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Infection/Inflammation| Volume 163, ISSUE 2, P409-414, February 2018

Septic predictor index: A novel platform to identify thermally injured patients susceptible to sepsis

  • Author Footnotes
    1 These authors contributed equally.
    Peter Chen
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Sunnybrook Research Institute, Toronto, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally.
    Mile Stanojcic
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Sunnybrook Research Institute, Toronto, Ontario, Canada
    Search for articles by this author
  • Marc G. Jeschke
    Correspondence
    Reprint requests: Marc G. Jeschke, MD, PhD, Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre; Division of Plastic Surgery, Department of Surgery, Department of Immunology, University of Toronto; Sunnybrook Research Institute, 2075 Bayview Ave., Rm D704, Toronto, Ontario, M4N 3M5, Canada.
    Affiliations
    Sunnybrook Research Institute, Toronto, Ontario, Canada

    Division of Plastic Surgery Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally.
Published:November 09, 2017DOI:https://doi.org/10.1016/j.surg.2017.08.010

      Background

      During the past decades' sepsis has become the major cause of death in severely burned patients. Despite the importance of burn sepsis, its diagnosis, let alone its prediction, is difficult if not impossible. Recently, we have demonstrated burn patients have increased NLRP3 inflammasome activation in white adipose tissue. We aimed to delineate a unique immune profile that can be used to identify septic outcomes in severely burned patients.

      Methods

      Adult burn patients (n = 37) admitted to our burn center between June 2013–2015 were enrolled in this study. White adipose tissue from the site of injury and plasma were collected from severely burned patients (>20% total body surface area) within 96 hours after thermal injury, indiscriminate of sex or age.

      Results

      We found that patients exhibiting aberrantly high levels of proinflammatory interleukin-1β and decreased macrophages at the site of injury are highly susceptible to development of sepsis. Septic patients also had increased anti-inflammatory (interleukin-10, interleukin-1RA) cytokines in plasma. The Septic Predictor Index was generated as a quotient for the site of injury macrophage proportion and interleukin-1β production. All patients who eventually develop sepsis had septic predictor index values >0.5. Septic patients with Septic Predictor Index values >1 all had sepsis onset within 12 days post-injury, whereas patients with Septic Predictor Index values between 0.5–1 all had later onset (>12 days).

      Conclusion

      The Septic Predictor Index can determine sepsis onset accurately in thermally injured patients a priori and further enables surgeons to develop clinical studies and focused therapies specifically designed for septic cohorts.
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      References

        • Ong Y.S.
        • Samuel M.
        • Song C.
        Meta-analysis of early excision of burns.
        Burns. 2006; 32: 145-150
        • Pereira C.T.
        • Barrow R.E.
        • Sterns A.M.
        • et al.
        Age-dependent differences in survival after severe burns: a unicentric review of 1,674 patients and 179 autopsies over 15 years.
        J Am Coll Surg. 2006; 202: 536-548
        • Kudsk K.A.
        • Croce M.A.
        • Fabian T.C.
        • et al.
        Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma.
        Ann Surg. 1992; 215 (discussion 511-3): 503-511
        • Snell J.A.
        • Loh N.H.
        • Mahambrey T.
        • et al.
        Clinical review: the critical care management of the burn patient.
        Crit Care. 2013; 17: 241
        • Jeschke M.G.
        • Pinto R.
        • Kraft R.
        • et al.
        Morbidity and survival probability in burn patients in modern burn care.
        Crit Care Med. 2015; 43: 808-815
        • Kraft R.
        • Herndon D.N.
        • Finnerty C.C.
        • et al.
        Occurrence of multiorgan dysfunction in pediatric burn patients: incidence and clinical outcome.
        Ann Surg. 2014; 259: 381-387
        • Kayambu G.
        • Boots R.J.
        • Paratz J.D.
        Early rehabilitation in sepsis: a prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article).
        BMC Anesthesiol. 2011; 11: 21
        • Faix J.D.
        Biomarkers of sepsis.
        Crit Rev Clin Lab Sci. 2013; 50: 23-36
        • Cannon J.G.
        • Tompkins R.G.
        • Gelfand J.A.
        • et al.
        Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever.
        J Infect Dis. 1990; 161: 79-84
        • Stanojcic M.
        • Chen P.
        • Harrison R.A.
        • et al.
        Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose tissue following thermal injury.
        Crit Care Med. 2014; 42: 1357-1364
        • Martinon F.
        • Burns K.
        • Tschopp J.
        The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
        Mol Cell. 2002; 10: 417-426
        • Greenhalgh D.G.
        • Saffle J.R.
        • Holmes J.H.
        • et al.
        American Burn Association consensus conference to define sepsis and infection in burns.
        J Burn Care Res. 2007; 28: 776-790
        • Singer M.
        • Deutschman C.S.
        • Seymour C.W.
        • et al.
        The Third International Consensus definitions for sepsis and septic shock (Sepsis-3).
        JAMA. 2016; 315: 801-810
        • Jeschke M.G.
        • Patsouris D.
        • Stanojcic M.
        • et al.
        Pathophysiologic response to burns in the elderly.
        EBioMedicine. 2015; 2: 1536-1548
        • Stanojcic M.
        • Chen P.
        • Xiu F.
        • et al.
        Impaired immune response in elderly burn patients: new insights into the immune-senescence phenotype.
        Ann Surg. 2016; 264: 195-202
        • Saraf M.K.
        • Herndon D.N.
        • Porter C.
        • et al.
        Morphological changes in subcutaneous white adipose tissue after severe burn injury.
        J Burn Care Res. 2016; 37: e96-103
        • Varma T.K.
        • Durham M.
        • Murphey E.D.
        • et al.
        Endotoxin priming improves clearance of Pseudomonas aeruginosa in wild-type and interleukin-10 knockout mice.
        Infect Immun. 2005; 73: 7340-7347
        • Cioffi Jr, W.G.
        • Burleson D.G.
        • Jordan B.S.
        • et al.
        Effects of granulocyte-macrophage colony-stimulating factor in burn patients.
        Arch Surg. 1991; 126: 74-79
        • Heard S.O.
        • Fink M.P.
        • Gamelli R.L.
        • et al.
        Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute traumatic brain injury or cerebral hemorrhage. The Filgrastim Study Group.
        Crit Care Med. 1998; 26: 748-754
        • Lorenz W.
        • Reimund K.P.
        • Weitzel F.
        • et al.
        Granulocyte colony-stimulating factor prophylaxis before operation protects against lethal consequences of postoperative peritonitis.
        Surgery. 1994; 116: 925-934
        • Ono Y.
        • Kunii O.
        • Kobayashi K.
        • et al.
        Evaluation of opsonophagocytic dysfunctions in severely burned patients by luminol-dependent chemiluminescence.
        Microbiol Immunol. 1993; 37: 563-571
        • Bohannon J.
        • Fang G.
        • Cui W.
        • et al.
        Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury.
        Shock. 2009; 32: 435-441
        • Bohannon J.
        • Cui W.
        • Cox R.
        • et al.
        Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection.
        J Immunol. 2008; 180: 3038-3048
        • Fine J.S.
        • Rojas-Triana A.
        • Jackson J.V.
        • et al.
        Impairment of leukocyte trafficking in a murine pleuritis model by IL-4 and IL-10.
        Inflammation. 2003; 27: 161-174
        • Olszyna D.P.
        • Pajkrt D.
        • Lauw F.N.
        • et al.
        Interleukin 10 inhibits the release of CC chemokines during human endotoxemia.
        J Infect Dis. 2000; 181: 613-620
        • Saxena A.
        • Chen W.
        • Su Y.
        • et al.
        IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium.
        J Immunol. 2013; 191: 4838-4848
        • Pal M.
        • Febbraio M.A.
        • Whitham M.
        From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation.
        Immunol Cell Biol. 2014; 92: 331-339
        • Pedersen B.K.
        Muscular interleukin-6 and its role as an energy sensor.
        Med Sci Sports Exerc. 2012; 44: 392-396
        • Steensberg A.
        • van Hall G.
        • Osada T.
        • et al.
        Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6.
        J Physiol. 2000; 529: 237-242
        • Pedersen B.K.
        Exercise-induced myokines and their role in chronic diseases.
        Brain Behav Immun. 2011; 25: 811-816
        • Pedersen B.K.
        • Febbraio M.A.
        Muscles, exercise and obesity: skeletal muscle as a secretory organ.
        Nat Rev Endocrinol. 2012; 8: 457-465
        • Patel B.M.
        • Paratz J.D.
        • Mallet A.
        • et al.
        Characteristics of bloodstream infections in burn patients: an 11-year retrospective study.
        Burns. 2012; 38: 685-690
        • Shupp J.W.
        • Pavlovich A.R.
        • Jeng J.C.
        • et al.
        Epidemiology of bloodstream infections in burn-injured patients: a review of the national burn repository.
        J Burn Care Res. 2010; 31: 521-528
        • Cohen J.
        • Brun-Buisson C.
        • Torres A.
        • et al.
        Diagnosis of infection in sepsis: an evidence-based review.
        Crit Care Med. 2004; 32: S466-S494
        • Ramzy P.I.
        • Herndon D.N.
        • Wolf S.E.
        • et al.
        Comparison of wound culture and bronchial lavage in the severely burned child: implications for antimicrobial therapy.
        Arch Surg. 1998; 133: 1275-1280
        • Jeschke M.G.
        • Chinkes D.L.
        • Finnerty C.C.
        • et al.
        Pathophysiologic response to severe burn injury.
        Ann Surg. 2008; 248: 387-401
        • Gauglitz G.G.
        • Williams F.N.
        • Herndon D.N.
        • et al.
        Burns: where are we standing with propranolol, oxandrolone, recombinant human growth hormone, and the new incretin analogs?.
        Curr Opin Clin Nutr Metab Care. 2011; 14: 176-181
        • Jeschke M.G.
        • Finnerty C.C.
        • Suman O.E.
        • et al.
        The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute phase postburn.
        Ann Surg. 2007; 246: 351-362
        • Kobayashi M.
        • Jeschke M.G.
        • Asai A.
        • et al.
        Propranolol as a modulator of M2b monocytes in severely burned patients.
        J Leukoc Biol. 2011; 89: 797-803
        • Muthu K.
        • He L.K.
        • Szilagyi A.
        • et al.
        Propranolol restores the tumor necrosis factor-alpha response of circulating inflammatory monocytes and granulocytes after burn injury and sepsis.
        J Burn Care Res. 2009; 30: 8-18