The effect of conservative fluid management on Toll-like receptor 4 signal pathway of peripheral blood mononuclear cells and cardiac function in patients with septic shock

Abstract

Objective To evaluate the effect of different fluid resuscitation strategies on the cardiac function in patients with septic shock. Methods Forty-eight patients met diagnostic criteria of septic shock were enrolled prospectively between January 2014 and April 2015. Patients were divided into conservative late fluid management (CLFM) group (n=20) and liberal late fluid management (LLFM) group (n=28) after achieving early goal-directed therapy within 24 h. Haemodynamic parameters, mRNA levels in Toll-like receptor 4 (TLR4) signal pathway and serum levels of myocardial damage markers were compared. Student t-test was used to compare means between two groups. Quantitative data that were not normally distributed were compared by Mann-Whitney U test. Qualitative data were compared using χ2 test. Multivariable Logistic regression analysis was used to identify the independent predictors for prognosis. Results The cardiac function index (CFI) in CLFM group were (5.01±1.41)/min and (5.39±1.48)/min on day 3 and day 7, respectively, and the cardiac index (CI) were (3.43±0.50) and (3.73±0.76) mL·min-1·m-2 on day 3 and day 7, respectively. The CFI and CI in LLFM group were (4.28±1.22)/min, (4.22±1.63)/min and (3.31±1.24), (3.09±1.14) mL·min-1·m-2respectively on day 3 and day 7. The differences between two groups were statistically significant on day 7 (t=2.546, 2.185, both P<0.05). The TLR4 mRNA levels were 3.0±1.1 in CLFM group compared to 4.8±1.4 in LLFM group on day 3 (t=4.786, P<0.01) and 1.6±0.5 compared to 4.0±1.1 on day 7 (t=9.089, P<0.01). Nuclear factor (NF)-κB mRNA levels were 3.5±1.1 in CLFM group compared to 6.8±1.5 in LLFM group on day 3 (t=8.354, P<0.01) and 2.4±0.5 compared to 5.7±0.9 (t=14.820, P<0.01) on day 7. The levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β in CLFM group were lower than those in LLFM group on day 3 and day 7 (all P<0.01). Multivariable Logistic regression analysis showed that fluid balance (OR=1.236, 95%CI: 0.78-1.692, P=0.033), CFI (OR=3.263, 95%CI: 1.136-7.936, P=0.027) and acute physiology and chronic health evaluation Ⅱ(OR=2.064, 95%CI: 1.248-2.898, P=0.003) were the independent predictors for 28-day mortality. Conclusions CLFM may inhibit the product of myocardial depressant factors TNF-α and IL-1β through attenuating TLR4/NF-κB signal pathway activation and thus to improve myocardial function and decrease mortality. Key words: Fluid therapy; Shock, septic; Myocardial depressant factor; Toll-like receptor 4