Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials.
Pubmed ID: 30359616
Pubmed Central ID: PMC6414787
Publication Date: 03/01/2019
Affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, NY; First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, University of Athens Medical School, Athens, Greece. Electronic address: email@example.com.
MeSH Terms: Humans, Male, Female, Middle Aged, Prevalence, Bilirubin, Treatment Outcome, Prognosis, Severity of Illness Index, Time Factors, Predictive Value of Tests, Respiration, Artificial, Vasoconstrictor Agents, Oxygen, Critical Care, Oxygen Consumption, Airway Extubation, Respiratory Distress Syndrome
Grants: KL2 TR000458, P01 HL108801, R01 HL055330, T32 HL134629, KL2 TR002385, P01 HL114501
Authors: Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos II
Cite As: Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos II. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest 2019 Mar;155(3):474-482. Epub 2018 Oct 22.
- Acute Respiratory Distress Network (ARDSNet) Studies 01 and 03 Lower versus higher tidal volume, ketoconazole treatment and lisofylline treatment (ARMA/KARMA/LARMA)
- Acute Respiratory Distress Network (ARDSNet) Studies 06 and 08 Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo for the Treatment of Acute Lung Injury (ALTA)
- Acute Respiratory Distress Network (ARDSNet) Studies 07, 08, 09, 11, and 12 Early Versus Delayed Enteral Feeding to Treat People with Acute Lung Injury or Acute Respiratory Distress Syndrome (EDEN)
- Acute Respiratory Distress Network (ARDSNet) Studies 10 and 12 Statins for Acutely Injured Lungs from Sepsis (SAILS)
- Acute Respiratory Distress Network (ARDSNet) Study 04 Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury (ALVEOLI)
- Acute Respiratory Distress Network (ARDSNet) Study 05 Fluid and Catheter Treatment Trial (FACTT)
BACKGROUND: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it. METHODS: A secondary analysis was performed of patient level data from six ARDS Network randomized controlled trials. We defined rapidly improving ARDS, contrasted with ARDS > 1 day, as extubation or a Pao<sub>2</sub> to Fio<sub>2</sub> ratio (Pao<sub>2</sub>:Fio<sub>2</sub>) > 300 on the first study day following enrollment. RESULTS: The prevalence of rapidly improving ARDS was 10.5% (458 of 4,361 patients) and increased over time. Of the 1,909 patients enrolled in the three most recently published trials, 197 (10.3%) were extubated on the first study day, and 265 (13.9%) in total had rapidly improving ARDS. Patients with rapidly improving ARDS had lower baseline severity of illness and lower 60-day mortality (10.2% vs 26.3%; P < .0001) than ARDS > 1 day. Pao<sub>2</sub>:Fio<sub>2</sub> at screening, change in Pao<sub>2</sub>:Fio<sub>2</sub> from screening to enrollment, use of vasopressor agents, Fio<sub>2</sub> at enrollment, and serum bilirubin levels were useful predictive variables. CONCLUSIONS: Rapidly improving ARDS, mostly defined by early extubation, is an increasingly prevalent and distinct subphenotype, associated with better outcomes than ARDS > 1 day. Enrollment of patients with rapidly improving ARDS may negatively affect the prognostic enrichment and contribute to the failure of therapeutic trials.