新斯的明对急性胰腺炎合并腹内高压治疗价值的临床研究

发布时间：2018-08-25 15:29

【摘要】：背景:急性胰腺炎(acute pancreatitis,AP)是一个世界范围内高死亡率的疾病,尤其重症急性胰腺炎的死亡率达36%-50%。急性胰腺炎发病过程中可出现多种并发症,其中腹内高压(IAH)或腹腔间隔室综合征(ACS)为急性胰腺炎的一种特殊并发症,预后差、病死率高。目前认为IAH是ACS的前奏,IAH向ACS的演变速度在不同SAP患者中差异较大,IAH期可以看成是病情演变成为ACS的重要“窗口期”和转折点,也是非手术治疗的重要时期。而急性胰腺炎发病过程中,胰液渗出导致的麻痹性肠梗阻是引发腹内压增高的重要原因之一,所以积极治疗麻痹性肠梗阻导致的腹内高压可以明显缓解急性胰腺炎患者症状。新斯的明作为抗胆碱酯酶药,通过与乙酰胆碱在胆碱能传递位点竞争性地与胆碱酯酶结合,阻遏乙酰胆碱的水解,增强胆碱能作用而提高兴奋性副交感活性,使患者机体表现为毒蕈碱样(M样)作用,从而恢复病人的肠蠕动。当急性胰腺炎患者胃肠道M受体兴奋时能够增强胃肠道蠕动,可促使患者肛门排气、排便,所以药物新斯的明对于改善急性胰腺炎患者麻痹性肠梗阻,降低急性胰腺炎患者腹内压可能具有一定效果。目前国内尚无新斯的明治疗AP合并IAH的前瞻性临床对照研究,具有创新性与实用性。目的:1.探讨新斯的明改善急性胰腺炎导致的麻痹性肠梗阻,降低患者腹腔内压力的治疗价值。2.明确新斯的明对降低急性胰腺炎患者器官衰竭及改善预后的治疗价值。方法:本临床随机对照试验于2015年8月1日至2016年2月29日在南昌大学第一附属医院消化内科展开,本研究获得医院伦理委员会的批准,并在NIH注册,注册号为:NCT02543658。患者参与实验之前均签署知情同意书。根据亚特兰大急性胰腺炎诊断标准,即临床符合以下3项中的2项可诊断为急性胰腺炎:与急性胰腺炎符合的腹痛;血淀粉酶和(或)脂肪酶至少3倍正常上限;增强CT/MRI或腹部超声呈急性胰腺炎改变。期间共483例病人诊断为急性胰腺炎,其中轻症急性胰腺炎患者229例,中度重症急性胰腺炎患者187例,重症急性胰腺炎患者67例。腹内高压(iah)诊断标准:每4-6小时测量一次腹内压,连续3次平均腹内压≥12mmhg。符合急性胰腺炎合并腹内高压入组条件的患者有33例,根据随机分组,分为实验组(a组)、对照组(b组)。对照组为常规治疗组;实验组在常规治疗基础上给予肌肉注射新斯的明。结果:本研究的33位患者中男性24人(72.7%),女性9人(27.3%),其中重症急性胰腺炎患者25人(75.7%),中度重症急性胰腺炎患者8人(24.3%),无轻症患者。患者不同时间点测得的粪便量之间统计学上具有差异(f=19.410,p=0.000)。实验组及对照组粪便量均呈上升趋势,实验组高于对照组(f=8.509,p=0.007)。用药后第1、2、3天实验组的粪便量高于对照组(p?0.05),其余各时间点实验组与对照组无显著差异(p?0.05),实验组与对照组之间存在交互作用(f=3.756,p=0.006)。患者不同时间点所测得的腹内压之间统计学上有差异(f=35.820,p=0.000)。实验组及对照组腹内压均呈逐渐下降趋势,实验组与对照组统计学上无明显差异(f=2.566,p=0.119)。第3天实验组的腹内压低于对照组(p=0.036),其余各时间点实验组及对照组统计学上无差异(p?0.05),实验组与对照组之间不存在交互作用(f=1.250,p=0.282);测量实验组及对照组患者治疗前腹内压及治疗后24h,48h,72h腹内压下降百分比、72h内达标率(降到12mmhg以下),发现24h实验组下降率较对照组高,差异具有统计学意义(f=5.270,p=0.029),其余各时间点无统计学差异(p?0.05)。两组患者达到腹内压ii级的患者共15例,其中实验组7例,对照组8例,治疗后实验组患者24h,48h,72h腹内压下降百分比、72h内达标率及降到i级(15mmhg)的时间均优于对照组,差异有统计学意义(p?0.05)。实验组第5天腹内压恢复至正常患者数与对照组相比明显增加,差异具有统计学意义(p=0.038),其余各时间点无统计学意义(p?0.05);两组之间器官衰竭持续时间统计学上无明显差异(p=0.465)。两组患者在重症监护时间、总住院时间及预后上的差异无统计学意义(p?0.05)。结论:(1)新斯的明可以改善急性胰腺炎患者麻痹性肠梗阻症状;(2)新斯的明可以降低腹内压ii级以上急性胰腺炎患者的腹内压;(3)本研究进行过程中未发生药物新斯的明的安全不良事件;(4)新斯的明降低腹内压i级急性胰腺炎患者的腹内压较常规治疗无明显优势;(5)本研究中新斯的明对于改善急性胰腺炎患者的器官衰竭持续时间、重症监护时间、总住院时间及预后的作用有限;(6)由于本研究样本量较小,实验结果存在一定偏差,尚需扩大样本量加以论证。
[Abstract]:BACKGROUND: Acute pancreatitis (AP) is a worldwide disease with high mortality, especially severe acute pancreatitis (SAP) with a mortality rate of 36% - 50%. Several complications may occur during the onset of acute pancreatitis, of which intraabdominal hypertension (IAH) or abdominal compartment syndrome (ACS) is a special complication of acute pancreatitis. At present, IAH is considered to be the prelude of ACS. The rate of evolution of IAH to ACS varies greatly among different SAP patients. IAH can be regarded as an important "window" and turning point for the development of ACS, and also an important period for non-surgical treatment. Neostigmine, as an anti-cholinesterase drug, is enhanced by competitive binding with acetylcholine at the cholinergic transmission site to inhibit the hydrolysis of acetylcholine. Cholinergic enhances excitatory parasympathetic activity and restores the intestinal peristalsis of patients with acute pancreatitis. When M receptors in the gastrointestinal tract are excited, the gastrointestinal peristalsis of patients with acute pancreatitis can be enhanced, and the anal exhaust and defecation of patients can be promoted. Therefore, neostigmine can improve the patients with acute pancreatitis. There is no prospective clinical controlled study of neostigmine in the treatment of AP complicated with IAH in China, which is innovative and practical. Objective: 1. To explore the effect of neostigmine on the improvement of paralytic intestinal obstruction caused by acute pancreatitis and the reduction of intraperitoneal pressure in patients with acute pancreatitis. Methods: A randomized controlled trial was conducted in the Department of Gastroenterology, First Affiliated Hospital of Nanchang University from August 1, 2015 to February 29, 2016. The study was approved by the Hospital Ethics Committee and registered in NIH with the registration number N:N. According to the diagnostic criteria of Atlanta acute pancreatitis, two of the following three items can be diagnosed as acute pancreatitis: abdominal pain consistent with acute pancreatitis; blood amylase and/or lipase at least three times the normal upper limit; enhanced CT/MRI or abdominal ultrasound showing acute pancreatitis A total of 483 patients were diagnosed as acute pancreatitis, including 229 patients with mild acute pancreatitis, 187 patients with moderate severe acute pancreatitis and 67 patients with severe acute pancreatitis. 33 patients were randomly divided into experimental group (group a) and control group (group b). The control group was treated with routine therapy, and the experimental group was given neostigmine intramuscularly on the basis of routine therapy. Results: Among the 33 patients in this study, 24 (72.7%) were male and 9 (27.3%) were female, including 25 (75.3%) with severe acute pancreatitis. There were statistically significant differences (f = 19.410, P = 0.000) in the amount of feces measured at different time points. The amount of feces in the experimental group and the control group showed an upward trend. The amount of feces in the experimental group was higher than that in the control group (f = 8.509, P = 0.007). The amount of feces in the experimental group was higher than that in the control group on the first, second and third days after treatment. There was no significant difference between the experimental group and the control group at the other time points (p? 0.05). there was interaction between the experimental group and the control group (f = 3.756, P = 0.006). the intraabdominal pressure of the patients at different time points was statistically different (f = 35.820, P = 0.000). the intraabdominal pressure of the experimental group and the control group showed a gradual downward trend, and the experimental group and the control group showed a gradual downward trend. The intraabdominal pressure of the experimental group was lower than that of the control group on the third day (p = 0.036), and there was no significant difference between the experimental group and the control group at other time points (p? 0.05). There was no interaction between the experimental group and the control group (f = 1.250, P = 0.282). 24 hours, 48 hours, 72 hours of intra-abdominal pressure decreased percentage, within 72 hours of the standard rate (down to 12 mmHg below), found that 24 hours of the experimental group than the control group, the decline rate was statistically significant (f = 5.270, P = 0.029), the rest of the time point no statistical difference (p? 0.05). Two groups of patients reached intra-abdominal pressure level II patients in 15 cases, including 7 cases in the experimental group, 8 cases in the control group, after treatment. The decrease percentage of intra-abdominal pressure at 24, 48 and 72 hours, the time of reaching the standard within 72 hours and the time of lowering to grade I (15mmhg) in the experimental group were all better than those in the control group (p?0.05). The number of patients whose intra-abdominal pressure returned to normal on the fifth day in the experimental group was significantly higher than that in the control group (p=0.038), and there was no statistical significance at the other time points. There was no significant difference in the duration of organ failure between the two groups (p = 0.465). there was no significant difference in the duration of intensive care, total hospitalization and prognosis between the two groups (p? 0.05). conclusion: (1) neostigmine can improve the symptoms of paralytic intestinal obstruction in patients with acute pancreatitis; (2) neostigmine can reduce intraabdominal pressure I Intra-abdominal pressure in patients with grade I or above acute pancreatitis; (3) Neostigmine did not occur during the study; (4) Neostigmine had no significant advantage in reducing intra-abdominal pressure in patients with grade I acute pancreatitis as compared with conventional treatment; (5) Neostigmine was shown to improve the persistence of organ failure in patients with acute pancreatitis. Time, intensive care time, total hospitalization time and prognosis are limited. (6) Because the sample size of this study is small, there are some deviations in the experimental results, it is necessary to expand the sample size to demonstrate.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R576

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