Scenario

A 10-week-old infant, born at 30 weeks’ gestation, was admitted from the emergency department with respiratory deterioration, proven subsequently as respiratory syncytial virus (RSV) bronchiolitis. Despite applying continuous positive airway pressure (CPAP) on the high dependency unit (HDU), there were frequent apnoeic episodes. You wonder as a paediatric registrar if caffeine has a role in treating bronchiolitis-related apnoea and can prevent further escalation to invasive ventilation.

Structured clinical question

In infants presenting with bronchiolitis-related apnoea (patient), does caffeine citrate (intervention) reduce the need for invasive ventilation (outcome)?

Search

Primary sources: PubMed using keywords ‘bronchiolitis OR viral bronchiolitis’ AND ‘apnea OR apnoea’ AND ‘caffeine OR caffeine citrate OR xanthine OR methylxanthine’ resulted in 297 articles, 5 relevant. Further Medline and Embase searched gained an extra 24 with 12 potentially relevant.

Secondary search on Cochrane database produced one randomised controlled trial (RCT)1 and no systematic reviews. No restrictions were applied to the search strategy.

Four articles were excluded,2–5 as these were reviews and evidence-based medicine articles. Two more articles (in the form of a Letter to the Editor) were excluded6 7 as these were critical appraisals of an RCT.1

The table of evidence (table 1) summarises the most relevant articles in this context.

Commentary

Bronchiolitis is one of the leading causes of hospitalisation during infancy and a financial burden to the healthcare system, especially in the winter months. Apnoea is a common complication of bronchiolitis,8 which results in the need for respiratory support, including invasive ventilation. In infants with RSV-positive bronchiolitis, the incidence of apnoea was reported to be 1.2%–23.8% in one study.4 This creates a great deal of pressure on the bed capacity in the intensive care units given the fact that most of the affected patients are expreterm babies who are at high risk of apnoeas.9

In most district hospitals in the UK, non-invasive support such as nasal CPAP and high-flow oxygen therapy can nowadays be provided on HDUs or paediatric wards, but once intubated, transfer to a Paediatric Intensive Care Unit is required. In addition, intubation and invasive ventilation invariably increase the risk of developing ventilator-associated pneumonia and secondary bacterial infections.10 High-flow oxygen therapy has also reduced the need for intubation in babies with bronchiolitis with increased work of breathing, but not when apnoea is the primary problem.11 12

Caffeine was first used to treat prematurity-related apnoea and to minimise the need for invasive ventilation, therefore it is thought to have a similar effect in bronchiolitis-related apnoea. There is currently a need for evidence to support this, either using a loading dose followed by maintenance dose or loading dose alone. A single dose of caffeine citrate did not significantly reduce apnoeic episodes associated with bronchiolitis, according to the most recent and only RCT.1 Controversies, however, have been raised when different regimens have been used resulting in different conclusions, although these were from retrospective and anecdotal studies13–17 with small sample sizes in general.

It is clear that there are challenges in conducting clinical trials in paediatrics in general, reflected by the small number of recruits in each study. Therefore, joint research among intensive care, emergency and paediatric departments is critical in overcoming some of these challenges in determining the effectiveness of caffeine in bronchiolitis-related apnoea.7