REVIEW ARTICLE © 2011 SNL All rights reserved

Management of in the neonatal unit: options, challenges and controversies

Awareness of the importance of pain in newborn babies has increased during recent years, but it remains a challenging area of clinical practice. This article reviews current knowledge, addresses some of the challenges and controversies surrounding neonatal pain and suggests an approach to in the neonatal intensive care unit.

Elaine M Boyle ain is unavoidable in modern neonatal their pain. The experience of pain is MBChB, MD, MSc Pintensive care. Advances in obstetric subjective and in adults and older children, Department of Health Sciences, and early neonatal care have led to the we rely on self-report to allow us to University of Leicester survival of increasing numbers of sick and identify and quantify pain and to monitor [email protected] preterm of gestational age as low as the effectiveness of pain-relieving 23 weeks. For these tiny patients, life- interventions. Since this is impossible in saving therapy means that a wide range of babies, we will never know precisely how stresses associated with diagnostic, the newborn baby perceives painful therapeutic and nursing interventions are conditions or invasive interventions. all part of day-to-day life. There is no However, it is reasonable to suppose that doubt that our knowledge and expertise in experiences reported as painful or managing these babies has grown, but how distressing by articulate adults, would be have we progressed in the management of similarly perceived by a preverbal . pain that they experience on a daily basis? We have turned therefore to interpretation It is only a few years since it was of infant behaviour to assist us in detecting common practice to give no analgesia to their pain. However, the behavioural newborn babies, as they were thought to be repertoire of the neonate is very limited developmentally too immature to process and there is no single response or information about painful stimuli. We have behaviour that we can attribute, with come a long way since then and today it is certainty, to the presence of pain. The widely, if not universally, accepted that situation becomes even more complex if even very preterm neonates are sufficiently we attempt to distinguish between developed, anatomically and different types of pain and quantify the Keywords physiologically, both to perceive and to severity. Finally, we still have much to respond to pain1. However, results of a newborn; premature; pain; analgesia; learn about infants’ responses to pain and recent Canadian survey comparing practice sedation; pain assessment about the risks and benefits of different today with that of 12 years ago suggested methods of pain relief and how they are Key points that, although attention to pain has affected by gestation, postnatal age and Boyle E.M. Management of pain in the improved, the management of procedural severity of illness. neonatal unit: options, challenges and pain in most centres, continues to fall short 2 controversies. Infant 2011; 7(3): 88-91. of current recommendations . In all The effects of neonatal pain 1. Pain management is a crucial part of branches of medicine and nursing we From a purely humanitarian perspective, neonatal intensive care. strive to keep patients comfortable and treating pain in newborn babies is a 2. Assessment of chronic pain in babies is pain free, and so perhaps we should ask desirable aspiration, but appropriate pain particularly challenging. ourselves why it is so difficult for us to get management is important for a number of 3. A range of pharmacological and non- this right in the smallest and most reasons other than the avoidance of pharmocological pain-relieving vulnerable of our patients. distress and suffering. Many researchers measures is available for use in babies. have now described long-term adverse 4. The aim of pain management should be Why are babies so challenging? effects following prolonged or repeated to achieve maximum comfort for Pain management in the newborn is exposure to pain in the neonatal period. babies, while minimising adverse complicated for a number of reasons, not Studies in both animals and humans have effects of treatment. least of which is their inability to describe shown altered behavioural responses to

88 VOLUME 7 ISSUE 3 2011 infant REVIEW ARTICLE pain and these may persist through the COMFORTneo17 are the only ones in milk, holding, comforting and suckling. childhood and perhaps longer3-8. existence and none is widely used. One randomised placebo-controlled trial Interestingly, there appears to be a There are, however, inherent difficulties found that breast milk significantly difference between term and preterm in using pain scores. Physiological decreased pain responses and crying time infants in their later responses following indicators such as increase in heart rate or associated with venepuncture in term painful experiences in the neonatal period. lack specificity for pain and neonates22. Animal studies have suggested Studies have shown that term-born infants may often occur as a result of other that effects of milk may be who had circumcision without analgesia, conditions; different methods of securing mediated and related to the sugar content23. and infants exposed to multiple heel pricks endotracheal tubes may distort or obscure For mothers who feel able to be present for measurement of blood sugar levels had facial features, limiting their use in when their baby is having a painful exaggerated behavioural responses to later ventilated babies. In addition, it is difficult procedure these may be appropriate, immunisation7-8. In contrast, preterm to differentiate between pain and agitation simple and safe options for pain relief. infants who experienced neonatal intensive and the effects of analgesia versus However, parents are not always present to care were reported by their parents to be sedation, especially in critically ill infants comfort or feed babies during invasive less sensitive to pain than their peers6. in whom severity of illness may further interventions and, understandably, many These effects are likely to be as a result of complicate assessment. prefer to avoid watching painful stressful procedures occurring during a Research to identify novel methods of procedures. Other behavioural measures critical period of anatomical and detecting and quantifying chronic pain in that can be administered by staff caring for physiological development of the neonates is ongoing. Investigators continue babies have therefore been studied. and nervous system9. to build on the knowledge of behavioural The simplest interventions that have responses14,18. It is likely that, in coming been shown to promote physiological Assessment of pain years, the use of non-invasive techniques, stability during painful procedures are Most research in neonatal pain assessment such as near infrared spectroscopy, may handling techniques such as containment, has centred mainly on acute pain. There provide greater insight into more specific and facilitated tucking24. Non- are now more than 40 clinical tools pain indicators19. nutritive sucking on a dummy/pacifier, available to allow assessment of the either alone or in combination with presence and severity of pain associated Management of pain sucrose, has also been the subject of with invasive procedures10. Most use a Of course, prevention is better than cure research and has been shown to reduce scoring system; some are used clinically at and it is clear that we must avoid non- pain responses25. Concerns have been the cot side while others are more essential painful procedures. Limiting raised about the possibility of non- frequently used in research studies. invasive interventions to the absolute nutritive sucking adversely affecting the Behavioral indicators and in particular, minimum required for the safe medical establishment of in preterm facial expressions, appear to be the most management of the baby is central to good babies. A recent study found no evidence specific indicators of pain and have been clinical practice. Nevertheless, there are to support withholding dummies/pacifiers included in most tools11,12. Some have frequent occasions when invasive on these grounds26. combined these with physiological procedures are clinically indicated even indicators such as heart rate and though they may be potentially distressing Pharmacological measures saturation to develop multidimensional for the infant. The choice of procedure or Sucrose scores13. methods used may be important. For Sucrose has been extensively studied27. For In contrast, there are relatively few example, venepuncture appears to be less many years sweet solutions have been validated tools designed for measurement painful than heel prick and heel prick known to have a calming effect in crying of the ongoing or ‘chronic’ pain that might using a spring-loaded mechanical device is babies. The mechanism of action of be experienced during prolonged less painful than using a manual lancet20. sucrose has not been fully defined, but it mechanical ventilation or inflammatory A number of non-pharmacological may be mediated by the activation of conditions such as necrotising entero- measures have been studied, as well endogenous ; sweet taste appears to colitis. It may be that responses to this sort as drug therapies, and all may be useful be important. A Cochrane Review of pain are different from those to acute in managing pain. These are summarised concluded that intraoral sucrose reduces pain or indeed that responses may change below. procedural pain in neonates28. It has been with the duration and progression of pain, shown to decrease the duration of crying but they have been much less studied. The Behavioural and environmental and reduce behavioural responses in babies lack of such tools probably reflects our (non-pharmacological) measures having heel prick or venepuncture and, for poor understanding of these responses to Skin-to-skin contact between mothers and these procedures, is more effective than the chronic pain and the difficulties associated babies () has been shown to use of topical local anaesthetic creams29. A with observation and interpretation of an be effective in reducing pain responses wide range of volumes and concentrations infant’s condition over a prolonged period associated with heel prick. Breastfeeding has been investigated and the optimal dose of time rather than in relation to a short- during a painful procedure has also been has not yet been determined; doses lived painful intervention14. To date, the reported to have analgesic effects21. It is between 0.012g-0.12g were effective28. The EDIN (Echelle Douleur Inconfort difficult to be sure how much is analgesic effect of sucrose appears to peak Nouveau-Né)15, the N-PASS (Neonatal contributed by each of the individual at around two minutes after admini- Pain, Agitation and Sedation Scale)16, and components involved in breastfeeding – stration into the mouth and last for several infant VOLUME 7 ISSUE 3 2011 89 REVIEW ARTICLE minutes. Most work has been done in J Pediatr 2007;150:151-56. 5. Grunau R.E., Whitfield M.F., Petrie J. Children's infants of more than 27 weeks’ gestation. Paracetamol is commonly used in term No adverse effects have been reported with judgements about pain at age 8-10 years: do babies thought to have acute pain extremely low birthweight (< or = 1000g) children administration of single doses of sucrose. following an invasive procedure or differ from full birthweight peers? J Child Psychol Studies of the long-term effects are very traumatic delivery. Until recently, it has Psychiatry 1998;39:587-94. few, and only one has studied been used less frequently in preterm 6. Grunau R.V., Whitfield M.F., Petrie J.H. Pain 30 sensitivity and temperament in extremely low- neurodevelopmental outcomes . This infants in the UK. An intravenous study showed worse motor development birth-weight premature toddlers and preterm and preparation is available that is suitable for full-term controls. Pain 1994;58:341-46. and attention at 36-40 weeks of gestation intermittent administration in ventilated 7. Taddio A., Katz J., Ilersich A.L., Koren G. Effect of in babies born at <31 weeks of gestation neonates. However, its safety and efficacy neonatal circumcision on pain response during who had repeated sucrose doses. Potential have not been fully evaluated in the subsequent routine vaccination. Lancet 1997;349:599-603. mechanisms for effects of sucrose on preterm population40 and pharmacokinetic development have been suggested31 and 8. Taddio A., Shah V., Gilbert-MacLeod C., Katz J. studies are ongoing. Conditioning and in newborns expo- further work is needed to assess the long- sed to repeated heel lances. JAMA 2002;288:857-61. term effects of sucrose therapy. Conclusion 9. Loizzo A., Loizzo S., Capasso A. Neurobiology of pain A recent study by Slater et al measured It is now widely accepted that pain relief is in children: an overview. Open Biochem J 2009;3: 18-25. brain and activity in babies a crucial part of the management of babies 10. Duhn L.J., Medves J.M. A systematic integrative given sucrose and showed that, although in the neonatal unit. There are a large sucrose reduced observed pain behaviour review of infant pain assessment tools. Adv number of different measures for pain Neonatal Care 2004;4:126-40. in these babies, it did not have any control available, ranging from simple 11. Grunau R.V., Craig K.D. Pain expression in neonates: significant effect on spinal pain or holding techniques to potent analgesic facial action and cry. Pain 1987;28:395-410. activation of pain networks in the brain32. 12. Craig K.D., Whitfield M.F., Grunau R.V. et al. Pain in medications. In all decision-making it is This led the authors to question whether the preterm neonate: behavioural and physiological important to ensure that the chosen sucrose is, in fact, an effective analgesic or indices. Pain 1993;52:287-99. treatment or preventive measure is 13. Stevens B., Johnston C., Taddio A. et al. The whether its only effect lies in the blunting appropriate for the type of procedure and premature infant pain profile: evaluation 13 years of behavioural responses. degree of discomfort likely to be after development. Clin J Pain 2010;26:813-30. Although these studies raise questions 14. Boyle E.M., Freer Y., Wong C.M. et al. Assessment of experienced. It is always preferable to start about both the efficacy and safety of persistent pain or distress and adequacy of with simple measures first and, in some sucrose, the evidence is insufficient to analgesia in preterm ventilated infants. Pain cases, drug therapy can be avoided 2006;124:87-91. inform practice and therefore sucrose altogether. Should medication be required, 15. Debillon T., Zupan V., Ravault N. et al. Development currently remains one of the treatments the safest strategy, as with any drug, is to and initial validation of the EDIN scale, a new tool of choice for the pain of minor invasive use the minimum dose that is effective in for assessing prolonged pain in preterm infants. procedures. Arch Dis Child Fetal Neonatal Ed 2001;85:F36-41. achieving the desired response. There are 16. Hummel P., Puchalski M., Creech S.D., Weiss M.G. Opioid analgesia risks and benefits to all therapies and these Clinical reliability and validity of the N-PASS: Opioids are the most extensively studied must be fully considered, with the aim of neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol 2008;28:55-60. pharmacological analgesic agents used in maximising comfort while minimising adverse effects. 17. van Dijk M., Roofthooft D.W., Anand K.J. et al. neonatal intensive care and is Taking up the challenge of measuring prolonged probably the most commonly used. It is a Achieving optimum pain management pain in (premature) neonates: the COMFORTneo potent analgesic, suitable for severe or in neonatal intensive care is challenging, scale seems promising. Clin J Pain 2009;25:607-16. prolonged pain and also has sedative particularly with respect to chronic pain, 18. Holsti L., Grunau R.E. Initial validation of the Behavioral Indicators of Infant Pain (BIIP). Pain properties, which can be desirable in some which is extremely difficult to assess and quantify. Our knowledge remains limited 2007;132:264-72. babies. also carry with them 19. Bartocci M., Bergqvist L.L., Lagercrantz H., Anand undesirable effects such as hypotension33,34, and further work is needed to explore K.J. Pain activates cortical areas in the preterm decreased gut motility35 and increased infant responses to pain further, to newborn brain. Pain 2006;122:109-17. duration of ventilation36. The effects of maximise efficacy and safety of treatment, 20. McIntosh N., van Veen L., Brameyer H. Alleviation of morphine on acute procedural pain in and to optimise short- and long-term the pain of heel prick in preterm infants. Arch Dis outcomes for babies. Child Fetal Neonatal Ed 1994;70:F177-81. preterm ventilated neonates have been 21. Gray L., Miller L.W., Philipp B.L., Blass E.M. studied and morphine does not appear to References Breastfeeding is analgesic in healthy newborns. provide adequate analgesia37. Routine pre- 2002;109:590-93. emptive use of continuous analgesia 1. Anand K.J., Hickey P.R. Pain and its effects in the 22. Upadhyay A., Aggarwal R., Narayan S. et al. human neonate and . N Engl J Med in sick, ventilated preterm neonates is not Analgesic effect of expressed breast milk in 1987;317:1321-29. procedural pain in term neonates: a randomized, 38 recommended . Opiate withdrawal is well 2. Johnston C., Barrington K.J., Taddio A. et al. Pain in placebo-controlled, double-blind trial. Acta Paediatr recognised in older children and adults and Canadian NICUs: have we improved over the past 2004;93:518-22. in infants exposed to drugs in utero. 12 years? Clin J Pain 2011;27:225-32. 23. Blass E.M., Fitzgerald E. Milk-induced analgesia and Withdrawal following therapeutic doses of 3. Anand K.J., Coskun V., Thrivikraman K.V. et al. Long- comforting in 10-day-old rats: opioid mediation. opiates has been little studied in neonates, term behavioral effects of repetitive pain in Pharmacol Biochem Behav 1988;29:9-13. neonatal rat pups. Physiol Behav 1999;66:627-37. 24. Cignacco E., Axelin A., Stoffel L. et al. Facilitated but signs consistent with withdrawal have 4. Grunau R.E., Haley D.W., Whitfield M.F. et al. tucking as a non-pharmacological intervention for been observed in babies after a relatively Altered basal cortisol levels at 3, 6, 8 and 18 months neonatal pain relief: Is it clinically feasible? Acta short duration of treatment39. in infants born at extremely low gestational age. Paediatrica 2010;Jul 6 (Epub ahead of print).

90 VOLUME 7 ISSUE 3 2011 infant REVIEW ARTICLE

25. Field T., Goldson E. Pacifying effects of nonnutritive neonates younger than 31 weeks’ postconceptional in preterm infants: secondary results from the sucking on term and preterm neonates during age. Pediatrics. 2002;110:523-28. NEOPAIN trial. Arch Dis Child Fetal Neonatal Ed heelstick procedures. Pediatrics 1984;74:1012-15. 31. Holsti L., Grunau R.E. Considerations for using 2008;93:F362-67. 26. Collins C.T., Ryan P., Crowther C.A. et al. Effect of sucrose to reduce procedural pain in preterm 36. Bhandari V., Bergqvist L.L., Kronsberg S.S. et al. bottles, cups, and dummies on breast feeding in infants. Pediatrics. 2010;125:1042-47. Morphine administration and short-term preterm infants: a randomised controlled trial. 32. Slater R., Cornelissen L., Fabrizi L. et al. Oral sucrose pulmonary outcomes among ventilated preterm BMJ 2004;329:193-98. as an analgesic drug for procedural pain in newborn infants. Pediatrics 2005;116:352-59. 27. Harrison D., Bueno M., Yamada J. et al. Analgesic infants: a randomised controlled trial. Lancet 37. Carbajal R., Lenclen R., Jugie M. et al. Morphine effects of sweet-tasting solutions for infants: 2010;376:1225-32. does not provide adequate analgesia for acute current state of equipoise. Pediatrics 2010;126: 33. Anand K.J.S., Hall R.W., Desai N. et al for the procedural pain among preterm neonates. 894-902. NEOPAIN Investigators Group. Effects of morphine Pediatrics. 2005;115:1494-500. 28. Stevens B., Yamada J., Ohlsson A. Sucrose for analgesia in ventilated preterm neonates: primary 38. Bellu R., de Waal K.A., Zanini R. Opioids for analgesia in newborn infants undergoing painful outcomes from the NEOPAIN randomised trial. neonates receiving mechanical ventilation. procedures. Cochrane Database Syst Rev 2010(1): Lancet 2004;363:1673-82. Cochrane Database Syst Rev 2008(1):CD004212. CD001069. 34. Hall R.W., Kronsberg S.S., Barton B.A. et al. 39. Arnold J.H., Truog R.D., Orav E.J. et al. Tolerance and 29. Gradin M., Eriksson M., Holmqvist G. et al. Pain Morphine, hypotension and adverse outcomes dependence in neonates sedated with reduction at venipuncture in newborns: oral among preterm neonates: who’s to blame? during extracorporeal membrane oxygenation. glucose compared with local anesthetic cream. Secondary results from the NEOPAIN trial. Pediatrics Anesthesiology 1990;73:1136-40. Pediatrics 2002;110:1053-57. 2005;115:1351-59. 40. Palmer G.M., Atkins M., Anderson B.J. et al. IV 30. Johnston C.C., Filion F., Snider L. et al. Routine 35. Menon G., Boyle E.M., Bergqvist L.L. et al. acetaminophen pharmacokinetics in neonates after sucrose analgesia during the first week of life in Morphine analgesia and gastrointestinal morbidity multiple doses. Br J Anaesth 2008;101:523-30.

19th Annual International Neonatal Conference and Ventilatory Workshop

2, 3 and 4 June 2011 University of Durham, Queenʼs Campus, South Tees Hospitals Ebsworth Building, Stockton NHS Foundation Trust

Pre-conference “Advanced Ventilatory Workshop” – 2 June 2011 Annual Neonatal Conference – 3 and 4 June 2011

Topics include: Improving Neonatal Resuscitation • Newer Developments in Respiratory Care of the Newborn Understanding Neonatal Haemodynamics • Advances in Neonatal Neurology Preventing Necrotising Enterocolitis and the Use of Probiotics Preterm Nutrition: Knowns and Unknowns Neonatal Sepsis • Gastro Oesophageal Reflux in Newborns Neonatal Outcomes: Trends and Newer Developments

Registration and fees: Advanced Ventilatory Workshop £250 (1 day). Annual Neonatal Conference £325 – 2 days, £165 – 1 day. Combined Ventilatory Workshop and Conference £495 (3 days)

For an application form, please contact Conferences and Courses Department, Academic Centre, The James Cook University Hospital, Marton Road, Middlesbrough, TS4 3BW Telephone 01642 282534, Fax 01642 282535, Email [email protected] OR APPLY ONLINE – WWW.NEONATALCONFERENCE.CO.UK

infant VOLUME 7 ISSUE 3 2011 91