As educators, we love—and are always humbled by—those moments when we get to say, “I don’t know.” For some of these questions, you may already know the answers. For others, you may never have thought to ask the question. For all, questions, comments, concerns, and critiques are encouraged. Welcome to the Kids Korner.

While it may have been warm outside a few weeks ago, the cold days to have returned, which means the bronchiolitics and croupers are on their way, too.

Question: Under what age (in months) is there a significant association with central apnea in respiratory syncytial virus (RSV)-positive bronchiolitis?

The association between RSV-positive bronchiolitis and central apnea was recognized as early as the late 1960s.^1,2 In an early multicenter retrospective study of 274 infants younger than 6 months with RSV-positive bronchiolitis, the overall incidence of apnea was found to be 20.4 percent (95% CI, 16.1–25.6%).¹ While this study provided no p-values, the data suggested that the highest-risk group for apnea was infants under three months of age. Additionally, the authors recognized that premature infants were more likely to develop apnea. Since then, there have been other studies that have found similar results, with an association between RSV-positive bronchiolitis and central apnea, but the overall incidence varies widely. The incidence ranges from ^1.2 percent to 23.8 percent, with more recent studies in the 5 percent to 10 percent range.^3,4 So why do we care? Ultimately, the reason we care about this topic is because studies recurrently recognize that apnea can be the first sign of RSV-positive bronchiolitis.

A retrospective study by Kneyber et al looked at 185 infants under 12 months of age who were admitted with RSV-positive bronchiolitis over a four-year period.⁵ They found that age was a statistically significant independent risk factor for RSV-associated apnea and that infants younger than 2 months were the highest-risk group.⁵ Along with age, a number of studies have identified prematurity (commonly defined as <37 weeks gestation) as a significant risk factor as well.^2,3

A retrospective study by Kneyber et al looked at 185 infants under 12 months of age who were admitted with RSV-positive bronchiolitis over a four-year period.5 They found that age was a statistically significant independent risk factor for RSV-associated apnea and that infants younger than 2 months were the highest-risk group.⁵

Recent studies continue to demonstrate an association between bronchiolitis and central apnea or need for a significant medical intervention in children younger than 2 months of age. A 2014 study by Pruikkonen et al retrospectively reviewed the cases of 353 children younger than 6 months of age with bronchiolitis and found that 19 percent of hospitalized infants with bronchiolitis required a major medical intervention—defined as supplemental oxygen, intravenous fluids or antibiotics, or admission to the ICU.⁴ While not all of these interventions were secondary to apnea, all apneic events occurred in children younger than 2 months. Ninety-two percent of patients requiring medical interventions were RSV-positive, and the largest majority of these interventions were necessary within the first five days of symptom onset.

While we are currently unaware of any prospective studies addressing which infants need to be admitted with specific regard to age, prospective observational studies of hospitalized bronchiolitic infants have also found an increased risk of apnea in hospitalized infants younger than 2 months and an increased odds of the need for intubation or continuous positive pressure ventilation.^6,7

Summary: With the current data, the best cutoff for identifying term infants with an increased risk of central apnea in RSV-positive bronchiolitis is probably two months. Multiple studies also recognize that apnea can be one of the first presenting signs of RSV-positive bronchiolitis, particularly in the first five days. Prematurity is also a well-recognized risk factor.

Q: After receiving nebulized epinephrine for croup, how long do patients need to be observed before they can be safely discharged?

Initial studies involving children with croup were rather conservative and recommended admission after giving a single nebulized epinephrine treatment. We now recognize that this is not necessary, and subsequent observation periods have progressively gotten shorter.

A prospective study by Rizos et al evaluated a two-hour observation time following the administration of nebulized racemic epinephrine and intramuscular dexamethasone administration in the emergency department.⁸ The authors followed 654 consecutive patients with croup. Of these 654 children, 174 kids with moderate or severe croup required a nebulized racemic epinephrine treatment. Of these 174 children, 92 were discharged. None of the patients developed rebound phenomenon (eg, rebound stridor) after two hours of observation following their nebulized epinephrine treatment. Other retrospective studies have found similar results.⁹

A 2013 Cochrane review on this topic identified a single randomized prospective study and found no statistical difference in croup score two hours after administration of nebulized epinephrine when comparing placebo versus nebulized epinephrine.10 This suggests that the effects of the nebulized epinephrine had subsided by the two-hour mark. This study was limited, though, including only 10 children in each treatment arm.

Summary: Early studies were more conservative and recommended three to four hours of observation after administering a nebulized epinephrine treatment. There have been prospective and retrospective studies that suggest a two-hour observation period is probably adequate.

Dr. Jones is assistant professor of pediatric emergency medicine at the University of Kentucky in Lexington. Dr. Cantor is professor of emergency medicine and pediatrics, director of the pediatric emergency department, and medical director of the Central New York Poison Control Center at Upstate Medical University in Syracuse, New York.

References

1. Bruhn FW, Mokrohisky ST, McIntosh K. Apnea associated with respiratory syncytial virus infection in young infants. J Pediatr. 1977;90:382-6.
2. Church NR, Anas NG, Hall CB, et al. Respiratory syncytial virus-related apnea in infants: demographics and outcome. Am J Dis Child. 1984;138:247-50.
3. Willwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emerg Med. 2006;48:441-7.
4. Pruikkonen H, Uhari M, Dunder T, et al. Infants under 6 months with bronchiolitis are most likely to need major medical interventions in the 5 days after onset. Acta Paediatr. 2014;103:1089-93.
5. Kneyber MC, Brandenburg AH, de Groot R, et al. Risk factors for respiratory syncytial virus associated apnoea. Eur J Pediatr. 1998;157:331-5.
6. Schroeder AR, Mansbach JM, Stevenson M, et al. Apnea in children hospitalized with bronchiolitis. Pediatrics. 2013;132:e1194-201.
7. Mansbach JM, Piedra PA, Stevenson MD, et al. Prospective multicenter study of children with bronchiolitis requiring mechanical ventilation. Pediatrics. 2012;130:e492-500.
8. Rizos JD, DiGravio BE, Sehl MJ, et al. The disposition of children with croup treated with racemic epinephrine and dexamethasone in the emergency department. J Emerg Med. 1998;16:535-9.
9. Kelley PB, Simon JE. Racemic epinephrine use in croup and disposition. Am J Emerg Med. 1992;10:181-3.
10. Bjornson C, Russell K, Vandermeer B, et al. Nebulized epinephrine for croup in children. Cochrane Database Syst Rev. 2013;10:CD006619.