Neonatal cerebrovascular autoregulation.

Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes

Intraoperative fluid therapy in neonates

The evidence base for the administration of intraoperative fluids in neonates is poor and extrapolated from adults and children. Differences from adults and children in physiology and anatomy of neonates inform our practice.Keywords: fluid responsiveness, fluid therapy, intraoperative, neonate

Placental function, body composition and cardiovascular autonomic function

Hypertension is an important modifiable risk factor for cardiovascular disease. An important recent advancement in hypertension research is an understanding that hypertension often may have a developmental origin. Birthweight is associated with hypertension across the lifespan and adult cardiovascular disease, such that those at both ends of the spectrum are at increased risk. Nonetheless, birthweight is a crude surrogate of fetal growth and it may be that quantification of body composition, may more accurately identify the “at risk” individual. A causative mechanism linking birthweight and cardiovascular risk is yet to be identified but may involve changes to the structure and function of organs including the placenta which may impair development and predispose individuals to later cardiovascular disease. The aims of this thesis were to investigate the associations between placental function, body composition and cardiovascular autonomic function. Studies outlines in this thesis indicate different mechanism control fat mass and fat free mass in the newborn and that placental weight partly mediates the association of maternal factors with newborn body composition. While low birthweight has previously been shown to be associated altered autonomic function in the infant our studies suggests that body fatness may provide information beyond that obtained from birthweight assessment alone. Previous studies have shown altered blood pressure control in those born preterm, our studies found altered cardiovascular outcomes even in the late preterm newborn. Assessment of body composition in children and adolescents at rest and in response to an exercise test suggests worsening of autonomic control due to adiposity and may develop over time during childhood and adolescence. Collectively, these results emphasise the implications of altered in-utero and early life exposures on cardiovascular outcomes

Magnetic Resonance Imaging of the Neonatal Cardiovascular System : Impact of Patent Ductus Arteriosus

The incidence of premature birth is increasing in absolute number and as a proportion of all births around the world. Many pathologies seen in this cohort are related to abnormal blood supply. Fetal and premature cardiovascular systems differ greatly as to maintain adequate blood flow to the developing organs in the uterine and extra-uterine environments require very different circulations. Subsequently following preterm birth the immature cardiovascular system undergoes abrupt adaptations, often resulting in the prolonged patency of the fetal shunt, ductus arteriosus. The impact of a patent ductus arteriosus (PDA) is poorly understood. However it is thought that large ductal shunt volumes may result in congestive cardiac failure and systemic hypo-­‐perfusion. Cardiac MRI has contributed greatly to the understanding of many cardiovascular diseases and congenital defects in paediatric and adult patients. Translating these imaging techniques to assess the preterm cardiovascular system requires careful optimization due to their condition, size and significantly increased heart rate. The work presented in this thesis employs multiple functional CMR techniques to investigate the preterm cardiovascular system in the presence and absence of PDA and the resultant cardiac function. A novel technique utilizing PC MRI to quantify PDA shunt volume and its impact on flow distribution is presented. Despite large shunt volumes, systemic circulation remained within normal range, although slight reduction is detectable when assessed at group level. Subsequently the impact of PDA and associated increased work load on left ventricular dimensions and function was then investigated using SSFP imaging. Results indicated that cardiac function was maintained even in the presence of large shunt volumes. Finally 4D PC sequences were employed to evaluate pulse wave velocity and flow regime within the preterm aorta, demonstrating the feasibility of hemodynamic assessment in this cohort. The findings of these studies provide insight into the impact of PDA. The reliable measurement and assessment of preterm cardiovascular system provides the potential to improve the understanding of the development and effects of certain pathologies seen in this cohort.Open Acces

Intervention levels for the support of blood pressure in extremely preterm infants

PhDBackground The true relationship between different cardiovascular variables are complex. A varied practice exists in the cardiovascular management of extremely preterm infants, including intervention levels for blood pressure (BP). Adverse outcomes may be secondary to low BP, anti-hypotensive treatment, or both. Aim To test the hypothesis that alterations in BP and cardiac output (CO) have an effect on cerebral blood flow (CBF), that these cardiovascular measures effect electroencephalographic (EEG) continuity and that different BP intervention levels will result in different rates of inotrope usage and achieved levels of BP in infants born <29 weeks gestation using patients recruited to a clinical pilot study. Methods Infants had measurements of CO and CBF using ultrasound, EEG recording and BP profiles downloaded for the first postnatal week. Infants were randomised to different levels of mean arterial BP at which they received cardiovascular support: Active(<30mmHg), Moderate(< Gestational age mmHg) or Permissive(signs of poor perfusion or <19mmHg). Once this BP threshold was breached, all infants were managed using the same treatment guideline. Cranial ultrasound scans were reviewed blind to study allocation. The relationship between physiological measurements was explored. The validity and reliability of CBF measurements were examined using flow phantom models. Results Sixty infants were recruited, had detailed measurements performed, and randomly assigned to one of three arms. CO was not related to CBF or BP. Inotrope usage, and invasively measured BP on day 1 were highest in the Active and lowest in the Permissive arm. There were no differences in haemodynamic or EEG parameters, or non-cerebral clinical complications. EEG continuity and CBF were directly related to BP. The validity and reliability of CBF was acceptable. Composite rates of grade 2–4 intraventricular haemorrhage, periventricular leucomalacia or parenchymal cysts were significantly different on post-hoc analysis between the three arms (Active 0/19, Moderate 6/20, Permissive 2/21;p=0.014). Conclusion Alterations in BP and CO did not affect CBF. Different BP intervention levels resulted in different rates of inotrope usage and levels of achieved BP. Although EEG continuity was not different between the three arms, this study found an increasing mean arterial BP was associated with increasing cerebral electrical activity and higher EEG continuity.Barts and The London Charit