High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill patients - A randomized, double-blind clinical trial
Mohammad Sistanizad, Mehran Kouchek, Mirmohammad Miri, Sara Salarian, Seyedpouzhia Shojaei, Fatemeh Moeini Vasegh, Hossein Seifi Kafshgari, Roja Qobadighadikolaei
European Journal of Integrative Medicine, doi:10.1016/j.eujim.2020.101271
Introduction: Mechanical ventilation can increase the rate of free radicals in the systemic circulation due to its effect on the inflammatory system. Previous research has suggested that vitamin D has antioxidant properties. This study aimed to evaluate the effect of vitamin D on total Antioxidant Capacity (TAC) and its relationship with ICU patients' outcomes . Methods: In this prospective randomized clinical trial, 36 ventilated ICU patients were randomly allocated to receive either a single intramuscular vitamin D 300,000 IU or its placebo. Serum Vitamin D and TAC were measured before and on day 7 after the intervention. Clinical Pulmonary Infection Score (CPIS) and sequential organ failure assessment (SOFA) scores were measured daily for seven days and on days 14 and 28. Results: Thirty patients completed the study. The results show that injection of vitamin D leads to a significant increase in the mean changes of vitamin D level on the seventh day of the study ( + 3.5 ± 1.3 vs -0.4 ± 0.2 P = 0.00) and TAC levels (3.2 ± 3.9 vs -2.0 ± 2.6 P = 0.00. ICU length of stay was 18.3 ± 8.4 and 25.4 ± 6.6 days in the intervention and placebo arms of the study. Twelve patients in the placebo group and 5 in the vitamin D group died within the 28 day study period. The duration of mechanical ventilation was 15.7 ± 9.3 vs. 22.6 ± 9.1 days in vitamin D and placebo arms, respectively. Conclusion: : Administration of vitamin D may increase TAC levels and decrease the length of stay and duration of mechanical ventilation in ICU patients.
Author contributions MS: study design, data collection, data analysis, conducting the study, and drafting the manuscript. MK: study design, conducting the study, and supervised the study. MMM, SPS, and SS: study design and conducting the study. FMV: data collection, statistical analysis. HSK: statistical analysis and reviewing the paper. RQG: reviewing the paper, writing the final approval, and data analysis.
Declaration of Competing Interest The authors declared that there is no conflict of interest.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.eujim.2020.101271 .
References
Amrein, Christopher, Mcnally, Understanding vitamin D deficiency in intensive care patients, Intensive Care Med
Amrein, Papinutti, Mathew, Vila, Parekh, Vitamin D and critical illness: what endocrinology can learn from intensive care and vice versa, Endocr. Connect
Amrein, Schnedl, Holl, Riedl, Christopher et al., 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
Amrein, Sourij, Wagner, Holl, Pieber et al., 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
Amrein, Zajic, Schnedl, Waltensdorfer, Fruhwald et al., Vitamin D status and its association with season, hospital and sepsis mortality in critical illness, Crit. Care
Aygencel, Turkoglu, Tuncel, Cand I R, Bildac I et al., Is vitamin D insufficiency associated with mortality of critically ill patients?, Crit. Care Res. Pract
Bacon, Gamble, Horne, Scott, Reid, High-dose oral vitamin D 3 supplementation in the elderly, Osteoporos. Int
Baeke, Takiishi, Korf, Gysemans, Mathieu, Vitamin D: modulator of the immune system, Curr. Opin. Pharmacol
Bikle, Nonclassic actions of vitamin D, J. Clin. Endocrinol. Metab
Braun, Chang, Mahadevappa, Gibbons, Liu et al., Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill, Crit. Care Med
Chirumbolo, Bjørklund, Sboarina, Vella, The role of vitamin D in the immune system as a pro-survival molecule, Clin. Ther
De Haan, Groeneveld, De Geus, Egal, Struijs, Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis, Crit. Care
Gorman, Zafirau, Lim, Clarke, Dhamrait et al., High-dose intramuscular vitamin D provides long-lasting moderate increases in serum 25-hydroxvitamin D levels and shorter-term changes in plasma Calcium, J. AOAC Int
Han, Jones, Tangpricha, Brown, Hao et al., High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial, J. Clin. Transl. Endocrinol
Higgins, Wischmeyer, Queensland, Sillau, Sufit et al., Relationship of vitamin D deficiency to clinical outcomes in critically ill patients, J. Parenter. Enter. Nutr
Jeng, Yamshchikov, Judd, Blumberg, Martin et al., Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis, J. Transl. Med
Leyba, Gonzalez, Alonso, Guidelines for specialized nutritional and metabolic support in the critically-ill patient. update. consensus SEMICYUC-SENPE: Septic patient, Nutr. Hosp
Luna, Blanzaco, Niederman, Matarucco, Baredes et al., Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome, Crit. Care Med
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Martucci, Mcnally, Parekh, Zajic, Tuzzolino et al., Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths, Crit. Care
Matthews, Ahmed, Wilson, Griggs, Danner, 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
Mcnally, Nama, O'hearn, Sampson, Amrein et al., Vitamin D deficiency in critically ill children: a systematic review and meta-analysis, Crit. Care
Mcnally, Vitamin D as a modifiable risk factor in critical illness: questions and answers provided by observational studies, J. Pediatr
Miri, Kouchek, Dahmardeh, Sistanizad, Effect of high-dose vitamin D on duration of mechanical ventilation in ICU patients, Iran, J. Pharm. Res. IJPR
Miroliaee, Salamzadeh, Shokouhi, Fatemi, Ardehali et al., Effect of vitamin D supplementation on procalcitonin as prognostic biomarker in patients with ventilator associated pneumonia complicated with vitamin D deficiency, Iran, J. Pharm. Res. IJPR
Mistraletti, Paroni, Umbrello, D'amato, Sabbatini et al., Melatonin pharmacological blood levels increase total antioxidant capacity in critically ill patients, Int. J. Mol. Sci
Mokhtari, Hekmatdoost, Nourian, Antioxidant efficacy of vitamin D, J. Parathyr. Dis
Moromizato, Litonjua, Braun, Gibbons, Giovannucci et al., Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill, Crit. Care Med
Palacios, Gonzalez, Is vitamin D deficiency a major global public health problem?, J. Steroid Biochem. Mol. Biol
Perron, Lee, Efficacy of high-dose vitamin D supplementation in the critically ill patients, Inflamm. Allergy-Drug Targets, Formerly Curr. Drug Targets-Inflammation Allergy)
Prietl, Treiber, Pieber, Amrein, Vitamin D and immune function, Nutrients
Quraishi, Bittner, Blum, Mccarthy, Bhan et al., Prospective study of vitamin D status at initiation of care in critically ill surgical patients and risk of 90-day mortality, Crit. Care Med
Quraishi, Mccarthy, Blum, Cobb, Camargo, Plasma 25-hydroxyvitamin D levels at initiation of care and duration of mechanical ventilation in critically ill surgical patients, J. Parenter. Enter. Nutr
Raman, Orun ; Jin, Han, Md, Sc, Vitamin D to improve outcomes by leveraging early treatment: long-term brain outcomes in vitamin D deficient patients (VIOLET-BUD) trial registration
Seligman, Seligman, Teixeira, Comparing the accuracy of predictors of mortality in ventilator-associated pneumonia, J. Bras. Pneumol
Venkatram, Chilimuri, Adrish, Salako, Patel et al., Vitamin D deficiency is associated with mortality in the medical intensive care unit, Crit. Care
Vieth, Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards, J. Nutr
Yang, Wang ; Zhonghua, He, Hu, Value of the clinical pulmonary infection score for the prognosis of ventilator-associated pneumonia, J. Tuberc. Respir. Dis
Youssef, Ranasinghe, Grant, Peiris, Vitamin D's potential to reduce the risk of hospital-acquired infections, Dermatoendocrinol
Zajic, Amrein, Vitamin D deficiency in the ICU: a systematic review, Minerva Endocrinol
Zhang, Wan, Sun, Kan, Wang, Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies, Crit. Care
Zittermann, Kuhn, Dreier, Knabbe, Gummert et al., Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery, Eur. Heart J
{ 'indexed': {'date-parts': [[2024, 2, 5]], 'date-time': '2024-02-05T23:24:38Z', 'timestamp': 1707175478536},
'reference-count': 42,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2021, 2, 1]],
'date-time': '2021-02-01T00:00:00Z',
'timestamp': 1612137600000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}],
'funder': [ { 'DOI': '10.13039/501100005851',
'name': 'Shahid Beheshti University of Medical Sciences',
'doi-asserted-by': 'publisher'}],
'content-domain': { 'domain': [ 'clinicalkey.jp', 'clinicalkey.com', 'clinicalkey.es', 'clinicalkey.fr',
'clinicalkey.com.au', 'elsevier.com', 'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2021, 2]]},
'DOI': '10.1016/j.eujim.2020.101271',
'type': 'journal-article',
'created': { 'date-parts': [[2020, 12, 26]],
'date-time': '2020-12-26T15:48:39Z',
'timestamp': 1608997719000},
'page': '101271',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 6,
'title': 'High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill '
'patients - A randomized, double-blind clinical trial',
'prefix': '10.1016',
'volume': '42',
'author': [ {'given': 'Mohammad', 'family': 'Sistanizad', 'sequence': 'first', 'affiliation': []},
{'given': 'Mehran', 'family': 'Kouchek', 'sequence': 'additional', 'affiliation': []},
{'given': 'MirMohammad', 'family': 'Miri', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sara', 'family': 'Salarian', 'sequence': 'additional', 'affiliation': []},
{'given': 'Seyedpouzhia', 'family': 'Shojaei', 'sequence': 'additional', 'affiliation': []},
{'given': 'Fatemeh', 'family': 'Moeini Vasegh', 'sequence': 'additional', 'affiliation': []},
{'given': 'Hossein', 'family': 'Seifi Kafshgari', 'sequence': 'additional', 'affiliation': []},
{'given': 'Roja', 'family': 'Qobadighadikolaei', 'sequence': 'additional', 'affiliation': []}],
'member': '78',
'reference': [ { 'key': '10.1016/j.eujim.2020.101271_bib0001',
'doi-asserted-by': 'crossref',
'first-page': '26',
'DOI': '10.1210/jc.2008-1454',
'article-title': 'Nonclassic actions of vitamin D',
'volume': '94',
'author': 'Bikle',
'year': '2009',
'journal-title': 'J. Clin. Endocrinol. Metab.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0002',
'doi-asserted-by': 'crossref',
'first-page': 'R304',
'DOI': '10.1530/EC-18-0184',
'article-title': 'Vitamin D and critical illness: what endocrinology can learn from '
'intensive care and vice versa',
'volume': '7',
'author': 'Amrein',
'year': '2018',
'journal-title': 'Endocr. Connect.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0003',
'doi-asserted-by': 'crossref',
'first-page': 'i6583',
'DOI': '10.1136/bmj.i6583',
'article-title': 'Vitamin D supplementation to prevent acute respiratory tract '
'infections: systematic review and meta-analysis of individual '
'participant data',
'volume': '356',
'author': 'Martineau',
'year': '2017',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0004',
'doi-asserted-by': 'crossref',
'first-page': '2502',
'DOI': '10.3390/nu5072502',
'article-title': 'Vitamin D and immune function',
'volume': '5',
'author': 'Prietl',
'year': '2013',
'journal-title': 'Nutrients'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0005',
'doi-asserted-by': 'crossref',
'first-page': '660',
'DOI': '10.1186/s13054-014-0660-4',
'article-title': 'Vitamin D deficiency as a risk factor for infection, sepsis and '
'mortality in the critically ill: systematic review and meta-analysis',
'volume': '18',
'author': 'de Haan',
'year': '2014',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0006',
'doi-asserted-by': 'crossref',
'first-page': '894',
'DOI': '10.1016/j.clinthera.2017.03.021',
'article-title': 'The role of vitamin D in the immune system as a pro-survival molecule',
'volume': '39',
'author': 'Chirumbolo',
'year': '2017',
'journal-title': 'Clin. Ther.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0007',
'doi-asserted-by': 'crossref',
'first-page': '138',
'DOI': '10.1016/j.jsbmb.2013.11.003',
'article-title': 'Is vitamin D deficiency a major global public health problem?',
'volume': '144',
'author': 'Palacios',
'year': '2014',
'journal-title': 'J. Steroid Biochem. Mol. Biol.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0008',
'first-page': '275',
'article-title': 'Vitamin D deficiency in the ICU: a systematic review',
'volume': '39',
'author': 'Zajic',
'year': '2014',
'journal-title': 'Minerva Endocrinol.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0009',
'first-page': '273',
'article-title': 'Efficacy of high-dose vitamin D supplementation in the critically ill '
'patients',
'volume': '12',
'author': 'Perron',
'year': '2013',
'journal-title': 'Inflamm. Allergy-Drug Targets (Formerly Curr. Drug Targets-Inflammation '
'Allergy).'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0010',
'doi-asserted-by': 'crossref',
'first-page': '671',
'DOI': '10.1097/CCM.0b013e318206ccdf',
'article-title': 'Association of low serum 25-hydroxyvitamin D levels and mortality in '
'the critically ill',
'volume': '39',
'author': 'Braun',
'year': '2011',
'journal-title': 'Crit. Care Med.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0011',
'doi-asserted-by': 'crossref',
'first-page': '1961',
'DOI': '10.1007/s00134-015-3937-4',
'article-title': 'Understanding vitamin D deficiency in intensive care patients',
'volume': '41',
'author': 'Amrein',
'year': '2015',
'journal-title': 'Intensive Care Med'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0012',
'doi-asserted-by': 'crossref',
'first-page': '1365',
'DOI': '10.1097/CCM.0000000000000210',
'article-title': 'Prospective study of vitamin D status at initiation of care in '
'critically ill surgical patients and risk of 90-day mortality',
'volume': '42',
'author': 'Quraishi',
'year': '2014',
'journal-title': 'Crit. Care Med.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0013',
'doi-asserted-by': 'crossref',
'first-page': '287',
'DOI': '10.1186/s13054-017-1875-y',
'article-title': 'Vitamin D deficiency in critically ill children: a systematic review '
'and meta-analysis',
'volume': '21',
'author': 'McNally',
'year': '2017',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0014',
'doi-asserted-by': 'crossref',
'first-page': '99',
'DOI': '10.1016/j.jped.2013.12.002',
'article-title': 'Vitamin D as a modifiable risk factor in critical illness: questions '
'and answers provided by observational studies',
'volume': '90',
'author': 'McNally',
'year': '2014',
'journal-title': 'J. Pediatr. (Rio. J).'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0015',
'doi-asserted-by': 'crossref',
'first-page': 'R104',
'DOI': '10.1186/cc10120',
'article-title': 'Short-term effects of high-dose oral vitamin D3 in critically ill '
'vitamin D deficient patients: a randomized, double-blind, '
'placebo-controlled pilot study',
'volume': '15',
'author': 'Amrein',
'year': '2011',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0016',
'doi-asserted-by': 'crossref',
'first-page': '1407',
'DOI': '10.1007/s00198-008-0814-9',
'article-title': 'High-dose oral vitamin D 3 supplementation in the elderly',
'volume': '20',
'author': 'Bacon',
'year': '2009',
'journal-title': 'Osteoporos. Int.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0017',
'doi-asserted-by': 'crossref',
'first-page': '1117',
'DOI': '10.1093/jn/136.4.1117',
'article-title': 'Critique of the considerations for establishing the tolerable upper '
'intake level for vitamin D: critical need for revision upwards',
'volume': '136',
'author': 'Vieth',
'year': '2006',
'journal-title': 'J. Nutr.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0018',
'doi-asserted-by': 'crossref',
'first-page': '200',
'DOI': '10.1186/s13054-019-2472-z',
'article-title': 'Trying to identify who may benefit most from future vitamin D '
'intervention trials: a post hoc analysis from the VITDAL-ICU study '
'excluding the early deaths',
'volume': '23',
'author': 'Martucci',
'year': '2019',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0019',
'doi-asserted-by': 'crossref',
'first-page': '97',
'DOI': '10.1097/CCM.0b013e31829eb7af',
'article-title': 'Association of low serum 25-hydroxyvitamin D levels and sepsis in the '
'critically ill',
'volume': '42',
'author': 'Moromizato',
'year': '2014',
'journal-title': 'Crit. Care Med.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0020',
'doi-asserted-by': 'crossref',
'first-page': '684',
'DOI': '10.1186/s13054-014-0684-9',
'article-title': 'Association between vitamin D deficiency and mortality in critically '
'ill adult patients: a meta-analysis of cohort studies',
'volume': '18',
'author': 'Zhang',
'year': '2014',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0021',
'first-page': '11',
'article-title': 'Antioxidant efficacy of vitamin D',
'volume': '5',
'author': 'Mokhtari',
'year': '2016',
'journal-title': 'J. Parathyr. Dis.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0022',
'first-page': '1067',
'article-title': 'Effect of high-dose vitamin D on duration of mechanical ventilation in '
'ICU patients',
'volume': '18',
'author': 'Miri',
'year': '2019',
'journal-title': 'Iran. J. Pharm. Res. IJPR.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0023',
'first-page': '59',
'article-title': 'High dose vitamin D administration in ventilated intensive care unit '
'patients: a pilot double blind randomized controlled trial',
'volume': '4',
'author': 'Han',
'year': '2016',
'journal-title': 'J. Clin. Transl. Endocrinol.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0024',
'first-page': '67',
'article-title': 'Guidelines for specialized nutritional and metabolic support in the '
'critically-ill patient. update. consensus SEMICYUC-SENPE: Septic '
'patient',
'volume': '26',
'author': 'Leyba',
'year': '2011',
'journal-title': 'Nutr. Hosp.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0025',
'doi-asserted-by': 'crossref',
'first-page': '167',
'DOI': '10.4161/derm.20789',
'article-title': "Vitamin D's potential to reduce the risk of hospital-acquired "
'infections',
'volume': '4',
'author': 'Youssef',
'year': '2012',
'journal-title': 'Dermatoendocrinol'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0026',
'doi-asserted-by': 'crossref',
'first-page': '273',
'DOI': '10.1177/0148607114566276',
'article-title': 'Plasma 25-hydroxyvitamin D levels at initiation of care and duration of '
'mechanical ventilation in critically ill surgical patients',
'volume': '40',
'author': 'Quraishi',
'year': '2016',
'journal-title': 'J. Parenter. Enter. Nutr.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0027',
'first-page': '1254',
'article-title': 'Effect of vitamin D supplementation on procalcitonin as prognostic '
'biomarker in patients with ventilator associated pneumonia complicated '
'with vitamin D deficiency',
'volume': '16',
'author': 'Miroliaee',
'year': '2017',
'journal-title': 'Iran. J. Pharm. Res. IJPR.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0028',
'doi-asserted-by': 'crossref',
'first-page': '759',
'DOI': '10.3390/ijms18040759',
'article-title': 'Melatonin pharmacological blood levels increase total antioxidant '
'capacity in critically ill patients',
'volume': '18',
'author': 'Mistraletti',
'year': '2017',
'journal-title': 'Int. J. Mol. Sci.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0029',
'doi-asserted-by': 'crossref',
'first-page': '1520',
'DOI': '10.1001/jama.2014.13204',
'article-title': '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',
'volume': '312',
'author': 'Amrein',
'year': '2014',
'journal-title': 'Jama'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0030',
'doi-asserted-by': 'crossref',
'first-page': '28',
'DOI': '10.1186/1479-5876-7-28',
'article-title': 'Alterations in vitamin D status and anti-microbial peptide levels in '
'patients in the intensive care unit with sepsis',
'volume': '7',
'author': 'Jeng',
'year': '2009',
'journal-title': 'J. Transl. Med.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0031',
'doi-asserted-by': 'crossref',
'first-page': '482',
'DOI': '10.1016/j.coph.2010.04.001',
'article-title': 'Vitamin D: modulator of the immune system',
'volume': '10',
'author': 'Baeke',
'year': '2010',
'journal-title': 'Curr. Opin. Pharmacol.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0032',
'first-page': '2013',
'article-title': 'Is vitamin D insufficiency associated with mortality of critically ill '
'patients?',
'author': 'Aygencel',
'year': '2013',
'journal-title': 'Crit. Care Res. Pract.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0033',
'series-title': 'https://clinicaltrials.gov/ct2/show/NCT03733418 Principal Investigator '
'Jin H. Han, MD, M. Sc.',
'article-title': 'Vitamin D to improve outcomes by leveraging early treatment: long-term '
'brain outcomes in vitamin D deficient patients (VIOLET-BUD) trial '
'registration',
'author': 'Raman',
'year': '2020'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0034',
'doi-asserted-by': 'crossref',
'first-page': '1358',
'DOI': '10.1093/eurheartj/ehs468',
'article-title': 'Vitamin D status and the risk of major adverse cardiac and '
'cerebrovascular events in cardiac surgery',
'volume': '34',
'author': 'Zittermann',
'year': '2013',
'journal-title': 'Eur. Heart J.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0035',
'doi-asserted-by': 'crossref',
'first-page': '713',
'DOI': '10.1177/0148607112444449',
'article-title': 'Relationship of vitamin D deficiency to clinical outcomes in critically '
'ill patients',
'volume': '36',
'author': 'Higgins',
'year': '2012',
'journal-title': 'J. Parenter. Enter. Nutr.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0036',
'doi-asserted-by': 'crossref',
'first-page': '37',
'DOI': '10.1016/j.amjsurg.2011.07.021',
'article-title': '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',
'volume': '204',
'author': 'Matthews',
'year': '2012',
'journal-title': 'Am. J. Surg.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0037',
'doi-asserted-by': 'crossref',
'first-page': 'R47',
'DOI': '10.1186/cc13790',
'article-title': 'Vitamin D status and its association with season, hospital and sepsis '
'mortality in critical illness',
'volume': '18',
'author': 'Amrein',
'year': '2014',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0038',
'doi-asserted-by': 'crossref',
'first-page': 'R292',
'DOI': '10.1186/cc10585',
'article-title': 'Vitamin D deficiency is associated with mortality in the medical '
'intensive care unit',
'volume': '15',
'author': 'Venkatram',
'year': '2011',
'journal-title': 'Crit. Care.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0039',
'doi-asserted-by': 'crossref',
'first-page': '1337',
'DOI': '10.5740/jaoacint.17-0087',
'article-title': 'High-dose intramuscular vitamin D provides long-lasting moderate '
'increases in serum 25-hydroxvitamin D levels and shorter-term changes '
'in plasma Calcium',
'volume': '100',
'author': 'Gorman',
'year': '2017',
'journal-title': 'J. AOAC Int.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0040',
'first-page': '751',
'article-title': 'Value of the clinical pulmonary infection score for the prognosis of '
'ventilator-associated pneumonia, Zhonghua Jie He He Hu Xi Za Zhi= '
'Zhonghua Jiehe He Huxi',
'volume': '29',
'author': 'Yang',
'year': '2006',
'journal-title': 'Zazhi= Chinese J. Tuberc. Respir. Dis.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0041',
'doi-asserted-by': 'crossref',
'first-page': '676',
'DOI': '10.1097/01.CCM.0000055380.86458.1E',
'article-title': 'Resolution of ventilator-associated pneumonia: prospective evaluation '
'of the clinical pulmonary infection score as an early clinical '
'predictor of outcome',
'volume': '31',
'author': 'Luna',
'year': '2003',
'journal-title': 'Crit. Care Med.'},
{ 'key': '10.1016/j.eujim.2020.101271_bib0042',
'doi-asserted-by': 'crossref',
'first-page': '495',
'DOI': '10.1590/S1806-37132011000400012',
'article-title': 'Comparing the accuracy of predictors of mortality in '
'ventilator-associated pneumonia',
'volume': '37',
'author': 'Seligman',
'year': '2011',
'journal-title': 'J. Bras. Pneumol.'}],
'container-title': 'European Journal of Integrative Medicine',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S1876382020314529?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S1876382020314529?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2021, 3, 19]],
'date-time': '2021-03-19T12:08:38Z',
'timestamp': 1616155718000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S1876382020314529'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 2]]},
'references-count': 42,
'alternative-id': ['S1876382020314529'],
'URL': 'http://dx.doi.org/10.1016/j.eujim.2020.101271',
'relation': {},
'ISSN': ['1876-3820'],
'subject': [],
'container-title-short': 'European Journal of Integrative Medicine',
'published': {'date-parts': [[2021, 2]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'High dose vitamin D improves total serum antioxidant capacity and ICU outcome '
'in critically ill patients - A randomized, double-blind clinical trial',
'name': 'articletitle',
'label': 'Article Title'},
{ 'value': 'European Journal of Integrative Medicine',
'name': 'journaltitle',
'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.eujim.2020.101271',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': '© 2020 Elsevier GmbH. All rights reserved.',
'name': 'copyright',
'label': 'Copyright'}],
'article-number': '101271'}