Abstract
BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly. The aim of this study was to analyze whether IL-6 rs1800795 polymorphism is associated with septic shock-related death in European white patients who underwent major surgery.MethodsWe performed a retrospective study on 202 septic shock patients who underwent major cardiac or abdominal surgery. The septic shock was established according to the international septic shock definition. The primary outcome variable was the death within 90 days after diagnosis of septic shock. The IL-6 rs1800795 polymorphism was genotyped by Sequenom’s MassARRAY platform.ResultsThe median age of the patients was 73 years, 63.4% were male, and more than 40% of patients had heart disease and hypertension. Overall, the survival analysis showed that 111 (55%) patients died with a survival median of 39 days (95% CI 30.7; 47.2). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). Patients with IL-6 rs1800795 CC genotype had higher mortality rate than the IL-6 rs1800795 GG/CG genotype at days 7 [31.6% (6/19) vs. 10.4% (19/183); log-rank test (p = 0.005)] and 28 [57.9% (11/19) vs. 33.3% (61/183); log-rank test (p = 0.009)], and 90 [68.4% (13/19) vs. 53.5% (98/183); log-rank test (p = 0.006)]. The IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death during the first 7 days [adjusted hazard ratio (aHR 4.65; p = 0.002), 28 days (aHR 2.50; p = 0.006), and 90 days (aHR 2.28; p = 0.006)] with septic shock. When patients were stratified by type of surgery, those with IL-6 rs1800795 CC genotype who underwent cardiac surgery had higher risk of death during the first 7 days (aHR 18.39; p = 0.001) and 28 days (aHR 6.1; p = 0.025) than IL-6 rs1800795 GG/GC carrier, whereas patients with IL-6 rs1800795 CC genotype who underwent abdominal surgery had higher risk of death during all follow-up (aHR 1.98; p = 0.050) than IL-6 rs1800795 GG/GC carrier.ConclusionsThe presence of IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death in patients who underwent major cardiac or abdominal surgery. These findings need robust validation in bigger independent cohorts.
Highlights
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly
The presence of IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death in patients who underwent major cardiac or abdominal surgery
When the population was stratified according to IL-6 rs1800795 genotype, we only found significant differences in chronic obstructive pulmonary disease (COPD) frequencies (p = 0.027)
Summary
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly. Despite advances in treatment and supportive care in recent years, septic shock is a major healthcare problem, affecting millions of people around the world each year and killing a high percentage of patients in hospitals [2], especially in intensive care unit (ICU) [2, 3]. In these patients, early and aggressive treatment has not improved survival [4], and patients that survive to sepsis remain at increased risk to death in the following months and years [5]. Proinflammatory cytokines may activate the suppressor of cytokine signaling-3 (SOCS3) and may modulate the cytokine signaling, usually preventing, but in some cases aggravating the outcome of infections [9]
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