A Combined Microdialysis and FDG-PET Study for Detection of Brain Injury in Comatose Survivors Resuscitated From Out-of-hospital Cardiac Arrest - a Pilot Study

Background Survival rates around 50 % are reported in comatose patients treated with hypothermia in Intensive Care Unit (ICU) after out-of-hospital cardiac arrest (OHCA). The high risk of ICU death is generally due to the primary hypoxic-ischemic insult, and subsequently secondary brain damage caused by prolonged insufficient cerebral blood flow (CBF), disturbed autoregulation, ischemia-reperfusion injury and compromised cerebral energy metabolism injury. Conclusive evidence of secondary cerebral ischemia following cardiac arrest has been elusive. Secondary injury is a significant determinant of neurologic outcome, and alleviating its deleterious effects is a mainstay of post-cardiac arrest management. This far, the clinicians still need more accurate monitoring methods to identify and manage potential reversible ongoing brain ischemia, and predicting early neurological outcome in the ICU. Methods measuring global brain ischemia and reflecting metabolic perturbations after resuscitation are needed for a more individualized post-resuscitation care-and target-driven therapy to improve patient outcome.

Jugular bulb microdialysis (JBM) allows global cerebral metabolic variables of the draining venous blood to be monitored continuously and provides data on substrate supply and metabolism at the cellular level in the brain. The ability to measure global brain metabolites concentration of glucose, pyruvate, lactate, lactate to pyruvate ratio (LPR), glutamate and glycerol at the bedside has provided the option of utilizing JBM as a clinical brain-monitor. High LPR > 30 is considered a robust indicator of anaerobic metabolism (low pyruvate) and is an independent predictor of mortality and unfavorable outcome in traumatic brain injury among patients monitored with MD (1-6).

Our group has recently published that I) metabolic monitoring in the jugular bulb is representative of the overall cerebral metabolism and can be used in the diagnosis of compromised global cerebral metabolism during cardiac surgery (7) and II) global JBM indicating isolated early brain injury was found after OHCA and consecutive resuscitation (study in press) III) preliminary JBM data indicates that approximately 30 % of comatose OHCA survivors (cerebral performance category 3-5, poor neurological outcome) are suffering from early secondary brain ischemia (8).

Further advances in the knowledge of cerebral metabolism have been achieved by applying positron emission tomography (PET) of 18-Fluor deoxyglucose ([F-18]-FDG) to OHCA patients, enabling cerebral metabolic rate of glucose CMRglc to be quantified (9-10). PET provides a global metabolic map of the whole brain but only for the duration of the scan. FDG-PET measurement is primarily a marker of glucose uptake, which cannot be used to determine the fate of this brain fuel. At the same time, the JBM variables have the potential of displaying several options regarding the fate of glucose and signs of metabolic crisis. It is in this context that the present study attempts to determine if there is a metabolic crisis due to ischemia or due to mechanisms other than ischemia by examining global brain tissue with combined positron emission tomography and jugular bulb microdialysis. The sensitivity of JBM to detect relevant secondary brain injury in cardiac arrest patients is further investigated through comparative imaging with PET-CT.

Aim The study aim to use 18-Fluorodeoxyglucose positron emission tomography (PET) combined with jugular bulb microdialysis to investigate pathophysiological brain derangements following cardiac arrest.