Letter to the Editor. Vitamin D supplementation in neurocritical patients

View More View Less
  • 1 Center of Biomedical Research (CIB), University of Cartagena, Cartagena de Indias, Colombia;
  • 2 National Autonomous University of Nicaragua, Managua, Nicaragua;
  • 3 National Police Hospital Managua, Nicaragua; and
  • 4 Narayana Medical College Hospital, Andhra Pradesh, India
Free access

If the inline PDF is not rendering correctly, you can download the PDF file here.

TO THE EDITOR: Vitamin D is a steroid hormone that is involved in multiple physiological and pathological events. In pathologies such as arterial hypertension, cancer, and infectious diseases, its protective role has been determined. Serum levels of vitamin D (particularly lower than normal values) have been explored to consider its role as a potential biomarker in clinical practice. Karsy et al.1 provide an important insight into the supplementation of vitamin D and clinical outcomes in a neurocritical care unit (Karsy M, Guan J, Eli I, et al: The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY). J Neurosurg [epub ahead of print September 13, 2019. DOI: 10.3171/2018.11.JNS182713]). Although it is generally considered a trend in increased mortality when vitamin D levels are below 28 ng/mL, no supplementation strategy has proven to be optimal to achieve the best functional levels, since the pharmacokinetic profile of vitamin D supplementation remains not fully understood.2 In conclusion, despite the physiological evidence of the potential benefits of vitamin D, multicenter clinical trials are urgently needed to establish the real benefit of vitamin D in subpopulations of neurocritical patients.

RECTIFY is a well-designed, randomized, double-blind controlled trial and intent-to-treat analysis. The major limitation of the study is that the role of only one factor (hypovitaminosis D and its supplementation) was determined to predict outcome in a very heterogeneous population. The primary outcome of hospital length of stay (LOS) might not be a good indicator to measure, as vitamin D deficiency reflects the long-term physiology of the body. In addition, hospital stay in cases of craniocerebral conditions (traumatic event vs aneurysms vs stroke) will be different from those of spinal disorders (traumatic vs degenerative). In addition, based on apparently small subsamples, it is difficult to draw the strong conclusion of “supplementation in vitamin D–deficient neurocritical care patients did not result in appreciable improvement in outcomes and likely does not play a role in acute clinical recovery.” The choice of primary outcome as hospital LOS is less relevant than mortality, and the authors do not justify this weakness of the study. The representation of nonwhite patients is very low (vitamin D3, 6.6%; placebo, 8.4%), and race was unknown/not reported in many cases (vitamin D3, 13.4%; placebo, 17.3%), which is associated with limiting external validity. It has been established that lifestyle alterations, demographics, and sunlight exposure and modulators of this have an important role in vitamin D levels on a population and individual basis.3 How do authors interpret their data based on this information?

Another important aspect is that critically ill patients with sepsis are usually screened with random biomarkers to evaluate when to start and stop antibiotics, and supplementation with vitamin D may interfere with procalcitonin levels; however, it is not clear whether this is a correlation or a causation.5 Hypomagnesemia is frequently observed in the majority of sepsis patients, probably because magnesium is an important cofactor for the activation of vitamin D.4

Disclosures

The authors report no conflict of interest.

References

  • 1

    Karsy M, Guan J, Eli I, Brock AA, Menacho ST, Park MS: The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY). J Neurosurg [epub ahead of print September 13, 2019. DOI: 10.3171/2018.11.JNS182713]

    • Search Google Scholar
    • Export Citation
  • 2

    Langlois PL, D’Aragon F, Manzanares W: Vitamin D in the ICU: More sun for critically ill adult patients? Nutrition 61:173178, 2019

  • 3

    Merchant RA, van Dam RM, Tan LWL, Lim MY, Low JL, Morley JE: Vitamin D binding protein and vitamin D levels in multi-ethnic population. J Nutr Health Aging 22:10601065, 2018

    • Search Google Scholar
    • Export Citation
  • 4

    Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A: Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM 109:453459, 2016

    • Search Google Scholar
    • Export Citation
  • 5

    Wolf TA, Wimalawansa SJ, Razzaque MS: Procalcitonin as a biomarker for critically ill patients with sepsis: effects of vitamin D supplementation. J Steroid Biochem Mol Biol 193:105428, 2019

    • Search Google Scholar
    • Export Citation
View More View Less
  • 1 Clinical Neurosciences Center, University of Utah, Salt Lake City, UT;
  • 2 Pacific Neuroscience Institute, John Wayne Cancer Institute, Santa Monica, CA; and
  • 3 University of Virginia, Charlottesville, VA

Response

We thank Dr. Moscote-Salazar et al. for their insightful comments regarding the RECTIFY trial. To address their first point, we agree that some of the external validity of this study may be limited by our population as with any single-center clinical trial; however, a predominantly Caucasian population in a northern latitude, such as Utah, would be the predicted group where vitamin D levels would be endemically low and where supplementation could be most helpful.4–7 It is likely that if vitamin D supplementation for neurosurgical clinical outcomes is not helpful here, it may not be in most other North American centers as well.

Second, regarding patient outcomes, certainly LOS is affected by the number of factors involved in discharge disposition. We anticipated this clinical heterogeneity would be balanced in treatment and placebo groups because of the design of a randomized clinical trial. Our underlying subgroups did include different subspecialties (e.g., tumor, spine, trauma); however, this would be expected in a typical neurocritical care population, and thus reflects a real-world scenario. Our subgroup analysis did not show a benefit for vitamin D supplementation in specific disease categories or clinical subgroups. Our previous pilot data suggested improvement in LOS and 3-month Glasgow Outcome Scale scores depending on vitamin D level, regardless of specific subspeciality.2,3 Similarly, other studies included heterogeneous populations to study the role of vitamin D,1 because vitamin D levels have been shown to be involved in multiple diseases.8 This prior literature suggested to us that vitamin D could be useful in a variety of diseases, but this does not eliminate the possibility that vitamin D may work better in a more homogeneous population.

We did not specifically evaluate vitamin D in the context of other clinical biomarkers (e.g., procalcitonin) in neurosurgical patients, but this is an active area of interest in our group. Whether interventions could improve clinical outcomes and biomarkers could serve as a surrogate of risk stratification in neurosurgery remains to be seen.

References

  • 1

    Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, : Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA 312:15201530, 2014

    • Search Google Scholar
    • Export Citation
  • 2

    Guan J, Karsy M, Brock AA, Eli IM, Ledyard HK, Hawryluk GW, : A prospective analysis of hypovitaminosis D and mortality in 400 patients in the neurocritical care setting. J Neurosurg 127:17, 2017

    • Search Google Scholar
    • Export Citation
  • 3

    Guan J, Karsy M, Brock AA, Eli IM, Manton GM, Ledyard HK, : Vitamin D status and 3-month Glasgow Outcome Scale scores in patients in neurocritical care: prospective analysis of 497 patients. J Neurosurg 128:16351641, 2018

    • Search Google Scholar
    • Export Citation
  • 4

    Guan J, Karsy M, Eli I, Bisson EF, McNally S, Taussky P, : Increased incidence of hypovitaminosis D among patients requiring treatment for cerebral aneurysms. World Neurosurg 88:1520, 2016

    • Search Google Scholar
    • Export Citation
  • 5

    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, : Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:19111930, 2011

    • Search Google Scholar
    • Export Citation
  • 6

    Ravindra VM, Godzik J, Guan J, Dailey AT, Schmidt MH, Bisson EF, : Prevalence of vitamin D deficiency in patients undergoing elective spine surgery: a cross-sectional analysis. World Neurosurg 83:11141119, 2015

    • Search Google Scholar
    • Export Citation
  • 7

    Thacher TD, Clarke BL: Vitamin D insufficiency. Mayo Clin Proc 86:5060, 2011

  • 8

    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP: Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035, 2014

    • Search Google Scholar
    • Export Citation

If the inline PDF is not rendering correctly, you can download the PDF file here.

Contributor Notes

Correspondence Luis Rafael Moscote-Salazar: rafaelmoscote21@gmail.com.

INCLUDE WHEN CITING Published online December 20, 2019; DOI: 10.3171/2019.10.JNS192721.

Disclosures The authors report no conflict of interest.

  • 1

    Karsy M, Guan J, Eli I, Brock AA, Menacho ST, Park MS: The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY). J Neurosurg [epub ahead of print September 13, 2019. DOI: 10.3171/2018.11.JNS182713]

    • Search Google Scholar
    • Export Citation
  • 2

    Langlois PL, D’Aragon F, Manzanares W: Vitamin D in the ICU: More sun for critically ill adult patients? Nutrition 61:173178, 2019

  • 3

    Merchant RA, van Dam RM, Tan LWL, Lim MY, Low JL, Morley JE: Vitamin D binding protein and vitamin D levels in multi-ethnic population. J Nutr Health Aging 22:10601065, 2018

    • Search Google Scholar
    • Export Citation
  • 4

    Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A: Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM 109:453459, 2016

    • Search Google Scholar
    • Export Citation
  • 5

    Wolf TA, Wimalawansa SJ, Razzaque MS: Procalcitonin as a biomarker for critically ill patients with sepsis: effects of vitamin D supplementation. J Steroid Biochem Mol Biol 193:105428, 2019

    • Search Google Scholar
    • Export Citation
  • 1

    Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, : Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA 312:15201530, 2014

    • Search Google Scholar
    • Export Citation
  • 2

    Guan J, Karsy M, Brock AA, Eli IM, Ledyard HK, Hawryluk GW, : A prospective analysis of hypovitaminosis D and mortality in 400 patients in the neurocritical care setting. J Neurosurg 127:17, 2017

    • Search Google Scholar
    • Export Citation
  • 3

    Guan J, Karsy M, Brock AA, Eli IM, Manton GM, Ledyard HK, : Vitamin D status and 3-month Glasgow Outcome Scale scores in patients in neurocritical care: prospective analysis of 497 patients. J Neurosurg 128:16351641, 2018

    • Search Google Scholar
    • Export Citation
  • 4

    Guan J, Karsy M, Eli I, Bisson EF, McNally S, Taussky P, : Increased incidence of hypovitaminosis D among patients requiring treatment for cerebral aneurysms. World Neurosurg 88:1520, 2016

    • Search Google Scholar
    • Export Citation
  • 5

    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, : Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:19111930, 2011

    • Search Google Scholar
    • Export Citation
  • 6

    Ravindra VM, Godzik J, Guan J, Dailey AT, Schmidt MH, Bisson EF, : Prevalence of vitamin D deficiency in patients undergoing elective spine surgery: a cross-sectional analysis. World Neurosurg 83:11141119, 2015

    • Search Google Scholar
    • Export Citation
  • 7

    Thacher TD, Clarke BL: Vitamin D insufficiency. Mayo Clin Proc 86:5060, 2011

  • 8

    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP: Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035, 2014

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 89 89 0
Full Text Views 45 45 12
PDF Downloads 44 44 9
EPUB Downloads 0 0 0