Caffeine in preterm infants: where are we in 2020?

Abstract

The incidence of preterm birth is increasing, leading to a growing population with potential long-term pulmonary complications. Apnoea of prematurity (AOP) is one of the major challenges when treating preterm infants; it can lead to respiratory failure and the need for mechanical ventilation. Ventilating preterm infants can be associated with severe negative pulmonary and extrapulmonary outcomes, such as bronchopulmonary dysplasia (BPD), severe neurological impairment and death. Therefore, international guidelines favour non-invasive respiratory support. Strategies to improve the success rate of non-invasive ventilation in preterm infants include pharmacological treatment of AOP. Among the different pharmacological options, caffeine citrate is the current drug of choice. Caffeine is effective in reducing AOP and mechanical ventilation and enhances extubation success; it decreases the risk of BPD; and is associated with improved cognitive outcome at 2 years of age, and pulmonary function up to 11 years of age. The commonly prescribed dose (20 mg·kg−1 loading dose, 5–10 mg·kg−1 per day maintenance dose) is considered safe and effective. However, to date there is no commonly agreed standardised protocol on the optimal dosing and timing of caffeine therapy. Furthermore, despite the wide pharmacological safety profile of caffeine, the role of therapeutic drug monitoring in caffeine-treated preterm infants is still debated. This state-of-the-art review summarises the current knowledge of caff­eine therapy in preterm infants and highlights some of the unresolved questions of AOP. We speculate that with increased understanding of caffeine and its metabolism, a more refined respiratory management of preterm infants is feasible, leading to an overall improvement in patient outcome.

Caffeine for the Treatment of Apnea in the Neonatal Intensive Care Unit: A Systematic Overview of Meta-Analyses

“…Despite some SRMAs demonstrating the benefits of caffeine in reducing the duration of MV, none of them reported whether caffeine reduces the need for CPAP, which is a substitute for invasive ventilation that does not need an endotracheal tube and is a preferred mode of ventilation for clinicians, avoiding neonate discomfort. Based on other literature, however, and although caffeine has been suggested to be beneficial for improving respiratory function via enhancing CPAP success [35], recent evidence demonstrated that early administration of caffeine (first 3 days of life) does not provide a reduction in the risk of CPAP and extubation failure [36].…”

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age

“…Furthermore, some drugs have a wide therapeutic range, such as caffeine: a therapeutic level of caffeine is considered between 5 and 25 mg/L, while toxic levels are reached with >40-50 mg/L [146]. A retrospective study on infants born less than 29 weeks GA demonstrated that those with an average caffeine concentration higher than 14.5 mg/L had significantly lower incidence of chronic lung disease and patent ductus arteriosus, fewer days on mechanical ventilation and oxygen, less need for diuretics and lower length of stay [147].…”

Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats

“…Data from initial clinical studies of caffeine therapy show a reduction in BPD rates [ 19 , 20 ] and significant improvement of lung function [ 21 ]. The discussed early prophylactic caffeine treatment before extubation is partly associated with a reduced incidence of BPD [ 22 – 24 ] but also linked with a higher mortality compared to a later start of caffeine administration (>3 postnatal days) [ 25 , 26 ].…”