Hypertonic lactate to improve cerebral perfusion and glucose availability after acute brain injury

Abstract

Objectives: Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Design: Prospective study (clinicaltrials.gov NCT01573507). Setting: Academic ICU. Patients: Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Interventions: Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 μmol/kg/min) administered 39 hours (26-49 hr) from injury. Measurements and Main Results: We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral micro-dialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdi-alysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). Conclusions: This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.