基于随机双盲安慰剂对照试验的一氧化碳吸入疗法在新生儿肺炎应用的安全性研究

目的探讨一氧化碳(CO)吸入疗法在足月新生儿中应用的安全性以及抗炎、抗氧化作用。方法纳入2013年3~6月第三军医大学附属大坪医院NICU住院的肺炎足月新生儿,随机分为8组,分别予以空氧气体(安慰剂)和10、20、30、40、50、60、70 mg·L-1浓度的CO吸入2 h;吸入安慰剂气体或CO期间持续观察受试者的反应,监测心率、血氧饱和度、呼吸和血压等生命体征,检测吸入前(0 h)和吸入后2和5 h时点血清碳氧血红蛋白(COHb)浓度,评估吸入CO的安全性;检测晚期氧化蛋白产物(AOPPs)、总抗氧化能力(TAOC)、丙二醛(MDA)和巨噬细胞炎症蛋白-2(MIP-2)水平,评估吸入CO的抗炎和抗氧化作用。结果 48例足月新生儿符合纳入和排除标准进入观察,每组各6例。8组间胎龄、年龄、体重、白蛋白、Hb和WBC计数等基线指标差异均无统计学意义。1CO 70 mg·L-1组1例因不良事件退出研究,其余受试者均完成试验;COHb在不同时点和8组间差异均无统计学意义(P0.05);2随着吸入CO浓度的增加,MIP-2总体上呈下降趋势(P=0.000),3个观察时点差异总体上有统计学意义(P=0.001);TAOC水平8组间比较差异无统计学意义(P=0.917),不同时点差异有统计学意义(P=0.005);AOPPs和MDA在不同时点以及不同组间差异均无统计学意义(P0.05)。结论吸入CO浓度≤60 ppm在新生儿肺炎中的应用是安全的,且具有抗炎和改善氧化应激状态的作用。

Safety and feasibility of inhaled carbon monoxide treatment for neonates with stabilized pneumonia: a randomized-blinded study

Objective The aim of the present study was to investigate the feasibility, safety and anti-inflammatory and anti-oxidant properties of carbon monoxide (CO) inhalation in term infants. Methods Neonates with pneumonia in NICU of Daping Hospital of Third Military Medical University from March 2013 to June 2013 were randomly divided into 8 groups, respectively inhaled 0, 10, 20, 30, 40, 50, 60, 70 mg·L-1 of CO for 2 h; during CO inhalation,observating the reaction of subjects, continuous monitoring of heart rate, blood oxygen saturation, respiration and blood pressure and other vital signs, detecting the serum levels of carboxyhemoglobin (COHb) concentration before inhalation (0 h) and 2 and 5 h after inhalation to evaluate the feasibility and safety of inhaled CO. The total antioxidant capacity (TAOC), malondialdehyde (MDA) and macrophage inflammatory protein-2 (MIP-2) levels before inhalation (0 h) and 2 and 5 h after inhalation were detected to evaluate anti-inflammatory and antioxidant effects of CO. Results 48 infants met the inclusion and exclusion criteria and were taken into the observation, 6 cases in each group. Baseline index between 8 groups did not significantly differ. ①One neonate in 70 mg·L-1 group was discontinued for adverse effects and others enrolled patients were completed the study ultimately. There were no significant changes of carboxyhaemoglobin among 8 groups.②With the increase of iCO concentration, macrophage inflammatory protein-2 showed a reducing trend among groups (F=212.437, P<0.001) and time points (F=4.603, P=0.001), and TAOC showed sigificant difference between three times points (F=9.618, P=0.005). No significant changes of advanced oxidation protein products and malondialdedyde concentrations during the course of iCO were found among time points and groups. Conclusion iCO≤60 mg·L-1 in term neonates with pneumonia in a stable phase was feasible and safe, and induced anti-inflammatory and anti-oxidant effects. Application of inhalation CO therapy in neonates is worthy of further study.