乌司他丁对急性呼吸窘迫综合征患者预后影响的临床研究

目的研究乌司他丁对急性呼吸窘迫综合征（ARDS）患者预后、免疫调节、肾上腺皮质功能及全身炎症反应调控等方面的影响。方法将2004年12月至2009年11月重症监护病房（ICU）收治的ARDS患者随机分为乌司他丁组和对照组各30例，两组均按照常规治疗，乌司他丁组加用乌司他丁50万U，2次／d，治疗7d。记录机械通气时间、ICU住院时间、28d病死率，治疗前后进行急性生理学与慢性健康状况评分系统I（APACHE1I）评分、急性肺损伤Murray评分、器官功能障碍Marshall评分，并于治疗前及治疗结束时（第8日）静脉注射促肾上腺皮质激素250μg，放射免疫法测定注射前（TO）及注射后30min（T30）、60min（T60）血浆皮质醇水平，计算T30或T60最大值与TO的差值（ATmax），以△Atmax≤248．4nmol／L作为相对肾上腺皮质功能不全诊断标准统计肾上腺皮质功能不全发生率；分别检测治疗前后外周血人白细胞DR抗原（HLA．DR）和淋巴细胞亚群（CD44^＋／CD8^＋）、白细胞介素-6（IL-6）、IL-10水平变化。结果乌司他丁组治疗后Murray评分（1．5±1．5）分、Marshall评分（2．9±2．7）分、外周血IL-6（3．4±1．9）／μmol／L、IL-10（1．5±0．8）μmol／L3均较对照组分别为（4．3±3．1）分、（6．3±4．1）分、（8．9±10．2）／μmol／L、（4．2±4．8）μmol／L3明显下降（P均〈0．01），HLA-DR（41．1±10．1）、CD4^＋（58．0±10．7）、CD4^＋／CD8^＋比值（1．9±0．3）则均较对照组（分别为30．6±15．0、50．5±16．2、1．4±0．7）显著升高（P〈0．05或P〈0．01）；乌司他丁组肾上腺皮质功能不全发生率（45．2％）较对照组（83．3％）明显降低（P〈0．01），△Tmax明显升高（328．4±278．3）μmol／L比（172．8±110．8）μmol／L，P均〈0．01；乌司他丁组机械通气时间（4．0±3．3）d及ICU住院时间（（8．4±4．2）d较对照组明分别为（5．9±3．8）d、（12．0±7．6）d明显缩短（P〈0．05）；28d病死率乌司他丁组较对照组降低11．2％（35．5％比46．7％），但差异无统计学意义（P〉0．05）。结论乌司他丁可以改善脏器功能状态。降低机械通气和ICU住院时间，其机制可能是调节ARDS患者免疫功能，降低ARDS肾上腺皮质功能不全发生率，调控炎症反应。

Control clinical study of the effect of Ulinastatin on prognosis of acute respiratory distress syndrome patients

Objective To study the effect of Ulinastatin on prognosis,immune function,adrenal function and inflammatory reaction during the treatment of acute respiratory distress syndrome (ARDS). Methods From December 2004 to November 2009, a clinical study was conducted on consecutive adult patients with ARDS in intensive care unit (ICU). The patients were divided into Ulinastatin group ( 30 patients) and control group (30 patients). Both groups were treated with the routine therapy of ARDS and in addition, Ulinastatin was used in a dose of 500,000 U twice a day for 7 ays in Ulinastatin group. Duration of mechanical ventilation (MV)and ICU length of stay,28-day mortality, acute physiology and chronic health evaluation I(APACHE Ⅱ ), Murray and Marshall scores were recorded in both groups. Every patient was given one of corticotrophin 250 μg intravenously before and after treatment and plasma contisol level was detected by radio-immunoassay before the (TO) and 30 minutes (T30)and 60 minutes (T60)after the, The ratio of adrenal insufficiency was evaluated according to diagnostic criteria of ralative adrenal insufficiency, which was defined as the diffenence between TO and the highest value of T30 or T60( △ Tmax) ≤248. 4 nmol/L. Human leukocyte antigen-DR( HLA-DR), subpopulations of T lymphocyte ( CD4 +/CD8 + ), interleukin-6 ( IL-6 ), IL-10 in peripheral blood was also determined. Results Murray ( 1.5 ± 1.5 ) and Marshall score (2.9 ± 2.7 ) and the level of IL-6 (( 3.4 ± 1.9) μmol/L,IL-10( (1.5 ± 0.8 ) μmol/Lin the Ulinastatin group were decreased significantly after the use of Ulinastatin compared with control group4.3 ± 3.1,6.3 ± 4.1, ( 8.9 ± 10.2) μmol/L, (4.2 ± 4.8 ) μmol/L, respectively, all P ＜ 0. 01, while the values ofHLA-DR(41.1 ± 10.1 ), CD4 + (58.0 ± 10.7), CD4 +/CD8 + ( 1.9 ± 0.3 ) were increased compared with control group(30.6 ± 15.0,50.5 ± 16.2,1.4 ±0.7,respectively,P ＜0.05 or P ＜0.01.The ratio of adrenal insufficiency in Ulinastatin group(45.2% )was lower than that of control group( 83.3% ),while that of ATmax( 328.4 ± 278.3 )/μmol/Lwas higher than that of control group( 172.8 ± 110.8 )/μmol/L ,both P ＜ 0.01. MV duration (4.0 ± 3.3 ) daysand ICU length of stay ( 8.4 ± 4. 2) dayswere less than those of control group (5.9 ± 3.8 ) days, ( 12.0 ± 7.6 ) days, both P ＜ 0.053, and 28-day mortality in Ulinastatin group was 35.5% ,which was 11.2% less than that of control group(46.7% ) ,but there was no statistically significant difference between two groups ( P ＞ 0.05 ). Conclusion Ulinastatin improves organ function, decreases MV duration and ICU length of stay in ARDS patients. The underlying mechanism may involve modulation of the immune function, decrease in the degree of adrenal insufficiency, and modulation of regulating inflammatory reaction.