Reappraisal of Ventilator-Free Days in Critical Care Research.
Ontology highlight
ABSTRACT:
SUBMITTER: Yehya N
PROVIDER: S-EPMC6812447 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) regulates numerous intracellular signaling pathways involved in inflammation and apoptosis. We hypothesized that genetic variation in MAP3K1 might be associated with outcomes in patients with acute respiratory distress syndrome (ARDS), and that these variants would alter MAP3K1-mediated changes in inflammation and transcriptional regulation. To test this hypothesis, we genotyped single-nucleotide polymorphisms covering linkage disequilibrium bins in MAP3K1 in 306 subjects with ARDS from the ARDSNet FACTT (Fluid and Catheter Treatment Trial) study, and tested for associations between MAP3K1 single-nucleotide polymorphisms and ventilator-free days (VFDs) and mortality. We then validated these associations in a separate cohort of 241 patients with ARDS from Harborview Medical Center (Seattle, WA). We found the variant allele of rs832582 (MAP3K1906Val) was significantly associated with decreased VFDs using multivariate linear regression (-6.1 d, false discovery rate?=?0.06) in the FACTT cohort. In the Harborview Medical Center cohort, subjects homozygous for MAP3K1906Val also had decreased VFDs (-15.1 d, false discovery rate?<?0.01), and increased 28-day mortality (all subjects homozygous for the rare allele died). In whole blood stimulated with various innate immune agonists ex vivo, MAP3K1906Val was associated with increased IL-1?, IL-6, IL-8, monocyte chemoattractant protein 1, and TNF-? production. Transcriptome analysis of whole blood stimulated with Toll-like receptor 4 agonist ex vivo demonstrated enrichment of inflammatory gene sets in subjects homozygous for MAP3K1906Val. Our findings show a robust association between the variant allele of rs832582 (MAP3K1906Val) and decreased VFDs in patients with ARDS and suggest that this variant may predispose individuals to a greater inflammatory response.
| S-EPMC5941309 | biostudies-literature
Project description:BackgroundMucoactive agents are often prescribed for the management of airway secretions. However, it is unclear whether they improve respiratory outcomes in mechanically ventilated patients.MethodsWe examined the association between the early administration of mucoactive agents in ventilated patients and increased ventilator-free days (VFDs). This retrospective observational study was conducted in two intensive care units (ICUs) of a tertiary care hospital in Japan. We applied 1:1 propensity score matching between the early mucoactive agent group and the on-demand mucoactive agent group. We compared VFDs during the first 28 days of ICU stay as the primary outcome between the groups.ResultsIn total, 662 participants were eligible for this study, and 94 participants (47 in each group) were included in the analysis. There was no difference in the median VFDs between the groups [21 days; interquartile (IQR) 1-24 for the early group vs. 20 days; IQR 13-24 for the on-demand group; P=0.53]. The median ICU-free days were 19 (range, 12-22) days and 19 (range, 13-22) days for the early and on-demand mucoactive agent groups, respectively (P=0.72).ConclusionsEarly administration of mucoactive agents was not associated with increased VFDs.
| S-EPMC10061474 | biostudies-literature
Project description:ImportanceIt remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS).ObjectiveTo determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy.Design, setting, and participantsA randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands.InterventionsInvasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484).Main outcomes and measuresThe primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax.ResultsIn total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55).Conclusions and relevanceIn patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy.Trial registrationClinicalTrials.gov Identifier: NCT02153294.
| S-EPMC6248136 | biostudies-literature
Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AMs) in patients with acute respiratory distress syndrome (ARDS) could identify dynamic biologic processes that are associated with clinical outcomes. Objectives: To identify associations between AM transcriptional programs and the composite endpoint of ventilator-free days (VFDs) over the course of ARDS. Methods: We performed unbiased genome-wide transcriptional profiling of AMs purified from bronchoalveolar lavage fluid collected from patients with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset. We assessed pathway enrichment in subjects with VFDs > 0 (VFD-Extubated/Alive) versus VFDs = 0 (VFD-Intubated/Dead) at each time point. Measurements and Main Results: We found highly divergent AM transcriptional patterns at all time points between ARDS patients based on their VFD status (FDR < 0.05). “M1-like” and pro-inflammatory gene sets such as IL-6-JAK-STAT signaling were significantly enriched in AMs isolated on Day 1 in VFD-Extubated/Alive versus VFD-Intubated/Dead subjects. In contrast, many of these same gene sets were associated with the VFD-Intubated/Dead subjects on Day 8. In patients who had samples from each time point, we identified multiple AM gene clusters whose temporal expression patterns were associated with VFD status. The relationship between AM expression profiles and VFDs was distinct in subjects with Direct (pulmonary) versus Indirect (extrapulmonary) ARDS. Conclusion: Clinically meaningful outcomes over the course of ARDS are associated with highly distinct AM transcriptional programs. Our findings suggest that interventions targeting the alveolar immune response should be tested within strictly defined time periods.
2019-03-31 | GSE116560 | GEO
Project description:ObjectivesThere is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors.DesignSecondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days.SettingLarge academic tertiary-care PICU.PatientsChildren with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation.InterventionsImplementation of a ventilator-weaning pathway on May 2016.Measurements and main resultsOf 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders.ConclusionsVentilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials.
| S-EPMC7854887 | biostudies-literature
Project description:ImportanceIt remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation.ObjectiveTo determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization.Design, setting, and participantsRandomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands.InterventionsOn-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473).Main outcomes and measuresThe primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events.ResultsNine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001).Conclusions and relevanceAmong ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization.Trial registrationclinicaltrials.gov Identifier: NCT02159196.
| S-EPMC5885882 | biostudies-literature
Project description:BackgroundCritical care ventilators are frequently used to provide noninvasive ventilation (NIV) support to critically ill patients. Questions remain regarding carbon dioxide (CO2) clearance while using a critical care ventilator and dual limb circuit with various patient interfaces. The purpose of this study is to determine the positive end expiratory pressure (PEEP) level required to effectively washout CO2 for full-face and oronasal masks when using a dual limb circuit.MethodThis randomized crossover trial was conducted at an academic medical center in the Midwest United States. After obtaining informed consent, eight healthy volunteers were placed on a 980 Puritan Bennett (Medtronic, Minneapolis, MN) ventilator operating in the NIV mode. All subjects performed 20 min of breathing on four levels of PEEP (0, 2, 4, and 5 cm H2O) and pressure support of 5 cm H2O. NIV settings were applied to four masks (two oronasal and two full-face masks) that were randomly selected with a 5-min washout period between each mask. The fraction of inspired carbon dioxide (F ICO2) was sampled/monitored with a nasal cannula using a Capnostream 20p monitor (Medtronic, Minneapolis, MN) and reported as percentages. A Kruskal-Wallis test was used to reveal significant differences across PEEP levels. Pairwise comparisons of the groups were made using Mann-Whitney tests with a family-wise error correction.ResultsMedian (IQR) F ICO2 was significantly lower 0.0% (0%-0.92%) at PEEP of 5 compared to 1.83% (0.66%-4.0%; p < 0.001) at PEEP of 0 or 1.0% (0.33%-2.66%; p = 0.002) at PEEP of 2. F ICO2 was significantly lower 0.5% (0%-1.92%) at PEEP of 4 compared to PEEP of 0 (p = 0.001).ConclusionA PEEP level of at least 5 cm H2O associated with the reported leak was required to minimize the likelihood of CO2 rebreathing while using a critical care ventilator to provide NIV with a double limb circuit and full-face or oronasal masks.
| S-EPMC9328670 | biostudies-literature
Project description:BackgroundEnrollment challenges for critical care research are common. Contributing factors include short enrollment windows, the crisis nature of critical illness, lack of research staff, unavailable legal proxy, family dynamics, and language barriers.ObjectiveTo describe enrollment statistics for an ongoing critical care nursing trial, barriers to recruitment, and strategies to enhance enrollment.MethodsTwo years' worth of recruitment and enrollment data from an oral care intervention trial in critically ill adults receiving mechanical ventilation at 1 hospital were analyzed. Recruitment logs include number of patients screened, eligible, enrolled, and declined and patients' sex, race, and ethnicity.ResultsTarget enrollment (15.5 patients per month) was based on experience and historical data. Strategies implemented to promote enrollment included providing study personnel at least 18 hours per day for 7 days per week, regular rounds, communication with direct care staff, and Spanish consent processes. In 2 years, 6963 patients were screened; 1551 (22%) were eligible. Consent was sought from 366 (24% of eligible patients). Enrollment averaged 13.3 patients per month (86% of projected target). The main factor impeding enrollment was unavailability of a legal proxy to provide consent (88%). The refusal rates of white (11%), black (13%), and Hispanic (16%) patients did not differ significantly. However, those classified as Asian or as more than 1 race declined significantly more often (35%) than did white or black patients (P = .02).ConclusionsUnavailability of a legal proxy within a short enrollment window was the major challenge to enrollment. Various factors influenced consent decisions. Clinical study design requires more conservative estimates.
| S-EPMC6015765 | biostudies-literature
Project description:ObjectiveTo characterise the research profile of UK critical care physiotherapists including experience, training needs, and barriers and enablers to engagement in critical care research. 'Research' was defined broadly to encompass activities related to quantitative and qualitative studies, service evaluations, clinical audit and quality improvements.DesignClosed-question online survey, with optional free-text responses.SettingUK critical care community.ParticipantsUK critical care physiotherapists, regardless of clinical grade or existing research experience.Results268 eligible survey responses were received during the 12-week study period (21 incomplete, 7.8%). Respondents were based in university-affiliated (n=133, 49.6%) and district general (n=111, 41.4%) hospitals, and generally of senior clinical grade. Nearly two-thirds had postgraduate qualifications at master's level or above (n=163, 60.8%). Seven had a doctoral-level qualification. Respondents reported a range of research experience, predominantly data acquisition (n=144, 53.7%) and protocol development (n=119, 44.4%). Perceived research training needs were prevalent, including topics of research methods, critical literature appraisal, protocol development and statistical analysis (each reported by ≥50% respondents). Multiple formats for delivery of future research training were identified. Major barriers to research engagement included lack of protected time (n=220, 82.1%), funding (n=177, 66.0%) and perceived experience (n=151, 56.3%). Barriers were conceptually categorised into capability, opportunity and motivation themes. Key enabling strategies centred on greater information provision about clinical research opportunities, access to research training, secondment roles and professional networks.ConclusionsUK critical care physiotherapists are skilled, experienced and motivated to participate in research, including pursuing defined academic research pathways. Nonetheless wide-ranging training needs and notable barriers preclude further involvement. Strategies to harness the unique skills of this profession to enhance the quality, quantity and scope of critical care research, benefiting from a multiprofessional National Clinical Research Network, are required.
| S-EPMC5988191 | biostudies-literature
Project description:ImportanceDexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis.ObjectivesTo examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation.Design, setting, and participantsOpen-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours.InterventionsPatients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam.Main outcomes and measuresThe co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes.ResultsOf the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively.Conclusions and relevanceAmong patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further.Trial registrationclinicaltrials.gov Identifier: NCT01760967.
| S-EPMC5469298 | biostudies-literature