The youngest, most fragile patients often face many painful procedures in their first weeks of life, yet there has been little research and evidence-based protocols established outlining the most effective assessments and treatments for neonates.
Erin Keels, APRN, MS, NNP-BC, of Nationwide Children’s Hospital in Columbus, Ohio and lead author of new guidance from the American Academy of Pediatrics (AAP), says while there is new data available on pain management in neonates for pediatricians, there is still much work to be done.
Around the same time the previous AAP policy statement on neonatal pain from 2006 was due to be reviewed, a meta-analysis of studies on non-pharmacologic interventions and pharmacologic therapies for neonates was conducted, says Keels. That meta-analysis revealed large gaps in assessment and treatment protocols, as well as evidence about what interventions work.
“Relative to the 2006 statement, we have better outcomes data related to the usefulness of nonpharmacologic interventions such as skin-to-skin care/contact, breastfeeding, sensorial sensation, and strategic positioning/tucking,” Keels says. “At the same time, we continue to be challenged for long-term neurodevelopmental outcomes with repeated/excessive use of sucrose or glucose and other medication-based therapies.”
Previous guidelines developed by the AAP and the Canadian Pediatric Society addressed the need to assess neonatal pain and provided recommendations on preventing and minimizing pain as well as promptly and adequately treating unavoidable pain.
Despite these previous efforts, Keels says neonatal pain continues to be “inconsistently assessed and inadequately managed.”
Keels cites a French study from 2008 that revealed only 21% of infants were provided interventions and medications aimed at alleviating pain before procedures, and only 34% continued to receive some kind of pain relief following their procedures.
Preventing and treating pain in neonate is not only the ethical thing to do, but it is also important to prevent long-term negative effects of treatment, Keels says.
“Exposure to repeated painful stimuli early in life is known to have short- and long-term adverse sequelae,” Keels notes. “These sequelae include physiologic instability, altered brain development, and abnormal neurodevelopment, somatosensory, and stress response systems, which can persist into childhood. Nociceptive pathways are active and functional as early as 25 weeks’ gestation and may elicit a generalized or exaggerated response to noxious stimuli in immature newborn infants.”
Neonates who are born with the greatest risk of neurodevelopmental impairment resulting from preterm birth are also most likely to encounter painful stimuli in the hospital setting or neonatal intensive care unit (NICU). Although there is still much to be learned about the best ways to prevent and relieve pain in neonates, Keels says there are proven and safe therapies that are underused for painful procedures.
“Every healthcare facility caring for neonates should implement a pain prevention program that includes strategies for minimizing the number of painful procedures performed and a pain assessment and management plan that includes routine assessment of pain; pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures; and measures for minimizing pain associated with surgery and other major procedures,” Keels states in her study.
Assessment of pain in neonates can be precarious because the infant is unable to report or communicate the presence or severity of his or her pain.
There are reliable pain assessment tools recommended by pediatric groups like AAP (Neonatal Facial Coding System, Premature Infant Pain Profile [PIPP], Neonatal Pain and Sedation Scale, Behavioral Infant Pain Profile, and Douleur Aiguë du Nouveau-né). These tools reflect assessments of physiologic and behavioral responses to pain, Keels says, but more research is needed.
There are a number of factors that play a role in what type of pain assessment would best benefit a neonatal client, including gestational age and behavioral state. A number of new technologies to measure pain, including functional magnetic resonance imaging, heart rate variability, and more are currently being studied and show promise, Keels says.
In the meantime, researchers reported that the Behavioral Indicators of Infant Pain and the Neonatal Facial Coding Systems were more effective in detecting behavioral cues for pain than the PIPP alone. However, Keels says it is unlikely that a single comprehensive assessment tool can be used in all situations.
“More research needs to be performed to assess the intensity of both acute and chronic pain at the bedside, to differentiate signs and symptoms of pain from those attributable to other causes, and to understand the significance of situations when there is no perceptible response to pain,” Keels says.
When pain is identified, finding effective and appropriate methods to relieve that pain is another challenge in neonates.
Nonpharmacologic methods for pain relief may include swaddling combined with positioning, facilitated tucking, nonnutritive sucking, and massage, and have all been shown to offer relief for mild to moderate pain. Skin-to-skin care—with or without complementary sucrose administration, breastfeeding, and sensorial stimulation has also been found to be highly effective in managing mild to moderate pain in neonates, Keel notes.
Sucrose and glucose administration as a source of analgesic is extensively used for mild to moderate pain, although there are still many unknowns to this treatment including appropriate dosing, mechanism of action, soothing versus analgesic effects, and long-term consequences, Keels says.
Maximum benefits have been shown when sucrose is administered about 2 minutes before painful stimulus, with the effects lasting about 4 minutes, Keels says. Therefore, longer procedures—including circumcision—may require multiple doses for optimal and continued effect. Keels says sucrose is believed to evoke an analgesic effect through opiate, endorphin, and possibly dopamine or acetylcholine pathways, and it is most effective when combined with other pain management strategies like swaddling and non-nutritive sucking.
Still, while there appears to be benefit from sucrose administration, the science isn’t really there.
“Although the evidence that oral sucrose alleviates procedurally related pain and stress, as judged by clinical pain scores, appears to be strong, a small randomized controlled trial found no difference in either nociceptive brain activity on electroencephalography or spinal nociceptive reflex withdrawal on electromyography between sucrose or sterile water administered to term infants before a heel lance,” Keels says. “This masked study did find, however, that clinical pain scores were decreased in the infants receiving sucrose, and several methodologic concerns limit the conclusions that can be drawn from the trial.”
Another question to be answered in the administration of sucrose is dosage, Keels says. No optimal dose has been determined, but an oral dose of 0.1 to 1 milliliters of 24% sucrose (or 0.2 to 0.5 mL/kg) before painful procedures is recommended.
Long-term effects of sucrose administration are also in questions, with one study of 107 preterm infants born before 31 weeks gestation who received more than 10 doses of sucrose in the first 24 hours of life faring worse on neurodevelopmental scores as 32, 36, and 40 weeks gestation. One infant in the study even developed hyperglycemia coincident with frequent sucrose dosing, she adds.
“When sucrose is used as a pain management strategy, it should be prescribed and tracked as a medication. More research is needed to better understand the effects of sucrose use for analgesia,” Keels says.
Glucose is also effective in decreasing pain responses, with 20% to 30% glucose solutions reducing pain scores and crying.
Opioids are also used in newborns, with fentanyl and morphine among the most commonly used to persistent pain, but research on appropriate dosing and long-term effects of these medications are insufficient.
Opioids, however, come with at a price—side effects including hypotension, respiratory depression, constipation, urinary retention, bradycardia, and more. Benzodiazepines are also frequently used in the NICU for sedation, Keels says, and there is evidence of minor analgesic effects, although when used in combination with opioids, benzodiazepines could exacerbate respiratory depression and hypotension related to the opioid use.
Other medications like methadone, ketamine, and propofol have been proposed for use in neonates, but have not been well studied and are either not widely used or not used at all.
Oral or intravenous acetaminophen is also used in neonates, although, intravenous formulations have not been approved by the US Food and Drug Administration. Acetaminophen has been limited to post-operative pain control, and preliminary data shows it decrease the amount of morphine needed, Keels notes.
Nonsteroidal anti-inflammatory use has been limited to the closure of patent ductous arteriosus.
Topical anesthesia is also used, with the most frequently used agents being tetracain gel and Eutectic Mixture of Local Anesthetics (a combination of lidocaine and prilocaine). Topicals are most often used during venipuncture, central venous catheter insertion, and peripheral arterial puncture, but are not effective in some more extensive therapies and toxicity is a concern in neonates.
“There are significant research gaps regarding the assessment, management, and outcomes of neonatal pain; and there is a continuing need for studies evaluating the effects of neonatal pain and pain prevention strategies on long-term neurodevelopmental, behavioral, and cognitive outcomes,” Keels says. “The use of pharmacologic treatments for pain prevention and management in neonates continues to be hampered by the paucity of data on the short- and long-term safety and efficacy of these agents. At the same time, repetitive pain in the NICU has been associated with adverse neurodevelopmental, behavioral, and cognitive outcomes, calling for more research to address gaps in knowledge.”
Keels recommends that pediatricians work to achieve the goals in assessing and treating pain in neonates:
1. Prevent or minimize pain by using written, evidence-based guidelines and both pharmacologic and nonpharmacologic therapies.
2. Assess pain in neonates using validated neonatal paid assessment tools both initially and on a continuing basis.
3. Use therapeutic strategies such tucking, nonnutritive sucking, and breastfeeding for short-term relief during mild to moderately painful procedures.
4. Use oral sucrose and/or glucose along with other pain management strategies during mild to moderately painful procedures, and track the use of sucrose/glucose as a medication.
5. Weigh benefits and burdens of pharmacologic treatment and monitor carefully for any side effects.
6. Continue to receive education and promote additional research on recognition, assessment, and management of neonatal pain.
“Clinical providers should continue to be mindful of the causes of pain in neonates and limit/avoid unnecessary or non-urgent procedures while incorporating these evidence-based, nonpharmacologic strategies into their foundation of practice,” Keels says. “Integrating family into procedural pain management through skin-to-skin care/contact, breastfeeding, sensorial sensation, holding and/or offering a pacifier with sucrose can be very useful to a neonate. At the same time, it improves collaboration, communication, and the overall family experience during these stressful situations.”