Despite significant advances in our understanding of the pathophysiology of acute lung injury, a lung-protective strategy of mechanical ventilation remains the only therapy with a proven survival ...advantage. Numerous pharmacologic therapies have failed to show benefit in multicenter clinical trials. The paradigm of early, goal-directed therapy of sepsis suggests greater clinical benefit may derive from initiating therapy prior to the onset of respiratory failure that requires mechanical ventilation. Thus, there is heightened interest in more accurate and complete characterization of high-risk patient populations and identification of patients in the early stage of acute lung injury, prior to the need for mechanical ventilation. This article discusses the growing literature on clinical predictors of acute lung injury (including risk factors for specific subgroups) with an emphasis on transfusion-related risk factors and recent research targeting the early identification of high-risk patients and those with early acute lung injury prior to the onset of respiratory failure.
Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of ...hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute.Clinical trial registered with www.clinicaltrials.gov (NCT04193878).
Many critically ill patients are transferred to other care facilities instead of to home at hospital discharge.
To identify patient-related factors associated with hospital discharge to a care ...facility after critical illness and to estimate the magnitude of risk associated with each factor.
Retrospective cohort study of 548 survivors of critical illness in a medical intensive care unit. Multivariable logistic regression was used to identify independent risk factors for discharge to a care facility. Only the first 72 hours of intensive care were analyzed.
Approximately one-quarter of the survivors of critical illness were discharged to a care facility instead of to home. This event occurred more commonly in older patients, even after adjustment for severity of illness and comorbid conditions (odds ratio OR 1.8 for patients ≥ 65 years of age vs patients < 65 years; 95% confidence interval CI, 1.1-3.1; P = .02). The risk was greatest for patients who received mechanical ventilation (OR, 3.4; 95% CI, 2.0-5.8; P < .001) or had hospitalizations characterized by severe cognitive dysfunction (OR, 8.1; 95% CI, 1.3-50.6; P = .02) or poor strength and/or mobility (OR, 31.7; 95% CI, 6.4-157.3; P < .001). The model showed good discrimination (area under the curve, 0.82; 95% CI, 0.77-0.86).
The model, which did not include baseline function or social variables, provided good discrimination between patients discharged to a care facility after critical illness and patients discharged to home. These results suggest that future research should focus on the debilitating effects of respiratory failure and on conditions with cognitive and neuromuscular sequelae.
Background:Acute lung injury (ALI) has been primarily defined in patients who require positive pressure ventilation. As a result, the clinical characteristics of patients with early ALI (EALI) prior ...to the need for mechanical ventilation have not been well characterized. Early identification of patients with ALI and the impending need for positive pressure ventilation could define a study population for trials of novel therapies.
Methods:We analyzed clinical data from 93 patients at 12, 24, and 48 hours prior to the standard diagnosis of ALI. The time of ALI diagnosis was defined when patients were mechanically ventilated and met the 1994 American–European Consensus Conference diagnostic criteria for ALI.
Results:The majority of patients with ALI presented to the hospital more than 24 hours prior to developing ALI. Specifically, 73% presented more than 12 hours prior to diagnosis, and 57% presented more than 24 hours prior to diagnosis. Of patients hospitalized for at least 12 hours prior to ALI diagnosis, 94% had either bilateral infiltrates on chest radiograph, tachypnea, or an oxygen requirement greater than 2 L/min; 79% and 48% had 2 and 3 of these abnormalities, respectively.
Conclusion:The majority of hospitalized patients who are destined to develop ALI demonstrate tachypnea, increased oxygen requirements, and/or bilateral infiltrates on chest radiograph more than 12 hours prior to meeting criteria for diagnosis. Some patients with EALI may be identified prior to meeting diagnostic criteria during a potential therapeutic window.
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
IMPORTANCE: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical ...illness from COVID-19. OBJECTIVES: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. EXPOSURES: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. MAIN OUTCOMES AND MEASURES: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. RESULTS: A total of 2215 patients (mean SD age, 60.5 14.5 years; 1436 64.8% male; 1738 78.5% with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio OR, 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30–5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46–4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. CONCLUSIONS AND RELEVANCE: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
To estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and cardiopulmonary resuscitation in critically ill adults with coronavirus disease 2019 (covid-19).
...Multicenter cohort study.
Intensive care units at 68 geographically diverse hospitals across the United States.
Critically ill adults (age ≥18 years) with laboratory confirmed covid-19.
In-hospital cardiac arrest within 14 days of admission to an intensive care unit and in-hospital mortality.
Among 5019 critically ill patients with covid-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation. Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14)
60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest. Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14)
67 (14) years). The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status. Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older.
Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among older patients.
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