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      Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus.

      The Journal of Pediatrics
      Blood Flow Velocity, drug effects, Brain, blood supply, enzymology, Cerebrovascular Circulation, Cyclooxygenase Inhibitors, pharmacology, therapeutic use, Dose-Response Relationship, Drug, Ductus Arteriosus, Patent, therapy, Echoencephalography, Electron Transport Complex IV, metabolism, Female, Humans, Ibuprofen, administration & dosage, Indomethacin, Infant, Newborn, Infant, Premature, Diseases, Male, Oximetry, Oxygen Inhalation Therapy, Regional Blood Flow, Ultrasonography, Doppler

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          Abstract

          To compare the effects on cerebral perfusion and oxygenation of intravenous ibuprofen and indomethacin as treatment for patent ductus arteriosus in preterm infants. Sixteen infants receiving mechanical ventilation (< 31 weeks gestation) with patent ductus arteriosus received either 0.2 mg/kg indomethacin (n = 8) or 10 mg/kg ibuprofen (n = 8) infused over 1 minute. Near-infrared spectroscopy was used to measure changes in cerebral blood volume and in oxidized cytochrome oxidase concentration. Cerebral blood flow velocity in the pericallosal artery was measured using Doppler ultrasonography. Indomethacin caused a significant reduction of CBV (maximal changes in cerebral blood volume: -320 +/- 171 microL/100 gm) and, in four of eight patients, a fall in oxidized cytochrome oxidase concentration (maximal change in oxidized cytochrome oxidase concentration in the eight patients: -0.68 +/- 0.98 mumol/L, NS). Cerebral blood flow velocity fell significantly. Ibuprofen caused no significant reduction of cerebral blood volume, oxidized cytochrome oxidase concentration, or cerebral blood flow velocity, whereas a significant increase of cerebral blood volume (+207 +/- 200 microL/100 gm) was observed after 60 minutes. Ductus closure was seen in six of eight infants after the first dose of indomethacin and in five of eight infants after the first dose of ibuprofen. The therapeutic cycle involved administration of a second and third dose, provided no side effects occurred. Treatment was effective in all infants. Compared with indomethacin, treatment with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability; the observed increase in cerebral blood volume requires further investigation.

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          Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study.

          Among 3559 newborn infants with birth weight less than 1750 gm, 421 developing a hemodynamically significant patent ductus arteriosus were entered into a randomized trial to evaluate the role of indomethacin in the management of PDA. Indomethacin given concurrently with usual medical therapy at the time of diagnosis resulted in ductal closure in 79%, versus 35% with placebo (P less than 0.001). Indomethacin as backup to usual medical treatment resulted in similar closure rates. To assess overall effects through hospital discharge, three management strategies were compared. Although mortality did not differ significantly, infants given indomethacin only if usual therapy failed (strategy 2) had a lower incidence of bleeding than those to whom indomethacin was given with initial medical therapy (strategy 1) and lower rates of pneumothorax and retrolental fibroplasia than those to whom no indomethacin was administered, with surgery the only backup to medical therapy (strategy 3). Thus the administration of indomethacin only when medical treatment fails appears to be the preferable approach for the management of symptomatic PDA in premature infants.
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            Measurement of Optical Path Length for Cerebral Near-Infrared Spectroscopy in Newborn Infants

            The time taken for an extremely short pulse of near-infrared laser light to traverse the heads of 6 preterm infants was measured after death. The values obtained were used to calculate a differential path length factor (DPF), defined as the mean distance travelled by the photons divided by the distance between the points where light entered and left the head. The DPF was found to be 4.39 +/- 0.28. Knowledge of this factor will permit accurate quantitative measurements to be made by near-infrared spectroscopy of a range of indices of cerebral oxygenation and haemodynamics in live infants.
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              Randomized trial of early closure of symptomatic patent ductus arteriosus in small preterm infants.

              As a result of randomized assignment, 15 preterm infants weighing 1,500 gm or less at birth and who had a symptomatic PDA were treated according to a medical management protocol, and ten according to an early surgical closure protocol. All infants required mechanical ventilation at the time of study entry, which was one week after birth. Birth weight, gestational age, age at onset of congestive failure, age at study entry, and the initial morbidity of members of the two groups were similar. The nine surviving infants managed according to the surgical closure protocol were weaned from mechanical ventilation sooner, had a decreased need for digoxin and furosemide, achieved gastrointestinal function sooner, and had a smaller hospital bill than the 12 survivors of the medical management group. These results indicate that infants with a symptomatic PDA still requiring mechanical ventilation at one week after birth will benefit from surgical closure of the ductus at that time.
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