observational study at a university hospital in Japan. Patients aged ≥20 years, who received mechanical ventilation for at least 48 h were enrolled. A total of 413 patient cases were analyzed. Light sedation was associated with significantly shorter 28-day ventilator-free days compared with deep sedation in patients with severe lung injury (0 [IQR 0-5] days vs. 16 [0-19] days, P = .038). In the groups of patients with moderate and mild lung injury, the sedation depth was not associated with ventilator-free days. After adjusting for the positive end-expiratory pressure and APACHE II score, it was found that light sedation decreased the number of ventilator-free days in patients with severe lung injury (-10.8 days, 95% CI -19.2 to -2.5, P = .012). Early light sedation for severe lung injury may be associated with fewer ventilator-free days.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Inhaled Sedation in Patients with COVID-19-Related Acute Respiratory Distress Syndrome: An International Retrospective Study

The coronavirus disease 2019 (COVID-19) pandemic and the shortage of intravenous sedatives has led to renewed interest in inhaled sedation for patients with acute respiratory distress syndrome (ARDS). We hypothesized that inhaled sedation would be associated with improved clinical outcomes in COVID-19 ARDS patients. Retrospective international study including mechanically ventilated patients with COVID-19 ARDS who required sedation and were admitted to 10 European and US intensive care units. The primary endpoint of ventilator-free days through day 28 was analyzed using zero-inflated negative binomial regression, before and after adjustment for site, clinically relevant covariates determined according to the univariate results, and propensity score matching. A total of 196 patients were enrolled, 78 of whom died within 28 days. The number of ventilator-free days through day 28 did not differ significantly between the patients who received inhaled sedation for at least 24 h (n = 111) and those who received intravenous sedation only (n = 85), with medians of 0 (interquartile range [IQR] 0-8) and 0 (IQR 0-17), respectively (odds ratio for having zero ventilator-free days through day 28, 1.63, 95% confidence interval [CI], 0.91-2.92, p = 0.10). The incidence rate ratio for the number of ventilator-free days through day 28 if not 0 was 1.13 (95% CI, 0.84-1.52, p = 0.40). Similar results were found after multivariable adjustment and propensity matching. The use of inhaled sedation in COVID-19 ARDS was not associated with the number of ventilator-free days through day 28.

Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece

BackgroundSpontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.MethodsIn this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.ResultsA total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], −0.5 to 1; P=0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, −3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).ConclusionsAmong patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.)

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation

BackgroundInvasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown.MethodsIn a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge.ResultsA total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P=0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups.ConclusionsAmong critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.)

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19

The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. ClinicalTrials.gov Identifier: NCT04468126.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist