BACKGROUND/OBJECTIVE: Traumatic brain injury (TBI) is a life-threatening critical neurological injury resulting in widespread metabolic dysfunction in need of novel metabolic therapy. Exogenous lactate appears to improve brain metabolism, but the dose of lactate required remains uncertain. However, the ideal dose of lactate remains unclear. We present a comparison of low vs high dose exogenous sodium lactate infusion in a small cohort and the previous existing literature. We propose a systematic protocol to better study the question of dose-effect n in a future larger study. METHODS: We analyzed the metabolic and physiologic effects of various doses of exogenous sodium lactate infusion (ELI) in the existing published literature and our own, single center cohort of patients with coma from severe TBI. Low dose ELI targeting arterial lactate concentration of 2-3 mMol was compared with high dose ELI targeting 4-6 mM. Effects of ELI on brain metabolism and intracranial pressure (ICP) were reviewed. A precision high-dose protocol was piloted and results compared against the existing literature. RESULTS: Across various studies, metabolic response to ELI was variable and not consistently beneficial. High-dose ELI targeting arterial concentration of 4-6 mM resulted in consistent metabolic improvement and in ICP reduction (p < 0.01). The precision high dose protocol reliably resulted in higher arterial concentration. CONCLUSIONS: High dose ELI appears to have more consistent beneficial effects on brain metabolism and intracranial pressure. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02776488. Date registered: 2016-05-17. Retrospectively Registered.