Combination of recombinant human growth hormone and propranolol decreases hypermetabolism and inflammation in severely burned children

Pediatr Crit Care Med. 2008 Mar;9(2):209-16. doi: 10.1097/PCC.0b013e318166d414.

Abstract

Objective: Recombinant human growth hormone (rhGH) is a salutary modulator of posttraumatic metabolic responses. However, rhGH administration is associated with deleterious side effects, such as hyperglycemia, increased free fatty acids, and triglycerides, which limit its use. Administration of beta-blocker attenuates cardiac work and resting energy expenditure after severe thermal injury and improves fat metabolism and insulin sensitivity. Therefore, the combination of rhGH plus propranolol appears ideal. The aim of the present study was to determine whether rhGH plus propranolol improves hypermetabolism and the inflammatory and acute phase response after severe burn without causing adverse side effects.

Design: Prospective randomized control trial.

Setting: Shriners Hospitals for Children.

Patients: Fifteen pediatric patients with burns > 40% total body surface area, 0.1-16 yrs of age, admitted within 7 days after burn. Fifteen children were matched for burn size, age, gender, inhalation injury, and infection and served as controls.

Interventions: Patients in the experimental group received rhGH (0.2 mg/kg/day) and propranolol (to decrease heart rate by 15%) for > or = 15 days.

Measurements and main results: Outcome measurements included resting energy expenditure, body composition, acute phase proteins, and cytokines. Both cohorts were similar in age, burn size, gender, and accompanying injuries. Percent predicted resting energy expenditure significantly decreased in patients receiving rhGH/propranolol (Delta -5% +/- 8%) compared with controls (Delta +35% +/- 20%) (p < .05). rhGH/propranolol administration significantly decreased serum C-reactive protein, cortisone, aspartate aminotransferase, alanine aminotransferase, free fatty acids, interleukin-6, interleukin-8, and macrophage inflammatory protein-1beta when compared with controls, while growth hormone/propranolol increased serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, growth hormone, prealbumin, and interleukin-7 when compared with placebo (p < .05).

Conclusions: rhGH in combination with propranolol attenuates hypermetabolism and inflammation without the adverse side effects found with rhGH therapy alone.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / immunology
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Burns / drug therapy
  • Burns / immunology*
  • Child
  • Cytokines / blood
  • Cytokines / drug effects
  • Drug Therapy, Combination
  • Energy Metabolism / drug effects*
  • Female
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / immunology
  • Human Growth Hormone / pharmacology
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Inflammation / drug therapy
  • Male
  • Propranolol / administration & dosage
  • Propranolol / immunology
  • Propranolol / pharmacology
  • Propranolol / therapeutic use*
  • Prospective Studies
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Texas
  • Trauma Severity Indices*

Substances

  • Adrenergic beta-Antagonists
  • Cytokines
  • Recombinant Proteins
  • Human Growth Hormone
  • Propranolol