Effects of lactate-based therapies on intracranial pressure and brain metabolism of patients with acute brain injury: a systematic review

Sodium lactate–based solutions have been proposed as an alternative to conventional osmotic therapies for intracranial pressure (ICP) control in acute brain injury (ABI). Beyond their osmotic properties, lactate may also act as a cerebral metabolic substrate, although its effects appear context-dependent. The aim of this systematic review was to synthesize available data on lactate-based therapies in ABI, focusing on their effects on intracranial dynamics, cerebral metabolism and neurological outcomes to guide future clinical translation. We performed a systematic review of preclinical and clinical studies evaluating exogenous sodium lactate administration in ABI, including traumatic brain injury, ischemic stroke, and cardiac arrest. Outcomes of interest included intracranial pressure control, cerebral metabolism, cerebral perfusion and oxygenation, systemic hemodynamics, safety, and functional recovery. Twelve preclinical and twelve clinical studies were included. Across most models, sodium lactate was effective in reducing ICP and at least as effective and safe as mannitol or hypertonic saline in clinical settings. Several studies reported improved systemic hemodynamic tolerance compared with conventional osmotherapy. Preclinical and clinical metabolic data demonstrated that lactate can be taken up and oxidized by the injured brain; however, metabolic benefits were inconsistent and appeared dependent on preserved oxidative metabolism, baseline metabolic status, timing, and dose. Functional outcome data were limited but suggested potential cognitive and neurological benefits in both experimental and selected clinical settings. Sodium lactate is an effective therapy for intracranial hypertension and may offer additional metabolic and systemic advantages in ABI patients under specific conditions. Its metabolic effects appear critically dependent on preserved oxidative capacity, highlighting the need for improved patient selection and the potential role of metabolic monitoring to guide therapy. The impact of lactate-based treatments on meaningful functional outcomes remains uncertain and warrants further investigation in targeted clinical trials.