title: Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury.
abstract: BACKGROUND
  Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined.
  
  
  METHODS
  Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily.
  
  
  RESULTS
  Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 μmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 μmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 μmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 μmol/ l; p < 0.05, ANOVA, post hoc Dunn's test).
  
  
  CONCLUSIONS
  High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT02130674. Registered 5 April 2014.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Nägeli
authors.forename: Mario
authors.initials: M
authors.lastname: Fasshauer
authors.forename: Jutta
authors.initials: J
authors.lastname: Sommerfeld
authors.forename: Angela
authors.initials: A
authors.lastname: Fendel
authors.forename: Giovanna
authors.initials: G
authors.lastname: Brandi
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
mesh_terms: D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D001930:Brain Injuries / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D004151:Dipeptides / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism*; D005973:Glutamine / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D004151:Dipeptides; D005973:Glutamine; D018698:Glutamic Acid; D000409:Alanine