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A 2 week old infant, born at 36 weeks gestation was admitted to the paediatric ward in November with a 24 hour history of runny nose, cough, and episodes of shallow breathing and apnoeas. This was thought to be due to bronchiolitis, and the consultant paediatrician suggested starting the baby on caffeine (theophylline derivative with less side effects). As the resident middle grade doctor, I knew that caffeine has been used widely in neonatal units for apnoea of prematurity, but I wondered if there was any evidence for its use in this clinical situation.
Structured clinical question
In infants with bronchiolitis [patient] does caffeine [intervention] reduce or prevent apnoeas [outcome]?
Search strategy and outcome
Cochrane database of systematic reviews: No directly relevant study found, but there was one systematic review on the efficacy of methylxanthines in reducing apnoea of prematurity1 and another systematic review on the prophylactic use of caffeine to prevent postoperative apnoea following general anaesthesia in ex-preterm infants.2
Medline plus (no limits): Search terms: Infants and bronchiolitis/respiratory syncytial virus infections/virus/infection and apnoea/apnea and caffeine/xanthine/methylxanthine/phosphodiesterase inhibitors/theophylline
There was one retrospective review3 and two case reports4,5 (in the form of letters to the editor) directly addressing the problem (table 2). There was also one randomised controlled trial on the usefulness of aminophylline in reducing apnoeas and intubation in term infants during prostaglandin E1 infusion.6
Searches were performed in August 2004.
Recurrent apnoea is a common problem in otherwise well preterm infants. By term equivalent age, infants have usually “outgrown” their tendency to spontaneous apnoea. However, with an additional stress, such as infection (for example, bronchiolitis) or administration of drugs that depress the central nervous system (for example, general anaesthesia, prostaglandin), then apnoea and oxygen desaturations can recur.
Caffeine is recognised to reduce apnoea and the need for mechanical ventilation in preterm infants with apnoea of prematurity.1 In addition caffeine prevents apnoea, bradycardia, and episodes of desaturation in growing preterm infants following general anaesthesia,2 while aminophylline, which is another widely used theophylline derivative, was found to be effective for the prevention of apnoea and intubation during prostaglandin E1 infusion in term infants6 (table 3). While these data are supportive, there may be significant differences in the mechanism of apnoea in general anaesthesia and viral induced apnoea.
We could only find three reports3–5 involving a total of 10 infants, all of whom were born preterm and presented with bronchiolitis associated apnoeas approximately around term equivalent age. These reports have concluded that theophylline derivatives are effective in reducing the incidence of apnoeas and avoided the need for mechanical ventilation in this clinical situation (table 1).
Caffeine has a more favourable therapeutic index than aminophylline. No major adverse effects were reported from the studies included in the systematic reviews.1,2 Jitteriness, tachycardia, and raised blood glucose are the common side effects, but routine drug level monitoring is not necessary at standard dosage.7
While these three reports claim that the use of caffeine helped avoid intubation in infants with viral infection induced apnoea, there are no data from randomised controlled trials confirming these benefits. As intubation for apnoea in bronchiolitis is uncommon, a large multicentre trial would be needed.
CLINICAL BOTTOM LINE
In addition to its proven efficacy in apnoea of prematurity, caffeine has also been shown to reduce the incidence of apnoea in ex-preterm infants following general anaesthesia and in term infants following prostaglandin infusion.
There is only limited evidence from case reports for the use of caffeine in infants presenting with bronchiolitis associated apnoeas.