Human growth hormone for treating burns and skin graft donor sites

Growth hormone is produced by the pituitary gland. For decades, it could only be obtained by extraction from pituitary glands but more recently it has been produced through genetic engineering and made available for therapy as recombinant human growth hormone (rhGH). The aim of this review was to determine the effects of rhGH when used to treat burns and skin graft donor sites and to determine its safety compared with other treatments.

A burn that affects more than 40% of total body surface area affects the entire body. In people with such large burns, metabolism increases, as represented by a higher heart rate. This state of increased metabolism is called hypermetabolism. Hypermetabolism consumes high levels of energy Part of this energy is obtained through the breakdown of the patient’s own muscles, which leads to wasting. This breaking down of tissues into smaller molecules to release energy is called catabolism. However, such catabolism does not provide sufficient energy for the hypermetabolic state. This shortage of energy and building molecules leads to prolonged burn wound and donor site healing. In children, this shortage also leads to growth retardation. This catabolic state can be treated with anabolic agents that reverse the protein breakdown. One of the anabolic agents recommended for such a treatment approach is recombinant growth hormone.

We found 13 eligible randomised controlled trials (RCTs) involving 701 people for inclusion in this review. There is some evidence that recombinant growth hormone therapy in people with burns covering more than 40% of the total body surface area helps burn wounds and donor sites heal more rapidly and reduce the length of hospital stay, without increased mortality or increased scarring. We found it difficult to assess the quality of these studies due to poor reporting therefore we cannot be completely confident in their results.

Authors' conclusions: 

There is some evidence that using rhGH in people with large burns (more than 40% of the total body surface area) could result in more rapid healing of the burn wound and donor sites in adults and children, and in reduced length of hospital stay, without increased mortality or scarring, but with an increased risk of hyperglycaemia. This evidence is based on studies with small sample sizes and risk of bias and requires confirmation in higher quality, adequately powered trials.

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Background: 

Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is frequently an increase in protein breakdown and a decrease in protein synthesis. This change in protein metabolism correlates with poor wound healing of the burn and donor sites.

Objectives: 

To determine the effects of rhGH on the healing rate of burn wounds and donor sites in people with burns.

Search strategy: 

For this first update we searched the Cochrane Wounds Group Specialised Register (searched 04 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2014, Issue 3); Ovid MEDLINE (1950 to September Week 4 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations September 8, 2014); Ovid EMBASE (1980 to 2014 Week 35); and EBSCO CINAHL (1982 to 8 September 2014).

Selection criteria: 

Randomised controlled trials (RCTs) comparing rhGH with any comparator intervention, e.g. oxandrolone or placebo, in adults or children with burns.

Data collection and analysis: 

Two review authors independently selected studies, assessed trial quality and extracted data. The primary outcomes were the healing of the burn wound and donor sites and the occurrence of wound infections. The secondary outcomes were mortality rate, length of hospital stay, scar assessment, and adverse events: hyperglycaemia and septicaemia.

Main results: 

We included 13 RCTs (701 people). Six of the RCTs included only children aged 1 to 18 years and seven involved only adults (from 18 to 65 years of age). The mean TBSA of the included participants was greater than 49%. Twelve studies compared rhGH with placebo and one study compared rhGH with oxandrolone. Two trials found that compared with placebo, burn wounds in adults treated with rhGH healed more quickly (by 9.07 days; 95% confidence interval (CI) 4.39 to 13.76, I² = 0%). The donor site healing time was significantly shorter in rhGH-treated adults compared with placebo-treated participants (by 3.15 days; 95% CI 1.54 to 4.75, I² = 0%). Two studies in children with the outcome of donor site healing time could be pooled and the donor site healing time was shorter in the rhGH-treated children (by 1.70 days; 95% CI 0.87 to 2.53, I² = 0%). No studies reporting the outcome of wound infection were found. The incidence of hyperglycaemia was higher in adults during rhGH treatment compared with placebo (risk ratio (RR) 2.43; 95% CI 1.54 to 3.85), but not in children. Pooling the studies of adults and children yielded a significantly higher incidence of hyperglycaemia in the rhGH-treated participants (RR 2.65; 95% CI 1.68 to 4.16).

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