血清冷诱导RNA结合蛋白与脓毒性休克患者病情严重程度及预后的相关性

目的探讨血清冷诱导RNA结合蛋白(CIRP)与脓毒性休克患者病情严重程度及预后的相关性。方法回顾性选取2018年1月至2020年1月海南医学院第二附属医院急诊重症监护室(EICU)收治的脓毒性休克患者107例为研究对象。收集患者一般资料、急性生理和慢性健康状况评估系统Ⅱ(APACHEⅡ)评分、序贯器官衰竭估计(SOFA)评分、CIRP、血乳酸(Lac)、血清肌酐(s Cr)、血白细胞计数(WBC)、中性粒细胞百分比(NeuR)及降钙素原(PCT)。根据患者28 d预后情况将其分为死亡组和存活组。采用Pearson相关分析探讨脓毒性休克患者CIRP与SOFA评分及APACHEⅡ评分的相关性;采用Logistic回归分析探讨脓毒性休克患者28 d死亡的危险因素;绘制受试者工作特征(ROC)曲线并评估各指标对脓毒性休克患者28 d死亡的预测价值。结果随访28 d后,25例(23.4%)患者死亡(死亡组),82例(76.6%)患者存活(存活组)。死亡组APACHEⅡ评分、SOFA评分、CIRP、血Lac、s Cr及PCT水平明显高于存活组(P <0.05)。Pearson相关分析结果显示,脓毒性休克患者CIRP与SOFA评分及APACHEⅡ评分均呈正相关(r=0.337,P=0.005;r=0.249,P=0.039)。多因素Logistic回归分析结果显示,APACHEⅡ评分[OR=1.138,95%CI(1.066,1.214)]、SOFA评分[OR=1.326,95%CI(1.174,1.478)]、CIRP[OR=1.322,95%CI(1.141,1.502)]及PCT[OR=1.055,95%CI(1.003,1.108)]为脓毒性休克患者28 d死亡的危险因素(P <0.05)。CIRP、SOFA评分、APACHEⅡ评分、PCT预测脓毒性休克患者28 d死亡的ROC曲线下面积(AUC)分别为0.915[95%CI(0.823,0.969)]、0.834[95%CI(0.726,0.913)]、0.798[95%CI(0.684,0.885)]、0.685[95%CI(0.562,0.792)]。CIRP预测脓毒性休克患者28 d死亡的AUC大于SOFA评分、APACHEⅡ评分、PCT预测脓毒性休克患者28 d死亡的AUC(Z=2.134,P=0.041;Z=2.348,P=0.026;Z=3.64,P <0.001)。CIRP的最佳临界值为2.6μg/L时,预测脓毒性休克患者28 d死亡的敏感度为96.8%,特异度为73.7%。结论血清CIRP与脓毒性休克患者病情严重程度及预后密切相关,为28 d死亡的独立危险因素,可作为评价脓毒性休克患者预后的较好指标。     

Plasmapheresis in severe sepsis and septic shock: a prospective,randomised, controlled trial

OBJECTIVE: To determine the therapeutic efficacy and safety of plasmapheresis in the treatment of patients with severe sepsis and septic shock. DESIGN: Prospective, randomised, clinical trial with a planned, midstudy, interim analysis. SETTING: Intensive care unit in a university hospital in Archangels, Russia. PATIENTS: Consecutive patients with severe sepsis or septic shock. INTERVENTIONS: One hundred and six patients were randomised to receive either standard therapy or an add-on treatment with plasmapheresis. MEASUREMENTS AND RESULTS: The primary endpoint was 28-day survival. Septic shock was diagnosed in 57% of the plasmapheresis-treated patients and 54% of the control patients. Mean APACHE III score at entry was 56.4 in the plasmapheresis group and 53.5 in the control group. The 28-day, all-cause mortality rate was 33.3% (18/54) in the plasmapheresis group and 53.8% (28/52) in the control group. This represents a relative risk for fatal outcome in the plasmapheresis group of 0.61, an absolute risk reduction of 20.5% and a number of patients needed to treat of 4.9. Apart from six transient episodes of hypotension and one allergic reaction to fresh frozen plasma, no adverse reactions were attributable to the plasmapheresis treatment in this study. CONCLUSIONS: Plasmapheresis may be an important adjuvant to conventional treatment to reduce mortality in patients with severe sepsis or septic shock. Plasmapheresis is a safe procedure in the treatment of septic patients. A prospective randomised multicentre trial is warranted to confirm our results and to determine which subgroups of septic patients will benefit most from this treatment modality.     

High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety

OBJECTIVE: To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN: Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING: Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS: We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS: Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS: In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS: Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.     

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality

OBJECTIVE: To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. DESIGN: Prospective cohort study. SETTING: University hospital intensive care unit. PATIENTS: A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. CONCLUSIONS: Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.     

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.     

Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group

Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant adverse events.     

Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome.

OBJECTIVE: To determine the effect of selenium replacement on morbidity and mortality in patients with systemic inflammatory response syndrome (SIRS). DESIGN: Controlled, randomized prospective open-label pilot study comparing patients with and without selenium replacement. SETTING: Intensive care unit of a university hospital for internal medicine. PATIENTS: Forty-two patients with SIRS caused by infection and a minimal Acute Physiology and Chronic Health Evaluation (APACHE) II score of 15 points on the day of admission were included. The selenium replacement group of patients (Se+; n = 21) received sodium selenite for 9 days (535 microg [6.77 micromol] for 3 days, 285 microg [3.61 micromol] for 3 days, and 155 microg [1.96 micromol] for 3 days) and thereafter, 35 microg (0.44 micromol) per day iv. The control group (Se-, n = 21) received 35 microg of sodium selenite throughout the total treatment period. INTERVENTIONS: Morbidity and clinical outcome was monitored by scoring using the APACHE III score, occurrence of acute renal failure, need and length of mechanical ventilation, and hospital mortality. Blood samples on days 0, 3, 7, and 14 were analyzed for serum selenium concentration and glutathione peroxidase (GSH-Px) activity. MEASUREMENTS AND MAIN RESULTS: The median APACHE II score at admission, age, gender, underlying diseases, serum selenium levels, and GSH-Px activities at admission were identical in both groups. In Se+ patients, serum selenium levels and GSH-Px activity normalized within 3 days, whereas in controls, both variables remained significantly low (p < .0001). The APACHE III score decreased significantly in both groups but was significantly lower in the Se+ group (day 3, p > .05; day 7, p = .018; and day 14, p = .045 Se+ compared with Se-). Hemodialysis with continuous veno-venous hemodialysis because of acute renal failure was necessary in nine Se- compared with three Se+ patients (p = .035). Overall mortality in the Se- group was 52% vs. 33.5% in the Se+ group (p = .13). CONCLUSIONS: Selenium replacement in patients with SIRS seems to improve clinical outcome and to reduce the incidence of acute renal failure requiring hemodialysis.     

Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure

OBJECTIVE: Concentrations of group IIA secretory phospholipase A, an inflammatory response mediator, are increased in the plasma of patients with sepsis and septic shock, and the extent of elevation is correlated with mortality. LY315920Na/S-5920 is a selective inhibitor of group IIA secretory phospholipase A that has been shown to inhibit serum group IIA secretory phospholipase A enzyme activity in patients with severe sepsis. The primary objectives of this study were to determine whether there was a dose-response relationship between two doses of LY315920Na/S-5920 compared with placebo in the reduction of 28-day all-cause mortality in patients with severe sepsis and to determine whether LY315920Na/S-5920 had an acceptable safety profile.(2) (2) (2) DESIGN: Multicenter, double-blind, placebo-controlled trial of two doses of LY315920Na/S-5920 in a parallel design. PATIENTS: A total of 586 patients with severe sepsis at 72 institutions in the United States.INTERVENTIONS Patients enrolled within 72 hrs from onset of first sepsis-induced organ failure were randomized (1:1:1) to low-dose LY315920Na/S-5920 (target plasma concentration of 200 ng/mL, n = 196), high-dose LY315920Na/S-5920 (800 ng/mL, n = 194), or placebo (n = 196). Study medication was administered as a constant-rate intravenous infusion for 168 hrs. MEASUREMENTS AND MAIN RESULTS: The study was stopped prematurely because it was unlikely that a statistically significant difference in mortality between LY315920Na/S-5920 and placebo would be found. There was no effect of LY315920Na/S-5920 on the primary end point of 28-day all-cause mortality across the entire study population. The 28-day all-cause mortality was distributed as follows: placebo group, 33.2% (65/196 patients); low-dose LY315920Na/S-5920, 37.2% (73/196); and high-dose LY315920Na/S-5920, 36.1% (70/194); p = .525. However, in a prospectively planned analysis, there was a favorable overall dose-response effect on 28-day all-cause mortality in patients administered LY315920Na/S-5920 within 18 hrs of onset of the first sepsis-induced organ failure. Among these patients, 28-day all-cause mortality was distributed as follows: placebo group, 43.5% (20/46 patients); low-dose LY315920Na/S-5920, 31.4% (16/51); and high-dose LY315920Na/S-5920, 20.8% (10/48); p = .018. CONCLUSIONS: Administration of LY315920Na/S-5920 had an acceptable safety profile in patients with severe sepsis. There was no overall survival benefit associated with the use of LY315920Na/S-5920 in this study. However, prospectively planned secondary analyses suggested that treatment with LY315920Na/S-5920 was associated with an improvement in survival in patients treated within 18 hrs of the first sepsis-induced organ failure.     

Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study

Introduction

Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients.

Methods

A prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded.

Results

Sixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups.

Conclusion

Continuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844.     

Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality. OBJECTIVES: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC. PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination. RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.     

Comparison of Predisposition, Insult/Infection, Response, and Organ dysfunction, Acute Physiology And Chronic Health Evaluation II, and Mortality in Emergency Department Sepsis in patients meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle

Purpose

The aim of the study was to examine the performance of the Predisposition, Insult/Infection, Response, and Organ dysfunction (PIRO) model compared with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Mortality in Emergency Department Sepsis (MEDS) scoring systems in predicting in-hospital mortality for patients presenting to the emergency department (ED) with severe sepsis or septic shock.

Materials and Methods

This study was an analysis of a prospectively maintained registry including adult patients with severe sepsis or septic shock meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle over a 6-year period. The registry contains data on patient demographics, sepsis category, vital signs, laboratory values, ED length of stay, hospital length of stay, physiologic scores, and outcome status. The discrimination and calibration characteristics of PIRO, APACHE II, and MEDS were analyzed.

Results

Five-hundred forty-one patients with age 63.5 ± 18.5 years were enrolled, 61.9% in septic shock, 46.9% blood-culture positive, and 31.8% in-hospital mortality. Median (25th and 75th percentile) PIRO, APACHE II, and MEDS scores were 6 (5 and 8), 28 (22 and 34), and 12 (9 and 15), with predicted mortalities of 48.5% (40.1 and 63.9), 66.0% (42.0 and 83.0), and 16.0% (9.0 and 39.0), respectively. The area under the receiver operating characteristic curves for PIRO was 0.71 (95% confidence interval, 0.66-0.75); APACHE II, 0.71 (0.66-0.76); and MEDS, 0.63 (0.60-0.70). The standardized mortality ratio was 0.70 (0.08-1.41), 0.70 (−0.46 to 1.80), and 4.00 (−8.53 to 16.62), respectively. Actual mortality significantly increased with increasing PIRO score in patients with APACHE II 25 or more (P < .01).

Conclusions

The PIRO, APACHE II, and MEDS have variable abilities to early discriminate and estimate in-hospital mortality of patients presenting to the ED meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle. The PIRO may provide additional risk stratification in patients with APACHE II 25 or more. More studies are required to evaluate the clinical applicability of PIRO in high-risk patients with severe sepsis and septic shock.     

The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series

OBJECTIVE: To review all cases of septic shock treated with vasopressin to determine the effects on hemodynamic and renal function and to document any adverse effects. SETTING: A 14-bed mixed medical-surgical ICU of St. Paul's Hospital, a 450-bed tertiary referral hospital affiliated with the University of British Columbia. PATIENTS: All ICU patients who received vasopressin for treatment of severe septic shock between August 5, 1997, and March 21, 1999. RESULTS: We identified 50 patients: age 60 (+/-14); APACHE II score 27 (+/-7). Baseline data (T0) was compared to data at T4, T24 and T48 (4, 24 and 48 h) on infusion. Mean arterial pressure (MAP) increased by 18% from T0 to T4 and remained stable at T24 (p=0.006) and T48 (p=0.008). Systolic pulmonary artery pressure (PAP) was unchanged at 45+/-13 mmHg. Mean cardiac index (CI) decreased by 11% at T4 (p=0.03). Urine output increased 79% at T4 (p=0.005) and further increases were not significant at T24 and T48. Mean pressor dosage decreased by 33% at T4 (p=0.001), by 53% at T24 (p=0.002) and by 48% at T48 (p=0.01). Hospital mortality was 85%. There were six cardiac arrests; all but one occurred at a vasopressin dose of 0.05 U/min or more. CONCLUSIONS: In this group of patients with severe septic shock, vasopressin infusion increased MAP and urine output and decreased catecholamine requirements. Doses higher than 0.04 U/min were not associated with increased effectiveness and may have been associated with higher adverse effects.     

连续性血液净化对重症肺炎合并多器官功能衰竭的回顾性分析

目的 评价连续性血液净化(CBP)治疗重症肺炎呼吸衰竭继发休克伴急性肾功能衰竭的效果 及其与预后的关系。方法 25例不同程度多器官功能衰竭(MOF)重症肺炎患者采用CBP治疗,按其转归分 为撤机出院组、死于感染性休克组、远期死于重症肺炎组。评价CBP治疗前1 d,治疗后24、48和72 h各项实 验室指标及危重病评分变化。结果 ①25例患者中A组7例,B组9例,C组9例;治愈率28％,总病死率 72％。②B组患者接受CBP治疗时间平均不到48 h被迫终止。单因素分析提示:B组治疗前血糖显著高于 A组[(13．17±5．84)mmol／L比(8．07±2．28)mmol／L,P<0．05],纤维蛋白原显著高于C组[(5．75± 3．08)g／L比(3．10±1．06)g／L,P<0．05],B组在CBP治疗48 h后纤维蛋白原和所需多巴胺浓度均较A、 C组显著升高[(8．24±3．57)g／L比(5．13±0．94)g／L和(3．01±1．22)g／L,(12．00±6．93)μg·kg-1·min-1 比(1．00±2．45)μg·kg-1·min-1和(2．89±4．37)μg·kg-1·min-1;P均<0．05]。③A组治疗前急性生理学 与慢性健康状况Ⅲ(APACHEⅢ)评分较B、C组低[(89．43±11．28)分比(108．00±15．10)分和(104．67± 13．77)分,P均<0．05];A、C组治疗72 h后与B组比较APACHEⅡ变化率[(-10．43±4．89)分和(-9．11± 3．76)分比(-2．33±4．39)分,P<0．01]、APACHEⅢ变化率[(-21．57±13．53)分和(-14．33±8．32)分比 (2．33±12．18)分,P<0．01]、MODS评分变化率[(-2．14±2．19)分和(-1．00±1．87)分比(0．56±1．88)分, P<0．05]差异均有显著性。结论 ①CBP能有效救治部分重症肺炎呼吸衰竭继发休克伴急性肾功能衰竭患 者。③APACHEⅢ评分在治疗前后均是敏感的评价指标,初步提示APACHEⅢ90-100分的区域是此类患者 应用CBP的指征。③治疗前血糖和纤维蛋白原水平是潜在风险因子,纤维蛋白原的持续升高提示预后较差。     

Amino acid alterations and encephalopathy in the sepsis syndrome

OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy. DESIGN: Retrospective analysis. SETTING: Medical wards and medical ICU of a university hospital. PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium. INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs. 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs. 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs. 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs. 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05). Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality. APACHE II scores were higher in the septic shock patients (30 +/- 2 vs. 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs. 12%, p less than .01). Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs. 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs. 61 +/- 7 mmol/L, p less than .05) than patients who survived. CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease.     

Protein C zymogen in severe sepsis: a double-blinded,placebo-controlled,randomized study

Purpose

To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock.

Methods

This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality.

Results

The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072).

Conclusion

Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

     

Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome

OBJECTIVE: We investigated the efficacy of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome (ARDS) by post hoc analysis of a previously completed clinical trial. DESIGN: Retrospective analysis of a placebo-controlled, randomized, double-blind trial of low doses of corticosteroids in septic shock. SETTING: Nineteen intensive care units in France. PATIENTS: Among the 300 septic shock patients enrolled, we selected those meeting standard criteria for ARDS at inclusion. INTERVENTIONS: Seven-day treatment with 50 mg of hydrocortisone every 6 hrs and 50 microg of 9-alpha-fludrocortisone once a day. MEASUREMENTS AND MAIN RESULTS: There were 177 patients with ARDS (placebo, n = 92; corticosteroids, n = 85) including 129 (placebo, n = 67; corticosteroids, n = 62) nonresponders and 48 (placebo, n = 25; corticosteroids, n = 23) responders. In nonresponders, there were 50 deaths (75%) in the placebo group and 33 deaths (53%) in the steroid group (hazard ratio 0.57, 95% confidence interval 0.36-0.89, p = .013; relative risk 0.71, 95% confidence interval 0.54-0.94, p = .011). The number of days alive and off the ventilator was 2.6 +/- 6.6 in the placebo group and 5.7 +/- 8.6 in the steroid group (p = .006). There was no significant difference between groups in responders. There was no significant difference between groups in the two subsets of patients without ARDS. Adverse events rates were similar in the two groups. CONCLUSIONS: This post hoc analysis shows that a 7-day treatment with low doses of corticosteroids was associated with better outcomes in septic shock-associated early ARDS nonresponders, but not in responders and not in septic shock patients without ARDS.     

心肌脂肪酸结合蛋白在脓毒症临床预后的预测价值研究

目的 探讨心肌脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)在脓毒症患者临床预后的预测价值,提高脓毒症患者救治率.方法 采用前瞻性病例对照研究,纳入2014年10月至2015年10月就诊于新疆医科大学第一附属医院脓毒血症患者共50例,根据2012年脓毒症诊疗指南分为脓毒症组(16例)、严重脓毒症组(14例)、脓毒性休克组(20例);根据28 d后是否存活分为死亡组(22例)与存活组(28例).记录性别、年龄、族别等基本资料,入急诊6h内完善急性生理与慢性健康状况(APACHEⅡ)评分,H-FABP,B型脑钠利肽(B-typenatriuretic,BNP)、肌酸激酶(creatine kinase,CK)、肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)、肌钙蛋白(troponin-T,cTn-T)等指标.统计学采用SPSS 21.0软件,计量资料t检验或秩和检验、计数资料采用x2检验,非正态分布资料采用秩合检验,对生存状况进行ROC曲线分析.结果 脓毒性休克组的H-FABP明显高于严重脓毒症组和脓毒症组(P＜0.01).脓毒性休克组28天死亡率(80％)与严重脓毒症组28 d病死率高于脓毒症组28天死亡率(12.5％)(P＜0.01).死亡组H-FABP、BNP、cTn-T、CK、CK-MB均明显高于存活组,两组间差异具有统计学意义(P＜0.05);对H-FABP和BNP行ROC曲线结果提示H-FABP (AUC=0.748,P=0.003,95％CI:0.605 ～0.890)优于BNP (AUC =0.714,P=0.010,95％ CI:0.573 ～0.856),当H-FABP取 9.902 ng/mL,敏感度82.1％,特异度63.6％.H-FABP对28 d病死率的预测具有一定价值.结论 脓毒性休克组病死率明显高于严重脓毒血症及脓毒症组.H-FABP相比BNP、CK、CK-MB,对脓毒症患者预后具有较大的预测价值,随病情加重而增高.H-FABP可以预测28 d病死率.     

Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department

Introduction

Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.

Methods

This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann–Whitney U tests.

Results

On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days’ follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.

Conclusion

Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.     

Early Goal-directed Therapy, Corticosteroid, and Recombinant Human Activated Protein C for the Treatment of Severe Sepsis and Septic Shock in the Emergency Department

Objectives: To describe our experience with early goal‐directed therapy (EGDT), corticosteroid administration, and recombinant human activated protein C (rhAPC) administration in patients with severe sepsis or septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥25 in the emergency department (ED). Methods: This was a retrospective case series of a prospectively maintained ED sepsis registry. Data are presented as median (25th, 75th percentile). The setting was an academic tertiary ED with approximately 60,000 annual patient visits. Patients with severe sepsis or septic shock and an APACHE II score ≥25 entered in an ED sepsis registry over a four‐month period were included. Patients who received rhAPC in the intensive care unit were excluded. Central venous catheterization for central venous pressure and central venous oxygen saturation monitoring, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, inotropes, corticosteroids, and rhAPC were initiated by the emergency physicians and continued in the intensive care unit by intensivists. Results: Twenty‐four patients were enrolled. Patient characteristics were as follows: age, 79.5 (68.0, 83.5) years; APACHE II score, 31.5 (29.8, 36.0); ED length of stay, 6.5 (4.0, 10.5) hours; predicted mortality, 76.7% (71.9, 86.4); and in‐hospital mortality, 45.8%. All patients received broad‐spectrum antibiotics, 54.2% completed EGDT, 33.3% received corticosteroids, and 33.3% received rhAPC. Time of antibiotic administration was 1.5 (1.0, 2.0) hours, time of central venous pressure/central venous oxygen saturation monitoring was 1.0 (0.5, 2.5) hour, and time of rhAPC administration was 9.5 (6.8, 10.5) hours after patients met criteria for severe sepsis or septic shock. In‐hospital mortality of patients who received rhAPC in addition to other therapies was 25.0%. Conclusions: EGDT, corticosteroid administration, and rhAPC administration are feasible in the ED setting. While these evidence‐based therapies individually have been shown to improve outcomes for patients with severe sepsis or septic shock, further studies are needed to examine their combined effectiveness during the early stages of this disease.     

Comparison of disease severity scoring systems in septic shock

OBJECTIVE: To compare six disease severity scoring systems as predictors of mortality in septic shock when used in the first 24 hrs of diagnosis. The six scoring systems tested were: Multiorgan Failure; the Acute Organ System Failure; the Acute Physiology and Chronic Health Evaluation (APACHE II); the Multisystem Organ Failure scoring system; the Mortality Prediction Model; and the grading of sepsis. DESIGN: Retrospective, case series, consecutive sample. SETTING: Adult ICUs of three teaching hospitals. PATIENTS: Seventy-one patients from 12 to 84 yrs, fulfilling specific criteria for the diagnosis of septic shock, who were admitted to the ICU during 15 consecutive months. MEASUREMENTS AND MAIN RESULTS: The Multiorgan Failure scoring system, Acute Physiology and Chronic Health Evaluation (APACHE II), and Acute Organ System Failure scoring system were found, with our modifications, to be statistically significant predictors of mortality. Predictive data for these three scoring systems were as follows: Multiorgan Failure scoring system p = .008, mean number of points of survivors 5.2 +/- 1.5 (SD), mean number of points of nonsurvivors 6.3 +/- 1.5; APACHE II p = .013, mean number of points of survivors 21.1 +/- 5.9, mean number of points of nonsurvivors 24.6 +/- 6.0; and Acute Organ System Failure scoring system p = .011. None of the other three scoring systems showed significant predictive ability: Multisystem Organ Failure scoring system p = .072, Mortality Prediction Model p = 0.091, and the grading of sepsis p = .27. There was a significant (p = .004) difference in the survival rate of the three hospitals. CONCLUSION: The Multiorgan Failure scoring system, APACHE II, and the Acute Organ System Failure scoring system, with minor modifications, were found to be useful prognostic tools for patients with septic shock and allowed us to compare the performance and treatment programs of different ICUs.