目的 探索经一氧化氮吸入(inhaled nitric oxide,iNO)治疗的新生儿持续肺动脉高压(persistent pulmonary hypertension of the newborn,PPHN)患儿死亡的早期影响因素,以便于早期识别高危儿。 方法 回顾性选取2017年7月至2021年3月于南京医科大学附属儿童医院新生儿医疗中心接受iNO治疗的105例PPHN患儿(胎龄≥34周、入院日龄<7 d)为研究对象。收集患儿的一般资料及临床资料,根据出院时临床结局分为存活组(n=79)和死亡组(n=26)。采用单因素及多因素Cox回归分析探讨经iNO治疗的PPHN患儿死亡的影响因素。采用受试者工作特征(receiver operating characteristic,ROC)曲线计算独立影响因素预测患儿死亡的截断值。 结果 105例经iNO治疗的PPHN患儿,其中死亡26例(26/105,24.8%)。多因素Cox回归分析提示,iNO治疗非早期反应(HR=8.500,95%CI:3.024~23.887,P<0.001)、1 min Apgar评分≤3分(HR=10.094,95%CI:2.577~39.534,P=0.001)、入院12 h内最低PaO2/FiO2值较低(HR=0.067,95%CI:0.009~0.481,P=0.007)及最低pH值较低(HR=0.049,95%CI:0.004~0.545,P=0.014)是PPHN患儿死亡的独立影响因素。ROC分析显示,入院12 h内最低PaO2/FiO2值及最低pH值预测PPHN患儿死亡的截断值分别为50、7.2,灵敏度、特异度分别为84.6%、73.4%及76.9%、65.8%,曲线下面积分别为0.783、0.746。 结论 需iNO治疗的PPHN患儿病死率高,iNO治疗非早期反应、1 min Apgar评分≤3分、入院12 h内最低PaO2/FiO2值<50及最低pH值<7.2为此类患儿死亡的独立影响因素。监测及评估上述指标,将有助于早期识别高危儿,制定治疗策略,以改善PPHN患儿预后。
Abstract
Objective To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO). Methods A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk. Results A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2. Conclusions Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.
关键词
持续肺动脉高压 /
一氧化氮 /
影响因素 /
新生儿
Key words
Persistent pulmonary hypertension /
Nitric oxide /
Risk factor /
Neonate
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参考文献
1 Steurer MA, Baer RJ, Oltman S, et al. Morbidity of persistent pulmonary hypertension of the newborn in the first year of life[J]. J Pediatr, 2019, 213: 58-65.e4. PMID: 31399244. DOI: 10.1016/j.jpeds.2019.06.053.
2 Walsh-Sukys MC, Tyson JE, Wright LL, 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): 14-20. PMID: 10617698. DOI: 10.1542/peds.105.1.14.
3 Nakwan N, Jain S, Kumar K, et al. An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment and outcome[J]. J Matern Fetal Neonatal Med, 2020, 33(12): 2032-2037. PMID: 30318951. DOI: 10.1080/14767058.2018.1536740.
4 Lai MY, Chu SM, Lakshminrusimha S, et al. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn[J]. Pediatr Neonatol, 2018, 59(1): 15-23. PMID: 28923474. DOI: 10.1016/j.pedneo.2016.09.011.
5 Nelin LD, Potenziano JL. Inhaled nitric oxide for neonates with persistent pulmonary hypertension of the newborn in the CINRGI study: time to treatment response[J]. BMC Pediatr, 2019, 19(1): 17. PMID: 30636626. PMCID: PMC6330425. DOI: 10.1186/s12887-018-1368-4.
6 Clark RH, Kueser TJ, Walker MW, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group[J]. N Engl J Med, 2000, 342(7): 469-474. PMID: 10675427. DOI: 10.1056/NEJM200002173420704.
7 Macrae DJ, Field D, Mercier JC, et al. Inhaled nitric oxide therapy in neonates and children: reaching a European consensus[J]. Intensive Care Med, 2004, 30(3): 372-380. PMID: 14722629. DOI: 10.1007/s00134-003-2122-3.
8 DiBlasi RM, Myers TR, Hess DR. Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure[J]. Respir Care, 2010, 55(12): 1717-1745. PMID: 21122181.
9 朱雯, 程锐, 杨洋, 等. 血管活性-正性肌力药物评分对新生儿持续肺动脉高压患儿死亡的早期预测价值[J]. 中华新生儿科杂志, 2021, 36(6): 12-17. DOI: 10.3760/cma.j.issn.2096-2932.2021.06.003.
10 中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257. PMID: 30934196. DOI: 10.3760/cma.j.issn.0578-1310.2019.04.005.
11 Zeng X, McMahon GM, Brunelli SM, et al. Incidence, outcomes, and comparisons across definitions of AKI in hospitalized individuals[J]. Clin J Am Soc Nephrol, 2014, 9(1): 12-20. PMID: 24178971. PMCID: PMC3878695. DOI: 10.2215/CJN.02730313.
12 Muniraman HK, Song AY, Ramanathan R, et al. Evaluation of oxygen saturation index compared with oxygenation index in neonates with hypoxemic respiratory failure[J]. JAMA Netw Open, 2019, 2(3): e191179. PMID: 30924897. PMCID: PMC6450323. DOI: 10.1001/jamanetworkopen.2019.1179.
13 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 5版. 北京: 人民卫生出版社, 2019.
14 Zhao Y, Liang L, Liu G, et al. Asphyxia and neonatal respiratory distress syndrome are independent predictors of the non-response to inhaled nitric oxide in the newborns with PPHN[J]. Front Pediatr, 2021, 9: 665830. PMID: 34095030. PMCID: PMC8172584. DOI: 10.3389/fped.2021.665830.
15 段佳佳, 邢景月, 王举, 等. 一氧化氮吸入治疗新生儿持续肺动脉高压疗效及预后影响因素分析[J]. 中华新生儿科杂志, 2021, 36(2): 48-52. DOI: 10.3760/cma.j.issn.2096-2932.2021.02.009.
16 Hwang SJ, Lee KH, Hwang JH, et al. Factors affecting the response to inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn infants[J]. Yonsei Med J, 2004, 45(1): 49-55. PMID: 15004868. DOI: 10.3349/ymj.2004.45.1.49.
17 Morel AA, Shreck E, Mally PV, et al. Clinical characteristics and factors associated with term and late preterm infants that do not respond to inhaled nitric oxide (iNO)[J]. J Perinat Med, 2016, 44(6): 663-668. PMID: 26352080. DOI: 10.1515/jpm-2015-0210.
18 Bischoff AR, Giesinger RE, Neary E, et al. Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxemic term and near-term neonates[J]. Pediatr Pulmonol, 2021, 56(5): 982-991. PMID: 33434418. DOI: 10.1002/ppul.25252.
19 Khemani RG, Rubin S, Belani S, et al. Pulse oximetry vs. PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk[J]. Intensive Care Med, 2015, 41(1): 94-102. PMID: 25231293. DOI: 10.1007/s00134-014-3486-2.
20 Khemani RG, Thomas NJ, Venkatachalam V, et al. Comparison of SpO2 to PaO2 based markers of lung disease severity for children with acute lung injury[J]. Crit Care Med, 2012, 40(4): 1309-1316. PMID: 22202709. DOI: 10.1097/CCM.0b013e31823bc61b.
21 Khemani RG, Smith LS, Zimmerman JJ, et al. Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Consensus Conference[J]. Pediatr Crit Care Med, 2015, 16(5 Suppl 1): S23-S40. PMID: 26035358. DOI: 10.1097/PCC.0000000000000432.
22 Rawat M, Chandrasekharan PK, Williams A, et al. Oxygen saturation index and severity of hypoxic respiratory failure[J]. Neonatology, 2015, 107(3): 161-166. PMID: 25592054. PMCID: PMC4405613. DOI: 10.1159/000369774.
23 Black SM, Heidersbach RS, McMullan DM, et al. Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension[J]. Am J Physiol, 1999, 277(5): H1849-H1856. PMID: 10564139. DOI: 10.1152/ajpheart.1999.277.5.H1849.
24 Lakshminrusimha S, Russell JA, Steinhorn RH, et al. Pulmonary arterial contractility in neonatal lambs increases with 100% oxygen resuscitation[J]. Pediatr Res, 2006, 59(1): 137-141. PMID: 16326983. PMCID: PMC2094524. DOI: 10.1203/01.pdr.0000191136.69142.8c.
25 Nu?ez A, Benavente I, Blanco D, et al. Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy[J]. An Pediatr (Engl Ed), 2018, 88(4): 228.e1-228.e9. PMID: 28648366. DOI: 10.1016/j.anpedi.2017.05.005.
26 Lakshminrusimha S, Saugstad OD. The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy[J]. J Perinatol, 2016, 36 Suppl 2: S3-S11. PMID: 27225963. DOI: 10.1038/jp.2016.43.
27 Kinsella JP. Inhaled nitric oxide in the term newborn[J]. Early Hum Dev, 2008, 84(11): 709-716. PMID: 18930613. DOI: 10.1016/j.earlhumdev.2008.08.002.
28 王丹华. 对Apgar评分的再认识[J]. 中华围产医学杂志, 2021, 24(3): 165-168. DOI: 10.3760/cma.j.cn113903-20201214-01226.