title: Pathophysiologic response to severe burn injury.
abstract: OBJECTIVE
  To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial.
  
  
  BACKGROUND
  A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated.
  
  
  METHODS
  Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course.
  
  
  RESULTS
  Average age was 8 +/- 0.2 years, and average burn size was 56 +/- 1% TBSA with 43 +/- 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (-0.05% +/- 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (-4.1% +/- 1.9%); P < 0.05. Patients lost 3% +/- 1% of their bone mineral content (BMC) and 2 +/- 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 +/- 0.2 infections and 17% sepsis.
  
  
  CONCLUSIONS
  In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with derangements that are greater and more protracted than previously thought.
authors.affiliation: Shriners Hospitals for Children, University Texas Medical Branch, Galveston, Texas 77550, USA. majeschk@utmb.edu
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
authors.forename: David L
authors.initials: DL
authors.lastname: Chinkes
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kulp
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Suman
authors.forename: William B
authors.initials: WB
authors.lastname: Norbury
authors.forename: Ludwik K
authors.initials: LK
authors.lastname: Branski
authors.forename: Gerd G
authors.initials: GG
authors.lastname: Gauglitz
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mlcak
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
mesh_terms: D000293:Adolescent; D001830:Body Surface Area; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008660:Metabolism / Q000502:physiology*; D011446:Prospective Studies
references.citation: J Appl Physiol (1985). 2001 Sep;91(3):1168-75
references.pmid: 11509512
references.citation: Am J Pathol. 2007 Apr;170(4):1210-8
references.pmid: 17392161
references.citation: Am J Physiol Cell Physiol. 2007 Jun;292(6):C2103-11
references.pmid: 17287365
references.citation: Ann Surg. 2007 Sep;246(3):351-60; discussion 360-2
references.pmid: 17717439
references.citation: J Surg Res. 1978 Nov;25(5):394-403
references.pmid: 713539
references.citation: J Surg Res. 1997 Apr;69(1):166-70
references.pmid: 9202664
references.citation: Ann Surg. 1998 Jul;228(1):106-11
references.pmid: 9671074
references.citation: Shock. 2002 Sep;18(3):272-6
references.pmid: 12353930
references.citation: Nutr Metab (Lond). 2007 Apr 23;4:9
references.pmid: 17451602
references.citation: Mol Med. 2002 May;8(5):238-46
references.pmid: 12359954
references.citation: Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi. 1998 May;14(3):211-3
references.pmid: 10452069
references.citation: Biochem Biophys Res Commun. 1998 Feb 4;243(1):269-72
references.pmid: 9473516
references.citation: J Trauma. 2003 Mar;54(3):555-61
references.pmid: 12634538
references.citation: J Clin Invest. 1986 Mar;77(3):900-7
references.pmid: 2869053
references.citation: Curr Opin Clin Nutr Metab Care. 1999 May;2(3):201-5
references.pmid: 10456248
references.citation: Clin Endocrinol (Oxf). 1993 Nov;39(5):499-518
references.pmid: 8252737
references.citation: Ann Surg. 1992 Dec;216(6):648-55
references.pmid: 1466618
references.citation: Regul Pept. 2002 May 15;105(2):75-81
references.pmid: 11891007
references.citation: Crit Care Med. 2007 Feb;35(2):579-83
references.pmid: 17205022
references.citation: Pediatr Crit Care Med. 2008 Mar;9(2):209-16
references.pmid: 18477935
references.citation: Arch Surg. 1994 Dec;129(12):1301-4; discussion 1304-5
references.pmid: 7986160
references.citation: Surgery. 2002 Aug;132(2):341-7
references.pmid: 12219032
references.citation: Burns. 2004 Sep;30(6):565-8
references.pmid: 15302422
references.citation: Ann Surg. 2005 Feb;241(2):334-42
references.pmid: 15650645
references.citation: Ann Surg. 1974 Oct;180(4):653-69
references.pmid: 4412350
references.citation: J Am Coll Surg. 2006 Mar;202(3):536-48
references.pmid: 16500259
references.citation: J Trauma. 1995 Sep;39(3):526-30; discussion 530-2
references.pmid: 7473919
references.citation: Ann Surg. 2005 May;241(5):759-67; discussion 767-8
references.pmid: 15849511
references.citation: Ann Surg. 2007 Feb;245(2):214-21
references.pmid: 17245174
references.citation: Lancet. 1988 Feb 27;1(8583):438-40
references.pmid: 2893867
references.citation: N Engl J Med. 2001 Nov 8;345(19):1359-67
references.pmid: 11794168
references.citation: Ann Surg. 2005 Sep;242(3):384-9, discussion 390-1
references.pmid: 16135924
references.citation: Crit Care Med. 2002 Nov;30(11):2438-42
references.pmid: 12441751
references.citation: J Clin Invest. 1996 Jan 15;97(2):339-48
references.pmid: 8567953
references.citation: Arch Surg. 2004 Jun;139(6):641-7
references.pmid: 15197091
references.citation: Int J Biochem Cell Biol. 2005 Oct;37(10):1948-61
references.pmid: 16109499
references.citation: J Trauma. 1999 Nov;47(5):904-10; discussion 910-1
references.pmid: 10568720
references.citation: J Trauma. 2001 Sep;51(3):540-4
references.pmid: 11535907
references.citation: J Trauma. 2006 May;60(5):968-71; discussion 971
references.pmid: 16688056
references.citation: Pediatrics. 2007 Jan;119(1):e109-16
references.pmid: 17130281
references.citation: Mol Immunol. 2007 Jul;44(13):3317-23
references.pmid: 17403539
references.citation: N Engl J Med. 2006 Feb 2;354(5):449-61
references.pmid: 16452557
references.citation: Crit Care. 2007;11(4):R90
references.pmid: 17716366
references.citation: J Burn Care Res. 2006 Mar-Apr;27(2):131-9; discussion 140-1
references.pmid: 16566555
references.citation: J Burn Care Rehabil. 1996 Nov-Dec;17(6 Pt 1):518-21
references.pmid: 8951538
references.citation: J Bone Miner Res. 1993 Mar;8(3):337-45
references.pmid: 8456588
references.citation: Ann Surg. 1999 May;229(5):713-20; discussion 720-2
references.pmid: 10235530
references.citation: J Trauma. 2001 Oct;51(4):736-9
references.pmid: 11586168
references.citation: Ann Surg. 2000 Oct;232(4):455-65
references.pmid: 10998644
references.citation: Crit Care Med. 1995 Jan;23(1):78-83
references.pmid: 8001391
references.citation: Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H795-804
references.pmid: 15388499
references.citation: Am Surg. 1966 Jul;32(7):448-52
references.pmid: 5938617
references.citation: J Clin Endocrinol Metab. 2005 Dec;90(12):6498-507
references.pmid: 16174716
references.citation: Ann Surg. 2006 Jul;244(1):121-30
references.pmid: 16794397
references.citation: Am J Physiol. 1977 Apr;232(4):E415-8
references.pmid: 15459
references.citation: Ann Surg. 2006 Jan;243(1):115-20
references.pmid: 16371745
references.citation: Osteoporos Int. 2004 Jun;15(6):468-74
references.pmid: 15205718
references.citation: Am J Physiol. 1995 Jan;268(1 Pt 1):E75-84
references.pmid: 7840186
references.citation: Ann Surg. 2004 Apr;239(4):553-60
references.pmid: 15024317
references.citation: Surgery. 2000 Aug;128(2):312-9
references.pmid: 10923010
references.citation: Lancet. 2004 Jun 5;363(9424):1895-902
references.pmid: 15183630
references.citation: Endocr Rev. 1982 Spring;3(2):164-217
references.pmid: 6806085
references.citation: Arch Surg. 1991 Jan;126(1):38-43
references.pmid: 1898697
references.citation: Osteoporos Int. 2005 Jun;16(6):631-5
references.pmid: 15452689
references.citation: Shock. 1998 Sep;10(3):155-60
references.pmid: 9744642
references.citation: Ann Allergy Asthma Immunol. 2004 Mar;92(3):377-8
references.pmid: 15049404
references.citation: Surg Clin North Am. 1978 Dec;58(6):1173-87
references.pmid: 32634
references.citation: Am J Physiol. 1986 Mar;250(3 Pt 1):E306-11
references.pmid: 2869694
references.citation: Biochem Soc Trans. 1995 Nov;23(4):1019-25
references.pmid: 8654673
references.citation: N Engl J Med. 1998 Feb 19;338(8):485-92
references.pmid: 9443925
references.citation: J Pediatr Endocrinol Metab. 2002 Feb;15(2):129-38
references.pmid: 11874177
references.citation: Ann Surg. 2002 Aug;236(2):218-25
references.pmid: 12170027
references.citation: Ann Surg. 1988 Oct;208(4):484-92
references.pmid: 3052328
references.citation: N Engl J Med. 2001 Oct 25;345(17):1223-9
references.pmid: 11680441
references.citation: J Burn Care Res. 2006 Sep-Oct;27(5):742-8
references.pmid: 16998409
references.citation: N Engl J Med. 1999 Sep 9;341(11):785-92
references.pmid: 10477776
references.citation: J Burns Wounds. 2006 Aug 08;5:e5
references.pmid: 16921418
references.citation: Nat Clin Pract Endocrinol Metab. 2006 Jan;2(1):20-31
references.pmid: 16932250
references.citation: Metabolism. 1979 Oct;28(10):1031-9
references.pmid: 491960
references.citation: Shock. 1998 Oct;10(4):298-306
references.pmid: 9788663
references.citation: J Trauma. 2000 Oct;49(4):673-7; discussion 677-8
references.pmid: 11038085
references.citation: Ann Surg. 2001 Apr;233(4):556-64
references.pmid: 11303139
references.citation: Crit Care Med. 2001 Oct;29(10):1936-42
references.pmid: 11588456
references.citation: J Pediatr. 1995 Feb;126(2):252-6
references.pmid: 7844672
references.citation: Horm Res. 1997;48 Suppl 5:83-7
references.pmid: 9434050
references.citation: Surg Clin North Am. 1976 Oct;56(5):999-1018
references.pmid: 982246
references.citation: Ann Surg. 1957 Apr;145(4):479-87
references.pmid: 13412024
references.citation: Ann Surg. 1995 Jun;221(6):649-56; discussion 656-9
references.pmid: 7794069
references.citation: Burns. 2006 May;32(3):335-42
references.pmid: 16529869
references.citation: Shock. 2007 Aug;28(2):172-7
references.pmid: 17529902
references.citation: Shock. 2006 Jul;26(1):13-9
references.pmid: 16783192
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5287-91
references.pmid: 1711226
references.citation: Shock. 2007 Jan;27(1):4-9
references.pmid: 17172973
references.citation: J Pathol. 1997 Mar;181(3):257-66
references.pmid: 9155709
references.citation: J Cell Physiol. 2007 May;211(2):364-70
references.pmid: 17219405
references.citation: Burns. 2004 Dec;30(8):761-71
references.pmid: 15555787
references.citation: Br Med Bull. 1985 Jul;41(3):257-64
references.pmid: 3896381