Top

European Journal of Trauma and Emergency Surgery

Published in:

01-10-2018 | Review Article

Using IL-6 concentrations in the first 24 h following trauma to predict immunological complications and mortality in trauma patients: a meta-analysis

Authors: Zhi Qiao, Weikang Wang, Luxu Yin, Peng Luo, Johannes Greven, Klemens Horst, Frank Hildebrand

Published in: European Journal of Trauma and Emergency Surgery | Issue 5/2018

Abstract

Purpose

In previous studies, interleukin-6 (IL-6) has been shown to have a high predictive value for the development of complications and mortality after trauma; however, there is some uncertainty around these results. The aim of this meta-analysis was to assess the value of early IL-6 levels (within the first 24 h after trauma) for predicting post-traumatic complications [acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), sepsis, multiple organ failure (MOF), and multiple organ dysfunction syndrome (MODS)] and mortality.

Methods

A systemic literature review (from January 01, 1990, to June 03, 2017) of English-language articles was carried out using Pubmed, the Cochrane Central Register of Controlled Trials, Embase, and Web of Science. The search terms used were IL-6 (IL6, IL-6, interleukin 6, or interleukin-6); trauma (trauma*, polytrauma*, multitrauma*, injury, or injury severity score); complications (complication*, ARDS, SIRS, sepsis, MOF, or MODS); and mortality (survival, death). Eleven publications (775 patients) out of 1812 fulfilled the criteria. Fixed-effective models were used for data analysis. Statistical heterogeneity was estimated by a Chi-squared Q test and I ² statistics, and publication bias was assessed with Egger’s test.

Results

Results showed that the concentrations of IL-6 within the first 24 h after trauma were significantly higher in the group of patients who had complications or who died [standardized mean difference (SMD) = 0.399; 95% confidence interval (CI) 0.217, 0.580; I ² = 0.0%; P(heterogeneity) = 0.489]. Subgroup results showed a significant correlation for mortality [SMD = 0.610; 95% CI 0.322, 0.898; I ² = 0.0%; P(heterogeneity) = 0.708] and MOF/MODS [SMD = 0.334; 95% CI 0.028, 0.639; I ² = 0.0%; P(heterogeneity) = 0.512] with IL-6, but not for sepsis [SMD = 0.194; 95% CI − 0.095, 0.484; I ² = 0.0%; P(heterogeneity) = 0.512]. Significance was also found in both ISS ≥ 9 [SMD = 0.461, 95% CI 0.131, 0.791, I ² = 5.6%, P(heterogeneity) = 0.365] and ISS ≥ 16 [SMD = 0.372, 95% CI 0.155, 0.588, I ² = 1.5%, P(heterogeneity) = 0.413].

Conclusion

In conclusion, this meta-analysis showed that serum concentration of IL-6 within the first 24 h after trauma could be useful for the prediction of post-traumatic complications, particularly MOF/MODS and mortality.

Osler T, Glance LG, Hosmer DW. Complication-associated mortality following trauma: a population-based observational study. Arch Surg (Chicago, Ill: 1960). 2012;147(2):152–8. https://doi.org/10.1001/archsurg.2011.888.CrossRef

Jawa RS, Anillo S, Huntoon K, Baumann H, Kulaylat M. Interleukin-6 in surgery, trauma, and critical care part II: clinical implications. J Intensive Care Med. 2011;26(2):73–87. https://doi.org/10.1177/0885066610395679.CrossRefPubMed

Gebhard F, Pfetsch H, Steinbach G, Strecker W, Kinzl L, Bruckner UB. Is interleukin 6 an early marker of injury severity following major trauma in humans? Arch Surg (Chicago., Ill: 1960). 2000;135(3):291–5.CrossRef

Cuschieri J, Bulger E, Schaeffer V, Sakr S, Nathens AB, Hennessy L, et al. Early elevation in random plasma IL-6 after severe injury is associated with development of organ failure. Shock (Augusta Ga). 2010;34(4):346 – 51. https://doi.org/10.1097/SHK.0b013e3181d8e687.CrossRef

Partrick DA, Moore FA, Moore EE, Biffl WL, Sauaia A, Barnett CC. Jr. Jack A. Barney Resident Research Award winner. The inflammatory profile of interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 in postinjury multiple organ failure. Am J Surg. 1996;172(5):425–9 (discussed 9–31).CrossRef

Ciriello V, Gudipati S, Stavrou PZ, Kanakaris NK, Bellamy MC, Giannoudis PV. Biomarkers predicting sepsis in polytrauma patients: current evidence. Injury. 2013;44(12):1680–92. https://doi.org/10.1016/j.injury.2013.09.024.CrossRefPubMed

Giannoudis PV, Smith MR, Evans RT, Bellamy MC, Guillou PJ. Serum CRP and IL-6 levels after trauma. Not predictive of septic complications in 31 patients. Acta Orthop Scand. 1998;69(2):184–8.CrossRef

Giamarellos-Bourboulis EJ, Mouktaroudi M, Tsaganos T, Koutoukas P, Spyridaki E, Pelekanou A, et al. Evidence for the participation of soluble triggering receptor expressed on myeloid cells-1 in the systemic inflammatory response syndrome after multiple trauma. J Trauma. 2008;65(6):1385–90. https://doi.org/10.1097/TA.0b013e31814699cc.CrossRefPubMed

Dekker AB, Krijnen P, Schipper IB. Predictive value of cytokines for developing complications after polytrauma. World J Crit Care Med. 2016;5(3):187–200. https://doi.org/10.5492/wjccm.v5.i3.187.CrossRefPubMedPubMedCentral

10.

Akkose S, Ozgurer A, Bulut M, Koksal O, Ozdemír F, Ozguç H. Relationships between markers of inflammation, severity of injury, and clinical outcomes in hemorrhagic shock. Adv Ther. 2007;24(5):955–62. https://doi.org/10.1007/BF02877699.CrossRefPubMed

11.

Jastrow KM 3rd, Gonzalez EA, McGuire MF, Suliburk JW, Kozar RA, Iyengar S, et al. Early cytokine production risk stratifies trauma patients for multiple organ failure. J Am Coll Surg. 2009;209(3):320–31. https://doi.org/10.1016/j.jamcollsurg.2009.05.002.CrossRefPubMed

12.

Bogner V, Keil L, Kanz KG, Kirchhoff C, Leidel BA, Mutschler W, et al. Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients. Eur J Med Res. 2009;14(7):284–91.CrossRef

13.

Yagmur Y, Ozturk H, Unaldi M, Gedik E. Relation between severity of injury and the early activation of interleukins in multiple-injured patients. Eur Surg Res. 2005;37(6):360–4. https://doi.org/10.1159/000090337.CrossRefPubMed

14.

Haasper C, Kalmbach M, Dikos GD, Meller R, Muller C, Krettek C, et al. Prognostic value of procalcitonin (PCT) and/or interleukin-6 (IL-6) plasma levels after multiple trauma for the development of multi organ dysfunction syndrome (MODS) or sepsis. Technol Health Care. 2010;18(2):89–100. https://doi.org/10.3233/thc-2010-0571.CrossRefPubMed

15.

Maier B, Lefering R, Lehnert M, Laurer HL, Steudel WI, Neugebauer EA, et al. Early versus late onset of multiple organ failure is associated with differing patterns of plasma cytokine biomarker expression and outcome after severe trauma. Shock (Augusta Ga). 2007;28(6):668–74.

16.

Tranca S, Oever JT, Ciuce C, Netea M, Slavcovici A, Petrisor C, et al. sTREM-1, sIL-2Ralpha, and IL-6, but not sCD163, might predict sepsis in polytrauma patients: a prospective cohort study. Eur J Trauma Emerg Surg. 2016. https://doi.org/10.1007/s00068-016-0678-1.CrossRefPubMed

17.

Lausevic Z, Lausevic M, Trbojevic-Stankovic J, Krstic S, Stojimirovic B. Predicting multiple organ failure in patients with severe trauma. Can J Surg Journal canadien de chirurgie. 2008;51(2):97–102.PubMed

18.

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101(6):1644–55.CrossRef

19.

Goris RJ, te Boekhorst TP, Nuytinck JK, Gimbrere JS. Multiple-organ failure. Generalized autodestructive inflammation? Arch Surg (Chicago., Ill: 1960). 1985;120(10):1109–15.CrossRef

20.

Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC. Postinjury multiple organ failure: a bimodal phenomenon. J Trauma. 1996;40(4):501–10 (discussion 10–2).CrossRef

21.

Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23(10):1638–52.CrossRef

22.

Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818–24. https://doi.org/10.1164/ajrccm.149.3.7509706.CrossRef

23.

Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265(3):621–36.CrossRef

24.

Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003;24(1):25–9.CrossRef

25.

Giannoudis PV, Hildebrand F, Pape HC. Inflammatory serum markers in patients with multiple trauma. Can they predict outcome? J Bone Jt Surg (British volume). 2004;86(3):313–23.CrossRef

26.

Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959–70. https://doi.org/10.2217/imt-2016-0020.CrossRefPubMed

27.

Lustenberger T, Kern M, Relja B, Wutzler S, Stormann P, Marzi I. The effect of brain injury on the inflammatory response following severe trauma. Immunobiology. 2016;221(3):427–31. https://doi.org/10.1016/j.imbio.2015.11.011.CrossRefPubMed

28.

Mors K, Braun O, Wagner N, Auner B, Voth M, Stormann P, et al. Influence of gender on systemic IL-6 levels, complication rates and outcome after major trauma. Immunobiology. 2016;221(8):904–10. https://doi.org/10.1016/j.imbio.2016.03.005.CrossRefPubMed

29.

Winfield RD, Delano MJ, Cuenca AG, Cendan JC, Lottenberg L, Efron PA, et al. Obese patients show a depressed cytokine profile following severe blunt injury. Shock (Augusta Ga). 2012;37(3):253–6. https://doi.org/10.1097/SHK.0b013e3182449c0e.CrossRef

30.

Relja B, Menke J, Wagner N, Auner B, Voth M, Nau C, et al. Effects of positive blood alcohol concentration on outcome and systemic interleukin-6 in major trauma patients. Injury. 2016;47(3):640–5. https://doi.org/10.1016/j.injury.2016.01.016.CrossRefPubMed

31.

Tschoeke SK, Hellmuth M, Hostmann A, Ertel W, Oberholzer A. The early second hit in trauma management augments the proinflammatory immune response to multiple injuries. J Trauma. 2007;62(6):1396–403 (discussion 403–4). https://doi.org/10.1097/TA.0b013e318047b7f0.CrossRef

32.

Husebye EE, Lyberg T, Opdahl H, Aspelin T, Stoen RO, Madsen JE, et al. Intramedullary nailing of femoral shaft fractures in polytraumatized patients. A longitudinal, prospective and observational study of the procedure-related impact on cardiopulmonary- and inflammatory responses. Scand J Trauma Resusc Emerg Med. 2012;20:2. https://doi.org/10.1186/1757-7241-20-2.CrossRefPubMedPubMedCentral

33.

LaPar DJ, Rosenberger LH, Walters DM, Hedrick TL, Swenson BR, Young JS, et al. Severe traumatic head injury affects systemic cytokine expression. J Am Coll Surg. 2012;214(4):478–86 (discussion 86–8). https://doi.org/10.1016/j.jamcollsurg.2011.12.015.CrossRef

34.

Hager P, Permert J, Wikstrom AC, Herrington MK, Ostenson CG, Strommer L. Preoperative glucocorticoid administration attenuates the systemic stress response and hyperglycemia after surgical trauma in the rat. Metabolism. 2009;58(4):449–55. https://doi.org/10.1016/j.metabol.2008.10.021.CrossRefPubMed

35.

Frink M, van Griensven M, Kobbe P, Brin T, Zeckey C, Vaske B, et al. IL-6 predicts organ dysfunction and mortality in patients with multiple injuries. Scand J Trauma Resusc Emerg Med. 2009;17:49. https://doi.org/10.1186/1757-7241-17-49.CrossRefPubMedPubMedCentral

36.

Paunel-Gorgulu A, Flohe S, Scholz M, Windolf J, Logters T. Increased serum soluble Fas after major trauma is associated with delayed neutrophil apoptosis and development of sepsis. Crit Care (London, England). 2011;15(1):R20. https://doi.org/10.1186/cc9965.CrossRef

Title: Using IL-6 concentrations in the first 24 h following trauma to predict immunological complications and mortality in trauma patients: a meta-analysis
Authors: Zhi Qiao
Weikang Wang
Luxu Yin
Peng Luo
Johannes Greven
Klemens Horst
Frank Hildebrand
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Trauma and Emergency Surgery / Issue 5/2018
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI: https://doi.org/10.1007/s00068-017-0880-9

At a glance: The STEP trials

Springer Medicine

Using IL-6 concentrations in the first 24 h following trauma to predict immunological complications and mortality in trauma patients: a meta-analysis

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2018

Functional outcome and economic burden of operative management of patellar fractures: the pivotal role of onerous implants

Physical therapists as first-line diagnosticians for traumatic acute rotator cuff tears: a prospective study

The outcome of proximal fifth metatarsal fractures: redefining treatment strategies

Translational research: what is the value of experimental studies in comparison with clinical studies to help understand clinical problems?

Altered long-term health-related quality of life in patients following patella fractures: a long-term follow-up study of 49 patients

Diagnostics and early treatment in prehospital and emergency-room phase in suspicious pelvic ring fractures