Recombinant human growth hormone for treating burns and donor sites
- PMID: 25222766
- PMCID: PMC7119450
- DOI: 10.1002/14651858.CD008990.pub3
Recombinant human growth hormone for treating burns and donor sites
Abstract
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 methods: 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).
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.
Conflict of interest statement
There are no known conflicts of interests.
Figures
Update of
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Recombinant human growth hormone for treating burns and donor sites.Cochrane Database Syst Rev. 2012 Dec 12;12:CD008990. doi: 10.1002/14651858.CD008990.pub2. Cochrane Database Syst Rev. 2012. Update in: Cochrane Database Syst Rev. 2014 Sep 15;(9):CD008990. doi: 10.1002/14651858.CD008990.pub3. PMID: 23235668 Updated.
References
References to studies included in this review
Barret 1999 {published data only}
-
- Barret JP, Dziewulski P, Jeschke MG, Wolf SE, Herndon DN. Effects of recombinant human growth hormone on the development of burn scarring. Plastic and Reconstructive Surgery 1999;104(3):726‐9. - PubMed
Chen 2005 {published data only}
-
- Ghen GX, Han CM. Influence of recombinant human growth hormone on the prognosis of patients with severe burns a prospective multi‐center clinical trial. Zhonghua Shao Shang Za Zhi [Chinese Journal of Burns] 2005;21(5):347‐9. - PubMed
Demling 1999 {published data only}
-
- Demling RH. Comparison of the anabolic effects and complications of human growth hormone and the testosterone analog, oxandrolone, after severe burn injury. Burns 199;25(3):215‐21. - PubMed
de Oliveira 2004 {published data only}
-
- Oliveira GV, Sanford AP, Murphy KD, Oliveira HM, Wilkins JP, Wu X, et al. Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children. Wound Repair and Regeneration 2004;12(4):404‐11. - PubMed
Gilpin 1994 {published data only}
Herndon 1990 {published data only}
Jeschke 2000 {published data only}
-
- Jeschke MG, Barrow RE, Herndon DN. Recombinant human growth hormone treatment in pediatric burn patients and its role during the hepatic acute phase response. Critical Care Medicine 2000;28(5):1578‐84. - PubMed
Losada 2002 {published data only}
-
- Losada F, García‐Luna PP, Gómez‐Cia T, Garrido M, Pereira JL, Marín F, et al. Effects of human recombinant growth hormone on donor‐site healing in burned adults. World Journal of Surgery 2002;26(1):2‐8. - PubMed
Lu 2004 {published data only}
-
- Lu CJ, Lin C, Xu JJ, Zhang P, Cao GZ, Hong BS. The influence of combined supplementation of glutamine and recombinant human growth hormone on the protein metabolism in severely burned patients. Chinese Journal of Burns 2004;20(4):220‐2. - PubMed
Luo 2000 {published data only}
-
- Luo X, Cen Y, Yu R, Zhao J. Effectiveness of recombinant human growth hormone treatment for severe burn injury. Journal of West China University of Medical Sciences 2000;31(3):399‐401. - PubMed
Pelzer 2000 {published data only}
-
- Pelzer M, Hartmann B, Blome‐Eberwein S, Raff T, Germann G. Effect of recombinant growth hormone on wound healing in severely burned adults. A placebo controlled, randomized double‐blind phase II study. Der Chirurg 2000;71(11):1352‐8. - PubMed
Przkora 2006 {published data only}
Sun 1998 {published data only}
-
- Sun Y, Zhou Y, Jiang Z. The effect of growth hormone on wound healing rate in adult burns. Chinese Journal of Plastic Surgery and Burns 1998;14(4):277‐80. - PubMed
References to studies excluded from this review
Aarsland 1996 {published data only}
Branski 2009 {published data only}
Chai 2002a {published data only}
-
- Chai J, Hao D, Wu Y, Shen C, Guo Z, Sheng Z. Severely burned patients after surgery: recombinant human growth hormone therapy its metabolic effects. Zhonghua Wai Ke Za Zhi [Chinese Journal of Burns] 2002;40(2):107‐11. - PubMed
Chai 2002b {published data only}
-
- Chai J, Hao D, Wu Y, Shen C, Sheng Z. The effects of recombinant human growth hormone on the metabolism of branch chain amino acid in severely burned patients. Zhonghua Shao Shang Za Zhi [Chinese Journal of Burns] 2002;18(4):229‐31. - PubMed
Chrysopoulo 1999 {published data only}
-
- Chrysopoulo MT, Jeschke MG, Ramirez RJ, Barrow RE, Herndon DN. Growth hormone attenuates tumor necrosis factor alpha in burned children. Archives of Surgery 1999;134(3):283‐6. - PubMed
Hart 2001 {published data only}
Hart 2002 {published data only}
Herndon 1995 {published data only}
Jeschke 2008 {published data only}
-
- Jeschke MG, Finnerty CC, Kulp GA, Przkora R, Mlcak R, Herndon DN. Combination of recombinant human growth hormone and propranolol decreases hypermetabolism and inflammation in severely burned children. Pediatric Critical Care Medicine 2008;9(2):209‐16. - PubMed
Klein 1998 {published data only}
-
- Klein GL, Wolf SE, Langman CB, Rosen CJ, Mohan S, Keenan BS, et al. Effects of therapy with recombinant human growth hormone on insulin‐like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury. Journal of Clinical Endocrinology and Metabolism 1998;83(1):21‐4. - PubMed
Low 1999 {published data only}
-
- Low JF, Herndon DN, Barrow RE. Effect of growth hormone on growth delay in burned children: a 3‐year follow‐up study. Lancet 1999;354(9192):1789. - PubMed
Mlcak 2005 {published data only}
-
- Mlcak RP, Suman OE, Murphy K, Herndon DN. Effects of growth hormone on anthropometric measurements and cardiac function in children with thermal injury. Burns 2005;31(1):60‐6. - PubMed
Suman 2003 {published data only}
-
- Suman OE, Thomas SJ, Wilkins JP, Mlcak RP, Herndon DN. Effect of exogenous growth hormone and exercise on lean mass and muscle function in children with burns. Journal of Applied Physiology 2003;94(6):2273‐81. - PubMed
Suman 2004 {published data only}
-
- Suman OE, Mlcak RP, Herndon DN. Effects of exogenous growth hormone on resting pulmonary function in children with thermal injury. Journal of Burn Care and Rehabilitation 2004;25(3):287‐93. - PubMed
Additional references
Aili 2001
-
- Aili Low JF, Barrow RE, Mittendorfer B, Jeschke MG, Chinkes DL, Herndon DN. The effect of short‐term growth hormone treatment on growth and energy expenditure in burned children. Burns 2001;27(5):447‐52. - PubMed
Baryza 1995
-
- Baryza MJ, Baryza GA. The Vancouver Scar Scale: an administration tool and its interrater reliability. Journal of Burn Care and Rehabilitation 1995;16(5):535‐8. - PubMed
Blades 1982
-
- Blades B, Mellis N, Munster A. A burn specific health scale. Journal of Trauma 1982;22(10):872‐5. - PubMed
Bryant 2007
Crowe 1998
-
- Crowe JM, Simpson K, Johnson W, Allen J. Reliability of photographic analysis in determining change in scar appearance. Journal of Burn Care and Rehabilitation 1998;19(2):183‐6. - PubMed
Deeks 2011
-
- Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta‐analyses. Higgins JPT, Green S, (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0.[updated March 2011] The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Demling 2000
-
- Demling RH, Seigne P. Metabolic management of patients with severe burns. World Journal of Surgery 2000;24(6):673‐80. - PubMed
Draaijers 2004
-
- Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE, Middelkoop E, Kreis RW, et al. The patient and observer scar assessment scale: a reliable and feasible tool for scar evaluation. Plastic and Reconstructive Surgery 2004;113(7):1960‐5. - PubMed
Egger 1997
Gore 1991
-
- Gore DC, Honeycutt D, Jahoor F, Rutan T, Wolfe RR, Herndon DN. Effect of exogenous growth hormone on glucose utilization in burn patients. Journal of Surgical Research 1991;51(6):518‐23. - PubMed
Gore 2001
-
- Gore DC, Chinkes D, Heggers J, Herndon DN, Wolf SE, Desai M. Association of hyperglycaemia wit increased mortality after severe burn injury. Journal of Trauma 2001;51(3):540‐4. - PubMed
Hart 2000
Herndon 2004
-
- Herndon DN, Tompkins RG. Support of the metabolic response to burn injury. Lancet 2004;363(9424):1895‐902. - PubMed
Higgins 2003
Higgins 2011a
-
- Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Higgins 2011b
-
- Higgins JPT, Deeks JJ (editors). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011] The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Jeschke 1999a
-
- Jeschke MG, Herndon DN, Wolf SE, DebRoy MA, Rai J, Lichtenbelt BJ, et al. Recombinant human growth hormone alters acute phase reactant proteins, cytokine expression, and liver morphology in burned rats. Journal of Surgical Research 1999;83(2):122‐9. - PubMed
Jeschke 1999b
-
- Jeschke MG, Chrysopoulo MT, Herndon DN, Wolf SE. Increased expression of insulin‐like growth factor‐I in serum and liver after recombinant human growth hormone administration in thermally injured rats. Journal of Surgical Research 1999;85(1):171‐7. - PubMed
Krysiak 2007
-
- Krysiak R, Gdula‐Dymek A, Bednarska‐Czerwinska A, Okopien B. Growth hormone therapy in children and adults. Pharmacological Reports 2007;59(5):500‐16. - PubMed
Lefebvre 2011
-
- Lefebvre C, Manheimer E, Glanville J (editors). Chapter 6: Searching for studies.. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Mock 2008
-
- Mock C, Peck M, Peden M, Krug E (editors). A WHO plan for burn prevention and care. Geneva: World Health Organization, 2008.
Nedelec 2000
-
- Nedelec B, Shankowsky HA, Tredget EE. Rating the resolving hypertrophic scar: comparison of the Vancouver Scar Scale and scar volume. Journal of Burn Care and Rehabilitation 2000;21(3):205‐12. - PubMed
Pereira 2005
-
- Pereira CT, Murphy KD, Herndon DN. Altering metabolism. Journal of Burn Care and Rehabilitation 2005;26(3):194‐9. - PubMed
Przkora 2005
Przkora 2006a
-
- Przkora R, Barrow RE, Jeschke MG, Suman OE, Celis M, Sanford AP, et al. Body composition changes with time in pediatric burn patients. Journal of Trauma 2006;60(5):968‐71. - PubMed
Ramirez 1998
RevMan 2011 [Computer program]
-
- The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Scott‐Conner 1986a
-
- Scott‐Conner CE, Coil JA Jr, Conner HF, Mack ME. Wound Closure Index: a guide to prognosis in burned patients. Journal of Trauma 1986;26(2):123‐7. - PubMed
SIGN 2011
-
- Scottish Intercollegiate Guidelines Network (SIGN). Search filters. www.sign.ac.uk/methodology/filters.html#random 2011.
Singh 1998
-
- Singh KP, Prasad R, Chari PS, Dash RJ. Effect of growth hormone therapy in burn patients on conservative treatment. Burns 1998;24(8):733‐8. - PubMed
Sullivan 1990
-
- Sullivan T, Smith J, Kermode J, McIver E, Courtemanche DJ. Rating the burn scar. Journal of Burn Care and Rehabilitation 1990;11(3):256‐60. - PubMed
Takala 1999
-
- Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, et al. Increased mortality associated with growth hormone treatment in critically ill adults. New England Journal of Medicine 1999;341(11):785‐92. - PubMed
Van Loon 1998
-
- Loon K. Safety of high doses of recombinant human growth hormone. Hormone Research 1998;49(Suppl 2):78‐81. - PubMed
Vercelli 2009
-
- Vercelli S, Ferriero G, Sartorio F, Stissi V, Franchignoni F. How to assess postsurgical scars: a review of outcome measures. Disability and Rehabilitation 2009;31(25):2055‐63. - PubMed
Yeong 1997
-
- Yeong EK, Mann R, Engrav LH, Goldberg M, Cain V, Costa B, et al. Improved burn scar assessment with use of a new scar‐rating scale. Journal of Burn Care and Rehabilitation 1997;18(4):353‐5. - PubMed
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