茵陈蒿汤治疗脓毒症相关肝损伤的临床应用研究

The clinical research of yinchenhao decoction for treatment of liver injury induced by sepsis

目的探讨茵陈蒿汤在治疗脓毒症相关肝损伤中的临床应用。方法选择2014年1月至2015年12月入住南京中医药大学附属南京市中西医结合医院重症医学科诊断为脓毒症相关肝损伤的患者40例，按随机数字表法分为常规治疗对照组和茵陈蒿汤治疗组，每组20例。常规治疗对照组按照2012年严重脓毒症和脓毒性休克治疗指南进行标准治疗，包括抗感染、液体复苏、眦管活性药物等及其他对症治疗；茵陈蒿汤治疗组杠标准治疗基础上鼻饲茵陈蒿汤（茵陈18g，栀子9g，生大黄9g），每日1剂，连续使用7d。分别于治疗前和治疗后3d和7d观察并记录两组患者肝功能、腹腔内压、肠内营养热仁数、痰培养和尿培养情况、肠道菌群移位率，治疗终点的实际病死率、重症加强治疗病房（ICU）住院时间。单因素分析影响脓毒症并发肝损伤患者预后的危险因素。采用logistic回归分析筛出独立危险因素。结果两组治疗后天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总胆红素（TBil）、直接胆红素（DBil）、腹内压均较治疗前降低，肠内营养热k／体质量比值较治疗前升高，且以茵陈蒿汤治疗组治疗后7d反映器官功能损伤各项指标的变化较常规治疗对照组更湿著[AST（U／L）102．5±12．6比175．4±18．5，ALT（U／L）127．6±15．5比180．9±16．3，TBil（mmol／L）15．7±3．6比23．0±4．7．DBil（mmol／L）6．9±3．4比9．2．±3．5，腹内压（mmHg，1mmHg=0．133kPa）10．6±2．5比14．4±2．1；肠内营养热书／体质量（kJ／kg）比值106．69±15．90比63．60±14．64，均P〈0．05]；菌陈蒿汤治疗组的肠道菌群移位率[25．0％（5／20）比55．0％（11／20）]、实际病死率／预期病死率[（0．50±0．03）％比（0．86±0．07）％]、ICU住院时间（t1：20．2±5．9比28．9±8．2）均明显低于常规治疗对照组（均P〈0．05）。Pearson相关性分析显示，性别、年龄与患者死亡和ICU住院时间无明娃相关性（均P〉0．05）。茵陈蒿汤治疗与脓毒症并发肝损伤患者的死亡（r=-0．465，P=0．03）和ICU住院时间（r=-0．412，P=0．034）均呈负相关。急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分与脓毒症并发肝损伤患者死亡（r=0．335，P=0．03）和ICU住院时间（r=0．389，P=0．04）均呈正相关；多变量logistic回归分析显示，脓毒症相关肝损伤患者使用茵陈蒿汤治疗后可以使死亡风险降低25％[优势比（OR）=0．75，95％可信区间（95％C1）=0．85～1．24，P=0．012]。结论茵陈蒿汤能佩著改善脓毒症相关肝损伤患者的肝功能，提高肠内营养耐受性，降低腹内压和防止肠道菌群移位，且能降低患苦的病死率和ICU住院时间。

Objective To study the clinical application of yinchenhao decoction for treatment of liver injury induced by sepsis. Methods Forty patients with liver injury induced by sepsis admitted to department of Critical Care Medicine at Affiliated Nanjing Integrated Traditional Chinese and Western Medicine Hospital of Nanjing Traditional Chinese Medicine University from January 2014 and December 2015 were enrolled, and they were randomly divided into a conventional treatment control group （20 cases） and a yinchenhao treatment group （20 cases）. According to the severe sepsis and septic shock treatment guidelines in 2012, all the patients in the two groups were treated by standard treatment, including anti-infection, fluid resuscitation, vascular active drugs, etc. and other symptomatic treatment; on the basis of slandard lreatment, the patients in yinchenhao treatment group were additionally treated with nasogastric yinchenhao decoction （ingredients： herba artemisiae scopariae 18 g, fructus gardeniae 9 g, raw rhubarb 9 g）, 1 dose daily for consecutive 7 days. Liver function, intra-abdominal pressure, sputum and urine cuhnre, the calorie of enteral nutrition and rate of intestinal bacterial translocation in patients of the two groups were recorded respectively before and after treatment for 3, 7 days; the actual mortality and length of stay in intensive care unit （ICU） in the treatment endpoint. Risk factor for the prognosis of patients with liver injury induced by sepsis were analyzed by univariate analysis, independent risk fac.tors for prognosis were analyzed by logistic regression analysis. Results After treatment in the two groups, the levels of aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, total bilirubin （TBil）, direct bilirubin （DBil） and intra-abdominal pressure were all reduced, ratio of the enteral nutrition kcal/body weight was higher than that before treatment, and 7 days after treatment, the degrees of changes in indexes reflecting organ functional injury in yinehenhao treatment group were more significant than those in the conventional treatment control group lAST （U/L）： 102.5 ±12.6 vs. 175.4 ±18.5, ALT （U/L）： 127.6 ±15.5 vs. 180.9 ±16.3, TBil （mmol/L）： 15.7 ± 3.6 vs. 23.0 ±4.7, DBil （mmol/L）： 6.9 ±3.4 vs. 9.2 ±3.5, intra-abdominal pressure （mmHg, 1 mmHg = 0.133 kPa） 10.6 ± 2.5 vs. 14.4 ±2.1, ratio of enteral nutrition kcal/weight （kJ/kg） 106.69 ± 15.90 vs. 63.60 ± 14.64, all P 〈 0.05]. The rate of intestinal bacteria transloeation [25.0% （5/20） vs. 65.0% （11/20）] and the actual/expected mortality [（0.50 ± 0.03）% vs. （0.86 ± 0.07）%], length of stay in ICU （day： 20.2±5.9 vs. 28.9 ± 8.2） in the yinehenhao treatment group were significantly lower than those in the conventional treatment control group （all P 〈 0.05）. Pearson correlation analysis showed that gender and age had no significant correlation with death and length of stay in the ICU （all P 〉 0.05）. Yinchenhao decoction treatment was negatively correlated with the mortality （r = -0.465, P = 0.03） and length of stay in ICU （r = -0.412, P = 0.034） for the patients with liver injury induced by sepsis. APACHE Ⅱ score was positively correlated with the death （r = 0.335, P = 0.335） and the length of stay in ICU （r = 0.389, P = 0.389） of sepsis patients complicated with liver injury. Multivariate logistic regression analysis revealed that patients with liver injury induced by sepsis treated with yinchenhao decoction can lower the risk of death by 25% [oddis ratio （OR） = 0.75, 95% confidence interval （95%CI） = 0.85 - 1.24, P = 0.012]. Conclusions Yinchenhao decoction can significantly improve the liver function, elevate enteral nutrition tolerance, reduce intra-abdominal pressure and prevent intestinal bacterial translocation for patients with liver injury induced by sepsis. In addition, the therapy can reduce the mortality and the length of stay in ICU of the patients.