西地那非治疗新生儿持续性肺动脉高压的Meta-分析
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摘要
目的系统评价西地那非治疗新生儿持续性肺动脉高压(PPHN)的有效性和安全性,为临床治疗提供参考依据。方法计算机检索Pub Med、The Cochrane Library、Ovid-Embase、中国期刊全文数据库(CJFD)、万方数据库和中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM),收集西地那非治疗新生儿PPHN的随机对照试验(RCTs),严格根据纳入排除标准,对纳入文献进行内在偏倚风险评估、资料提取、运用Rev Man5. 3软件进行数据合并。结果最终纳入9个RCTs。Meta-分析结果显示:与基础治疗相比,加用西地那非能降低病死率[RR=0. 16,95%CI(0. 06,0. 41),P <0. 01],降低肺动脉压[MD=13. 69,95%CI(3. 98,23. 40),P <0. 01],升高氧分压[MD=6. 51,95%CI(5. 13,7. 89),P <0. 01],降低二氧化碳分压[MD=16. 04,95%CI(11. 33,20. 74),P <0. 01],且差异均有统计学意义;但在升高血氧饱和度[MD=14. 34,95%CI(-3. 72,32. 40),P> 0. 01],降低氧合指数[MD=21. 43,95%CI(-3. 98,46. 84),P=0. 01]方面,两组差异无统计学意义。结论西地那非在降低PPHN患儿的病死率和肺动脉压,升高氧分压和降低二氧化碳分压方面具有一定优势,局限于纳入研究数量和随访时间,在缩短其住院时间和机械通气时间等方面尚不明确,且缺乏长期安全性评估结果。
Objective To evaluate the efficacy and safety of sildenafil in the treatment of persistent pulmonary hypertension in newborns,and to provide evidence-based reference for clinical treatment. Methods Databases including Pub Med,the Cochrane Library,Ovid-EMbase,CJFD,Wanfang Data,CBM and VIP were searched to collect RCTs about PPHN treated with sildenafil in newborns. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation according to the clinical inclusion and exclusion criteria. Results A total of 9 RCTs were included. The results of meta-analysis showed that,compared with basic therapy,sildenafil could significantly reduce the mortality[RR = 0. 16,95% CI( 0. 06,0. 41),P < 0. 01]and pulmonary arterial pressure[MD = 13. 69,95% CI( 3. 98,23. 40),P < 0. 01],increase oxygen partial pressure [MD = 6. 51,95% CI( 5. 13,7. 89),P <0. 01],and reduce carbon dioxide partial pressure[MD = 16. 04,95% CI( 11. 33,20. 74),P < 0. 01]. The difference was statistically significant,but there was no statistically significant difference in the increase of oxygen saturation[MD = 14. 34,95% CI(-3. 72,32. 40),P > 0. 01] or in the decrease of oxygenation indexes[MD = 21. 43,95% CI(-3. 98,46. 84),P = 0. 01]. Conclusions Current evidence suggests that sildenafil can improve the mortality and pulmonary arterial pressure during the treatment of PPHN,and is effective for increasing oxygen partial pressure and decreasing carbon dioxide partial pressure. Because of the limited amount of inclusion and follow-up time of research,the mechanism by which the length of hospital stay and the duaration of mechanical ventilation are shortened is not clear. Moreover,long-term safety evaluation results are lacking.
Objective To evaluate the efficacy and safety of sildenafil in the treatment of persistent pulmonary hypertension in newborns,and to provide evidence-based reference for clinical treatment. Methods Databases including Pub Med,the Cochrane Library,Ovid-EMbase,CJFD,Wanfang Data,CBM and VIP were searched to collect RCTs about PPHN treated with sildenafil in newborns. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation according to the clinical inclusion and exclusion criteria. Results A total of 9 RCTs were included. The results of meta-analysis showed that,compared with basic therapy,sildenafil could significantly reduce the mortality[RR = 0. 16,95% CI( 0. 06,0. 41),P < 0. 01]and pulmonary arterial pressure[MD = 13. 69,95% CI( 3. 98,23. 40),P < 0. 01],increase oxygen partial pressure [MD = 6. 51,95% CI( 5. 13,7. 89),P <0. 01],and reduce carbon dioxide partial pressure[MD = 16. 04,95% CI( 11. 33,20. 74),P < 0. 01]. The difference was statistically significant,but there was no statistically significant difference in the increase of oxygen saturation[MD = 14. 34,95% CI(-3. 72,32. 40),P > 0. 01] or in the decrease of oxygenation indexes[MD = 21. 43,95% CI(-3. 98,46. 84),P = 0. 01]. Conclusions Current evidence suggests that sildenafil can improve the mortality and pulmonary arterial pressure during the treatment of PPHN,and is effective for increasing oxygen partial pressure and decreasing carbon dioxide partial pressure. Because of the limited amount of inclusion and follow-up time of research,the mechanism by which the length of hospital stay and the duaration of mechanical ventilation are shortened is not clear. Moreover,long-term safety evaluation results are lacking.
引文
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[2] Walsh-Sukys M C,Tyson J E,Wright L L,et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide:practice variation and outcomes[J].Pediatrics,2000,105(1 Pt 1):14.
[3]王琳,侯洁.西地那非联合硫酸镁治疗新生儿持续性肺动脉高压的临床研究[J].北方药学,2014(4):45-46.
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[7]张耀东,谭利娜,王彩君,等.西地那非治疗新生儿持续性肺动脉高压的系统分析[J].中国医院药学杂志,2014,34(22):1933-1938.
[8]蒋璐灿,全淑燕,李佳莲,等.西地那非治疗新生儿持续性肺动脉高压的系统评价[J].中国药房,2017,28(9):1211-1215.
[9] Bendapudi P,Rao G G,Greenough A. Diagnosis and management of persistent pulmonary hypertension of the newborn[J]. Paediatr Respir Rev,2015,16(3):157-61.
[10] March U. Handbook for systematic reviews of interventions[J]. N-S Arch Phormacol,2009,5(2):S38.
[11] Vargas-Origel A,Gómez-Rodríguez G,Aldana-Valenzuela C,et al. The use of sildenafil in persistent pulmonary hypertension of the newborn.[J]. Am J Perinat,2010,27(3):225-30.
[12] Baquero H,Soliz A,Neira F,et al. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn:a pilot randomized blinded study[J]. Pediatrics,2006,117(4):1077.
[13] Roberto Herrera Torres,et al. Oral sildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns[J]. Rev Mex Pediatr,2006,73(4):159-163.
[14]单明琳.西地那非联合高频振荡通气治疗新生儿持续肺动脉高压的效果研究[J].中国继续医学教育,2016,8(15):133-135.
[15]李江鸿.西地那非联合肺表面活性物质治疗胎粪吸入综合征伴持续肺动脉高压患儿临床疗效[J].山西医科大学学报,2014,45(2):126-128.
[16]王岩.西地那非联合硫酸镁治疗新生儿持续性肺动脉高压的临床效果[J].中外医疗,2016,35(12):46-47.
[17]张继英,俞建德.高频通气联合西地那非治疗新生儿持续性肺动脉高压的临床疗效[J].中国妇幼健康研究,2015(2):271-273.
[18]赵赛,程怀平,田兆方.枸橼酸西地那非片联合多巴胺治疗对新生儿持续肺动脉高压血清炎性因子水平的影响[J].儿科药学杂志,2015(8):14-17.
[19]王媛媛,张成元,李忠良.枸橼酸西地那非治疗新生儿持续性肺动脉高压及改善右心功能研究[J].中国临床研究,2012,25(7):667-669.
[20] Shah P S,Ohlsson A. Sildenafil for pulmonary hypertension in neonates[J]. Cochrane Database Syst Rev,2011,39(8):CD005494.
[21] Krystle M,Perez,Laughon M. Sildenafil in term and premature infants:a systematic review[J]. Clin Ther,2015,37(4):2598-2608.
[22] Huddleston A J,Knoderer C A,Morris J L,et al. Sildenafil for the treatment of pulmonary hypertension in pediatric patients[J]. Pediatr Cardiol,2009,30(7):871-882.
[23] Peiravian F,Amirghofran A A,Borzouee M,et al. Oral sildenafil to control pulmonary hypertension after congenital heart surgery[J]. Asian Cardiovase Thorac Ann,2007,15(2):113-117.
[24] Alain F,Ghazwan B,Mary B T,et al. Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease[J]. Intensive Care Med,2011,37(3):502-509.
[25] Huddleston A J,Knoderer C A,Morris J L,et al. Sildenafil for the treatment of pulmonary hypertension in pediatric patients[J]. Pediatr Cardiol,2009,30(7):871-882.
[26] Schulz K F,Chalmers I,Hayes R J,et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials[J]. JAMA,1995,273(5):408-12.
[27] Odgaard-Jensen J,Vist G E,Timmer A,et al. Randomisation to protect against selection bias in healthcare trials[J]. Cochrane Database Syst Rev, 2011(4):MR000012.
[28] Savovic J,Jones H E,Altman D G,et al. Influence of reported study design characteristics on intervention effect estimates from randomized,controlled trials[J].Ann Intern Med,2012,157(6):429-38.
[2] Walsh-Sukys M C,Tyson J E,Wright L L,et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide:practice variation and outcomes[J].Pediatrics,2000,105(1 Pt 1):14.
[3]王琳,侯洁.西地那非联合硫酸镁治疗新生儿持续性肺动脉高压的临床研究[J].北方药学,2014(4):45-46.
[4] Center for Drug Evaluation and Research. Drug Safety and Availability-FDA Drug Safety Communication:FDA recommends against use of Revatio(sildenafil)in children with pulmonary hypertension[J]. Pedicitr Cardiol,2013:1628-1636.
[5] Milman H A,Arnold S B. Neurologic,psychological,and aggressive disturbances with sildenafil[J]. Ann Pharmacother,2002,36(8):1129-1134.
[6]黄慧.西地那非治疗新生儿持续性肺动脉高压的进展[J].药物与人,2014(6):36.
[7]张耀东,谭利娜,王彩君,等.西地那非治疗新生儿持续性肺动脉高压的系统分析[J].中国医院药学杂志,2014,34(22):1933-1938.
[8]蒋璐灿,全淑燕,李佳莲,等.西地那非治疗新生儿持续性肺动脉高压的系统评价[J].中国药房,2017,28(9):1211-1215.
[9] Bendapudi P,Rao G G,Greenough A. Diagnosis and management of persistent pulmonary hypertension of the newborn[J]. Paediatr Respir Rev,2015,16(3):157-61.
[10] March U. Handbook for systematic reviews of interventions[J]. N-S Arch Phormacol,2009,5(2):S38.
[11] Vargas-Origel A,Gómez-Rodríguez G,Aldana-Valenzuela C,et al. The use of sildenafil in persistent pulmonary hypertension of the newborn.[J]. Am J Perinat,2010,27(3):225-30.
[12] Baquero H,Soliz A,Neira F,et al. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn:a pilot randomized blinded study[J]. Pediatrics,2006,117(4):1077.
[13] Roberto Herrera Torres,et al. Oral sildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns[J]. Rev Mex Pediatr,2006,73(4):159-163.
[14]单明琳.西地那非联合高频振荡通气治疗新生儿持续肺动脉高压的效果研究[J].中国继续医学教育,2016,8(15):133-135.
[15]李江鸿.西地那非联合肺表面活性物质治疗胎粪吸入综合征伴持续肺动脉高压患儿临床疗效[J].山西医科大学学报,2014,45(2):126-128.
[16]王岩.西地那非联合硫酸镁治疗新生儿持续性肺动脉高压的临床效果[J].中外医疗,2016,35(12):46-47.
[17]张继英,俞建德.高频通气联合西地那非治疗新生儿持续性肺动脉高压的临床疗效[J].中国妇幼健康研究,2015(2):271-273.
[18]赵赛,程怀平,田兆方.枸橼酸西地那非片联合多巴胺治疗对新生儿持续肺动脉高压血清炎性因子水平的影响[J].儿科药学杂志,2015(8):14-17.
[19]王媛媛,张成元,李忠良.枸橼酸西地那非治疗新生儿持续性肺动脉高压及改善右心功能研究[J].中国临床研究,2012,25(7):667-669.
[20] Shah P S,Ohlsson A. Sildenafil for pulmonary hypertension in neonates[J]. Cochrane Database Syst Rev,2011,39(8):CD005494.
[21] Krystle M,Perez,Laughon M. Sildenafil in term and premature infants:a systematic review[J]. Clin Ther,2015,37(4):2598-2608.
[22] Huddleston A J,Knoderer C A,Morris J L,et al. Sildenafil for the treatment of pulmonary hypertension in pediatric patients[J]. Pediatr Cardiol,2009,30(7):871-882.
[23] Peiravian F,Amirghofran A A,Borzouee M,et al. Oral sildenafil to control pulmonary hypertension after congenital heart surgery[J]. Asian Cardiovase Thorac Ann,2007,15(2):113-117.
[24] Alain F,Ghazwan B,Mary B T,et al. Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease[J]. Intensive Care Med,2011,37(3):502-509.
[25] Huddleston A J,Knoderer C A,Morris J L,et al. Sildenafil for the treatment of pulmonary hypertension in pediatric patients[J]. Pediatr Cardiol,2009,30(7):871-882.
[26] Schulz K F,Chalmers I,Hayes R J,et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials[J]. JAMA,1995,273(5):408-12.
[27] Odgaard-Jensen J,Vist G E,Timmer A,et al. Randomisation to protect against selection bias in healthcare trials[J]. Cochrane Database Syst Rev, 2011(4):MR000012.
[28] Savovic J,Jones H E,Altman D G,et al. Influence of reported study design characteristics on intervention effect estimates from randomized,controlled trials[J].Ann Intern Med,2012,157(6):429-38.