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.

Neuropathobiology of COVID-19: The Role for Glia

“…Perinatal environment of SARS-CoV-2-infection impacting on neurodevelopmental pathologies is also preponderant. With the increase of preterm births and admissions to the neonatal intensive care unit, COVID-19 may add to the perinatal stress that is known to be deleterious on brain development (Schepanski et al, 2018 ; McPherson et al, 2020 ). Indeed, many epidemiological studies suggest that early-life adversity can be associated with an increased occurrence of neurodevelopmental, neurological or neuropsychiatric disorders later in life (Halligan et al, 2007 ; Lupien et al, 2009 ; Knuesel et al, 2014 ).…”

Altered hypothalamic DNA methylation and stress-induced hyperactivity in a novel model of early life stress

“…Studies designed to investigate the contribution of such stressors to the long-term effects of PTB are difficult, because of the presence of multiple confounders such as illness severity or length of the NICU stay. Nevertheless, studies which have attempted to correct for various confounders have shown that the number of painful procedures experienced associates with alterations in brain development [15][16][17] suggesting that some stressors may indeed have long term consequences.…”

What do we know about pain in neonates?

“…Meanwhile, attentive clinical evaluation can guide prevention and non-pharmacological as well as pharmacological strategies for the treatment of pain. 5…”

“…Promising findings are emerging from electroencephalography, near‐infrared spectroscopy, and measurement of autonomic or endocrine responses, but optimal measures are yet to be determined, and these will remain an objective proxy for an essentially subjective experience. Meanwhile, attentive clinical evaluation can guide prevention and non‐pharmacological as well as pharmacological strategies for the treatment of pain 5 …”