布洛芬导致极低出生体质量儿胃出血等严重不良反应及其高危因素

High risk factors of Ibuprofen-induced severe adverse reactions including gastric hemorrhage in very low birth weight neonates

目的研究布洛芬致极低出生体质量(VLBW)早产儿不良反应发生率及其高危因素。方法对象为2017年收治于深圳市宝安区妇幼保健院使用布洛芬关闭动脉导管的VLBW早产儿。采集指标包括患儿胎龄、出生体质量、出血的高危因素,及围产期母亲因素等。采集布洛芬使用前后凝血功能、肾功能和血清总胆红素等指标变化。记录布洛芬使用后1周内消化道出血等严重不良反应。结果67例VLBW早产儿口服布洛芬致胃出血22例、肺出血11例、颅内出血9例,发生率分别高达33%、16%和13%。此外布洛芬可导致其他不良反应:凝血功能障碍(血小板<100×109/L18例,发生率为27%);肾功能损害血肌酐(Scr)升高9例发生率为13%,尿素氮(BUN)升高10例发生率为15%;血清总胆红素升高21例,发生率为31%。进一步分析布洛芬致胃出血的高危因素,出生1周内血小板<100×109/L与胃出血显著相关。出生1周内国际标准化比值(INR)>2、使用头孢三代抗生素(>7d)和糖皮质激素并未增加胃出血事件。此外,产前母亲因素与布洛芬致胃出血无显著相关性。结论布洛芬导致VLBW早产儿胃出血等严重不良反应,应密切监测血小板计数、肾功能和血清胆红素水平,必要时加用抑酸剂,减停布洛芬。

Objective This study aims to investigate the incidence of Ibuprofen-induced adverse reactions in VLBW preterm neonates and its high risk factors.Methods The VLBW premature neonates,who were treated with Ibuprofen to close ductus arteriosus in our hospital in 2017,were included as the subjects in the study.The indicators such as gestational age,birth weight,high risk factors of hemorrhage and perinatal maternal factors were included.The changes of coagulation function,renal function and serum total bilirubin before and after the use of Ibuprofen were collected.The serious adverse reactions such as gastrointestinal bleeding occurred within one week after the use ofIbuprofen were recorded.Results Sixty-seven VLBW preterm neonates received Ibuprofen orally to close ductus arteriosus.Ibuprofen caused gastric hemorrhage,pulmonary hemorrhage and intracranial hemorrhage,with the inci-dence of 33%,16% and 13% respectively.In addition,Ibuprofen caused other adverse reactions: coagulation dysfunction (the incidence of platelet count < 100×109/L was 27%),renal dysfunction (the incidence of Scr elevation was 13%,and the incidence of BUN elevation was 15%) and serum total bilirubin elevation with the incidence of 31%.The risk factors of Ibuprofen-induced gastric hemorrhage was further determined.Platelet count < 100×109/L within one week of birth was significantly associated with gastric hemorrhage.INR>2 within one week of birth,and the use of third generation Cephalosporins (> 7 days) and glucocorticoids did not increase the events of gastric hemorrhage.In addition,there was no significant correlation between prenatal maternal factors and Ibuprofen-induced gastric hemor-rhage.Conclusion The incidence of Ibuprofen-induced serious adverse reactions such as gastric hemorrhage in VLBW.Platelet count,renal function and serum bilirubin level should be closely monitored.If necessary,acid suppressant should be added,and Ibuprofen should be reduced or discontinued.