Elevated Intracranial Pressure, Low Cerebral Perfusion Pressure, and Impaired Brain Metabolism Correlate with Fatal Outcome After Severe Brain Injury

Hejčl, Aleš; Bolcha, Martin; Procházka, Jan; Hušková, E.; Sameš, Martin

doi:10.1055/s-0031-1275745

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…39 We believe that these classification algorithms are limited by not considering other common physiological TBI derangements than MD that have been shown to result in deranged LPR in prospective studies, such as high ICP, and low CPP or PbtO 2 . 38,40,41 However, these studies did not follow a structured, tiered protocol as in the current study specifically targeting LPR. Overall, while different pathological states incorporating microdialysate markers have been described, this is the first study to fully incorporate other multimodal metrics using a tiered therapeutic protocol targeting LPR establishing a state that we can reliably attribute to mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 97%

Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Khellaf

García

Tajsic

et al. 2021

J Cereb Blood Flow Metab

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Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral ‘mitochondrial dysfunction’ (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification. Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(−12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.

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