3.1. Patient selection
Patient selection process was shown in Figure S1. Criteria of exclusion as follows:(1) aged ≤16 years (n= 200) ;(2) duration of stay in ICU <24 hours(n=1037). (3) patients without ICU mortality data(n=38); (4) patients lacked Mg (n=1461). Finally, we enrolled totally 2026 eligible patients.
3.2. Baseline characteristics
Baseline characteristics of patients were shown in supplementary material (Table S1). We categorized the patients into two groups: those with and without hypomagnesemia based on the total Mg levels. The mean age was 61.8 years (female: 44.8%). Compared with patients without hypomagnesemia, those with hypomagnesemia had a significantly lower SOFA score, SBP, BMI, lower levels of PLT count, hemoglobin, creatinine, calcium and had a lower incidence of hypertension and renal disease.
Table 1. The endpoints in patients without and with hypomagnesemia
|
Hypomagnesemia
|
P-value
|
Total
|
Without
|
With
|
N
|
2026
|
1537
|
489
|
|
ICU mortality, N (%)
|
277 (13.7)
|
186 (12.1)
|
91 (18.6)
|
<0.001
|
ICU stay time, hour
|
166.1 ± 323.3
|
151.7 ± 169.0
|
211.1 ± 584.1
|
<0.001
|
Mechanical ventilation, N (%)
|
924 (45.6)
|
631 (41.1)
|
293 (59.9)
|
<0.001
|
Note: Continuous variables were presented as mean ± SD, categorical variables were presented as numbers (%). For continuous variable, Kruskal Wallis rank sum test is used. If the counting variable has a theoretical number <10, it is obtained by Fisher’s exact probability test.
Abbreviations: ICU, intensive care unit.
3.3. The outcomes
Table 1shows the primary and secondary outcomes in patients without and with hypomagnesemia.TheICU mortalitywas significantly difference (P < 0.001) between the hypomagnesemia group (18.6%) and the non-hypomagnesemia group (12.1%). Compared with the patients without hypomagnesemia, those with hypomagnesemia had a longer ICU stay, with an average ICU stay of 211.1 hours (P < 0.001), and a higher risk of mechanical ventilation use (59.9% vs 41.1%, P < 0.001).
Table 2. The results of univariate analysis of ICU mortality
Variables
|
ICU mortality
|
OR (95%CI)
|
P-value
|
No Mean ± SD/N (%)
|
Yes Mean ± SD/N (%)
|
Overall
|
1749
|
277
|
|
|
Age, years
|
61.9 ± 17.4
|
61.0 ± 16.6
|
1.00 (0.99, 1.00)
|
0.463
|
Gender, N (%)
|
|
|
|
|
Female
|
795 (45.5)
|
111 (40.1)
|
Ref
|
|
Male
|
952 (54.5)
|
166 (59.9)
|
1.25 (0.96, 1.62)
|
0.092
|
Race/ethnicity, N (%)
|
|
|
|
|
Caucasian
|
1303 (74.5)
|
206 (74.4)
|
Ref
|
|
African American
|
201 (11.5)
|
21 (7.6)
|
0.66 (0.41, 1.06)
|
0.086
|
Hispanic
|
91 (5.2)
|
15 (5.4)
|
1.04 (0.59, 1.84)
|
0.885
|
Asian
|
34 (1.9)
|
12 (4.3)
|
2.23 (1.14, 4.38)
|
0.020
|
Native American
|
8 (0.5)
|
0 (0.0)
|
|
0.968
|
Other/Unknown
|
112 (6.4)
|
23 (8.3)
|
1.30 (0.81, 2.08)
|
0.278
|
SOFA score
|
|
|
|
|
≤ 6
|
1269 (72.6)
|
86 (31.0)
|
Ref
|
|
> 6
|
480 (27.4)
|
191 (69.0)
|
5.87 (4.46, 7.73)
|
<0.001
|
Hypertension
|
|
|
|
|
No
|
842 (48.1)
|
129 (46.6)
|
Ref
|
|
Yes
|
907 (51.9)
|
148 (53.4)
|
1.07 (0.83, 1.37)
|
0.627
|
Coronary artery disease
|
|
|
|
|
No
|
1612 (92.2)
|
252 (91.0)
|
Ref
|
|
Yes
|
137 (7.8)
|
25 (9.0)
|
1.17 (0.75, 1.82)
|
0.497
|
Congestive heart failure
|
|
|
|
|
No
|
1640 (93.8)
|
253 (91.3)
|
Ref
|
|
Yes
|
109 (6.2)
|
24 (8.7)
|
1.43 (0.90, 2.26)
|
0.131
|
Diabetes
|
|
|
|
|
No
|
1425 (81.5)
|
211 (76.2)
|
Ref
|
|
Yes
|
324 (18.5)
|
66 (23.8)
|
1.38 (1.02, 1.86)
|
0.038
|
Chronic pulmonary disease
|
|
|
|
|
No
|
1651 (94.4)
|
253 (91.3)
|
Ref
|
|
Yes
|
98 (5.6)
|
24 (8.7)
|
1.60 (1.00, 2.55)
|
0.048
|
Stroke
|
|
|
|
|
No
|
1531 (87.5)
|
245 (88.4)
|
Ref
|
|
Yes
|
218 (12.5)
|
32 (11.6)
|
0.92 (0.62, 1.36)
|
0.668
|
Malignant cancer
|
|
|
|
|
No
|
1621 (92.7)
|
259 (93.5)
|
Ref
|
|
Yes
|
128 (7.3)
|
18 (6.5)
|
0.88 (0.53, 1.47)
|
0.624
|
Renal disease
|
|
|
|
|
No
|
1663 (95.1)
|
253 (91.3)
|
Ref
|
|
Yes
|
86 (4.9)
|
24 (8.7)
|
1.83 (1.14, 2.94)
|
0.012
|
SBP, mmHg
|
130.6 ± 15.4
|
128.1 ± 18.2
|
0.99 (0.98, 0.99)
|
0.019
|
DBP, mmHg
|
69.2 ± 10.6
|
68.5 ± 12.1
|
0.99 (0.98, 1.01)
|
0.335
|
BMI, kg/m2
|
27.8 ± 6.7
|
28.6 ± 7.0
|
1.02 (1.00, 1.04)
|
0.075
|
WBC count, ×103/μL
|
11.5 ± 7.8
|
14.6 ± 17.4
|
1.05 (1.02, 1.07)
|
0.000
|
HB, g/mL
|
12.5 ± 2.1
|
12.1 ± 2.3
|
0.91 (0.86, 0.97)
|
0.002
|
PLT, ×103/uL
|
212.7 ± 76.2
|
203.4 ± 96.4
|
1.00 (1.00, 1.00)
|
0.069
|
Calcium, mg/dL
|
8.6 ± 0.7
|
8.3 ± 0.8
|
0.62 (0.52, 0.74)
|
<0.001
|
Creatinine, mg/dL
|
1.1 ± 1.1
|
1.4 ± 1.5
|
1.20 (1.10, 1.31)
|
<0.001
|
Abbreviations: SD, standard deviation; SOFA, sequential organ failure assessment; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; HB, hemoglobin; PLT, platelet.
3.4. The results of univariate analysis of ICU mortality
Table 2 showed the results of univariate analysis. The univariate analysis demonstrated that the patients with higher levels of WBC count, creatinine, lower SOFA score and the history of diabetes, chronic pulmonary disease and renal disease had higher risk of ICU mortality, whereas SBP, hemoglobin and Ca were negatively related with the risk of ICU mortality.
3.5. Association of hypomagnesemia with ICU mortality
Table 3 shows that hypomagnesemia was related to increased risk of ICU mortality, prolonged ICU length of stay and increased use of mechanical ventilation in patients with ICH. In model 1, patients with hypomagnesemia had a 66% increased risk of ICU mortality (OR = 1.66, 95% CI: 1.26-2.19, P < 0.001) and a 115% increased use of mechanical ventilation (OR = 2.15, 95% CI: 1.74-2.64, P < 0.001) compared with patients without hypomagnesemia. Furthermore , patients with hypomagnesemia had 59.38 hours longer hospital stays (β = 59.38, 95% CI: 26.58-92.19, P < 0.001) compared with those without hypomagnesemia. In model 3, compared to patients without hypomagnesemia, the risk of ICU mortality in patients with hypomagnesemia increased by 38% (OR = 1.38, 95% CI: 1.01-1.88, P = 0.042) and the risk of mechanical ventilation increased by 67% (OR = 1.67, 95% CI: 1.28-2.19, P < 0.001). Compared to patients without hypomagnesemia, ICU stay time in patients with hypomagnesemia increased by 45.11 hour (β = 45.11, 95% CI:10.62-79.61, P = 0.010) .
Table 3. Association of hypomagnesemia with ICU mortality
Endpoints
|
Model 1
|
|
Model 2
|
|
Model 3
|
OR (95%CI)
|
P-value
|
|
OR (95%CI)
|
P-value
|
|
OR (95%CI)
|
P-value
|
ICU mortality
|
|
|
|
|
|
|
|
|
Non-hypomagnesemia
|
Ref
|
|
|
Ref
|
|
|
Ref
|
|
Hypomagnesemia
|
1.66 (1.26, 2.19)
|
<0.001
|
|
1.67 (1.27, 2.21)
|
<0.001
|
|
1.38 (1.01, 1.88)
|
0.042
|
ICU stay time, hour
|
|
|
|
|
|
|
|
|
Non-hypomagnesemia
|
Ref
|
|
|
Ref
|
|
|
Ref
|
|
Hypomagnesemia
|
59.38 (26.58, 92.19)
|
<0.001
|
|
56.63 (23.71, 89.56)
|
<0.001
|
|
45.11 (10.62, 79.61)
|
0.010
|
Mechanical ventilation
|
|
|
|
|
|
|
|
|
Non-hypomagnesemia
|
Ref
|
|
|
Ref
|
|
|
Ref
|
|
Hypomagnesemia
|
2.15 (1.74, 2.64)
|
<0.001
|
|
2.12 (1.71, 2.62)
|
<0.001
|
|
1.67 (1.28, 2.19)
|
<0.001
|
Model 1: no covariates were adjusted.
Model 2: adjusted for age, gender, race/ethnicity.
Model 3: adjusted for: age, gender, race/ethnicity, SOFA score, comorbidities (hypertension, coronary artery disease, congestive heart failure, diabetes, chronic pulmonary disease, stroke, malignant cancer, renal disease), systolic blood pressure, diastolic blood pressure, white blood cell, hemoglobin, platelet, calcium, creatinine.
Abbreviations: OR, odds ratio; 95%CI, 95% confidence interval; ICU, intensive care units.
3.6. Subgroup analysis
Figure 1 showed that the stratification and interaction analyses of the relationship between hypomagnesemia and ICU mortality. The results obtained from the stratified analysis corroborated the findings observed in the multivariable logistic regression analysis. The interaction analysis showed that there were significant statistically interactions in the subgroups of stroke (P = 0.021).
Figure 1. Association between hypomagnesemia and ICU mortality according to subgroup. Each stratification adjusted for age, gender, race/ethnicity, SOFA score, comorbidities (hypertension, coronary artery disease, congestive heart failure, diabetes, chronic pulmonary disease, stroke, malignant cancer, renal disease), mean systolic blood pressure, mean diastolic blood pressure, white blood cell, hemoglobin, platelet, calcium, creatinine, except the stratification factor itself.
3.7. Kaplan–Meier survival curve
As shown in Figure 2, the results of Kaplan-Meier survival curve shows that patients in the non-hypomagnesemia group had a significantly higher survival rate than those with hypomagnesemia within 30 days of ICU stay (P = 0.030).