The prevention, assessment, and treatment of neonatal pain and agitation continues to challenge clinicians and researchers. Substantial progress has been made in the past three decades, but numerous outstanding questions remain. In this setting, clinicians must establish safe and compassionate standardized practices that consider available efficacy data, long-term outcomes, and research gaps. Novel approaches with limited data must be carefully considered against historic standards of care with robust data suggesting limited benefit and clear adverse effects. This review summarizes available evidence while suggesting practical clinical approaches to pain assessment and avoidance, procedural analgesia, postoperative analgesia, sedation during mechanical ventilation and therapeutic hypothermia, and the issues of tolerance and withdrawal.
Critically ill neonates are exposed to frequent painful procedures and agitating stimuli, with a negative impact on long-term outcome in the most vulnerable patients. Despite extensive research, the optimal approach to assessment, nonpharmacologic care, and pharmacotherapy remains elusive in most circumstances. Investigators must prioritize study designs that ethically generate novel data, ideally in collaboration with regulatory agencies to reduce the exclusively off-label utilization of medications discussed in this review. Even in the absence of scientific consensus, neonatal units must develop algorithms for the avoidance and treatment of pain and agitation in common clinical situations. Strong consideration should be given to the short-term and long-term safety of available interventions in the setting of limited data regarding objective efficacy. Existing analgesia or sedation practices should be maintained only where sufficient historic data support that standard. In the absence of data supporting efficacy, safety, and long-term benefit, novel interventions should be strongly considered in current clinical practice.

Authors :
Christopher McPherson 1,2 ● Cynthia M. Ortinau1 ● Zachary Vesoulis1
Christopher McPherson mcphersonc@wustl.edu
1 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
2 Department of Pharmacy, St. Louis Children’s Hospital, St. Louis, MO, USA

Journal of Perinatology (2021) 41:383–395