Brain Lactate Metabolism in Humans With Subarachnoid Hemorrhage

Abstract

Background and Purpose-Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Methods-Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO 2 ) were studied. Samples with elevated CMD lactate (Ͼ4 mmol/L) were matched to PbtO 2 and CMD pyruvate and categorized as hypoxic (PbtO 2 Ͻ20 mm Hg) versus nonhypoxic and hyperglycolytic (CMD pyruvate Ͼ119 mol/L) versus nonhyperglycolytic. Results-Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75% Generally considered a product of anaerobic metabolism, endogenous lactate is pivotal for neuronal survival, 3,4 particularly in conditions of acute injury. 5,6 Cerebral microdialysis (CMD) enables quantification of brain metabolites in cerebral extracellular fluid and provides information about energy metabolism and the extent of aerobic versus anaerobic glycolysis. 7 Further insights can be obtained by combining CMD with brain oxygen (PbtO 2 ) monitoring to quantify the extent of brain hypoxia. 8 Brain lactate metabolism after subarachnoid hemorrhage (SAH) has not been fully elucidated. We hypothesized that elevations of brain lactate occur in poor-grade SAH patients either as the consequence of cerebral hyperglycolysis or as the consequence of brain hypoxia, and that differences in the patterns of elevated brain lactate may be associated with outcome. Patients and MethodsWe studied comatose patients with aneurysmal SAH admitted to the Division of Neurocritical Care, Hospital of the University of Pennsylvania, Philadelphia, and in the Department of Critical Care, Lausanne University Hospital, Switzerland, over a 4-year period and who underwent combined CMD-PbtO 2 monitoring. Approval was obtained by local Institutional Review Board. Patients had at least 24 hours of valid intracranial monitoring and were alive for Ͼ5 days. Intracranial monitoring was performed as part of standard care, as previously described. 9 Patients were managed according to a standard protocol in both centers; 10 therapeutic targets were set to avoid cerebral perfusion pressure Ͻ60 mm Hg and PbtO 2 Ͻ20 mm Hg. CMD catheters (CMA 70; CMA Microdialysis AB; flow rate, 0.3 L/min) and PbtO 2 probes (Licox; Integra Neurosciences) were inserted via a triple-lumen bolt and placed into visually normal white matter. CMD samples were collected every 60 minutes and analyzed for concentrations of lactate, pyruvate, and glucose. Outcome at 6 months was assessed with the modified Rankin Scale score by 1 neurologist and 1 neurointensive care nurse who were blinded to physiological data.First hour of monitored data, artifacts, and data points outside physiological ranges were excluded. Brain lactate elevations ...

Systematic and Comprehensive Literature Review of Publications on Direct Cerebral Oxygenation Monitoring

“…They report that: "Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia 28% (interquartile range 9%-95%) in nonsurvivors". This study supports the current clinical practise that pbtO2 below 20mmHg signals cerebral ischemia and may call for therapeutic interventions [217].…”

“…There are publications also from Australia [38,[198][199][200], Austria [53,85], Brazil [58], Canada [93,118,132,135,139], China [9, 201,202], Croatia [203], the Czech Republic [204], Denmark [134]; Finland [134], France [43,77,114,205,206], Greece [207], Hungary [141], India [208], Japan [140,146,167,209], Portugal [64]; Russia [210,211], Singapore [2,4,10,16,74,212,213]; Serbia [214]; South Africa [26,28,35], South Korea [127], Sweden [90,134,215], Switzerland [11,216,217]...…”

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

“…80,81 Lactate and Clinical Outcome Elevated extracellular lactate levels in 'normal' non-hypoxic white matter after subarachnoid hemorrhage were associated with better outcome compared with patients with hypoxic white matter. 82 Reference was made to lactate metabolism that was not measured in this and the authors' subsequent TBI study, 39 and the rise in lactate level must be due to glucose metabolism. This is an important distinction because the context presented in the introductions and discussions of these reports is that the lactate may be metabolized as neuronal fuel in injured brain.…”

Unraveling the complexities of invasive multimodality neuromonitoring

“…Consistent with this view, a prior study showed that patients with SAH who had isolated lactate elevations experienced better than expected outcomes, whereas patients in whom elevated lactate coincided with brain hypoxia fared poorly. 43 Finally, extracellular levels of the excitatory neurotransmitter glutamate also correlate with markers of secondary brain injury and poor outcome. 7,65 Seizures and reduced CPP are both associated with abnormally elevated glutamate after TBI.…”