Clinical study and long term evaluation of immunomodulation therapy on trauma, severe sepsis and multiple organ dysfunction syndrome patients HUANG Shun wei, GUAN Xiang dong, CHEN Juan, OU YANG Bin. Surgery Intensive Care Unit, the First Affiliated Hospital of Sun Yat Sen University, Guangzhou 510080, Guangdong, China
        【Abstract】Objective To study the clinical effect and long term evaluation of immunomodulation therapy on trauma, severe sepsis and multiple organ dysfunction syndrome (MODS) patients.

        Methods Prospective, randomized, blind and controlled clinical analysis of 70 patients conforming to the enrolled standard was carried out. They were divided into two groups at random. One was control group (n=34) with regular therapy, and the treatment group (n=36) with ulinastatin plus thymosinα1 on the base of regular therapy for 1 week. The immunological indexes were determined before and after therapy on the 1 st, 3 rd, 7 th, 14 th and 28 th day, including the changes in lymphocyte count, CD14＋ monocytes human leukocyte antigen (locus) DR (HLADR), clinical data and long term follow up.

        Results During hospitalization, 20 patients died in the control group and 13 patients died in the treatment group. There was significant difference between two groups (P＜0.05＝. After 7 up to 28 days of therapy, the counts of lymphocyte and CD14＋ monocytes HLADR were significantly higher than those in control group (all P＜0.05＝. The duration of using mechanical ventilation and pressor agent in the treatment group were shorter than those in the control group (both Ｐ<０.０１). The length of stay and the cost in the intensive care unit (ICU) were not significantly increased in the treatment group (both P＞0.05). The long term survival time in the treatment group was much longer than that in the control group (P＜0.05＝.

        Conclusions Immunomodulation therapy can improve the prognosis of trauma, severe sepsis and MODS patients in a period of 28 days of observation, and lymphocyte counts and CD14＋ monocytes HLADR were increased significantly, showing that immunosuppression can be ameliorated. Immunomodulation therapy can shorten the time of mechanical ventilation and the use of pressor agent, and it does not increase the length of stay and the cost in ICU, and therefore the cost effectiveness is high. It also can prolong the longterm survival time. The results show that immunomodulation therapy is one of successful therapeutic strategies in the care of critical illness.

        【Key words】trauma；severe sepsis；multiple organ dysfunction syndrome；immunomodulation therapy

        创伤性严重脓毒症和多器官功能障碍综合征(MODS)的治疗问题是近年来危重病医学一直关注的研究热点〔1〕。机体炎症反应和免疫功能紊乱被视为创伤性严重脓毒症和MODS发生、发展的中心环节。有效的免疫调理治疗(抗炎治疗联合免疫刺激治疗)被认为是最终取得治疗突破的根本途径〔2〕。通过对创伤性严重脓毒症和MODS患者进行免疫调理治疗的观察和初步研究，旨在揭示危重病患者免疫学指标的动态变化和远期疗效，为危重患者的免疫学监测和免疫调理治疗提供理论依据，亦为日后制定更实用、更有效的免疫治疗方法和疗程奠定基础。
        1 资料与方法
        1.1 研究对象：将2004年1月—2005年6月本院收治的70例创伤性严重脓毒症和MODS患者纳入本研究中。其中男58例，女12例；平均年龄(55±１７）岁。所有病例均满足1990年Shoemaker等〔3〕制定的腹部外科高危患者指标和1991年美国胸科医师协会/危重病医学会(ACCP/SCCM)推荐的诊断标准〔4〕。
        1.2 治疗方法：采用前瞻、随机、单盲和对照的临床研究。凡符合入选标准的患者随机分为两组：①对照组34例，按经典重症监护室(ICU)治疗方案，参照2003年“拯救脓毒症战役”(surviving sepsis campaign，SSC)会议制定的“脓毒症治疗指南”〔5〕，不具备相应治疗条件（如人体活化蛋白C治疗）者除外。②治疗组36例，除经典ICU治疗方案外，同时接受抗炎治疗药物蛋白酶抑制剂(乌司他丁)200 kU静脉滴注，每日3次，连续3 d，然后改用10 kU，每日3次，连续4 d。同时增加免疫刺激治疗药物胸腺肽α1，每次皮下或肌肉注射1.6 mg，每日2次，连续3 d，继而改为1.6 mg，每日1次，连续4 d。 

        1.3 观察指标：观察治疗前及治疗后1、3、7、14和28 d淋巴细胞计数和CD14+单核细胞人白细胞DR抗原(HLADR)水平的动态变化。以28 d为观察时间，判断患者预后转归情况。以2005年9月为随访观察终点，“+”表示仍然生存。
        1.4统计学方法：采用SPSS 10.0软件进行统计学处理。两组免疫学指标结果以均数±标准差(x±s)表示；两组临床资料以中位数(Ｍ)表示；用KaplanMeier方法作生存分析，结果以Ｍ、标准误和95%可信区间表示。两组差异显著性检验用两独立样本均数t检验，Ｐ<０.０５为差异有统计学意义。
        2 结果
        2.1 一般情况：70例患者中共死亡33例，均死于MODS；其中对照组死亡20例，治疗组死亡13例，两组比较差异有显著性(Ｐ<０.０５)。手术构成：移植科占51%，胃肠外科占19%，肝胆外科占13%，血管外科占9%，其他占8%。