Supraphysiological 25-hydroxy vitamin D3 level at admission is associated with illness severity and mortality in critically ill patients
Ravikar Ralph, John Victor Peter, Anugrah Chrispal, Anand Zachariah, Joseph Dian, Tunny Sebastian, Bala Venkatesh, Kurien Thomas
Journal of Bone and Mineral Metabolism, April 2014
We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37 % (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5 % (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers.
Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75 % (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5 % (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7 % (95 % confidence interval 1.2–11.4; p = 0.03), respectively.
In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality.
A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality.
Extrinsic factors interfering with test results were ruled out.
A biological hypothesis to explain this observation is proposed.
Further clarification of mechanisms leading to this observation is warranted.
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References
- Bikle D (2009) Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94:26–34 CrossRef
- Weenink J, Straaten O, Yap H (2010) High prevalence of severe vitamin D deficiency in intensive care patients. Crit Care 14:S198 CrossRef
- Amrein K, Amrein S, Holl A (2010) Vitamin D, parathyroid hormone and serum calcium levels and their association with hospital mortality in critically ill patients. Critical Care 14:S198 CrossRef
- Venkatram S, Chilimuri S, Adrish M, Salako A, Patel M, Diaz-Fuentes G (2011) Vitamin D deficiency is associated with mortality in the medical intensive care unit. Crit Care 15:R292 CrossRef
- Lee P, Eisman JA, Center JR (2009) Vitamin D deficiency in critically ill patients. N Engl J Med 360:1912–1914 CrossRef
- McKinney JD, Bailey BA, Garrett LH, Peiris P, Manning T, Peiris AN (2011) Relationship between vitamin D status and ICU outcomes in veterans. J Am Med Dir Assoc 12:208–211 CrossRef
- Krishnan A, Ochola J, Mundy J, Jones M, Kruger P, Duncan E et al (2010) Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care 14:R216 CrossRef
- Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PVLN, Sarma KVS et al (2007) High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr 85:1062–1067
- Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281 CrossRef
- Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963 CrossRef
- Schoenfeld DA, Bernard GR (2002) Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med 30:1772–1777 CrossRef
- Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D (2010) Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study. Intensive Care Med 36:1609–1611 CrossRef
- Zittermann A, Kuhn J, Dreier J, Knabbe C, Gummert JF, Börgermann J (2013) Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. Eur Heart J 34:1358–1364 CrossRef
- Cecchi A, Bonizzoli M, Douar S (2011) Vitamin D deficiency in septic patients at ICU admission is not a mortality predictor. Minerva Anestesiol 77:1184–1189
- Braun A, Chang D, Mahadevappa K, Gibbons FK, Liu Y, Giovannucci E et al (2011) Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med 39:671–677 CrossRef
- Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, Yetley EA, Looker AC, Schleicher RL et al (2013) Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab 98:3001–3009 CrossRef
- Roche. Elecsys and Cobas e analyzers Users’s manual. 2010
- Martinez ME, Gonzalez J, Sanchez-Cabezudo MJ, Peña JM, Vazquez JJ, Felsenfeld A (1993) Evidence of absorptive hypercalciuria in tuberculosis patients. Calcif Tissue Int 53:384–387
- Insogna KL, Dreyer BE, Mitnick M, Ellison AF, Broadus AE (1988) Enhanced production rate of 1,25-dihydroxyvitamin D in sarcoidosis. J Clin Endocrinol Metab 66:72–75 CrossRef
- Vieth CHAPTER 61.pdf [Internet]. http://www.direct-ms.org/sites/default/files/Vieth%20CHAPTER%2061.pdf (cited 16 Feb 2013)
- Norman AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88:491S–499S CrossRef
- Rosenstreich SJ, Rich C, Volwiler W (1971) Deposition in and release of vitamin D3 from body fat: evidence for a storage site in the rat. J Clin Invest. 50:679–687 CrossRef
- Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury SW (1972) The distribution and storage of vitamin D and its metabolites in human tissues. Clin Sci 43:413–431
- Hashemipour S, Larijani B, Adibi H, Javadi E, Sedaghat M, Pajouhi M et al (2004) Vitamin D deficiency and causative factors in the population of Tehran. BMC Public Health 25:38 CrossRef
- Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR et al (2009) Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med [Internet] 7:28 CrossRef
Many questions from the abstract
- How long between vitamin D measurement and death?
- Had the patients been taking lots of vitamin D?
- Were their bodies getting too much for some other reason?
- Was this group out in the sun A LOT?
- What is the biological hypothesis proposed in the $40 study?
- Which cofactors were inbalanced: Calcium, Magnesium, Vitamin K2, or what?
Vitamin D is a poor monotherapy for levels > 50 ng or so. - Virtually all other studies of critcal care patients have found very low levels - why were17% of their patients so high?
See also VitaminDWiki
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321 items - Is 50 ng of vitamin D too high, just right, or not enough
- Low Magnesium in 40 percent of critical care patients – increased hospital days and death - Jan 2014
- Trauma and surgery category listing with associated searches
- Search VitaminDWiki for ICU OR “critical care” OR “intensive care” OR “acute care” 569 items as of April 2014
Increased mortality if more than 100 ng of vitamin D – not much detail – April 20148412 visitors, last modified 31 May, 2015, This page is in the following categories (# of items in each category)