Journal Mobile Options
Table of Contents
Vol. 89, No. 2, 2006
Issue release date: February 2006
Biol Neonate 2006;89:69–74

Brain Hemodynamic Effects of Doxapram in Preterm Infants

Dani C. · Bertini G. · Pezzati M. · Pratesi S. · Filippi L. · Tronchin M. · Rubaltelli F.F.
Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence, Florence, Italy

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Doxapram is a respiratory stimulant widely used for the treatment of idiopathic apnea of prematurity, although it has been demonstrated that it can induce a transient decrease of cerebral blood flow and that isolated mental delay in infants weighing <1,250 g is associated with the total dosage and duration of doxapram therapy. Objectives: To evaluate the effects of doxapram on cerebral hemodynamics in preterm infants using cerebral Doppler ultrasonography and near-infrared spectroscopy. Methods: Preterm infants who required treatment with doxapram for apnea of prematurity unresponsive to caffeine were treated with doxapram at an hourly dose of 0.5 mg·kg–1·h–1, followed by 1.5 and 2.5 mg·kg–1·h–1. Results: 20 preterm infants were studied. Doxapram induced a significant decrease of oxygenated hemoglobin (O2Hb) and cerebral intravascular oxygenation (HbD = O2Hb – HHb) and an increase of HHb and CtOx concentrations, while cerebral blood volume and cerebral blood flow velocity did not change. Conclusions: Doxapram infusion induces the increase of cerebral oxygen consumption and requirement and the contemporary decrease of oxygen delivery probably mediated by a decrease of cerebral blood flow. Caution must be recommended in prescribing this drug for apnea of prematurity.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Schroeder H, Boyet S, Nehlig A: Effects of caffeine and doxapram perfusion on local cerebral glucose utilization in conscious rats. Eur J Pharmacol 1989;167:245–254.
  2. Hascoet JM, Hamon I, Boutroy MJ: Risks and benefits of therapies for apnea in premature infants. Drug Saf 2000;23:362–379.

    External Resources

  3. Eyal F, Alpan G, Sagi E, Glick B, Peleg O, Dgani Y: Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study. Pediatrics 1985;75:709–713.
  4. Barrington KJ, Finer NN, Petrs KL, Barton J: Physiologic effects of doxapram in idiopathic apnea of prematurity. J Pediatr 1986;108:125–129.
  5. Bairam A, Faulon M, Monin P, Vert P: Doxapram for the initial treatment of idiopathic apnea of prematurity. Biol Neonate 1992;61:209–213.
  6. Henderson-Smart DJ, Steer P: Doxapram versus methylxanthine for apnea in preterm infants. Cochrane Database Syst Rev 2000;4:CD000075.
  7. De Villiers GS, Walele A, Van der Merwe, Kalis NN: Second-degree atrioventricular heart block after doxapram administration. J Pediatr 1998;133:149–150.
  8. Maillard C, Boutroy MJ, Fresson J, Barbè F, Hascoet JM: QT interval lengthening in premature infants treated with doxapram. Clin Pharmacol Ther 2001;70:540–545.
  9. Tay-Uyboco J, Kwiatkowski K, Cates DB, Seifert B, Hasan SU, Rigatto H: Clinical and physiological responses to prolonged nasogastric administration of doxapram for apnea of prematurity. Biol Neonate 1991;59:190–200.
  10. Poets C, Darraj S, Bohnorst B: Effects of doxapram on episodes of apnea, bradycardia and hypoxaemia in preterm infants. Biol Neonate 1999;76:207–213.
  11. Miletich DJ, Ivankovich AD, Albrecht RF: The effects of doxapram on cerebral blood flow and peripheral hemodynamics in the anesthetized and unanesthetized goat. Anesth Analg 1976;55:279–285.
  12. Roll C, Horsch S: Effect of doxapram on cerebral blood flow velocity in preterm infants. Neuropediatrics 2004;35:126–129.
  13. Sreenan C, Etches PC, Demianczuk N, Robertson CMT: Isolated mental developmental delay in very low birth weight infants: association with prolonged doxapram therapy for apnea. J Pediatr 2001:139:832–837.
  14. Nehlig A: Effects of respiratory stimulants on cerebral metabolism and blood flow. Biol Neonate 1994;65:258–264.
  15. National Institutes of Health Consensus Development Panel on Infantile Apnea and Home Monitoring. Pediatrics 1987;79:292–299.
  16. Papile LA, Burstein J, Burstein R, Keffler H: Incidence and evolution of the subependymal intraventricular hemorrhage: a study of infants weighing less than 1,500 grams. J Pediatr 1978;92:529–534.
  17. Dani C, Bertini G, Reali MF, Tronchin M, Wiechmann L, Martelli E, Rubaltelli FF: Brain hemodynamic changes in preterm infants after maintenance dose caffeine and aminophylline treatment. Biol Neonate 2000;78:27–32.
  18. Wyatt JS, Cope M, Delpy DT: Measurement of optical path length for cerebral near-infrared spectroscopy in newborn infants. Dev Neurosci 1990;12:140–142.
  19. Tsuji M, duPlessis A, Taylor G, Crocker R, Volpe JJ: Near-infrared spectroscopy detects cerebral ischemia during hypotension in piglets. Pediatr Res 1998;44:591–595.
  20. Wyatt JS, Edwards AD, Cope M: Responses of cerebral blood volume to changes in arterial carbon dioxide tension in term and preterm infants. Pediatr Res 1991;30:570–573.

    External Resources

  21. Pourcelot L: Diagnostic ultrasound for cerebral vascular disease; in Donald I, Levi S (eds): Present and Future of Diagnostic Ultrasound. Rotterdam, Kooyker Scientific, 1976, pp 141–147.
  22. Barbè F, Hansen C, Badonnel Y, Legagneur H, Vert P, Boutroy MJ: High-performance liquid chromatography quantification of doxapram and metabolites and severe adverse effects in preterm infants. Ther Drug Monit 1999;21:547–552.
  23. Hirsh K, Wang SC: Selective respiratory stimulating action of doxapram compared to pentylenetetrazol. J Pharmacol Exp Ther 1974;189:1–11.
  24. Edwards AD, Browns GC, Cope M: Quantification of concentration changes in neonatal human cerebral oxizided cytochrome oxidase. J Appl Physiol 1991;71:1907–1913.
  25. Nishin T, Mokashi A, Lahiri S: Stimulation of carotid chemoreceptors and ventilation by doxapram in the cat. J Appl Physiol 1982;52:1261–1265.
  26. Nelle M, Hoecker C, Linderkamp O: Effects of bolus tube feeding on cerebral blood flow velocity in neonates. Arch Dis Child Fetal Neonatal Ed 1997;76:54–56.
  27. Roll C, Huning B, Kaunicke M, Krug J, Horsch S: Umbilical artery catheter blood sampling decreases cerebral blood volume and oxygenation in very low birthweight infants. Acta Paediatr 2000;89:862–866.
  28. Roll C, Horsch S, Knief J, Husing J, Hanssler L: Comparison of effects of endotracheal suction and surfactant administration on hemodynamics and oxygenation of premature infants – a near-infrared spectroscopy study. Z Geburtshilfe Neonatol 2001;205:104–109.
  29. McDonnell M, Ives NK, Hope PL: Intravenous aminophylline and cerebral blood flow in preterm infants. Arch Dis Child 1992;67:416–418.
  30. Mosca F, Bray M, Lattanzio M, Fumagalli M, Tosetto C: Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus. J Pediatr 1997;131:549–554.
  31. Uehara H, Yoshioka H, Nagai H, Ochiai R, Naito T, Hasegawa K, Sawada T: Doxapram accentuates white matter injury in neonatal rats following bilateral carotid artery occlusion. Neurosci Lett 2000;281:191–194.
  32. Anderson-Beck R, Wilson L, Brazier S, Hughes IE, Peers C: Doxapram stimulates dopamine release from the intact rat carotid body in vitro. Neurosci Lett 1995;187:25–28.
  33. Perlman JM: Cerebral blood flow in premature infants: regulation, measurement, and pathophysiology of intraventricular hemorrhage; in Polin RA, Fox WW (eds): Fetal and Neonatal Physiology. Philadelphia, Saunders, 1998, pp 2175–2186.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50