長療程吲哚美辛治療極低出生體重兒動脈導(dǎo)管開放的療效

1、長療程吲哚美辛治療極低出生體重兒動脈導(dǎo)管開放的療效<    【摘要】   目的： 探討延長吲哚美辛療程 治療 開放性動脈導(dǎo)管（PDA）的療效和安全性。方法:46例合并PDA早產(chǎn)兒病例隨機(jī)分為吲哚美辛治療組24例和布洛芬治療組22例。吲哚美辛組每次口服吲哚美辛0.2 mg/kg，1次/12 h，第3次服藥后412 h復(fù)查心臟彩色多普勒，PDA關(guān)閉者不再服藥，未關(guān)閉者繼續(xù)按原劑量服藥兩次，間隔時間相同，第5次服藥后412 h再次復(fù)查心臟彩色多普勒。布洛芬組首次給予10 mg/kg，第2、第3次分別為5 mg/kg，每次間隔24 h，共服藥3次

2、，分別于第3次服藥后412 h、3236 h（相當(dāng)于吲哚美辛組第5次服藥后412 h）復(fù)查心臟彩色多普勒，治療期間作血肌酐（SCr）、血鈉、血小板、血清膽紅素檢查、記錄尿量。比較兩組的關(guān)閉率及副作用的發(fā)生情況。結(jié)果：吲哚美辛組5次服藥關(guān)閉率（95.83%）較3次服藥關(guān)閉率（62.50%）高，差異有 統(tǒng)計(jì) 學(xué)意義（P0.05），吲哚美辛組和布洛芬組第3次服藥后的關(guān)閉率分別為62.50%和63.64%，差異無統(tǒng)計(jì)學(xué)意義（P0.05），而第5次服藥后（或相當(dāng)時間）兩組的關(guān)閉率分別為95.83%和68.18%，吲哚美辛組關(guān)閉率高于布洛芬組，差異有統(tǒng)計(jì)學(xué)意義（P0.05），吲哚美辛組低鈉和少尿例數(shù)高于布

3、洛芬組，差異有統(tǒng)計(jì)學(xué)意義（P0.05），而膽紅素達(dá)到光療標(biāo)準(zhǔn)例數(shù)低于布洛芬組（P0.05）。兩組均無消化道出血和壞死性腸炎發(fā)生。結(jié)論：延長吲哚美辛療程可以提高PDA關(guān)閉率，未增加藥物副作用。 【關(guān)鍵詞】   極低體重兒；開放性動脈導(dǎo)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    開放性動脈導(dǎo)管（patent ductus arteriosus，PDA）是早產(chǎn)兒比較常見的并發(fā)癥，體重 5001 500 g的早產(chǎn)極低體重兒（very low birth weight，VLBW）發(fā)病率約30%。吲哚美辛作為前列腺素合成酶抑制劑，可抑制前列腺素的合成，促進(jìn)PDA關(guān)閉，自20世紀(jì)70年代始用于治療PDA，并取得較好的效果。近年來不少報(bào)道對VLBW合并PDA，布洛芬同樣有效，而且部分報(bào)道布洛芬在對腎功能損害等方面的副作用更低，安全性更好15。但最近循證 醫(yī)學(xué) 認(rèn)為延長吲哚美辛

13、的療程可以降低PDA的復(fù)發(fā)率6。本研究旨在分析延長吲哚美辛的療程是否可以提高PDA的關(guān)閉率，以及長療程吲哚美辛口服的安全性。     1  對象和方法     1.1  研究對象    2004年月6月2006年12月我院NICU共收治胎齡35周的VLBW 396例，其中合并PDA 46例，PDA的診斷均符合下列條件：胸骨左緣2、3肋間聞及收縮期或連續(xù)性雜音， 機(jī)械 通氣過程中無明顯原因血?dú)鈵夯枵{(diào)高呼吸機(jī)參數(shù)，心臟彩色多普勒探及動脈導(dǎo)管以及導(dǎo)管內(nèi)探及收縮期、舒張期雙期喘流，確診PDA

14、且血小板計(jì)數(shù)大于100×109/L、無消化道出血和腎功能損害，且排除凝血功能障礙、壞死性小腸結(jié)腸炎（NEC）者為本組研究對象。按住院號單雙分為吲哚美辛口服（吲哚美辛組）24例和布洛芬口服（布洛芬組）22例。    吲哚美辛組胎齡<28周1例、30周2例、32周9例、34周8例、35周4例；布洛芬組28周1例、30周2例、32周8例、34周8例、35周3例；出生體重、性別、生后小時齡、是否雙胎、合并癥、圍產(chǎn)期因素等方面有可比性，見表1。表1  兩組 臨床 資料比較    1.2  治療方法 

15、   確診PDA后給予吲哚美辛（山西臨汾奇林藥業(yè)有限公司）或布洛芬混懸液（廣東華南藥業(yè)有限公司）口服，吲哚美辛組每次給予吲哚美辛0.2 mg/kg，間隔12 h，服藥第3次后412 h作心臟彩色多普勒檢查，如果PDA已關(guān)閉，不再用藥，否則，再按相同劑量和間隔時間用2次，共5次。布洛芬組口服布洛芬混懸液，首劑10 mg/kg，以后每間隔24 h后給藥一次，每次5 mg/kg，共3次服藥后不管PDA關(guān)閉與否，均不再給藥。    1.3  療效及副作用觀察    兩組均于用藥第3次后412 h作心臟彩色多普勒檢

16、查，判斷PDA是否關(guān)閉，吲哚美辛組PDA未閉者，再給藥2次，在第5次用藥后412 h再作心臟彩色多普勒檢查，而布洛芬組共服藥3次，于服藥第3次后412 h作心臟彩色多普勒檢查，不關(guān)閉也不再用藥，但在第3次用藥后3236 h（相當(dāng)于吲哚美辛組第5次服藥后復(fù)查時間）復(fù)查心臟彩色多普勒，比較兩組3次用藥后PDA關(guān)閉率，和吲哚美辛組5次用藥后PDA關(guān)閉率，以及布洛芬組用藥412 h 和3236 h后關(guān)閉率。用藥前檢測凝血功能、血小板計(jì)數(shù)、血肌酐（SCr）、血Na+、血清總膽紅素和直接膽紅素、大便潛血，用藥期間監(jiān)測SCr 1次，每天監(jiān)測血Na+、血清總膽紅素和直接膽紅素、血小板計(jì)數(shù)1次，記錄24 h尿量

17、，用藥后檢測 SCr、大便潛血，治療期間正常喂養(yǎng)。    1.4  統(tǒng)計(jì)學(xué)方法    用SPSS 13.0統(tǒng)計(jì)學(xué) 軟件 作2分析或t檢驗(yàn)，P0.05為有統(tǒng)計(jì)學(xué)意義     2  結(jié)果     2.1  兩組PDA關(guān)閉率和病死率比較    吲哚美辛組5次服藥關(guān)閉率較3次服藥高，差異有顯著性意義；兩組3次服藥后PDA關(guān)閉率差異無統(tǒng)計(jì)學(xué)意義，但吲哚美辛組繼續(xù)服藥2次后關(guān)閉率明顯提高，而布洛芬組未繼續(xù)服藥，關(guān)閉例數(shù)也有所提高，但仍低于吲哚美辛組5次服藥關(guān)閉率，差異有統(tǒng)計(jì)學(xué)意義，