Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients

Abstract

An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic “flow” phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48–60 h after injury in 20 severely injured (injury severity score [ISS] = 31 ± 2), highly catabolic (N loss = 19 ± 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 ± 5% basal energy expenditure [BEE]), adult (age 46 ± 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 × REE calories, 250 mg N·kg −1·d −1). Group H ( n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg·kg −1·d −1) and Group C ( n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (−41 ± 18 vs −121 ± 19 mg N·kg −1·d −1, P = 0.001); whole body protein synthesis rate is 28 ± 2% ( P = 0.05) higher; protein synthesis efficiency is higher (62 ± 2% vs 48 ± 3%, P = 0.010); plasma glucose level is significantly elevated (256 ± 25 vs 202 ± 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 ± 0.20 vs 1.56 ± 0.6 mg N·kg −1·min −1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis ( P = 0.006) and free fatty acid reesterification ( P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized ( P < 0.05) and 3-methylhistidine excretion is significantly low ( P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.