The Effect of Thiamine, Ascorbic Acid, and the Combination of Them on the Levels of Matrix Metalloproteinase-9 (MMP-9) and Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) in Sepsis Patients

Figures & data

Table 1 Normality Test in 147 Subjects

Variables	p-value
Age	0.200*
Sex	0.001
Mean arterial pressure (MAP)	0.200*
Lactate	0.001
SOFA score	0.010
Neutrophil and lymphocyte ratio (NLR)	0.004
MMP-9 pre treatment	0.001
MMP-9 post treatment	0.031
TIMP-1 pre treatment	0.001
TIMP-1 post treatment	0.001

Note: *Kruskall Wallis test, normal distribution if p>0.05.

Abbreviations: MAP, Mean Arterial Pressure; SOFA, Sequential Organ Failure Assessment; MMP-9, Matrix metalloproteinase-9; TIMP-1, Tissue Inhibitor Of Matrix Metalloproteinase-1.

Figure 1 Flow of Patients Through the Ascorbic Acid, Thiamine and Combination of Them in Septic Patients.

Table 2 Baseline Characteristics of the Study Population

Characteristics	NaCl 0.9%	Thiamine	Ascorbic Acid	Combination
Age, years (mean ± SD)	48.8 ± 18.4	52.3 ± 16.8	53.3 ± 11.7	50.7 ± 11.1
Sex
Male, n (%)	10 (38.5)	10 (50.0)	12 (50.0)	11 (68.8)
Female, n (%)	16 (61.5)	10 (50.0)	12 (50.0)	5 (31.3)
MAP, mmHg (mean ± SD)	94.8 ± 17.0	97.6 ± 25.4	91.4 ± 16.0	92.4 ± 16.0
Lactate, mmol/L median (min-maks)	2.0 (1–10.0)	1.3 (1.0–5.5)	1.0 (1–10.0)	2.0 (1.0–4.0)
SOFA, median (min-max)	6 (2–18)	7 (3–14)	7 (2–18)	6 (2–12)
NLR, median (min-max)	10.6 (2.5–30.3)	14.4 (0.2–86.8)	13.9 (1.6–69.3)	10.7 (1.4–64.6)

Abbreviations: MAP, Mean Arterial Pressure; SOFA, Sequential Organ Failure Assessment.

Figure 2 Kaplan Meier survival curve in non-survival subjects within 72 hours of observation.

Figure 3 Scatterplot graph of MMP-9 and TIMP-1 levels in sepsis patients who did not survive during observation.

Figure 4 Scatterplot graph of MMP-9, TIMP-1 levels, and MMP-9/TIMP-1 ratio in sepsis patients who did not survive during observation.

Figure 5 Scatterplot graph of changes in MMP-9, TIMP-1 level, and MMP-9/TIMP-1 ratio in sepsis patients who survived during observation.

Table 3 Comparison of MMP-9 Level in 3 Groups

MMP-9 Level (ng/mL)	NaCl 0.9% (n=26)	Thiamine (n=20)	Ascorbic Acid (n=24)	Combination (n=16)	p-value
Before treatment
Mean ± SD	983.8 ± 544.0	1312.8 ± 419.5	1133.1 ± 551.1	1289.3 ± 564.4	0.166
After treatment
Mean ± SD	1236.6 ± 658.3	1168.9 ± 455.5	938.0 ± 587.7	1057.8 ± 561.1	0.455
Difference
Mean ± SD	252.8 ± 646.8	−143.8 ± 436.3	−195.0 ± 458.4	−231.5 ± 345.5	0.113
p-value	0.662	0.135	0.04	0.026

Abbreviations: MMP-9, Matrix metalloproteinase-9. Statistical significance if p<0.05, CI 95%.

Table 4 Comparison of TIMP-1 Level in 3 Groups

TIMP-1 Level (ng/mL)	NaCl 0.9% (n=26)	Thiamine (n=20)	Ascorbic Acid (n=24)	Combination (n=16)	p-value
Before treatment
Mean ± SD	644.5 ± 371.1	581.8 ± 131.8	569.6 ± 161.2	587.1 ± 146.4	0.939
After treatment
Mean ± SD	783.2 ± 330.7	584.8 ± 185.0	540.0 ± 167.7	552.3 ± 194.5	0.016
Difference
Mean ± SD	138.7±320.5	2.9 ± 121.3	−29.6 ± 121.5	−34.7 ± 139.1	0.076
p-value	0.045	0.709	0.304	0.379

Abbreviations: TIMP-1, Tissue Inhibitor Of Matrix Metalloproteinase-1. Statistical significance if p<0.05, CI 95%.

Table 5 Linear Regression Analysis Between the Balance of MMP-9/TIMP-1 with Levels of MMP-9 and TIMP-1 in Sepsis Patients

Variables	NaCl 0.9% (n=26)	Thiamine (n=20)	Ascorbic Acid (n=24)	Combination (n=16)
MMP-9
Beta	0.415*	0.445*	0.457*	0.070
R^2	0.172	0.198	0.209	0.005
p-value	0.035	0.05	0.025	0.798
TIMP-1
Beta	−0.120	−0.520*	−0.383	−0.173
R^2	0.014	0.270	0.147	0.030
p-value	0.558	0.019	0.064	0.522

Notes: *Pearson correlation test, independent-t test, Statistical significance if p<0.05, CI 95%.

Abbreviations: MMP-9, Matrix metalloproteinase-9; TIMP-1, Tissue Inhibitor Of Matrix Metalloproteinase-1.