Correspondence
Vitamin D Deficiency in Critically Ill Patients
N Engl J Med 2009; 360:1912-1914April 30, 2009
- Article
To the Editor:
Vitamin D deficiency is rarely considered or treated in critically ill patients. However, we recently reported three cases of life-threatening hypocalcemia secondary to vitamin D deficiency,1,2 highlighting potential acute complications. The prevalence of vitamin D deficiency and its significance in the intensive care unit (ICU) are unknown.
We performed a prospective study of the vitamin D status in ICU patients (Table 1Table 1
Characteristics of 42 Critically Ill Patients Referred for Endocrinologic Evaluation.) referred to the Department of Endocrinology, St. Vincent's Hospital, Sydney, between January 2007 and January 2008. Demographic, physiological, and biochemical variables were recorded, including the Simplified Acute Physiology Score II (SAPS II) (on a scale of 0 to 163, with higher scores indicating more severe organ dysfunction).3 Among approximately 1100 ICU patients per year, the mean (±SD) serum level of 25-hydroxyvitamin D in 42 referred patients was 41±22 nmol per liter (16±9 ng per milliliter), with a high prevalence of hypovitaminosis D (Table 1). Moreover, three patients died (from metastatic thymic carcinoma, glioma, and lymphoma), and all patients who died had undetectable levels of 25-hydroxyvitamin D. The SAPS II in patients with sufficient, insufficient, and deficient levels of vitamin D were 34±11, 45±13, and 51±13, with predicted mortality rates of 16%, 35%, and 45%, respectively.3
The level of 25-hydroxyvitamin D correlated with the level of ionized calcium (r=0.78, P<0.01) and the SAPS II (r=−0.52, P<0.01) but not with the level of serum albumin. The SAPS II also correlated with the level of ionized calcium (r=−0.36, P=0.02), but the only independent predictors of the SAPS II were the level of 25-hydroxyvitamin D (β=−0.59, P<0.001) and age (β=0.33, P<0.02). The level of serum creatinine and use or nonuse of corticosteroids and calcium or vitamin D supplements were not predictors of the SAPS II.
The current study involving patients in the ICU reveals a high prevalence of hypovitaminosis D that was associated with adverse outcomes, independently of hypocalcemia and hypoalbuminemia. Supplementation with calcium (at a mean dose of 645±307 mg per day), vitamin D (at a mean dose of 820±280 IU per day), or both before admission was not protective.
The cause of hypovitaminosis D is probably multifactorial. Although limited exposure to sunlight during chronic illness is probably an important factor, altered vitamin D and parathyroid metabolism during critical illness cannot be ruled out.
Vitamin D deficiency is associated with increased mortality.4 This study cannot establish causality between hypovitaminosis D and adverse outcomes. However, vitamin D has pleiotropic effects in immunity, endothelial and mucosal functions, and glucose and calcium metabolism. The association between hypovitaminosis D and common conditions (e.g., the systemic inflammatory response syndrome, septicemia, and cardiac and metabolic dysfunctions) in critically ill patients may be important. Vitamin D–deficient and vitamin D–insufficient states may worsen existing immune and metabolic dysfunctions in critically ill patients, leading to worse outcomes.
A total of 17% of the ICU patients in our study had undetectable levels of vitamin D. Referral bias may have led to the selection of a cohort of patients with worse vitamin D status, as compared with unreferred patients, but hypocalcemia was identified as a reason for referral in only 5% of the patients. These findings highlight the need for consideration of vitamin D status and supplementation in patients in the ICU.
Paul Lee, M.B., B.S.
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
p.lee@garvan. org. au John A. Eisman, M.B., B.S., Ph.D.
St. Vincent's Hospital, Sydney, NSW 2010, AustraliaJacqueline R. Center, M.B., B.S., Ph.D.
Garvan Institute of Medical Research, Sydney, NSW 2010, AustraliaDr. Eisman reports receiving consulting fees from Amgen, deCODE Genetics, Eli Lilly, GE Lunar, Merck Sharpe & Dohme, Novartis, Roche–GlaxoSmithKline, Sanofi-Aventis, Servier, and Wyeth Australia and grant support from Novartis, Merck, and Sanofi-Aventis; and Dr. Center, lecture fees from Eli Lilly and Sanofi-Aventis. No other potential conflict of interest relevant to this letter was reported.
This letter (10.1056/NEJMc0809996) was updated on May 11, 2011, at NEJM.org.
4 References1
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Lee P ,Samaras K ,Glanville A ,Center JR . Transplant recipients on the edge of the hypocalcaemia abyss. J Heart Lung Transplant 2009;28:93-95
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Le Gall JR ,Lemeshow S ,Saulnier F . A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993;270:2957-2963[Erratum, JAMA 1994;271:1321.]
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Melamed ML ,Michos ED ,Post W ,Astor B . 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008;168:1629-1637
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- Citing Articles (21)
Citing Articles
1
L. Ray Matthews, Yusuf Ahmed, Kenneth L. Wilson, Diane D. Griggs, Omar K. Danner. (2012) Worsening severity of vitamin D deficiency is associated with increased length of stay, surgical intensive care unit cost, and mortality rate in surgical intensive care unit patients. The American Journal of Surgery
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Bala Venkatesh, Ben Davidson, Katherine Robinson, Ranald Pascoe, Charles Appleton, Mark Jones. (2012) Do random estimations of vitamin D3 and parathyroid hormone reflect the 24-h profile in the critically ill?. Intensive Care Medicine 38:1, 177-179
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Andrea B. Braun, Fiona K. Gibbons, Augusto A. Litonjua, Edward Giovannucci, Kenneth B. Christopher. (2012) Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality*. Critical Care Medicine 40:1, 63-72
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Lisa Flynn, Lisa Hall Zimmerman, Kelly McNorton, Mortimer Dolman, James Tyburski, Alfred Baylor, Robert Wilson, Heather Dolman. (2011) Effects of vitamin D deficiency in critically ill surgical patients. The American Journal of Surgery
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Karin Amrein, Bala Venkatesh. (2011) Vitamin D and the critically ill patient. Current Opinion in Clinical Nutrition and Metabolic Care1
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K Robien, L G Strayer, N Majhail, D Lazovich, K S Baker, A R Smith, D A Mulrooney, L J Burns. (2011) Vitamin D status among long-term survivors of hematopoietic cell transplantation. Bone Marrow Transplantation 46:11, 1472-1479
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Paul Lee. (2011) Vitamin D metabolism and deficiency in critical illness. Best Practice & Research Clinical Endocrinology & Metabolism 25:5, 769-781
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D. Cheyron, O. Lucidarme. (2011) La vitamine D : une nouvelle cible pour les réanimateurs ?. Réanimation 20:4, 327-334
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Paul Welsh, Mike J. L. Peters, Naveed Sattar. (2011) Is vitamin D in rheumatoid arthritis a magic bullet or a mirage? The need to improve the evidence base prior to calls for supplementation. Arthritis & Rheumatism 63:7, 1763-1769
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Christian Markus Lange, Jörg Bojunga, Elizabeth Ramos-Lopez, Michael von Wagner, Angela Hassler, Johannes Vermehren, Eva Herrmann, Klaus Badenhoop, Stefan Zeuzem, Christoph Sarrazin. (2011) Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy. Journal of Hepatology 54:5, 887-893
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Andrea Braun, Domingo Chang, Karthik Mahadevappa, Fiona K. Gibbons, Yan Liu, Edward Giovannucci, Kenneth B. Christopher. (2011) Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill*. Critical Care Medicine 39:4, 671-677
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Richard D. Fremont, Todd W. Rice. (2011) Vitamin D: Could Mom really be right?*. Critical Care Medicine 39:4, 885-886
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Paul Lee. (2011) How deficient are vitamin D deficient critically ill patients?. Critical Care 15:2, 154
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Sindhaghatta Venkatram, Sridhar Chilimuri, Muhammad Adrish, Abayomi Salako, Madanmohan Patel, Gilda Diaz-Fuentes. (2011) Vitamin D deficiency is associated with mortality in the medical intensive care unit. Critical Care 15:6, R292
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Karin Amrein, Harald Sourij, Gerit Wagner, Alexander Holl, Thomas R Pieber, Karl Heinz Smolle, Tatjana Stojakovic, Christian Schnedl, Harald Dobnig. (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. Critical Care 15:2, R104
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Michael A. Via, Emily Jane Gallagher, Jeffrey I. Mechanick. (2010) Bone physiology and therapeutics in chronic critical illness. Annals of the New York Academy of Sciences 1211:1, 85-94
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J. Rojas-Rivera, C. De La Piedra, A. Ramos, A. Ortiz, J. Egido. (2010) The expanding spectrum of biological actions of vitamin D. Nephrology Dialysis Transplantation 25:9, 2850-2865
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Olivier Lucidarme, Elmi Messai, Thierry Mazzoni, Michel Arcade, Damien Cheyron. (2010) Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study. Intensive Care Medicine 36:9, 1609-1611
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J.M. Mata-Granados, J. Vargas-Vasserot, C. Ferreiro-Vera, M.D. Luque de Castro, R. Guerrero Pavón, J.M. Quesada Gómez. (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. The Journal of Steroid Biochemistry and Molecular Biology 121:1-2, 452-455
CrossRef20
Paul Lee, Priya Nair, John A. Eisman, Jacqueline R. Center. (2009) Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality?. Intensive Care Medicine 35:12, 2028-2032
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Armin Zittermann, Jan F Gummert, Jochen Börgermann. (2009) Vitamin D deficiency and mortality. Current Opinion in Clinical Nutrition and Metabolic Care 12:6, 634-639
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