Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (37)
- Singer M, "The third international consensus definitions for sepsis and septic shock(Sepsis-3)", JAMA, 315, pp.801~810 (2016)
- Rudd KE, "Global, regional, and national sepsis incidence and mortality, 1990-2017 : analysis for the Global Burden of Disease Study", Lancet, 395, pp.200~211 (2020)
- Gotts JE, "Sepsis : pathophysiology and clinical management", BMJ, 353, pp.i1585~ (2016)
- Laterre PF, "Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab(HAM8101)in septic shock patients : the AdrenOSS-2 phase 2a biomarker-guided trial", Intensive Care Med, 47, pp.1284~1294 (2021)
- Kashiouris MG, "The emerging role of vitamin c as a treatment for sepsis", Nutrients, 12, pp.292~ (2020)
- Barabutis N, "Hydrocortisone and ascorbic acid synergistically prevent and repair lipopolysaccharide-induced pulmonary endothelial barrier dysfunction", Chest, 152, pp.954~962 (2017)
- Donnino MW, "Thiamine deficiency in critically ill patients with sepsis", J Crit Care, 25, pp.576~581 (2010)
- Assouline B, "Thiamine, ascorbic acid, and hydrocortisone as a metabolic resuscitation cocktail in sepsis : a meta-analysis of randomized controlled trials with trial sequential analysis", Crit Care Med, 49, pp.2112~2120 (2021)
- Sato R, "Effect of IV high-dose vitamin C on mortality in patients with sepsis : a systematic review and meta-analysis of randomized controlled trials", Crit Care Med, 49, pp.2121~2130 (2021)
- Lamontagne F, "Intravenous vitamin C in adults with sepsis in the intensive care unit", N Engl J Med, 386, pp.2387~2398 (2022)
- Iglesias J, "A 33-mRNA classifier is able to produce inflammopathic, adaptive, and coagulopathic endotypes with prognostic significance : the outcomes of metabolic resuscitation using ascorbic acid, thiamine, and glucocorticoids in the early treatment of sepsis(ORANGES)trial", J Pers Med, 11, pp.9~ (2020)
- Kim WY, "Subphenotypes in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine : a retrospective cohort analysis", Nutrients, 11, pp.2976~ (2019)
- Rhodes A, "Surviving sepsis campaign : international guidelines for management of sepsis and septic shock : 2016", Intensive Care Med, 43, pp.304~377 (2017)
- Knaus WA, "APACHE II : a severity of disease classification system", Crit Care Med, 13, pp.818~829 (1985)
- Vincent JL, "The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction", failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine, 1996, pp.22, 707~710
- Khanna A, "Angiotensin II for the treatment of vasodilatory shock", N Engl J Med, 377, pp.419~430 (2017)
- ARDS Definition Task Force, "Acute respiratory distress syndrome : the Berlin Definition", JAMA, 307, pp.2526~2533 (2012)
- de Grooth HJ, "Vitamin C for sepsis and acute respiratory failure", JAMA, 323, pp.792~ (2020)
- Nagin DS, "Group-based multi-trajectory modeling", Stat Methods Med Res, 27, pp.2015~2023 (2018)
- Magrini A, "Assessment of agricultural sustainability in European Union countries : a group-based multivariate trajectory approach", AStA Adv Stat Anal, 106, pp.673~703 (2022)
- Calfee CS, "Subphenotypes in acute respiratory distress syndrome : latent class analysis of data from two randomised controlled trials", Lancet Respir Med, 2, pp.611~620 (2014)
- Calfee CS, "Acute respiratory distress syndrome subphenotypes and differential response to simvastatin : secondary analysis of a randomised controlled trial", Lancet Respir Med, 6, pp.691~698 (2018)
- Antcliffe DB, "Transcriptomic signatures in sepsis and a differential response to steroids. from the VANISH Randomized Trial", Am J Respir Crit Care Med, 199, pp.980~986 (2019)
- Fowler AA 3rd, "Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis", J Transl Med, 12, pp.32~ (2014)
- Zhang J, "Pilot trial of high-dose vitamin C in critically ill COVID-19 patients", Ann Intensive Care, 11, pp.5~ (2021)
- Bhavani SV, "Identifying novel sepsis subphenotypes using temperature trajectories", Am J Respir Crit Care Med, 200, pp.327~335 (2019)
- Kellum JA, "Relationship between alternative resuscitation strategies, host response and injury biomarkers, and outcome in septic shock : analysis of the protocol-based care for early septic shock study", Crit Care Med, 45, pp.438~445 (2017)
- Kang S, "Targeting interleukin-6 signaling in clinic", Immunity, 50, pp.1007~1023 (2019)
- Stanic B, "IL-10-overexpressing B cells regulate innate and adaptive immune responses", J Allergy Clin Immunol, 135, pp.771~780 (2015)
- Matsumoto H, "The clinical importance of a cytokine network in the acute phase of sepsis", Sci Rep, 8, pp.13995~ (2018)
- Weidhase L, "Is Interleukin-6 a better predictor of successful antibiotic therapy than procalcitonin and C-reactive protein? : a single center study in critically ill adults", BMC Infect Dis, 19, pp.150~ (2019)
- Härtel C, "Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes", Cytokine, 27, pp.101~106 (2004)
- van der Poll T, "The immunopathology of sepsis and potential therapeutic targets", Nat Rev Immunol, 17, pp.407~420 (2017)
- Black S, "C-reactive Protein", J Biol Chem, 279, pp.48487~48490 (2004)
- Nakamura K, "C-reactive protein clustering to clarify persistent inflammation, immunosuppression and catabolism syndrome", Intensive Care Med, 46, pp.437~443 (2020)
- Frommelt MA, "Letter on Update to the vitamin C, thiamine, and steroids in sepsis(VICTAS)protocol", Trials, 21, pp.350~ (2020)
- Jung SY, "Vitamin C for ≥ 5 days is associated with decreased hospital mortality in sepsis subgroups : a nationwide cohort study", Crit Care, 26, pp.3~ (2022)
