Intranasal Analgesia in Preterm and Term Neonates

The prevention, recognition, and treatment of pain is crucial in the management of neonates. Infants do not tolerate pain better than adults; indeed, the immaturity of the endogenous antalgic system means they exhibit an increased stress response. Pain has been associated with worse cognitive and motor scores, reduced growth trend, reduced brain maturation, and altered corticospinal tract structure. The use of the intranasal route for drug delivery is currently expanding because it has many advantages. In certain contexts, it is preferable over the oral route because of the faster entry of drugs into the circulation, the absence of structural changes by the gastrointestinal environment, and the absence of the hepatic first-pass effect. The pharmacokinetics and pharmacodynamics of drugs commonly used for pain management have peculiar characteristics in infants, especially premature infants. In this article, we summarise the evidence regarding pain management in infants using intranasally administered drugs. We then provide a practical guide to the use of intranasal drugs currently being studied in the neonatal population, focusing on appropriate dosages and indications. Intranasal fentanest appears to be an attractive therapeutic alternative for procedural and palliative neonatal pain management when intravenous access is unavailable in preterm infants. Intranasal midazolam is a valid alternative to consider in term or near-term neonates, especially when the aim is to obtain sedation (and not analgesia, i.e. during magnetic resonance imaging), ketamine has favourable cardiovascular effects and should be considered in specific patients and situations. Intranasal dexmedetomidine is well tolerated in premature neonates. Additionally, endonasal dexmedetomidine can be used in combination with other anaesthetic, sedative, hypnotic, and opioid drugs to allow for dose reduction in sedated neonates.