Clinical PotpourriVitamin D kinetics in the acute phase of critical illness: A prospective observational study☆
Introduction
The widely recognized role of vitamin D (25-hydroxyvitamin D; 25(OH)D3) in the human body is usually linked to extracellular calcium metabolism by intestinal absorption regulation and skeletal mineralization [1], [2], [3]. However, its function is much more complex. The non-classic (pleiotropic) vitamin D mechanisms of action rely on its binding to the nuclear receptor (VDR) and the formation of a heterodimer with the retinoid X receptor. The abovementioned interaction regulates the transcription of DNA into RNA by binding to genomic sequences called vitamin D response elements (VDREs) in many tissues and subsequently mediates the regulation of cell proliferation, differentiation, apoptosis, angiogenesis, hormone secretion, membrane stabilization, anti-inflammatory action, blood pressure regulation, blood sugar control and, finally, regulation of innate and adaptive immunity [1], [3], [4], [5], [6], [7], [8].
Dysregulated vitamin D pleiotropy caused by vitamin D deficiency, which is currently linked with cancer, autoimmune, infectious and cardiovascular diseases, is well recognized in intensive care patients [1]. Vitamin D deficiency is linked to morbidity and life-threatening organ dysfunction due to a dysregulated host response to infection (sepsis) in the intensive care unit (ICU) [9], [10], [11], [12], [13], [14], [15]. However, a few studies did not confirm such dependencies, and it seems that this is still an area of uncertainty [16], [17]. Several studies performed in ICUs report a relationship between an extremely low serum vitamin D concentration (severe deficiency) and mortality in intensive care patients [11], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. However, most of those trials were retrospective, and the vitamin D concentration was measured only once (at a certain point of time, usually at admission). We still do not know if vitamin D is a modifiable factor, which, if properly corrected, could substantially influence the patient outcome or another simple marker of the poor condition of the patient. Typically, the course of the early resuscitation phase of a critical illness is dynamic, potentially influencing vitamin D kinetics (serum level changes in time). There are only a few prospective observational or interventional clinical trials studying vitamin D kinetics in critically ill patients [26], [29], [30], [31], [32], [33], [34]. The methodology of these trials is heterogeneous, which makes any comparisons or generalizations very difficult or even impossible to perform.
The main objective of this study was to assess the vitamin D kinetics in critically ill patients by performing periodic serum vitamin D measurements in short time intervals (every 12 h) in the initial phase of a critical illness. Defining the typical vitamin D kinetic profile could potentially be helpful for planning supplementation regimens and future randomized prospective trial designs to adequately study the relationship between vitamin D deficiency correction and mortality rate reduction in critically ill patients. We hypothesized that the serum vitamin D levels are unstable in the initial, acute phase of a critical illness.
Section snippets
Materials and methods
This was a prospective observational study conducted from September 2015 to September 2016 in a single, eleven-bed, medical/surgical ICU. Written informed consent was obtained from the patients' relatives. The study was approved by the Regional Ethics Committee in Opole, Poland (protocol number: 214/2015; the date of approval: 25/03/2015), it was registered before the recruitment of participants (clinicaltrials.gov NCT02414386) and was carried out according to the principles of the Declaration
Results
A total of 363 patients were evaluated for participation in the trial. After the initial evaluation, 343 patients were excluded from the study. Exclusion reasons were the following: no circulatory failure, no respiratory failure, vitamin D measurement was not performed, end-stage renal disease, acute kidney injury treated with renal replacement therapy, admission from another ICU or readmission, acute liver failure, age < 18. The study flow chart is depicted in Fig. 1. In 127 (35%) patients with
Discussion
According to the widely used definition, a serum vitamin D level of < 20 ng/mL is defined as a deficiency, a level between 20 and 30 ng/mL as an insufficiency, and a level > 30 ng/mL as a normal value [7], [39], [40]. This prospective, single-center observational study revealed that the typical intensive care population of patients is extremely prone to vitamin D deficiency in the acute phase of a critical illness. In a group of 127 patients, 115 (90.5%) of them had vitamin D deficiency (serum plasma
Conclusions
The intensive care population of patients is extremely prone to severe vitamin D deficiency. We observed that the vitamin D serum levels are changeable during critical illness. Large, randomized, placebo-controlled trials are needed to assess whether a correction of severe vitamin D deficiency in the acute phase of a critical illness could influence outcomes or if the vitamin D levels can only be used as a simple tool for monitoring the condition of the patient.
Sources of financial support for the work
Department of Anesthesiology and Critical Care, PS ZOZ Wojewodzkie Centrum Medyczne w Opolu, Aleja Witosa 26, 45-418, Opole, Poland (institutional).
Conflicts of interest
None.
Author contributions
TC, AC designed the trial. TC, AC, RG, MC supervised the conduct of the trial and data collection. TC drafted the manuscript, takes responsibility for the paper as a whole. TC, RG, MG, MP, MM, MM, OC, RS, MRS, MO, KF, JS undertook recruitment of participants. TC managed the data, including quality control. RK provided statistical advice on study design and analyzed the data. TC, RG, RK, MC contributed substantially to the final version of the manuscript.
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Work should be attributed to the Department of Anesthesiology and Critical Care, PS ZOZ Wojewodzkie Centrum Medyczne w Opolu, Aleja Witosa 26, 45-418, Opole, Poland.