ABSTRACT
The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.
ABSTRACT
BACKGROUND: Perceived health is one of the strongest determinants of subjective well-being, but it has received little attention among survivors of ARDS. RESEARCH QUESTION: How well do self-reported measures of physical, emotional, and social functioning predict perceived overall health (measured using the EQ-5D visual analog scale [EQ-5D-VAS]) among adult survivors of ARDS? Are demographic features, comorbidity, or severity of illness correlated with perceived health after controlling for self-reported functioning? STUDY DESIGN AND METHODS: We analyzed the ARDSNet Long Term Outcomes Study (ALTOS) and Improving Care of Acute Lung Injury Patients (ICAP) Study, two longitudinal cohorts with a total of 823 survivors from 44 US hospitals, which prospectively assessed survivors at 6 and 12 months after ARDS. Perceived health, evaluated using the EQ-5D-VAS, was predicted using ridge regression and self-reported measures of physical, emotional, and social functioning. The difference between observed and predicted perceived health was termed perspective deviation (PD). Correlations between PD and demographics, comorbidities, and severity of illness were explored. RESULTS: The correlation between observed and predicted EQ-5D-VAS scores ranged from 0.68 to 0.73 across the two cohorts and time points. PD ranged from -80 to +34 and was more than the minimum clinically important difference for 52% to 55% of survivors. Neither demographic features, comorbidity, nor severity of illness were correlated strongly with PD, with |r| < 0.25 for all continuous variables in both cohorts and time points. The correlation between PD at 6- and 12-month assessments was weak (ALTOS: r = 0.22, P < .001; ICAP: r = 0.20, P = .02). INTERPRETATION: About half of survivors of ARDS showed clinically important differences in actual perceived health vs predicted perceived health based on self-reported measures of functioning. Survivors of ARDS demographic features, comorbidities, and severity of illness were correlated only weakly with perceived health after controlling for measures of perceived functioning, highlighting the challenge of predicting how individual patients will respond psychologically to new impairments after critical illness.