We thank Dr Eichenwald and the American Academy of Pediatrics for their report, “Apnea of Prematurity.”1 Working in a large 84-bed level IV NICU, we have seen firsthand the impact that an Apnea and Bradycardia Guideline can have on length of stay (LOS), parent and staff satisfaction, and other outcomes. Since we introduced our Apnea and Bradycardia Guideline 2 years ago, we have seen a reduction in our very low birth weight LOS by 24% (Vermont Oxford Network [VON] database), which we attribute in part to standardization of what we consider clinically significant events, and how we manage these events. Although the definition of apnea is not evidence based and considerable variability exists in the literature, we question the definition of an apneic spell as defined by Dr Eichenwald—cessation of breathing of >20 seconds or heart rate of <100 beats per minute when accompanied by cessation of breathing <20 seconds—because most sources define bradycardia in this situation as <80 beats per minute (and even lower at higher gestational ages). These sources also cite a minimum time period during which a bradycardic event needs to occur to be considered significant. A higher heart rate and/or lower event duration threshold may lead to unnecessary prolonged observation in the hospital for a physiologic and benign condition.
We are aware of the literature suggesting caffeine level monitoring is unnecessary because caffeine has a wide therapeutic index for the treatment of apnea of prematurity.2 Our experience is that levels in the upper normal therapeutic range (15–20 mcg/mL) yield a greater response, especially for very low birth weight neonates, and that caffeine level monitoring is essential to attain these desired levels because caffeine clearance is variable. Our findings coincide with those of Dr Gal, who demonstrated a proportional caffeine level to apnea of prematurity response relationship (even for levels 40+ mcg/mL).3 Also, some studies admit to failing to reach therapeutic levels with standard caffeine dosing, and these same studies suggest a dose-response relationship with higher levels achieving greater efficacy.2 There is also evidence correlating caffeine concentration maintenance above 14.5 mcg/mL with reduced chronic lung disease rates in neonates ≤29 weeks postmenstrual age.4 We continue to report chronic lung disease rates in the best VON quartile (VON database), which we attribute, in part, to maintenance of caffeine levels in the upper normal therapeutic range.
Another concern recently raised is that a significant number of infants do not have subtherapeutic caffeine levels (defined as <5 mcg/mL) 7 days after discontinuation of caffeine (the number of days often cited in the literature at which an infant can safely be discharged off caffeine), and many of these infants continue to have pathologic apnea.5 A benefit of obtaining caffeine levels after discontinuation of caffeine before discharge would be for calculation or estimation of patient-specific pharmacokinetic parameters to be used for prediction of subtherapeutic levels to help ensure safer discharge.5 We feel that this new practice will decrease the risk of patients developing postdischarge hypoxic or apneic events and possibly decrease the likelihood of readmissions for these serious events.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
- Copyright © 2016 by the American Academy of Pediatrics