枸橼酸咖啡因联合经鼻间歇正压通气治疗对极早产呼吸暂停患儿肺功能的影响及机制研究

Effect and mechanism of caffeine citrate combined with nasal intermittent positive pressure ventilation on lung function in extremely premature infants with apnea

目的探究枸橼酸咖啡因+经鼻间歇正压通气(NIPPV)治疗对极早产呼吸暂停患儿肺功能的影响及机制。方法选取徐州医科大学附属医院2021年3月至2022年3月收治的极早产呼吸暂停患儿75例,采用随机数字表法将患儿分为对照组(37例)与观察组(38例)。对照组在常规综合干预基础上行氨茶碱+NIPPV治疗,观察组在常规综合干预基础上行枸橼酸咖啡因+NIPPV治疗,2组均连续治疗1周。比较2组临床疗效及治疗期间并发症发生情况。记录治疗前后2组肺功能指标、血氧饱和度、血清内皮素、β-内啡肽、克拉拉细胞分泌蛋白16(CC16)水平及诱导痰中转化生长因子β_(1)(TGF-β_(1))和结缔组织生长因子(CTGF)mRNA表达量。结果观察组总有效率高于对照组,治疗期间并发症发生率低于对照组(均P<0.05)。治疗后,观察组潮气量、潮气呼气峰流量、每分钟通气量、达峰时间比均高于对照组[(9.0±1.0)ml/kg比(8.4±0.8)ml/kg、(38.3±1.2)ml/s比(35.2±1.4)ml/s、(0.60±0.16)L/(min·kg)比(0.44±0.13)L/(min·kg)、(35.7±1.2)%比(33.1±1.1)%](均P<0.05);观察组脑血氧饱和度、肠道血氧饱和度均高于对照组(均P<0.05);观察组血清内皮素水平高于对照组,β-内啡肽、CC16水平均低于对照组(均P<0.05);观察组诱导痰中TGF-β_(1)、CTGF mRNA表达量均高于对照组(均P<0.05)。结论枸橼酸咖啡因+NIPPV治疗极早产儿呼吸暂停安全有效,显著改善患儿肺功能,减少并发症发生,可能与改善氧代谢、降低血清CC16水平、抑制诱导痰炎症有关。

Objective To investigate the effect and mechanism of caffeine citrate combined with nasal intermittent positive pressure ventilation(NIPPV)on lung function in extremely premature infants with apnea.Methods From March 2021 to March 2022,75 cases of extremely premature infants with apnea admitted to the Affiliated Hospital of Xuzhou Medical University were enrolled.They were divided into the control group(37 cases)and the observation group(38 cases)by the random number table method.The control group was treated with aminophylline combined with NIPPV based on the general comprehensive intervention,and the observation group was treated with caffeine citrate combined with NIPPV based on the general comprehensive intervention.The clinical efficacy and the incidence of complications during treatment were compared between the two groups.The lung function index,blood oxygen saturation,serum levels of endothelin(ET),β-endorphin(β-EP)and Clara cell secretory protein-16(CC16)and expressions of transforming growth factor-β_(1)(TGF-β_(1))and connective tissue growth factor(CTGF)mRNA in induced sputum of the two groups were recorded.Results Compared to the control group,the total effective rate was higher and the complication rate during treatment was lower in the observation group(both P<0.05).After treatment,tidal volume,peak tidal expiratory flow,minute ventilation and ratio of time to peak tidal expiratory flow to total expiratory time were higher in the observation group than those in the control group[(9.0±1.0)ml/kg vs(8.4±0.8)ml/kg,(38.3±1.2)ml/s vs(35.2±1.4)ml/s,(0.60±0.16)L/(min·kg)vs(0.44±0.13)L/(min·kg),(35.7±1.2)%vs(33.1±1.1)%](all P<0.05).Cerebral oxygen saturation and sausage oxygen saturation were higher in the observation group than those in the control group(both P<0.05).Compared to the control group,the serum level of ET was higher and levels ofβ-EP and CC16 were lower in the observation group(all P<0.05).Expressions of TGF-β_(1) and CTGF mRNA in induced sputum were higher in the observation group than those in the control group(both P<0.05).Conclusions Caffeine citrate combined with NIPPV is safe and effective in the treatment of extremely premature infants with apnea,which can significantly improve lung function and reduce complications,possibly by improving oxygen metabolism,reducing serum CC16 level and inhibiting inflammation in induced sputum.