Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Duke University Medical Center, Durham, NC, USA
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
Jean and George Brumley Jr. Neonatal Perinatal Research Institute, Duke University Medical Center, Durham, NC, USA
Address for correspondence: Margarita Bidegain, Duke University Medical Center, 2424 Hock Plaza, Suite 504, DUMC Box 2739, Durham, NC 27710, USA. Tel.: +1 919 681 6024; Fax: +1 919 681 6065; E-mail: firstname.lastname@example.org.
Abstract: BACKGROUND: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety data are sparse. The objective of this study is to evaluate the safety of intranasal midazolam and intranasal fentanyl in infants admitted to the Neonatal Intensive Care Unit (NICU). METHODS: We retrospectively identified all infants receiving intranasal midazolam or fentanyl in the NICU from 2009 to 2015. We recorded indication for use and vital signs and determined the proportion of infants experiencing the following adverse events: death within 24 hours, hypotension, bradycardia, worsening respiratory status, and chest wall rigidity. Vital signs 4 hours before and after each dose were compared using the Wilcoxon signed-rank test. RESULTS: We identified 17 infants (gestational ages 23– 41 weeks) receiving 25 intranasal doses. None of the infants died or developed hypotension, bradycardia, or chest wall rigidity. Intranasal delivery was most commonly used for sedation during magnetic resonance imaging studies. Other indications include analgesia or sedation for retinopathy of prematurity surgery, intubation, and peripherally inserted central catheter placement. One infant receiving intranasal midazolam experienced worsening respiratory status. Vital signs before and after dosing were not significantly different. CONCLUSIONS: Intranasal midazolam and fentanyl use in term and preterm infants appeared safe and well-tolerated in this small cohort of infants. Larger, prospective studies evaluating the safety and efficacy of intranasal midazolam and fentanyl use in infants are warranted.
Keywords: Intranasal drug delivery, drug safety, infant pharmacology, procedural