氦氧混合气吸入联合经鼻间歇正压通气治疗新生儿呼吸窘迫综合征的随机对照研究

Nasal intermittent positive pressure ventilation with heliox treatment for preterm neonates with respiratory distress syndrome: a randomized controlled trial

目的评价氦氧混合气吸入联合经鼻间歇正压通气(NIPPV)对新生儿呼吸窘迫综合征(NRDS)的疗效及其对炎症因子和心肌损伤标志物的影响。方法纳入2012年12月至2013年5月在第三军医大学大坪医院NICU住院的NRDS早产儿,随机分配进入试验组或对照组。试验组吸入氦氧混合气(70∶30),3h后更换气源为30%空氧混合气直至撤除NIPPV。对照组使用30%空氧混合气直至撤除NIPPV。在研究开始前(0h)和开始后1、2及3h测定经皮氧分压及经皮二氧化碳分压,于研究开始前(0h)和开始后3h留取血标本测定IL-6和心肌损伤标志物(肌酸激酶、肌酸激酶同工酶-MB)水平,3h时点留取血标本测定炎症因子(丙二醛、髓过氧化物酶、TNF-α、诱导型一氧化氮合酶)水平,于患儿撤除NIPPV后记录其呼吸机使用时间。结果试验组比对照组明显缩短了新生儿的NIPPV使用时间(39.3hvs57.8h,P=0.02)。吸入后3h时点,两组新生儿的经皮氧分压和二氧化碳分压较吸入前均明显改善(P<0.001)。试验组CO2清除率显著优于对照组(10.39mmHgvs6.0mmHg,P=0.03)。两组3h时点IL-6、丙二醛、髓过氧化物酶、TNF-α及诱导型一氧化氮合酶水平差异均无统计学意义(P>0.05)。对照组肌酸激酶、肌酸激酶同工酶-MB水平高于试验组,但两组差异无统计学意义(P>0.05)。新生儿NIPPV使用时间与基线IL-6水平呈正相关(r=0.474,P=0.006)。研究期间试验组未观察到低体温不良反应的发生。结论氦氧混合气吸入联合NIPPV可提高NRDS早产儿的CO2清除率,缩短其NIPPV使用时间,且安全性较好。

Objective Helium-oxygen mixture （heliox） was suggested to be beneficial in preterm infants in previous studies, but the evidence was limited. The aim of the study was to assess the effectiveness of nasal intermittent positive pressure ventilation （NIPPV） with heliox （70% helium and 30% oxygen） on length of ventilation （LoV） and cardiopulmonary protection in preterm infants with RDS. Methods Infants 〈 37 weeks of gestational age diagnosed as RDS and required ventilation support with NIPPV in the first hour after birth were eligible for the study. Infants were randomly assigned to be supported with heliox or 30% air-oxygen mixture groups during the first 3 hours of enrollment, followed by air-oxygen mixture until NIPPV was no longer needed. The main outcome was the LoV to achieve clinical stability. Analysis followed intention to treat principle. Results 36 infants （ 19 in the heliox and 17 in the control groups） were allocated to the treatment from December 2012 to May 2013. Heliox administration significantly decreased LoV in test group compared with the control group （ 39.29 hours vs 57.80 hours, P = 0.02 ）. Carbon dioxide elimination was better in the heliox group than that in the control group （ 10.39 mmHg vs 6.0 mmHg, P = 0.03 ）. Analysis of lung inflammation cytokines and myocardial injury markers showed no statistical significance between the two groups （ P 〉 0.05 ）. LoV was significantly and positively correlated with IL-6 level at baseline （ r = 0.474, P = 0. 006）. No side effects of hypothermia were found in the whole study. Conclusions Heliox delivered with NIPPV was safe and effective in reducing LoV and increasing carbon dioxide elimination, but seemed to be ineffective in attenuating lung inflammation and myocardial damage in preterm neonates with RDS.