ICU 2020.1.28 · PDF file ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on...

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Transcript of ICU 2020.1.28 · PDF file ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on...

  • ICU 2020.1.28

  • INTRODUCTION

    vitamin D D2 D7

    vitaminD2 D3 vitamin D2 ergocalciferol vitamin D3 cholecalciferol

    vitamin D3 vitamin D

  • vitamin D

    INTRODUCTION

    25-hydroxy vitamin D 25OHD

    1,25-dihydroxy vitamin D(1,25OH₂D)

    vitamin D receptor(VDR)

  • INTRODUCTION

    vitamin D Ca P

    2

    /

  • INTRODUCTION

    2 in vitro 1,25OH₂D IL-1β IL-2 IL-6 IL-17 TNF-α IFN- γ

    1,25OH₂D ARDS IL-8 vitamin D

    Nat Rev Endocrinol. 2011;7(6):337-345.

    Steroids. 2011;76(12):1305-1309.

  • INTRODUCTION

    / vitamin D

    vitamin D II

    vitamin D

    PLoS One. 2014;9(1):e86755.

    Am J Physiol Lung Cell Mol Physiol. 2005;289(4):L617-626.

    Science. 2006;311(5768):1770-1773.

  • INTRODUCTION

    • 40 50 vitamin D ICU

    • Institute of Medicine

    N Engl J Med. 1998;338(12):777-783.

    vitamin D

  • INTRODUCTION

    JC 2014/12/16

    vitamin D

  • INTRODUCTION

    JC 2014/12/16

    vitamin D

    30 90 365

  • INTRODUCTION

    ICU vitamin D calcitriol Placebo

    Am J Respir Crit Care Med. 2014;190(5):533-541.

    vitamin D

    ICU 40 vitamin D 25OHD 12ng/ml

    IL-1,IL-6 Crit Care Med. 2015;43(9):1928-1937.

  • INTRODUCTION

    ICU vitamin D50 25OHD

    J Clin Transl Endocrinol. 2016;4:59-65.

    vitamin D 20 ARDS

    Thorax. 2015;70(7):617-624.

  • INTRODUCTION

    vitamin D

    vitamin D ARDS

  • INTRODUCTION

    ICU vitamin D RCT

    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: 1520-30

  • INTRODUCTION

    Medical University of Graz ( )

    2010 5 2012 3

    ICU 18 48 25OHD 20 ng/ml

    vitamin D Placebo 1 1

    ICU cardio surgical neurological medical mixed surgical 2 5

  • INTRODUCTION

    ICU JC 2014/12/16

    3000 IU/

  • INTRODUCTION

    Primary Endpoint

    Secondary Endpoints ICU (day28 and 6 month)

    25OHD≧30ng/ml (day7) vitamin D

    (Ca P 25OHD 1,25OH₂D PTH Ca

    (CRP PCT)

    ( ,NT-proBNP)

  • 492 Placebo vitamin D 475 6

  • INTRODUCTION

    ICU

    Charlson SAP score TISS-28

    65 1/3

    Charlson 10

    TISS-28 Ns 78 Simplified Therapeutic Intervention Scoring System

  • INTRODUCTION

    3/4 ICU

    ICU 1/4

  • INTRODUCTION

    Primary Endpoint

  • INTRODUCTION

    Secondary Endpoints 28 6 vitamin D

  • INTRODUCTION

    vitamin D 25OHD≦12ng/ml 42%

  • INTRODUCTION

    7 25OHD vitamin D 28 30ng/ml

    vitamin D

  • INTRODUCTION

    Subgroup vitamin D

  • INTRODUCTION

    subgroup vitamin D

    vitamin D

    6 vitamin D 7% Placebo

    …vitamin D ICU

  • INTRODUCTION

    vitamin D

    vitamin D subgroup

    vitamin D

  • INTRODUCTION

    vitamin D ARDS vitamin D

    National Heart, Lung, and Blood Institute( )

    Prevention and Early Treatment of Acute Lung Injury(PETAL) Network

  • INTRODUCTION

    vitamin D

    vitamin D ARDS

    ICU

    PETAL network ICU

    vitamin D

  • Vitamin D to Improve Outcomes by Leveraging Early Treatment VIOLET trial

    ARDS vitamin D vitamin D 90

  • METHODS

    44

    2017 4 2018 7

    ICU Inclusion/Exclusion Criteria

    vitamin D Placebo 1 1

  • METHODS

    Inclusion Criteria 18 ICU ARDS 1 vitamin D

  • METHODS

    Inclusion Criteria 18 ICU ARDS 1 vitamin D

    ICU

  • METHODS

    Inclusion Criteria 18 ICU ARDS 1 vitamin D

    SOFA 2 MAP12000

  • METHODS

    Inclusion Criteria 18 ICU ARDS 1 vitamin D

    vitamin D 25OHD 20ng/ml

  • METHODS

    Exclusion Criteria IC ICU 12

    Ca 10.2 /dl Ca >5.2 /dl 1

    48

    a b c 24 d /

  • METHODS

  • METHODS ICU ARDS

    vitamin D

  • METHODS vitamin D 12

    vitamin D Placebo 1 1

  • METHODS 2 54 vitamin D

    vitamin D Placebo

  • METHODS

    LC/MS/MS Ca 25OHD

    vitamin D Primary Endpoint

    vitamin D Secondary Endpoints

  • METHODS

    Vitamin D • 1 vitamin D

    FDA Point of care test Fast Pack System®

    • 2 Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS)

    Vitamin D Ca

  • METHODS

    Primary Endpoint 90

  • METHODS

    Secondary Endpoints

  • METHODS

    Secondary Endpoints

    90

    90

    28 90

  • METHODS

    Secondary Endpoints

    7 ARDS

    3 25OHD IL-6

    a. →P/F FiO₂ SpO₂ PEEP b. →1 Cr RRT c. →1

    Berlin

    300 3 25OHD IL-6

  • METHODS

    Secondary Endpoints

    14 Ca

    90

    vitamin D 2 300

    25OHD 3 Ca

    90

  • METHODS

    Statistic Analysis 5%

    Placebo 20% vitamin D 15%

    80 vitamin D

    α 0.05 87.4 3000

  • METHODS

    Statistic Analysis Data and Safety Monitoring Board DSMB

    3 750 1500 2250

  • METHODS

    / BMI Vitamin D 25OHD LS/MS/MS ARDS

    / SOFA score Lung Injury Prediction Score(LIPS) ARDS ICU

    subgroup

  • RESULTS

    1360

  • RESULTS 15924 13300

    2614 vitamin D

    1360 vitamin D

  • RESULTS

    1360 vitamin D Placebo

    690 vitamin D 2

    668 Placebo

  • RESULTS

    Placebo 528 Primary Endpoint

    vitamin D 531 Primary Endpoint

    LC/MS/MS 2

    vitamin D vitamin D 538 Placebo 540

    7 12

  • RESULTS

    55

  • RESULTS

    ARDS 3 3 3

    2 1 8 ICU

  • RESULTS

    Charlson SOFA LIP score

    30% ARDS 7% 30%

  • RESULTS

    25OHD

    Ca

  • RESULTS Primary Endpoint

    Vitamin D 23.5% (125 of 531) VS Placebo 20.6% (109 of 528 ) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P = 0.26)

    90

  • RESULTS Secondary Endpoints clinical

    90

  • RESULTS Secondary Endpoints clinical

    90 28

  • RESULTS Secondary Endpoints clinical

    28 90

  • 7 ARDS ARDS Vitamin D 4.1% Placebo 4.5%

    RESULTS Secondary Endpoints physiological

  • RESULTS Secondary Endpoints physiological

    7 P/F AKI Cr

    SOFA score

  • RESULTS Secondary Endpoints physiological

    3 25OHD vitamin D 25OHD

    75.9% 30 120 ng/ml

    3 IL-6

  • RESULTS Secondary Endpoints safety

    vitamin D 18 Placebo 19

    14 Ca 90 90

  • RESULTS Secondary Endpoints subgroup)

    25OHD

    vitamin D

    vitamin D

  • vitamin Dvitamin D

  • vitamin Dvitamin D

    ARDS Placebo

  • DISCUSSION

    • 54 vitamin D vitamin D

    • Endpoints Placebo

  • DISCUSSION

    • subgroup vitamin D vitamin D

    • ARDS vitamin D

    vitamin D

    • vitamin D

  • DISCUSSION

    VITdAL-ICU trial ICU 3 75

    vitamin D

    99

    VIOLET trial ICU 14 ARDS

    vitamin D LS/MS/MS 2

  • LIMITATION

    vitamin D

    vitamin D

  • • vitamin D ICU

    vitamin D

    • ARDS

    APACHE SAPS

  • • ICU ICU

    • ICU ICU

  • • 1 • VITdAL-ICU trial Amrein • vitamin D

    30 2017 8 10 2023 2

    ICU 72 48 vitamin D 25OHD≦12ng/ml

    ICU 72 loading dose 54 vitamin D 90 4000 /

  • Primary Endpoint 28

    Secondary Endpoint ICU 90 1 ICU

    5 SOFA 90 ICU

    90

    ICU vitamin D vitamin D

  • • vitamin D RCT

    negative study

    • ICU vitamin D

  • vitamin D

    • negative study NEJM 5 6 vitamin D