Advertisement

European Journal of Trauma and Emergency Surgery

, Volume 44, Issue 5, pp 679–687 | Cite as

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

  • Zhi Qiao
  • Weikang Wang
  • Luxu Yin
  • Peng Luo
  • Johannes Greven
  • Klemens Horst
  • Frank Hildebrand
Review Article

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.

Keywords

IL-6 Trauma Mortality Sepsis MODS MOF 

Notes

Compliance with ethical standards

Conflict of interest

Zhi Qiao is supported by the China Scholarship council (no. 201508080049). Weikang Wang, Luxu Yin, Peng Luo, Johannes Greven, Klemens Horst, and Frank Hildebrand declare that they have no conflict of interest.

Ethical standards

This analysis collected secondary data, and no ethics committee approval was required.

References

  1. 1.
    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.CrossRefGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    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.CrossRefGoogle Scholar
  5. 5.
    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).CrossRefGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    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.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefPubMedGoogle Scholar
  9. 9.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.Google Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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).CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 23.
    Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265(3):621–36.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefGoogle Scholar
  32. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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.CrossRefGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 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.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Zhi Qiao
    • 1
  • Weikang Wang
    • 1
  • Luxu Yin
    • 1
  • Peng Luo
    • 1
  • Johannes Greven
    • 1
  • Klemens Horst
    • 1
  • Frank Hildebrand
    • 1
  1. 1.Department of Trauma and Reconstructive SurgeryRWTH Aachen University HospitalAachenGermany

Personalised recommendations