Cerebral perfusion markers in full-term neonates as a measure of Hypoxic-Ischemic Encephalopathy during and immediately following Hypothermia Treatment
AuthorForster, Danielle Elizabeth
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2022-06-25.
© 2020 Danielle Elizabeth Forster
Hypoxic-Ischaemic Encephalopathy (HIE) is a leading cause of neonatal mortality and morbidity. Therapeutic Hypothermia (TH) is the only treatment for HIE, which has reduced the rate of mortality and morbidity although still around fifty per cent of infants affected die or have a neurodevelopmental disability, such as cerebral palsy. Every infant with HIE receives the same TH protocol: 72 hours at 33.5 degrees Celsius, before being rewarmed slowly over 12 hours. The infants with moderate-severe HIE are at the highest risk of disability or death. Should it be possible to identify those infants at greatest risk during the TH, they could be targeted for modified TH treatment or for additional adjuvant treatments such as allopurinol, melatonin or ethyropeitin. The severity of the HIE, and prognosis on outcome, is challenging while the infant is cooled, as the cooling itself reduces the prognostic power of many of the previously accepted assessment methods. MRI (Magnetic Resonance Imaging) is the gold standard, but moving infants to an MRI whilst cooled is problematic, and the HIE injury to the brain may not be evident for several days. The objective of this research study was to find a clinical parameter which would identify those infants at highest risk of a poor outcome. HIE is characterised by hyper-perfusion, cerebral blood flow (CBF) exceeding metabolic demand, consequent from a physiological response preferentially redirecting blood flow to the brain during a hypoxic episode. Thus, a marker of cerebral perfusion that could classify HIE infants by the degree of hyper-perfusion was sought. Initially the Resisitive Index (RI), as determined by measuring the Cerebral Blood Flow Velocities (CBFV’s) using Doppler Ultrasound (DUS), was investigated as a possible cerebral perfusion marker. The RI is an accepted measure of the resistance of the cerebral arteries and an RI < 0.55 is considered to be indicative of a previous hypoxic event. In the first part of this study, the RI was evaluated in 80 healthy and 18 HIE infants and found to be unreliable; some infants with HIE and a poor outcome did not have an RI < 0.55, whereas some infants without HIE did. Moreover, DUS is not continuous; it is a one-off measurement requiring a skilled operator. A pursuit for another cerebral perfusion marker ensued. Frequency-Domain Near Infrared Spectroscopy (FD-NIRS) promised absolute measurements of oxy- and deoxy-Haemoglobin (HbO and HbR) in the brain tissue. Increased CBF was expected to result in a higher than normal concentration of blood and therefore Haemoglobin in the brain tissue. The results from the second part of this research study of 40 healthy and 6 HIE infants suggest that hyper-perfusion is expressed in the concentration of HbO in the brain tissue, and that this is most related to poor outcome. The limited HIE population in this study prevents generalisation from this finding, though suggests that there is justification for further research using FD-NIRS to monitor infants with HIE.
KeywordsHypoxic-Ischemic Encephalopathy; HIE; perinatal asphyxia; birth asphyxia; doppler ultrasound; DUS; cranial ultrasound; CUS; resistive index; RI; pulsatility index; PI; cerebral blood flow velocity; CBFV; therapeutic hypothermia; near-infrared spectroscopy; NIRS; frequency-domain near-infrared spectroscopy; FD-NIRS
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