Predictive value of sepsis-induced coagulopathy score on 30-day mortality in septic patients / 中华危重病急救医学

Objective:To evaluate the predictive effect of sepsis-induced coagulopathy (SIC) score level on the prognosis of septic patients under sepsis 3.0 criteria.Methods:A retrospective single-center observational study was conducted on the septic patients admitted to the department of critical care medicine and the department of emergency in Guangdong Provincial People's Hospital from August 2016 to July 2021. The baseline data, laboratory indexes and SIC scores of the patients were collected on the first and fourth (4th) day after hospitalization. Whether the patients were survival within 30 days after enrollment was recorded. Univariate and multivariate Logistic regression were used to analyze the independent risk factors for 30-day mortality in septic patients. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of SIC score on the 30-day prognosis of septic patients.Results:A total of 173 patients met the inclusion criteria including 111 (64%) survivors and 62 (36%) non-survivors. There were significant differences in lymphocyte count (LYM), sequential organ failure assessment (SOFA), oxygenation index (PaO 2/FiO 2) and cardiovascular SOFA score between the survival group and the non-survival group. And there were no significant differences in other indexes. On the first day of admission, there were statistically significant differences in PaO 2/FiO 2, cardiovascular SOFA score, LYM, SIC score between the non-survival group and the survival group. There were significant differences in international normalized ratio (INR), prothrombin activity (PTA), prothrombin time (PT), PaO 2/FiO 2, cardiovascular SOFA score, LYM, C-reactive protein (CRP) and procalcitonin (PCT) between the two groups on the 4th day after admission. The mortality of septic patients increased with the increase of SIC score. Binary Logistic regression analysis showed that SIC score and LYM on the 4th day after admission were independent risk factors for 30-day mortality in septic patients (both P < 0.05). The ROC curve showed that SIC score had a certain predictive value for the 30-day prognosis of septic patients [area under the ROC curve (AUC) = 0.712, 95% confidence interval (95% CI) was 0.629-0.794, P < 0.001]. The predictive value of SIC score combined with LYM was better than that of the two alone (AUC = 0.748, 95% CI was 0.688-0.828, P < 0.001). Conclusions:The SIC score has a certain predictive value for the 30-day prognosis of septic patients. The predictive value of SIC score combined with LYM is better than that of the two alone, which is expected to be a potential indicator for early assessment of the condition and prognosis of septic patients.

β1 receptor blocker decreases the myocardial inflammation in the sepsis adult rats through inhibition of TLR4/NF-κB signaling pathway / 中华危重病急救医学

Objective? To?explore?whether?β1?receptor?blocker?could?decrease?the?myocardial?inflammation??through?the?Toll-like?receptor?4/nuclear?factor-κB?(TLR4/NF-κB)?signaling?pathway?in?the?sepsis?adult?rats.? Methods? ?Sixty?male?Wistar?rats?(250-300?g)?aged?3?months?old?were?allocated?to?four?groups?by?random?number?table?(n?=?15):?sham?operation?group?(S?group),?sepsis?model?group?(CLP?group),?β1?receptor?blocker?esmolol?intervention?group??(ES?group),?and?inhibitor?of?the?TLR4?E5564?intervention?group?(E5564?group).?The?rat?sepsis?model?was?established?by?cecal?ligation?and?puncture?(CLP);?S?group?of?rats?underwent?only?an?incision.?Rats?in?S?group,?CLP?group?and?E5564?group?were?subcutaneous?injected?with?0.9%?sodium?chloride?(NaCl)?2.0?mL/kg.?Besides,?the?rats?in?ES?group?were?injected?with?esmolol?(15?mg·kg-1·h-1)?by?micro?pump?through?the?caudal?vein.?The?rats?in?E5564?group?were?injected?with?E5564?(0.3?mg·kg-1·h-1)?by?micro?pump?through?the?caudal?vein?1?hour?before?the?CLP?surgery.?Samples?were?collected?6?hours?after?the?modelling?in?each?group.?The?average?arterial?pressure?(MAP)?and?cardiac?output?index?(CI)?were?monitored?by?PU?electrical?conduction?ECG?monitor.?The?levels?of?serum?cardiac?troponin?I?(cTnI),?interleukin-1β?? (IL-1β)?and?tumor?necrosis?factor-α(TNF-α)?were?detected?by?enzyme?linked?immunosorbent?assay?(ELISA).?The?expressions?of?TLR4,?NF-κB?p65,?IL-1β,?TNF-α?in?myocardial?tissue?was?detected?by?Western?Blot.? Results? There?was?no?significant?difference?in?MAP?in?each?group.?Compared?with?the?S?group,?the?CI?in?the?CLP?group?was?significantly?decreased,?the?levels?of?serum?cTnI,?IL-1β,?TNF-α?were?significantly?increased,?the?protein?expressions?of?myocardial?tissue?TLR4,?NF-κB?p65,?IL-1β?and?TNF-α?were?significantly?increased.?Compared?with?the?CLP?group,?the?CI?in?the?ES?group?and?E5564?group?were?significantly?increased?(mL·s-1·m-2:?58.6±4.3,?58.9±4.4?vs.?41.2±3.9,?both?P?<?0.01),?the?levels?of?serum?cTnI,?IL-1β?and?TNF-α?were?significantly?decreased?[cTnI?(μg/L):?1?113.81±26.64,?1?115.74±25.90?vs.?1?975.96±42.74;?IL-1β(ng/L):?39.6±4.3,?38.9±4.4?vs.?61.2±3.9;?TNF-α?(ng/L):?43.1±2.8,?48.7±2.6?vs.?81.3±4.4,?all?P?<?0.01],?the?protein?expressions?of?myocardial?tissue?NF-κB?p65,?IL-1β,??TNF-αwere?significantly?decreased?(NF-κB?p65/β-actin:?0.31±0.03,?0.43±0.04?vs.?0.85±0.08;?IL-1β/β-actin:?0.28±0.05,?0.32±0.03?vs.?0.71±0.06;?TNF-α/β-actin:?0.18±0.04,?0.28±0.03?vs.?0.78±0.07,?all?P?<?0.01),?but?there?was?no?significant?difference?in?protein?expression?of?TLR4?(TLR4/β-actin:?0.89±0.07,?0.87±0.09?vs.?0.95±0.09,?both?P?>?0.05).?There?was?no?significant?difference?in?CI,?the?levels?of?serum?cTnI,?IL-1β,?TNF-α,?and?the?protein?expressions?of?myocardial?tissue?TLR4,?NF-κB?p65,?IL-1β,?TNF-αbetween?ES?group?and?E5564?group?(all?P?>??0.05).? Conclusion? β1?receptor?blocker?esmolol?may?inhibit?myocardial?inflammatory?response?in?sepsis?adult?rats?through?TLR4/NF-κB?signaling?pathway,?thereby?alleviating?sepsis-induced?myocardial?injury.

β1 receptor blocker decreases the myocardial inflammation in the sepsis adult rats through inhibition of TLR4/NF-ΚB signaling pathway / 中华危重病急救医学

OBJECTIVE@#To explore whether β1 receptor blocker could decrease the myocardial inflammation through the Toll-like receptor 4/nuclear factor-ΚB (TLR4/NF-ΚB) signaling pathway in the sepsis adult rats.@*METHODS@#Sixty male Wistar rats (250-300 g) aged 3 months old were allocated to four groups by random number table (n = 15): sham operation group (S group), sepsis model group (CLP group), β1 receptor blocker esmolol intervention group (ES group), and inhibitor of the TLR4 E5564 intervention group (E5564 group). The rat sepsis model was established by cecal ligation and puncture (CLP); S group of rats underwent only an incision. Rats in S group, CLP group and E5564 group were subcutaneous injected with 0.9% sodium chloride (NaCl) 2.0 mL/kg. Besides, the rats in ES group were injected with esmolol (15 mg×kg-1×h-1) by micro pump through the caudal vein. The rats in E5564 group were injected with E5564 (0.3 mg×kg-1×h-1) by micro pump through the caudal vein 1 hour before the CLP surgery. Samples were collected 6 hours after the modelling in each group. The average arterial pressure (MAP) and cardiac output index (CI) were monitored by PU electrical conduction ECG monitor. The levels of serum cardiac troponin I (cTnI), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The expressions of TLR4, NF-ΚB p65, IL-1β, TNF-α in myocardial tissue was detected by Western Blot.@*RESULTS@#There was no significant difference in MAP in each group. Compared with the S group, the CI in the CLP group was significantly decreased, the levels of serum cTnI, IL-1β, TNF-α were significantly increased, the protein expressions of myocardial tissue TLR4, NF-ΚB p65, IL-1β and TNF-α were significantly increased. Compared with the CLP group, the CI in the ES group and E5564 group were significantly increased (mL×s-1×m-2: 58.6±4.3, 58.9±4.4 vs. 41.2±3.9, both P < 0.01), the levels of serum cTnI, IL-1β and TNF-α were significantly decreased [cTnI (μg/L): 1 113.81±26.64, 1 115.74±25.90 vs. 1 975.96±42.74; IL-1β (ng/L): 39.6±4.3, 38.9±4.4 vs. 61.2±3.9; TNF-α (ng/L): 43.1±2.8, 48.7±2.6 vs. 81.3±4.4, all P < 0.01], the protein expressions of myocardial tissue NF-ΚB p65, IL-1β, TNF-α were significantly decreased (NF-ΚB p65/β-actin: 0.31±0.03, 0.43±0.04 vs. 0.85±0.08; IL-1β/β-actin: 0.28±0.05, 0.32±0.03 vs. 0.71±0.06; TNF-α/β-actin: 0.18±0.04, 0.28±0.03 vs. 0.78±0.07, all P < 0.01), but there was no significant difference in protein expression of TLR4 (TLR4/β-actin: 0.89±0.07, 0.87±0.09 vs. 0.95±0.09, both P > 0.05). There was no significant difference in CI, the levels of serum cTnI, IL-1β, TNF-α, and the protein expressions of myocardial tissue TLR4, NF-ΚB p65, IL-1β, TNF-α between ES group and E5564 group (all P > 0.05).@*CONCLUSIONS@#β1 receptor blocker esmolol may inhibit myocardial inflammatory response in sepsis adult rats through TLR4/NF-ΚB signaling pathway, thereby alleviating sepsis-induced myocardial injury.

Esmolol improves clinical outcome and tissue oxygen metabolism in patients with septic shock through controlling heart rate / 中华危重病急救医学

ObjectiveTo investigate whether esmolol could improve clinical outcome and tissue oxygen metabolism by controlling heart rate (HR) in patients with septic shock.Methods A single-center double-blinded randomized controlled trial was conducted. The patients suffering from septic shock received 6-hour early goal directed therapy (EGDT) with pulmonary artery wedge pressure≥ 12 mmHg (1 mmHg = 0.133 kPa) or central venous pressure (CVP)≥ 12 mmHg requiring norepinephrine to maintain mean arterial pressure (MAP)≥ 65 mmHg and HR≥95 bpm admitted to intensive care unit (ICU) of Guangdong General Hospital from September 2013 to September 2014 were enrolled. They were randomly divided into esmolol group and control group by computer-based random number generator. All patients received conventional basic treatment, while those in the esmolol group received in addition persistent esmolol infusion by micro pump with dosage of 0.05 mg·kg-1·min-1 with the dosage adjusted to maintain HR lower than 100 bpm within 24 hours. The patients in control group did not receive drug intervention for HR. The primary end-points consisted of length of stay in ICU and 28-day mortality. The secondary end-points included hemodynamic parameters [HR, MAP, CVP, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI)] and tissue oxygen metabolism parameters [central venous oxygen saturation (ScvO2), lactate level (Lac)]before and 24, 48, 72 hours after the treatment.Results A total of 48 patients with septic shock were enrolled with 24 patients in esmolol group and 24 in control group.① The primary end-points: compared with control group, the length of stay in the ICU in the esmolol group was significantly shortened (days: 13.75±8.68 vs. 21.70±6.06,t = 3.680, P = 0.001), and 28-day mortality was significantly lowered [25.0% (6/24) vs. 62.5% (15/24),χ2 = 6.857,P = 0.009].② The secondary end-points: there were no significant difference in the hemodynamic and tissue metabolism parameters before treatment between two groups. No significant difference was found between before and after treatment of all above parameters in control group. HR and Lac in the esmolol group were obviously declined, SVI, SVRI, ScvO2 were gradually increased, but no significant difference in MAP, CVP, and CI was found. Compared with the control group, HR in the esomolol group was significantly lowered (bpm: 84.4±3.5 vs. 111.2±7.2,P< 0.01), SVRI and ScvO2 were significantly increased from 24 hours [SVRI (kPa·s·L-1·m-2): 137.9±1.6 vs. 126.9±1.3, ScvO2: 0.652±0.017 vs. 0.620±0.017, bothP< 0.01]; SVI was significantly increased (mL/m2: 39.9±2.2 vs. 36.8±1.7,P< 0.01) and Lac level significantly declined from 48 hours (mmol/L: 2.8±0.3 vs. 3.4±0.3,P< 0.01).Conclusion The results demonstrate that HR controlled by a titrated esmolol infusion given to septic shock patients was associated with an improvement in tissue metabolism, reduction in the length of ICU stay and lowering of 28-day mortality.