16 At the confluence of nonpharmacologic and pharmacologic therapy, sucrose continues to require careful investigation despite decades of widespread utilization. 14, 15 Nonpharmacologic comfort measures have also been widely implemented for minor procedural pain however, the optimal bundle of interventions remains undefined due to gaps in available evidence. 13 However, investigation of the relative short- and long-term safety of newer analgesic and anesthetic agents challenges investigators and clinicians. In the modern era, provision of analgesia prior to major procedures ranging from endotracheal intubation to invasive surgery represents standard neonatal care. 10, 11 After tissue damage, preterm infants experience prolonged hyperalgesia and allodynia, leading to chronic periods of nociception and stress. 8 In fact, preterm infants have lower flexor reflex thresholds and poor localization and discrimination of sensory input, leading to increased hormonal and physiologic responses to painful stimuli compared to older patients. 8, 9 Ascending pathways mediating nociception connect peripheral sensory neurons to the thalamus between 20 and 24 weeks of gestation, while descending inhibitory pathways mature beyond term gestation. 7 Careful investigation, including basic science and clinical research, documented the unique susceptibility of preterm infants to adverse metabolic, behavioral, and clinical responses to acute pain, sparking a revolution in pain science in the neonatal intensive care. 6 The traditional definition of pain relying on self-reported perception and emotional experience presents challenges in non-verbal populations, including but not limited to preterm infants. In this article, the panel will review the topic in detail, addressing factors related to (a) the link between pain and aberrant maturation in the developing brain (b) methods to assess pain in the NICU (c) nonpharmacologic and pharmacologic management of pain and agitation in preterm infants and (d) knowledge gaps and future research directions.Īs recently as 30 years ago, preterm infants underwent major surgical procedures without perioperative or postoperative analgesia. In April 2019, an expert panel met at the annual Neonatal Neurocritical Care Special Interest Group ( meeting to review approaches to measuring and managing pain in the NICU. 5 An important modifiable factor that has been gaining interest in the clinical and research setting is pain in the neonatal intensive care unit (NICU). 2, 3, 4 More recent studies are shifting the paradigm of brain injury in the preterm infant from a “one-hit brain injury” to overall alteration in trajectory of brain maturation. 1 Neurodevelopmental challenges in infants born preterm often follow severe intraventricular hemorrhage (IVH) and white matter injury (WMI). Despite advances in neonatal intensive care, preterm birth remains a leading cause of neurodevelopmental disability. Improved neonatal intensive care has reduced the mortality and increased the survival of preterm infants. The rate of preterm birth is rising around the world. Chronic sedation during invasive mechanical ventilation represents an ongoing challenge appropriate containment and an optimal environment should be standard when indicated, low-dose morphine infusion may be utilized cautiously and dexmedetomidine infusion may be considered as an emerging adjunct. Rapidly acting opioids (fentanyl or remifentanil) form the backbone of analgesia for moderately painful procedures. Sucrose may be utilized judiciously as an adjunctive therapy for minor painful procedures. Nonpharmacologic interventions should be consistently utilized prior to mild to moderately painful procedures. Considering benefits and risks of available treatments, units must develop a stepwise algorithm to prevent, assess, and treat pain.
Both nonpharmacologic and pharmacologic approaches are used to reduce the negative impact of pain and agitation in the preterm infant, with concerns emerging over the adverse effects of analgesia and sedatives. Although many tools have been validated to assess acute pain, few methods are available to assess chronic pain or agitation (a clinical manifestation of neonatal stress). The adverse neurobiological impact of pain and stress in the preterm infant has been well documented, including neuroimaging and neurobehavioral outcomes. Preterm infants are exposed to frequent painful procedures and agitating stimuli over the many weeks of their hospitalization in the neonatal intensive care unit (NICU).
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