In this issue of the
Journal
, Hills and colleagues
1
report the results of a trial of simvastatin in critically ill patients with Covid-19, conducted within the international Randomized, Embedded, ...Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP). Most of the enrolled patients met the global definition of acute respiratory distress syndrome (ARDS).
2
Given disappointing findings from previous trials of pharmacologic therapies (including simvastatin) for ARDS, it is of great interest that although simvastatin did not meet the prespecified criteria for superiority to standard care with respect to organ support–free days through day 21, there was a 95.9% posterior probability of . . .
Angiotensin II for the Treatment of Vasodilatory Shock Khanna, Ashish; English, Shane W; Wang, Xueyuan S ...
New England journal of medicine/The New England journal of medicine,
08/2017, Letnik:
377, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Patients with vasodilatory shock were randomly assigned to angiotensin II or placebo. At 3 hours, more patients in the angiotensin II group than in the placebo group had an increase in mean arterial ...pressure of at least 10 mm Hg or to at least 75 mm Hg.
In a multicenter trial in 566 patients with critical illness who had delirium, the use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the duration of delirium ...or coma. Side effects and extrapyramidal disorders occurred at similar rates in all groups.
Objectives
To estimate the effect of pre‐intensive care unit (ICU) health categories on mortality during and after critical illness, focusing specifically on the effect of pre‐ICU frailty on short‐ ...and long‐term mortality.
Design
Retrospective cohort study.
Setting
Medicare claims data from 2004 to 2008.
Participants
A nationally representative sample of elderly Medicare beneficiaries admitted to an ICU in 2005.
Measurements
Participants were classified into four pre‐ICU health categories (robust, cancer, chronic organ failure, frailty) using claims data from the year before admission, allowing for assignment to multiple categories. The association between pre‐ICU health category and hospital and 3‐year mortality was assessed using multivariable logistic regression and Cox proportional hazards models.
Results
Of 47,427 elderly individuals in the ICU, 18.8% were robust, 28.6% had cancer, 68.1% had chronic organ failure, and 34.0% were frail; 41.3% qualified for multiple categories. Overall hospital mortality was 12.6%, with the lowest mortality for robust participants (9.7%). Participants with pre‐ICU frailty had higher hospital mortality than those with the same pre‐ICU health categories without frailty. (Adjusted odds ratios ranged from 1.27 (95% confidence interval (CI) 1.10–1.47) to 1.52 (95% CI = 1.35–1.63).) Robust hospital survivors had the lowest 3‐year mortality (24.6%). Pre‐ICU frailty conferred higher 3‐year mortality than pre‐ICU categories without frailty. (Adjusted hazard ratios ranged from 1.54 (95% CI = 1.45–1.64) to 1.84 (95% CI = 1.70–1.99).)
Conclusion
Critically ill elderly adults can be categorized according to pre‐ICU health categories. These categories, particularly pre‐ICU frailty, may be important for understanding risk of death during and after critical illness.
In acute respiratory distress syndrome (ARDS), the effect of positive end-expiratory pressure (PEEP) may depend on the extent to which multiorgan dysfunction contributes to risk of death, and the ...precision with which PEEP is titrated to attenuate atelectrauma without exacerbating overdistension.
To evaluate whether multiorgan dysfunction and lung mechanics modified treatment effect in the EPVent-2 (Esophageal Pressure-guided Ventilation 2) trial, a multicenter trial of esophageal pressure (Pes)-guided PEEP versus empirical high PEEP in moderate to severe ARDS.
This
reanalysis of the EPVent-2 trial evaluated for heterogeneity of treatment effect on mortality by baseline multiorgan dysfunction, determined via Acute Physiology and Chronic Health Evaluation II (APACHE-II). It also evaluated whether PEEP titrated to end-expiratory transpulmonary pressure near 0 cm H
O was associated with survival.
All 200 trial participants were included. Treatment effect on 60-day mortality differed by multiorgan dysfunction severity (
= 0.03 for interaction). Pes-guided PEEP was associated with lower mortality among patients with APACHE-II less than the median value (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92) and may have had the opposite effect in patients with higher APACHE-II (hazard ratio, 1.69; 95% confidence interval, 0.93-3.05). Independent of treatment group or multiorgan dysfunction severity, mortality was lowest when PEEP titration achieved end-expiratory transpulmonary pressure near 0 cm H
O.
The effect on survival of Pes-guided PEEP, compared with empirical high PEEP, differed by multiorgan dysfunction severity. Independent of multiorgan dysfunction, PEEP titrated to end-expiratory transpulmonary pressure closer to 0 cm H
O was associated with greater survival than more positive
negative values. These findings warrant prospective testing in a future trial.
A New Global Definition of Acute Respiratory Distress Syndrome Matthay, Michael A; Arabi, Yaseen; Arroliga, Alejandro C ...
American journal of respiratory and critical care medicine,
2024-Jan-01, 2024-01-01, 20240101, Letnik:
209, Številka:
1
Journal Article
Recenzirano
Odprti dostop
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.
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
) identify patients with the currently accepted conceptual framework for ARDS,
) facilitate rapid ARDS diagnosis for clinical care and research,
) be applicable in resource-limited settings,
) be useful for testing specific therapies, and
) be practical for communication to patients and caregivers.
The committee made four main recommendations:
) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min;
) use Pa
:Fi
⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry Sp
:Fi
⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia;
) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and
) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices.
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.
Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the NHLBI. Decades of clinical research in acute ...respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising preclinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data," causal inference using observational data, novel clinical trial designs, preclinical disease modeling, and understanding of recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state of, research priorities for, and future directions in adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including
) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment response with the goal of developing targeted, personalized interventions;
) optimizing preclinical models by incorporating comorbidities, cointerventions, and organ support;
) developing and applying novel clinical trial designs; and
) advancing mechanistic understanding of injury and recovery to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.
IMPORTANCE: Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS). ...OBJECTIVE: To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP–fraction of inspired oxygen (Fio2) in moderate to severe ARDS. DESIGN, SETTING, AND PARTICIPANTS: Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018. INTERVENTIONS: Participants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes. MAIN OUTCOMES AND MEASURES: The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy. RESULTS: Two hundred patients were enrolled (mean SD age, 56 16 years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% 95% CI, 41.7% to 57.5%; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% 95% CI, −11.1% to 14.6%; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median interquartile range: 22 15-24 vs 21 16.5-24 days; median difference, 0 95% CI, −1 to 2 days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 3.9% vs 12/98 12.2%; risk difference, −8.3% 95% CI, −15.8% to −0.8%; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2. CONCLUSIONS AND RELEVANCE: Among patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01681225
This trial comparing treatment strategies that emphasized the use of vasopressors or intravenous fluids for early treatment of sepsis-induced hypotension showed no difference in 90-day mortality ...before discharge home.
Purpose
Latent class analysis (LCA) has identified hyper- and non-hyper-inflammatory subphenotypes in patients with acute respiratory distress syndrome (ARDS). It is unknown how early inflammatory ...subphenotypes can be identified in patients at risk of ARDS. We aimed to test for inflammatory subphenotypes upon presentation to the emergency department.
Methods
LIPS-A was a trial of aspirin to prevent ARDS in at-risk patients presenting to the emergency department. In this secondary analysis, we performed LCA using clinical, blood test, and biomarker variables.
Results
Among 376 (96.4%) patients from the LIPS-A trial, two classes were identified upon presentation to the emergency department (day 0): 72 (19.1%) patients demonstrated characteristics of a hyper-inflammatory and 304 (80.9%) of a non-hyper-inflammatory subphenotype. 15.3% of patients in the hyper- and 8.2% in the non-hyper-inflammatory class developed ARDS (p = 0.07). Patients in the hyper-inflammatory class had fewer ventilator-free days (median interquartile range, IQR 2823–28 versus 2827–28; p = 0.010), longer intensive care unit (32–6 versus 00–3 days; p < 0.001) and hospital (96–18 versus 53–9 days; p < 0.001) length of stay, and higher 1-year mortality (34.7% versus 20%; p = 0.008). Subphenotypes were identified on day 1 and 4 in a subgroup with available data (n = 244). 77.9% of patients remained in their baseline class throughout day 4. Patients with a hyper-inflammatory subphenotype throughout the study period (n = 22) were at higher risk of ARDS (36.4% versus 10.4%; p = 0.003).
Conclusion
Hyper- and non-hyper-inflammatory subphenotypes may precede ARDS development, remain identifiable over time, and can be identified upon presentation to the emergency department. A hyper-inflammatory subphenotype predicts worse outcomes.
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