强化与非强化胰岛素治疗重型创伤性脑损伤后高血糖症的随机对照临床试验

摘要

目的 探讨强化胰岛素治疗(ⅡT)在重型创伤性脑损伤(TBI)后急性高血糖症的治疗过程中的适宜血糖浓度. 方法 将连云港市东方医院和连云港市第一人民医院自2014年6月至2016年9月招募的208例重型TBI后高血糖症患者,按随机数字表法分为ⅡT组(n=156)和非ITT组(n=52).根据目标血糖水平将ⅡT组患者分为重度组、中度组、轻度组,血糖水平分别为4.4～7.0、7.1～10.0、10.1～13.0 mmol/L,每组52例.治疗后6个月采用Kaplan-Meier法进行生存分析.比较各组患者治疗后不同时间改良Rankin量表(mRS)、巴氏指数(BI)、格拉斯哥预后评分(GOS)、糖化血红蛋白和脑脊液乳酸含量、格拉斯哥昏迷评分(GCS)、急性生理学及慢性健康评估Ⅱ(APACHEⅡ)评分、重症监护病房(ICU)住院天数、不良事件的发生率. 结果 ⅡT组患者入院7d内血糖均控制在目标范围内.Log-rank检验显示轻度和中度组患者治疗后6个月生存率高于非ITT组、重度组,差异均有统计学意义(x2=4.237,P=0.040;x2=5.621,P=0.018);与非ITT组、重度组比较,轻度和中度组患者治疗后3个月mRS评分降低,治疗后1、3、6个月GOS评分、BI指数增加,差异有统计学意义(P＜0.05);与非ITT组、轻度和中度组比较,重度组患者治疗后7d糖化血红蛋白降低,差异有统计学意义(P＜0.05).与非ITT组、重度组比较,轻度和中度组患者治疗后7d脑脊液乳酸含量,治疗后7d、14 d APACHEⅡ评分,ICU住院天数,不良事件发生率均降低,差异有统计学意义(P＜0.05);轻度和中度组患者血糖水平为(8.40±0.39) mmol/L. 结论 适当强度的ⅡT可促进TBI患者的短中期预后,且ⅡT治疗TBI后急性高血糖症的血糖适宜范围为(8.40±0.39) mmol/L.%Objective To explore the appropriate target ranges of blood glucose in intensive insulin therapy (ⅡT) for acute hyperglycemia following traumatic brain injury (TBI).Methods A randomized,open-label and controlled clinical trial was performed on 208 patients,admitted to our hospitals from Junuary 2014 to Sepember 2016.They were divided into ⅡT group (n=156),who were subdivided into slight (10.1-13.0 mmol/L),moderate (7.1-10.0 mmol/L),and strict (4.4-7.0 mmol/L) control blood glucose groups (n=52),and non-ⅡT group (n=52).Survival analysis 6 months after treatment was performed by Kaplan-Meier method.Modified Rankin scale (mRS) scores and Barthel index (BI),Glasgow Outcome scale (GOS) scores,concentrations of lactic acid in cerebrospinal fluid (CSF) and glycosylated hemoglobin,Glasgow coma scale (GCS) scores,Acute Physiology and Chronic Health Evaluation (APACHE Ⅱ) scores,Length of staying in intensive care unit (ICU) and incidence of adverse events were compared between the patients from different groups at different treatment times.Results Blood glucose level within 7 d of admission in patients ofⅡT group was in target ranges.The survival rate of patients from slight and moderate control blood glucose groups was significantly higher than that in the non-ⅡT group and strict control blood glucose group 6 months after treatment (x2=4.237,P=0.040;x2=5.621,P=0.018).As compared with those in the non-ⅡT group and strict control blood glucose group,the mRS scores 3 months after treatment were significantly decreased,and GOS scores and BI one,3 and 6 months after treatment were significantly increased in patients from slight and moderate control blood glucose groups (P＜0.05).As compared with that in the non-ⅡT group,and slight and moderate control blood glucose groups,the glycosylated hemoglobin level 7 d after treatment was significantly decreased in strict control blood glucose group (P＜0.05).As compared with those in the non-ⅡT group and strict control blood glucose group,the concentration of lactic acid in CSF 7 d after treatment,APACHE Ⅱ scores 7 and 14 d after treatment,length of staying in ICU and incidence of adverse events were significantly decreased in patients from slight and moderate control blood glucose groups (P＜0.05).The mean value of blood glucose in slight and moderate control blood glucose groups was (8.40±0.39) mmol/L.Conclusion Proper ⅡT improves the outcomes of TBI patients and (8.40±0.39) mmol/L are established as the target ranges in ⅡT for TBI.