Pathophysiologic response to severe burn injury.
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.
Jeschke
Marc G
MG
Shriners Hospitals for Children, University Texas Medical Branch, Galveston, Texas 77550, USA. majeschk@utmb.edu
Chinkes
David L
DL
Finnerty
Celeste C
CC
Kulp
Gabriela
G
Suman
Oscar E
OE
Norbury
William B
WB
Branski
Ludwik K
LK
Gauglitz
Gerd G
GG
Mlcak
Ronald P
RP
Herndon
David N
DN
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
J Appl Physiol (1985). 2001 Sep;91(3):1168-75
11509512
Am J Pathol. 2007 Apr;170(4):1210-8
17392161
Am J Physiol Cell Physiol. 2007 Jun;292(6):C2103-11
17287365
Ann Surg. 2007 Sep;246(3):351-60; discussion 360-2
17717439
J Surg Res. 1978 Nov;25(5):394-403
713539
J Surg Res. 1997 Apr;69(1):166-70
9202664
Ann Surg. 1998 Jul;228(1):106-11
9671074
Shock. 2002 Sep;18(3):272-6
12353930
Nutr Metab (Lond). 2007 Apr 23;4:9
17451602
Mol Med. 2002 May;8(5):238-46
12359954
Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi. 1998 May;14(3):211-3
10452069
Biochem Biophys Res Commun. 1998 Feb 4;243(1):269-72
9473516
J Trauma. 2003 Mar;54(3):555-61
12634538
J Clin Invest. 1986 Mar;77(3):900-7
2869053
Curr Opin Clin Nutr Metab Care. 1999 May;2(3):201-5
10456248
Clin Endocrinol (Oxf). 1993 Nov;39(5):499-518
8252737
Ann Surg. 1992 Dec;216(6):648-55
1466618
Regul Pept. 2002 May 15;105(2):75-81
11891007
Crit Care Med. 2007 Feb;35(2):579-83
17205022
Pediatr Crit Care Med. 2008 Mar;9(2):209-16
18477935
Arch Surg. 1994 Dec;129(12):1301-4; discussion 1304-5
7986160
Surgery. 2002 Aug;132(2):341-7
12219032
Burns. 2004 Sep;30(6):565-8
15302422
Ann Surg. 2005 Feb;241(2):334-42
15650645
Ann Surg. 1974 Oct;180(4):653-69
4412350
J Am Coll Surg. 2006 Mar;202(3):536-48
16500259
J Trauma. 1995 Sep;39(3):526-30; discussion 530-2
7473919
Ann Surg. 2005 May;241(5):759-67; discussion 767-8
15849511
Ann Surg. 2007 Feb;245(2):214-21
17245174
Lancet. 1988 Feb 27;1(8583):438-40
2893867
N Engl J Med. 2001 Nov 8;345(19):1359-67
11794168
Ann Surg. 2005 Sep;242(3):384-9, discussion 390-1
16135924
Crit Care Med. 2002 Nov;30(11):2438-42
12441751
J Clin Invest. 1996 Jan 15;97(2):339-48
8567953
Arch Surg. 2004 Jun;139(6):641-7
15197091
Int J Biochem Cell Biol. 2005 Oct;37(10):1948-61
16109499
J Trauma. 1999 Nov;47(5):904-10; discussion 910-1
10568720
J Trauma. 2001 Sep;51(3):540-4
11535907
J Trauma. 2006 May;60(5):968-71; discussion 971
16688056
Pediatrics. 2007 Jan;119(1):e109-16
17130281
Mol Immunol. 2007 Jul;44(13):3317-23
17403539
N Engl J Med. 2006 Feb 2;354(5):449-61
16452557
Crit Care. 2007;11(4):R90
17716366
J Burn Care Res. 2006 Mar-Apr;27(2):131-9; discussion 140-1
16566555
J Burn Care Rehabil. 1996 Nov-Dec;17(6 Pt 1):518-21
8951538
J Bone Miner Res. 1993 Mar;8(3):337-45
8456588
Ann Surg. 1999 May;229(5):713-20; discussion 720-2
10235530
J Trauma. 2001 Oct;51(4):736-9
11586168
Ann Surg. 2000 Oct;232(4):455-65
10998644
Crit Care Med. 1995 Jan;23(1):78-83
8001391
Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H795-804
15388499
Am Surg. 1966 Jul;32(7):448-52
5938617
J Clin Endocrinol Metab. 2005 Dec;90(12):6498-507
16174716
Ann Surg. 2006 Jul;244(1):121-30
16794397
Am J Physiol. 1977 Apr;232(4):E415-8
15459
Ann Surg. 2006 Jan;243(1):115-20
16371745
Osteoporos Int. 2004 Jun;15(6):468-74
15205718
Am J Physiol. 1995 Jan;268(1 Pt 1):E75-84
7840186
Ann Surg. 2004 Apr;239(4):553-60
15024317
Surgery. 2000 Aug;128(2):312-9
10923010
Lancet. 2004 Jun 5;363(9424):1895-902
15183630
Endocr Rev. 1982 Spring;3(2):164-217
6806085
Arch Surg. 1991 Jan;126(1):38-43
1898697
Osteoporos Int. 2005 Jun;16(6):631-5
15452689
Shock. 1998 Sep;10(3):155-60
9744642
Ann Allergy Asthma Immunol. 2004 Mar;92(3):377-8
15049404
Surg Clin North Am. 1978 Dec;58(6):1173-87
32634
Am J Physiol. 1986 Mar;250(3 Pt 1):E306-11
2869694
Biochem Soc Trans. 1995 Nov;23(4):1019-25
8654673
N Engl J Med. 1998 Feb 19;338(8):485-92
9443925
J Pediatr Endocrinol Metab. 2002 Feb;15(2):129-38
11874177
Ann Surg. 2002 Aug;236(2):218-25
12170027
Ann Surg. 1988 Oct;208(4):484-92
3052328
N Engl J Med. 2001 Oct 25;345(17):1223-9
11680441
J Burn Care Res. 2006 Sep-Oct;27(5):742-8
16998409
N Engl J Med. 1999 Sep 9;341(11):785-92
10477776
J Burns Wounds. 2006 Aug 08;5:e5
16921418
Nat Clin Pract Endocrinol Metab. 2006 Jan;2(1):20-31
16932250
Metabolism. 1979 Oct;28(10):1031-9
491960
Shock. 1998 Oct;10(4):298-306
9788663
J Trauma. 2000 Oct;49(4):673-7; discussion 677-8
11038085
Ann Surg. 2001 Apr;233(4):556-64
11303139
Crit Care Med. 2001 Oct;29(10):1936-42
11588456
J Pediatr. 1995 Feb;126(2):252-6
7844672
Horm Res. 1997;48 Suppl 5:83-7
9434050
Surg Clin North Am. 1976 Oct;56(5):999-1018
982246
Ann Surg. 1957 Apr;145(4):479-87
13412024
Ann Surg. 1995 Jun;221(6):649-56; discussion 656-9
7794069
Burns. 2006 May;32(3):335-42
16529869
Shock. 2007 Aug;28(2):172-7
17529902
Shock. 2006 Jul;26(1):13-9
16783192
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5287-91
1711226
Shock. 2007 Jan;27(1):4-9
17172973
J Pathol. 1997 Mar;181(3):257-66
9155709
J Cell Physiol. 2007 May;211(2):364-70
17219405
Burns. 2004 Dec;30(8):761-71
15555787
Br Med Bull. 1985 Jul;41(3):257-64
3896381