Special article: The association of sepsis with multiple organ dysfunction syndrome

Multiple organ dysfunction syndrome (MODS), a clinical condition that involves relentless organ dysfunction accompanied by abnormal organ system interactions, is triggered primarily by sepsis and trauma. An understanding of the three basic pathophysiological processes involved (acute-phase; release of chemicals from agents responsible for infection; and interaction of substrate production, availability, and utilization in the response to injury or infection) and the factors that operate in the acute-phase response is critical for the appropriate use and development of agents to modify the chain of events leading to MODS. This article addresses the unregulated activation of the systemic inflammatory cascade, the effects of alterations of oxygen uptake and oxygen delivery relationships, and treatment approaches regarding the triggering agent, the syndrome itself, and cardiovascular failure. Copyright © 2000 by W.B. Saunders Company     

Pediatric sepsis and multiple organ dysfunction syndrome

Systemic inflammatory response syndrome may be viewed as the systemic expression of cytokine signals that normally function on an autocrine or paracrine level. Sepsis is defined as systemic inflammatory response syndrome caused by an infection. Multiple organ dysfunction syndrome may represent the end stage of severe systemic inflammatory response syndrome or sepsis. Many cells are involved, including endothelial cells and leukocytes and multiple proinflammatory and antiinflammatory mediators (cytokines, oxygen free radicals, coagulation factors, and so forth). Various pathophysiologic mechanisms have been postulated. The most popular theory is that the inflammatory process loses its autoregulatory capacity; however, microcirculatory dysregulation and apoptosis may also be important, and a new paradigm posits a complex nonlinear system. Many new treatments have been studied recently. The usefulness of immune modulating diets remains to be evaluated. Molecular immunomodulation is still of unclear value. The therapy of sepsis and multiple organ dysfunction syndrome remains mainly supportive.     

Systemic inflammatory response syndrome

Despite advances in perinatal care in the past decade, sepsis and its complications continue to present problems for the neonate, remaining a major cause of neonatal morbidity and mortality. Sepsis research is focusing on how the neonate (host) responds to bacteria. The newborn may develop a systemic reaction to bacteria that induces the release of substances known as inflammatory mediators. Termed the systemic inflammatory response syndrome (SIRS), this reaction is believed to be responsible for the signs and symptoms of sepsis. This article introduces the neonatal nurse to SIRS, providing an overview of various inflammatory mediators and cytokines, their clinical consequences, and potential new therapies in the management of SIRS.     

脓毒症3.0在儿童脓毒症诊断的运用——我们还有很多工作要做

脓毒症定义自1991年首次提出以来,定义主要内容由感染+全身炎症反应综合征演变为感染+器官功能障碍,而器官功能障碍通过序贯器官功能衰竭评估(sequential organ failure assessment,SOFA)评分的增加来表示.这一核心内容体现在2016年发布的脓毒症3.0中.在脓毒症3.0中SOFA评分在脓毒症的识别与诊断中具有突出地位,但该诊断标准主要是针对于成人,该诊断标准在儿童中如何应用,我们需要思考哪些问题,本文将对此进行探讨.     

连续血液净化技术治疗小儿脓毒症

脓毒症的病理生理机制在于全身炎症反应综合征,连续血液净化可以通过滤过、吸附等清除中大分子炎症递质,降低组织炎症递质水平,改善心肺等主要器官功能,有助于脓毒症的治疗。连续血液净化技术在儿童脓毒症的救治中具有良好的应用前景。     

线粒体融合-分裂在脓毒症发病机制中的作用

脓毒症是感染导致的全身炎症反应综合征,进一步发展可导致感染性休克和多器官功能障碍综合征.脓毒症具有高发病率及病死率,是危重症领域的研究热点.近年来,亚细胞相关研究提示线粒体损害在脓毒症患者(尤其是脓毒症休克患者)的病情发展中起着非常重要的作用.线粒体是细胞内高度动态变化的细胞器,在细胞内不断融合与分裂,形成动态平衡的网状结构.脓毒症时,线粒体融合与分裂失衡,导致细胞内分子、细胞以及器官均发生功能障碍.该文就线粒体融合-分裂改变在脓毒症发病机制中作用的研究进展作一综述.     

兰尼碱受体磷酸化在脓毒性心肌病中的作用

脓毒症是指是感染引起的全身性炎症反应,是感染、烧伤、严重创伤、大手术、病理产科、中毒及心肺复苏术后常见的并发症,也是诱发脓毒症性休克、多器官功能障碍综合征的重要原因.心脏作为脓毒症所致的多器官功能障碍的主要靶器官之一,脓毒症时常诱发不同程度功能障碍,而心功能障碍可导致脓毒症进一步恶化.兰尼碱受体是一种大分子复杂蛋白组成的受体,是Ca2+通道的成分之一,对于肌肉收缩和心脏节律的调节是必不可少的,参与调节肌浆网释放Ca2+.该文对脓毒症心功能衰竭时,钙离子通道中兰尼碱受体作一综述.     

脓毒症与线粒体功能障碍

脓毒症为各种病原菌侵入机体后引起的全身炎症反应综合征。脓毒症、严重脓毒症、脓毒症休克、多脏器功能衰竭为疾病的进展过程。线粒体被称为“动力工厂”,为各脏器维持正常功能提供能量。脓毒症时免疫异常、多种炎症因子的激活及释放、细胞内信号传递异常及氧化应激等可引起线粒体功能障碍。最近研究提出,线粒体自噬在线粒体功能障碍中也起着一定作用。该文就脓毒症时引起机体线粒体损伤的机制进行综述。     

严重感染的血液净化治疗

严重感染(脓毒症)的根本机制在于全身炎症反应综合征,连续血液净化可以通过滤过、吸附等清除中、大分子量炎症介质,有助于脓毒症的治疗.临床应用和实验研究证实了连续血液净化技术可稳定严重脓毒症患者的心肺功能.连续血液滤过透析、连续血浆滤过吸附、高容量血液滤过技术通过降低血浆和组织中炎症介质水平而起治疗作用.连续血液净化技术在儿童脓毒症的救治中具有良好的应用前景.

Abstract：

The key mechanism of severe infection (sepsis) is systemic inflammatory reaction syndrome. Continuous blood purification (CBP) is helpful for treatment of sepsis through removing medium and large molecular weight inflammatory mediators. Clinical application and lab researches have confirmed that CBP can stabilize cardiopulmonary function in patients with severe sepsis. Continuous veno-venous hemodiafiltration, continuous plasma filtration absorption and high volume hemofiltration can play a role in lowering inflammatory mediators in plasma and tissue. CBP has revealed a good prospect in the treatment of severe sepsis in children.     

严重感染的血液净化治疗

严重感染（脓毒症）的根本机制在于全身炎症反应综合征,连续血液净化可以通过滤过、吸附等清除中、大分子量炎症介质,有助于脓毒症的治疗。临床应用和实验研究证实了连续血液净化技术可稳定严重脓毒症患者的心肺功能。连续血液滤过透析、连续血浆滤过吸附、高容量血液滤过技术通过降低血浆和组织中炎症介质水平而起治疗作用。连续血液净化技术在儿童脓毒症的救治中具有良好的应用前景。     

严重感染的血液净化治疗

严重感染(脓毒症)的根本机制在于全身炎症反应综合征,连续血液净化可以通过滤过、吸附等清除中、大分子量炎症介质,有助于脓毒症的治疗.临床应用和实验研究证实了连续血液净化技术可稳定严重脓毒症患者的心肺功能.连续血液滤过透析、连续血浆滤过吸附、高容量血液滤过技术通过降低血浆和组织中炎症介质水平而起治疗作用.连续血液净化技术在儿童脓毒症的救治中具有良好的应用前景.     

血小板在脓毒症中的研究进展

脓毒症为感染致全身免疫失调的炎症反应综合征,血小板在脓毒症发生发展中起着重要作用。血小板可通过黏附、聚集、活化、脱颗粒作用与病原微生物相反应,以达到保护机体的作用。同时,脓毒症时血小板还可与中性粒细胞等免疫细胞相互作用,参与微血栓、炎症的形成。因此,血小板有抗微生物效应及与其他先天免疫细胞协作,形成复杂的血管内免疫防御...     

Septic shock: Pathogenesis and treatment

Septic shock is the host’s inflammatory response to infection. There are multiple endogenous mediators responsible for the pathogenesis of septic shock. Cytokines, nitric oxide and prostaglandins are some of the major mediators. The term sepsis syndrome allows for an earlier diagnosis and treatment. Management of septic shock is focused in maintaining hemodynamic stability and an adequate oxygen delivery and utilization. Careful attention to each organ-system is of paramount importance to prevent complications and improve outcome. Experimental therapies to modulate the inflammatory response are promising.     

New insights into the pathogenesis of pulmonary inflammation in preterm infants

Chronic lung disease (CLD) and bronchopulmonary dysplasia are associated with a significant inflammatory response of the airways and the interstitium of the lungs. Besides inflammatory cells, various cytokines, lipid mediators, proteolytic enzymes and toxic oxygen radicals may play an essential role in the pathogenesis of this disease. Intrauterine exposure to chorioamnionitis or proinflammatory cytokines has been shown to induce a pulmonary and systemic inflammatory response in the fetus. In this subgroup, antenatal infection may prime the lung such that minimally injurious postnatal events provoke an excessive inflammatory response in the airways and the pulmonary tissue. Inflammation and lung injury most certainly affect normal alveolization and pulmonary vascular development in preterm infants with CLD.     

高容量血液滤过在儿科的应用进展

高容量血液滤过(high volume hemofiltration,HVHF)是血液净化领域的一项重要发展,具有稳定血流动力学、清除炎症因子和体内代谢毒素等作用,同时HVHF在治疗中也存在一些弊端.目前HVHF在全身性炎症反应综合征、儿童脓毒症、脓毒性休克、多器官功能障碍、急性肾损伤、急性中毒等儿科危重疾病中的应用逐渐增多,已经成为儿科急救医学领域一项重要的救治技术.     

SIRS标准需要摒弃吗?

2016年2月,美国危重病学会与欧洲危重病学会在第45届危重病医学年会上联合发布了脓毒症3.0定义及诊断标准.自此,脓毒症的定义被修订为感染引起机体反应失调从而导致危及生命的器官功能障碍,将使用脓毒症相关序贯器官衰竭评分(sequential organ failure assessment,SOFA)或快速SOFA(qSOFA)对脓毒症进行甄别,而不再是全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)标准.虽然SIRS标准存在敏感度高、特异度较低等缺陷,但在过去的20多年里,全球的脓毒症病死率的确有明显下降.脓毒症3.0仍存在不足之处,无儿童标准,未来尚需对其进行验证.在早期识别方面,SIRS标准仍有其应用价值.如何同时提高脓毒症诊断的敏感性和特异性,以及脓毒症3.0对重症领域的影响等均值得进一步研究.     

脓毒症的血液净化治疗

脓毒症是机体对感染反应失调而引起的危及生命的器官功能障碍。目前临床上尚无针对脓毒症炎性反应的确切对症治疗方法。血液净化治疗通过非特异性清除内毒素和（或）炎症介质而发挥免疫调理作用,显示出良好的应用前景。然而目前多数有关血液净化治疗脓毒症的研究结果并未显示其可以明显改善患者预后。该文就脓毒症血液净化免疫调节机制及不同血液净化方法利弊的研究进展进行介绍。     

Mechanisms initiating lung injury in the preterm

Bronchopulmonary dysplasia (BPD)/chronic lung disease occurs primarily in very low birth weight infants (VLBW) often without antecedent severe respiratory distress syndrome. The BPD in these VLBW infants results in less fibrosis than the traditional BPD but the normal process of alveolarization seems to be disrupted. This review develops the thesis that BPD in VLBW infants results from inflammatory mediators interfering with the signaling required for normal late gestational lung development. Proinflammatory mediators may be elevated because of fetal exposure, postnatal infection or by release from preterm lungs ventilated at either low or high lung volumes. The preterm lung is highly susceptible to injury during resuscitation or more chronic mechanical ventilation because the gas volumes/kg body weight of the lungs are small. An understanding of what causes cytokine release and how cytokines influence lung development is necessary to develop targeted therapies to minimize BPD. However, care strategies that minimize inflammation and ventilator-induced lung injury should help decrease BPD.     

CSF cytokine levels in preterm infants may reflect systemic inflammation and are independent of gestation

Background

Among preterm infants, high concentrations of inflammatory mediators in cerebrospinal fluid (CSF) are associated with poor outcome. Previous studies have not indicated whether CSF concentrations of inflammatory mediators are associated with important confounders such as gestational age.

Aims

To examine associations between CSF concentrations of inflammatory mediators and gestational age, maternal features suggestive of inflammation, characteristics of the CSF sample or the presence of a systemic inflammatory response.

Study design and subjects

Aliquots of CSF obtained during routine investigation of potential sepsis among infants born before 35 weeks gestation were assayed for 17 mediators of inflammation using a fluorescent multi-bead analyser. Other information was collected from routine clinical records.

Results

39 infants were assessed. CSF levels of mediators of inflammation were not correlated with gestational age. CSF red blood cell counts were correlated with CSF concentrations of IL-6, GM-CSF and IL-17 (each p < 0.003). CSF lactate was correlated with CSF concentrations of IL-1β, IL-6, GM-CSF, G-CSF, IFN-γ and MIP-1β. CSF concentrations of IL-1β, IL-6, G-CSF, TNF-α and IFN-γ were higher in infants with a raised CRP within 24 h of delivery (each p < 0.003).

Conclusions

CSF concentrations of inflammatory mediators most probably reflect inflammatory pathologies and are not influenced by gestational age. They may also, however, reflect contamination with blood or systemic inflammation. CSF concentrations of inflammatory mediators may not provide a specific indicator of CNS inflammation.     

Immune reconstitution inflammatory syndrome and solid organ transplant recipients: Are children protected?

McLin VA, Belli DC, Posfay‐Barbe KM. Immune reconstitution inflammatory syndrome and solid organ transplant recipients: Are children protected?
Pediatr Transplantation 2010: 14: 19–22. © 2010 John Wiley & Sons A/S. Abstract: The IRIS was initially described in HIV‐positive patients as a sudden clinical deterioration after the introduction of highly active retroviral therapy. It is believed that IRIS is caused by a restored and exaggerated inflammatory immune response to different infectious or non‐infectious triggers. This abnormal response is the consequence of an imbalance between pro‐inflammatory and anti‐inflammatory states. Recently, IRIS has also been reported in adult SOT recipients, causing local and systemic manifestations, and compromising long‐term graft function and patient survival. However, IRIS has to date not been reported in pediatric SOT recipients. Here we review what is known and speculated about the pathogenesis of IRIS and propose that children may be relatively protected from IRIS.