• Jin H Han, Adit A Ginde, Samuel M Brown, Adrienne Baughman, Erin M Collar, E Wesley Ely, Michelle N Gong, Aluko A Hope, Peter C Hou, Catherine L Hough, Theodore J Iwashyna, James C Jackson, Akram Khan, Onur M Orun, Mayur B Patel, Rameela Raman, Todd W Rice, Nancy Ringwood, Matthew W Semler, Nathan I Shapiro, Daniel S Talmor, Wesley H Self, and Vitamin D to Improve Outcomes by Leveraging Early Treatment Network Investigators.
• Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, TN; Department of Emergency Medicine, Vanderbilt University Medical Center, TN; Geriatric Research, Education, and Clinical Center, Tennessee Valley Healthcare System, Healthcare System. Electronic address: jin.h.han@vumc.org.
• Chest. 2021 Sep 1; 160 (3): 909-918.

BackgroundLong-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition.Research QuestionDoes a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function?Study Design And MethodsThis study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group.ResultsNinety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42).InterpretationIn vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function.Trial RegistryClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.Published by Elsevier Inc.

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