Hypertonic Sodium Lactate to Alleviate Functional Deficits Following Diffuse Traumatic Brain Injury: An Osmotic or a Lactate-Related Effect?

Abstract

There has been growing interest in the use of hypertonic sodium lactate (HSL) solution following traumatic brain injury (TBI) in humans. However, little is known about the effects of HSL on functional deficits with respect to the hyperosmotic nature of HSL. We have compared the effects of HSL solution and isotonic saline solution using sensorimotor and cognitive tests for 14days post-trauma in animals. Thirty minutes after trauma (impact-acceleration model), anesthetized rats were randomly allocated to receive a 2-h infusion of isotonic saline solution (TBI-saline group) or HSL (TBI-HSL group) (n = 10 rats per group). In another series of experiments using a similar protocol, the effects of equiosmolar doses of HSL and hypertonic saline solution (HSS) were compared in TBI rats (n = 10 rats per group). Blood lactate and ion concentrations were measured during the 2-h infusions. Compared to the TBI-saline group, the TBI-HSL group had a reduced latency to complete the adhesive removal test: 6s (5-9) (median [25-75th centiles]) versus 13s (8-17) on day 7, and 5s (5-9) versus 11s (8-26) on day 14 (P < 0.05), respectively, and a shorter delay to complete the radial arm maze test on day 7: 99s (73-134) versus 176s (127-300), respectively (P < 0.05). However, no differences were found between the TBI-HSL and TBI-HSS groups in neurocognitive tests performance. Compared to the TBI-saline group, the HSL and HSS groups had higher serum osmolality: 318mOsm/Kg (315-321) and 315mOsm/Kg (313-316) versus 307mOsm/Kg (305-309), respectively (P < 0.05), and the HSL group had a higher serum lactate concentration: 6.4mmol/L (5.3-7.2) versus 1.5mmol/L (1.1-1.9) and 1.6mmol/L (1.5-1.7), respectively (P < 0.05). These results indicate that improvements in cognitive and sensorimotor tests with HSL infusion post-TBI could be related to elevation of serum osmolality, not to exogenous administration of lactate.