The influence of pain, agitation, and their management on the immature brain

Abstract

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). The adverse neurobiological impact of pain and stress in the preterm infant has been well documented, including neuroimaging and neurobehavioral outcomes. 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). 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. Considering benefits and risks of available treatments, units must develop a stepwise algorithm to prevent, assess, and treat pain. Nonpharmacologic interventions should be consistently utilized prior to mild to moderately painful procedures. Sucrose may be utilized judiciously as an adjunctive therapy for minor painful procedures. Rapidly acting opioids (fentanyl or remifentanil) form the backbone of analgesia for moderately painful procedures. 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.

Fig. 1

Growth of the thalamus associated with neonatal pain: The left image illustrates a deformation-based morphometry t-statistic map reflecting reductions in thalamus volume associated with early skin-breaking procedures overlaid on a magnetic resonance image developed as a T1-weighted image template from a median postmenstrual age of 32 weeks. The right scatterplot illustrates the association between volume loss in the lateral thalamus and an increasing exposure to skin-breaking procedures between birth and magnetic resonance imaging. Reproduced with permission from Duerden et al..