UBC Theses and Dissertations
The pathophysiology of hypoxic ischemic brain injury after cardiac arrest Sekhon, Mypinder Myp
The pathophysiology of hypoxic ischemic brain injury comprises of an initial primary injury during circulatory arrest followed by the secondary injury following return of spontaneous circulation. Management strategies are aimed at mitigating the negative consequences of secondary injury to improve long term neurological outcome. This thesis aimed to: 1) delineate the underlying cerebrovascular pathophysiology of secondary injury following return of spontaneous circulation; and, 2) establish important physiologic relationships between the physiologic determinants of cerebral oxygen delivery and brain tissue oxygenation in hypoxic ischemic brain injury. Study 1 investigated the burden of brain hypoxia following return of spontaneous circulation and determined the relationships between physiologic determinants of cerebral oxygen delivery with brain tissue oxygenation. Episodes of brain hypoxia were prevalent following resuscitation. Study 2 sought to delineate the state of autoregulation in hypoxic ischemic brain injury patients and identify the optimal within- individual mean arterial pressure. Overall, autoregulation was dysfunctional during ∼50% of the monitoring but with significant heterogeneity. Study 3 investigated the temporal patterns of intracranial pressure and compliance in hypoxic ischemic brain injury patients after return of spontaneous circulation. Overall, hypoxic ischemic brain injury was characterized by low intracranial pressure but abnormal intracranial compliance. Study 4 examined the mechanisms of brain hypoxia after cardiac arrest and determined the presence of diffusion limitation of oxygen delivery physiology in hypoxic ischemic brain injury patients. The results identified distinct physiologic phenotypes in that diffusion limitation of oxygen delivery accounted for the predominant mechanism of brain hypoxia after resuscitation in half of the cohort; the remaining patients in the study exhibited physiologic patterns consistent with dependence upon augmentation of cerebral oxygen delivery. Collectively, the results of this thesis indicate that brain hypoxia is prevalent after return of spontaneous circulation and autoregulation seems to be dysfunctional; however, significant heterogeneity exists with respect to the vasomotor control of cerebral blood flow and optimal perfusion pressures. Finally, there appear to be distinct physiologic phenotypes with respect to oxygen transport in the cerebral microvasculature and the presence of diffusion limitation being a novel mechanism of brain hypoxia after cardiac arrest.
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