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.
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.
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).
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Meta-analysis of early excision of burns.Burns. 2006; 32: 145-150
- 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
- Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma.Ann Surg. 1992; 215 (discussion 511-3): 503-511
- Clinical review: the critical care management of the burn patient.Crit Care. 2013; 17: 241
- Morbidity and survival probability in burn patients in modern burn care.Crit Care Med. 2015; 43: 808-815
- Occurrence of multiorgan dysfunction in pediatric burn patients: incidence and clinical outcome.Ann Surg. 2014; 259: 381-387
- 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
- Biomarkers of sepsis.Crit Rev Clin Lab Sci. 2013; 50: 23-36
- Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever.J Infect Dis. 1990; 161: 79-84
- Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose tissue following thermal injury.Crit Care Med. 2014; 42: 1357-1364
- The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.Mol Cell. 2002; 10: 417-426
- American Burn Association consensus conference to define sepsis and infection in burns.J Burn Care Res. 2007; 28: 776-790
- The Third International Consensus definitions for sepsis and septic shock (Sepsis-3).JAMA. 2016; 315: 801-810
- Pathophysiologic response to burns in the elderly.EBioMedicine. 2015; 2: 1536-1548
- Impaired immune response in elderly burn patients: new insights into the immune-senescence phenotype.Ann Surg. 2016; 264: 195-202
- Morphological changes in subcutaneous white adipose tissue after severe burn injury.J Burn Care Res. 2016; 37: e96-103
- Endotoxin priming improves clearance of Pseudomonas aeruginosa in wild-type and interleukin-10 knockout mice.Infect Immun. 2005; 73: 7340-7347
- Effects of granulocyte-macrophage colony-stimulating factor in burn patients.Arch Surg. 1991; 126: 74-79
- 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
- Granulocyte colony-stimulating factor prophylaxis before operation protects against lethal consequences of postoperative peritonitis.Surgery. 1994; 116: 925-934
- Evaluation of opsonophagocytic dysfunctions in severely burned patients by luminol-dependent chemiluminescence.Microbiol Immunol. 1993; 37: 563-571
- Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections after severe burn injury.Shock. 2009; 32: 435-441
- Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection.J Immunol. 2008; 180: 3038-3048
- Impairment of leukocyte trafficking in a murine pleuritis model by IL-4 and IL-10.Inflammation. 2003; 27: 161-174
- Interleukin 10 inhibits the release of CC chemokines during human endotoxemia.J Infect Dis. 2000; 181: 613-620
- IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium.J Immunol. 2013; 191: 4838-4848
- From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation.Immunol Cell Biol. 2014; 92: 331-339
- Muscular interleukin-6 and its role as an energy sensor.Med Sci Sports Exerc. 2012; 44: 392-396
- 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
- Exercise-induced myokines and their role in chronic diseases.Brain Behav Immun. 2011; 25: 811-816
- Muscles, exercise and obesity: skeletal muscle as a secretory organ.Nat Rev Endocrinol. 2012; 8: 457-465
- Characteristics of bloodstream infections in burn patients: an 11-year retrospective study.Burns. 2012; 38: 685-690
- Epidemiology of bloodstream infections in burn-injured patients: a review of the national burn repository.J Burn Care Res. 2010; 31: 521-528
- Diagnosis of infection in sepsis: an evidence-based review.Crit Care Med. 2004; 32: S466-S494
- Comparison of wound culture and bronchial lavage in the severely burned child: implications for antimicrobial therapy.Arch Surg. 1998; 133: 1275-1280
- Pathophysiologic response to severe burn injury.Ann Surg. 2008; 248: 387-401
- 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
- The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute phase postburn.Ann Surg. 2007; 246: 351-362
- Propranolol as a modulator of M2b monocytes in severely burned patients.J Leukoc Biol. 2011; 89: 797-803
- 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
Published online: November 09, 2017
Accepted: August 30, 2017
Supported by grants from the Canadian Institutes of Health Research (123336), Canadian Foundation for Innovation Leader's Opportunity Fund (Project #25407), National Institutes of Health (2R01GM087285-05A1, R01 GM087285-01), and Physicians' Services Incorporated Foundation: Health Research Grant Program.
© 2017 Elsevier Inc. All rights reserved.