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Vol. 98, No. 3, 2010
Issue release date: September 2010

Effect of Indomethacin Infused over 30 Minutes on Cerebral Fractional Tissue Oxygen Extraction in Preterm Newborns with a Patent Ductus Arteriosus

Keating P. · Verhagen E. · van Hoften J. · ter Horst H. · Bos A.F.
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Background: A significant patent ductus arteriosus (PDA) is a common finding in the first days of life and, if persistent, is associated with an increased morbidity and mortality in the preterm newborn. Objectives: Our aim was to investigate, using near-infrared spectroscopy, the effect of indomethacin on the fractional tissue (cerebral) oxygen extraction (FTcOE) in a group of preterm newborns undergoing medical treatment for a PDA. Methods: This is a prospective, observational study. A cohort of 18 preterm newborns (<32 weeks) undergoing treatment for a PDA with indomethacin were monitored continuously for mean arterial blood pressure, arterial oxygen saturation (SpO2) and regional cerebral oxygen saturation (rcSO2). Measurements were started 1 h before and continued for 4 h after the first indomethacin dose. A final measurement (1 h) was made within 24 h of completing the full course. FTcOE = [SpO2 – rcSO2]/SpO2 was then calculated. To analyze the data, we chose to average the measurements over 1-hour periods. Results: There was a significant increase in the FTcOE (0.06, 95% CI 0.04–0.09, p < 0.001) noticeable within the 1st hour after the start of indomethacin administration, which peaked in the 2nd hour (FTcOE increased by 0.08, 95% CI 0.04–0.11, p < 0.001) and lasted for the full 4-hour period measured. Conclusion: Indomethacin, infused over 30 min, significantly increased the FTcOE in the preterm newborn, the effect lasting at least 4 h. This may represent a protective response to the indomethacin-induced reduction in cerebral blood flow demonstrated by others and warrants further investigation.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Behrman R, Martin C, Snider AR, Katz S, Peabody J, Brady J: Abnormal cerebral blood flow patterns in preterm infants with a large patent ductus arteriosus. J Pediatr 1982;101:587–593.
  2. Ichihashi K, Shiraishi H, Endou H, Kuramatsu T, Yano S, Yanagisawa M: Cerebral and abdominal arterial hemodynamics in preterm infants with patent ductus arteriosus. Acta Paediatr Jpn 1990;32:349–356.
  3. Perlman J, Hill A, Volpe J: The effect of patent ductus arteriosus on flow velocity in the anterior cerebral arteries: ductal steal in the premature newborn infant. J Pediatr 1981;99:767–771.
  4. Van Bel FV, Van Zoeren DV, Schipper J, Gult GL, Baan J: Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants. J Pediatr 1990;116:965–970.
  5. Christmann V, Liem KD, Semmekrot BA, Bor M: Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin. Acta Paediatr 2002;91:440–446.
  6. Colditz P, Murphy D, Rolfe P, Wilkinson AR: Effect of infusion rate of indomethacin on cerebrovascular responses in preterm neonates. Arch Dis Childhood 1989;64:8–12.
  7. Lemmers P, Toet M, van Schelven L, Van Bel F: Cerebral oxygenation and cerebral oxygen extraction in the preterm infant: the impact of respiratory distress syndrome. Exp Brain Res 2006;173:458–467.
  8. Naulaers G, Meyns B, Devlieger H: Use of tissue oxygenation index and fractional tissue oxygen extraction as non-invasive parameters for cerebral oxygenation. Neonatology 2007;92:120–126.
  9. Petrova A: Near-infrared spectroscopy in the detection of regional tissue oxygenation during hypoxic events in preterm infants undergoing critical care. Pediatr Crit Care Med 2006;449.
  10. Brazy J, Lewis D, Mitnick M, vander Vliet F: Noninvasive monitoring of cerebral oxygenation in preterm infants: preliminary observations. Pediatrics 1985;75:217–225.
  11. Wray S, Cope M, Delpy D, Wyatt J, Reynolds EO: Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation. Biochim Biophys Acta 1988;933:184–192.
  12. Naulaers G, Meyns B, Devlieger H: Use of tissue oxygenation index and fractional tissue oxygen extraction as non-invasive parameters for cerebral oxygenation. Neonatology 2007;92:120–126.
  13. Pryds O, Greisen G, Johansen KH: Indomethacin and cerebral blood flow in premature infants treated for patent ductus arteriosus. Eur J Pediatr 1988;147:315–316.
  14. Liem KD, Hopman JCW, Kollee LAA, Oeseburg B: Effects of repeated indomethacin administration on cerebral oxygenation and haemodynamics in preterm infants: combined near infrared spectrophotometry and Doppler ultrasound study. Eur J Pediatr 1994;153:504–509.
  15. Edwards AD, Wyatt JS, Richardson C, Potter A, Reynolds EOR, Cope M, et al: Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet 1990;335:1491–1495.
  16. Sangem M, Asthana S, Amin S: Multiple courses of indomethacin and neonatal outcomes in premature infants. Pediatr Cardiol 2008;29:878–884.
  17. Lemmers PMA, Toet MC, van Bel F: Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants. Pediatrics 2008;121:142–147.
  18. Hammerman C, Aramburo MJ: Prolonged indomethacin therapy for the prevention of recurrences of patent ductus arteriosus. J Pediatr 1990;117:771–776.

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