Evaluation of the Cardiovascular Effects of Clonidine in Neonates Treated for Neonatal Abstinence Syndrome

J Pediatr Pharmacol Ther. 2018 Nov-Dec;23(6):473-478. doi: 10.5863/1551-6776-23.6.473.

Abstract

Objectives: Neonatal abstinence syndrome (NAS) is characterized by withdrawal symptoms in neonates exposed to legal or illegal substances in utero, and it is often managed with medications such as opiates, phenobarbital, and clonidine. Clonidine use is increasing, but further safety data regarding its use in neonates are warranted. This study evaluated the effects of clonidine on heart rate and blood pressure in neonates treated for NAS at doses up to 24 mcg/kg/day.

Methods: A retrospective review via the electronic medical record of infants at least 35 weeks' gestation treated adjunctively with clonidine for NAS in the neonatal intensive care unit at St Elizabeth was conducted. Heart rate, and systolic and diastolic blood pressure were recorded at baseline, while on different dose ranges of clonidine (small: ≤1.5 mcg/kg per dose every 3 hours; medium: >1.5 to 2 mcg/kg per dose every 3 hours; and large: >2 mcg/kg to 3 mcg/kg per dose every 3 hours), and upon discontinuation.

Results: A total of 64 infants treated with clonidine for NAS between August 2015 and December 2016 were included. Heart rate decreased in all clonidine dose ranges compared with baseline (average reduction of 7 bpm [CI: -12 to -2], 9 bpm [CI: -16 to -2], and 10 bpm [CI: -18 to -1] for the small, medium, and large dose ranges, respectively; p < 0.0001). Systolic and diastolic blood pressure were not significantly different from baseline when infants were receiving any dose of clonidine, except diastolic blood pressure while on medium-dose range clonidine, where diastolic blood pressure was higher than baseline (p = 0.0128). Increases in systolic and diastolic blood pressure were evident upon discontinuation of clonidine (p < 0.0001 and p = 0.0156, respectively).

Conclusions: Clonidine doses up to 24 mcg/kg/day are well tolerated in neonates ≥35 weeks' gestation treated for NAS. Any decreases in heart rate are likely clinically insignificant, and increases in blood pressure upon discontinuing clonidine are mild and may be mitigated further with extended discontinuation protocols. Further trials should be conducted to evaluate the long-term safety of clonidine in this population.

Keywords: neonatal abstinence syndrome.