Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: Effects on nitrogen balance, insulin resistance, and substrate oxidation
Abstract
Objectives: To estimate the efficacy and metabolic effects of growth hormone substitution as intravenous pulses together with alanyl-glutamine supplementation and tight blood glucose control in prolonged critical illness. Design: Prospective double-blind, randomized trial with open-label control arm.
Setting: Intensive care unit of tertiary level hospital. Patients: Thirty multiple trauma patients (median Injury Severity Score 34).
Interventions: Patients were randomized, at day 4 after trauma, to receive intravenous alanyl-glutamine supplementation (0.3 g/kg.day-1 from day 4 until day 17) and intravenous growth hormone (administered days 7-17, full dose 50 µg/kg.day-1 from day 10 onward) (group 1, n = 10) or alanyl-glutamine and placebo (group 2, n = 10). Group 3 (n = 10) received isocaloric isonitrogenous nutrition (proteins 1.5 g/kg.day-1) without alanyl-glutamine.
Measurements and Main Results: Cumulative nitrogen balance for the whole study period was -97 +- 38 g of nitrogen for group 1, -193 +- 50 g of nitrogen for group 2, and -198 +- 77 g of nitrogen for group 3 (p < .001). This represents a daily saving of 300 g of lean body mass in group 1.
Insulin-mediated glucose disposal, during euglycemic clamp, as a measure of insulin sensitivity, significantly worsened between days 4 and 17 in group 1 but improved in groups 2 and 3. Group 1 required significantly more insulin to control blood glucose, resulting in higher insulinemia (~70 mIU in group 1 vs. ~25 mIU in groups 2 and 3).
Despite this, growth hormone treatment caused an increase in plasma nonesterified fatty acid (~0.5-0.6 mM in group 1 in comparison with ~0.2-0.3 mM in groups 2 and 3) but did not influence lipid oxidation. There were no differences in morbidity, mortality, or 6-month outcome among the groups.
Conclusions: Treatment with frequent intravenous pulses of low-dose growth hormone together with alanyl-glutamine supplementation improves nitrogen economy in patients with prolonged critical illness after multiple trauma but worsens insulin sensitivity. Tight blood glucose control is possible but requires higher doses of insulin.