The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury

Abstract

Rationale: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking.

Objectives: To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment.

Methods: As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post-hospital discharge.

Measurements and main results: Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02).

Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation.

Figure 1.

Enrollment and outcomes. ACOS = Adult Respiratory Distress Syndrome Cognitive Outcomes Study. *Of 1,001 Fluid and Catheter Treatment Trial (FACTT) subjects who underwent randomization, 227 were ineligible for long-term follow-up as part of Economic Analysis of the Pulmonary-Artery Catheter (EA-PAC) because no regulatory approval was in place and 119 declined consent (33). ^†Subjects were categorized as ineligible if the time window to be tested had elapsed because of the regulatory halt, as incapable if self-determined or determined by a surrogate to be physically or mentally incapable of telephone-based neuropsychological testing, and as lost to follow-up if consent was obtained but the subject was not tested. Of 53 subjects categorized as lost to follow-up, no contact information was available for 1 subject, no telephone service was available for 1 subject, no explanation was provided for 1 subject, and the remaining 50 subjects were recorded as “lost to follow-up.” ^‡Of 52 subjects tested at 2 months, 32 were retested at 12 months. The reasons for 20 subjects being tested at 2 months but not at 12 months were that 11 patients were lost to follow-up, 5 declined, 3 died, and 1 was incarcerated. Subjects were not required to undergo testing at 2 months to be tested at 12 months.

Figure 2.

Long-term cognitive impairment according to fluid management strategy. Impairment in a domain was defined as a score greater than 2 SD below the population norm. Cognitive impairment was defined as impairment in memory, verbal fluency, or executive function in the 75 survivors completing testing in each of these cognitive domains. Memory, verbal fluency, or executive function was assessed in 92, 96, and 76 subjects, respectively. Proportions of impaired subjects are specified by domain, according to fluid-management strategy. Error bars reflect upper bound of 95% confidence interval. Cons = conservative fluid strategy; Lib = liberal fluid strategy.