| BackgroundsCongenital heart disease (shunt) associated pulmonary hypertension is due to a lot of left-to-right shunt by cardiovascular malformations. Because of shear force damage with the increasing pulmonary blood flow, endothelial system released endothelia which result in pulmonary arterial hypertension, pulmonary resistance increasing, heart and lung function impaired, exercise tolerance decreased, eventually develop into small pulmonary artery occlusion or fibrosis. In the development of CHD (shunt) associated PAH, pulmonary vascular lesions is not uniform, which results in bloodstream of distal pulmonary vascular bed weakened. Increased vaso-constrictive substances can result in regional pulmonary vascular lesions, such as small pulmonary arteries narrowing, vessels blocking. Endothelia receptor antagonist (Bosentan 125mg per pill, Ectelion company) can reduce pulmonary arterial hypertension (PAH) and pulmonary vascular resistance(PVR) by antagonizing endothelia receptor A and B. The long-term use of Endothelia receptor antagonist can reverse pulmonary fibrosis. There are some treatment experiences and related published reports on pulmonary hypertension in adults and the older-age children, but few in younger than 6 month infants. Until now, there are no reasonable alternative observation end points of exercise tolerance. We first present "30 ml milk feeding time" as the point of exercise tolerance in the younger than 6 month infants with CHD associated PAH through a large number of clinical cases and analysis of statistics.Methods60 cases which were younger than 6 month infants with CHD associated PAH from Jan.to Dec.in 2008 in Jinan Children Hospital were distinguished into two groups by random number method. Cases in the control group were received general treatment, which were oral digoxin 0.01mg/(kg.d),1 time per day; oral spironolactone 3mg/(kg.d), 3 times per day; oral captopril 1.5mg/(kg.d),3 times per day. Cases in the treatment group were received general treatment plus endothelin receptor antagonist Bosentan (preoperative 6.25mg,2 times per day,7 days; postoperative 12.5mg,2 times per day,1-4 weeks). The control group:male 18 cases, female 12 cases; age 1～6 months, average (3.5±1.2) months; weight 3～7.5 kg, average (5.0±2.1) kg; disease Ventricular septal defects (VSD) 20 cases, combined with Atrial Septal defects (ASD) 2 cases, Ventricular septal defect diameter≥8mm; patent ductus arteriosus (PDA) 3 cases, the arterial duct diameter≥7mm; anomalous pulmonary venous drainage 5 cases, total anomalous pulmonary venous drainage (TAPVD) 3 cases, partial anomalous pulmonary venous drainage (PAPVD) 2 cases, all combined with ASD; atrioventricular septal defect (AVSD) 2 cases, complete atrioventricular septal defect (CAVSD) 1 case, partial atrioventricular septal defect(PAVSD) 1 case. The treatment group:male 20 cases, female 10 cases; age 1-6 months, average (3.5±1.3) months; weight 3～6.8 kg, average (4.5±2.0) kg, disease:VSD 21 cases, combined with ASD 3 cases, PDA 2 cases, VSD diameter≥8mm; huge ASD1 case, cp22mm; PDA 1 case, (?)11mm; anomalous pulmonary venous drainage 3 cases, TAPVD 2 cases, PAPVD 1 case, all combined with ASD; double outlet of right ventricle (DORV) 1 case; AVSD 3 cases, CAVSD 2 cases, PAVSD 1 case. The pulmonary systolic blood pressure of cases measured by echo in two groups was all exceeded 60 mmHg, pulmonary average pressure was exceeded 45 mmHg; heart function of cases were exceededⅡclass by New York Heart Association (NYHA) standard.Patient's age, weight, preoperative pulmonary systolic pressure, preoperative cardiac function classification (NYHA), preoperative arterial blood gas analysis, operation time, aorta block time and cardiopulmonary time in two groups had no statistical significances. Cardioplegia constituents, surgery, anesthesia, cardiopulmonary bypass and ultrafiltration method, postoperative intake and output control, machine-assisted ventilation mode and setting parameters in two groups were basically the same. In the two groups, Milrinone was used to improve heart function; Nitroprusside, adenosine, NO inhalation, prostaglandin E1 and prostacyclin I2 were not.Cases in the control group were received general treatment, cases in the treatment group were received general treatment plus endothelin receptor antagonist Bosentan (preoperative 6.25mg,2 times per day,7 days; postoperative 12.5mg,2 times per day,1-4 weeks).We compared pulmonary arterial pressure and exercise tolerance (under 30 ml milk feeding time evaluation) differences among medication before, after 1 week of medication and surgery after 1 week. We compared mechanical ventilation time differences between the control group and the treatment group.Data was analysized by SPSS 11.0 statistic software. Data (x±s) fitted for normal distribution was analysized by t inspection (α=0.05). P<0.05 was defined as different significant differences.Results①Short-term low-dose of Endothelin receptor antagonist (Bosentan) can significantly reduce pulmonary systolic pressure on congenital heart disease (shunt) associated PAH. Pulmonary systolic pressure of the group with the treatment of preoperative Bosentan 6.25mg/time, 2 times/day, for 7 days has significant differences compared with of the control group (P=0.002); Pulmonary systolic pressure of the group with the treatment of postoperative Bosentan 12.5mg/time,2 times/day, for 1 week has significant differences compared with of the control group (P=0.001). Table 1.②Mechanical ventilation time with the treatment of perioperative low-dose of Bosentan has significant differences compared with of the control group (P=0.001). Table 2.③There are some treatment experiences and related published reports on pulmonary hypertension in adults and the older-age children, but few in younger than 6 month infants. Until now, there are no reasonable alternative observation end points of exercise tolerance. We first present "30 ml milk feeding time" as the point of exercise tolerance in the younger than 6 month infants with CHD associated PAH through a large number of clinical cases and analysis of statistics. The treatment of short-term low-dose of Endothelin receptor antagonist (Bosentan) can significantly reduce "30 ml milk feeding time" on congenital heart disease (shunt) associated PAH, which reduce from 20.14min to 14.71min after treatment 1week, and then to 6.63min after surgery 1 week. Table 3Conclusions①The treatment of short-term low-dose of Endothelin receptor antagonist (Bosentan) can significantly reduce the pulmonary systolic pressure of patients with congenital heart disease shunt associated PAH.②Perioperative use of small doses of Endothelin receptor antagonist, Bosentan can significantly shorten the mechanical ventilation time of patients with congenital heart disease shunt associated PAH.③It is objective and reasonable to apply "30 ml milk feeding time" as alternative observation endpoint of exercise tolerance in infants which were younger than 6 months. The treatment of short-term low-dose of Endothelin receptor antagonist (Bosentan) can significantly shorten the "30 ml milk feeding time".④There were no adverse reactions in the course of the therapy with low-dose, short-term Bosentan. The liver function reviewed at postoperative 1 month was at the normal range. It was well tolerated. |
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