The human imperative to provide comfort and prevent pain in newborn babies is shared by many neonatal health caregivers. The American Academy of Pediatrics (AAP) Prevention and Management of Pain and Stress in the Neonate updated policy statement also emphasizes the need for effective prevention and treatment of pain in infants (1). Neurodevelopmental adverse effects of repetitive pain are greatest in premature infants, a complex population with high exposure to procedures and medications (2, 3), with the most immature infants receiving the highest number of painful events (1). The assessment and management of pain in the newborn has greatly advanced during the past three decades (4, 5). The need for procedural analgesia for neonates is well established (1, 2, 3, 4, 5, 6, 7, 8). Consistency on the use of pain and sedation continues to vary among clinicians and practice site (9, 10, 11). Not all institutions have instituted preventative protocols with nonpharmacologic and pharmacologic therapies for painful procedures in newborns (10, 11). A paucity of pharmacokinetic (PK) and pharmacodynamic (PD) data remains for many analgesics and sedatives secondary to the varying infant gestational ages and weights (12). Comorbid conditions, complex drug regimens, ethical issues, and genetic polymorphisms (13, 14, 15, 16, 17) complicate studies in critically ill neonates. For example, newborns and children who are CYP2D6 ultra metabolizers have experienced respiratory depression from therapeutic doses of codeine and tramadol (18, 19). Due to the increased incidence of these cases, codeine and tramadol have an age restriction on many formularies (19). Neonatal pain management requires careful selection and dosing of medications, appropriate assessment and monitoring, and ability to promptly recognize and manage adverse effects (20, 21, 22, 23). Improvements in neonatal pain management are driven by advances in developmental neurobiology, developmental PK and PD of analgesics, and the development of age-appropriate tools for pain assessment and by best evidence in clinical practice for this vulnerable population (14, 22, 23).

This chapter offers general guidelines for analgesia and sedation in newborn infants undergoing procedures that are frequently performed in the neonatal intensive care unit (1, 7, 8, 9). Selection of the optimal sedative for the management of stress in ventilated infants remains less clear and is beyond the scope of this chapter (24, 25, 26, 27).

1. The clinical assessment of pain in the newborn is imprecise. The Neonatal Pain Agitation and Sedation Scale (N-PASS) assesses ongoing pain, agitation, and sedation levels in term and premature neonates (22). Neonatal pain scales vary in content, utility, reliability, and ease of use and include physiologic, behavioral, and contextual parameters (see Appendix B.1) (21, 22, 23).