严重脓毒症和脓毒性休克早期目标导向治疗

严重脓毒症是PICU患儿死亡的主要原因之一.尽管抗生素和综合治疗手段不断改进,但其病死率依然居高不下.目前,研究证实早期目标导向治疗能显著降低严重脓毒症和脓毒性休克患者的病死率.本文介绍了目前国内外专家公认的早期目标导向治疗方案,旨在指导儿科医师尽早规范化地治疗严重脓毒症患儿,改善预后,提高生存率.     

严重脓毒症和脓毒性休克的几个热点问题

近十余年,国际和国内危重病学家就脓毒症进行了大量研究,提出了全身炎症反应综合征(SIRS)、感染、脓毒症(sepsis)、严重脓毒症、脓毒性休克的概念,并对其发病机制、诊断治疗提出了新的指南。本文就小儿严重脓毒症和脓毒性休克的定义和诊断、血流动力学-氧代谢监测、早期目标指导治疗等问题进行讨论。     

早期识别脓毒症、严重脓毒症及脓毒性休克

早期识别严重脓毒症和脓毒性休克,及早启动有效干预,实施早期目标导向治疗是降低其病死率、改善预后的关键.本文重点介绍脓毒症分阶段诊断系统（即PIRO分级系统）、系统的预警及快速反应系统等临床识别方法;多种生物学标记物及蛋白质组学和代谢组学在脓毒症和严重脓毒症诊断中的价值.目前尚无单一完美的指标可以早期识别脓毒症,因此,临床医生更应该结合患者症状、体征和生物学标记物综合判断,动态观察监测参数变化,从而做出合理的判断和决策.     

新生儿脓毒症及脓毒性休克诊疗策略

脓毒症是指各种病原微生物(包括细菌、真菌、病毒及原虫)入侵机体血液循环,产生毒素所造成的全身性感染.新生儿脓毒症早期症状多不典型,特别是早产儿,起病急,进展迅速,极易发生脓毒性休克,甚至危及生命.因此,早期识别、准确诊断和积极干预新生儿脓毒症及脓毒性休克,对降低病死率及改善预后至关重要.     

2016国际脓毒症和脓毒性休克管理指南解读

国际专家组对"拯救脓毒症运动:2012版脓毒症和脓毒性休克管理指南"进行了更新,结果发表于Critical Care Medicine杂志.专家组提出了93条关于脓毒症和脓毒性休克早期管理及复苏的推荐意见.众多国际专家就脓毒症患者的最佳管理形成了较多强烈推荐意见.虽然有相当数量的推荐意见证据级别较弱,但以证据为基础的推荐意见用于脓毒症及脓毒性休克的早期管理是改善预后的基础.     

儿童脓毒性休克诊治专家共识--我们需要关注哪些变化

《儿童脓毒性休克（感染性休克）诊治专家共识（2015版）》已发表,是在国际指南的引领下,并结合国内外大量研究文献,在2006年制定的《儿科感染性休克（脓毒性休克）诊断治疗推荐方案》基础上,主要就儿童脓毒性休克定义、诊断和早期集束化治疗方案进行了部分修订。《儿童脓毒性休克（感染性休克）诊治专家共识（2015版）》的制定旨在指导临床一线医师对儿童脓毒性休克早期识别和早期积极干预,并进一步降低病死率和改善预后。     

儿童脓毒症生物标记物的研究进展

脓毒症是机体对感染的反应失调而导致危及生命的器官功能障碍,是当今危重病医学所面临的焦点和难点问题.目前世界范围内儿童脓毒症的发生率仍居高不下,若治疗不及时可发展成脓毒性休克、多器官功能障碍综合征,严重威胁人类健康.因此脓毒症的早期识别、诊断、治疗对降低病死率有重要意义.而生物标记物在脓毒症的早期诊断、病情及预后判断,疗效评估中发挥重要作用.本文就近年来脓毒症的生物标记物进行总结.     

严重脓毒症血制品应用和免疫支持治疗

严重脓毒症和脓毒性休克是在脓毒症基础上并发器官功能衰竭或者组织灌注不足为特征的临床综合征,其病死率高.虽然早期足量快速的液体复苏是严重脓毒症和脓毒性休克治疗的关键,但白蛋白、血浆、红细胞、血小板、丙种球蛋白等血制品输注,以及血液净化、乌司他丁联合胸腺肽和抗CD14单克隆抗体等免疫支持也起着一定作用.     

脓毒症的诊治进展

脓毒症（sepsis）是一种发病率和病死率都很高的疾病。在美国,每年约有75万人发生脓毒症,其中约有21．5万人死亡（病死率高达28．7％）,其病死人数几乎与因急性心肌梗死死亡的人数一样多。脓毒症发展到严重脓毒症以及脓毒性休克是一个连续的过程,在此过程中疾病的严重性逐步加深,病死率逐步升高。如果延迟识别、诊断和治疗,将会增加脓毒症的病死率,并消耗大量的医疗资源。所以早期识别和治疗严重脓毒症和脓毒性休克是非常重要的。     

高动力型脓毒性休克诊断与治疗

脓毒性休克也称感染性休克,是儿童常见危重症,早期规范干预治疗可降低病死率、改善预后。高动力型脓毒性休克也称暖休克,早期常不能被及时发现及治疗。临床医生应进一步提高对高动力型脓毒性休克的诊断治疗水平。     

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

OBJECTIVE: Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. DESIGN: Consensus conference. METHODS: This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. RESULTS: Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. CONCLUSION: We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.     

Recent advances in sepsis and septic shock

Sepsis remains a common problem in all age groups. Recently surviving sepsis campaign has taken up a worldwide initiative by publishing international guidelines 2008 with a hope to disseminate information regarding management of sepsis for all age groups. This article presents a review of recent advances as they apply to pediatric age group supported by the available evidence with reference to standard definitions of pediatric sepsis and septic shock and management in the emergency room and pediatric intensive care unit.     

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??Hemofiltration and renal replacement therapy are usually preferred as adjunct therapy for sepsis to improve hemodynamics and fluid balance??as well as to remove noxious molecules and inflammatory factors. It is well known that continuous renal replacement therapy??CRRT?? is an important adjunct therapy for sepsis-associated kidney injury. Recently?? blood purification is widely used to treat septic shock?? acute respiratory distress syndrome??ARDS???? severe acute pancreatitis and electrolyte imbalance. Currently?? there are four differentpatternsofblood purification used including continuous veno-venous hemofiltration??CVVH???? high volume hemofiltration??HVHF???? continuous veno-venous hemodiafiltration??CVVHDF?? and plasma exchange??PE?? in pediatric sepsis. However??there is no standard recommendation for blood purification model and the optimal timing in pediatric sepsis.     

维生素D缺乏症与儿童脓毒症及脓毒性休克相关性的系统评价

目的:采用系统评价的方法分析维生素D缺乏症(Vitamin D deficiency,VDD)与儿童脓毒症及脓毒性休克之间的关系,探讨不同VDD对其发生及预后的影响。方法:应用Medline、EBSCO host、Web of Science数据库以及中国知网和万方数据库,系统性检索维生素D与危重症儿童的观察性队列研究,根据Newcastle-Ottawa scale文献质量评估标准评估文献质量,采用统一的脓毒症及脓毒性休克的诊断标准和临床指标,分别提取25(OH)-D浓度及与脓毒性休克的相关数据,综合分析两种不同VDD与儿童脓毒症及脓毒性休克的关系。结果:共检索到658篇文献,最终纳入文献8篇,包括1 367例危重症患儿。系统评价结果显示,重度VDD患儿发生脓毒症及脓毒性休克的风险性明显上升,合并 RR值分别为1.71(95% CI1.11-2.63, P=0.01)和2.05(95% CI1.35-3.10, P<0.001),显著高于VDD患儿相应的发病率;此外与非重度VDD患儿相比,重度VDD的cv-SOFA评分明显增加( RR0.68,95% CI0.45-0.91, P<0.001)。VDD与重度VDD患儿均未在脓毒症病死率及血管活性药物维持时间方面表现出统计学差异。 结论:在危重症儿童中,重度VDD与脓毒症及脓毒性休克的发生密切相关,而且合并重度VDD可使脓毒症患儿的cv-SOFA评分显著上升,明显优于VDD标准。     

A history of adjunctive glucocorticoid treatment for pediatric sepsis: moving beyond steroid pulp fiction toward evidence-based medicine.

OBJECTIVES: To review the history of clinical use of corticosteroids with particular reference to adjunctive therapy for severe pediatric sepsis and, in this context, to provide an overview of what is known, what is not known, and what research questions are particularly relevant at this time. DATA SOURCE: Literature review using PubMed, cross-referenced article citations, and the Internet. CONCLUSIONS: The history of corticosteroid use in clinical medicine has been colorful, noisy, and always controversial. Therapeutic corticosteroid indications that initially seemed rational have frequently been refuted on closer, rigorous clinical trial inspection. Although it may be prudent to provide stress-dose steroids to children with septic shock who are clinically at risk for adrenal insufficiency (chronic or recent steroid use, purpura fulminans, etomidate or ketoconazole administration, hypothalamic, pituitary, adrenal disease), the safety and efficacy of stress-dose steroids as general adjunctive therapy for pediatric septic shock have not been established. Glucocorticoid administration does add potential risk to critically ill children. In particular, although adjunctive corticosteroids may hasten resolution of unstable hemodynamics in septic shock, this may occur at the metabolic cost of hyperglycemia. Clinical practice that fosters innovative therapy (off-label use) over research probably represents bad medical and social policy. Accordingly, pediatric critical care researchers have a responsibility to generate pediatric-specific evidence-based medicine for adjunctive corticosteroid therapy for severe sepsis in children.     

促肾上腺皮质激素刺激对脓毒症及脓毒性休克患儿肾上腺功能评估的意义

目的 探讨小剂量(1μg/1.73 m2)促肾上腺皮质激素(ACTH)刺激实验评估儿童脓毒症和脓毒性休克肾上腺功能状态的价值.方法 患儿入院24h内完成基础皮质醇(T0)测定,静脉注射1μg/1.73m2 ACTH,30 min后测定血液皮质醇(T1),根据T0和皮质醇增值(△max=T1-T0)判断肾上腺功能,以△max≤90μg/L为肾上腺功能障碍(AI)指标.结果 62例中,脓毒症53例,脓毒性休克9例,病死率为27.4%(17/62).肾上腺功能障碍(adrenal insufficiency,AI)发生率40.3%(25/62),其中脓毒症和脓毒性休克患儿AI发生率分别是39.6%和44.4%,差异无显著统计学意义(P>0.05).两组脓毒症和脓毒性休克平均T0和T1分别是(318.6±230.4)μg/L、(452.3±230.7)μg/L和(454.7±212.7)μg/L、(579.3±231.9)μg/L,差异无统计学意义(P>0.05).存活组和死亡组患儿T0、T1分别是(320.5±223.9)μg/L、(462.3±212.0)μg/L和(384.3±258.3)μg/L、(500.7±470.6)μg/L,两组AI发生率分别是37.8%和47.1%,差异无统计学意义(P>0.05).T0和T1水平与儿童危重病例评分(PCIS)有关(P<0.05),AI发生率与PCIS、PRISMⅢ和器官功能障碍数目无关(P>0.05).结论 儿童脓毒症和脓毒性休克患儿AI发生率较高.小剂量ACTH刺激实验可以判断严重感染患者肾上腺功能,可为激素治疗提供依据.     

儿童严重脓毒症及脓毒性休克大量液体复苏的新观点

及时识别和治疗儿童脓毒性休克是改善预后,降低病死率的关键。然而,目前仍缺乏儿童脓毒症液体复苏的统一认识。最近关于发热和灌注不足儿童的大量液体复苏的支持疗法研究结果更是引发人们对儿童液体复苏容量治疗的激烈讨论。该文就大量液体复苏的支持疗法的现状和可能机制进行分析。     

Serum TNF levels in neonatal sepsis and septic shock

Tumor necrosis factor (TNF-alpha) has been implicated as a principal mediator in the pathogenesis of septic shock. TNF-alpha was measured by immunoradiometric assay in serum samples from 23 full-term infants with sepsis (15 with severe infection and 8 with septic shock) and in 20 healthy full-term newborns. Serum TNF-alpha levels were significantly higher in the group with sepsis, at the time of admission to the neonatal intensive care unit, than in the healthy neonates. The highest TNF levels were found in those newborns with septic shock, particularly in those who died. Although the method is far too slow for any clinical routine work, our results suggest that the presence of elevated serum TNF-alpha levels could be considered a sensitive and specific test for predicting septic shock and its clinical outcome.     

Cytokine inhibitors for sepsis and septic shock

Lipopolysaccharide and other bacterial products stimulate the immune cells of the host to elicit secondary inflammatory mediators, including cytokines. The 2 primary proinflammatory cytokines elicited in septic shock are tumor necrosis factor (TNF) and interleukin-1 (IL-1). Because of the importance of these cytokines in the biologic response to sepsis, they stand out as potential targets for adjunctive therapies of sepsis. This review focuses on therapies designed to inhibit the responses of TNF and IL-1, including studies in animals and humans evaluating TNF monoclonal antibodies, TNF receptor fusion proteins, IL-1 receptor antagonists, IL-1 receptor antibodies, and phosphodiesterase inhibitors. In general, the human trials have been disappointing in comparison with corresponding animal studies. As of yet, no cytokine inhibitor therapy that significantly decreases mortality in patients with severe sepsis or septic shock has been found. Copyright © 2001 by W.B. Saunders Company