Long-term cognitive function following haloperidol versus placebo treatment in ICU patients with delirium.

Purpose We report the cognitive outcomes at 1-year in the Agents Intervening against Delirium in the ICU (AID-ICU) trial. Methods We conducted the pre-planned 1-year follow-up study at three selected Danish sites assessing cognitive outcomes in the AID-ICU trial, which randomised acutely admitted, adult ICU patients with delirium effects to haloperidol versus placebo. The primary outcome was the global index score for cognitive function at 1-year, assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included domain-specific cognitive functions in RBANS and executive function, measured by Trail-Making Tests A & B (TMT A & B). Analyses were conducted in the intention-to-treat population with non-survivors assigned lowest possible scores and multiple imputation of missing data. Results In total, 624 of 632 randomly assigned patients were included; however, 1-year cognitive outcomes were missing for 116 patients in the haloperidol group and 93 in the placebo group. Median global cognitive index scores were 40 (IQR: 40–75) in the haloperidol group versus 40 (40–72) in the placebo group (mean difference 2; 95% CI: -3 to 7; P = 0.48). We found no statistically significant differences in secondary cognitive outcomes. Conclusions We found no statistically significant differences between haloperidol and placebo for 1-year cognitive function in acutely admitted, adult ICU patients with delirium. However, due to uncertainty of the estimates we were unable to rule out any clinically important effects of haloperidol on cognitive function.