Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study

Zhongguo Dang Dai Er Ke Za Zhi. 2022 Mar 15;24(3):240-248. doi: 10.7499/j.issn.1008-8830.2109144.
[Article in English, Chinese]


Objectives: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.

Methods: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.

Results: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).

Conclusions: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

目的: 探讨需要辅助通气和枸橼酸咖啡因治疗的早产儿枸橼酸咖啡因的最佳维持剂量。方法: 回顾性收集2019年1月1日至2019年12月31日江苏省30家三级医院新生儿重症监护病房中需要辅助通气和枸橼酸咖啡因治疗的早产儿566例(胎龄≤34周)的临床资料。依据生后24 h内给予枸橼酸咖啡因负荷剂量20 mg/kg后接受高(每日10 mg/kg)或低(每日5 mg/kg)维持剂量治疗将早产儿分为高剂量组(n=405)和低剂量组(n=161)。对两组早产儿咖啡因应用期间有创/无创通气相关数据进行比较分析。结果: 与低剂量组比较,高剂量组早产儿辅助通气时对高浓度氧的需求明显降低(P<0.05),无创通气撤除后的吸氧总时间及住院期间总吸氧时间均显著缩短(P<0.01),再次无创通气的比例明显降低(P<0.01),肺表面活性物质及吸入性布地奈德的使用率均显著减少(P<0.05),呼吸暂停及BPD的发生率显著降低(P<0.01),但早产儿喂养不耐受的发生率明显上升(P=0.032)。两组在体重变化、早产儿视网膜病变发生率、脑室内出血发生率、坏死性小肠结肠炎发生率、病死率、咖啡因应用时间等方面比较差异无统计学意义(P>0.05)。结论: 初步多中心研究表明高维持剂量枸橼酸咖啡因(每日10 mg/kg)对治疗我国早产儿人群总体是有益的,并未增加常见不良反应的发生。而对于喂养不耐受的风险,还需要进一步的论证分析,以尽可能排除混杂因素的干扰。.

Keywords: Caffeine; Maintenance dose; Preterm infant; Respiration.

Publication types

  • Multicenter Study

MeSH terms

  • Caffeine* / therapeutic use
  • Citrates
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Respiration, Artificial*
  • Retrospective Studies


  • Citrates
  • Caffeine
  • caffeine citrate