Laurent Carteron1,2,3, Daria Solari1,2, Camille Patet1,2, Hervé Quintard4, John-Paul Miroz1,2, Jocelyne Bloch5, Roy T Daniel5, Lorenz Hirt6, Philippe Eckert1, Pierre J Magistretti7,8,9, Mauro Oddo1,2. 1. Department of Intensive Care Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland. 2. Neuroscience Critical Care Research Group, CHUV, University of Lausanne, Lausanne, Switzerland. 3. Department of Anesthesiology and Intensive Care Medicine, University Hospital of Besançon, University of Bourgogne - Franche-Comté, Besançon, France. 4. Department of Anesthesia and Intensive Care, Nice University Hospital, Nice, France. 5. Department of Clinical Neurosciences, Service of Neurosurgery, CHUV, University of Lausanne, Lausanne, Switzerland. 6. Department of Clinical Neurosciences, Service of Neurology, CHUV, University of Lausanne, Lausanne, Switzerland. 7. Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia. 8. Centre de Neurosciences Psychiatriques, Department of Psychiatry, CHUV, Lausanne, Switzerland. 9. Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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 microdialysis 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 microdialysis 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.
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 microdialysis 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 microdialysis 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.
Authors: Peter P de Smalen; Tom J van Ark; Robert J Stolker; Arnaud J P E Vincent; Markus Klimek Journal: J Neurosurg Anesthesiol Date: 2020-01 Impact factor: 3.969