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