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- Multimodal neuromonitoring in children with severe traumatic brain injuryPublication . Abecasis, Francisco; Oliveira, Vitor Augusto Rocha de; Czosnyka, MarekTraumatic brain injury (TBI) is a main cause of child morbidity and mortality worldwide. Survivors with severe neurological impairment represent an important burden to families and society. Modern neurocritical care management focuses on minimizing secondary brain injury and the use of management strategies based on multimodal brain monitoring has a potential to improve patient outcome. Cerebral autoregulation is an important mechanism allowing cerebral blood flow to stay constant despite fluctuations of cerebral perfusion pressure. It has been shown to be impaired in children with TBI and loss of autoregulation is associated with a poor outcome. There are several techniques that allow continuous calculation of autoregulation indices (and its surrogate - cerebrovascular reactivity) using intracranial pressure, blood flow velocity or cerebral oxygenation and its correlation to arterial blood pressure or cerebral perfusion pressure (CPP). The aim of this thesis was to study the accuracy of different methods of neuromonitoring, ranging from non-invasive and invasive acquisition of signals involved in cerebral haemodynamics to the study of cerebral autoregulation in children with TBI. The secondary objective was to study the association of autoregulation impairment with clinical outcome. In the introduction, traumatic brain injury in children and the theoretical principles of neuromonitoring are presented in detail with focus on the parameters used in the studies performed throughout the thesis. The cerebral autoregulation principles are also reviewed. The main body of the thesis is divided in four sections: In the first section, I review the role of neurovascular sonography in paediatric traumatic brain injury. Namely, the role of TCD in estimating intracranial pressure and cerebral perfusion pressure; evaluating cerebral autoregulation and continuous monitoring; detecting regional variations on cerebral haemodynamics and in the diagnosis of brain death. In the second section, I document through several clinical cases the usefulness of TCD for bedside decisions in the paediatric emergency department and in the paediatric intensive care unit. Five patients with different types of acute brain injury are presented. TCD was useful in the identification of intracranial hypertension in traumatic brain injury, hydrocephalus and central nervous system infection; identification of decreased cerebral perfusion pressure in hypovolemic shock and the diagnosis of impending cerebral circulatory arrest in a child with meningococcal septicaemia. I discuss the importance of TCD in each scenario through a revision of relevant literature and with my own experience. In the third section, I assess TCD as a non-invasive method to estimate cerebral perfusion pressure in children with severe traumatic brain injury. In order to accomplish this objective the feasibility of a novel non-invasive method of cerebral perfusion pressure estimation (nCPP) using a TCD-spectral accounting method in children with severe TBI was tested. There was a good correlation between invasive cerebral perfusion pressure and nCPP and nCPP monitoring with TCD appears to be a feasible method for cerebral perfusion pressure assessment in paediatric TBI. The novel spectral nCPP tested in this study has a decent correlation with invasive CPP and can predict low CPP with excellent accuracy at the 70-mmHg threshold. In the fourth and final section of this thesis, I present the results of a prospective cohort study performed throughout the four years of the thesis development. All children admitted to our paediatric intensive care unit with severe TBI were included to study three different methods of monitoring autoregulation: pressure-reactivity index (PRx), transcranial Doppler derived mean flow velocity index (Mx) and near-infrared spectroscopy derived cerebral oximetry index (COx). This is the first study to compare these three different methods of monitoring cerebral autoregulation in a group of children. PRx seems to be the most robust index to access cerebrovascular reactivity in children with TBI. It allows calculation of optimal CPP for the individual patient and has promising prognostic value. The main conclusions of this thesis are: • Transcranial Doppler is a useful technique to assist the clinical decisions at the bedside in children with acute brain injury; • Multimodal neuromonitoring is feasible in paediatric patients with TBI; • PRx seems to be the most sensitive index for cerebral autoregulation monitoring in children and has prognostic value; • Non-invasive continuous neuromonitoring is promising but it is still not accurate enough to replace invasive monitoring.