Vitamin D loading doses reduce ICU mortality by 30 percent – meta-analysis April 2017

Note: Another meta-analysis in May 2017 at the bottom of this page did NOT find any benefit
5 of the RCTs analyzed were the same

RCT	May 2017	April 2017
Amrein 2011	May	April
Leaf 2014	May	April
Amrein 2014	May	April
Quraishi 2015	May	April
Nair 2015	May	-
Han 2016	May	April
Grossmann 2012	-	April
Alizadeh 2016	-	April

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Vitamin D and outcomes in adult critically ill patients. A systematic review and meta-analysis of randomized trials

Journal of Critical Care, Volume 38, April 2017, Pages 109–114, https://doi.org/10.1016/j.jcrc.2016.10.029
Alessandro Putzua, , Alessandro Bellettib, , Tiziano Cassinaa, , Sara Clivioa, , Giacomo Montib, , Alberto Zangrillob, c, , Giovanni Landonib, c, ,
a Department of Cardiovascular Anesthesia and Intensive Care, Fondazione Cardiocentro Ticino, Lugano, Switzerland
b Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
c Vita-Salute San Raffaele University, Milan, Italy

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Purpose
Low vitamin D blood levels are associated with high mortality in critically ill patients. There is controversy about vitamin D supplementation in this population. The objective of this meta-analysis was to evaluate if vitamin D administration reduces mortality in critically ill patients.

Materials and methods
Online databases were searched up to September 1st, 2016 for randomized placebo-controlled trials on the use of vitamin D in adult patients with critical illness. The primary end point was mortality among trials with low risk of bias. The secondary end points were length of hospital stay, length of intensive care unit stay, length of mechanical ventilation, and adverse events.

Results
Seven studies published between 2011 and 2016, for a total of 716 patients, were included in the analysis. Vitamin D administration was associated with significantly lower mortality compared with placebo (101/320 [32%] in the vitamin D group vs 123/307 [40%] in the placebo group; odds ratio, 0.70 [95% confidence interval, 0.50 to 0.98]; P = .04; I2 = 0%). No differences in adverse events and other secondary end points were found.

Conclusions
In critically ill patients, vitamin D administration might be associated with a reduction in mortality without significant adverse events. A large multicenter randomized trial should conclusively confirm these findings.

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Association between vitamin D deficiency and adverse outcomes in critically ill adult patients
letter to editor on the above study costs $36

• "We have read with great interest the recent systematic review and meta-analysis by Langlois et al., entitled “Vitamin D supplementation in the critically ill: A systematic review and meta-analysis” [1] available online the May 13th 2017 (In press version) issue of Clinical Nutrition. In this review, the authors performed a comprehensive literature search and proceeded to evaluate the clinical benefits of vitamin D administration in critically ill patients. However, while this article is timely updated and well written, several methodological constraints should be addressed."

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1 month later another meta-analysis did NOT find a benefit

Vitamin D supplementation in the critically ill: A systematic review and meta-analysis
Clinical Nutrition, online 11 May 2017, https://doi.org/10.1016/j.clnu.2017.05.006
Pascal L. Langloisa, Celeste Szwecb, Frédérick D'Aragona, Daren K. Heylandc, d, William Manzanarese, ,

Introduction
Vitamin D insufficiency is reported in up to 50% of the critically ill patients and is associated with increased mortality, length of stay (LOS) in intensive care unit (ICU) and hospital, and respiratory disorders with prolonged ventilation. Benefits of vitamin D supplementation remain unclear. The aim of this systematic review was to evaluate the clinical benefits of vitamin D administration in critically ill patients.

Methods
We searched Medline, Embase, CINAHL and Cochrane database for randomized controlled trials (RCT) conducted on heterogeneous ICU patients comparing vitamin D administration to placebo. Evaluated outcomes included mortality, infectious complications, hospital/ICU LOS and length of mechanical ventilation. Two independent reviewers assessed eligibility, risk of bias and abstracted data. Data was pooled using a random effect model to estimate the relative risk (RR) or weighted mean difference. Pre-defined subgroup analysis included oral-enteral vs. parenteral administration, high vs. low dose, vitamin d deficient patient, high vs. low quality trials.

Results
Six RCTs (695 patients) met study inclusion. No reduction in mortality was found (P = 0.14). No differences in ICU and hospital LOS, infection rate and ventilation days existed. In the subgroup analysis, the oral-enteral group, there was no improvement in mortality (P = 0.12) or hospital LOS (P = 0.16). Daily doses >300,000 IU did not improve mortality (P = 0.12) and ICU LOS (P = 0.12).

Conclusions
In critically ill patients, Vitamin D administration does not improve clinical outcomes. The statistical imprecision could be explained by the sparse number of trials.

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