142例全身炎症反应综合征临床分析

目的提高对危重患儿发生全身炎症反应综合征（SIRS）早期诊断的认识。方法分析142例SIRS患儿的临床资料,患儿至少符合2个SIRS标准,包括发热、呼吸急促、心动过速、白细胞计数异常、C反应蛋白增高。结果142例患儿中多脏器功能障碍综合症（MODS）2例占1．4％,死亡1例占0．7％。结论全身炎症反应综合征的早期诊断和积极治疗可降低MODS的发病率及死亡率。     

微剂量肝素治疗危重新生儿伴SIRS的疗效观察

目的观察早期使用微剂量肝素对危重新生儿伴全身炎症反应综合征（SIRS）的治疗效果的影响。方法对符合诊断标准的60例SIRS新生儿随机分组进行前瞻性对照研究,对照组30例,给予原发病及保护重要脏器等常规治疗;治疗组30例,在常规治疗基础上早期加用微剂量肝素按5～10U／kg给予,每6h皮下注射1次,共用3d。结果两组治疗前后比较,治疗后血小板计数明显升高,CRP水平明显下降（均P〈0．05）与对照组比较,多脏器功能不全（MODS）发生率有显著改善,P〈0．05,SIRS的持续时间缩短,死亡率也明显降低（P〈0．05）。结论微剂量肝素治疗危重新生儿伴全身炎症反应综合征,疗效确切,且无出血等副作用,临床容易掌握,不需实验室监护,可缩短SIRS持续时间,降低MODS的发生率及病死率。     

Toll样受体基因多态性研究与脓毒症

脓毒症和脓毒性休克是危重患者的主要死亡原因。美国疾病控制中心(CDC)统计资料显示，每年约有75万例脓毒症患者，其中约21万例死亡。在我国，脓毒症和多器官功能障碍综合征(MODS)的患病率及死亡率与国外报道一致。近几十年来，虽然对危重症患者进行积极监护和有效的支持治疗，脓毒症和脓毒性休克的病死率仍居高不下。几个大宗临床实验研究显示，抗炎症治疗并未能预期降低脓毒症患者死亡率。危重症监护(ICU)医师注意到，危重患者脓毒症的易感性存在高度的个体差异。而且，对相似的治疗，不同患者反应和预后可能完全不同。对死于脓毒症的患者进行尸检并不能明确其死亡原因。长期以来认为脓毒症是失控的炎症反应，即机体对细菌感染的过度反应，是伴有感染的全身炎症反应综合征(SIRS)。     

小儿脓毒症的研究进展

严重感染性疾病的病死率因有效的抗感染和器官功能支持治疗得以降低,但脓毒症仍然是危重症患儿死亡的重要原因之一。本文阐述了脓毒症的发病机制和治疗进展,旨在更好地提高脓毒症患儿的抢救成功率。1脓毒症的定义脓毒症是指由感染引起的全身炎症反应(systemic inflam-matory response syndrome,SIRS),细菌、病毒、支原体、真菌或     

112例急诊ICU收治的糖尿病酮症酸中毒预后因素研究

目的:研究分析影响糖尿病酮症酸中毒预后的因素,从而为临床预防和治疗提供参考。方法:对我院急诊ICU收治的112例糖尿病酮症酸中毒患者进行回顾性分析,按照患者预后分为死亡组和存活组,分析其危险因素。结果:112例患者,死亡29例(25.89%),存活83例(74.11%),死亡组和存活组的平均年龄,基础病情况,机械通气率,系统性炎症反应综合征发生率(SIRS),脓毒症性休克发生率,24h内最差的序贯器官衰竭评分(SOFA)等各项分析指标均具有显著差异,组间对比,P0.05。结论:基础疾病,是否机械通气,有无发生系统性炎症反应综合征,脓毒症性休克以及24h内SOFA评分等均是影响糖尿病酮症酸中毒患者预后的危险因素,在临床治疗和预防中应加以重视。     

脓毒症中细胞因子的研究进展

脓毒症（Sepsis）是严重创（烧）伤、休克、感染、外科大手术后常见的并发症,是由于感染而导致的全身性炎症反应综合征（SIRS）的临床表现。如果脓毒症早期持续的SIRS得不到有效的控制,进一步发展可导致脓毒性休克、多器官功能障碍综合征（MODS）,而MODS的进一步发展为多脏器功能衰竭（MOF）,MOF是临床危重患者的最主要死亡原因之一。     

不同剂量乌司他丁治疗急性百草枯中毒的临床对照研究

目的：探讨不同剂量乌司他丁( UTI)治疗急性百草枯( PQ)中毒的临床效果。方法回顾性分析2013年1月—2015年12月收治的急性PQ中毒患者158例。根据患者使用UTI的情况分为4组：对照组、低剂量组(30万U/d)、中剂量组(40万U/d)、高剂量组(60万U/d)。比较各组患者急性呼吸窘迫综合征( ARDS)、肺纤维化及多器官功能障碍综合征( MODS)发生率,28 d死亡率,死亡病例存活时间。结果高剂量组的ARDS、肺纤维化及MODS发生率,28 d死亡率低于对照组(P<0．05)。低、中和高剂量组的死亡病例存活时间长于对照组(P<0．05)。结论高剂量UTI用于治疗急性PQ中毒可以减轻PQ所致脏器损害,降低患者死亡率,早期足量使用UTI救治急性PQ中毒更具有治疗优势。     

全身炎症反应综合征评分对严重创伤患者预后的预测作用

目的探讨全身炎症反应综合征评分（SIRS）对严重创伤患者预后的预测价值。方法129例严重创伤患者均于入院时进行SIRS评分，以住院期间的感染率、器官功能不全发生情况和死亡率为结局终点评价指标，评价预后。结果129例严重创伤患者发生感染52例（40.3％）；发生器官功能不全28例（21．7％）；死亡8例（6．2％）。而感染者、发生器官功能不全者和出现死亡者，其SIRS评分均较高（P〉0．05）。并且SIRS评分对感染、器官功能不全及死亡的预测均有价值，AUC〉0．5（P〈0．05）。结论SIRS评分对严重创伤患者预后具有很好的预测价值，并且简单易行．适合临床应用。     

重症肝病与全身炎症反应综合征

全身炎症反应综合征（SIRS）是各种致病困素触发机体免疫产生的过度的炎症、凝血及削弱的纤溶反应的一种临床过程：其中感染引起的全身炎症反应又称为脓毒症（sepsis）．是导致危重病患者多器官功能不全（MODS）和死亡的重要原因。肝硬化、肝衰竭等重症肝病患者感染率高，可诱发肝性脑病等严重并发症而降低患者生存率。近年发现SIRS／sepsis参与了病情的演进：针对炎症发生发展各个环节，及时有效的干预治疗可望延缓病情恶化。     

血清降钙素原联合序贯器官衰竭估计评分在小儿脓毒症中的诊断及预后价值

目的：观察血清降钙素原（PCT）、C 反应蛋白（CRP）联合序贯器官衰竭估计（SOFA）评分对小儿脓毒症的诊断及预后评估价值。方法128例脓毒症患儿分为全身炎症反应综合征（SIRS）组25例,轻度组45例,严重组31例,休克组27例。根据预后将其分为存活组与死亡组。比较各组血清PCT、CRP 及SOFA 评分。结果①患儿的血清PCT、CRP及SOFA评分均高于正常,且均随病情加重呈上升趋势,除严重组与休克组的CRP水平接近外,其他相邻两组的比较,差异均有统计学意义。②死亡组血清PCT、CRP 及SOFA 评分均高于存活组,PCT 与SOFA评分两组差异有统计学意义;CRP水平差异无统计学意义。③血清PCT、CRP与SOFA评分均是脓毒症患者发生的独立危险因素。结论血清PCT 联合SOFA 评分对脓毒症患儿的诊断及预后评估有一定意义。     

What is the pathophysiology of the septic host upon admission?

The enormous case-fatality rate of severe sepsis and septic shock has resulted in considerable efforts being made towards understanding their complex mechanisms of pathogenesis. This has been done with the hope that agents that interfere with the pathways of pathogenesis and modulate the immune response of the host may be candidates for therapy. Disappointing results from most trials of immunomodulators in sepsis have led to understanding that the progression of patients to multiple organ dysfunction syndrome involves blunting of the pro-inflammatory cytokine storm. Instead, the compensatory anti-inflammatory response syndrome (CARS) develops, which is characterised by immunoparalysis. Components of this syndrome are impaired phagocytosis by neutrophils, decreased expression of HLA-DR on monocytes, impairment of ex vivo cytokine stimulation of monocytes, CD4 lymphopenia due to apoptosis of lymphocytes and predominance of anti-inflammatory T(h)2 and regulatory T-cell responses over pro-inflammatory T(h)1 and T(17) responses. CARS is not the sole explanation for the failure of trials of immunomodulators in sepsis. Recent data from the Hellenic Sepsis Study Group demonstrate that components of CARS upon transition from sepsis to severe sepsis/shock differ in relation to the underlying type of infection. These data underscore that the pathogenesis of sepsis presents considerable heterogeneity from one patient to another. That heterogeneity should be taken into consideration when deciding to administer an immunomodulator.     

靶向血管生成素/酪氨酸蛋白激酶-2(Ang/Tie2)通路的脓毒症治疗药物的研究进展

脓毒症是一种由细菌等病原微生物侵入机体引起的全身炎症反应综合征,常伴有器官功能障碍、组织灌注不良、低血压甚至脓毒性休克。血管功能障碍与脓毒症之间存在明确的关系。血管生成素/酪氨酸蛋白激酶-2(Ang/Tie2)通路可以作为控制炎症、防止血管渗漏药物研发的重要靶点,为脓毒症治疗提供新的可能性。靶向Ang/Tie2通路的脓毒症治疗药物有重组人Ang1腺病毒、Ang1类似物、Ang2抑制剂、重组人Ang2和Tie2激动剂。总结了靶向Ang/Tie2通路的脓毒症治疗药物的研究进展,以期为脓毒症治疗药物的开发提供思路。     

The lung in sepsis: guilty or innocent?

The mortality rate of severe sepsis is still high (20 to 65%) despite the advances in critical care. The most important determinant of the prognosis in this condition is the occurrence of multiple organ dysfunction syndrome (MODS). The lung is the most frequently identified organ to fail in sepsis and is also the most frequent primary site of infection. The development of acute respiratory distress syndrome (ARDS) is common in those cases. The current understanding of the pathogenesis of ARDS suggests that the degree of inflammatory response and its sustained leukocyte activation may determine the clinical evolution of ARDS. The way that mechanical ventilation is delivered is responsible for the start and/or the perpetuation of a pro-inflammatory cascade activation that, due to the loss of the alveolar compartmentalization in ARDS, can reach the bloodstream and induce MODS. On the other hand, during sepsis, the alveolar compartmentalization is lost, allowing the passage of cytokines, released to the bloodstream by any other organ, to the pulmonary endothelium. These cytokines, especially IL-1, TNF-alpha and IL-8, have important roles in the lung dysfunction. Experimental and clinical studies have been demonstrated that ventilation strategies using low tidal volumes and limitation of airway pressures can block cytokines and reduce mortality of patients with respiratory failure. The studies are still insufficient to determine the role of pharmacological therapies in those patients.     

The epidemiology of sepsis

Sepsis is a common and devastating syndrome that represents a significant healthcare burden worldwide. The average annual cost to care for patients with sepsis has been estimated to being $16.7 billion. Uniform definitions have been developed for the spectrum of sepsis syndrome, including the systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock. SIRS describes the clinical manifestations derived from an acute yet nonspecific illness, whereas an infectious etiology is required for the diagnosis of sepsis. As sepsis progresses, organ system dysfunction becomes apparent (severe sepsis) with the final development of fluid refractory cardiovascular dysfunction (septic shock). Pulmonary, gastrointestinal, genitourinary, and primary bloodstream infections account for the majority of infectious sources in septic patients. Since 1987, gram positive bacteria have become the most common organisms responsible for the development of sepsis. Several risk factors for the development of sepsis have been identified including male sex, race, age, comorbid medical conditions, alcohol abuse, and a lower socioeconomic status. Seasonal variations also exist, with sepsis being more common in the winter months. Fortunately, the case fatality rates for both sepsis and severe sepsis have diminished over the last two decades. However, patients who survive their episode of sepsis continue to have increased morbidity and mortality up to five years after their initial illness.     

Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis

Treatment of sepsis remains a significant challenge with persisting high mortality and morbidity. Early and appropriate antibacterial therapy remains an important intervention for such patients. To optimise antibacterial therapy, the clinician must possess knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antibacterials and how these parameters may be affected by the constellation of pathophysiological changes occurring during sepsis. Sepsis, and the treatment thereof, increases renal preload and, via capillary permeability, leads to 'third-spacing', both resulting in higher antibacterial clearances. Alternatively, sepsis can induce multiple organ dysfunction, including renal and/or hepatic dysfunction, causing a decrease in antibacterial clearance. Aminoglycosides are concentration-dependent antibacterials and they display an increased volume of distribution (V(d)) in sepsis, resulting in decreased peak serum concentrations. Reduced clearance from renal dysfunction would increase the likelihood of toxicity. Individualised dosing using extended interval dosing, which maximises the peak serum drug concentration (C(max))/minimum inhibitory concentration ratio is recommended. Beta-lactams and carbapenems are time-dependent antibacterials. An increase in V(d) and renal clearance will require increased dosing or administration by continuous infusion. If renal impairment occurs a corresponding dose reduction may be required. Vancomycin displays predominantly time-dependent pharmacodynamic properties and probably requires higher than conventionally recommended doses because of an increased V(d) and clearance during sepsis without organ dysfunction. However, optimal dosing regimens remain unresolved. The poor penetration of vancomycin into solid organs may require alternative therapies when sepsis involves solid organs (e.g. lung). Ciprofloxacin displays largely concentration-dependent kill characteristics, but also exerts some time-dependent effects. The V(d) of ciprofloxacin is not altered with fluid shifts or over time, and thus no alterations of standard doses are required unless renal dysfunction occurs. In order to optimise antibacterial regimens in patients with sepsis, the pathophysiological effects of systemic inflammatory response syndrome need consideration, in conjunction with knowledge of the different kill characteristics of the various antibacterial classes. In conclusion, certain antibacterials can have a very high V(d), therefore leading to a low C(max) and if a high peak is needed, then this would lead to underdosing. The V(d) of certain antibacterials, namely aminoglycosides and vancomycin, changes over time, which means dosing may need to be altered over time. Some patients with serum creatinine values within the normal range can have very high drug clearances, thereby producing low serum drug levels and again leading to underdosing.     

Effectiveness of statins in reducing the rate of severe sepsis: a retrospective evaluation

STUDY OBJECTIVES: To determine whether use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is associated with a reduced rate of severe sepsis, and to further characterize the effect of statins on the frequency of organ dysfunction in patients with severe sepsis. DESIGN: Retrospective cohort study. SETTING: University-associated teaching hospital. PATIENTS: Fifty-three patients admitted with sepsis; 16 were receiving statins and 37 were not receiving statins (controls) before admission. MEASUREMENTS AND MAIN RESULTS: Patients were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patient demographics, vital signs, and laboratory values were collected from their electronic medical records. The primary end point was rate of severe sepsis, defined in accordance with guidelines from the American College of Chest Physicians and the Society of Critical Care Medicine. Secondary end points were in-hospital mortality rate and rate of five categories of organ dysfunction (cardiovascular, renal, pulmonary, hematologic, and metabolic). Preadmission statin therapy, compared with no statin therapy, was associated with a 30% lower rate of severe sepsis (56% vs 86%, p<0.02). In-hospital mortality was not significantly different between groups (38% vs 49%, p=0.33); however, the rate of cardiovascular dysfunction, defined as hypotension requiring vasopressor therapy, was significantly lower in the statin group (38% vs 73%, p<0.02). No significant differences in the other organ dysfunction categories were noted between groups. CONCLUSION: Statins appear to prevent sepsis from becoming severe, most notably through prevention of sepsis-induced hypotension. This potential role for statins in the prevention and treatment of severe sepsis should be further evaluated in a randomized controlled trial.     

Sepsis: links between pathogen sensing and organ damage

The host's inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial inflammatory response in early sepsis and to bolster this response in late sepsis. The persistence of MODS after the initial inflammatory surge can also be a determining factor to host survival. MODS is due to the cellular damage and death induced by sepsis. The mechanism of this cell death depends in part upon mitochondrial dysfunction. Damaged mitochondria have increased membrane permeability prompting their autophagic removal if few mitochondria are involved but apoptotic cell death may occur if the mitochondrial losses are more extensive. In addition. severe loss of mitochondria results in low cell energy stores, necrotic cell death, and increased inflammation driven by the release of cell components such as HMGB1. Therapies, which aim at improving cellular energy reserves such as the promotion of mitochondrial biogenesis by insulin, may have a role in future sepsis therapies. Finally, both the inflammatory responses and the susceptibility to organ failure may be modulated by nutritional status and micronutrients, such as zinc, Therapies aimed at micronutrient repletion may further augment approaches targeting PRR function and mitochondrial viability.     

脓毒症的治疗药物及其作用机制研究进展

脓毒症是由严重感染引起的综合征,可导致器官功能障碍甚至患者死亡。由于老龄化、抗菌药物耐药性急剧增加等因素,脓毒症的发病率和死亡率居高不下。脓毒症发生机制错综复杂,涉及细胞焦亡、凝血功能和线粒体功能障碍、细胞自噬等。针对脓毒症的治疗药物研究一直是医药领域的热点。通过检索中国知网、万方、PubMed等中外数据库近5年来关于脓毒症治疗药物的相关研究文献并认真研读分析后作一综述,以期为临床有效治疗脓毒症、降低病死率提供理论参考。     

免疫细胞在脓毒血症中的作用及机制研究进展

脓毒血症是由危及生命的感染所引起的宿主炎症反应,伴随着严重的器官功能衰竭和障碍。近年来,尽管医学和医疗技术都取得了巨大进步,脓毒血症的病死率仍高达30%~70%。脓毒血症本质上是机体对感染性因素的反应,初始免疫反应是一种过度炎症状态,随后迅速发展为免疫抑制状态。了解参与脓毒血症期间器官损伤发展中的宿主细胞介导的免疫反应是至关重要的。总结了各类免疫细胞在人和小鼠脓毒血症期间的作用变化及机制研究进展。