Objective To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis. Study design Eligible infants aged #4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit. Results A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported. Conclusions A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis. (J Pediatr 2016;177:204-11). Trial registration Clinicaltrials.gov: NCT01435486. V iral bronchiolitis is the most common lower respiratory tract infection in infants, leading to 15 hospitalizations per 1000 person-years. Of these, 1.6% to 4% are admitted with apnea. 1-4 Bronchiolitis-associated apnea, a subset of apnea associated with respiratory viruses, appears to be a mixed central and obstructive apnea resulting from a complex interplay of respiratory drive suppression and airway secretions driven by a hyperactive laryngochemoreflex, somnogenic cytokines, and in some cases by virus-specific respiratory suppressant surface proteins. [5] [6] [7] Caffeine is a standard treatment for apnea of prematurity 8,9 and postextubation apnea in preterm infants, 10 and has been used to ameliorate apnea complicating bronchiolitis on the basis of case reports and observational studies. 11-17 Caffeine increases central respiratory drive and chemoreceptor sensitivity to CO 2 and improves skeletal muscle contractions, reducing diaphragm fatigue and leading to better ventilation. 18 Increased metabolic demand, diuresis, tachycardia, dysrhythmias, feeding intolerance, reduced weight gain, and seizures are the reported short-term side effect of caffeine. 19 Although evidence from prospective studies for caffeine used to treat apnea in bronchiolitis is lacking, the drug is commonly used in an attempt to avoid intubation and is considered a standard of care in some institutions. 11,17,20 Thus, we compared blinded intravenous caffeine citrate with placebo for shortening the time to resolution of acute bronchiolitis-associated apnea.
Output: Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial