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Presentation at the annual convention of the Philippine Society for Parenteral and Enteral Nutrition 7 Oct 2014 at Dhusit Thani Hotel, Makati City.
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Vitamin D in Critical Illness
Iris Thiele Isip Tan MD, MScAssoc. Prof. 4, UP College of Medicine
Chief, UP Medical Informatics Unit
Sunlight by Rishi Bandopadhay https://flic.kr/p/7wrAGT
7 Oct 2014
Tuesday, October 7, 14
Vitamin D Metabolism
Image from http://www.well.ox.ac.uk/aug-10-vitamin-d-influences-over-200-genes
Vit D3cholecalciferoloily fish & egg yolk
Vit D2ergocalciferolplant sources
Tuesday, October 7, 14
The vitamin D endocrine system.
Norman A W Am J Clin Nutr 2008;88:491S-499S
©2008 by American Society for Nutrition
Tuesday, October 7, 14
Tissues that express the vitamin D receptor
Adipose Adrenal Bone Bone Marrow Brain Breast Cancer cells
Cartilage Colon Eggshell gland Epididymis Hair follicle Intestine Kidney Liver (fetal) Lung
Lymphocytes (B & T) Muscle, embryonic Muscle, smooth Osteoblast Ovary Pancreas B cell
Parathyroid Parotid Pituitary Placenta Prostate Retina Skin Stomach Testis Thymus
Thyroid Uterus Yolk sac (bird)
Norman A W Am J Clin Nutr 2008;88:491S-499S
Tuesday, October 7, 14
Does vitamin D replacement improve outcomes in critical illness?
Does low vitamin D affect outcomes in critical illness?
Is there vitamin D deficiency in critical illness?
Sunset by Maria Rosaria Sannino, https://flic.kr/p/tQ7S2
Toronto General Hospital interior by mars_discovery _districthttps://flic.kr/p/2A3Taj
Tuesday, October 7, 14
Is there vitamin D deficiency in critical illness?
Sunset by Maria Rosaria Sannino, https://flic.kr/p/tQ7S2
Tuesday, October 7, 14
P: 42 critically ill patients referred for endocrinologic eval
I: 25(OH)D levelsO: MortalityM: prospective
Lee et al. NEJM 2009;360:18
All patients who died had undetectable 25(OH)D
Consider vit D status in critically ill: hypocalcemia as reason for referral only 5%
Tuesday, October 7, 14
Lee et al. NEJM 2009;360:18
SAPS II* score & predicted mortality and vitamin D status
Sufficient: 34+11; 16%Insufficient: 45+13; 35%Deficient: 51+13; 45%
* Simplified Acute Physiology Score II
Tuesday, October 7, 14
Cross-sectional study of vitamin D status [25(OH)D & DBP] & systemic LL-37 (cathelicidin)
levels in critically ill patients (with and without sepsis)
Journal of Translational Medicine 2009;7:28
Tuesday, October 7, 14
n=24Critically ill in ICU diagnosed with sepsis*
n=25Critically ill in ICU without sepsis
n=21Healthy, non-hospitalized controls*
* As defined by the American College of Chest Physicians & Society of Critical Care Medicine consensus panel (2001)
1 2 3
* Adults without known acute or chronic diseases, no hospitalizations for any illness previous 12 months, not taking any medications or vitamin supplements
Journal of Translational Medicine 2009;7:28
Tuesday, October 7, 14
Lower 25(OH)D levels in critically ill vs healthy controls
Jeng et al. Journal of Translational Medicine 2009;7:28
Vit D insufficiency
25(OH)D < 30 ng/mL
Grp 1 (Sepsis): 100%Grp 2 (No sepsis): 92%Grp 3 (Controls): 66.5%
Tuesday, October 7, 14
Subjects with sepsis had lower DBP levels vs those without sepsis
Jeng et al. Journal of Translational Medicine 2009;7:28
Tuesday, October 7, 14
Vitamin D & ImmunomodulationLL-37
CathelicidinAdams JS & Hewison M. Nat Clin Pract Endocrinol Metab 2008 Feb;4(2):80-90.
Tuesday, October 7, 14
Lower LL-37 levels in critically ill vs healthy controls
Jeng et al. Journal of Translational Medicine 2009;7:28
Tuesday, October 7, 14
Positive relationship between 25(OH)D and LL-37 levels in all three groups
Jeng et al. Journal of Translational Medicine 2009;7:28
Tuesday, October 7, 14
Does vitamin D replacement improve outcomes in critical illness?
Does low vitamin D affect outcomes in critical illness?
Is there vitamin D deficiency in critical illness? Yes
Sunset by Maria Rosaria Sannino, https://flic.kr/p/tQ7S2
Toronto General Hospital interior by mars_discovery _districthttps://flic.kr/p/2A3Taj
Tuesday, October 7, 14
Does low vitamin D affect outcomes in critical illness?
Toronto General Hospital interior by mars_discovery _district https://flic.kr/p/2A3Taj
Tuesday, October 7, 14
P: Veterans in ICU n = 136 (42 SICU & 94 MICU) I: 25(OH)D levelsO: length of ICU stay, mortalityM: retrospective
McKinney et al, J Am Med Dir Assoc 2011;12:208-211
Tuesday, October 7, 14
McKinney et al, J Am Med Dir Assoc 2011;12:208-211
Average 25(OH)D level 24.6 +12.1 ng/mLVitamin D insufficiency (<30 ng/mL): 60%
Vitamin D deficiency (<20 ng/mL): 38%
Tuesday, October 7, 14
ICU stay >3 daysVitamin D replete: 29%
Vitamin D deficient: 58%
Timing of vitamin D blood draw was unrelated to deficiency status
Vit D deficient: 16.2 daysVit D replete: 12.7 days
p=0.440
McKinney et al, J Am Med Dir Assoc 2011;12:208-211
Tuesday, October 7, 14
McKinney et al, J Am Med Dir Assoc 2011;12:208-211
Survived n=81 (59%)Died in ICU n=16 (12%)
Died after discharge n=39 (29%)
Tuesday, October 7, 14
SurvivalVitamin D replete: 69%
Vitamin D deficient: 44%p=0.004
Death after admission for vit D deficient RR =1.81McKinney et al, J Am Med Dir Assoc 2011;12:208-211
Tuesday, October 7, 14
Low serum 25(OH)D & mortality in the critically illBraun et al. Crit Care Med 2011 April; 39(4):671-7
P: 2,399 patients in 209 medical & surgical ICU beds
I: 25(OH)D measured prior to hospitalization between 1998 & 2009
O: 30, 90 and 365-day post ICU admission mortality, in hospital mortality
M: multicenter observational study
Tuesday, October 7, 14
DEFICIENCY25(OH)D <15 ng/mL
30-day OR 1.69 [1.26–2.26]; p <0.0001
OR 1.0
Low pre-admission 25(OH)D is a significant predictor of mortality in the critically ill Braun et al. Crit Care Med 2011 April; 39(4):671-7
INSUFFICIENCY25(OH)D <16-29
SUFFICIENCY25(OH)D >30 ng/mL
Adjusted OR
90-day OR 1.67 [1.28–2.17]; p=0.001
365-day OR 1.72 [1.35–2.19]; p=0.001
In-hospital OR 1.67 [1.27–2.33]; p=0.001
30-day OR 1.36 [1.03–1.79]; p =0.029
90-day OR 1.51 [1.19–1.93]; p=0.001
365-day OR 1.44 [1.15–1.79]; p=0.001
In-hospital OR 1.34 [1.01–1.79]; p=0.04
Tuesday, October 7, 14
P: 258 consecutive patients admitted to SICU I: 25(OH)D by HPLC and tandem mass spectrometry O: length of stay, mortality rate and costM: Prospective observational
Tuesday, October 7, 14
0
5
10
15
20
MILD MODERATE SEVERE
13.33
7.295.17
Matthews et al, Am J Surg Juy 2012;204(1):37-43
Vit D deficiency & ICU outcomesDa
ys
n=96 (37.2%)27-39 ng/mL 14-26 ng/mL <13 ng/mLn=18 (7%) n=138 (53.5%)
25(OH)Ddeficiency
13.33 + 19.957.29 + 15.3
5.17 + 6.5
COSTS
p = 0.002
$51,413.33 + 75,123.00
$28,123.65 + 59,752.00
$20,414.11 + 25,714.3
p = 0.027
Mortality n=17 (12.3%)n=11 (11.5%)p = 0.047
Mild/normal vs moderate/severe
Tuesday, October 7, 14
P: 130 hospitalized patients on mechanical ventilation I: 25(OH)DO: Mortality rateM: Prospective observational single center study
Tuesday, October 7, 14
Average vit D 14.0 + 6.9 ng/mL
Vit D deficient (<20 ng/mL)n=107
Ave 11.7 ng/mL
Vit D >20 ng/mLn=23
Ave 24.9 ng/mL
Arnson et al, Q J Med 2012;105:633-639Tuesday, October 7, 14
P: 50 healthy controls, 51 ICU controls, 105 ICU patients with sepsis I: 25(OH)D by HPLC and tandem mass spectrometry within first 24 h of ICU admissionO: Correlation with disease severity (APACHE II, SAPS II, SOFA)
M: Prospective observational single center study
Long-xiang et al, Chinese Medical Journal 2013;126(14)Tuesday, October 7, 14
Long-xiang et al, Chinese Medical Journal 2013;126(14)
Tuesday, October 7, 14
APACHE II SAPS II
SOFA Very low negative correlations between 25(OH)D & scoring systems
Long-xiang et al, Chinese Medical Journal 2013;126(14)
No difference in 28- and 90-day survival
Tuesday, October 7, 14
Does vitamin D replacement improve outcomes in critical illness?
Does low vitamin D affect outcomes in critical illness? Yes?
Is there vitamin D deficiency in critical illness? Yes
Sunset by Maria Rosaria Sannino, https://flic.kr/p/tQ7S2
Toronto General Hospital interior by mars_discovery _districthttps://flic.kr/p/2A3Taj
Tuesday, October 7, 14
Does vitamin D replacement improve outcomes in critical illness?
Tuesday, October 7, 14
+ 100 IU oral vitamin D intake
= + 1 ng/mL (2.5 nmol/L)
serum 25(OH)D
Rule of ThumbPatient with a starting serum 25(OH)D of 15 ng/mL would require 1,500 IU/d to bring his level to 30 ng/mL
Heaney R. Clin J Am Soc Nephrol 2008;3:1535-41
Tuesday, October 7, 14
Institute of MedicineTolerable Upper
Intake Level (TUIL)2,000 IU/day No-observed-adverse-
effect-level (NOAEL)10,000 IU/day
Heaney R. J Musculoskelet Neuronal Interact 2006:6(4):334
Serum 25(OH)D 32 ng/mL = minimum
daily intake of 2,600 IU vitamin D
(US residents)
Tuesday, October 7, 14
P: 25 patients with 25(OH)D < 20 ng/mL I: Single dose 540,000 IU (13.5 mg) of cholecalciferol dissolved in 45 ml herbal oil vs placebo via feeding tube; 200 IU cholecalciferol daily for placebo group
O: mean 25(OH)D increaseM: randomized, double-blind placebo controlled
Tuesday, October 7, 14
Limitations of Vit D administrationDosingContraindication for IM injection in most ICU patientsUnavailability of parenteral high-dose vit D formulationsUnreliable GI absorption after oral dosing due to multifactorial GI dysfunction, changes in GI blood supply & motility, sepsis and multiorgan failure
Amrein et al, Critical Care 2011;15:R104
Tuesday, October 7, 14
540,000 IU of Vit D3
3 bottles of Oleovit D3 solution (commercially available, Austria)400 IU vitamin D3/dropdissolved in 45 ml of herbal oil
Amrein et al, Critical Care 2011;15:R104
Tuesday, October 7, 14
Amrein et al, Critical Care 2011;15:R104
Tuesday, October 7, 14
8/10 had normalization of 25(OH)D levels (>30 ng/mL)Highest achieved was 64 ng/mL on day 3Two patients in Vit D group demonstrated small (7 ng/mL) or no increase (1 ng/mL) in 25(OH)D levels
Tuesday, October 7, 14
Does vitamin D replacement improve outcomes in critical illness? Don’t know
Does low vitamin D affect outcomes in critical illness? Yes?
Is there vitamin D deficiency in critical illness? Yes
Sunset by Maria Rosaria Sannino, https://flic.kr/p/tQ7S2
Toronto General Hospital interior by mars_discovery _districthttps://flic.kr/p/2A3Taj
Tuesday, October 7, 14
#hcsmPH#HealthXPH tweet chat Saturday 9–10 pm
@endocrine_witch
Tuesday, October 7, 14