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.

创伤性脑损伤 (TBI) 后，脑乳酸/丙酮酸比 (LPR) 升高反映了能量代谢受损。升高的 LPR 与 TBI 后的不良结果和死亡率相关。我们前瞻性地招募了需要神经重症监护和多模式监测的 TBI 患者，并采用了针对 LPR 的分层管理方案。我们确定了尽管有足够的脑葡萄糖和氧气供应但 LPR 持续升高的患者，我们在临床上将其归类为脑“线粒体功能障碍”（MD）。在患有 TBI 和 MD 的患者中，我们通过逆向透析将 2,3- ¹³ C ₂琥珀酸二钠 (12 mmol/L) 注入大脑的监测区域。我们恢复了¹³通过微透析和利用核磁共振波谱 (NMR) 进行 C 标记的代谢物进行鉴定和定量。

在接受完整监测的 33 名患者中，73% 在监测期间的某个时间点患有 MD。在 5 名多模态定义的 MD 患者中，琥珀酸盐给药导致 LPR 降低（-12%）和脑葡萄糖升高（+17%）。微透析液的 NMR 证明外源性¹³ C 标记的琥珀酸盐通过三羧酸循环在细胞内代谢。通过使用包含颅内压、脑组织氧合和微透析参数的分层临床算法靶向 LPR，我们确定了需要神经重症监护的 TBI 患者的 MD。在这些情况下，局部琥珀酸盐给药改善了能量代谢，LPR 降低证明了这一点。琥珀酸盐值得进一步研究用于 TBI 治疗。