口服普萘洛尔治疗早产儿视网膜病的疗效与安全性研究

摘要

目的 探讨早产儿视网膜病(retinopathy of prematurity,ROP)患儿口服普萘洛尔治疗前、后血管内皮生长因子(vascular endothelial growth factor ,VEGF)和sE－选择素的变化,分析普萘洛尔治疗ROP的安全性和有效性.方法 前瞻性选择2015 年8 月至2017 年8 月本院收治的胎龄＜32周、经眼底筛查患有2期ROP且无附加病变的早产儿.应用随机分配软件按照1∶1比例随机分为普萘洛尔治疗组和对照组,治疗组口服普萘洛尔0.5 mg/( kg· d),12 h 1次,用药时间持续至视网膜血管完全发育或者出院前,服用时间不超过30 d.对照组口服同等剂量安慰剂.分析两组患儿VEGF和sE－选择素的变化及口服普萘洛尔的不良反应发生情况.结果 共纳入84例患儿,其中对照组43例,治疗组41例.治疗组重度ROP发生率明显低于对照组(17.1%比37.2%),需全麻下激光手术治疗的眼睛只数所占比例明显低于对照组(3.7%比12.8%),差异有统计学意义(P＜0.05).治疗组普萘洛尔治疗10 d后血清sE－选择素水平显著低于对照组,差异有统计学意义( P＜0.001);两组血清VEGF水平差异无统计学意义(P＞0.05).两组患儿均无死亡,普萘洛尔治疗组治疗20 d和30 d时血钾显著高于对照组[(4.2 ±0.9) mmol/L比(3.8 ±0.4) mmol/L,(4.4 ±0.9) mmol/L 比(3.9 ±0.4) mmol/L],差异有统计学意义(P＜0.05),但血钾值均在正常范围.两组其他不良反应发生情况差异无统计学意义(P＞0.05).结论 普萘洛尔治疗ROP可能有一定疗效,口服用药无明显不良反应发生.%Objective To study the changes of vascular endothelial growth factor ( VEGF) and sE－Selectin in serum before and after oral propranolol therapy for retinopathy of prematurity (ROP), and to study the safety and efficacy of oral administration of propranolol in the treatment of ROP.Method Preterm infants whose gestational age ＜32 weeks and ROP Ⅱstage without plus disease were selected as the objects of our study.The infants were randomly enrolled into treatment and placebo groups in a 1∶1 allocation.The propranolol dosage was 0.25 mg/(kg· d), twice daily orally.The duration of treatment was to complete retinal vessel development or discharge , the longest oral propranolol treatment did not exceed 30 days. Result The incidence of severe ROP in the treatment group was significantly reduced (17.1%vs.37.2%, P＝0.033), and the number requiring laser treatment of the eyes was significantly reduced (3.7%vs.12.8%, P＝0.048).After 10 days of treatment, the serum sE－Selectin decreased significantly in the treatment group, it was significantly lower than that in the placebo group ( P＜0.001).There were no mortalities in the treatment group and the placebo group.The heart rate of the treatment group was lower than that of the placebo group, however, there was no significant difference between the two groups (P＞0.05).There were no significant differences in mean arterial pressure , body weight gain, and urine volume between the two groups (P＞0.05).The serum potassium level in the treatment group was significantly higher than that in the placebo group after the treatment of 20 days and 30 days, [(4.2 ±0.9) mmol/L vs.(3.8 ± 0.4) mmol/L, ( 4.4 ±0.9 ) mmol/L vs.( 3.9 ±0.4 ) mmol/L ], the differences were statistically significant (P＜0.05).However, all the children had normal serum potassium.During treatment, there was no significant differences between the two groups for the incidence of oxygen inhalation and the number of apnea in all children (P＞0.05).Conclusion Propranolol may have a certain therapeutic effect on the progression of ROP.The oral administration was relatively safe and without significant adverse effects.