title: Anti-inflammatory effect of aprotinin: a meta-analysis.
abstract: It is important to define the extent, and any limitations, of potential anti-inflammatory regimens used in cardiac surgery to guide the rational combination of drugs to suppress the systemic inflammatory response. Aprotinin (Trasylol) is an anti-fibrinolytic agent with reported anti-inflammatory properties. In this study, we investigated the published data on aprotinin's effect on acute phase protein and cytokine levels in cardiac surgery patients. Randomized placebo-controlled trials of aprotinin published between 1985 and 2007, in adult cardiac surgery using cardiopulmonary bypass, reporting tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10 levels were included for review. Two independent reviewers graded each paper and collected information on inflammatory markers. RevMan 4.3 statistical software was used to calculate and plot the weighted mean difference between placebo and aprotinin groups. Thirteen studies met the review criteria. None of the inflammatory markers were reduced by high-dose aprotinin treatment. Low-dose aprotinin significantly reduced IL-10 levels after protamine administration (-41.3 pg/ mL; 95% CI: -59.5, -23.1), but this result was gone by the first post-operative day. These meta-analyses showed no significant effect of aprotinin on acute phase proteins or systemic cytokine markers of inflammation during clinical adult cardiac surgery using cardiopulmonary bypass. While recognizing that other host defense systems, such as coagulation and complement, contribute to the overall systemic inflammatory response, the evidence presented here does not support the clinical use of aprotinin as an anti-inflammatory agent on its own.
authors.affiliation: The Dartmouth Institute for Health Policy and Clinical Practice and Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. jbrown@Dartmouth.edu
authors.forename: Jeremiah R
authors.initials: JR
authors.lastname: Brown
authors.forename: Andrew W J
authors.initials: AW
authors.lastname: Toler
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kramer
authors.forename: R Clive
authors.initials: RC
authors.lastname: Landis
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology*; D006348:Cardiac Surgical Procedures; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000209:Acute-Phase Proteins; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D007611:Aprotinin
references.citation: J Thorac Cardiovasc Surg. 2001 Jul;122(1):123-8
references.pmid: 11436044
references.citation: J Thorac Cardiovasc Surg. 1993 Jul;106(1):1-9; discussion 9-10
references.pmid: 7686593
references.citation: J Cardiothorac Vasc Anesth. 2000 Dec;14(6):682-6
references.pmid: 11139109
references.citation: J Card Surg. 2006 Jul-Aug;21(4):336-41
references.pmid: 16846409
references.citation: N Engl J Med. 2006 Jan 26;354(4):353-65
references.pmid: 16436767
references.citation: Cochrane Database Syst Rev. 2001;(1):CD001886
references.pmid: 11279735
references.citation: Ann Thorac Surg. 2006 Feb;81(2):619-24
references.pmid: 16427862
references.citation: Cardiovasc Drugs Ther. 2002 Jan;16(1):37-42
references.pmid: 12085976
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120
references.citation: J Thorac Cardiovasc Surg. 2003 Jan;125(1):32-5
references.pmid: 12538980
references.citation: Anesth Analg. 2001 Apr;92(4):830-6
references.pmid: 11273910
references.citation: Ann Thorac Surg. 2004 Feb;77(2):644-50
references.pmid: 14759453
references.citation: J Thorac Cardiovasc Surg. 2004 Sep;128(3):442-8
references.pmid: 15354106
references.citation: Anesth Analg. 2004 Feb;98(2):285-290
references.pmid: 14742356
references.citation: Thorac Cardiovasc Surg. 1999 Apr;47(2):111-8
references.pmid: 10363611
references.citation: Arzneimittelforschung. 1983;33(4):479-94
references.pmid: 6191764
references.citation: J Extra Corpor Technol. 2007 Dec;39(4):281-4
references.pmid: 18293820
references.citation: Cardiovasc Drugs Ther. 2003 Jul;17(4):343-8
references.pmid: 14618096
references.citation: Ann Thorac Surg. 1993 Feb;55(2):552-9
references.pmid: 8431082
references.citation: Control Clin Trials. 1996 Feb;17(1):1-12
references.pmid: 8721797
references.citation: J Extra Corpor Technol. 2007 Dec;39(4):291-5
references.pmid: 18293823
references.citation: Lancet. 1999 Nov 27;354(9193):1896-900
references.pmid: 10584742
references.citation: Am J Pathol. 1982 Oct;109(1):15-26
references.pmid: 6181692
references.citation: Anesthesiology. 2004 Feb;100(2):225-33
references.pmid: 14739793
references.citation: J Cardiothorac Vasc Anesth. 2001 Oct;15(5):603-10
references.pmid: 11688002
references.citation: J Thorac Cardiovasc Surg. 2004 Jul;128(1):83-91
references.pmid: 15224025
references.citation: J Cardiothorac Vasc Anesth. 1997 Feb;11(1):29-31
references.pmid: 9058216
references.citation: Semin Cardiothorac Vasc Anesth. 2006 Jun;10(2):132-42
references.pmid: 16959740
references.citation: J Thorac Cardiovasc Surg. 2008 May;135(5):999-1006
references.pmid: 18455576
references.citation: Ann Thorac Surg. 2000 Apr;69(4):1192-7
references.pmid: 10800818
references.citation: Heart Surg Forum. 2008;11(5):E316-22
references.pmid: 19131308
references.citation: Circulation. 2001 Sep 18;104(12 Suppl 1):I265-9
references.pmid: 11568067
references.citation: N Engl J Med. 2008 May 29;358(22):2319-31
references.pmid: 18480196
references.citation: J Cardiovasc Pharmacol. 2007 Jan;49(1):39-45
references.pmid: 17261962
references.citation: Ann Thorac Surg. 1998 Jan;65(1):66-9
references.pmid: 9456097
references.citation: J Thorac Cardiovasc Surg. 2008 Mar;135(3):487-91
references.pmid: 18329457
references.citation: Cardiovasc Surg. 2001 Aug;9(4):403-6
references.pmid: 11420167
references.citation: Ann Thorac Surg. 2003 Jan;75(1):210-5; discussion 215-6
references.pmid: 12537218
references.citation: Ann Thorac Surg. 1998 Sep;66(3):747-53; discussion 753-4
references.pmid: 9768925
references.citation: Ann Thorac Surg. 2000 Apr;69(4):1084-91
references.pmid: 10800798
references.citation: Perfusion. 2000 Nov;15(6):495-9
references.pmid: 11131212
references.citation: J Thorac Cardiovasc Surg. 2006 Jan;131(1):21-7
references.pmid: 16399290
references.citation: Ann Thorac Surg. 1997 Jan;63(1):50-6
references.pmid: 8993240
references.citation: J Thorac Cardiovasc Surg. 1995 Dec;110(6):1658-62
references.pmid: 8523876
references.citation: Scand Cardiovasc J. 2001 Feb;35(1):50-4
references.pmid: 11354573
references.citation: J Thorac Cardiovasc Surg. 2003 Nov;126(5):1498-503
references.pmid: 14666025
references.citation: J Thorac Cardiovasc Surg. 2003 Jan;125(1):184-90
references.pmid: 12539003