Objective To investigate the clinical features of patients with sepsis-induced cholestatic jaundice and the risk factors for death.Methods A retrospective analysis was performed for the clinical data of 139 patients with sepsis-induced cholestatic jaundice who were admitted to Surgical Intensive Care Unit, Critical Care Medicine Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, from August 2011 to August 2019, and the patients were divided into survival group with 62 patients and death groupwith 77 patients. Age, sex, Acute Physiology and Chronic Health Evaluation II(APACHEII) score, and infection sites were recorded; re-lated laboratory data at five time points were recorded, including total bilirubin(TBil), direct bilirubin(DBil), indirect bilirubin(IBil),prothrombin time(PT), international normalized ratio(INR), aspartate aminotransferase(AST), alanine aminotransferase(ALT), whiteblood cell count(WBC), neutrophils(NEU), procalcitonin(PCT), and lactic acid(Lac); the peak values of TBil, DBil, and IBil werealso recorded, as well as duration of use of vasoactive agent, duration of mechanical ventilation, number of times of artificial liver plasma ex-change, length of stay in the intensive care unit(ICU), Child-Pugh class, and jaundice grade. The independent samplest-test was usedfor comparison of normally distributed continuous data with homogeneity of variance between groups, and the Mann-WhitneyUtest wasused for comparison of non-normally distributed continuous data with heterogeneity of variance between groups; the chi-square test wasused for comparison of categorical data between groups; a binary logistic regression analysis was used to investigate the risk factors for death.Results The mortality rate of patients with sepsis-induced cholestatic jaundice was 55. 4%. Compared with the death group, the survivalgroup had significantly lower levels of TBil, DBil, and IBil on days 14, 21, and 28 and significantly lower peak values of TBil, DBil, andIBil(TBil:Z=-3. 230,-8. 197, and-9. 281,t=-5. 371, allP< 0. 01; DBil:Z=-4. 708,-8. 633,-9. 579, and-8. 238,P< 0. 01; IBil:Z=-2. 402,-6. 522,-8. 113, and-5. 300, allP< 0. 01). The survival group had a higher proportion of patients withmoderate jaundice, while the death group had a higher proportion of patients with severe jaundice (χ2 =57.633,P< 0. 01). Compared withthe death group, the survival group had significantly lower PT and INR at all time points(at diagnosis and on days 7, 14, 21, and 28)(PT:Z=-3. 173,-3. 467,-2. 660,-2. 261, and-3. 120, allP< 0. 05; INR:Z=-3. 141,-2. 754,-3. 230,-2. 560, and-3. 229, allP< 0. 05) and significantly lower levels of AST on days 7, 14, 21, and 28(Z=-2. 484,-3. 200,-3. 298, and-4. 277, allP< 0. 05) and ALT on days 14, 21, and 28(Z=-2. 635,-2. 667, and-4. 656, allP< 0. 01). Compared with thedeath group, the survival group had significantly lower levels of WBC and NEU on days 7, 14, and 21(WBC:Z=-3. 229,-2. 987, and-4. 537, allP< 0. 01; NEU:t =-3.332,Z=-3. 107 and-4. 485, allP< 0. 01), as well as significantly lower PCT at diagnosis andon days 14, 21, and 28(Z =-4. 844,-2. 215,-2. 869, and-7. 442, allP< 0. 05) and Lac at all time points(at diagnosis and ondays 7, 14, 21, and 28)(Z=-4. 316,-2. 913,-3. 068,-8. 578, and-9. 341, allP< 0. 01). Compared with the death group, thesurvival group had significantly shorter duration of use of vasoactive agent(Z=-6. 421,P< 0. 01), duration of mechanical ventilation(Z =-2.005,P< 0. 05), duration of artificial liver(Z =-4.822,P< 0. 01), and length of stay in the ICU(t =-3.005,P< 0. 01).TBil(odds ratio [OR] = 0. 959, 95% confidence interval [ CI]: 0. 929-0. 991,P< 0. 05), DBil( OR = 1. 056, 95% CI: 1. 009-1. 105,P< 0. 05), IBil(OR = 1. 071, 95% CI: 1. 006-1. 140,P< 0. 05), WBC on day 7(OR = 31. 365, 95% CI: 2. 878-41. 761,P< 0. 05), WBC on day 14(OR = 5. 859, 95% CI: 1. 073-31. 999,P< 0. 05), NEU on day 7(OR = 0. 007, 95% CI: 0. 003-0. 409,P< 0. 05), NEU on day 14(OR = 0. 132, 95% CI: 0. 023-0. 765,P< 0. 05), PCT at diagnosis(OR = 1. 062, 95% CI: 1. 017-1. 110,P< 0. 05), PCT on day 7(OR = 0. 920, 95% CI: 0. 855-0. 990,P< 0. 05), PCT on day 28(OR = 12. 711, 95% CI: 3. 532-45. 745,P< 0. 05), duration of use of vasoactive agent(OR =1. 657, 95% CI: 1. 337-2. 053,P<0. 05), duration of mechanical ventilation(OR =0. 783, 95% CI: 0. 634-0. 967,P<0. 05), and duration of artificial liver(OR =1. 534, 95% CI: 1. 065-2. 208,P<0. 05) were independ-ent risk factors for death in patients with sepsis-induced cholestatic jaundice.Conclusion Patients with sepsis-induced cholestatic jaundicehave a high mortality rate. The survival group has significantly lower levels and peak values of bilirubin than the death group in the middle andlate stages of the disease, and there is a higher proportion of patients with moderate jaundice in the survival group and a higher proportion of pa-tients with severe jaundice in the death group. Compared with the death group, the survival group has significantly lower degree of coagulationdisorder, levels of AST and ALT, infection indices WBC, NEU, and PCT, and perfusion index Lac. Compared with the death group, the sur-vival group has significantly better duration of use of vasoactive agent, duration of artificial liver support, duration of mechanical ventilation,and length of stay in the ICU. Bilirubin levels, infection indices WBC, NEU, and PCT, vasoactive agent, duration of mechanical ventilation,and duration of artificial liver support are independent risk factors for death in patients with sepsis-induced cholestatic jaundice.
[1] HU YJ, SONG JC. Research Progress on markers of endothelial cell dysfunction in sepsis[J]. Clin J Med Offic, 2020, 48(3):355-358.(in Chinese)胡艳晶,宋景春.脓毒症时内皮细胞功能损伤标志物研究进展[J].临床军医杂志,2020, 48(3):355-358.
|
[2] MINEMURA M, TAJIRI K, SHIMIZU Y. Liver involvement in systemic infection[J]. World J Hepatol, 2014, 6(9):632-642.
|
[3] KORTGEN A, PAXIAN M, WERTH M, et al. Prospective assessment of hepatic function and mechanisms of dysfunction in the critically ill[J]. Shock, 2009, 32(4):358-365.
|
[4] JENNISKENS M, LANGOUCHE L, van den BERGHE G. Cholestatic alterations in the critical y il:Some new light on an old problem[J]. Chest, 2018, 153(3):733-743.
|
[5] STRNAD P, TACKE F, KOCH A, et al. Liver-guardian, modifier and target of sepsis[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(1):55-66.
|
[6] GRZÖGER M, RENNERT K, GISZAS B, et al. Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model[J]. Sci Rep, 2016, 6:21868.
|
[7] SINGER M, DEUTSCHMAN CS, SEYMOUR CW, et al. The third international consensus definitions for sepsis and septic shock(sepsis-3)[J]. JAMA, 2016, 315(8):801-810.
|
[8] MARSHALL JC. New translational research provides insights into liver dysfunction in sepsis[J]. PLoS Med, 2012, 9(11):e1001341.
|
[9] JÄGER B, DROLZ A, MICHL B, et al. Jaundice increases the rate of complications and one-year mortality in patients with hypoxic hepatitis[J]. Hepatology, 2012, 56(6):2297-2304.
|
[10] KAFFARNIK MF, LOCK JF, VETTER H, et al. Early diagnosis of sepsis-related hepatic dysfunction and its prognostic impact on survival:A prospective study with the LiMAx test[J].Crit Care, 2013, 17(5):R259.
|
[11] WANG D, YIN Y, YAO Y. Advances in sepsis-associated liver dysfunction[J]. Burns Trauma, 2014, 2(3):97-105.
|
[12] FAMULARO G, de SIMONE C, NICOTRA GC. Jaundice and the sepsis syndrome:A neglected link[J]. Eur J Intern Med,2003, 14(4):269-271.
|
[13] NESSELER N, LAUNEY Y, ANINAT C, et al. Liver dysfunction is associated with long-term mortality in septic shock[J]. Am J Respir Crit Care Med, 2016, 193(3):335-337.
|
[14] de JONG E, van OERS JA, BEISHUIZEN A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients:A randomised,controlled, open-label trial[J]. Lancet Infect Dis, 2016, 16(7):819-827.
|
[15] BAI ZH, SHI Y, WANG H, et al. Analysis of liver function characteristics in patients with sepsis admitted to emergency department[J]. J Clin Emerg, 2018, 19(11):771-774.(in Chinese)白郑海,时雨,王海,等.急诊脓毒症患者入院时肝功能特征分析[J].临床急诊杂志,2018, 19(11):771-774.
|
[16] HOSHINO K, KITAMURA T, NAKAMURA Y, et al. Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis[J]. J Intensive Care, 2017, 5(1):42.
|
[17] HUANG Q, ZHANG HB, LI JT, et al. Research advances in the mechanism of action of intestinal microecology in intrahepatic cholestasis[J]. J Clin Hepatol, 2019, 35(10):2355-2359.(in Chinese)黄倩,张海博,李京涛,等.肠道微生态在肝内胆汁淤积中的作用机制[J].临床肝胆病杂志,2019, 35(10):2355-2359.
|
[18] BHOGAL HK, SANYAL AJ. The molecular pathogenesis of cholestasis in sepsis[J]. Front Biosci(Elite Ed), 2013, 5:87-96.
|
[19] XIONG ZM. The value of PCT, CRP and FDP in the diagnosis of sepsis in children[J]. Trauma Crit Med, 2019, 7(5):328-330.(in Chinese)熊子明.PCT、CRP、FDP诊断儿童脓毒症价值研究[J].创伤与急危重病医学,2019, 7(5):328-330.
|
[20] DROLZ A, HORVATITS T, ROEDL K, et al. Shock liver and cholestatic liver in critically ill patients[J]. Med Klin Intensivmed Notfmed, 2014, 109(4):228-234.
|
[21] YU YC, CHEN CW. Current status and research interests of the diagnosis and treatment of cholestatic liver disease[J]. J Clin Hepatol, 2019, 35(2):241-246.(in Chinese)于乐成,陈成伟.胆汁淤积性肝病的诊治现状及研究方向[J].临床肝胆病杂志,2019, 35(2):241-246.
|