Systemic metabolic effects of combined insulin-like growth factor-I and growth hormone therapy in patients who have sustained acute traumatic brain injury.
OBJECTIVE
Hypermetabolism, hypercatabolism, refractory nitrogen wasting, hyperglycemia, and immunosuppression accompany traumatic brain injury (TBI). Pituitary dysfunction occurs, affecting growth hormone (GH) and plasma insulin-like growth factor-I (IGF-I) concentrations. The authors evaluated whether combination IGF-I/GH therapy improved metabolic and nutritional parameters after moderate to severe TBI.


METHODS
The authors conducted a prospective, randomized, double-blind study comparing combination IGF-I/GH therapy and a placebo treatment. Ninety-seven patients with TBI were enrolled in the study within 72 hours of injury and were assigned to receive either combination IGF-I/GH therapy or placebo. All patients received concomitant nutritional support. Insulin-like growth factor-I was administered by continuous intravenous infusion (0.01 mg/kg/hr), and GH (0.05 mg/kg/day) was administered subcutaneously. Placebo control group patients received normal saline solution in place of both agents. Nutritional and metabolic monitoring continued throughout the 14-day treatment period. The two groups did not differ in energy expenditure, nutrient intake, or use of insulin treatment. The mean daily serum glucose concentration was higher in the treatment group (123 +/- 24 mg/dl) than in the control group (104 +/- 11 mg/dl) (p < 0.03). A positive nitrogen balance was achieved within the first 24 hours in the treatment group and remained positive in that group throughout the treatment period (p < 0.05). This pattern was not observed in the control group. Plasma IGF-I concentrations were above 350 ng/ml in the treatment group throughout the study period. Overall, the mean plasma IGF-I concentrations were 1003 +/- 480.6 ng/ml in the treatment group and 192 +/- 46.2 ng/ml in the control group (p < 0.01).


CONCLUSIONS
The combination of IGF-I and GH produced sustained improvement in metabolic and nutritional endpoints after moderate to severe acute TBI.
Hatton
Jimmi
J
Colleges of Pharmacy, Public Health, and Medicine, University of Kentucky, Lexington, Kentucky 40536-0509, USA. jhatt1@uky.edu
Kryscio
Richard
R
Ryan
Melody
M
Ott
Linda
L
Young
Byron
B
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015600:Glasgow Coma Scale; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D001786:Blood Glucose; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I