Introduction
Materials and methods
Search strategy
Study selection
Data extraction and quality assessment
Statistical analysis
Results
Study selection and study characteristics
First author/Year of publication (reference) | Amrein et al ./2014 [22] | Aygencel et al ./2013 [19] | Hu et al ./2013 [18] | Nair et al ./2012 [21] | Higgins et al ./2012 [20] | Venkatram et al ./2011 [8] | Braun et al ./2011 [17] |
---|---|---|---|---|---|---|---|
Study design
| Single-center, retrospective | Single-center, prospective | Single-center, prospective | Multi-center, prospective | Multi-center, prospective | Single-center, retrospective | Multi-center, retrospective |
Country
| Austria | Turkey | China | Australia | Canada | USA | USA |
Patients
| Neurologic (30.2%), cardiac surgery (15.0%), respiratory disease (8.1%), trauma (5.8%), brain surgery (5.0%), infectious diseases, including sepsis at admission (4.4%) | Respiratory insufficiency (45%), organ dysfunctions (44%), invasive mechanical ventilation (44%), sepsis/septic shock (35.8%), renal replacement therapy (34%), nosocomial infection (35%) | Severe pneumonia with respiratory failure (47.2%), acute exacerbations of chronic obstructive pulmonary disease (19%), intra-abdominal infection (15.3%), mechanical ventilation (85.6%) | Cardiac (30%), infection/sepsis (26%), heart/lung/bone marrow transplant (21%), trauma (9%), metabolic (7%), neurological (7%) | Cardiovascular (14%), respiratory (29%), neurological (7%), metabolic (7%), gastrointestinal (3%), sepsis (5%), postoperative (35%) | Cardiac (4.8%), gastrointestinal (10.7%), metabolic (11.4%), neurological (12.5%), obstructive airway disease (13.7%), pulmonary (18.3%), others (10.9%), renal (5%), sepsis/septic shock (12.3%) | Medical (58.3%) Surgical (41.7%) |
Patients, n
| 655 | 201 | 216 | 100 | 196 | 437 | 2,399 |
Case patients, n (%)
| 394 (60.2%) | 139 (69.2%) | 95 (44.0%) | 24 (24.0%) | 50 (25.5%) | 340 (77.8%) | 637 (26.6%) |
Male patients, n (%)
| 412 (62.9%) | 113 (56.0%) | 120 (55.6%) | 65 (65.0%) | 121 (62.0%) | 208 (47.5%) | 1,030 (43.0%) |
Age, y, mean
| 65 (22)a | 66 (21)a | 64 (25)a | 52 ± 17b | 64 ± 14b | 56.6 ± 17.1b | 64.9 ± 16.6b |
Severity of illness
| 26 (16)a (SAPS II) | 23(11)a (APACHE II) | 21(8)a (APACHE II) | 21 ± 8b (APACHE II) | 20.2 ± 7.8b (APACHE II) | 67.0 ± 27.5b (APACHE IV) | / |
Definition of Vitamin D deficiency, insufficiency and sufficiency
| Deficient (<20 ng/ml), insufficient (≥20 and <30 ng/ml), normal (≥30 ng/ml) | Insufficient (<20 ng/ml), sufficient (≥20 ng/ml) | Deficient (<20 ng/ml), insufficient (≥20 and <30 ng/ml), sufficient (≥30 ng/ml) | Deficient (<10 ng/ml), insufficient(10 to 20 ng/ml), sufficient(>20 ng/ml) | Deficient (≤12 ng/ml), insufficient (>12 to ≤24 ng/ml), sufficient (>24 ng/ml) | deficient (<20 ng/ml), insufficient (≥20 and <30 ng/ml), sufficient (≥30 ng/ml) | deficient(≤15 ng/mL, insufficient (16 to 29 ng/mL, sufficient (≥30 ng/ mL) |
Major clinical outcomes
| ICU and hospital mortality, ICU and hospital LOS | ICU mortality | Hospital mortality | Hospital mortality, ICU and hospital LOS | Hospital mortality, time-to-alive ICU discharge | Hospital mortality, hospital LOS | 30-day, 90-day, 365-day, and in-hospital morality |
Quality score
c
| 7 | 6 | 6 | 7 | 7 | 6 | 7 |
Overall results
Study | Year | Vitamin D classification | ICU length of stay (days) |
---|---|---|---|
2014 | Deficiency, <20 ng/ml | 6.9 (9.8)a | |
insufficiency, 20 to 30 ng/ml | 4.9 (7.7)a | ||
sufficiency, >30 ng/ml | 5.2 (6.5)a | ||
2013 | Insufficiency, <20 ng/ml | 9 (5, 14)b | |
sufficiency, ≥20 ng/ml | 8 (5, 13)b | ||
2013 | Deficiency, <20 ng/ml | 10.5 (6.8, 25.3)b | |
insufficiency, 20 to 30 ng/ml | 8.6 (6.9, 20.5)b | ||
sufficiency, >30 ng/ml | 15.2 (10.3, 23.6)b | ||
2012 | Deficiency, <10 ng/ml | 12 (2, 14)b | |
insufficiency,10 to 20 ng/ml | 7 (4, 15)b | ||
sufficiency, >20 ng/ml | 4 (3, 10)b | ||
2012 | Deficient, ≤12 ng/ml | 10.6 ± 8.4c | |
insufficient, 12 to 24 ng/ml | 6.8 ± 6.0c | ||
sufficient, >24 ng/ml | 5.9 ± 5.4c | ||
2011 | Deficiency, <20 ng/ml | 4.3 ± 4.5c | |
insufficiency, 20 to 30 ng/ml | 3.7 ± 3.9c | ||
sufficiency, >30 ng/ml | 4.2 ± 3.7c | ||
2011 | - | - |
Subgroup and sensitivity analyses
Analyses | Studies, n | Odds ratio (95% CI) |
Ρ
heterogeneity
|
I
2
|
---|---|---|---|---|
Subgroup analysis
| ||||
7 | 1.76 (1.38, 2.24) | 0.402 | 2.3% | |
25(OH)D level as a cutoff for vitamin D deficiency | ||||
3 | 2.12 (1.35, 3.34) | 0.198 | 38.3% | |
15 ng/ml [17] | 1 | 1.72 (1.27, 2.33) | - | - |
12 ng/ml [20] | 1 | 1.12 (0.45, 2.70) | - | - |
10 ng/ml [21] | 1 | 1.13 (0.18, 7.27) | - | - |
Sensitivity analysis
| ||||
3 | 1.63 (1.23, 2.17) | 0.623 | 0.0% | |
3 | 1.83 (1.03, 3.24) | 0.241 | 29.7% | |
One-study-out method | ||||
Amrein [22] | 1 | 1.79 (1.23, 2.70) | 0.284 | 20.5% |
Hu [18] | 1 | 1.67 (1.30, 2.15) | 0.511 | 0.0% |
Nair [21] | 1 | 1.77 (1.39, 2.26) | 0.298 | 18.3% |
Higgins [20] | 1 | 1.82 (1.42, 2.34) | 0.396 | 1.8% |
Venkatram [8] | 1 | 1.72 (1.35, 2.19) | 0.571 | 0.0% |
Braun [17] | 1 | 1.82 (1.23, 2.70) | 0.281 | 21.0% |
Fixed-effects versus random-effects model method | ||||
Fixed-effects model | 6 | 1.76 (1.38, 2.24) | 0.402 | 2.3% |
Random-effects model | 6 | 1.76 (1.37, 2.26) | 0.402 | 2.3% |
Publication bias
Discussion
Main findings
Possible mechanism
Clinical implications
Strengths and limitations
Conclusions
Key messages
-
Vitamin D deficiency is associated with increased incidence of hospital mortality in critically ill adult patients
-
Current evidence about vitamin D deficiency and increased ICU mortality is still not sufficient to draw a firm conclusion
-
More studies should probe further into the effect on ICU mortality in critically ill adult patients