Deficient Findings

High doses of vitamin D for critically ill patients yield minimal benefit

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A deficiency of vitamin D is a common risk factor for worse outcomes in critically ill patients. While vitamin D is best known for strong bone formation, it also helps fight infections, is a potent anti-inflammatory agent and is essential for lung development and function.

Now, a major study conducted by the National Heart, Lung and Blood Institute’s Prevention and Early Treatment of Acute Lung Injury (PETAL) network into whether high doses of vitamin D can improve health outcomes for critically ill patients has concluded that such supplements do not reduce mortality or improve other nonfatal outcomes.

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The results of the Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) study, which included contributions from over 200 researchers at 44 academic medical centers and investigators from Harvard Medical School and Beth Israel Deaconess Medical Center, are published online in the The New England Journal of Medicine.

For this study, lead author Adit Ginde, professor and director of research AMC in the Department of Emergency Medicine at the University of Colorado School of Medicine, and senior author Daniel Talmor, the Edward Lowenstein Professor of Anaesthesia at HMS and Beth Israel Deaconess, served as co-chairs of the protocol committee for the National Heart, Lung, and Blood Institute PETAL network.

“The VIOLET study did not show benefit from vitamin D supplementation in this population of critically ill patients,” said Ginde. “However, the study gives us a model to intervene in the earliest stage of critical illness, which will yield improved care and better health for our patients in the future.”

“In this study, we uniquely targeted patients who were vitamin D deficient and, therefore, might benefit from the intervention,” said Talmor. “Unfortunately, vitamin D didn’t turn out to help these patients, and we need to continue to search for appropriate therapies for these sickest of patients.”

The NHLBI PETAL Network conducted a controlled study of patients who needed admission into intensive care units. Among those cases, patients had pneumonia, sepsis, shock, respiratory failure and other critical conditions.

“This is the kind of important question that the PETAL network was designed to answer efficiently,” said James Kiley, director of the Division of Lung Diseases at the NHLBI. “This trial could not have been performed without the successful collaboration between emergency medicine and critical care that the PETAL network facilitated.”

From April 2017 through July 2018, 2,624 patients at 44 hospitals consented to participate in the study. Of those, 1,360 screened as vitamin D deficient and ultimately 1,078 were included in the final analysis. About half received vitamin D and half received a placebo, with the vitamin D group achieving rapid correction of vitamin D deficiency in the blood. Patients were followed for 90 days, and researchers found no difference in mortality rates, hospital length of stay or time on mechanical ventilation between the two groups.

“While we hoped that vitamin D supplementation might prove beneficial to critically ill patients, our large study does not support early testing for or treatment of vitamin D deficiency in those patients,” said Ginde.

This work was supported by grants from the National Heart, Lung, and Blood Institute (grants U01HL123009, U01HL122998, U01HL123018, U01HL123023, U01HL123008, U01HL123031, U01HL123004, U01HL123027, U01HL123010, U01HL123033, U01HL122989, U01HL123022, and U01HL123020).

Adapted from a Beth Israel Deaconess news release.