| Objective:Apnea of prematurity(AOP)is a common clinical issue in neonatal intensive care units(NICU).Caffeine citrate has the advantages of large safety range,few side effects,high therapeutic coefficient and long half-life in AOP treatment.As the first choice for AOP treatment,caffeine has been widely used as the main drug in western developed countries,and its safety and efficacy are recognized.At present,there are few research materials on the effectiveness and safety of citrate caffeine in AOP treatment and complications in clinical treatment in China.This study aims to use the clinical trial to investigate the differences in the clinical effects,adverse drug effects and complications of different maintenance doses of caffeine in the treatment of AOP,and to determine the optimal dosage of caffeine citrate in the AOP treatment,so as to provides a reference for application of caffeine.Methods:We enrolled preterm infants born in low birth weight in children’s hospital of Tai’an city or transferred to this hospital in the NICU and diagnosed with apnea from December2017 to December 2018.The baseline clinical data such as birth weight,gestational age,Apgar score after birth,and age of onset were collected,and study subjects were randomly divided into low maintenance dose group,medium maintenance dose group,and high maintenance dose group.The three groups were given the same treatment as caffeine citrate load 20mg/kg intravenously at first,and were treated with different maintenance doses after 24 hours 5mg/(kg·d),7.5mg/(kg·d),and 10mg/(kg·d),and were administered once every 24 hours.The number of adverse effects such as tachycardia and feeding intolerance was recorded during the treatment,and the treatment effectiveness and complications of the three groups were evaluated after treatment.The comparison between two or more groups of measurement data was performed by t test or ANOVA.Comparison between two groups was performed using a LSD method.Comparison between two or more groups of count data was used theχ~2 test and Fisher’s exact probability method.Results:1.Baseline characteristicsA total of 171 children diagnosed with AOP were enrolled in this study.The differences in gender(χ~2=0.216,P=0.898),gestational age(F=1.193,P=0.306),birth weight(F=1.360,P=0.260),age of onset(F=2.607,P=0.077),1 min Apgar score(F=0.919,P=0.401),and 10 min Apgar score(F=0.173,P=0.841)were not statistically significant in the low-dose,middle-dose,and high-dose groups.2.Effectiveness analysisEffectiveness rates in low-dose,middle-dose,and high-dose were 45.61%、50.00%and 74.14%,respectively.The differences in effectiveness rates were statistically significant among different groups(χ~2=11.062,P=0.004).The duration of apnea in different groups were 4.68±1.83(d),5.05±1.85(d),and 2.89±1.65(d),respectively.The differences in duration of apnea were statistically significant(F=24.087,P<0.001)among different groups.The duration of treatment among different groups were 15.13±4.42(d),15.13±3.01(d),and 14.16±4.40(d),respectively.The differences in duration of treatment were statistically significant(F=3.721,P=0.026).The time of hospital stay in different groups were 24.44±5.83(d),21.86±6.06(d),and 20.47±7.35(d),respectively.The differences in time of hospital stay were statistically significant among different groups(F=5.590,P=0.004).The number of apneas of different groups were 7.14±1.72(f),6.71±1.71(f),and 6.11±1.62(f),respectively.The differences in number of apneas were statistically significant among different groups(F=5.429,P=0.005).The duration of continuous positive ventilation of different groups were 5.09±2.21(d),5.66±2.61(d),and4.03±2.22(d),respectively.The differences in duration of continuous positive ventilation were statistically significant among different groups(F=7.035,P=0.001).The rates of non-invasive respiratory support of different groups were 52.63%,48.21%,and 8.62%,respectively.The differences in rates of non-invasive respiratory support were statistically significant among different groups(χ~2=29.245,P<0.001).In the comparison between low-dose and high-dose groups,the RRR and ARR were62.55%and 28.53%,and it revealed that the effectiveness rate in high-dose treatment had clinical implication.The NNT was 4 suggested that one patient benefited from the treatment in every 4 patients who received the high maintenance dose treatment.In the comparison between low-dose and middle-dose groups,the RRR and ARR were 9.63%and 4.39%,and it revealed that the effectiveness rate in middle-dose treatment had no clinical implication.The NNT was 23 suggested that one patient benefited from the treatment in every 23 patients who received the middle maintenance dose treatment.3.Analysis of adverse drug effectsThe rates of tachycardia in low-dose,middle-dose,and high-dose groups were17.54%,21.43%,and 24.14%,respectively.The difference in rates of tachycardia was not statistically significant among different groups(χ~2=0.759,P=0.684).The rates of feeding intolerance in low-dose,middle-dose,and high-dose groups were 12.28%,14.29%,and15.52%,respectively.The difference in rates of feeding intolerance was not statistically significant among different groups(χ~2=0.254,P=0.881).4.Comparison of serious complicationsThe rates of necrotizing enterocolitis in low-dose,middle-dose,and high-dose groups were 10.53%,10.71%,and 12.07%,respectively.The rates of bronchopulmonary dysplasia among different groups were 5.26%,7.14%,and 8.62%,respectively.The rates of intracranial hemorrhage among different groups were 8.77%,10.71%,and 10.34%,respectively.The rates of retinopathy of prematurity among different groups were 12.28%,10.71%,and 10.34%,respectively.There were no statistically significant differences in the rates of necrotizing enterocolitis(χ~2=0.083,P=0.960),in the rates of bronchopulmonary dysplasia(χ~2=0.499,P=0.779),in the rates of intracranial hemorrhage(χ~2=0.135,P=0.935),and in the rates of retinopathy of prematurity(χ~2=0.122,P=0.941)among different groups.Conclusions:1.The effectiveness rate in high maintenance dose group was significantly higher than that in low and medium maintenance dose group,whereas the duration of apnea,duration of treatment,time of hospital stay,number of apneas,duration of continuous positive ventilation,and rate of non-invasive respiratory support in the high maintenance dose group were lower than those in the low and medium maintenance dose group.2.The incidences of adverse effects such as tachycardia and feeding intolerance during treatment in the high maintenance dose group was not higher than those in the low and medium maintenance dose group.The incidences of severe complications such as necrotizing enterocolitis,bronchopulmonary dysplasia,intracranial hemorrhage and retinopathy of prematurity in high-maintenance group were not higher than those in the low and medium maintenance dose group.3.High maintenance dose group of caffeine citrate had better clinical effectiveness in the treatment of infants diagnosed with apnea of premature. |
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