Effect of Early High-Dose Vitamin #D3 Repletion on Cognitive Outcomes in Critically Ill Adults

Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition.

Research Question
Does a single high-dose (540,000 IU) enteral treatment of vitamin D3 given shortly after hospital admission in vitamin D deficient, critically-ill patients improve long-term global cognition or executive function?

Study Design and Methods
This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment versus placebo in critically-ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status. Executive function was measured with a composite score derived from three Delisโ€“Kaplan Executive Function System subscales. Outcomes were assessed at a median (interquartile range) of 443 (390, 482) days after randomization and compared using multivariable proportional odds regression. Adjusted odds ratios (ORs) >1.0 would indicate better outcomes in the vitamin D3 group compared with placebo.

Results
Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 and 48 patients randomized to placebo. The adjusted median (95%CI) RBANS score at follow-up was 79.6 (73.0, 84.0) in the vitamin D3 group and 82.1 (74.7, 84.6) in the placebo group (adjusted OR, 0.83; 95%CI, 0.50 to 1.38). The adjusted median (95%CI) executive function composite score was 8.1 (6.8, 9.0) and 8.7 (7.4, 9.3), respectively (adjusted OR, 0.72; 95%CI, 0.36 to 1.42).

Interpretation
In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function.

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