肠道标志物协助评价不同程度休克患者早期肠内营养的利弊

Intestinal markers assist in evaluating the advantages and disadvantages of early enteral nutrition in patients with different degrees of shock

目的通过肠道生物标志物肠型脂肪酸结合蛋白(I-FABP)、瓜氨酸的动态变化来协助评价不同程度休克患者早期肠内营养是否能够获益。方法①由2021年2月至2023年2月, 纳入南京医科大学附属苏州医院重症监护室目标患者133例, 观察期为入院7 d, 肠道生物标志物监测3次, 分别为:入院后24 h(D1)、入院第3天(D3)、入院第7天(D7)。②纳入患者根据入院48 h内接受去甲肾上腺素剂量分为:安全剂量组[接受去甲肾上腺素<0.3 μg/(kg·min)], 危险剂量组[接受去甲肾上腺素≥0.3 μg/(kg·min)]。③安全剂量组标按照指南推荐意见实施早期肠内营养, 危险剂量组随机予早期肠内营养(EEN)和延迟肠内营养(DEN)。④观察三组肠型脂肪酸结合蛋白、瓜氨酸的动态变化;比较危险剂量EEN/DEN不同时间点肠道生物标志物的差异。⑤记录危险剂量EEN/DEN组28 d内生存时间, 绘制Kaplan-Meier生存曲线。⑥纳入总体进行28 d死亡的单因素及多因素回归分析。结果①比较安全剂量EEN组/危险剂量EEN组基线资料, APACHE Ⅱ评分、动脉血乳酸、AGI分级、喂养中断、7 d内喂养总时间、28 d生存人数差异有统计学意义(P<0.05);比较危险剂量EEN组/危险剂量DEN组基线资料, 仅喂养中断数差异有统计学意义(P<0.05)。②安全剂量EEN组与危险剂量DEN组变化趋势相同:I-FABP从D3至D7开始有明显下降趋势(P<0.05);瓜氨酸从D1至D3降低, 但从D3至D7开始回升(P<0.05);危险剂量EEN组, I-FABP在监测期内无明显变化(P>0.05);瓜氨酸在D1至D3有明显下降(P<0.05);危险剂量EEN/DEN比较仅D7-I-FABP差异有统计学意义(P<0.05)。③比较危险剂量EEN/DEN生存曲线, DEN可以提高危险剂量下危重患者早期生存率(Breslow检验P = 0.0447)。④年龄(OR=1.069, 95%CI: 1.002~1.140, P=0.044)是28 d死亡的独立危险因素;BMI(OR=0.772, 95%CI: 0.604~0.987, P=0.039)、无喂养中断(OR=0.044, 95%CI: 0.004~0.455, P=0.009)、7 d内喂养总时间(OR=0.959, 95%CI: 0.923~0.997, P=0.036)是其保护因素。结论安全剂量下EEN和危险剂量下DEN能有效地逆转肠细胞的的坏死, 促进肠细胞功能的恢复。危险剂量EEN不能明确是28 d死亡的危险因素, 但其不仅增加了喂养中断发生率, 从肠道生物标志物的角度也不利于肠细胞功能的恢复。

Objective To evaluate whether early enteral nutrition could benefit patients with different degrees of shock by dynamic changes of intestinal biomarkers intestinal fatty acid-binding protein(I-FABP)and citrulline.Methods(1)From February 2021 to February 2023,133 target patients in the Intensive Care Unit of Suzhou Hospital Affiliated to Nanjing Medical University were enrolled.The observation period was 7 days after admission,and intestinal biomarkers were monitored three times:24 hours after admission(D1),the third day after admission(D3),and the seventh day after admission(D7).(2)The enrolled patients were divided into two groups according to the dose of norepinephrine received within 48 hours after admission:safe dose group[receiving norepinephrine<0.3μg/(kg·min)]and hazardous dose group[receiving norepinephrine≥0.3μg/(kg:min)].The safe dose group was given early enteral nutrition according to the guidelines,and the dangerous dose group was randomly(random number)given early enteral nutrition(EEN)and delayed enteral nutrition(DEN).(4)The dynamic changes of intestinal fatty acid binding protein and citrulline in three groups were observed;The differences of intestinal biomarkers at different time points of dangerous dose of EEN/DEN were compared.The survival time of EEN/DEN group within 28 days was recorded,and Kaplan-Meier survival curve was drawn.Univariate and multivariate regression analyses of 28-day mortality were performed for the included population.Results(I)The baseline data,APACHE II score,arterial blood lactic acid,AGI grade,feeding interruption,total feeding time within 7 days,and 28-day survival number were statistically different between safe dose EEN group and hazardous dose EEN group(P<0.05).Compared the baseline data of the dangerous dose EEN group and the dangerous dose DEN group,only the number of feeding interruptions was statistically different(P<0.05).(2)The trend of change in the safe dose EEN group was the same as that in the dangerous dose DEN group:I-FABP decreased significantly from D3 to D7(P<0.05);Citrulline decreased from D1 to D3,but increased from D3 to D7(P<0.05).In dangerous dose EEN group,I-FABP had no significant change during the monitoring period(P>0.05).Citrulline decreased significantly from D1 to D3(P<0.05).The EEN/DEN ratio at dangerous dose was significantly different only for D7-I-FABP(P<0.05).Compared with the survival curve of EEN/DEN at risk dose,DEN could improve the early survival rate of critically ill patients at risk dose(Breslow test P=0.0447).(4)Age(OR=1.069,95%CI:1.002-1.140,P=0.044)was independent risk factor for 28-day death.BMI(OR=0.772,95%CI:0.604-0.987,P=0.039),no feeding interruption(OR=0.044,95%CI:0.004-0.455,P=0.009),total feeding time within 7 days(OR=0.959,95%CI:0.923-0.997,P=0.036)were the protective factors.Conclusions EEN at the safe dose and DEN at the dangerous dose can effectively reverse the necrosis of enterocyte and promote the recovery of enterocyte function.EEN is not a clear risk factor for death at 28 days,but it not only increases the incidence of feeding interruption,but also do not conduct the recovery of intestinal cell function from the perspective of intestinal biomarkers.