经一氧化氮吸入治疗的新生儿持续肺动脉高压患儿死亡的早期影响因素分析

Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide

摘要:

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.