Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L‐lactate

Abstract

Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant Sodium L-Lactate infusion in eleven moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of Sodium L-Lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from 0.92 to 1.84 mM) results in an increase in AVDlac from −0.078 mM to 0.090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury.

The tortuous path of lactate shuttle discovery: From cinders and boards to the lab and ICU

“…Recognizing that lactate is produced under full aerobic conditions, as well as understanding the roles of lactate shuttling in biology, is providing new opportunities to treat the ill and injured. For example, exogenous L-lactate vascular infusion is being evaluated in the treatment of heart failure, 175 , 176 , 177 TBI, 19 , 113 , 178 , 179 pancreatitis, 104 , 110 hepatitis, 104 dengue fever, 21 and sepsis. 174 …”

Aqp9 Gene Deletion Enhances Retinal Ganglion Cell (RGC) Death and Dysfunction Induced by Optic Nerve Crush: Evidence that Aquaporin 9 Acts as an Astrocyte-to-Neuron Lactate Shuttle in Concert with Monocarboxylate Transporters To Support RGC Function and Survival

“…Conversely, as AQP9 and MCT2 appear to synergistically function to some degree, exogenous application of lactate may potentially enhance survival and function of RGCs. In fact, evidence is accumulating that such an application ameliorated metabolic deficiencies in traumatized brain [ 50 , 51 ]. Given the lack of effective treatments for traumatic optic neuropathy, the exogenous application of lactate might be a future target of study for the treatment of patients with traumatic optic neuropathy.…”

The anaerobic threshold: 50+ years of controversy

“…Aside from exercise, lactataemia also occurs in other conditions such as brain trauma (Brooks & Martin, 2014; Wolahan et al . 2018), sepsis (Marik & Bellomo, 2016), dengue (Somasetia et al . 2014), cancer (Warburg, 1956; Semenza, 2008; San‐Millan & Brooks, 2017), hepatitis and pancreatitis (Hoque et al .…”

“…Beyond exercise: what do elevations in blood [La − ] mean? Aside from exercise, lactataemia also occurs in other conditions such as brain trauma (Brooks & Martin, 2014;Wolahan et al 2018), sepsis (Marik & Bellomo, 2016), dengue (Somasetia et al 2014), cancer (Warburg, 1956;Semenza, 2008;San-Millan & Brooks, 2017), hepatitis and pancreatitis (Hoque et al 2014). In this regard it is important to note that in only one condition, physical exercise, are there definitive data on the significance and meaning of La − accumulation in a stressful condition; specifically, blood [La − ] rises during exercise when blood R a is greater than R d (Stanley et al 1985;Mazzeo et al 1986;Brooks et al 1991;Bergman et al 1999b;Messonnier et al 2013).…”