Age-dependent cerebral hemodynamic effects of indomethacin in the newborn piglet

Abstract

With recent discussions in the literature regarding prophylactic use of early (within the first 12 h after birth), low-dose indomethacin to reduce the incidence and severity of intraventricular hemorrhage, knowledge pertaining to the cerebral hemodynamic effects of indomethacin in this age group is of significant interest. The cerebral circulation is known to undergo significant changes during the first few days of postnatal life. In the present study, we have investigated the hypothesis that postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner. Near-infrared spectroscopy with indocyanine green was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction fraction in 39 newborn piglets. Piglets were grouped by age and received either 0.2 mg/kg indomethacin (14 were <13 h of age and 12 were >13 h of age) or saline (8 were <13 h of age and 5 were >13 h of age) infusions. In a subgroup of indomethacin-treated piglets (9 less than and 7 greater than 13 h of age), Doppler flow ultrasound was used to diagnose and monitor the presence and persistence of patent ductus arteriosus. Age was a significant factor in the cerebral hemodynamic response to indomethacin with piglets <13 h of age exhibiting delayed increases in cerebral blood flow and cerebral blood volume at 150 min post-indomethacin infusion.

Preservation of the metabolic rate of oxygen in preterm infants during indomethacin therapy for closure of the ductus arteriosus

“…Decreased CMRO 2 has been reported in animal studies; however, these changes were found either at a high dose (5 mg/kg) or during hypotension (32,33). Using the same infusion protocol and the same NIRS techniques, our group previously reported, in newborn piglets, that indomethacin significantly reduced CBF but had no effect on CMRO 2 (34). These results substantiate the main finding of the current clinical study.…”

Primer consenso clínico de SIBEN: enfoque diagnóstico y terapéutico del ductus arterioso permeable en recién nacidos pretérmino

“…La administración de indometacina produce cambios sustanciales en la hemodinámica cerebral de forma inmediata a aquélla. Esto ha sido evaluado en estudios clínicos realizados en niños prematuros por eco-Doppler 107,113,[229][230][231][232][233][234][235][236] , por NIRS (por sus siglas en inglés: Near Infra Red Spectroscopy) 144,[237][238][239] o por ambos métodos 238 , y también en animales neonatales 240,241 . Esencialmente, la administración de indometacina produce cambios en la hemodinámica y oxigenación cerebral que concuerdan con la disminución de la perfusión cerebral 113,144,[229][230][231][232][233][234][235][236][237][238][239] que persiste en el tiempo 234 .…”

SIBEN's First Clinical Consensus: Diagnostic and Therapeutic Approach to the Patent Ductus Arteriosus in Preterm Infants

“…INDO administration produces substantial changes in cerebral hemodynamics immediately after its administration. This has been evaluated in clinical studies in premature infants by noninvasive techniques such as Doppler ultrasound 107,113,[229][230][231][232][233][234][235][236] , NIRS (Near Infra Red Spectroscopy) 144,[237][238][239] or combined modalities 238 and also in animal models 240,241 .…”