Document Type : Original Article
Authors
1 Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Clinical Pharmacy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Intensive Care Unit, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Pathology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Objective: There is few data regarding the correlation between serum Vitamin D level
and unfavorable intensive care unit (ICU) outcome in postsurgical patients. In this study,
correlation between serum 25(OH)D level and length of ICU stay and in‑hospital mortality
has been evaluated in critically ill surgical patients.
Methods: Serum 25(OH)D has been evaluated in 70 surgical, critically ill patients.
Demographic, laboratory, and clinical data of the patients were collected. Correlation between
serum 25(OH) D level and duration of ICU stay and hospital mortality was evaluated using
two‑factor analysis of covariance. Multivariable Cox‑regression analysis was used for adjusting
the effect of season of blood sampling and type of surgery on the main variables. For all
the analyses, P values less than or equal to 0.05 were considered as statistically significant.
Findings: Serum 25(OH)D deficiency was identified in 52 (74.3%) of the patients. Patients
with serum Vitamin D levels < 30 ng/ml had longer length of ICU stay than those with
serum Vitamin D levels ≥ 30 ng/ml (7.8 ± 5.1 vs. 4.05 ± 2.12 days, P = 0.003). Although
hospital mortality was more common in Vitamin D deficient patients than sufficient ones
(25% in deficient group versus 22.2% in sufficient group), there was no significant difference
regarding hospital mortality rate between the groups.
Conclusion: Statistically significant association was found between low 25(OH)D level
and increased length of ICU stay in critically ill surgical patients. It could be explained by
favorable effects of Vitamin D on immune system functions, reducing tissue dysfunction, and
risk of organ failure and overall complications. However, there was no correlation between
serum Vitamin D level and patients’ in‑hospital mortality. Further, well‑designed prospective
clinical studies with adequate sample size are needed to evaluate correlation between serum
Vitamin D level and mortality in critically ill patients.
Keywords
- Holick MF, Chen TC. Vitamin D deficiency: A worldwide
problem with health consequences. Am J Clin Nutr
2008;87:1080S‑6S.
2. HolickMF. Vitamin D deficiency. N Engl J Med 2007;357:266‑81.
3. Deluca HF, Cantorna MT. Vitamin D: Its role and uses in
immunology. FASEB J 2001;15:2579‑85.
4. Gysemans CA, Cardozo AK, Callewaert H, Giulietti A,
Hulshagen L, Bouillon R, et al. 1,25‑Dihydroxyvitamin
D3 modulates expression of chemokines and cytokines in
pancreatic islets: Implications for prevention of diabetes in
nonobese diabetic mice. Endocrinology 2005;146:1956‑64.
5. Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge:
Vitamin D‑mediated human antimicrobial activity against
Mycobacterium tuberculosis is dependent on the induction of
cathelicidin. J Immunol 2007;179:2060‑3.
6. Higgins DM, Wischmeyer PE, Queensland KM, Sillau SH,
Sufit AJ, Heyland DK. Relationship of vitamin D deficiency
to clinical outcomes in critically ill patients. JPEN J Parenter
Enteral Nutr 2012;36:713‑20.
7. Lee P, Eisman JA, CenterJR. Vitamin D deficiency in critically
ill patients. N Engl J Med 2009;360:1912‑4. - 8. Matthews LR, Ahmed Y, Wilson KL, Griggs DD, Danner OK.
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. Am J
Surg 2012;204:37‑43.
9. Mata‑Granados JM, Vargas‑Vasserot J, Ferreiro‑Vera C, Luque
de Castro MD, Pavón RG, Quesada Gómez JM. 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
2010;121:452‑5.
10. Braun A, Chang D, Mahadevappa K, Gibbons FK,
Liu Y, Giovannucci E, et al. Association of low serum
25‑hydroxyvitamin D levels and mortality in the critically ill.
Crit Care Med 2011;39:671‑7.
11. Braun AB, Litonjua AA, Moromizato T, Gibbons FK,
Giovannucci E, Christopher KB. Association of low serum
25‑hydroxyvitamin D levels and acute kidney injury in the
critically ill. Crit Care Med 2012;40:3170‑9.
12. Arnson Y, Gringauz I, Itzhaky D, Amital H. Vitamin D
deficiency is associated with poor outcomes and increased
mortality in severely ill patients. QJM 2012;105:633‑9.
13. Amrein K, Zajic P, Schnedl C, Waltensdorfer A, Fruhwald S,
Holl A, et al. Vitamin D status and its association with season,
hospital and sepsis mortality in critical illness. Crit Care
2014;18:R47.
14. Aygencel G, Turkoglu M, Tuncel AF, Candir BA, Bildaci YD,
Pasaoglu H. Is Vitamin D insufficiency associated with
mortality of critically ill patients? Crit Care Res Pract
2013;2013:856747.
15. Venkatram S, Chilimuri S, Adrish M, Salako A, Patel M,
Diaz‑Fuentes G. Vitamin D deficiency is associated with
mortality in the medical intensive care unit. Crit Care
2011;15:R292.
16. Turan A, Hesler BD, You J, Saager L, Grady M, Komatsu R,
et al. The association of serum Vitamin D concentration with
serious complications after noncardiac surgery. Anesth Analg
2014;119:603‑12.
17. Flynn L, Zimmerman LH, McNorton K, Dolman M, Tyburski J,
Baylor A, et al. Effects of Vitamin D deficiency in critically ill
surgical patients. Am J Surg 2012;203:379‑82.
18. Garland CF, Kim JJ, Mohr SB, Gorham ED, Grant WB,
Giovannucci EL, et al. Meta‑analysis of all‑cause mortality
according to serum 25‑hydroxyvitamin D. Am J Public Health
2014;104:e43‑50.
19. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM,
Clinton SK, et al. The 2011 report on dietary reference intakes
for calcium and Vitamin D from the Institute of Medicine: What
clinicians need to know. J Clin Endocrinol Metab 2011;96:53‑8.
20. HolickMF. Vitamin D: Amillenium perspective. J Cell Biochem
2003;88:296‑307.
21. Leow L, Simpson T, Cursons R, Karalus N, Hancox RJ.
Vitamin D, innate immunity and outcomes in community
acquired pneumonia. Respirology 2011;16:611‑6.
22. Annweiler C, Pochic S, Fantino B, Legrand E, Bataille R,
Montero‑Odasso M, et al. Serum Vitamin D concentration and
short‑term mortality among geriatric inpatients in acute care
settings. Adv Ther 2010;27:245‑9.
23. Venkatesh B, Davidson B, Robinson K, Pascoe R, Appleton C,
Jones M. Do random estimations of Vitamin D3 and
parathyroid hormone reflect the 24‑h profile in the critically
ill? Intensive Care Med 2012;38:177‑9.
24. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O’Reilly DS,
et al. The relation between acute changes in the systemic
inflammatory response and plasma 25‑hydroxyvitamin D
concentrations after elective knee arthroplasty. Am J Clin Nutr
2011;93:1006‑11.
25. GindeAA, Mansbach JM, Camargo CA Jr. Association between
serum 25‑hydroxyvitamin D level and upper respiratory
tract infection in the Third National Health and Nutrition
Examination Survey. Arch Intern Med 2009;169:384‑90.
26. Ghashut RA, Talwar D, Kinsella J, Duncan A, McMillan DC.
The effect of the systemic inflammatory response on plasma
vitamin 25 (OH) D concentrations adjusted for albumin. PLoS
One 2014;9:e92614.
27. Kempker JA, Han JE, Tangpricha V, Ziegler TR, Martin GS.
Vitamin D and sepsis: An emerging relationship.
Dermatoendocrinol 2012;4:101‑8.
28. Heshmat R, Mohammad K, Majdzadeh SR, Forouzanfar MH,
BahramiA, Ranjbar Omrani GH, et al. Vitamin D deficiency in
Iran: A multi‑center study among different urban areas. Iran
J Public Health 2008;1:72‑8.
29. Lips P. Vitamin D status and nutrition in Europe and Asia.
J Steroid Biochem Mol Biol 2007;103:620‑5.
30. Moradzadeh K, Larijani B, Keshtkar A, Hossein‑Nezhad A,
Rajabian R, Nabipour I, et al. Normative values of Vitamin
D among Iranian population: A population based study. Int J
Osteoporos Metab Disord 2008;1:8‑15.
31. Zittermann A, Kuhn J, Dreier J, Knabbe C, Gummert JF,
Börgermann J. Vitamin D status and the risk of major adverse
cardiac and cerebrovascular events in cardiac surgery. Eur
Heart J 2013;34:1358‑64.
32. McKinney JD, Bailey BA, Garrett LH, Peiris P, Manning T,
Peiris AN. Relationship between Vitamin D status and ICU
outcomes in veterans. J Am Med Dir Assoc 2011;12:208‑11.
33. Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D.
Incidence and risk factors of Vitamin D deficiency in critically
ill patients: Results from a prospective observational study.
Intensive Care Med 2010;36:1609‑11.
34. Zhang YP, Wan YD, Sun TW, Kan QC, Wang Lx. Association
between Vitamin D deficiency and mortality in critically ill
adult patients: A meta‑analysis of cohort studies. Crit Care
2014;18:684.
35. Ralph R, PeterJV, ChrispalA, ZachariahA, Dian J, Sebastian T,
et al. Supraphysiological 25‑hydroxy Vitamin D3 level at
admission is associated with illness severity and mortality in
critically ill patients. J Bone Miner Metab 2015;33:239‑43.
36. Sempos CT, Durazo‑ArvizuRA, Dawson‑HughesB, YetleyEA,
Looker AC, Schleicher RL, et al. 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 2013;98:3001‑9.