Bedside Assessment of Global Cerebral Energy Metabolism utilizing Intravenous Microdialysis: With special reference to post-cardiac arrest care

Resuscitated out-of-hospital cardiac arrest (OHCA) is associated with a high risk of brain injury and mortality. Post-cardiac arrest care focuses on minimizing secondary brain injury and optimizing the chances of recovery. Brain-directed therapies, including e.g., hemodynamic support to optimize cerebral perfusion and oxygen delivery, remain an essential factor. Blood pressure derangements may attenuate secondary brain injury, but the optimal blood pressure target during post-resuscitation care is currently unknown. Bedside monitoring of cerebral metabolism can potentially ensure optimal clinical care in comatose patients due to post-cardiac arrest brain injury. However, until recently, no routine technique has been available for bedside assessment of cerebral energy metabolism after cardiac arrest. For more individualized post-resuscitation care and target-driven therapy to improve patient outcomes, markers measuring global cerebral energy metabolism and reflecting metabolic variations after resuscitation are required.

This thesis´ overall objectives were assessment of optimal blood pressure and characterizing changes in global cerebral energy metabolism using novel bedside microdialysis application in comatose patients resuscitated from OHCA. Therefore, this thesis aimed to assess I) whether the post-resuscitated brain exhibits persistent perturbations of energy metabolism monitored with jugular bulb microdialysis (JBM) and II) the effect of different blood pressure levels on global cerebral energy metabolism in comatose patients resuscitated from OHCA and III) biochemical patterns including brain ischemia between patients with unfavorable and favorable neurological outcome.

Paper I compared the effect of two mean arterial blood pressure (MAP) levels on global cerebral energy metabolism during cardiac surgery. The study showed that placing a microdialysis catheter in the jugular bulb was feasible for monitoring transient perturbations of variables reflecting intracerebral energy metabolism. Targeting a higher MAP during cardiopulmonary bypass did not significantly improve cerebral energy metabolism or oxygenation. Furthermore, the study established reference values for “normal” microdialysate values in human jugular venous blood in anesthetized patients without cerebral pathophysiology.

Paper II, a clinical trial protocol, described how Paper IV was conducted (rationale, objectives, design, methods, analysis plan) and ensured the safety of the trial subjects and integrity of the data collected.

Paper III was designed to investigate whether JBM might be used to monitor secondary deterioration of cerebral energy metabolism after OHCA. The study indicated that JBM was feasible and safe. Variables reflecting cerebral energy metabolism could be distinguished from systemic variables obtained from intraarterial microdialysis in patients with poor clinical outcome. Biochemical signs of ischemia and mitochondrial dysfunction were frequent and long-lasting after the return of spontaneous circulation (ROSC) and more pronounced in patients with unfavorable outcome.

Paper IV aimed at assessing the effect of different blood pressure levels on global cerebral energy metabolism in comatose patients resuscitated from OHCA. In this double-blinded trial, 60 comatose OHCA patients were randomly assigned to low (63 mmHg) or high (77 mmHg) MAP. Targeting a higher MAP 180 min after ROSC did not significantly improve cerebral energy metabolism or oxygenation within 96 hours of post-resuscitation care. We could predict poor neurological outcome based on specific metabolic patterns obtained by JBM.

Overall, the studies described in this thesis have given new insights into pathophysiological mechanisms following transient global cerebral ischemia after cardiac arrest. Microdialysis of cerebral venous blood in the jugular bulb have shown promise to give important information of cerebral energy metabolism. Main findings indicated persistent compromised cerebral oxidative metabolism in the majority of resuscitated comatose patients, and that mitochondrial oxidative energy metabolism can be evaluated online by performing microdialysis of the draining venous blood. However, detection of isolated cerebral metabolic perturbations in cardiac arrest patients were dependent on a certain degree of brain injury. Patients with a poor clinical outcome exhibited significantly worse biochemical patterns, illustrating that insufficient tissue reperfusion and oxygenation during the initial hours after ROSC were essential factors determining neurological outcome.

Future efforts to improve outcomes after OHCA may focus on treatment that augments cerebral energy metabolism during early post-resuscitation care.