title: Effect of a hypertonic balanced ketone solution on plasma, CSF and brain beta-hydroxybutyrate levels and acid-base status.
abstract: OBJECTIVE
  Although glucose is the main source of energy for the human brain, ketones play an important role during starvation or injury. The purpose of our study was to investigate the metabolic effects of a novel hypertonic sodium ketone solution in normal animals.
  
  
  METHODS
  Adult Sprague-Dawley rats (420-570 g) were divided into three groups of five, one control and two study arms. The control group received an intravenous infusion of 3 % NaCl at 5 ml/kg/h. The animals in the two study arms were assigned to receive one of the two formulations of ketone solutions, containing hypertonic saline with 40 and 120 mmol/l beta-hydroxybutyrate, respectively. This was infused for 6 h and then the animal was euthanized and brains removed and frozen.
  
  
  RESULTS
  Both blood and cerebrospinal fluid (CSF) levels of beta-hydroxybutyrate (BHB) demonstrated strong evidence of a change over time (p < 0.0001). There was also strong evidence of a difference between groups (p < 0.0001). Multiple comparisons showed all these means were statistically different (p < 0.05). Measurement of BHB levels in brain tissue found strong evidence of a difference between groups (p < 0.0001) with control: 0.15 mmol/l (0.01), BHB 40: 0.19 mmol/l (0.01), and BHB 120: 0.28 mmol/l (0.01). Multiple comparisons showed all these means were statistically different (p < 0.05). There were no differences over time (p = 0.31) or between groups (p = 0.33) or an interaction between groups and time (p = 0.47) for base excess.
  
  
  CONCLUSIONS
  The IV infusions of hypertonic saline/BHB are feasible and lead to increased plasma, CSF and brain levels of BHB without significant acid/base effects.
authors.affiliation: Department of Intensive Care , Griffiths University, Logan Hospital, QLD, 4131, Brisbane, Australia. hayden_white@health.qld.gov.au
authors.forename: Hayden
authors.initials: H
authors.lastname: White
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Venkatesh
authors.forename: Mark
authors.initials: M
authors.lastname: Jones
authors.forename: Simon
authors.initials: S
authors.lastname: Worrall
authors.forename: Teong
authors.initials: T
authors.lastname: Chuah
authors.forename: Jenny
authors.initials: J
authors.lastname: Ordonez
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001774:Blood Chemical Analysis; D001923:Brain Chemistry; D002555:Cerebrospinal Fluid / Q000737:chemistry; D007262:Infusions, Intravenous; D007657:Ketone Bodies / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D007657:Ketone Bodies; D012462:Saline Solution, Hypertonic; D020155:3-Hydroxybutyric Acid