Procedural and postoperative pain-reducing methods in newborns

Abstract: The neonate has a functioning nociceptive system. However, neonates are probably more vulnerable than the older infants and adults to the negative effects of pain. Untreated pain and stress stimuli may have long-term effects. It is, therefore, very important to find ways to reduce pain and painful stimuli in neonates. This thesis aims at improving management of neonatal pain in clinical practice. More specifically, evaluating the effects of various sampling methods and the use of topical anaesthesia during blood tests in neonates and determining the pharmacokinetics of an epidural infusion of bupivacaine for postoperative pain relief. Most neonates undergo screening for inborn errors of metabolism. Heel-lancing has hitherto been the method of choice for this test. This is a painful method. In adults and children, EMLA cream has proved to be an effective topical local anaesthetic. In a placebo-controlled and randomised study, the effect of EMLA was assessed when heel-lancing was performed in neonates undergoing the PKU test. EMLA had no clinically significant analgesic effect. To investigate whether other methods, such as venepuncture on the dorsal aspect of the hand, could be an alternative to heel-lancing, a prospective, randomised and double blind study was performed. The results clearly showed that venepuncture is more effective and less painful than heel-lancing for single blood tests in neonates. To determine whether the pain from venepuncture could be reduced by the use of EMLA, a placebo-controlled, randomised and double-blind study was performed. The test substance was applied to the dorsal aspect of the hand for 60 minutes. It was found that in comparison with a placebo, EMLA significantly reduced the pain caused by venepuncture and did not complicate puncture of the vein. Differences in skin thickness and in skin perfusion influence the effects of EMLA in adults. The skin perfusion and skin thickness m healthy neonates were studied m three regions: the forehead, the dorsum of the hand and the heel. The skin perfusion of the heel was found to be significantly higher than that m the dorsum of the hand and the forehead. No significant difference in skin thickness was detected between these regions. A rapid clearance of EMLA, due to high cutaneous blood flow may explain why EMLA is not effective when applied to the heel of a neonate. In adults, epidural infusions of local anaesthetics have become a routine method for treatment of per- and postoperative pain. Hardly any data are available about this method in the newborn. In a pharmacokinetic study, young infants received a continuous infusion of bupivacaine epidurally for postoperative pain relief. The dose administered was found to be high, since three adverse events occurred. It can therefore not be recommended as safe in this age group. In a following study, a substantially lower dose was used. The results showed that, using the lower dose, an epidural infusion of bupivacaine provides safe postoperative pain treatment in neonates for at least 48 hours. This method can, therefore, be recommended also in newborns. In conclusion, EMLA does not alleviate the pain caused by heel-lancing in neonates. The lack of effect probably results from a rapid clearance of EMLA, due to a high cutaneous blood flow in the heel. Heel-lancing hurts. Other methods should be used for taking single blood samples in neonates. Venepuncture has proved to be a less painful and more effective method and is therefore recommended. The use of EMLA, applied to the hand, further reduces the pain caused by venepuncture. Thus, these studies have provided results that are easily applicable in clinical practice for the benefit of the neonate. An epidural infusion of bupivacaine (0.2 mg/kg/h, 1.25 mg/ml) provides safe treatment of postoperative pain in neonates for at least 48 hours. The dose used seemed to be effective. Future studies are, however, needed to document the efficacy of regional anaesthetic techniques in this age group. The safety and pharmacokinetics of more prolonged infusions (>48h) also needs to be further studied. However, these techniques deserve more widespread use also in the treatment of neonatal pain.