OBJECTIVE: To explore the effects of different doses of caffeine citrate on intestinal flora of neonates with apnea. METHODS: Totally 110 neonates with apnea admitted into Hefei Binhu Hospital from Jan. 2018 to Jul.2020 were retrospectively extracted to be divided into low-dose group and high-dose group according to different administration methods of caffeine citrate. In the low-dose group（ n = 55）

the initial load was 20 mg/kg caffeine citrate with 3 ml 5% glucose injection infusion pump for 30 min

after 24 h

5 mg/kg caffeine citrate was intravenously injected

and 3 ml 5% glucose injection was added to the infusion pump for 30 min

and then medication was given once every 24 h. In the high-dose group（ n = 55）

the initial dose was the same as the low-dose group

after 24 h

10 mg/kg caffeine citrate was given

and 3 ml 5% glucose injection was added to the infusion pump for 30 min

and then medication was given once every 24 h. Both groups were treated continuously until one week after the disappearance of apnea symptoms. The intestinal flora

clinical efficacy and adverse drug reactions of two groups were observed. RESULTS: Compared with the low-dose group

after 7 d of treatment

the counts of G+and G-were higher in the high-dose group

while the counts of G-were lower

with statistically significant difference（ P<0. 05）. The total effective rate of the low-dose group was 98. 18%（ 54/55）

significantly higher than that of the high-dose group of87. 27%（ 48/55）

the difference was statistically significant（ P<0. 05）. On the first day of treatment

there was no significant difference in the frequency and severity of apnea between the low-dose group and the high-dose group（ P>0. 05）. Compared with the first day of treatment

the frequency of apnea and the severity score decreased significantly in both groups on the third day of treatment

and the difference was statistically significant（ P < 0. 05）.The incidence of feeding intolerance in the high-dose group was 18. 18%（ 10/55）

significantly higher than that in the low-dose group 5. 45%（ 3/55）

the difference was statistically significant（ P < 0. 05）. CONCLUSIONS: Caffeine citrate can destroy the establishment of normal intestinal flora in neonates. Therefore

the dosage should be reduced as far as possible while ensuring the efficacy

reducing the damage of drugs to intestinal microecology and improving the safety of treatment.