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吸入伊洛前列素和一氧化氮治疗先天性心脏病术后肺动脉高压

Inhaled iloprost and nitric oxide for pediatric pulmonary hypertension after congenital heart operation

摘要目的 探讨吸入伊洛前列素对先天性心脏病(CHD)术后早期机械通气和持续吸入一氧化氮(NO)的基础上,仍合并肺动脉高压(PH)病儿的疗效及对预后的影响,并初步探讨其作用机制.方法 30例CHD根治手术后在机械通气和持续一氧化氮(NO)吸入的基础上仍合并PAH的病儿,随机分为试验(T)组和对照(C)组.在原治疗基础上,T组给予伊洛前列素100 ng·kg-1·min-1,吸入10 min,C组给予0.9%NaCl 4ml吸入.每4h一次,连续治疗48 h.超声和心电监测观察病儿的血流动力学和呼吸机条件的改变.对比首次吸药前后血浆环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)浓度变化.结果 T组停止吸入伊洛前列素后20min,肺动脉收缩压(sPAP)和肺动脉收缩压/主动脉收缩压(sPAP/sBP)明显下降,分别为:(43.23±11.72)mm Hg(1 mm Hg=0.133 kPa)和0.48±0.13,均小于C组(53.13±13.60)mm Hg和0.60 ±0.15,P<0.05.停止吸药120 min,T组sPAP/sBP仍然小于C组(0.48±0.09对0.59±0.14,P<0.05).连续治疗24 h和48 h,T组sPAP和sPAP/sBP继续下降,均明显小于C组(P<0.01).停止首次吸药后20 min,T组cAMP(578.68±193.05)pg/dl较治疗前(406.64±179.18)pg/dl明显升高(P<0.01),也明显大于C组(392.26±94.46)pg/dl(P<0.01).C组2例因肺高压危象(PHC)死亡,T组无死亡.结论 CHD双心室矫正术后早期机械通气和持续吸入NO仍合并PH病儿,吸入伊洛前列素后可明显降低sPAP和sPAP/sBP.伊洛前列素可能减少肺高压危象(PHC)导致的死亡.其扩血管作用可能与血浆cAMP浓度升高有关.

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abstractsObjective To investigate the hemodynamic effects and mechanisms of aerosolized iloprost in children with pulmonary hypertension(PAH)after congenital heart surgery,in the setting of early ventilation and continuous nitric oxide(NO)inhalation were administered.To observe the outcomes of the patients after iloprnst therapy.Methods From April 2008 to April 2009,all postoperative children with PAH in ICU,Fuwai hospital had regularly been given ventilation and NO inhalation at a dose of 10 ppm for 2 hours since they were leaving the operation room,and then ultrasonic cardiography was used to evaluate the systolic pulmonary arterial pressure(sPAP=4×TIVmax+RAP).Thirty children were diagnosed as having postoperative PAH for sPAP/sBP≥0.5.They were divided into two groups(group T and group C)randomly,with ventilation and NO inhalation administered continuously,and were given inhaled iloprost at a dose of 100 ng·kg-1·min-1*10 min and inhaled 0.9% NaCl 4ml respectively,once every 4 hours for 48 hours.We used the 24-hour cardiac monitors and ultrasonic cardiography for hemodynamic monitoring in the patients of two groups at the six time points:baseline(t1),20 min later after the first inhalation(t2),120 min later after the first inhalation(t3),24 hours later after the treatment(t4),48 hours later after the treatment(t5) and 24 hours after ceasing the last inhalation(t6).We examine the blood cAMP and cGMP by ELISA assay before and after the first inhalation.We observed the blood coagulation,the liver and kidney function of these patients.The outcomes of these patients were also investigated.Results At t1,the sPAP and sPAP/sBP had no differences between the two groups.At t2,the sPAP(43.23±11.72)mmHg and sPAP/sBP(0.48±0.13)in group T were both lower than the sPAP(53.13±13.60)mmHg and sPAP/sBP(0.60±O.15)in group C(P<0.05).At t3,the sPAP/sBP of group T was also lower than that of group C(0.48±0.09 vs 0.59±0.14,P<0.05).At t4 and t5,the sPAP in group T were (39.84±12.87)and(34.99±12.98)mm Hg,with sPAP/sBP(0.42±0.15)and(0.36±0.14),were much lower than those in group C(P<0.01).From t1 to t2,the cAMP level increased sharply from(406.64±179.18)to(578.68±193.05)pg/dl in group T(P<0.01),and was also obviously higher than that in group C at t2(392.26±94.46)pg/dl(P<0.01).HR,BP and RAP showed no notable difference between two groups at every time point.So did the PIP.There were no differences in coagulation,liver and kidney function at t6.2 patients died from pulmonary hypertension crisis(PAH)in group C and no one in group T.One patient showed flush during the treatment in group T and recovered spontaneously after the inhalation.Nevertheless,none in group C.Conclusiou Inhaled iloprost significantly improved pulmonary hemodynamics in children with PAH after congenital heart operation even thongh they were ventilated and inhaling NO.Increased blood cAMP level was considered to be a contributing factor.Howeve,systemic BP remain unaffected after iloprost inhalation.Aerosolized iloprost may be associated with improvement in the survival and deczeased PHC.

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