Cerebral blood flow and oxygenation in infants after birth asphyxia. Clinically useful information?
Section snippets
Historical perspectives on luxury perfusion and impaired oxygen metabolism
Niels Lassen coined the term luxury-perfusion syndrome in a hypothesis paper in the Lancet in 1966 [1]. It was based on three observations. First, two animal experiments demonstrating reactive hyperaemia lasting for several hours following hypoxia–ischemia had been presented at two conferences the same year. Second, the year before experience had been reported with bright-red blood in the veins on the surface of the brain during surgery for tumours and in cases of infarction. Finally, Lassen
Hyperperfusion
The first suggestion of cerebral hyperperfusion after birth asphyxia was obtained in 1979 by Doppler ultrasound as a reduced pulsatility in the anterior cerebral artery. The pulsatility of blood flow velocity in a distributory artery is an indicator of the vascular resistance distal to the point of measurement and pulsatility in the anterior cerebral artery is negatively correlated – although weakly – to cerebral blood flow in newborn infants. That cerebral blood flow really is increased – i.e.
Cerebral oxygen metabolism
Four small studies have attempted to measure cerebral oxygen metabolism in the asphyxiated newborn infant (Table 1). The standard method with blood sampling from the jugular vein was used in nine infants [7]. Oxygen extraction in the four who died or were handicapped was 2 ml O2 per 100 ml blood whereas it was 5 ml per 100 ml in the five who recovered. Cerebral blood flow was measured by the Kety–Schmidt method and found three times higher in those who died or were handicapped. Therefore cerebral
The prognostic value
A Doppler ultrasound pulsatility index of flow velocity in the anterior cerebral artery below 0.55 was highly predictive of poor neurodevelopmental outcome in term infants who had clinical hypoxic–ischaemic encephalopathy after severe birth asphyxia [11]. This prognostic value is reduced when therapeutic hypothermia is used [12]. Similarly, abnormally high StO2 predicts poor neurodevelopmental outcome [13], and this appears still to be true when therapeutic hypothermia is used [14].
But again,
Reducing brain damage
The concept of reperfusion injury implies that at least part of the damage is due to excessive oxygenation. In principle, this can be attributed to excessive oxygen content of arterial blood or to excessive reperfusion.
While it has now been generally accepted that there is no need to use supplementary oxygen during resuscitation, the use of a hypoxic gas mixture was tested in a piglet model [15]. An FiO2 of 12–18% was sufficient to achieve a sagittal sinus blood oxygen saturation of 17–23% 2 h
Conclusions
Cerebral hyperoxygenation, abnormally increased perfusion, and lack of normal cerebral blood flow regulation are typically present in severe hypoxic–ischaemic encephalopathy. This can be utilized for prognostication. Whether the perfusion abnormalities at this secondary stage are detrimental, beneficial, or a mere epiphenomenon remains elusive. In contrast, incomplete reoxygenation of the brain during and following resuscitation is likely to compromise outcome. The clinical value of cerebral
Key guidelines
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Consider using Doppler ultrasound to diagnose cerebral hyperperfusion and/or near-infrared spectroscopy to diagnose cerebral hyperoxygenation, both indicators of secondary energy failure.
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Caution is indicated when using this information for prognosis. Although it does have good prognostic value, this value is reduced during hypothermia. It is unclear how much it adds to information from other sources, such as clinical history, neurological state, EEG, or imaging.
Research directions
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Cardiovascular compromise is common after birth asphyxia and it is possible that incomplete reoxygenation of the brain contributes to the primary injury. Cerebral oximetry in the first hours after resuscitation has potential to detect this and deserves testing in a clinical trial.
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There are no guidelines or clear evidence that one must attempt to normalise hyperperfusion or hyperoxygenation. It is unknown if these contribute to the injury or constitute a compensatory mechanism and must be
I have no conflicts of interest regarding the contents of this article.
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Cited by (19)
A Scoping Review of Cerebral Doppler Arterial Waveforms in Infants
2023, Ultrasound in Medicine and BiologyChanges in brain perfusion in successive arterial spin labeling MRI scans in neonates with hypoxic-ischemic encephalopathy
2019, NeuroImage: ClinicalCitation Excerpt :The severity of this second phase is related to poor outcome (Batista et al., 2007; Rosenbaum et al., 1997). It still remains unclear whether hyperperfusion contributes to the injury or, on the other hand, represents a compensatory mechanism (Greisen, 2014). Wintermark et al. raised the question of the timing of the transition between the hypoperfusion phase and the hyperperfusion phase during the first days of life (Wintermark et al., 2011).
It's All About the Brain—Neuromonitoring During Newborn Transition
2018, Seminars in Pediatric NeurologyCitation Excerpt :In term born infants with hypoxic ischemic encephalopathy (HIE), significantly elevated cerebral oxygenation values and reduced cerebral fractionated oxygen extraction values have been identified in the first 24 hours and found to correlate with poor neurodevelopmental outcomes at 2 years of age.47-49 The rise in cerebral oxygenation most likely reflects increased cerebral perfusion, decreased oxygen usage and impaired cerebral autoregulation.50,51 The possibility of using cerebral NIRS as a tool to assess cerebrovascular autoregulation and maintain cerebral blood flow in a range that results in optimal cerebral oxygenation might improve neurodevelopmental outcome in HIE infants and is a key priority for future research.
Neuroimaging and Other Neurodiagnostic Tests in Neonatal Encephalopathy
2016, Clinics in PerinatologyCitation Excerpt :Taken together, these studies suggest that infants with birth asphyxia and a later adverse outcome have higher cerebral oxygenation in the first 12 to 48 hours of life. It is unclear whether this hyperperfusion/hyperoxygenation contributes to the injury or represents a compensatory mechanism,66 and larger studies need to be undertaken to determine the best NIRS variable and cutoff value. There have been significant advances in our understanding of neonatal hypoxic-ischemic brain injury over the past years.
Cerebral Blood Flow of the Neonatal Brain after Hypoxic–Ischemic Injury
2023, American Journal of PerinatologyCerebral ischemia in the developing brain
2022, Journal of Cerebral Blood Flow and Metabolism