Acute Crit Care.  2023 Aug;38(3):286-297. 10.4266/acc.2023.00507.

Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea

• You SH
• Kweon OJ
• Jung SY
• Baek MS
• Kim WY

• KMID: 2547022
• DOI: http://doi.org/10.4266/acc.2023.00507

Abstract

Background
Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine.
Methods
This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1–2, 3–4, and 6–8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups.
Results
The median age was 78 years (interquartile range, 70–84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: –0.09±0.16 μg/kg/min vs. –0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. –4±3, P=0.002) between days 1 and 4.
Conclusions
There may be different subphenotypes in septic patients receiving the vitamin C protocol.

Keyword

ascorbic acid; hydrocortisone; immune system; septic shock; thiamine

Figure

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  Figure 1. Patient inclusion flowchart. ICU: intensive care unit.

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  Figure 2. Clustering of inflammatory responses in septic patients receiving the vitamin C protocol. Group-based multi-trajectory modeling reveals two subphenotypes of inflammatory immune responses (group 1, 41 patients; group 2, 54 patients). The mean changes in (A) lymphocyte counts, (B) C-reactive protein levels, (C) Interleukin (IL)-6 levels, (D) tumor necrosis factor (TNF)-α levels, and (E) IL-10 levels in groups 1 and 2 during the study period.

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  Figure 3. Mean changes in (A) vasopressor dose (norepinephrine equivalent) and (B) Sequential Organ Failure Assessment (SOFA) score by group during the study period. a)P<0.05, b)P<0.01 when group 1 and group 2 are compared using the Mann-Whitney U-test.

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