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      Vitamin D and critical illness: what endocrinology can learn from intensive care and vice versa

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          Abstract

          The prevalence of vitamin D deficiency in intensive care units ranges typically between 40 and 70%. There are many reasons for being or becoming deficient in the ICU. Hepatic, parathyroid and renal dysfunction additionally increases the risk for developing vitamin D deficiency. Moreover, therapeutic interventions like fluid resuscitation, dialysis, surgery, extracorporeal membrane oxygenation, cardiopulmonary bypass and plasma exchange may significantly reduce vitamin D levels. Many observational studies have consistently shown an association between low vitamin D levels and poor clinical outcomes in critically ill adults and children, including excess mortality and morbidity such as acute kidney injury, acute respiratory failure, duration of mechanical ventilation and sepsis. It is biologically plausible that vitamin D deficiency is an important and modifiable contributor to poor prognosis during and after critical illness. Although vitamin D supplementation is inexpensive, simple and has an excellent safety profile, testing for and treating vitamin D deficiency is currently not routinely performed. Overall, less than 800 patients have been included in RCTs worldwide, but the available data suggest that high-dose vitamin D supplementation could be beneficial. Two large RCTs in Europe and the United States, together aiming to recruit >5000 patients, have started in 2017, and will greatly improve our knowledge in this field. This review aims to summarize current knowledge in this interdisciplinary topic and give an outlook on its highly dynamic future.

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          Most cited references62

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          Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.

          Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor. To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture. A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008. 500,000 IU of cholecalciferol or placebo. Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels. Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing. Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures. anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.
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            Clinical practice. Hypoparathyroidism.

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              Vitamin D and immune function: an overview.

              Immunomodulatory actions of vitamin D have been recognised for over a quarter of a century, but it is only in the last few years that the significance of this to normal human physiology has become apparent. Two key factors have underpinned this revised perspective. Firstly, there are increasing data linking vitamin insufficiency with prevalent immune disorders. Improved awareness of low circulating levels of precursor 25-hydroxyvitamin D in populations across the globe has prompted epidemiological investigations of health problems associated with vitamin D insufficiency. Prominent among these are autoimmune diseases such as multiple sclerosis, type 1 diabetes and Crohn's disease, but more recent studies indicate that infections such as tuberculosis may also be linked to low 25-hydroxyvitamin D levels. The second factor expanding the link between vitamin D and the immune system is our improved knowledge of the mechanisms that facilitate this association. It is now clear that cells from the immune system contain all the machinery needed to convert 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D, and for subsequent responses to 1,25-dihydroxyvitamin D. Mechanisms such as this are important for promoting antimicrobial responses to pathogens in macrophages, and for regulating the maturation of antigen-presenting dendritic cells. The latter may be a key pathway by which vitamin D controls T-lymphocyte (T-cell) function. However, T-cells also exhibit direct responses to 1,25-dihydroxyvitamin D, notably the development of suppressor regulatory T-cells. Collectively these observations suggest that vitamin D is a key factor linking innate and adaptive immunity, and both of these functions may be compromised under conditions of vitamin D insufficiency.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                December 2018
                05 October 2018
                : 7
                : 12
                : R304-R315
                Affiliations
                [1 ]Thyroid Endocrinology Osteoporosis Institute Dobnig , Graz, Austria
                [2 ]Division of Endocrinology and Diabetology , Department of Internal Medicine, Medical University of Graz, Graz, Austria
                [3 ]Department of General Surgery , Medical University of Graz, Graz, Austria
                [4 ]Department of General Surgery , St. Elisabeth’s Hospital, Graz, Austria
                [5 ]Division of Endocrinology and Metabolism , Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
                [6 ]Clinician Scientist in Critical Care , Birmingham, Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
                Author notes
                Correspondence should be addressed to K Amrein: karin.amrein@ 123456medunigraz.at
                Article
                EC-18-0184
                10.1530/EC-18-0184
                6240147
                30352414
                0bfeffc8-93c4-4a06-897f-980e40d8bb49
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 22 September 2018
                : 05 October 2018
                Categories
                Review

                calcium,bone,stress response,vitamin d,critical care
                calcium, bone, stress response, vitamin d, critical care

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