Bedside interpretation of cerebral energy metabolism utilizing microdialysis in neurosurgical and general intensive care

Abstract

The microdialysis technique was initially developed for monitoring neurotransmitters in animals. In 1995 the technique was adopted to clinical use and bedside enzymatic analysis of glucose, pyruvate, lactate, glutamate and glycerol. Under clinical conditions microdialysis has also been used for studying cytokines, protein biomarkers, multiplex proteomic and metabolomic analyses as well as for pharmacokinetic studies and evaluation of blood-brain barrier function. This review focuses on the variables directly related to cerebral energy metabolism and the possibilities and limitations of microdialysis during routine neurosurgical and general intensive care. Our knowledge of cerebral energy metabolism is to a large extent based on animal experiments performed more than 40 years ago. However, the different biochemical information obtained from various techniques should be recognized. The basic animal studies analyzed brain tissue homogenates while the microdialysis technique reflects the variables in a narrow zone of interstitial fluid surrounding the probe. Besides the difference of the volume investigated, the levels of the biochemical variables differ in different compartments. During bedside microdialysis cerebral energy metabolism is primarily reflected in measured levels of glucose, lactate and pyruvate and the lactate to pyruvate (LP) ratio. The LP ratio reflects cytoplasmatic redox-state which increases instantaneously during insufficient aerobic energy metabolism. Cerebral ischemia is characterized by a marked increase in intracerebral LP ratio at simultaneous decreases in intracerebral levels of pyruvate and glucose. Mitochondrial dysfunction is characterized by a moderate increase in LP ratio at a very marked increase in cerebral lactate and normal or elevated levels of pyruvate and glucose. The patterns are of importance in particular for interpretations in transient cerebral ischemia. A new technique for evaluating global cerebral energy metabolism by microdialysis of the draining cerebral venous blood is discussed. In experimental studies it has been shown that pronounced global cerebral ischemia is reflected in venous cerebral blood. Jugular bulb microdialysis has been investigated in patients suffering from subarachnoid hemorrhage, during cardiopulmonary bypass and resuscitation after out of hospital cardiac arrest. Preliminary results indicate that the new technique may give valuable information of cerebral energy metabolism in clinical conditions when insertion of an intracerebral catheter is contraindicated.

Negligible In Vitro Recovery of Macromolecules from Microdialysis Using 100 kDa Probes and Dextran in Perfusion Fluid

“…To monitor these molecules, catheters with larger pore sizes are necessary [ 7 , 14 ], while measurement of small molecules must not be affected. The recovery of glucose, pyruvate, and lactate—with molecular weights of approximately 180 Da, 87 Da, and 90 Da, respectively [ 1 , 2 ]—has been widely studied and well-established in clinical practice [ 4 – 6 ]. Hutchinson et al [ 15 ] demonstrated equal relative recovery for small molecules using the 20 kDa and 100 kDa catheters under in vitro and in vivo conditions but did not validate the use of dextran.…”

“…Microdialysis catheters with a cut-off value of 20 kDa are in routine clinical use. These catheters easily allow the passage of small molecules such as glucose and its metabolites [ 5 , 6 ]. Recently, there has been an interest in assessing larger molecules in brain interstitial fluid.…”

A randomized, double-blind trial comparing the effect of two blood pressure targets on global brain metabolism after out-of-hospital cardiac arrest

“…The interpretations of observed changes in the levels of the biochemical variables after ROSC are based on our previous experimental studies of transient global cerebral ischemia evaluated from whole brain tissue homogenates as well as intracerebral microdialysis. These studies were summarized in a recent review [39].…”

“…Definitions of the biochemical patterns for cerebral ischemia and mitochondrial dysfunction were based on principles obtained from intracerebral microdialysis [22,39]. In this study, LP ratio > 16 at pyruvate < 70 µM was classified as a pattern indicating ischemia, and LP ratio > 16 at pyruvate > 70 µM demonstrated mitochondrial dysfunction [35,39].…”

“…The primary outcome was the difference between time-averaged means of microdialysis parameters and LP ratio (intervals of 12 h) between low vs high MAP group within 96 h of post-resuscitation care. Secondary outcomes of clinical interest were to compare (i) variables reflecting cerebral energy metabolism and patterns of ischemia and mitochondrial dysfunction in patients with unfavorable and favorable neurological outcome [39], (ii) cerebral oxygenation (rSO 2 ) between MAP groups, (iii) biochemical variables in relation to critical clinical episodes such as EEG-verified seizures and hypotension and (iv) neurological outcome at hospital discharge and 90 days after OHCA. Additional secondary outcomes were association between JBM markers, neurological outcome and brain injury defined by NSE levels at 48 h. As the study was planned and powered for the primary outcome, the secondary outcomes should be considered exploratory and interpreted with caution.…”