By Rachel Clements

Long-term Consequences of Pain Exposure

            The previously held belief that infants do not perceive pain is no longer held by most caregivers in the Neonatal Intensive Care Unit (NICU). Recent research shows that preterm infants have a lower threshold for pain than adults (Mehrnoush, Ashktorab, Heidarzadeh, Momenzadeh & Kahlafi, 2017a; Mehrnoush, Ashktorab, Heidarzadeh, Momenzadeh & Kahlafi 2017b), and one study stated that the threshold may even be as much as 30-50% lower than adults (Mehrnoush, Ashktorab, Heidarzadeh, Momenzadeh & Kahlafi, 2016). Premature infants are also more likely to experience long-term effects of repetitive pain (Kocek, Wilcox, Crank & Patra, 2016).  This increased sensitivity is due to the fact that infants develop nociceptive pathways as early as 23 weeks, but have not yet developed the descending neurotransmitters that are responsible for modulating pain (Aucott, Donohue, Atkins & Allen, 2002).

            The literature also shows that the pain experienced by premature infants is harmful in the long-term. Infants can experience developmental disabilities, cognitive, social and emotional problems because of pain exposure and shortening of the sensory area of the brain (Mehrnoush et al. 2016, 2017b; Zwimpfer & Elder, 2012). Aucott et al. (2002) states that in the long-term, a premature an infant’s response to pain may also be altered because of the structural reorganization that can occur in the nervous system, and they are also likely to show greater aversion to pain at ages eight to ten than their peers. At age 11, former extremely low birth weight infants who were exposed to surgical procedures display altered sensory perceptions (Marlow, 2013). It was even reported that without analgesia during surgery there was an increased morbidity (Rana et al, 2017). We can conclude from these studies that exposure to pain is harmful for premature infants and it is imperative that it is appropriately managed.

Harmful Consequences of Analgesics and Sedatives

            Sedatives and analgesics are regularly used in NICUs, especially benzodiazepines and opioids (Borenstein-Levin et al., 2016; Kocek et al., 2016; Mehrnoush et al., 2017a, 2017b, Rana et al., 2017). Opioids are depressive and can cause significant short-term effects such as increased days of mechanical ventilation, but are also suspected to cause apoptotic neurodegeneration (Kocek et al., 2016). Kocek et al. (2016) also found that infants who received higher or more frequent doses of opioids had an increased likelihood of necrotizing enterocolitis (NEC) and had more surgical procedures in addition to more days of being on mechanical ventilation. However, some studies showed use of opioids did not have an effect on the number of ventilated days (Borenstein-Levin et al., 2016).

Both benzodiazepines and opioids are related to slowing down the gut and slowing the passage of meconium, and frequent usage of these drugs increases the risk of infants needing a period of withdrawal from them (Rana et al. 2017). The study performed by Rana et al. (2017) showed that while decreasing the amount of analgesics and sedatives did not increase mortality, it did decrease the amount of days total parenteral nutrition (TPN) was required because the gut was not slowed by these medications.

            In the long term, infants who were exposed to opioids showed poorer outcomes than their peers in several areas including short-term memory, head circumference, cognitive scores, and social behaviors (Borenstein-Levin et al., 2016; Kocek et al., 2016). Kocek et al. (2016) found that for morphine equivalent drugs, an increase of 1mg/kg decreased the cognitive score by 0.238 points on the Bayley Scales of Infant and Toddler Development (BSITD-III). However, this study also showed that the behavioral difference between these children and their peers mostly resolved by age 7, though they say larger studies are needed to confirm this. Additionally, many long-term effects are still unknown (Borenstein-Levin et al., 2016).

            Long-term effects of benzodiazepines may be more serious than those of opioids, as recent studies are finding evidence of damage to the development of the hippocampus in premature infants, and animal models show neuroapoptosis and slowed neurogenesis (Borenstein-Levin et al., 2016). Interventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and death are also associated with continuous infusions beginning with a loading dose of midazolam in one study (Borenstein-Levin et al., 2016). There is also some evidence of longer NICU stays with use of benzodiazepines (Rana et al., 2017).

Effectiveness of Non-pharmacological Pain Management Techniques

            Many types of non-pharmacological methods of pain relief were identified and supported as effective by the literature. Methods included swaddling, pacifier, 24% oral sucrose, massaging, presence of a parent, and skin to skin holding (also called Kangaroo Care) (Aucott et al., 2002; Fleishman, Gleason, Mayaing, Zhou & Mangione-Smith, 2013; Mahrnoush et al., 2016, 2017b,; Rana et al., 2017; Zwimpfer & Elder, 2012). When soothing is assisted by an adult caregiver, infants develop the neural pathways to learn how to do this for themselves (Zwimpfer & Elder, 2012). A method called the “Tipple T Intervention” uses touch, taste (in the form of 24% oral sucrose) and talk as a non-pharmacologic method of pain management, and studies have showed this to reduce pain on assessment (Zwimpfer & Elder, 2012).

A common thread in most of the reviewed literature was the underutilization of non-pharmacologic pain management techniques (Borenstein-Levin et al., 2016; Kocek et al., 2016; Mehrnoush et al., 2016, 2017a, 2017b). One qualitative study found that nurses were not aware of these technique’s usefulness for pain management, but nurses still reported that these techniques did make the infants calmer (Mehrnoush et al., 2017b). Another study showed that nurses believed these interventions were more effective than analgesics or sedatives (Mehrnoush et al., 2016).  

Other studies showed varying levels of education of nurses determined the type of pain management an infant received. Nurses with bachelor’s degrees were more likely to use a combination of opioids and non-pharmacological methods, and nurses with lower levels of education used topical drugs. This same study also showed nurses with more experience were more likely to use pharmacological methods (Kostak, Inal, Efe, Bal Yilmaz & Senel, 2015).

Need for NICU Nurse Education for Pain Management

The literature as stated in the previous sections shows that varying ideas exist among NICU nurses about appropriate pain management. It is recommended that nurses manage pain using a combination of both pharmacological and non-pharmacological methods (Mahrnoush et al., 2016, Rana et al., 2017). What nurses do know is that premature infants do have pain and that analgesics and sedatives do have side effects, but less than 50% believe pain is properly managed (Mehrnoush et al., 2017a). What nurses do not understand, according to the research, is that premature infants do not have as high as a threshold for pain as adults or even term infants (Mehrnoush et al., 2017b). Also, nurses are primarily concerned only about the short-term effects of sedatives and analgesics, but understood that they needed more education on the subject (Mehrnoush et al., 2017a).

It is important to educate NICU nurses about appropriate pain management because nurses are the ones who are with the infants the most (Mehrnoush et al., 2016). One study showed administration of pain management is largely influenced by nurses’ attitudes and feelings (Mehrnoush et al., 2017a). Another study showed nurses’ empathy, education, knowledge, protocols and team work were also factors that determined appropriate pain management (Aymar, Lima, Santos, Moreno & Coutinho, 2014). Fleishman et al. (2013) suggest nurses are using more narcotics “perhaps to treat ourselves as much as our patients” (p. 337).

Several studies of barriers to appropriate pain management recommended staff education as an improvement measure (Mehrnoush et al., 2016, 2017a, 2017b). Several short-term studies have been done using education interventions to decrease the administration of sedatives and analgesics in preterm infants. A study in Brazil implemented guidelines for opioid and benzodiazepine administration and saw a reduction from 62.9% of infants receiving pharmacotherapy to 32.8% while still maintaining adequate management of pain. (Aymar et al., 2014). However, long-term studies showed that over time the percentage of premature infants that received morphine had not changed (Fleishman et al., 2013).

It is clear that an educational intervention about appropriate pain management for NICU nurses is needed. A review of the literature revealed that studies relating specifically to pain management in mechanically ventilated infants are few. Mechanical ventilation is known to be painful and agitating and is even considered a form of chronic pain (Fleishman et al., 2013). Therefore, a study is needed that explores interventions to improve appropriate pain management by nurses for mechanically ventilated neonates.

References

Aucott, S., Donohue, P. K., Atkins, E., & Allen, M. C. (2002). Neurodevelopmental care in the NICU. Mental Retardation and Developmental Disabilities Research Reviews,8, 298-308. doi:10.1002/mrdd.10040

Aymar, C. L., Lima, L. S., Santos, C. M., Moreno, E. A., & Coutinho, S. B. (2014). Pain assessment and management in the NICU: Analysis of an educational intervention for health professionals. Jornal De Pediatria (Versão Em Português),90(3), 308-315. doi:10.1016/j.jpedp.2013.09.008

Borenstein-Levin, L., Synnes, A., Grunau, R. E., Miller, S. P., Yoon, E. W., & Shah, P. S. (2017). Narcotics and sedative use in preterm neonates. The Journal of Pediatrics,180, 92-98. doi:10.101.

Fleishman, R., Gleason, C. A., Myaing, M. T., Zhou, C., & Mangione-Smith, R. (2013). Evaluating patterns of morphine use in a neonatal intensive care unit after NEOPAIN. Journal of Neonatal-Parinatal Medicine,6, 333-338. doi:10.3233/NPM-1371513

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Kocek, M., Wilcox, R., Crank, C., & Patra, K. (2016). Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2years. Early Human Development,92, 29-32. doi:10.1016/j.earlhumdev.2015.11.001

Kostak, M., Inal, S., Efe, E., Yilmaz, H. B., & Senel, Z. (2015). Determination of methods used by the neonatal care unit nurses for management of procedural pain in Turkey. Journal of Pakistan Medical Association,65(5). Retrieved from http://jpma.org.pk/AboutUs/php

Marlow, N. (2013). Anesthesia and long-term outcomes after neonatal intensive care. Pediatric Anesthesia,24(1), 60-67. doi:10.1111/pan.12304

Mehrnoush, N., Ashktorab, T., Heidarzadeh, M., Momenzadeh, S., & Khalafi, J. (2016). Pain management perceptions of the neonatal nurses in NICUs and neonatal units in Ardebil, Iran. Iranian Journal of Neonatology,7(4), 23-29. doi:10.22038/ijn.2016.7854

Mehrnoush, N., Ashktorab, T., Heidarzadeh, M., Momenzadeh, S., & Khalafi, J. (2017a). Factors influencing neonatal pain management from the perspectives of nurses and physicians in a neonatal intensive care unit: A qualitative study. Iranian Journal of Pediatrics,28(1). doi:10.5812/ijp.10015

Mehrnoush, N., Ashktorab, T., Heidarzadeh, M., & Momenzadeh, S. (2017b). Knowledge and Attitude of Personnel, Key Factors in Implementation of Neonatal Pain Management in NICU: A Qualitative Study. Journal Of Clinical And Diagnostic Research,11(11), 5-9. doi:10.7860/jcdr/2017/26290.10851

Rana, D., Bellflower, B., Sahni, J., Kaplan, A. J., Owens, N. T., Arrindell, E. L., . . . Dhanireddy, R. (2017). Reduced narcotic and sedative utilization in a NICU after implementation of pain management guidelines. Journal of Perinatology,37(9), 1038-1042. doi:10.1038/jp.2017.88

Zwimpfer, L., & Elder, D. (2012). Talking to and being with babies: The nurse-infant relationship as a pain management tool. Neonatal, Paediatric & Child Health Nursing,15(3), 10-14. Retrieved October 2, 2018, from http://www.cambridgemedia.com.au