体外循环技术在气管肿瘤手术中的应用

2004年3月25日,我院在体外膜肺氧合(ECMO)支持下行右全肺切除术,左主气管与总气管吻合术1例,手术成功,现报道如下：     

脓毒症致肺血管内皮细胞损伤机制的研究进展

ICU病房中,急性肺损伤(Acute lung injury,ALI)是脓毒症常见并发症并有较高发病率和死亡率.研究表明肺血管内皮细胞是脓毒症致ALI的重要靶细胞和效应细胞,肺血管内皮细胞功能紊乱和损伤在脓毒症致ALI发生、发展中有重要作用,本文概述脓毒症致肺血管内皮损伤的相关发病机制.     

脓毒症诊断的生物学标志物的研究进展

脓毒症是由致病微生物感染引发的全身炎症反应综合征(SIRS),合并血压降低且经快速液体复苏后血压仍不能恢复正常者称为脓毒性休克(Septic shock),其中一部分患者发展为多器官功能障碍综合症(MODS)。由于目前临床上仍缺乏早期敏感性诊断手段,脓毒症病死率居高不下。每10万人口中约50-300人会发生严重脓毒症,其短期死亡率达20%-25%,当发展为脓毒性休克时其死亡率达50%。随着分子生物学和现代生物技术的不断发展,人们发现多种生物标志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。因此深入了解脓毒症病理生理机制中不同生物标志物的意义及价值,对于脓毒症及其并发症的早期识别及干预,降低患者病死率及改善患者生活质量有积极意义。本文综述了近几年来对脓毒症的诊断和预后有一定价值的主要标志物及其应用。     

糖皮质激素在脓毒症治疗中的研究进展

脓毒症是由致病微生物感染引发的全身炎症反应综合征（SIRS),合并血压降低且经快速液体复苏后血压仍不能恢复正常者 称为脓毒性休克（Septic shock),其中一部分患者发展为多器官功能障碍综合症(MODS)。脓毒症病死率居高不下。每10 万人口中 约50-300 人会发生严重脓毒症,其短期死亡率达20%-25%,当发展为脓毒性休克时其死亡率达50%。整合消灭致病微生物、阻断 炎症介质和处理MODS等措施的" 集束化"治疗并未显著降低脓毒症患者的病死率。糖皮质激素具有强大的抗炎作用,但诸多 的临床研究对糖皮质激素疗效的评价褒贬不一,糖皮质激素是否有利于脓毒症的转归一直饱受争议[3]。本文仅就糖皮质激素在 严重脓毒症及脓毒性休克中的治疗进展综述如下,并希望能进一步探讨发生严重脓毒症及脓毒性休克时,机体对糖皮质激素反 应复杂性的原因,以及在以后的研究中对相对肾上腺皮质功能不全的诊断标准及对糖皮质激素用药和停药时机的选择更加明确。     

生物喋呤的生物学效应及其在脓毒症中的意义

研究表明,一氧化氮（ＮＯ）的过度产生可能是诱发脓毒性休克的最后共同通路,而生物喋呤为一氧化氮合酶（ＮＯＳ）重要的辅因子。多种免疫刺激因子均可诱导细胞内ＢＨ４合成显著增加,其可瑟ＮＯＳ紧密结合,调控ＮＯ的合成与释放。本文讨论了ＢＨ４的生物学效应,调控机制及其在脓毒症中的作用,并简要介绍其合成抑制剂在脓毒症防治中的潜在意义。     

高氧在临床应用中的研究进展

氧气是人类赖以生存的物质,是人体进行新陈代谢的关键,是人体生命活动的第一需要。在人类没有发现氧气之前,其对人类生存的重要性并不为人类所知。随着人类发现氧气并意识到其对人类生存的重要性之后,人类对氧气的研究越来越深入。起初,吸入高浓度氧仅用来治疗低氧血症等呼吸相关疾病,而后,氧气发展成为临床常用的一种辅助治疗手段,可用于多个科室多种疾病的辅助治疗。本研究小组通过动物实验发现高浓度氧吸入可明显降低脓毒症小鼠的病死率,并可以改善其组织病理,炎性细胞因子等的表达变化,也可以改善脑缺血再灌注小鼠的脑梗死面积及行为学表现等。本文主要概括了高浓度氧吸入对于全身各系统的影响作用并重点阐述了高浓度氧吸入对于脓毒症以及组织缺血再灌注的治疗作用。     

白细胞介素-16在脓毒症肝和肺组织中表达的免疫组织化学研究

观察白细胞介素－16（interleukin-16,IL-16)在脓毒症时肝和肺组织中的细胞定位及分布,并探讨其在脓毒症发病中的作用和意义。应用新型敏感的免疫组织化学方法（超敏感－SP法）检测本校近年收集的18例感染、败血症和脓毒症尸检肝和肺组织白细胞介素－16的原位表达,在肝组织中IL－16主要定位于肝窦枯否细胞、单核细胞以及部分中性粒细胞、阳性率达72.3%。肝细胞形态改变主要包括肝窦扩张充血,枯否细胞增生肿胀,肝细胞变性及不同程度的灶性坏死,在肺组织中IL－16定位于肺部质及感染灶内的巨噬细胞,中性粒细胞以及少量淋巴细胞,其阳性率达66.7％。肺组织形态改变主要包括肺泡壁毛细血管扩张充血,间质及肺泡壁内大量炎性细胞浸润,部分肺泡扩张,肺泡壁断裂;可灶性坏死,坏死区肺结构消失,纤维组织增生。同时,观察到IL－16随组织病理变化的加重表达增强的趋势。本研究结果提示IL－16可能在脓毒症所致脏器损害中发挥重要作用。     

脓毒症诊断与预后的血清学标志物研究进展

脓毒症可引起患者的多器官功能衰竭,从而导致严重烧伤、手术后、孕产妇、重症监护病房和新生儿监护病房的患者死亡。缺乏脓毒症急性相反应的患者病死率更高。寻找快速、简洁、敏感性和特异性高的脓毒症实验室诊断指标,已成为临床实验室长期以来的研究课题。     

一氧化氮合酶与脓毒症的研究进展

脓毒症在外科临床工作中较常见,治疗相当困难;本文主要概述了一氧化氮合酶的基因定位、结构特点以及一氧化氮合酶与脓毒症的关系,进一步说明由一氧化氮合酶介导的一氧化氮生成与脓毒症关系密切,而选择性一氧化氮合酶抑制剂在脓毒症各阶段恰当的应用可能是有效治疗脓毒症、降低病死率的一个重要途径,也将成为今后研究的热点。     

内皮细胞微粒与脓毒症研究进展

内皮细胞微粒是活化或凋亡的内皮细胞表面释放的直径1μm的小囊泡。它是反映内皮功能的标志物。研究表明在脓毒症的发生发展过程中,内皮细胞微粒在炎症反应、凝血反应、血管内皮功能等多方面能发挥有利和有害双方面的作用。脓毒症的研究进展和内皮细胞微粒密切相关。该文将就内皮细胞微粒与脓毒症研究进展做一简要综述。     

A Case of Vivax Malaria Complicated by Adult Respiratory Distress Syndrome and Successful Management with Extracorporeal Membrane Oxygenation

Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.     

Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation

To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h^-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.     

Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation

Background and Objectives

Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality.

Methods

Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality.

Results

Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI.

Conclusion

The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.     

肼对蓝膜的影响

利用紫外可见吸收光谱和动力学光谱法研究了无水肼对蓝膜的影响,研究结果表明:无水肼可以使蓝膜转化为紫膜,同时光循环也得到恢复,但是光循环中间体M412的衰减加快,这与金属阳离子加入到蓝膜溶液中时的现象是完全不同的(这个过程中M412的衰减是减慢的).同时研究了pH和温度对无水肼与蓝膜之间相互作用的影响.在无水肼加入到蓝膜溶液中时,重组反应的灵敏度是pH和温度依赖的.在pH4.8到pH2之间,灵敏度随酸性的增加而降低.在20～40℃之间,无水肼与蓝膜溶液的反应灵敏度随着温度的升高而降低.     

计算机在体外循环中的应用

计算机在医学领域的应用范围不断扩大,体外循环专业是临床医疗和生物工程紧密合作而产生的,计算机在该领域的应用也有其独特性。在体外循环领域计算机技术不仅直接同一些仪器设备相整合,而且在设备设计,智能化以及质量控制等方面的应用也不断增加。     

Plasma Concentrations of Oseltamivir and Oseltamivir Carboxylate in Critically Ill Children on Extracorporeal Membrane Oxygenation Support

Introduction

To evaluate the effect of extracorporeal membrane oxygenation (ECMO) support on pharmacokinetics of oseltamivir and oseltamivir carboxylate (OC) in children.

Methodology

Steady state 0–12 hour pharmacokinetic sampling was performed in new influenza A (H1N1) infected children treated with oseltamivir while on ECMO support. Cmax, Cmin and AUC_{0–12 h} were calculated. The age-specific oseltamivir dosage was doubled to counter expected decreased plasma drug concentrations due to increased volume of distribution on ECMO support.

Principal Findings

Three patients were enrolled aged 15, 6 and 14 years in this pharmacokinetic case series. For two children the OC plasma concentrations were higher than those found in children and adults not on ECMO. These increased plasma concentrations related to the increased oseltamivir dosage and decreased kidney function. In one patient suboptimal plasma concentrations coincided with a decreased gastric motility.

Conclusion

Oseltamivir pharmacokinetics do not appear to be significantly influenced by ECMO support. Caution is required in case of nasogastric administration and decreased gastric motility. Due to the limited number of (paediatric) patients available further multicenter studies are warranted.     

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice

Recent studies revealed that scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. However, the mechanisms underlying this protection remain largely unknown. In this study, using Scarb1^I179N mice, a mouse model specifically deficient in hepatic SR-BI, we report that hepatic SR-BI protects against cecal ligation and puncture (CLP)-induced sepsis as shown by 75% fatality in Scarb1^I179N mice, but only 21% fatality in C57BL/6J control mice. The increase in fatality in Scarb1^I179N mice was associated with an exacerbated inflammatory cytokine production. Further study demonstrated that hepatic SR-BI exerts its protection against sepsis through its role in promoting LPS clearance without affecting the inflammatory response in macrophages, the glucocorticoid production in adrenal glands, the leukocyte recruitment to peritoneum or the bacterial clearance in liver. Our findings reveal hepatic SR-BI as a critical protective factor in sepsis and point out that promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis.     

脓毒症分子机制及miRNA在脓毒症中的作用

脓毒症是外科重症监护病房(ICU)的主要死亡原因。近年来其发病呈上升趋势,且住院费用极昂贵,并缺乏有效的救治手段,已成为重症医学研究的重点。目前,关于脓毒症的发病机制并不清楚。研究表明,细胞内及细胞间多种信号通路如核因子κB(NF-κB)通路、丝裂原激活的蛋白激酶(MAPK)通路、JAK激酶/信号转导和转录激活子(JAK/STAT)通路、磷脂酰肌醇3激酶(PI3K/Akt)通路、胆碱能抗炎通路等及其下游的分子都参与脓毒症的发生发展。微小RNA(miRNA)作为小分子非编码RNA,通过转录后水平抑制靶基因的表达而参与细胞的多种过程。miRNA可以调控免疫细胞的分化及免疫反应,其不仅可以直接调控炎症因子的表达,还可作用于炎症信号传导通路的其他关键分子而间接调控脓毒症的发生发展。因此深入研究miRNA在脓毒症中的调节作用,可能为脓毒症的预防和治疗开拓新的思路。本文就参与脓毒症的信号通路及其下游分子以及miRNA进行总结,以利于进一步阐明脓毒症的病理生理机制,为脓毒症的预防和治疗找到合理有效的切入点。     

High Density Lipoprotein Protects against Polymicrobe-induced Sepsis in Mice

HDL has been considered to be a protective factor in sepsis; however, most contributing studies were conducted using the endotoxic animal model, and evidence from clinically relevant septic animal models remains limited and controversial. Furthermore, little is known about the roles of HDL in sepsis other than LPS neutralization. In this study, we employed cecal ligation and puncture (CLP), a clinically relevant septic animal model, and utilized apoA-I knock-out (KO) and transgenic mice to elucidate the roles of HDL in sepsis. ApoA-I-KO mice were more susceptible to CLP-induced septic death as shown by the 47.1% survival of apoA-I-KO mice versus the 76.7% survival of C57BL/6J (B6) mice (p = 0.038). ApoA-I-KO mice had exacerbated inflammatory cytokine production during sepsis compared with B6 mice. Further study indicated that serum from apoA-I-KO mice displayed less capacity for LPS neutralization compared with serum from B6 mice. In addition, apoA-I-KO mice had less LPS clearance, reduced corticosterone generation, and impaired leukocyte recruitment in sepsis. In contrast to apoA-I-KO mice, apoA-I transgenic mice were moderately resistant to CLP-induced septic death compared with B6 mice. In conclusion, our findings reveal multiple protective roles of HDL in CLP-induced sepsis. In addition to its well established role in neutralization of LPS, HDL exerts its protection against sepsis through promoting LPS clearance and modulating corticosterone production and leukocyte recruitment. Our study supports efforts to raise HDL levels as a therapeutic approach for sepsis.