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Published in: Critical Care 4/2010

Open Access 01-08-2010 | Research

A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients

Authors: Nicole E Spruijt, Tjaakje Visser, Luke PH Leenen

Published in: Critical Care | Issue 4/2010

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Abstract

Introduction

Following trauma, patients may suffer an overwhelming pro-inflammatory response and immune paralysis resulting in infection and multiple organ failure (MOF). Various potentially immunomodulative interventions have been tested. The objective of this study is to systematically review the randomized controlled trials (RCTs) that investigate the effect of potentially immunomodulative interventions in comparison to a placebo or standard therapy on infection, MOF, and mortality in trauma patients.

Methods

A computerized search of MEDLINE, the Cochrane CENTRAL Register of Controlled Trials, and EMBASE yielded 502 studies, of which 18 unique RCTs were deemed relevant for this study. The methodological quality of these RCTs was assessed using a critical appraisal checklist for therapy articles from the Centre for Evidence Based Medicine. The effects of the test interventions on infection, MOF, and mortality rates and inflammatory parameters relative to the controls were recorded.

Results

In most studies, the inflammatory parameters differed significantly between the test and control groups. However, significant changes in infection, MOF, and mortality rates were only measured in studies testing immunoglobulin, IFN-γ, and glucan.

Conclusions

Based on level 1b and 2b studies, administration of immunoglobulin, IFN-γ, or glucan have shown the most promising results to improve the outcome of trauma patients.
Appendix
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Literature
1.
go back to reference Peden M, McGee K, Krug E: Injury: A leading cause of the global burden of disease, 2000. Geneva, Switzerland: World Health Organization; 2002. Peden M, McGee K, Krug E: Injury: A leading cause of the global burden of disease, 2000. Geneva, Switzerland: World Health Organization; 2002.
2.
go back to reference Teixeira PG, Inaba K, Hadjizacharia P, Brown C, Salim A, Rhee P, Browder T, Noguchi TT, Demetriades D: Preventable or potentially preventable mortality at a mature trauma center. J Trauma 2007, 63: 1338-1346. discussion 1346-1337 10.1097/TA.0b013e31815078aeCrossRefPubMed Teixeira PG, Inaba K, Hadjizacharia P, Brown C, Salim A, Rhee P, Browder T, Noguchi TT, Demetriades D: Preventable or potentially preventable mortality at a mature trauma center. J Trauma 2007, 63: 1338-1346. discussion 1346-1337 10.1097/TA.0b013e31815078aeCrossRefPubMed
3.
go back to reference Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC: Postinjury multiple organ failure: a bimodal phenomenon. J Trauma 1996, 40: 501-510. discussion 510-502 10.1097/00005373-199604000-00001CrossRefPubMed Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC: Postinjury multiple organ failure: a bimodal phenomenon. J Trauma 1996, 40: 501-510. discussion 510-502 10.1097/00005373-199604000-00001CrossRefPubMed
4.
go back to reference Bone RC: Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996, 24: 1125-1128. 10.1097/00003246-199607000-00010CrossRefPubMed Bone RC: Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996, 24: 1125-1128. 10.1097/00003246-199607000-00010CrossRefPubMed
5.
6.
go back to reference Keel M, Trentz O: Pathophysiology of polytrauma. Injury 2005, 36: 691-709. 10.1016/j.injury.2004.12.037CrossRefPubMed Keel M, Trentz O: Pathophysiology of polytrauma. Injury 2005, 36: 691-709. 10.1016/j.injury.2004.12.037CrossRefPubMed
7.
go back to reference Moore EE, Moore FA, Harken AH, Johnson JL, Ciesla D, Banerjee A: The two-event construct of postinjury multiple organ failure. Shock 2005, 24: 71-74. 10.1097/01.shk.0000191336.01036.feCrossRefPubMed Moore EE, Moore FA, Harken AH, Johnson JL, Ciesla D, Banerjee A: The two-event construct of postinjury multiple organ failure. Shock 2005, 24: 71-74. 10.1097/01.shk.0000191336.01036.feCrossRefPubMed
8.
go back to reference Montejo JC, Zarazaga A, Lopez-Martinez J, Urrutia G, Roque M, Blesa AL, Celaya S, Conejero R, Galban C, Garcia de Lorenzo A, Grau T, Mesejo A, Ortiz-Leyba C, Planas M, Ordonez J, Jimenez FJ: Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr 2003, 22: 221-233. 10.1016/S0261-5614(03)00007-4CrossRefPubMed Montejo JC, Zarazaga A, Lopez-Martinez J, Urrutia G, Roque M, Blesa AL, Celaya S, Conejero R, Galban C, Garcia de Lorenzo A, Grau T, Mesejo A, Ortiz-Leyba C, Planas M, Ordonez J, Jimenez FJ: Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr 2003, 22: 221-233. 10.1016/S0261-5614(03)00007-4CrossRefPubMed
11.
go back to reference Bauer M, Redl H, Mari I: Prophylactic veno-venous haemofiltration and inflammatory response to multiple trauma. International Journal of Intensive Care 2001, 8: 194-199. Bauer M, Redl H, Mari I: Prophylactic veno-venous haemofiltration and inflammatory response to multiple trauma. International Journal of Intensive Care 2001, 8: 194-199.
12.
go back to reference Rommelsheim K: Preventive use of Pentaglobin in intensive care treatment of trauma patients. Anasth Intensivther Notfallmed 1989, 24: 162-166. 10.1055/s-2007-1001544CrossRefPubMed Rommelsheim K: Preventive use of Pentaglobin in intensive care treatment of trauma patients. Anasth Intensivther Notfallmed 1989, 24: 162-166. 10.1055/s-2007-1001544CrossRefPubMed
13.
go back to reference Dries DJ, Jurkovich GJ, Maier RV, Clemmer TP, Struve SN, Weigelt JA, Stanford GG, Herr DL, Champion HR, Lewis FR, et al.: Effect of interferon gamma on infection-related death in patients with severe injuries. A randomized, double-blind, placebo-controlled trial. Arch Surg 1994, 129: 1031-1041. discussion 1042CrossRefPubMed Dries DJ, Jurkovich GJ, Maier RV, Clemmer TP, Struve SN, Weigelt JA, Stanford GG, Herr DL, Champion HR, Lewis FR, et al.: Effect of interferon gamma on infection-related death in patients with severe injuries. A randomized, double-blind, placebo-controlled trial. Arch Surg 1994, 129: 1031-1041. discussion 1042CrossRefPubMed
14.
go back to reference Miller CL, Lim RC: Dextran as a modulator of immune and coagulation activities in trauma patients. J Surg Res 1985, 39: 183-191. 10.1016/0022-4804(85)90141-6CrossRefPubMed Miller CL, Lim RC: Dextran as a modulator of immune and coagulation activities in trauma patients. J Surg Res 1985, 39: 183-191. 10.1016/0022-4804(85)90141-6CrossRefPubMed
15.
go back to reference Vassar MJ, Fletcher MP, Perry CA, Holcroft JW: Evaluation of prostaglandin E1 for prevention of respiratory failure in high risk trauma patients: a prospective clinical trial and correlation with plasma suppressive factors for neutrophil activation. Prostaglandins Leukot Essent Fatty Acids 1991, 44: 223-231. 10.1016/0952-3278(91)90021-VCrossRefPubMed Vassar MJ, Fletcher MP, Perry CA, Holcroft JW: Evaluation of prostaglandin E1 for prevention of respiratory failure in high risk trauma patients: a prospective clinical trial and correlation with plasma suppressive factors for neutrophil activation. Prostaglandins Leukot Essent Fatty Acids 1991, 44: 223-231. 10.1016/0952-3278(91)90021-VCrossRefPubMed
16.
go back to reference Seekamp A, Van Griensven M, Dhondt E, Diefenbeck M, Demeyer I, Vundelinckx G, Haas N, Schaechinger U, Wolowicka L, Rammelt S, Stroobants J, Marzi I, Brambrink AM, Dziurdzik P, Gasiorowski J, Redl H, Beckert M, Khan-Boluki J: The effect of anti-L-selectin (aselizumab) in multiple traumatized patients - Results of a phase II clinical trial. Crit Care Med 2004, 32: 2021-2028. 10.1097/01.CCM.0000142396.59236.F3CrossRefPubMed Seekamp A, Van Griensven M, Dhondt E, Diefenbeck M, Demeyer I, Vundelinckx G, Haas N, Schaechinger U, Wolowicka L, Rammelt S, Stroobants J, Marzi I, Brambrink AM, Dziurdzik P, Gasiorowski J, Redl H, Beckert M, Khan-Boluki J: The effect of anti-L-selectin (aselizumab) in multiple traumatized patients - Results of a phase II clinical trial. Crit Care Med 2004, 32: 2021-2028. 10.1097/01.CCM.0000142396.59236.F3CrossRefPubMed
17.
go back to reference Seekamp A, Van Griensven M, Rusu C, Konig J, Khan-Boluki J, Redl H: The effect of anti-L-selectin (Aselizumab) on the posttraumatic inflammatory response in multiply traumatized patients. European Journal of Trauma 2005, 31: 557-567. 10.1007/s00068-005-1066-4CrossRef Seekamp A, Van Griensven M, Rusu C, Konig J, Khan-Boluki J, Redl H: The effect of anti-L-selectin (Aselizumab) on the posttraumatic inflammatory response in multiply traumatized patients. European Journal of Trauma 2005, 31: 557-567. 10.1007/s00068-005-1066-4CrossRef
18.
go back to reference Dries DJ, Walenga JM, Hoppensteadt D, Fareed J: Molecular markers of hemostatic activation and inflammation following major injury: effect of therapy with IFN-gamma. J Interferon Cytokine Res 1998, 18: 327-335. 10.1089/jir.1998.18.327CrossRefPubMed Dries DJ, Walenga JM, Hoppensteadt D, Fareed J: Molecular markers of hemostatic activation and inflammation following major injury: effect of therapy with IFN-gamma. J Interferon Cytokine Res 1998, 18: 327-335. 10.1089/jir.1998.18.327CrossRefPubMed
19.
go back to reference Bulger EM, Jurkovich GJ, Nathens AB, Copass MK, Hanson S, Cooper C, Liu PY, Neff M, Awan AB, Warner K, Maier RV: Hypertonic resuscitation of hypovolemic shock after blunt trauma: a randomized controlled trial. Arch Surg 2008, 143: 139-148. discussion 149 10.1001/archsurg.2007.41CrossRefPubMed Bulger EM, Jurkovich GJ, Nathens AB, Copass MK, Hanson S, Cooper C, Liu PY, Neff M, Awan AB, Warner K, Maier RV: Hypertonic resuscitation of hypovolemic shock after blunt trauma: a randomized controlled trial. Arch Surg 2008, 143: 139-148. discussion 149 10.1001/archsurg.2007.41CrossRefPubMed
20.
go back to reference Glinz W, Grob PJ, Nydegger UE, Ricklin T, Stamm F, Stoffel D, Lasance A: Polyvalent immunoglobulins for prophylaxis of bacterial infections in patients following multiple trauma. A randomized, placebo-controlled study. Intensive Care Med 1985, 11: 288-294. 10.1007/BF00273538CrossRefPubMed Glinz W, Grob PJ, Nydegger UE, Ricklin T, Stamm F, Stoffel D, Lasance A: Polyvalent immunoglobulins for prophylaxis of bacterial infections in patients following multiple trauma. A randomized, placebo-controlled study. Intensive Care Med 1985, 11: 288-294. 10.1007/BF00273538CrossRefPubMed
21.
go back to reference Nathens AB, Nester TA, Rubenfeld GD, Nirula R, Gernsheimer TB: The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial. Shock 2006, 26: 342-347. 10.1097/01.shk.0000228171.32587.a1CrossRefPubMed Nathens AB, Nester TA, Rubenfeld GD, Nirula R, Gernsheimer TB: The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial. Shock 2006, 26: 342-347. 10.1097/01.shk.0000228171.32587.a1CrossRefPubMed
22.
go back to reference Polk HC Jr, Cheadle WG, Livingston DH, Rodriguez JL, Starko KM, Izu AE, Jaffe HS, Sonnenfeld G: A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients. Am J Surg 1992, 163: 191-196. 10.1016/0002-9610(92)90099-DCrossRefPubMed Polk HC Jr, Cheadle WG, Livingston DH, Rodriguez JL, Starko KM, Izu AE, Jaffe HS, Sonnenfeld G: A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients. Am J Surg 1992, 163: 191-196. 10.1016/0002-9610(92)90099-DCrossRefPubMed
23.
go back to reference Rhee P, Morris J, Durham R, Hauser C, Cipolle M, Wilson R, Luchette F, McSwain N, Miller R: Recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) in traumatic hemorrhagic shock: results of a phase II clinical trial. Traumatic Shock Group. J Trauma 2000, 49: 611-619. discussion 619-620 10.1097/00005373-200010000-00007CrossRefPubMed Rhee P, Morris J, Durham R, Hauser C, Cipolle M, Wilson R, Luchette F, McSwain N, Miller R: Recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) in traumatic hemorrhagic shock: results of a phase II clinical trial. Traumatic Shock Group. J Trauma 2000, 49: 611-619. discussion 619-620 10.1097/00005373-200010000-00007CrossRefPubMed
24.
go back to reference Croce MA, Fabian TC, Patton JH Jr, Melton SM, Moore M, Trenthem LL: Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients. J Trauma 1998, 45: 273-280. discussion 280-272 10.1097/00005373-199808000-00012CrossRefPubMed Croce MA, Fabian TC, Patton JH Jr, Melton SM, Moore M, Trenthem LL: Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients. J Trauma 1998, 45: 273-280. discussion 280-272 10.1097/00005373-199808000-00012CrossRefPubMed
25.
go back to reference Marzi I, Buhren V, Schuttler A, Trentz O: Value of superoxide dismutase for prevention of multiple organ failure after multiple trauma. J Trauma 1993, 35: 110-119. discussion 119-120 10.1097/00005373-199307000-00018CrossRefPubMed Marzi I, Buhren V, Schuttler A, Trentz O: Value of superoxide dismutase for prevention of multiple organ failure after multiple trauma. J Trauma 1993, 35: 110-119. discussion 119-120 10.1097/00005373-199307000-00018CrossRefPubMed
26.
go back to reference Nakos G, Malamou-Mitsi VD, Lachana A, Karassavoglou A, Kitsiouli E, Agnandi N, Lekka ME: Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma. Crit Care Med 2002, 30: 1488-1494. 10.1097/00003246-200207000-00015CrossRefPubMed Nakos G, Malamou-Mitsi VD, Lachana A, Karassavoglou A, Kitsiouli E, Agnandi N, Lekka ME: Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma. Crit Care Med 2002, 30: 1488-1494. 10.1097/00003246-200207000-00015CrossRefPubMed
27.
go back to reference Rizoli SB, Rhind SG, Shek PN, Inaba K, Filips D, Tien H, Brenneman F, Rotstein O: The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial. Ann Surg 2006, 243: 47-57. 10.1097/01.sla.0000193608.93127.b1PubMedCentralCrossRefPubMed Rizoli SB, Rhind SG, Shek PN, Inaba K, Filips D, Tien H, Brenneman F, Rotstein O: The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial. Ann Surg 2006, 243: 47-57. 10.1097/01.sla.0000193608.93127.b1PubMedCentralCrossRefPubMed
28.
go back to reference Waydhas C, Nast-Kolb D, Gippner-Steppert C, Trupka A, Pfundstein C, Schweiberer L, Jochum M: High-dose antithrombin III treatment of severely injured patients: results of a prospective study. J Trauma 1998, 45: 931-940. 10.1097/00005373-199811000-00015CrossRefPubMed Waydhas C, Nast-Kolb D, Gippner-Steppert C, Trupka A, Pfundstein C, Schweiberer L, Jochum M: High-dose antithrombin III treatment of severely injured patients: results of a prospective study. J Trauma 1998, 45: 931-940. 10.1097/00005373-199811000-00015CrossRefPubMed
29.
go back to reference Browder W, Williams D, Pretus H, Olivero G, Enrichens F, Mao P, Franchello A: Beneficial effect of enhanced macrophage function in the trauma patient. Ann Surg 1990, 211: 605-612. discussion 612-603PubMedCentralPubMed Browder W, Williams D, Pretus H, Olivero G, Enrichens F, Mao P, Franchello A: Beneficial effect of enhanced macrophage function in the trauma patient. Ann Surg 1990, 211: 605-612. discussion 612-603PubMedCentralPubMed
30.
go back to reference de Felippe Júnior J, da Rocha e Silva Júnior M, Maciel FM, Soares Ade M, Mendes NF: Infection prevention in patients with severe multiple trauma with the immunomodulator beta1–3polyglucose (glucan). Surg Gynecol Obstet 1993, 177: 383-388.PubMed de Felippe Júnior J, da Rocha e Silva Júnior M, Maciel FM, Soares Ade M, Mendes NF: Infection prevention in patients with severe multiple trauma with the immunomodulator beta1–3polyglucose (glucan). Surg Gynecol Obstet 1993, 177: 383-388.PubMed
31.
go back to reference Livingston DH, Loder PA, Kramer SM, Gibson UE, Polk HC Jr: Interferon gamma administration increases monocyte HLA-DR antigen expression but not endogenous interferon production. Arch Surg 1994, 129: 172-178.CrossRefPubMed Livingston DH, Loder PA, Kramer SM, Gibson UE, Polk HC Jr: Interferon gamma administration increases monocyte HLA-DR antigen expression but not endogenous interferon production. Arch Surg 1994, 129: 172-178.CrossRefPubMed
32.
go back to reference Douzinas EE, Pitaridis MT, Louris G, Andrianakis I, Katsouyanni K, Karmpaliotis D, Economidou J, Sfyras D, Roussos C: Prevention of infection in multiple trauma patients by high-dose intravenous immunoglobulins. Crit Care Med 2000, 28: 8-15. 10.1097/00003246-200001000-00002CrossRefPubMed Douzinas EE, Pitaridis MT, Louris G, Andrianakis I, Katsouyanni K, Karmpaliotis D, Economidou J, Sfyras D, Roussos C: Prevention of infection in multiple trauma patients by high-dose intravenous immunoglobulins. Crit Care Med 2000, 28: 8-15. 10.1097/00003246-200001000-00002CrossRefPubMed
Metadata
Title
A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients
Authors
Nicole E Spruijt
Tjaakje Visser
Luke PH Leenen
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc9218

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