肠胃舒对危重症患者胃肠功能衰竭防治作用的临床研究
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摘要
胃肠功能衰竭是危重症患者常见的病症之一,主要表现为急性胃粘膜病变和中毒性肠麻痹,被称为是多脏器功能不全综合症(MODS)的“扳机因素”,有效防治胃肠功能衰竭是防止MODS的发生发展的主要手段,是降低危重症死亡率的关键。目前西医对此病理过程尚无有效的方法加以防治。中医药防治本病的研究日趋活跃,但大都停留在疗效观察阶段,对其作用机理、作用环节还缺乏系统研究。导师经过多年的临床实践研究,认为危重症患者发生胃肠功能衰竭的中医病机为毒邪乘虚侵袭,胃肠瘀血阻络,导致气机逆乱,升降失和,终致胃气败绝,阴阳离决。导师在中医理论指导下,采用辨病和辨证相结合的方法从泻热通腑、活血养阴入手制定出了肠胃舒,以防治危重症患者发生胃肠功能衰竭,缓解危重症病情,降低其死亡率。
     目的:研究肠胃舒对危重症患者胃肠功能衰竭的防治作用,并观察对可溶性血管细胞黏附分子-1(sVCAM-1)、白介素-6(IL-6)和内毒素的影响,以期探讨肠胃舒防治危重症患者胃肠功能衰竭的作用机理。
     方法:观察病例48例,均来源于本院急诊ICU2006年3月—2007年6月收住的危重症患者。按收住院先后顺序编号依照随机数字表,随机分为两组:防治组(肠胃舒)24例和对照组(吗叮啉悬液)24例。两组在性别、年龄、原发病、病情危重程度等方面经统计学处理,差异均无显著性意义(P﹥0.05),具有可比性(见附表1,2,3,4)。防治组予肠胃舒煎剂150ml,分上、下午2次鼻饲。(药物为生大黄9g,公英20g,麦冬15g,青皮15g,当归15g,赤白芍各12g,川芎9g,仙鹤草20g,黄连6g,清夏6g,瓜蒌15g,地榆20g,云苓20g。由本院制剂室浓煎)对照组予吗叮啉悬液20ml鼻饲,每6小时1次。两组均观察5天。其它治疗措施如抗感染、病因治疗、脏器功能支持、维持内环境稳定、营养支持、对症治疗等两组相同。观察两组胃肠功能衰竭发生及死亡情况,治疗前后APACHEⅡ评分变化及对血清sVCAM-1、IL-6和内毒素的影响。
     结果:1.两组胃肠功能衰竭发生率比较(见附图1,附表5):防治组发生急性胃粘膜病变3例(12.5%),发生中毒性肠麻痹2例(8.33%),二者同时发生2例(8.33%),其中死亡1例(4.17%),总发生率为29.17%;对照组发生急性胃粘膜病变5例(20.83%),发生中毒性肠麻痹7例(29.17%),二者同时发生4例(16.67%),其中死亡3例(12.5%),总发生率为66.67%,经卡方检验,p﹤0.01,两组比较统计学有显著性差异。提示防治组能有效防止危重症患者发生胃肠功能衰竭,其疗效显著优于对照组。2.两组APACHEⅡ评分变化比较(见附图2,附表6):防治组治疗前后APACHEⅡ评分分别为16.3±2.4分、8.3±3.1分,经t检验,p﹤0.01,两者比较统计学有显著性差异;对照组治疗前后APACHEⅡ评分分别为16.08±2.5分、11.1±4.8分,经t检验,p﹤0.01,两者比较统计学有显著性差异;治疗后两组比较,经t检验, p﹤0.05,两组比较统计学有差异。提示治疗后两组病例病情危重程度均较治疗前减轻,但防治组改善危重症患者病情疗效优于对照组。3.两组血清IL-6变化比较(见附图3,附表7):防治组治疗前后血清IL-6含量分别为314.4±39.0、160.3±45.8,经t检验,p﹤0.01,两者比较统计学有显著性差异;对照组治疗前后血清IL-6含量分别为313.5±37.4、242.6±46.6,经t检验,p﹤0.01,两者比较统计学有显著性差异;治疗后两组比较,经t检验,p﹤0.01,两组比较统计学有显著性差异。提示治疗后两组血清IL-6含量均较治疗前降低,但防治组抑制血清IL-6疗效显著优于对照组。4 .两组血清sVCAM-1变化比较(见附图4,附表8):防治组治疗前后血清sVCAM-1含量分别为23.74±2.15、16.53±2.46,经t检验,p﹤0.01,两者比较统计学有显著性差异;对照组治疗前后血清sVCAM-1含量分别为23.72±2.30、18.93±2.23,经t检验,p﹤0.01,两者比较统计学有显著性差异;治疗后两组比较,经t检验,p﹤0.01,两组比较统计学有显著性差异。提示治疗后两组血清sVCAM-1含量均较治疗前降低,但防治组抑制血清sVCAM-1疗效显著优于对照组。5.两组血清内毒素变化比较(见附图5,附表9):防治组治疗前后血清内毒素含量分别为1.000±0.115、0.689±0.119,经t检验,p﹤0.01,两者比较统计学有显著性差异;对照组治疗前后血清内毒素含量分别为0.999±0.121、0.964±0.108,经t检验,p﹥0.05,两者比较统计学无显著性差异;治疗后两组比较,经t检验, p﹤0.01,两组比较统计学有显著性差异。提示治疗后防治组血清内毒素含量较治疗前降低,防治组可有效清除血清内毒素,其疗效显著优于对照组。
     结论:本研究表明,肠胃舒能有效防止危重症患者发生胃肠功能衰竭,缓解危重症患者病情。其作用机理可能与本方能有效抑制血清sVCAM-1和IL-6的升高,清除内毒素有关。研究结果从临床疗效角度,验证了毒邪内蕴,胃肠瘀血阻络为发生胃肠功能衰竭的病机和发病关键,以泻热通腑、活血养阴为治则组方用药能有效防治危重症患者胃肠功能衰竭,为临床防治本病提供了新的方法和思路。
Gastrointestinal failure is one of the common disorders in critical patients,its main manifestations are acute gastric mucosal lesions and toxic enteroparalysis, it was known as the "trigger factors" of MODS. The effective prevent and cure of gastrointestinal failure is the main methods to prevent the development of MODS, and it is also the key point of reducing the death rate of critical patients. At present, Western medicine in this pathologic process has no effective prevention and treatment methods. Chinese medicine in the prevention and treatment of this disease has become increasingly active, but most remains in the observation stage of its mechanism, and it is also lack the systematic research in mechanism of action and link. After years of clinical practice study, my tutor believed that the Chinese pathogenesis of the critical patients in gastrointestinal failure was poison and evil invasion while it was weak, gastrointestinal blood stasis, leading qi-movement disturbance and disharmony movements to lead to stomach Gas lose and dissociation of yin and yang. Under the guidance of the theory of Chinese medicine, my tutor used the way that combined the differential diagnosis of diseases and differentiation of symptoms and signs and to begin with purging heat fu-unblocking therapy, promoting blood flow nourishing yin, and finally he work out the CHANGWEISHU, which was used to prevent and cure the gastrointestinal failure of critical patients, ease of critical illness, lower its mortality rate.
     Objective: To study the CHANGWEISHU on the function of preventing and curing the gastrointestinal failure of critical patients, and to observe its impact on soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6) and the endotoxin, so as to investigate the action mechanism of CHANGWEISHU on preventing and curing the gastrointestinal failure of critical patients.
     Methods:The cases of 48 observation cases were all from our emergency room ICU critical patients who lived there at the time of 2006 in March—2007 June. According to hospital sequence code in accordance with random number table, the cases were randomly divided into two groups: the prevention and cure group (CHANGWEISHU) 24 cases and the control group (Motilium suspension) 24 cases. After the process of statistics, two groups in gender, age, protopathy, severity of illness and other aspects of the statistical differences were not significant (P>0.05), so it had comparability (see Schedule 1,2,3,4).The prevention and cure group was to give CHANGWEISHU decoction 150ml, nasal feeding at morning and afternoon. (The drugs are Radixet rhizoma rhei 9g, Dandelion 20g,Ophiopogonis tuber 15g,Pericarpium citri reticulatae viride 15g,Angelica 15g, Erythro- white peony root 12g, Szechwan lovage rhizome 9g, Agrimony 20g,Coptis 6g,QingXia 6g,Snakegourd fruit 15g,Sanguisorba 20g,PORIA from Yunnan of China 20g. they were all thick fried by our hospital manufacturing laboratory).The control group was to give Motilium suspension 20ml ,nasal feeding every four hours once. Both groups were observed five days. Other measures, such as anti-infection treatment, the etilogical treatment, organ function support, maintain its internal environment stable, nutritional support, symptomatic treatment, and other measures were all the same. To observe the Gastrointestinal failure and the death condition, the score changes of APACHEⅡbefore and after treatment and the impact on serum sVCAM-1, IL-6 and endotoxin in two groups.
     Results: 1. Comparison of gastrointestinal failure rate in two groups (see Figure 1, Table 5): In the prevention and cure group, there were three cases of acute gastric mucosal lesions (12.5%), two cases of intestinal paralysis toxicity (8.33%), two simultaneous two cases (8.33%), including one case of death (4.17%). The total incidence rate was 29.17 percent. In the control group, there were five cases of acute gastric mucosal lesions (20.83%),seven cases of intestinal paralysis toxicity (29.17 %), two simultaneous four cases (16.67%), there cases of death (12.5%).The total incidence rate was 29.17 percent, the chi-square test showed p<0.01, there was significant difference between the two groups statistically. It showed that the prevention and cure group would effectively prevent the occurrence of critical patients with gastrointestinal failure; the effect was significantly better than the control group. 2. Comparison of APACHEⅡscore changes in two groups(see Figure 2, Table 6): in the prevention and cure group, APACHEⅡscores before and after treatment were 16.3±2.4 points, 8.3±3.1 points, the t-test showed p<0.01, there was significant statistical difference; in the control group, APACHEⅡscores before and after treatment were 16.08±2.5 points, 11.1±4.8 points, the t-test showed p<0.01, there was significant statistical difference;compared the two groups after treatment by the t-test, it showed p<0.05, there was significant statistical difference. Two cases of illness after treatment than before treatment severity lessened, but to improve prevention and cure group of patients with critical illness efficacy was significantly better than the control group. 3. Comparison of serum IL-6 changes in two groups(see Figure 3, Table 7): in the prevention and cure group, serum IL-6 levels before and after treatment were 314.4±39.0,160.3±45.8, the t-test showed p<0.01, there was significant statistical difference; in the control group, serum IL-6 levels before and after treatment were 313.5±37.4,242.6±46.6,the t-test showed p<0.01, there was significant statistical difference; compared the two groups after treatment by the t-test, it showed p<0.01, there was significant statistical difference. After treatment, serum IL-6 levels of two groups were all lower than before, but the prevention and cure group inhibitory effect of serum IL-6 was significantly better than the control group. 4.Comparison of serum sVCAM-1 changes in two groups(see Figure 4, Table 8): in the prevention and cure group, serum sVCAM-1 levels before and after treatment were 23.74±2.15,16.53±2.46, the t-test showed p<0.01, there was significant statistical difference; in the control group, serum sVCAM-1levels before and after treatment were 23.72±2.30,18.93±2.23,the t-test showed p<0.01, there was significant statistical difference; compared the two groups after treatment by the t-test, it showed p<0.01, there was significant statistical difference. After treatment, serum sVCAM-1 levels of two groups were all lower than before, but the prevention and cure group inhibitory effect of Serum sVCAM-1 was significantly better than the control group. 5. Comparison of serum endotoxin changes in two groups(see Figure 5, Table 9):in the prevention and cure group, serum endotoxin levels before and after treatment were 1.000±0.115,0.68923±0.119,the t-test showed p <0.01, there was significant statistical difference; in the control group, serum endotoxin levels before and after treatment were 0.999±0.121,0.964±0.108,the t-test showed p>0.05, there was no significant statistical difference; compared the two groups after treatment by the t-test, it showed p<0.01, there was significant statistical difference. After treatment, serum endotoxin levels of the prevention and cure group was lower than before, the prevention and cure group can effectively remove the endotoxin, their efficacy was significantly better than the control group.
     Conclusion: This study showed that CHANGWEISHU can effectively prevent gastrointestinal failure in critical patients, relive critical patient's condition. Its mechanism of action may relate with the reason that CHANGWEISHU can effectively inhibit the serum sVCAM-1 and IL-6 levels increased and remove the endotoxin. From the perspective of clinical curative effect, the finding showed that poison and evil was intrinsic and gastrointestinal blood stasis were the key to pathogenesis of the gastrointestinal failure. The way that purging heat fu-unblocking therapy, promoting blood flow nourishing yin can effectively prevent and cure the gastrointestinal failure of critical patients, it provided new methods and ideas for clinical prevention and cure this disease.
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