目的 探讨咖啡因联合洛贝林治疗新生儿原发性呼吸暂停（AOP）的临床疗效。方法 选取2016年2月-2017年6月在随州市中心医院诊治的原发性AOP患儿86例，随机分为对照组和治疗组，每组各43例。对照组静脉推注盐酸洛贝林注射液，0.3~3 mg/次，重复推注则间隔20~30 min，累计剂量不超过20 mg/d。治疗组静脉推注枸橼酸咖啡因注射液，与盐酸洛贝林注射液交替使用，首剂量20 mg/kg，24 h后以5 mg/kg维持，根据情况追加维持量10 mg/kg，1次/d。两组均连续治疗5 d，如呼吸暂停症状缓解，则继续治疗2 d。观察两组患者临床疗效，同时比较治疗前后两组患者临床症状改善情况、血浆β-内啡肽（β-EP）、内皮素（ET）、一氧化氮（NO）水平及智力发育指数（MDI）和运动发育指数（PDI）指数。结果 治疗后，对照组和治疗组临床有效率分别为74.42%和93.02%，两组比较差异具有统计学意义（P<0.05）。治疗48 h后，两组每日AOP发作次数均明显减少（P<0.05），且治疗组发作次数明显少于对照组（P<0.05）。治疗后，治疗组用药时间、AOP消失时间和给氧治疗时间均明显短于对照组（P<0.05）。治疗后，两组β-EP水平明显降低（P<0.05），ET和NO水平明显升高（P<0.05），且治疗后治疗组β-EP、ET、NO水平明显优于对照组（P<0.05）。治疗后，两组MDI和PDI指数均明显升高（P<0.05），且治疗组MDI和PDI指数均显著高于对照组（P<0.05）。结论 咖啡因联合洛贝林治疗新生儿原发性AOP可有效调节患儿β-EP、ET、NO水平，促进脑神经发育，疗效显著。

Objective To investigate the clinical efficacy of caffeine combined with lobeline in treatment of neonatal primary apnea (AOP). Methods Patients (86 cases) with primary apnea in Suizhou Central Hospital from February 2016 to June 2017 were randomly divided into control and treatment groups, and each group had 43 cases. Patients in the control group were intravenous injection administered with Lobeline Hydrochloride Injection, 0.3-3 mg/time, the interval time was 20-30 min for the next injection, and the cumulative dose was less than 20 mg/d. Patients in the treatment group were intravenous injection administered with Caffeine Citrate Injection alternate using with Lobeline Hydrochloride Injection, the initial dose was 20 mg/kg, maintained with 5 mg/kg after 24 h, and additional maintenance dose 10 mg/kg was administered according to the situation, once daily. Patients in two groups were treated for 5 d, if the apnea symptom was alleviated, then continued treatment for 2 d. After treatment, the clinical efficacy was evaluated, and the improvement of clinical symptoms, the plasma β-EP, ET and NO levels, the MDI and PDI indexes in two groups before and after treatment were compared. Results After treatment, the clinical efficacy in the control and treatment groups was 74.42% and 93.02%, respectively, and there were differences between two groups (P<0.05). After treatment for 48 h, the daily frequency of AOP in two groups was significantly decreased (P<0.05), and the frequency in the treatment group after treatment was significantly less than that in the control group (P<0.05). After treatment, the medication time, and disappearance time of AOP and oxygen treatment time in the treatment group after treatment was significantly shorter than that in the control group (P<0.05). After treatment, the β-EP levels in two groups were significantly decreased (P<0.05), but ET and NO levels were significantly increased (P<0.05), and the β-EP、ET and NO levels in the treatment group after treatment were significantly better than those in the control group (P<0.05). After treatment, the MDI and PDI indexes in two groups were significantly increased (P<0.05), and the MDI and PDI indexes in the treatment group after treatment were significantly higher than those in the control group (P<0.05). Conclusion Caffeine combined with lobeline in treatment of neonatal primary apnea can effectively regulate the β-EP, ET and NO levels, and promote the development of brain nerve with remarkable curative effect.