1. Non-steroidal anti-inflammatory drugs and neonatal analgesia:

    Dear editor,

    As clearly mentioned in the review of Anand and Hall in this journal, rapid advances have been made in the use of pharmacological analgesia and sedation due to improved knowledge on pharmacokinetics and –dynamics of various analgesics in neonates (1). Based on meta-analysis on the effectiveness of multimodal analgesia in postoperative non-neonatal patients, it is to be anticipated that non- selective cyclo-oxygenase (NS-COX) inhibitors might also be effective in the alleviation of pain in neonates (2). However, any administration of a given drug should be a balanced decision based on the potential (dis)advantages. We therefore would like to mention some recently reported observations on the impact of various NS-COX inhibitors based on data in part collected during the Multicenter Ibuproben Prophylaxis study, a randomized, placebo-controlled trial on the effects of ibuprofen administration on the incidence of intraventricular hemorrhage in extreme preterm neonates. Based on observations collected in the Leuven cohort of this MIPS trial, we documented a significant decrease in amikacin clearance (- 18 to 21 %) when ibuprofen was co-administered. This decrease was of similar magnitude when the impact was evaluated in preterm neonates up to 34 weeks and there was no additional difference in reduction of amikacin clearance when the impact of ibuprofen was compared with a historical cohort of preterm neonates treated with acetylsalicylic acid (3,4). Since aminoglycoside clearance reflects glomerular filtration rate, these data suggest that the administration of either ibuprofen or acetylsalicylic acid has an important impact on GFR, independent of the gestational age (3,4). It is to be anticipated that the impact of indomethacin will at least be of similar magnitude (5). The differences in impact of various NS -COX on regional perfusion - both renal and cerebral - can be further evaluated by integrating these additional, secondary outcome variables in the initial protocols of such multi-center RCT studies (3,4,6).

    In the meanwhile, based on the above mentioned observations, we fully agree with the authors that the use of NS-COX to treat pain in neonates is indeed limited based on the presently available knowledge.


    1.Anand K, et al. Pharmacological therapy for analgesia and sedation in the newborn. Arch Dis Child Fetal Neonatal Ed 2006;91;448-53.

    2.McQuay HJ, et al. Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. Health Technol Assess 1998;2:1-236.

    3.Allegaert K, et al. Limited predictability of amikacin clearance in extreme premature neonates at birth. Br J Clin Pharmacol 2006;61:39-48.

    4.Allegaert K, et al. The impact of ibuprofen on renal clearance in preterm infants is independent of the gestational age. Pediatr Nephrol 2005;20:740-3

    5.Fowlie P, et al. Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2003;88:F464-6.

    6.Naulaers G, et al. Ibuprofen and cerebral oxygenation and circulation. Arch Dis Child Fetal Neonatal Ed 2005;90:F75-6.

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