罗沙替丁预防应激性黏膜病变的随机对照研究

A randomized controlled study of roxatidine in the prevention of stress related mucosal disease

目的评价静脉罗沙替丁预防重症监护病房(intensive care unit,ICU)重症患者消化道出血的疗效,并与奥美拉唑进行比较。方法采用随机对照研究,纳入ICU预计入住时间不少于5 d、机械通气时间大于48 h、具有发生应激性黏膜病变(stress related mucosal disease,SRMD)危险因素的成年患者,随机(随机数字法)分为试验组(罗沙替丁组:注射用盐酸罗沙替丁醋酸酯75 mg溶于20 mL生理盐水注射液静脉推注,用药间隔12 h)及对照组(奥美拉唑组:注射用奥美拉唑40 mg溶于100 mL生理盐水注射液静脉滴注30 min,用药间隔12 h)。记录两组患者人口学资料、急性生理与慢性健康评分(APACHEⅡ)及入组第1天序贯脏器衰竭(SOFA)评分,及研究期间肠内营养及消化道出血情况;用药前、用药开始后每2 h测量胃液pH值,连续测量5 d,计算每24 h内pH均数及pH≥4的百分比;首次用药前及第5天用药结束后送检胃液细菌培养;第1~5天检测胃液及便潜血;记录是否出现应激性黏膜病变出血;住院时间、ICU及第28天病死率;不良反应等。采用SPSS 22.0软件进行数据分析,计量资料组间比较采用方差分析或秩和检验,计数资料组间比较采用卡方检验,以P<0.05为差异有统计学意义。结果2017年10月至2018年3月共入选患者91例,试验组46例,对照组45例,两组患者性别、年龄、体质量指数、肠内营养状况、APACHEⅡ评分及第1天SOFA评分差异均无统计学意义(P>0.05)。罗沙替丁醋酸酯能使胃液pH迅速升至≥4.0,并在监测期间持续稳定在pH≥4.0,奥美拉唑能使胃液pH迅速升至≥5.0,并在监测期间持续稳定在pH≥5.0。罗沙替丁治疗组患者在第二个24 h内平均胃液pH≥4.0达82.5%,并稳步上升,在第5天时90%的患者平均胃液pH≥4.0。两组消化道出血情况、ICU及住院时间以及28 d病死率均差异无统计学意义(P>0.05),研究期间无药物不良反应发生。Logistic回归分析未筛选出SRMD的危险因素。结论注射用盐酸罗沙替丁醋酸酯可迅速提高并维持胃液pH值至4.0以上,与奥美拉唑在抑制胃酸分泌、预防应激性黏膜病变合并消化道出血等方面具有相似的疗效和安全性。

Objective To evaluate the efficacy of roxatidine and omeprazolein on preventing gastrointestinal bleeding in critically ill patients.Methods A prospective cohort study was conducted in adult patients admitted to an intensive care unit(ICU),who had risk factors for stress related mucosal disease(SRMD),and had an estimated stay of no less than 5 days and mechanical ventilation for more than 48 h.Patients were randomized into the experiment group(Roxatidine 75 mg IV Q12 h)and control group(Omeprazole 40 mg IV Q12 h).Demographic data,acute physiology and chronic health score(APACHEⅡ)and SOFA score on day 1 were collected,intragastric pH values were tested every 2 hours for the first 5 days,the daily average of pH and proportion of patients with average pH≥4 were calculated.Stool occult blood were detected at day 1 and bacterial culture of gastric juice were performed before medication administration and on day 5 after medication administration.The implementation of enteral nutrition support,situation of gastrointestinal hemorrhage and adverse effects were analyzed.Furthermore,length of hospital stay and mortality in ICU and on the 28th day were acquired.SPSS 22.0 software was used for data analysis.Consecutive data were expressed as mean and standard deviation,categorical data were expressed as frequencies(percentage).Comparison of measurement data between groups was performed by analysis of variance or rank sum test.Comparison of count data between groups was performed by the Chi-square test.P<0.05 was regarded as statistically significant.Results A total of 91 patients were recruited and randomly separated into experimental group(n=46)and control group(n=45)from October 2017 to March 2018.There were no statistical differences in gender,age,body mass index(BMI),enteral nutrition status,APACHEⅡand SOFA score on day 1 between the two groups(all P>0.05).Roxatidine in the experiment group rapidly increased the intragastric pH to≥4.0 and continued to stabilize at pH≥4.0 during the monitoring period.Omeprazole increased and maintained intragastric pH≥5.0.The proportion of patients with average pH≥4.0 was 82.5%in the second 24 hours in the experiment group,and stably increased to 90%on day 5.There were no significant differences between groups in gastrointestinal bleeding,length of hospital stay,and mortality in ICU and on 28th day(all P>0.05).No drug related adverse effects occurred during the study period.Logistic-regression analysis did not screen for risk factors of SRMD.Conclusions Roxatidine acetate hydrochloride can rapidly elevate and maintain the gastric pH above 4.0,and has similar efficacy and safety as omeprazole in inhibiting gastric acid secretion and preventing SRMD with gastrointestinal bleeding.