title: Frequent intravenous pulses of growth hormone together with alanylglutamine supplementation in prolonged critical illness after multiple trauma: effects on glucose control, plasma IGF-I and glutamine.
abstract: OBJECTIVE
  We aim to demonstrate that low dose growth hormone (GH) administered in i.v. pulses every 3h is able to normalize IGF-I levels in subjects with prolonged critical illness, after multiple trauma. We also ask whether it is possible to control glycaemia during such a treatment and how alanylglutamine (AG) supplementation influences plasma glutamine concentration.
  
  
  METHODS
  We used a prospective double-blind (group 1 vs. 2), randomized trial with an open-label control arm (group 3). Thirty multiple trauma patients (median age: 36, 42, 46 years) were randomized on day 4 after trauma to receive (group 1, n=10) i.v. AG supplementation (0.3 g/kg day from day 4 till 17) and i.v. GH (0.05 mg/kg day divided into 8 boluses, maximum dose at 3 AM, administered on days 7-17) or AG and placebo (group 2, n=10). Group 3 (n=10) received isocaloric isonitrogenous (proteins 1.5 g/kg day) nutrition without AG. Glycaemia was controlled by i.v. insulin infusion according to a routine protocol.
  
  
  RESULTS
  GH treatment caused an increase of IGF-I (from median 169 on day 4 to 493 ng/ml on day 17), IGFBP-3 (from 2.4 to 3.2 microg/ml) and a fall in IGFBP-1 (from 11.5 to 3.1 microg/ml), whilst in both groups 2 and 3 these indices remained unchanged. At the end of the study (day 17) IGF-I and IGFBP-1 differed significantly among groups (p=0.008 resp. p=0.010, Kruskal-Wallis). Plasma glutamine remained below the normal range through the study in all groups (median: 0.18-0.30 mM), but had a tendency to rise in group 2 in contrast with a fall in groups 1 and 3 (NS). Group 1 required more insulin (p<0.01) than did the control group but median glycaemia was only 0.4-0.5 mM higher in group 1 (6.5 mM) than in groups 2 and 3 (6.1 resp. 6.0 mM).
  
  
  CONCLUSIONS
  GH (0.05 g/kg day) administered in i.v. pulses is able to normalize IGF-I levels in subjects with prolonged critical illness after trauma. During this treatment, the standard dose of AG prevents worsening of plasma glutamine deficiency and glucose control is possible using routine algorithms, but it requires higher insulin doses.
authors: Department of Anaesthesia and Critical Care Medicine, Charles University, 3rd Faculty of Medicine, Srobarova 50, Prague, Czech Republic. fduska@yahoo.com
authors: Frantisek
authors: F
authors: Duska
authors: Michal
authors: M
authors: Fric
authors: Jaroslav
authors: J
authors: Pazout
authors: Petr
authors: P
authors: Waldauf
authors: Petr
authors: P
authors: Tůma
authors: Jan
authors: J
authors: Pachl
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016638:Critical Illness; D004151:Dipeptides / Q000008:administration & dosage*; D004311:Double-Blind Method; D004333:Drug Administration Routes; D005260:Female; D005973:Glutamine / Q000097:blood*; D013006:Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000188:drug therapy*
chemical_list: D001786:Blood Glucose; D004151:Dipeptides; D005973:Glutamine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C054122:alanylglutamine