Characterization of an animal model of severe sepsis associated with respiratory dysfunction

PURPOSE: Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS: 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS: Septic pigs survived 17 hours on average (range, 16-18 h), and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS: Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.     

血必净注射液对大面积烧伤患者炎性介质和凝血功能的影响

目的观察血必净对大面积烧伤患者血清肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)以及血小板计数(PLT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)、活化部分凝血活酶时间(APTT)的影响。方法近4年总面积30%的烧伤患者24例,随机分为常规治疗组和血必净组,每组12例;常规治疗组根据体重、烧伤面积、烧伤深度行补液复苏,抗感染以及保护各脏器功能等对症支持治疗;血必净组在常规治疗组的基础上加用血必净注射液50mL配伍生理盐水100mL静脉滴注,2次/d。检测两组患者治疗第1、2、5和7天血清中TNF-α、IL-6浓度变化;第7天PLT、PT、TT、FIB、APTT的变化。结果 (1)治疗第1、2和5天,常规治疗组和血必净组TNF-α和IL-6均明显高于正常值(P0.05);治疗第5天和第7天,血必净组TNF-α和IL-6水平明显低于常规治疗组(P0.05);治疗第7天,常规治疗组TNF-α和IL-6水平显著高于正常值(P0.05),而血必净组和正常值比较差异无统计学意义(P0.05)。(2)常规治疗组PLT和FIB明显低于正常值和血必净组,而血必净组与正常值之间差异无统计学意义(P0.05)。常规治疗组APTT、PT和TT明显延长,与正常值相比有统计学意义(P0.05),血必净组APTT、PT和TT较常规治疗组显著缩短(P0.05),与正常值相比无统计学意义(P0.05)。结论血必净注射液可有效的抑制大面积烧伤患者血清中TNF-α和IL-6的释放,减轻APTT、PT和TT的异常。     

Severe sepsis bundles

Sepsis is a complex syndrome with its wide spectrum of severity, and is one of the most common causes of death in Critical Care Units. The Surviving Sepsis campaign launched in 2004, is aimed at improving diagnosis, management and survival of patients with sepsis. Care bundles are a group of best evidence based interventions which when instituted together, gives maximum outcome benefit. Care Bundles are simple, uniform and have universal practical applicability. Surviving Sepsis campaign guidelines in 2008 incorporated two sepsis care bundles. The Resuscitation bundle includes seven key interventions to be achieved in 6-h while four interventions have to be completed within 24-h in the Management bundle. Compliance with a bundle implies achieving all the specified goals in that bundle. Limitations to care bundles include the quality of the evidence on which they are based, and that the relative contributions of each element of the bundle are not known. Several observational studies support the hypothesis that sepsis care bundles have an important role in improving outcomes from sepsis. Critical Care Units should develop management strategies to ensure compliance with the sepsis bundles in order to decrease hospital mortality due to severe sepsis.     

Atropine treatment modifies LPS-induced inflammatory response and increases survival

Objective: To explore the effect that Atropine, a competitive antagonist for the muscarinic acetylcholine receptor (mAChR), has on the response to LPS. Subjects: Eight-week-old, male, B6 mice. Treatment: Mice were treated with Atropine prior to, or after LPS challenge. Methods: Survival was monitored and analyzed via Kaplan-Meier analysis using the log-rank test. The effects of atropine on the inflammatory response (TNF-α, IL-6 and IL-10) were monitored at various time intervals following LPS injection in mice that were treated and not treated with atropine. Results: Atropine administration prior to LPS induction of the inflammatory response resulted in reduced TNF-α and elevated IL-10 plasma levels without affecting the production of IL-6. This reduction in TNF-α levels was independent of the increase in IL-10 production. Atropine pretreatment improved the rate of survival from endotoxic shock in mice. The improved survival of mice after endotoxic shock could still be observed when atropine was administered several hours after LPS injection. Conclusion: The administration of atropine after injury may have a beneficial clinical effect. Received 23 July 2007; returned for revision 10 September 2007; accepted by G. Wallace 19 October 2007     

Genetic diversity and exotoxin A production of group A streptococci causing sepsis

The M protein and streptococcus pyrogenic exotoxin (SPE A) are important virulence factors in group A streptococci (GAS) infections. The emm types of GAS strains isolated from patients with sepsis were determined by sequencing the 5' N-terminus of the emm gene, encoding the M protein, and clonality analysis using pulsed-field gel electrophoresis. The presence of speA and production of SPE A were also examined. There were no predominant GAS clones. The emm genotypes were variable, and the most common genotype was emm13 (17.9%). The production prevalence of SPE A was 21.4%. The low mortality rate (7.1%) of GAS sepsis might be attributable to the low incidence of virulent strains such as emm1 (10.7%) and emm3 (7.1%), as well as to low production rate of SPE A.     

血管外肺水指数与降钙素原对革兰氏阴性杆菌烧伤脓毒症病情严重程度的评估作用

目的探讨血管外肺水指数(EVLWI)、降钙素原(PCT)对革兰氏阴性杆菌烧伤脓毒症病情严重程度的评估作用。 方法选择2015年3月至2019年3月武汉大学同仁医院暨武汉市第三医院烧伤科收治的20例血培养为革兰氏阴性杆菌烧伤脓毒症患者(革兰氏阴性杆菌烧伤脓毒症组)及18例血培养为非革兰氏阴性杆菌烧伤脓毒症患者(非革兰氏阴性杆菌烧伤脓毒症组)。2组患者均行脉搏指示连续心输出量(PiCCO)监测,并分别在诊断为脓毒症与脓毒症休克时记录EVLWI的数值变化,连续测量3次,取其平均值;同时在确诊脓毒症与脓毒症休克时立即行静脉血的采集,采集非抗凝血3 mL,离心后留取血清并行PCT的检测,记录2组PCT值。比较2组确诊脓毒症与脓毒症休克时EVLWI及PCT,对数据行t检验并行Bonferroni校正。绘制EVLWI及血清PCT预测革兰氏阴性杆菌烧伤脓毒症与脓毒症休克患者的受试者工作特征(ROC)曲线,计算诊断革兰氏阴性杆菌烧伤脓毒症或脓毒症休克的95%的置信区间、约登指数、最佳临界值、灵敏度和特异度。 结果诊断为脓毒症时,革兰氏阴性杆菌烧伤脓毒症组患者的EVLWI、PCT水平分别为(10.6±1.6) mL/kg、(6.64±1.63) ng/mL,均高于非革兰氏阴性杆菌烧伤脓毒症组[(7.9±1.7) mL/kg、(4.60±1.31) ng/mL],差异均有统计学意义(t＝5.043、4.206,P值均小于0.05)。诊断为脓毒症休克时,革兰氏阴性杆菌烧伤脓毒症组患者的EVLWI、PCT水平分别为(15.0±1.3) mL/kg、(12.87±2.65) ng/mL,均高于非革兰氏阴性杆菌烧伤脓毒症组[(10.7±1.5) mL/kg、(6.29±1.79) ng/mL],差异均有统计学意义(t＝9.608、8.867,P值均小于0.05)。通过绘制ROC曲线可以得知,应用EVLWI及PCT判断革兰氏阴性杆菌烧伤脓毒症及非革兰氏阴性杆菌烧伤脓毒症的最佳临界值分别为10.5 mL/kg、5.9 ng/mL;约登指数分别为50%、59%,灵敏度分别为50%、70%,特异度分别为100%、89%。EVLWI及PCT判断革兰氏阴性杆菌烧伤脓毒症休克及非革兰氏阴性杆菌烧伤脓毒症休克的最佳临界值分别为13.5 mL/kg、9.2 ng/mL;约登指数分别为90%、95%,灵敏度分别为90%、95%,特异度均为100%。 结论EVLWI及PCT可作为革兰氏阴性杆菌烧伤脓毒症病情严重程度的有效评估指标,可进一步提高革兰氏阴性杆菌烧伤脓毒症危险预测性的准确度。     

肾上腺素对内毒素致大鼠肠道损害的保护作用

目的 探讨肾上腺素对内毒素(lipopolysaccharide,LPS)所致大鼠肠道损害的保护作用及其作用机制.方法 50只SD大鼠随机分为5组(每组10只):对照组:大鼠静脉输注0.9％生理盐水24 ml/(kg·h);LPS组:大鼠静脉注射LPS 6m/kg后,静脉输注生理盐水2.4 ml/(kg·h);低、中和高剂量肾上腺素组:大鼠静脉注射LPS 6 mg/kg后,分别静脉输注肾上腺素0.12 μg/(kg·min)、0.3μg/(kg·min)和0.6μg(kg· min).在LPS注射前、注射后2h和注射后6h3个时点取血,检测血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10水平,并在24h观察肠道的组织病理学变化.结果 LPS组大鼠在LPS注射后2h血清TNF-α浓度为(1164±145) ng/L,IL-1β浓度为(521±68)ng/L,IL-10浓度为(303±20) ng/L,较对照组均明显升高(P＜0.05).病理结果显示,LPS组小肠黏膜充血、水肿、出血及炎症细胞浸润,上皮细胞坏死、脱落.高剂量肾上腺素组2h血清TNF-α浓度为(576±105) ng/L,2h和6h的IL-10浓度分别为(424±29) ng/L和(24.5±14) ng/L,与LPS组相比血清TNF-α水平明显降低(P＜0.05)且IL-10水平明显升高(P＜0.05),但IL-1β水平无明显变化(P＞0.05).高剂量肾上腺素组大鼠肠道病理损伤明显减轻.中、低剂量肾上腺素组各时间点血清细胞因子水平与LPS组比较,差异无统计学意义(P＞0.05),未见肠道病理损害减轻.结论 肾上腺素可以通过抗炎作用减轻LPS素诱导的肠道损害.     

脓毒症患儿血清皮质醇、促肾上腺皮质激素水平的测定及其临床意义

目的 动态监测脓毒症、严重脓毒症患儿血清皮质醇、促肾上腺皮质激素( adrenocorticotropic hormone,ACTH)水平的变化,探讨其与临床的关系.方法 以我院2010年9月至2011年1月收治的脓毒症患儿30例为研究对象,分为严重脓毒症组(10例)和脓毒症组(20例).在病程的急性期和恢复期分别检测血清皮质醇及ACTH水平,并与同期住院的10例非脓毒症患儿(对照组)进行对比分析.结果 急性期严重脓毒症组血清皮质醇[( 33.97±6.83) μg/ml]明显高于脓毒症组[(26.30±10.43) μg/ml]和对照组[(19.06±6.91) μg/ml],差异有统计学意义(P＜0.01).急性期严重脓毒症组血清ACTH[ (25.47±9.41) pg/ml]明显高于脓毒症组[(15.52±5.85) pg/ml]和对照组[(9.16±3.02) pg/ml],差异有统计学意义(P＜0.01).结论 脓毒症患儿发病早期机体存在应激反应,血清皮质醇、ACTH浓度明显升高;血清皮质醇、ACTH浓度升高的水平与病情严重程度有关,血清皮质醇、ACTH水平可作为评估患儿严重程度,判断预后的指标.     

早产儿假丝酵母菌败血症时血小板的变化

目的探讨早产儿假丝酵母菌败血症时血小板的变化。方法回顾性分析2008年2月至2010年2月在本院住院的假丝酵母菌败血症早产儿的临床表现,比较患儿入院时、发生真菌败血症时、抗真菌治疗2周后3个时间点的血常规特别是血小板的变化和C反应蛋白(CRP)变化。结果白假丝酵母菌败血症13例,近平滑假丝酵母菌败血症11例。24例患儿发生假丝酵母菌败血症时与入院时比较,WBC(×109/L)差异无统计学意义[(8.5±4.3)比(8.6±2.9),P>0.05]。PLT(×109/L)降低,CRP(mg/L)、血小板平均体积(MPV,fl)和血小板分布宽度(PDW,%)升高[PLT:(99.8±49.1)比(197.0±62.8),CRP:(29.3±34.5)比(2.7±3.4),MPV:(12.3±0.9)比(11.1±1.1),PDW:(17.6±3.2)比(13.6±2.7),P均<0.05]。近平滑假丝酵母菌组发生败血症时PLT明显低于白假丝酵母菌组[(73.0±40.9)比(122.5±44.8),P<0.05],其余血常规指标在3个不同时间点两组相比差异均无统计学意义(P>0.05)。结论早产儿真菌败血症时血常规变化最明显的指标是PLT降低,与白假丝酵母菌败血症相比,近平滑假丝酵母菌败血症PLT降低更明显,分析PLT可辅助指导真菌败血症的诊断和早期经验治疗。     

姜黄素在脓毒症中的免疫调节作用

脓毒症已成为现代危重病医学面临的普遍存在而又十分复杂的问题,加强脓毒症的研究,探索新的治疗方法和药物具有十分重要的理论价值和临床意义.姜黄素具有抗肿瘤、抗炎、抗病毒、抗菌、抗氧化等多种药理作用,且毒性低,具有良好的临床应用潜力.近20年又发现它是一种潜在的免疫调节剂,能够用于脓毒症和脓毒性休克的治疗.