1. McPherson, Christopher PharmD
  2. Smith, Joan R. PhD, RN, NNP-BC

Article Content

Three decades ago, neonatal pain research culminated in a landmark publications that brought clarity to the role of analgesia in premature neonates.1 Neonates, even those at the lowest limits of viability, have profound acute adverse reactions to painful stimuli from major surgery. Provision of analgesia prior to surgery dramatically diminishes these reactions and improves the outcomes of treated neonates.1 On this basis, administration of analgesia prior to major surgery has been a standard of care in neonatology. More recently, extensive evidence has emerged documenting the negative impacts of neonatal pain on neurodevelopment later in life.2


The most common analgesics utilized in neonates, opioids such as morphine and fentanyl, are both effective and imperfect. These drugs have well-described adverse effects, including respiratory depression and reduction in gastrointestinal motility. Respiratory depression prolongs the duration of invasive mechanical ventilation, driving the pathophysiology of bronchopulmonary dysplasia. Reduction in gastrointestinal motility prolongs the time required to achieve full enteral feedings, limiting exposure to the benefits of breast milk and prolonging the infection risks associated with intravenous catheters. Emerging evidence suggests that prolonged opioid exposure may also adversely impact the developing brain. Notably, randomized trials and observational studies suggest that lower doses are likely safer than higher doses.3,4


Balancing the short- and long-term impacts of neonatal pain and the agents utilized to control it represents one of the greatest challenges happening in neonatal intensive care units (NICUs). In the setting of major surgery, the risk-benefit calculation is simple. Major surgery in the absence of analgesia results in significant harm to the neonate, including increased ventilator settings and risk for intraventricular hemorrhage. The potential adverse effects, if any, of a single, high-dose analgesic exposure in this setting pale in comparison. The risk-benefit calculation is similarly straightforward for minor procedural pain, such as during venipuncture. Although the cumulative effects of repetitive minor pain are meaningful, high-dose or continuous infusion opioids are not indicated; oral sucrose and nonpharmacologic comfort measures (eg, facilitated tuck or skin-to-skin contact) represent the standard of care.5


Uncertainty exists between these extremes of acute and chronic pain. For example, premature neonates frequently require invasive mechanical ventilation. Although evaluation of pain and agitation in this population is challenging, the balance of data suggests that invasive ventilation is unpleasant. Regrettably, randomized controlled trials of morphine in this setting have produced negative short-term results (prolonged mechanical ventilation and time to full enteral feedings, as described earlier) and an unclear impact on long-term neurodevelopment.4 Consequently, guidelines caution against routine use of opioids for this indication.5 No guidance is provided to inform management of a premature neonate exhibiting nonspecific signs of stress or pain during invasive mechanical ventilation. Widespread variation in recent surveys highlights a persistent lack of clarity.


This uncertainty may be due, in part, to the lack of a single universal pain assessment tool to address the complex needs of all neonates-requiring neonatal teams to be trained and knowledgeable in a variety of pain assessment tools, including those validated in special populations (eg, extremely low birth weight, neurologically impaired, pharmacologically paralyzed).6 Pain can only be managed accurately if it is assessed accurately, and accurate assessment requires effective interdisciplinary teamwork and communication. Unfortunately, the lack of a single universal pain assessment tool and ambiguity in pain management guidance may result in conflict between the interdisciplinary healthcare team. For instance, bedside nurses intimately attuned to the suffering of their fragile patients often want immediate relief for their patients and may advocate for opioids, regardless of the evidence suggesting long-term adverse effects. Physicians, nurse practitioners (NPs), and pharmacists with advanced pharmacology training and potentially more frequent exposure to the literature suggesting adverse effects from these agents may become opioid opponents. In reality, neither polarity is optimal. Opioids benefit patients in pain while producing undesirable adverse effects. Both compassion for our fragile patients and knowledge of the potential risks of opioids are vital. Therefore, an empathetic caregiver constantly at the bedside with comprehensive knowledge of medical and pharmacologic literature should make decisions about initiation and titration of opioids in this population. Given the obvious challenges of mass producing the perfect arbiter of this debate (the parent, RN, NP, MD, PharmD, therapist with decades of neonatal experience), an interdisciplinary team approach using a shared mental model framework is essential to accurately assess and manage neonatal pain.


How can an interdisciplinary team with different perspectives navigate this emotional landmine of conflicting priorities and data? While characteristics of effective teamwork have been reported in the healthcare literature,7 interdisciplinary NICU teams can also learn from high-performing teams outside healthcare-including Google. Recently, Google's People Operations team examined more than 250 attributes of nearly 200 active interdisciplinary Google teams.8 The most successful teams consistently demonstrated 5 key attributes: psychological safety, dependability, structure and clarity, work with meaning for the individual, and work with impact (see Table 1). There is no argument that healthcare professionals in the NICU are dependable individuals with structured, meaningful work that has tremendous impact. Psychological safety can be more challenging, requiring team members to feel safe as they share their perspective. It is incumbent on all NICU providers to examine their current environment and ask the question: "Are all perspectives encouraged and valued in our culture?" This true interdisciplinary approach improves outcomes in other challenging areas of healthcare and is currently our greatest hope for negotiating this clinical conundrum.9 Our patients deserve nothing less.

Table 1 - Click to enlarge in new windowTable 1. Key attributes of a successful interdisciplinary team applied to pain management

-Christopher McPherson, PharmD


Clinical Pharmacist


Neonatal ICU


St Louis Children's Hospital


St Louis, Missouri


Assistant Professor


Department of Pediatrics


Washington University School of Medicine


St Louis, Missouri


-Joan R. Smith, PhD, RN, NNP-BC




Clinical Quality, Safety & Practice Excellence


St Louis Children's Hospital, Missouri




1. Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet. 1987;1:62-66. [Context Link]


2. Valeri BO, Holsti L, Linhares MB. Neonatal pain and developmental outcomes in children born preterm: a systematic review. Clin J Pain. 2015;31:355-362. [Context Link]


3. Steinhorn R, McPherson C, Anderson PJ, Neil J, Doyle LW, Inder T. Neonatal morphine exposure in very preterm infants-cerebral development and outcomes. J Pediatr. 2015;166:1200-1207.e1204. [Context Link]


4. McPherson C, Grunau RE. Neonatal pain control and neurologic effects of anesthetics and sedatives in preterm infants. Clin Perinatol. 2014;41:209-227. [Context Link]


5. American Academy of Pediatrics Committee on Fetus and Newborn, American Academy of Pediatrics Section on Surgery, Canadian Paediatric Society Fetus and Newborn Committee, Batton DG, Barrington KJ, Wallman C. Prevention and management of pain in the neonate: an update. Pediatrics. 2006;118:2231-2241. [Context Link]


6. Maxwell LG, Malavolta CP, Fraga MV. Assessment of pain in the neonate. Clin Perinatol. 2013;40:457-469. [Context Link]


7. O'Leary KJ, Sehgal NL, Terrell G, Williams MV. High Performance Teams, the Hospital of the Future Project Team. Interdisciplinary teamwork in hospitals: a review and practical recommendations for improvement. J Hosp Med. 2012;7:48-54. [Context Link]


8. Duhigg C. What Google learned from its quest to build the perfect team. The New York Times Magazine. February 25, 2016. https:// Accessed January 22, 2017. [Context Link]


9. Wheelan SA, Burchill CN, Tilin F. The link between teamwork and patients' outcomes in intensive care units. Am J Crit Care. 2003;12:527-534. [Context Link]