Vitamin D deficiency on admission to the emergency department is a mortality predictor for patients with septic shock treated with early protocol-driven resuscitation bundle therapy

Published:October 17, 2022DOI:



      Vitamin D is an important immune modulator and is associated with susceptibility to infection. However, past studies have reported inconsistent results regarding the association between vitamin D deficiency and mortality in patients with sepsis, and early-stage data regarding septic shock are limited. This study aimed to determine the relationship between vitamin D deficiency on admission to the emergency department (ED) and mortality in patients with septic shock.


      We analyzed prospectively collected data on adult patients with septic shock who were treated with protocol-driven resuscitation bundle therapy in the ED between September 2019 and February 2021. Septic shock was defined by the sepsis-3 definition and vitamin D deficiency was defined as a 25-hydroxyvitamin D <20 ng/ml. The primary outcome was 30-day mortality.


      A total of 302 patients were included, 236 (78.1%) patients had vitamin D deficiency; it was significantly higher in non-survivors than in survivors (89.3% vs. 73.9%, P=0.004). Mortality was higher in vitamin D deficient patients than in non-deficient patients (31.8% vs. 13.6%, P=0.004). In multivariate analysis, vitamin D deficiency (odds ratio [OR], 2.43; 95 % confidence interval [CI], 1.03–5.74), hyperlactatemia (OR, 3.65; 95 % CI, 1.95–6.83), Sequential Organ Failure Assessment scores (OR, 1.22; 95% CI, 1.09–1.36), and albumin levels (OR, 0.39; 95% CI, 0.21–0.73) were significantly associated with 30-day mortality.


      Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of the Medical Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Angus DC
        • Linde-Zwirble WT
        • Lidicker J
        • et al.
        Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.
        Read Online: Critical Care Medicine| Society of Critical Care Medicine. 2001; 29: 1303-1310
        • Dugar S
        • Choudhary C
        • Duggal A.
        Sepsis and septic shock: Guideline-based management.
        Cleveland Clinic Journal of Medicine. 2020; 87: 53-64
        • Levy MM
        • Evans LE
        • Rhodes A.
        The surviving sepsis campaign bundle: 2018 update.
        Intensive care medicine. 2018; 44: 925-928
        • Jeng L
        • Yamshchikov AV
        • Judd SE
        • et al.
        Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis.
        Journal of translational Medicine. 2009; 7: 28
        • Bouillon R.
        Vitamin D and cardiovascular disorders.
        Osteoporosis International. 2019; : 1-15
        • Giovannucci E
        • Liu Y
        • Rimm EB
        • et al.
        Prospective study of predictors of vitamin D status and cancer incidence and mortality in men.
        Journal of the National Cancer Institute. 2006; 98: 451-459
        • Hyppönen E
        • Läärä E
        • Reunanen A
        • et al.
        Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study.
        The Lancet. 2001; 358: 1500-1503
        • Pilz S
        • Dobnig H
        • Fischer JE
        • et al.
        Low vitamin D levels predict stroke in patients referred to coronary angiography.
        Stroke. 2008; 39: 2611-2613
        • Lucidarme O
        • Messai E
        • Mazzoni T
        • et al.
        Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study.
        Intensive care medicine. 2010; 36: 1609-1611
        • Braun A
        • Chang D
        • Mahadevappa K
        • et al.
        Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill.
        Critical care medicine. 2011; 39: 671
        • de Haan K
        • Groeneveld AJ
        • de Geus HR
        • et al.
        Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis.
        Critical care. 2014; 18: 1-8
        • Zhang Y-P
        • Wan Y-D
        • Sun T-W
        • et al.
        Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies.
        Critical care. 2014; 18: 684
        • Kow CS
        • Hadi MA
        • Hasan SS.
        Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on:“Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths” Nutrients 2020, 12 (4), 988.
        Nutrients. 2020; 12: 1626
        • Mangin M
        • Sinha R
        • Fincher K.
        Inflammation and vitamin D: the infection connection.
        Inflammation Research. 2014; 63: 803-819
        • van Etten E
        • Mathieu C.
        Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts.
        The Journal of steroid biochemistry and molecular biology. 2005; 97: 93-101
        • Vanherwegen A-S
        • Gysemans C
        • Mathieu C.
        Regulation of immune function by vitamin D and its use in diseases of immunity.
        Endocrinology and Metabolism Clinics. 2017; 46: 1061-1094
        • Singer M
        • Deutschman CS
        • Seymour CW
        • et al.
        The third international consensus definitions for sepsis and septic shock (Sepsis-3).
        Jama. 2016; 315: 801-810
        • Vincent J-L
        • Moreno R
        • Takala J
        • et al.
        The SOFA (Sepsis-related Organ Failure Assessment) score describes organ dysfunction/failure.
        Springer-Verlag, 1996
        • Holick MF
        • Binkley NC
        • Bischoff-Ferrari HA
        • et al.
        Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.
        The Journal of Clinical Endocrinology & Metabolism. 2011; 96: 1911-1930
        • Amrein K
        • Litonjua AA
        • Moromizato T
        • et al.
        Increases in pre-hospitalization serum 25 (OH) D concentrations are associated with improved 30-day mortality after hospital admission: A cohort study.
        Clinical Nutrition. 2016; 35: 514-521
        • Amrein K
        • Zajic P
        • Schnedl C
        • et al.
        Vitamin D status and its association with season, hospital and sepsis mortality in critical illness.
        Critical care. 2014; 18: R47
        • Azim A
        • Ahmed A
        • Yadav S
        • et al.
        Prevalence of vitamin D deficiency in critically ill patients and its influence on outcome: experience from a tertiary care centre in North India (an observational study).
        Journal of intensive care. 2013; 1: 14
        • Lee P
        • Eisman JA
        • Center JR.
        Vitamin D deficiency in critically ill patients.
        New England Journal of Medicine. 2009; 360: 1912-1914
        • Moromizato T
        • Litonjua AA
        • Braun AB
        • et al.
        Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill.
        Critical care medicine. 2014; 42: 97-107
        • Olejarova M
        • Dobisova A
        • Suchankova M
        • et al.
        Vitamin D deficiency-a potential risk factor for sepsis development, correlation with inflammatory markers, SOFA score and higher early mortality risk in sepsis.
        Bratislavske lekarske listy. 2019; 120: 284-290
        • Shojaei M
        • Sabzeghabaei A
        • Barhagh HV
        • Soltani S.
        The Correlation between serum level of Vitamin D and outcome of sepsis patients; a cross-sectional study.
        Archives of academic emergency medicine. 2019; 7
        • Ratzinger F
        • Haslacher H
        • Stadlberger M
        • et al.
        25 (OH) D and 1, 25 (OH) D vitamin D fails to predict sepsis and mortality in a prospective cohort study.
        Scientific reports. 2017; 7: 1-10
        • Venkatram S
        • Chilimuri S
        • Adrish M
        • et al.
        Vitamin D deficiency is associated with mortality in the medical intensive care unit.
        Critical care. 2011; 15: R292
        • Alberti C
        • Brun-Buisson C
        • Burchardi H
        • et al.
        Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study.
        Intensive care medicine. 2002; 28: 108-121
        • Ginde AA
        • Camargo Jr CA
        • Shapiro NI
        Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection.
        Academic Emergency Medicine. 2011; 18: 551-554
        • Matysiak-Luśnia K.
        Vitamin D in critically ill patients.
        Anaesthesiology intensive therapy. 2016; 48: 201-207
        • Caprio M
        • Mammi C
        • Rosano GM.
        Vitamin D: a novel player in endothelial function and dysfunction.
        Archives of medical science: AMS. 2012; 8: 4
        • Aird WC.
        The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome.
        Blood, The Journal of the American Society of Hematology. 2003; 101: 3765-3777
        • Cabrera-Cancio MR.
        Infections and the compromised immune status in the chronically critically ill patient: prevention strategies.
        Respiratory care. 2012; 57: 979-992
        • Moraes RB
        • Friedman G
        • Wawrzeniak IC
        • et al.
        Vitamin D deficiency is independently associated with mortality among critically ill patients.
        Clinics. 2015; 70: 326-332
        • Danai PA
        • Sinha S
        • Moss M
        • et al.
        Seasonal variation in the epidemiology of sepsis.
        Critical care medicine. 2007; 35: 410-415
        • Alves FS
        • Freitas FGR
        • Bafi AT
        • et al.
        Serum concentrations of vitamin D and organ dysfunction in patients with severe sepsis and septic shock.
        Revista Brasileira de terapia intensiva. 2015; 27: 376-382
        • Amrein K
        • Schnedl C
        • Holl A
        • 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. 2014; 312: 1520-1530
        • Ding F
        • Zang B
        • Fu J
        • Ji K
        Effect of vitamin D3 on the severity and prognosis of patients with sepsis: a prospective randomized double-blind placebo study.
        Zhonghua wei zhong bing ji jiu yi xue. 2017; 29: 106-110