Plasma concentrations of pro- and anti-inflammatory cytokines and outcome prediction in elderly hip fracture patients

Abstract

Background Hip fractures, particularly intertrochanteric fractures, frequently occur in the elderly, and they are associated with a high incidence of complications and mortality. The development of markers is essential to allow for adjustments to treatment strategies in patients, as it remains unclear why some patients endure organ failure and others do not under seemingly similar clinical conditions. Objective Our objective was to determine the kinetics of tumour necrosis factor (TNF)-a, interleukin (IL)-6 and IL-10 during the hospitalisation of patients and to examine the relationship of these parameters to outcome (mortality and complications) 6 months and 12 months postoperatively. Methods and subjects A total of 127 elderly patients, who underwent hip fracture surgery, were prospectively followed up for 12 months, and 60 healthy elderly volunteers were enrolled in the control group to examine the effects of trauma and surgery on the inflammatory response. The epidemiological characteristics, chronic medical conditions and type of operation and anaesthetic were recorded. Cognition was evaluated using the Mini-Mental State Examination, and TNF-a, IL-6 and IL-10 levels were assessed during admission and preoperatively (post-anaesthesia) as well as 1 h, 1 day, 3 days and 5 days postoperatively. During the follow-up period, serious complications and mortality within 1 year were evaluated. Results Overall, 96 patients survived, and 31 died within the 6-month postoperative period; 43 patients died, and 84 survived when examining the 12-month postoperative period. There were significant within-subject effects of time on TNF-a, IL-6 and IL-10 ( P < 0.001, P < 0.001 and P < 0.001). The above three cytokines were all significantly increased in the hip fracture patients compared with the control group. There were also differences in the kinetic patterns of all three parameters when the patients who died were compared with those who survived during the 6-month and 12-month postoperative periods. Multiple logistic regression analysis showed that TNF-a at 1 day (odds ratio (OR) = 1.020, P = 0.045) and 3 days (OR = 1.034, P = 0.037) postoperatively and IL-6 at 1 day (OR = 1.048, P = 0.000) postoperatively were independent predictors of mortality at 6 months; IL-6 (OR = 1.019, P = 0.025) and IL-10 (OR = 1.018, P = 0.042) at 1 day postoperatively were independent predictors of mortality at 1 year. The analysis of the receiver operating characteristics curve (ROC) showed that only IL-6 or IL-10 had the highest values for the area under the curve for mortality at 6 months and 12 months. Of the 84 patients who survived, 23 patients had 32 complications. The most common complication was pneumonia infection (11/84, 13%). TNF-a, IL-6 and IL-10 kinetics were found to differ in patients with complications compared to those without complications and in patients with infections compared with patients without complications. Multiple logistic regression analysis showed that IL-6 (OR = 1.081, P = 0.000) at 1 day postoperatively was an independent outcome predictor. Conclusion In elderly hip fracture patients, cytokine concentrations (TNF-a, IL-6 and IL-10) represented independent outcome predictors for adverse postoperative outcomes (mortality and complications). The inflammatory response played an important role in postoperative organ dysfunction in elderly hip fracture patients, and further study is needed to define whether decreasing the inflammatory response through cytokine antibodies or damage control strategies would decrease mortality and complication following hip fracture.