长疗程吲哚美辛治疗极低出生体重儿动脉导管开放的疗效

1、长疗程吲哚美辛治疗极低出生体重儿动脉导管开放的疗效<    【摘要】   目的： 探讨延长吲哚美辛疗程 治疗 开放性动脉导管（PDA）的疗效和安全性。方法:46例合并PDA早产儿病例随机分为吲哚美辛治疗组24例和布洛芬治疗组22例。吲哚美辛组每次口服吲哚美辛0.2 mg/kg，1次/12 h，第3次服药后412 h复查心脏彩色多普勒，PDA关闭者不再服药，未关闭者继续按原剂量服药两次，间隔时间相同，第5次服药后412 h再次复查心脏彩色多普勒。布洛芬组首次给予10 mg/kg，第2、第3次分别为5 mg/kg，每次间隔24 h，共服药3次

2、，分别于第3次服药后412 h、3236 h（相当于吲哚美辛组第5次服药后412 h）复查心脏彩色多普勒，治疗期间作血肌酐（SCr）、血钠、血小板、血清胆红素检查、记录尿量。比较两组的关闭率及副作用的发生情况。结果：吲哚美辛组5次服药关闭率（95.83%）较3次服药关闭率（62.50%）高，差异有 统计 学意义（P0.05），吲哚美辛组和布洛芬组第3次服药后的关闭率分别为62.50%和63.64%，差异无统计学意义（P0.05），而第5次服药后（或相当时间）两组的关闭率分别为95.83%和68.18%，吲哚美辛组关闭率高于布洛芬组，差异有统计学意义（P0.05），吲哚美辛组低钠和少尿例数高于布

3、洛芬组，差异有统计学意义（P0.05），而胆红素达到光疗标准例数低于布洛芬组（P0.05）。两组均无消化道出血和坏死性肠炎发生。结论：延长吲哚美辛疗程可以提高PDA关闭率，未增加药物副作用。 【关键词】   极低体重儿；开放性动脉导管；吲哚美辛；布洛芬    Abstract Objective:To determine whether prolonged oral indomethacin treatment course is efficacious and safe in closure of patent ductus arteriosus (P

4、DA) in very low birth w Ei ght (VLBW) infants. Methods:46 cases of premature infants with PDA confirmed by echocardiography whose gestational age small than 35 weeks, birth w EI ght less than 1,500 g were divided into two groups. One group infants were treated by oral indomethacin (indomethacin grou

5、p), another group infants were treated by ibuprofen (ibuprofen group). There were not significant difference in gestational age, gender, birth weight, age, and complication between the two groups. In indomethacin group infants, treatment was started with oral indomethacin 0.2 mg/kg body weight, foll

6、owed by the same dose at 12 hours intervals. Then echocardiography was performed at 412 hours after the third time taking drug. If it was indicated that PDA closed, treatment was discontinued. Otherwise, two additional same doses were given. Echocardiography was performed again to confirm if PDA clo

7、se or do not. In the ibuprofen group infants, all baby received oral ibuprofen suspension 10 mg/kg body weight for the first dose, followed at 24hour intervals by 2 additional doses of 5 mg/kg each. Echocardiography was performed to determine if PDA close or do not at 412 hours 3236 hours after the

8、third time taking drug. Serum sodium, serum creatinine, platelet count, serum bilirubin were measured and urine output was recorded during treatment course. Results:The closure rate after the fifth time taking medicine was high than that of the third taking medicine (95.83% vs 62.50%, P<0.05) in

9、indomethacin group. There was not significant difference in closure rate at the end of the third dose between indomethacin and ibuprofen with 62.5% and 63.64% respectively (P>0.05). But the closure rate was higher at 412 hours after the fifth taking drug in indomethacin group than that in ibuprof

10、en group (95.83% vs 68.18%, P<0.05). Cases number either serum sodium lower than 130 mmol/L or urine output lower than 1 mL/(kg·h) in indomethacin group was higher than those in ibuprofen group (P<0.05). Cases number whose serum bilirubin reach to phototherapy criteria in ibuprofen group

11、was higher than those in indomethacin group (P<0.05). Either group no cases develop intestinal perforation or necrotizing enterocolitis. Conclusions:Prolonged oral indomethacin course is effective and safe in VLBW with PDA.    Key words Very low birth weight infant; Patent ductus a

12、rteriosus; Indomethacin; Ibuprofen    开放性动脉导管（patent ductus arteriosus，PDA）是早产儿比较常见的并发症，体重 5001 500 g的早产极低体重儿（very low birth weight，VLBW）发病率约30%。吲哚美辛作为前列腺素合成酶抑制剂，可抑制前列腺素的合成，促进PDA关闭，自20世纪70年代始用于治疗PDA，并取得较好的效果。近年来不少报道对VLBW合并PDA，布洛芬同样有效，而且部分报道布洛芬在对肾功能损害等方面的副作用更低，安全性更好15。但最近循证 医学 认为延长吲哚美辛

13、的疗程可以降低PDA的复发率6。本研究旨在分析延长吲哚美辛的疗程是否可以提高PDA的关闭率，以及长疗程吲哚美辛口服的安全性。     1  对象和方法     1.1  研究对象    2004年月6月2006年12月我院NICU共收治胎龄35周的VLBW 396例，其中合并PDA 46例，PDA的诊断均符合下列条件：胸骨左缘2、3肋间闻及收缩期或连续性杂音， 机械 通气过程中无明显原因血气恶化需调高呼吸机参数，心脏彩色多普勒探及动脉导管以及导管内探及收缩期、舒张期双期喘流，确诊PDA

14、且血小板计数大于100×109/L、无消化道出血和肾功能损害，且排除凝血功能障碍、坏死性小肠结肠炎（NEC）者为本组研究对象。按住院号单双分为吲哚美辛口服（吲哚美辛组）24例和布洛芬口服（布洛芬组）22例。    吲哚美辛组胎龄<28周1例、30周2例、32周9例、34周8例、35周4例；布洛芬组28周1例、30周2例、32周8例、34周8例、35周3例；出生体重、性别、生后小时龄、是否双胎、合并症、围产期因素等方面有可比性，见表1。表1  两组 临床 资料比较    1.2  治疗方法 

15、   确诊PDA后给予吲哚美辛（山西临汾奇林药业有限公司）或布洛芬混悬液（广东华南药业有限公司）口服，吲哚美辛组每次给予吲哚美辛0.2 mg/kg，间隔12 h，服药第3次后412 h作心脏彩色多普勒检查，如果PDA已关闭，不再用药，否则，再按相同剂量和间隔时间用2次，共5次。布洛芬组口服布洛芬混悬液，首剂10 mg/kg，以后每间隔24 h后给药一次，每次5 mg/kg，共3次服药后不管PDA关闭与否，均不再给药。    1.3  疗效及副作用观察    两组均于用药第3次后412 h作心脏彩色多普勒检

16、查，判断PDA是否关闭，吲哚美辛组PDA未闭者，再给药2次，在第5次用药后412 h再作心脏彩色多普勒检查，而布洛芬组共服药3次，于服药第3次后412 h作心脏彩色多普勒检查，不关闭也不再用药，但在第3次用药后3236 h（相当于吲哚美辛组第5次服药后复查时间）复查心脏彩色多普勒，比较两组3次用药后PDA关闭率，和吲哚美辛组5次用药后PDA关闭率，以及布洛芬组用药412 h 和3236 h后关闭率。用药前检测凝血功能、血小板计数、血肌酐（SCr）、血Na+、血清总胆红素和直接胆红素、大便潜血，用药期间监测SCr 1次，每天监测血Na+、血清总胆红素和直接胆红素、血小板计数1次，记录24 h尿量

17、，用药后检测 SCr、大便潜血，治疗期间正常喂养。    1.4  统计学方法    用SPSS 13.0统计学 软件 作2分析或t检验，P0.05为有统计学意义     2  结果     2.1  两组PDA关闭率和病死率比较    吲哚美辛组5次服药关闭率较3次服药高，差异有显著性意义；两组3次服药后PDA关闭率差异无统计学意义，但吲哚美辛组继续服药2次后关闭率明显提高，而布洛芬组未继续服药，关闭例数也有所提高，但仍低于吲哚美辛组5次服药关闭率，差异有统计学意义，