Management of chronic pain in newborn infants

Abstract

Until the 1980s, there was a belief in the medical community that a newborn infant was unable to feel pain. Therefore, infants were often not given analgesia for invasive procedures. Since then, a large body of research has shown that nociceptive neural pathways are, in fact, well-established and active in infants born preterm and at term who are exposed to multiple painful procedures in neonatal intensive care. Painful stimuli result in (neuro)behavioural, physiological, cardiorespiratory, and hormonal changes. Structural and functional changes in brain development have been demonstrated after early exposure to pain, with some studies suggesting that early pain affects neurodevelopment and response to pain later in life. Non-pharmacological methods, such as oral sucrose, breast milk, reduction of environmental stress, swaddling, and skin-to-skin care, have been shown to be beneficial for mild to moderate pain. Benzodiazepines, opioids, barbiturates, acetaminophen, non-steroidal anti-inflammatory drugs, or dexmedetomidine are commonly used (often in combination) for pain management in newborn infants, with limited evidence available. Gabapentin has become increasingly popular, particularly for neurological disorders, irritability, and when chronic pain is suspected; however, there is currently little evidence on the safety, efficacy, potential long-term effects on neurodevelopment, risk of dependency, and, overall, no consensus on the prescription for infants. The paper by Burnsed et al. describes a small, retrospective, single-centre study in infants born preterm and at term with congenital abnormalities (mainly cardiac), in whom gabapentin was used for agitation, irritability, and/or pain. These were assessed before treatment and monitored with the Neonatal Pain, Agitation and Sedation Scale (N-PASS). Eighty-one per cent of the infants had a neurological diagnosis, i.e. intraor periventricular haemorrhage, posthaemorrhagic hydrocephalus, or focal infarct. Over half of the infants had more than two comorbidities. Almost all participants were treated with other (up to three) neurosedative drugs; there was a large range of treatment dose and duration. In those who had at least 2 weeks of treatment, a reduction was seen in N-PASS scores and in the number of other neurosedative medications administered. This carefully conducted retrospective study and the recent survey of gabapentin use across North American neonatal intensive care units are two of the few clinical studies that focus on chronic pain and use a standardized tool for behavioural assessment. These studies highlight some important problems relating to existing clinical neonatal pain management research in general: use of confusing terminology – the terms ‘agitation’, ‘irritability’, and ‘pain’ are often used interchangeably – which makes it difficult to assess nociceptive stress accurately. There are almost always heterogeneous patient groups in these studies and, importantly, the stage of brain development at treatment is rarely considered, even though this may affect response to treatment and long-term outcome. Incidentally, very little research has been carried out in the specific subgroup of newborn infants who are at risk for neurological impairment. There is a lack of consensus on the use of standardized assessment tools for neonatal pain or agitation/irritability, lack of controlling for non-pharmacological treatment, loss to follow-up, and lack of long-term outcome information. Furthermore, most research has focussed on procedural pain and very few studies have examined chronic pain specifically. From a clinical perspective, it would be important for guidelines to be developed that cover accurate recognition of procedural and chronic pain that needs treatment, use of standardized pain assessments for careful treatment monitoring, and evidence-based treatment protocols that consider a stepwise approach, including pharmacological and non-pharmacological interventions. However, for this to be possible, well designed randomized controlled trials in homogenous groups of patients with long-term neurodevelopmental follow-up are urgently needed; which, of course, is easier said than done.