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Effects of phenobarbital on cerebral blood flow during hypoxia
A Cortey1, P Monin, J M Hascoet
1INSERM, Unité 272 et Maternité Universitaire, Université de Nancy, France.
Insights
Phenobarbital (PB) may not effectively protect against hypoxic brain injury in newborns. Studies show PB pretreatment altered cerebral blood flow responses during hypoxia, suggesting cautious use in asphyxiated infants.
Area of Science:
- Neonatal Medicine
- Neuroscience
- Pharmacology
Background:
- Hypoxic brain injury is a significant concern in asphyxiated newborns.
- Phenobarbital (PB) is an anticonvulsant sometimes used to mitigate this injury.
- The precise effects of PB on cerebral blood flow (CBF) during hypoxia require further elucidation.
Purpose of the Study:
- To investigate the impact of Phenobarbital pretreatment on cerebral blood flow responses during varying degrees of hypoxia in a neonatal piglet model.
- To assess the efficacy of PB in preventing hypoxia-induced alterations in cerebral circulation.
Main Methods:
- Fifteen mechanically ventilated piglets were studied, with 7 receiving PB pretreatment (20 mg/kg) and 8 serving as controls.
- Hypoxia was induced by introducing carbon monoxide, with severity graded (I, II, III) based on available hemoglobin for oxygen transport.
- Cerebral blood flow was measured using radiolabeled microspheres, alongside monitoring of blood pressure, blood gases, and pH.
Main Results:
- Control piglets exhibited increased CBF during grade I, II, and III hypoxia, maintaining elevated levels above baseline.
- Piglets pretreated with PB showed a significant CBF increase only during grade II hypoxia.
- During severe grade III hypoxia, PB-pretreated piglets experienced a decrease in CBF to prehypoxic levels, despite reduced cerebral oxygen delivery.
Conclusions:
- Phenobarbital pretreatment may not consistently enhance or maintain cerebral blood flow during severe hypoxia in a neonatal model.
- The findings suggest that PB should be administered with caution in asphyxiated newborns due to potentially detrimental effects on cerebral circulation.
- Further research is warranted to understand the complex interactions between PB, hypoxia, and cerebral hemodynamics in neonates.
Abstract:
Phenobarbital (PB), at anticonvulsant dosages, has been used in an attempt to reduce hypoxic brain injury in asphyxiated newborn infants. The effects of PB pretreatment on the cerebral blood flow (CBF) response in hypoxia were studied in 15 curarized and mechanically ventilated piglets: 7 animals were pretreated with 20 mg/kg of PB (group 1) and 8 served as untreated controls (group 2). Successive aliquots (25 ml) of carbon monoxide were introduced into a closed ventilator circuit and CBF (measured with radiolabelled microspheres), arterial blood pressure, blood gases, arterial pH and PaO2 were subsequently determined at different levels of hypoxia. The amount of hemoglobin available for oxygen transport (i.e. total Hb-HbCO) was used to express hypoxic aggression and decreased from grade I (> 2 mmol/l) to grade II (1-2 mmol/l) to grade III (< 1 mmol/l). In the control group, CBF increased during grade-I hypoxia and continuously remained above baseline values during grade-II and grade-III hypoxia. In pretreated animals, however, only grade-II hypoxia was associated with a significant increase in CBF above baseline. In addition during grade-III hypoxia, CBF decreased to the prehypoxic values despite a fall in cerebral oxygen delivery and cardiac index. These data suggest that PB should be used with caution to prevent brain damage in the asphyxiated newborn infants.