Effects of indomethacin on cerebral haemodynamics in very preterm infants

Edwards, A. David; Wyatt, John; Richardson, C. E.; Potter, A.; Cope, M; Delpy, DT; Reynolds, E. O. R.

doi:10.1016/0140-6736(90)93030-s

Cited by 280 publications

(121 citation statements)

References 27 publications

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“…The ability of indomethacin to cross the bloodbrain barrier may be greater than other nonsteroidal antiinflammatory drugs because, although also strongly protein bound, the free indomethacin in plasma is greater than the free levels of others with the exception of salicylates (8). In newborn pigs (4, 5), and apparently newborn humans (10)(11)(12), hypercapnic cerebral vasodilation is reduced or abolished by indomethacin. This finding, coupled with measurements of cerebral synthesis of prostanoids induced by hypercapnia (4, 13) and the inability of radical scavengers to alter the responses (14), suggests that pros-tanoids play a role in hypercapnic cerebral vasodilation in newborn pigs and human infants.…”

Section: Resultsmentioning

confidence: 99%

Effects of Indomethacin on Cerebral Vasodilator Responses to Arachidonic Acid and Hypercapnia in Newborn Pigs

et al. 1993

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Section: Resultsmentioning

confidence: 99%

Effects of Indomethacin on Cerebral Vasodilator Responses to Arachidonic Acid and Hypercapnia in Newborn Pigs

et al. 1993

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“…The cerebral vasoconstrictive effects of indomethacin are frequently cited as a concern among neonatologists (13)(14)(15). However, neonatal indomethacin exposure has not been found to have a negative effect on cognitive outcome in 8 years follow-up studies (24).…”

Section: Comments and Conclusionmentioning

confidence: 99%

“…Although the decreased incidence of severe ICH might be expected to result in improved neurodevelopmental outcome among infants treated with prophylactic indomethacin, there have been lingering concerns about indomethacin's effects on cerebral perfusion and possible risks of brain ischemia (13)(14)(15). Therefore, a large, multicentered trial (TIPP-trial) was performed to evaluate the long term effects of prophylactic indomethacin on motor, sensory, and cognitive outcomes (16).…”

Section: Introductionmentioning

confidence: 99%

Indomethacin Prophylaxis for Preterm Infants: The Impact of 2 Multicentered Randomized Controlled Trials on Clinical Practice

Clyman¹,

Saha²,

Jobe³

et al. 2007

The Journal of Pediatrics

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Objectives-Two multicentered RCTs in premature infants TIPP, 2001) found beneficial effects of indomethacin prophylaxis on the incidences of patent ductus arteriosus (PDA), PDA ligation, and severe intracranial hemorrhage (ICH). The Ment-trial recommended its use. The TIPP-trial failed to find a benefit in its primary outcome (improved survival/ neurodevelopmental outcome). This negative result may have discouraged prophylactic indomethacin use.Study Design-We used the NICHD Neonatal Network Registry to determine the association between the two trials and the use of prophylactic indomethacin. We also statistically assessed the assumptions that led to the TIPP trial's negative results.Results-Use of prophylactic indomethacin among Network clinicians increased after publication of the Ment-trial and decreased after the TIPP-trial. Analysis of the TIPP-trial showed that the primary outcome's anticipated effect size (≥20%) was too large; a smaller effect size (<3%) would have been more appropriate based on the incidence of ICH in their population, and its association with neurodevelopmental outcome.. Conclusions-Two multicenteredRCTs were associated with changes in indomethacin prophylaxis. Following the Ment-trial, its use increased. Following the TIPP-trial, which reported negative results based on too large an anticipated effect size, its use decreased.

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“…The reason for the discrepancy between the two methods is unclear, but induced changes in the scattering properties of the brain would give rise to errors influencing the total Hb method rather than the oxygen method. (Pediatr Res 36: 20-24, 1994) Abbreviations CBV, cerebral blood volume CBV,, cerebral blood volume measured by the oxygen method CBV,, change in cerebral blood volume as detected by the total Hb method CBF, cerebral blood flow CBF,, cerebral blood flow measured by the oxygen method NIRS, near-infrared spectrophotometry Sat, arterial oxygen saturation [Hb], cerebral concentration of deoxyhemoglobin [HbO,], cerebral concentration of oxyhemoglobin FiO,, fraction of inspired oxygen 01, oxygenation index CI, confidence interval the oxyhemoglobin and deoxyhemoglobin signals, the total Hb, as an indicator for changes in CBV, and it has already been used in a number of reports (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Cerebrovascular Responses to Carbon Dioxide as Detected by Near-Infrared Spectrophotometry: Comparison of Three Different Measures

Brun

Greisen

1994

Pediatr Res

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Near-infrared spectrophotometry can be used to measure cerebral concentrations of oxyhemoglobin and deoxyhemoglobin. This has been applied to developing methods for quantifying cerebral blood volume glob i which is relevant for the investigation of the pathogenesis of brain injury in newborn infants as well as older infants. This study investigates the internal consistency between measurements of CBV using two methods: the oxygen method, which is able to determine absolute values of CBV, and the total Hb method, which can detect changes in CBV only. Cerebral blood flow (CBF) was also measured. Fifteen premature infants were examined. Due to practical problems, in only eight of these was a minimum of two CBF and two CBV values obtained both before and after a change in arterial Pco, of at least 0.5 kPa. A significant difference between the CBV-CO, reactivity found by the two methods was demonstrated: 0.89 mUlOO g/kPa (95% confidence interval = 0.63-1.26) for the oxygen method and 0.22 mUlOO g/kPa (95% confidence interval = 0.084.36) for the total Hb method. This finding is substantiated by the absolute values of CBV [mean value = 3.7 mUlOO g (SD = 1.1)], CBF [mean value = 11.3 mUlOO glmin (SD = 5.9)], and CBF reactivity 159 2 9% (SEM)]. All the values Measuring CBV is relevant in the investigation of the pathophysiology of hemorrhagic and hypoxic-ischemic brain injury. Methods used so far for absolute quantification such as radioactive erythrocyte labeling have not been feasible for clinical practice.NIRS is a method for measuring changes in [Hb] and [HbO,] using the Beer-Lambert relationship between the attenuation of the emitted light and the concentration of absorber. This has led to methods for quantifying CBF and CBV (1, 2). NIRS is a relatively fast, easily reproducible, noninvasive method that may appeal to clinicians for use in a number of settings. In particular it is tempting to use the directly available trace of the sum of correspond well with previous findings, although the CBV reactivity determined by the oxygen method has not been reported previously. The reason for the discrepancy between the two methods is unclear, but induced changes in the scattering properties of the brain would give rise to errors influencing the total Hb method rather than the oxygen method. (Pediatr Res 36: 20-24, 1994) Abbreviations CBV, cerebral blood volume CBV,, cerebral blood volume measured by the oxygen method CBV,, change in cerebral blood volume as detected by the total Hb method CBF, cerebral blood flow CBF,, cerebral blood flow measured by the oxygen method NIRS, near-infrared spectrophotometry Sat, arterial oxygen saturation [Hb], cerebral concentration of deoxyhemoglobin [HbO,], cerebral concentration of oxyhemoglobin FiO,, fraction of inspired oxygen 01, oxygenation index CI, confidence interval the oxyhemoglobin and deoxyhemoglobin signals, the total Hb, as an indicator for changes in CBV, and it has already been used in a number of reports (3-7).The aim of this study was to quantitate the CBV-CO, reactivity...

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Effects of indomethacin on cerebral haemodynamics in very preterm infants

Cited by 280 publications

References 27 publications

Effects of Indomethacin on Cerebral Vasodilator Responses to Arachidonic Acid and Hypercapnia in Newborn Pigs

Effects of Indomethacin on Cerebral Vasodilator Responses to Arachidonic Acid and Hypercapnia in Newborn Pigs

Indomethacin Prophylaxis for Preterm Infants: The Impact of 2 Multicentered Randomized Controlled Trials on Clinical Practice

Cerebrovascular Responses to Carbon Dioxide as Detected by Near-Infrared Spectrophotometry: Comparison of Three Different Measures

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