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Significant perturbation of vitamin D–parathyroid–calcium axis and adverse clinical outcomes in critically ill patients

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Abstract

Purpose

A prospective multicentre cohort study was conducted to determine the prevalence of hypovitaminosis D in adult critically ill patients, to characterize alterations in the parathyroid hormone (PTH)–vitamin D–calcium axis and to explore associations between hypovitaminosis D and adverse clinical outcomes.

Methods

Demographic, disease severity scores and clinical outcome data were collected in 100 consecutive patients with expected intensive care unit (ICU) admission of at least 2 days. Levels of 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-(OH)2-D), PTH and ionized calcium were measured on days 1, 3 and on day 7 or ICU discharge.

Results

The prevalence of vitamin D insufficiency (25 nmol/L ≤ 25-OH-D ≤ 50 nmol/L) and deficiency (25-OH-D < 25 nmol/L) were 54 and 24 %, respectively, and levels did not recover during ICU stay. Admission 25-OH-D levels correlated with 1,25-(OH)2-D (R = 0.61, p = 0.001), Simplified Acute Physiology Score (SAPS-II) (R = −0.3, p = 0.01), Acute Physiology and Chronic Health Evaluation (APACHE-II) scores (R = −0.2, p = 0.05), but not calcium (R = 0.16, p = 0.11) or PTH (R = −0.11, p = 0.31) levels. Vitamin D deficiency was associated with fewer hospital-free days, OR 3.15 (1.18–8.43) in univariate analysis. Secondary hyperparathyroidism (PTH > 7 pmol/L) was observed in 37.5 % of hypocalcaemic and 32.5 % of vitamin D insufficient/deficient patients, and was associated with higher SAPS-II [43 (31.3–60) vs. 36 (30–43), p = 0.03].

Conclusions

Hypovitaminosis D and secondary hyperparathyroidism are highly prevalent in critically ill patients. Low vitamin D status persists during ICU stay and is associated with worse disease severity and fewer hospital-free days.

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References

  1. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  PubMed  CAS  Google Scholar 

  2. Bikle D (2009) Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94:26–34

    Article  PubMed  CAS  Google Scholar 

  3. Diamond TH, Eisman JA, Mason RS, Nowson CA, Pasco JA, Sambrook PN, Wark JD, Working Group of the Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia, Osteoporosis Australia (2005) Vitamin D and adult bone health in Australia and New Zealand: a position statement. Med J Aust 182:281–285

    Google Scholar 

  4. Grover SR, Morley R (2001) Vitamin D deficiency in veiled or dark-skinned pregnant women. Med J Aust 175:251–252

    PubMed  CAS  Google Scholar 

  5. Inderjeeth CA, Nicklason F, Al-Lahham Y, Greenaway TM, Jones G, Parameswaran VV, David R (2000) Vitamin D deficiency and secondary hyperparathyroidism: clinical and biochemical associations in older non-institutionalised Southern Tasmanians. Aust N Z J Med 30:209–214

    Article  PubMed  CAS  Google Scholar 

  6. Sambrook PN, Cameron ID, Cumming RG, Lord SR, Schwarz JM, Trube A, March LM (2002) Vitamin D deficiency is common in frail institutionalised older people in northern Sydney. Med J Aust 176:560

    PubMed  Google Scholar 

  7. Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz MA (2001) Vitamin D status of women in the Geelong osteoporosis study: association with diet and casual exposure to sunlight. Med J Aust 175:401–405

    PubMed  CAS  Google Scholar 

  8. Lee P, Eisman JA, Center JR (2009) Vitamin D deficiency in critically ill patients. N Engl J Med 360:1912–1914

    Article  PubMed  CAS  Google Scholar 

  9. Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, Luque de Castro MD, Pavon RG, Quesada Gomez JM (2010) Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol 121:452–455

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  Google Scholar 

  11. 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

    Article  PubMed  Google Scholar 

  12. Braun A, Chang D, Mahadevappa K, Gibbons FK, Liu Y, Giovannucci E, Christopher KB (2011) Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med 39:671–677

    Article  PubMed  CAS  Google Scholar 

  13. Cecchi A, Bonizzoli M, Douar S, Mangini M, Paladini S, Gazzini B, Degl’Innocenti S, Linden M, Zagli G, Peris A (2011) Vitamin D deficiency in septic patients at ICU admission is not a mortality predictor. Minerva Anestesiol 77:1184–1189

    PubMed  CAS  Google Scholar 

  14. Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE (1981) APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med 9:591–597

    Article  PubMed  CAS  Google Scholar 

  15. 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

    Article  PubMed  Google Scholar 

  16. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the european society of intensive care medicine. Intensive Care Med 22:707–710

    Article  PubMed  CAS  Google Scholar 

  17. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG (1986) Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 63:954–959

    Article  PubMed  CAS  Google Scholar 

  18. Holick MF (2009) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19:73–78

    Article  PubMed  Google Scholar 

  19. R Development Core Team (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, http://www.R-project.org/

  20. Krishnan A, Ochola J, Mundy J, Jones M, Kruger P, Duncan E, Venkatesh B (2010) Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care 14:R216

    Article  PubMed  Google Scholar 

  21. Venkatesh B, Davidson B, Robinson K, Pascoe R, Appleton C, Jones M (2012) Do random estimations of vitamin D3 and parathyroid hormone reflect the 24-h profile in the critically ill? Intensive Care Med 38:177–179

    Article  PubMed  Google Scholar 

  22. Lee P (2011) Vitamin D metabolism and deficiency in critical illness. Best Pract Res Clin Endocrinol Metab 25:769–781

    Article  PubMed  CAS  Google Scholar 

  23. Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R (2003) Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab 88:4623–4632

    Article  PubMed  Google Scholar 

  24. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V (2009) Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 7:28

    Article  PubMed  Google Scholar 

  25. Dahl B, Schiodt FV, Ott P, Wians F, Lee WM, Balko J, O’Keefe GE (2003) Plasma concentration of Gc-globulin is associated with organ dysfunction and sepsis after injury. Crit Care Med 31:152–156

    Article  PubMed  CAS  Google Scholar 

  26. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 96:507–515

    Article  PubMed  CAS  Google Scholar 

  27. Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Fowlkes JL (2011) Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency? J Clin Endocrinol Metab 96:142–149

    Article  PubMed  CAS  Google Scholar 

  28. Hastbacka J, Pettila V (2003) Prevalence and predictive value of ionized hypocalcemia among critically ill patients. Acta Anaesthesiol Scand 47:1264–1269

    Article  PubMed  CAS  Google Scholar 

  29. Zaloga GP, Chernow B (1986) Hypocalcemia in critical illness. JAMA 256:1924–1929

    Article  PubMed  CAS  Google Scholar 

  30. Lee P, Nair P, Eisman JA, Center JR (2009) Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality? Intensive Care Med 35:2028–2032

    Article  PubMed  CAS  Google Scholar 

  31. Thacher TD, Clarke BL (2011) Vitamin D insufficiency. Mayo Clin Proc 86:50–60

    Article  PubMed  CAS  Google Scholar 

  32. Chen JS, Sambrook PN, March L, Cameron ID, Cumming RG, Simpson JM, Seibel MJ (2008) Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality. Clin Endocrinol (Oxf) 68:290–298

    CAS  Google Scholar 

  33. Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, Hinds CJ (1999) Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 341:785–792

    Article  PubMed  CAS  Google Scholar 

  34. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297

    Article  PubMed  Google Scholar 

  35. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124

    Article  PubMed  CAS  Google Scholar 

  36. Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, Stojakovic T, Schnedl C, Dobnig H (2011) Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care 15:R104

    Article  PubMed  Google Scholar 

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Acknowledgments

We gratefully acknowledge the contribution of David Gattas, Dorrilyn Rajabhandari, Heidi Buhr (Royal Prince Alfred Hospital, Sydney), Manoj Saxena, Rebecca Sidoli and Deborah Inskip (St George Hospital, Sydney) to patient enrolment and data collection.

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Authors and Affiliations

  1. Intensive Care Unit, St Vincents Hospital, Victoria Street, Darlinghurst, Sydney, Australia

    Priya Nair & Claire Reynolds

  2. Bone and Mineral Research Programme, Garvan Institute of Medical Research, Victoria Street, Darlinghurst, Sydney, Australia

    Priya Nair, Paul Lee, Nguyen Dinh Nguyen, John A. Eisman & Jacqueline R. Center

  3. Faculty of Medicine, University of New South Wales, Sydney, Australia

    John Myburgh, John A. Eisman & Jacqueline R. Center

  4. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia

    Paul Lee

  5. School of Medicine, University of Queensland, Brisbane, Australia

    Paul Lee

  6. Critical Care and Trauma Division, The George Institute for Global Health, Sydney, Australia

    Priya Nair & John Myburgh

  7. Intensive Care Unit, St George Hospital, Kogarah, Sydney, Australia

    John Myburgh

  8. Department of Endocrinology, St Vincents Hospital, Victoria Street, Darlinghurst, Sydney, Australia

    John A. Eisman & Jacqueline R. Center

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  1. Priya Nair
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  2. Paul Lee
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  3. Claire Reynolds
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Correspondence to Priya Nair.

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Nair, P., Lee, P., Reynolds, C. et al. Significant perturbation of vitamin D–parathyroid–calcium axis and adverse clinical outcomes in critically ill patients. Intensive Care Med 39, 267–274 (2013). https://doi.org/10.1007/s00134-012-2713-y

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  • DOI: https://doi.org/10.1007/s00134-012-2713-y

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