Autoregulation of cerebral blood flow in newborn babies

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Abstract

Autoregulation is the result of a basic property of vascular smooth muscle cells where transmural pressure modifies muscle tone. As a result, flow is kept more or less constant over a range of blood pressures. In foetal lambs autoregulation develops from 0.6 gestation, whereas in extremely preterm babies the evidence is conflicting. Static autoregulation, measuring at steady state, is developed with a lower threshold at or below 30 mm Hg. The upper limit has not been determined. Dynamic autoregulation, measuring before steady state, appears not to be operating in preterm babies. The reason for this discrepancy is unknown and the clinical relevance is uncertain. In term and preterm babies with hypoxic–ischaemic brain injury, or with arterial hypotension treated with dopamine static autoregulation has been found absent. For clinical practice the relation between pressure and blood flow is less important than the relation between arterial pCO2 and blood flow.

Introduction

Autoregulation is a property of arteries to constrict in response to an increase in transmural pressure, and to dilate in response to a decrease in pressure, with the effect of keeping blood flow more or less constant with a range of arterial blood pressures. This response has a limited capacity and as a result blood flow will decrease when blood pressure decreases below a lower threshold, and increase when blood pressure increases above an upper threshold (Fig. 1).

A direct relation of cerebral blood flow to systolic blood pressure was reported 25 years ago in a small group of newborn infants shortly after birth and it was proposed that autoregulation could be particularly fragile in the immature brain or even not yet be fully developed. This would render the immature brain particularly susceptible to ischaemia during low blood pressure and haemorrhage during high blood pressure. Since these types of brain injury are both common and serious in newborn babies the ‘lost autoregulation’ hypothesis has helped neonatologists to focus on blood pressure and circulation in addition to ventilation.

In spite of a considerable research effort, however, the characteristics of autoregulation in newborn babies is still not well defined and only little data in the literature links abnormal blood pressure to brain injury, brain damage or neurodevelopmental deficit. This can be compared to the parallel issue of CO2–CBF reactivity, where there is strong evidence for at robust and clinically very significant relation between pCO2 and CBF in newborn babies, and a significant association between hyperventilation and hypocapnia on one side and brain damage and cerebral palsy on the other [1].

The following text provides some background physiology on autoregulation, discusses the experimental evidence from animal and human studies of the immature brain, suggests some areas for new research, and some clinical guidelines.

Section snippets

Cerebrovascular resistance

Blood flow through the brain is the result of the pressure gradient from artery to vein, called the perfusion pressure. The perfusion pressure for the brain is usually the same as for all other organs of the body, although differences may exist due to pressure drop along the central arterial tree or due to increased intracranial pressure. Blood flow is limited by vascular resistance. Vascular resistance is due to the limited diameter of blood vessels, particularly arterioles and arteries, and

Animal studies

An autoregulatory plateau has been demonstrated in several animal species shortly after birth: dogs [6] lambs [7], and rat [8]. In foetal lamb, autoregulaton is not present at 60% gestation, and present at 90% gestation [9] and the lower threshold of the autoregulation is nearer the normal resting blood pressure, i.e. there is less vasodilator reserve, at 0.75 gestation, compared to 0.9 gestation [10]. In newborn lambs, autoregulation could be completely abolished for 4 to 7 h by 20 min of

A note on white matter ischaemia in preterm infants

The vasculature of the preterm human white matter is sparse corresponding to a very low perfusion rate. Flow imaging during arterial hypotension in 24 preterm infants with persistently normal brain ultrasound suggested that that CBF to the periventricular white matter may be selectively reduced at blood pressures below 30 mm Hg [29] and supports the concept of periventricular white matter being a ‘watershed area’ and therefore particularly vulnerable to ischaemia.

Research directions

  • Can the discrepancy between dynamic and static autoregulation in preterm neonates be confirmed, also in experimental animals?

  • What are the mechanisms accounting for the immaturity of dynamic compared to static autoregulation?

  • Does this immaturity really pose a risk of brain injury?

  • Is automated, continuous monitoring of pressure-flow reactivity and cerebral oxygenation feasible in clinical practice?

  • Can continuous monitoring of pressure-flow reactivity or cerebral oxygenation be used to guide care

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