Exogenous Lactate Infusion (ELI) in Severe TBI pilot study

Abstract

Objective Traumatic brain injury (TBI) is a life-threatening critical neurological injury in need of novel medical therapies. Metabolic dysfunction occurs after TBI and may be a target for medical therapy. The objective was to explore the safety of a short term an infusion of exogenous sodium lactate (ELI) as a potential medical therapy to enhance brain metabolism. Methods This was a non-randomized single arm, single center observational safety study of a three-hour infusion of exogenous sodium lactate (ELI) in 16 patients with coma from severe TBI. Patients were consented and enrolled from a convenience sample of TBI patients GCS 3–8 at time of infusion. Two doses of ELI were explored with 11 subjects receiving low dose ELI and 6 subjects receiving high dose ELI. Intracranial pressure (ICP), heart rate, brain tissue oxygen (PbtO2), serum sodium, serum pH and systemic oxygenation were monitored during the infusion. Assessment for acute kidney injury, cardiac arrythmias, and acute lung injury were performed. Assessment of mortality was performed at 30 days. Results Both low dose and high dose ELI resulted in elevations of serum lactate concentration (mean 1.6 ± 0.9 mMol vs 5.36 ± 0.71 mMol, respectively). During the high dose ELI, point of care monitoring of blood lactate levels permitted titration in the desired range. ICP was reduced during high dose ELI (p < 0.01) but not in the low dose arm (p < 0.058). PbtO2 was transiently reduced in the high dose ELI arm. Oxidative metabolism increased by 8% as measured by changes in superoxide dismutase (SOD 2) (p < 0.006). There were no serious adverse events and no mortality in either arm. Conclusions A three-hour infusion of exogenous sodium lactate appears to be safe and appears to result in short term changes in ICP and brain oxidative metabolism in patients with severe TBI. Trial Registration ClinicalTrials.gov ID NCT02776488. Retrospectively Registered, and planned next stage randomized trial.