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Challenges in understanding the impact of blood pressure management on cerebral oxygenation in the preterm brain
1The Ritchie Centre, Monash University Melbourne, VIC, Australia.
Insights
In preterm infants, inotropic medications like dopamine and adrenaline may improve cerebral blood flow and oxygenation. Further research is needed to confirm if maintaining blood pressure with these drugs is neuroprotective.
Area of Science:
- Neonatal Medicine
- Pediatric Neurology
- Pharmacology
Background:
- Systemic hypotension in preterm infants is linked to poor outcomes, including brain injury and neurodevelopmental issues.
- Inotropic medications are used to maintain organ perfusion, particularly in the brain, but their neuroprotective effects are uncertain.
- Concerns exist regarding potential cerebral vasoconstriction from alpha-adrenergic agents like dopamine and adrenaline.
Purpose of the Study:
- To review the effects of inotropic agents on cerebral perfusion and oxygenation in preterm infants.
- To evaluate the neuroprotective potential of maintaining mean arterial blood pressure (MAP) in hypotensive preterm neonates.
- To explore findings from both clinical studies and animal models regarding inotrope use in the preterm brain.
Main Methods:
- Review of clinical studies and animal models examining inotropic agents (dopamine, dobutamine, adrenaline) in preterm infants.
- Analysis of effects on cerebral blood flow (CBF), cerebral perfusion, oxygenation, MAP, plasma lactate, and blood glucose.
- Consideration of autoregulation in the context of limited cerebro-autoregulation in preterm infants.
Main Results:
- Dopamine and adrenaline can increase MAP and cerebral blood flow in preterm infants, despite concerns about vasoconstriction.
- Experimental studies in immature animals show increased cerebral perfusion and oxygenation with dopamine, dobutamine, and adrenaline.
- Adrenaline may cause transient increases in plasma lactate and blood glucose, suggesting it as a second-line therapy.
Conclusions:
- Inotropic agents appear to increase cerebral perfusion and oxygenation in preterm infants, but long-term neuroprotective effects require further investigation.
- Carefully designed prospective studies, potentially including permissive hypotension, are needed to clarify the relationship between inotropes and long-term outcomes.
- Preterm animal models can help elucidate the physiological effects of inotropes and their impact on developing brain histopathology.
Abstract:
Systemic hypotension in preterm infants has been related to increased mortality, cerebrovascular lesions, and neurodevelopmental morbidity. Treatment of hypotension with inotropic medications aims at preservation of end organ perfusion and oxygen delivery, especially the brain. The common inotropic medications in preterm infants include dopamine, dobutamine, adrenaline, with adjunctive use of corticosteroids in cases of refractory hypotension. Whether maintenance of mean arterial blood pressure (MAP) by use of inotropic medication is neuroprotective or not remains unclear. This review explores the different inotropic agents and their effects on perfusion and oxygenation in the preterm brain, in clinical studies as well as in animal models. Dopamine and adrenalin, because of their α-adrenergic vasoconstrictor actions, have raised concerns of reduction in cerebral blood flow (CBF). Several studies in hypotensive preterm infants have shown that dopamine elevates CBF together with increased MAP, in keeping with limited cerebro-autoregulation. Adrenaline is also effective in raising cerebral perfusion together with MAP in preterm infants. Experimental studies in immature animals show no cerebro-vasoconstrictive effects of dopamine or adrenaline, but demonstrate the consistent findings of increased cerebral perfusion and oxygenation with the use of dopamine, dobutamine, and adrenaline, alongside with raised MAP. Both clinical and animal studies report the transitory effects of adrenaline in increasing plasma lactate, and blood glucose, which might render its use as a 2nd line therapy. To investigate the cerebral effects of inotropic agents in long-term outcome in hypotensive preterm infants, carefully designed prospective research possibly including preterm infants with permissive hypotension is required. Preterm animal models would be useful in investigating the relationship between the physiological effects of inotropes and histopathology outcomes in the developing brain.
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