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Meta-Analysis
. 2018 Dec 24:2018:9061234.
doi: 10.1155/2018/9061234. eCollection 2018.

Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis

Jing Chen  1 , Lu Jin  1 , Xiao Chen  2
Affiliations
Meta-Analysis

Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis

Jing Chen et al. Biomed Res Int. .

Abstract

Background: Caffeine is widely used for the treatment of neonatal apnea, but there is no agreement on the optimum maintenance dose for preterm infants.

Objective: The aims of this meta-analysis were to compare the efficacy and safety of high versus low maintenance doses of caffeine citrate for the treatment of apnea in premature infants.

Methods: Literature searches were conducted using PubMed, Cochrane Library, OVID, Embase, Web of Science, Chinese Biomedical Literature, Weipu Journal, Wanfang, and CNKI databases up to September 2018. Only randomized controlled trials (RCTs) of caffeine citrate for apnea treatment in premature infants were included. Trials were divided into those testing high maintenance doses (10-20 mg/kg daily) and low maintenance doses (5-10 mg/kg daily) for comparison. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards.

Results: Among the 345 studies initially identified, thirteen RCTs involving 1515 patients were included. Compared to the low-dose group, the high-dose group exhibited greater effective treatment rate (RR: 1.37, 95%CI: 1.18 to 1.60, P<0.0001) and success rate for ventilator removal (RR: 1.74, 95%CI: 1.04 to 2.90, P=0.03), but higher incidence of tachycardia (RR: 2.02, 5%CI: 1.30 to 3.12, P=0.002). The high-dose group also demonstrated lower extubation failure rate (RR: 0.5, 95%CI: 0.35 to 0.71, P=0.0001), frequency of apnea (WMD: -1.55, 95%CI: -2.72 to -0.39, P=0.009), apnea duration (WMD: -4.85, 95%CI: -8.29 to -1.40, P=0.006), and incidence of bronchopulmonary dysplasia (RR: 0.79, 95%CI: 0.68 to 0.91, P=0.002). There were no significant group differences in other adverse events including in-hospital death (P>0.05).

Conclusions: Higher maintenance doses of caffeine citrate appear more effective and safer than low maintenance doses for treatment of premature apnea, despite a higher incidence of tachycardia.

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Figures

Figure 1
Figure 1
The flow chart of literature selection.
Figure 2
Figure 2
Risk of bias assessment summary of this meta-analysis.
Figure 3
Figure 3
(a) Forest plot of the effective rate between HD group and LD group. (b) Forest plot of the effective rate after excluding the outlier study between HD group and LD group.
Figure 4
Figure 4
Forest plot of tachycardia between HD group and LD group.
Figure 5
Figure 5
Forest plot of other adverse effects between HD group and LD group.
Figure 6
Figure 6
Forest plot of hospital mortality between HD group and LD group.
Figure 7
Figure 7
Forest plot of the success rate of ventilator removal between HD group and LD group.
Figure 8
Figure 8
Forest plot of the extubation failure rate between HD group and LD group.
Figure 9
Figure 9
Forest plot of the frequency of apnea between HD group and LD group.
Figure 10
Figure 10
Forest plot of apnea duration between HD group and LD group.
Figure 11
Figure 11
Forest plot of bronchopulmonary dysplasia between HD group and LD group.
Figure 12
Figure 12
Funnel plot for publication bias test for BPD.
Figure 13
Figure 13
Funnel plot for publication bias test for tachycardia.
Figure 14
Figure 14
Funnel plot for publication bias test for hospital mortality.
Figure 15
Figure 15
Sensitivity analysis of BPD for high versus low maintenance dose.
Figure 16
Figure 16
Sensitivity analysis of tachycardia for high versus low maintenance dose.
Figure 17
Figure 17
Sensitivity analysis of hospital mortality for high versus low maintenance dose.
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