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.     

脓毒性休克患儿血浆脑利钠肽水平变化及临床意义

目的 通过检测脓毒性休克患儿的血浆脑利钠肽(BNP)水平,探讨BNP水平检测在脓毒性休克临床诊治中的意义.方法 采用酶联免疫吸附法(ELISA)测定30例脓毒性休克患儿(脓毒性休克组)、30例脓毒症患儿(脓毒症组)及30例健康体检儿(对照组)空腹血浆BNP水平.结果 (1)脓毒症组血浆BNP水平明显高于对照组(P＜0.01);(2)脓毒性休克及脓毒症患儿血浆BNP水平急性期明显高于恢复期(P＜0.01);(3)死亡及多脏器功能衰竭的脓毒性休克患儿与存活者血浆BNP水平比较,前者明显高于后者(P＜0.01);(4)脓毒性休克患儿血浆BNP、心肌肌钙蛋白(cTnI)浓度间相关分析表明两者成正相关(r=0.91,P＜0.01).结论 血浆BNP水平可作为脓毒性休克早期诊断的一项重要指标,有助于检测心肌受损、评估病情严重程度、判定治疗方案的疗效及预测预后.     

脓毒性休克患儿血浆脑利钠肽水平变化及临床意义

目的 通过检测脓毒性休克患儿的血浆脑利钠肽(BNP)水平,探讨BNP水平检测在脓毒性休克临床诊治中的意义.方法 采用酶联免疫吸附法(ELISA)测定30例脓毒性休克患儿(脓毒性休克组)、30例脓毒症患儿(脓毒症组)及30例健康体检儿(对照组)空腹血浆BNP水平.结果 (1)脓毒症组血浆BNP水平明显高于对照组(P＜0.01);(2)脓毒性休克及脓毒症患儿血浆BNP水平急性期明显高于恢复期(P＜0.01);(3)死亡及多脏器功能衰竭的脓毒性休克患儿与存活者血浆BNP水平比较,前者明显高于后者(P＜0.01);(4)脓毒性休克患儿血浆BNP、心肌肌钙蛋白(cTnI)浓度间相关分析表明两者成正相关(r=0.91,P＜0.01).结论 血浆BNP水平可作为脓毒性休克早期诊断的一项重要指标,有助于检测心肌受损、评估病情严重程度、判定治疗方案的疗效及预测预后.     

再论儿童脓毒症——如何早期识别和治疗严重脓毒症和脓毒性休克

儿童严重脓毒症、脓毒性休克是PICU中患儿的主要死亡原因之一,早期识别、及时诊断、尽早治疗是改善预后、降低病死率之关键。该文再次强调了儿童脓毒症新定义,并推荐国外的儿童脓毒症筛查方案及早期目标导向治疗(EGDT)方案,旨在指导国内儿科医师的诊断和治疗,改善严重脓毒症、脓毒性休克儿童的预后,提高生存率。     

小儿感染性(脓毒性)休克的早期识别

感染性(脓毒性)休克的诊断关键是早期识别、密切监测.重症监护救治技术的巨大进步使儿科脓毒症病死率从97%(1966)降至9%(1999)[1].尽管如此,脓毒症的发病率仍逐年增高,严重脓毒症仍是ICU住院的主要病因之一;严重脓毒症,特别是脓毒性休克仍是导致患儿死亡的重要原因.     

脓毒性休克定义中加入血乳酸的意义

乳酸是反映休克组织灌注及细胞氧代谢的重要生物学标志物.2012年,"拯救脓毒症运动"国际指南建议将乳酸作为反映脓毒性休克组织灌注的量化指标之一.2016年欧美危重病协会颁布"第三届国际脓毒症及脓毒性休克诊断指南(Sepsis-3)",将脓毒性休克定义为:尽管充分的液体复苏,仍需要用血管升压药维持平均动脉压≥65mmHg(1mmHg=0.133kPa)和血乳酸≥2mmol/L(>18mg/dl),确定了乳酸在脓毒性休克诊断中的重要地位.乳酸≥4mmol/L是评估脓毒性休克患者预后不良的参考指标.以动态乳酸值为靶向指标的液体复苏与血管活性药物使用策略具有重要意义.乳酸清除率与早期乳酸面积可预测脓毒性休克死亡风险.     

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.     

新生儿脓毒症研究进展

新生儿脓毒症是新生儿期细菌或真菌侵入血液循环并在其中生长繁殖,产生毒素所造成的全身性感染.目前该类疾病的发病率和病死率仍占新生儿感染性疾病首位.根据新生儿自身特点该类疾病的临床表现不明显,给临床带来了一系列问题.本文就新生儿脓毒症的流行病学、病因、病理生理、临床特点及与成人脓毒性休克的异同点等方面作一综述,以加深对新生儿脓毒症的认识.     

脓毒性休克液体复苏和容量治疗研究进展

重症脓毒症常并发脓毒性休克.重症感染时,因严重的炎症反应,导致毛细血管渗漏、第三间隙液体积聚、血液异常分布、有效血容量减少,出现休克的临床表现.早期合理的液体复苏是降低脓毒性休克病死率的重要措施液体复苏时机掌握、容量控制、疗效评估至关重要.     

内外源性儿茶酚胺对脓毒性休克心肌的影响

为了阐述脓毒症发展到脓毒性休克内源性儿茶酚胺升高及外源性儿茶酚胺的大量应用对脓毒性休克心功能不全发生的作用,本文从儿茶酚胺与心脏、儿茶酚胺所致心脏毒性、脓毒性休克交感-肾上腺素系统激活状态及外源性儿茶酚胺类药物的应用阐述可能对心肌的影响.     

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.     

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.     

内皮素与新生儿败血性休克的研究

为了探讨内皮素在新生儿败血性休克中的作用，应用体外培养及放射免疫测定法，观察内毒素对人脐静脉血内皮细胞分泌内皮素的影响及山莨菪碱（６５４－２）的可能作用，并测定３２例败血症及２１例败血性休克新生儿血浆内皮素含量的变化。结果：（１）内毒素能刺激人脐静脉内皮细胞内皮素的分泌，呈时间及剂量依赖性；（２）６５４－２在体外能抑制内毒素刺激的内皮素的合成；（３）新生儿败血症及败血性休克时血浆内皮素水平明显增高，并与疾病严重程度及预后有关。提示：内皮素参与新生儿败血性休克的病理生理过程，为６５４－２治疗败血性休克提供了新的理论依据。     

Association of septic shock caused by early-onset group B streptococcal sepsis and periventricular leukomalacia in the preterm infant

Early-onset group B streptococcal sepsis frequently produces shock in preterm infants, a condition also felt to be contributory to the development of periventricular leukomalacia. During a 2-year study period, 628 preterm infants who were admitted to the neonatal intensive care unit underwent serial sonographic brain scanning; periventricular leukomalacia was diagnosed in eight infants (1.2%). The four infants (100%) who survived group B streptococcal sepsis with septic shock developed periventricular leukomalacia, whereas none of the four survivors (0%) of septic shock caused by other organisms and three of 27 survivors (11%) of shock not caused by infection developed periventricular leukomalacia. Because of the frequency of this lesion, it is suggested that all preterm survivors of group B streptococcal sepsis with septic shock should have serial sonography screening for detection of periventricular leukomalacia. Early detection will not assure cure but may facilitate prognostication, follow-up, and earlier institution of rehabilitative therapy to produce a better outcome.     

Alterations in antioxidant status during neonatal sepsis

Septicaemia is a major threat to survival during the early stages of life. There are several reports that suggest that reactive oxygen species (ROs) play a role in a wide variety of diseases. We estimated the activity of xanthine oxidase (XO), malondialdehyde (MDA) content, creatine phosphokinase (CPK) activity, activities of key enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (PO), and non-enzymatic antioxidants, viz. uric acid (UA) and albumin (ALB), in 30 neonates with sepsis and 20 age-matched controls. The babies were categorized as preterm/term, early onset/late onset, and shock/without shock, as per clinical and laboratory investigations. The study was carried out to evaluate the status of antioxidant enzymes and non-enzymatic antioxidants with a view to suggesting the introduction of antioxidant therapy in neonatal sepsis. The activities of serum XO, CPK, SOD and GPx, and the content of MDA were found to be significantly elevated in the neonates with sepsis when compared with controls. Conversely, the activity of PO and the levels of UA and ALB were decreased. The septic, full-term neonates registered significantly higher CPK activity (70%) than the preterm septic neonates. However, infants with late-onset and shock sepsis had a significant decrease in CPK activity (p < 0.05) compared with their corresponding sub-groups. Likewise, UA levels were found to be 28% depressed (p < 0.05) in the babies with late-onset sepsis and 51% increased (p < 0.001) in babies with shock compared with their respective sub-groups. Neonates with septic shock also registered a significant elevation in GPx activity (28%) compared with those without shock. This study suggests increased production of ROs in neonates with sepsis, as evidenced by the positive regulation of XO, SOD and GPx activity. The elevation of antioxidant enzymes, however, was not so effective as to protect from cellular damage and thereby result in higher MDA production. It is evident that antioxidant therapy might be useful in the management of neonates with sepsis but further detailed clinico-biochemical investigations are required to define effective antioxidant therapy.     

血乳酸在脓毒症患儿病情及预后评价中的意义

目的 探讨脓毒症患儿血乳酸水平对病情严重程度和预后的评价作用。方法 收集脓毒症患儿484例,其中普通脓毒症组310例、严重脓毒症组105例、脓毒症休克组69例,治疗前测动脉血乳酸值,对乳酸>2 mmol/L的脓毒症休克患儿,收集其早期液体复苏后血乳酸复查值。结果 随脓毒症严重程度增加,血乳酸值逐渐增加。ROC曲线分析发现,区别脓毒症休克和非脓毒症休克的血乳酸值为2.25 mmol/L时,其诊断灵敏度为82.6%,特异性为79.8%。乳酸≤1 mmol/L、乳酸~2 mmol/L、乳酸~4 mmol/L和乳酸>4 mmol/L患儿的病死率分别为8.5%、9.4%、27.2%、67.6%,乳酸>4 mmol/L的死亡风险为乳酸≤1 mmol/L的22.4倍。治疗前血乳酸>2 mmol/L的脓毒症休克患儿复苏后血乳酸水平≤2 mmol/L和>2 mmol/L的病死率分别为33.3%、69.2%。结论 血乳酸可作为脓毒症患儿病情严重程度及预后的评价指标,血乳酸值2.25 mmol/L对脓毒症休克具有较高的诊断价值;早期复苏使血乳酸水平恢复至正常可改善脓毒症休克患儿的预后。     

Serum TNF-alpha and free radical scavengers in neonatal septicemia

Tumor necrosis factor-alpha (TNF-alpha) and free radicals have been implicated in the pathogenesis of neonatal septicemia and its complications. This case control study was conducted between November 1996 to July 1997 to determine the levels of TNF-alpha and free radical scavengers viz. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the serum of 30 septic neonates and 20 healthy controls. Patients with neonatal sepsis registered significantly higher levels of TNF-alpha, SOD and GPX in comparison to controls (p < 0.05). The neonates with septic shock had five fold increase in TNF-alpha levels (2262 ±605.8 pg/ml) as compared to those without shock (738.8 ±28.8 pg/ml). There was no statistically significant difference in levels of antioxidant enzymes between neonates with shock and without shock. The levels of TNF-alpha and antioxidant enzymes were not affected by the type of organism isolated in blood culture.     

Total hydroperoxide and biological antioxidant potentials in a neonatal sepsis model

Oxidant/antioxidant imbalance plays an important role in septic shock. The present study examined changes in circulating oxidative components in a neonatal sepsis model. Subjects were 14 newborn mixed-strain piglets randomly divided into two groups: a cecal ligation and perforation (CLP) model (n = 7) and sham (n = 7). Blood samples for total hydroperoxide (TH), biological antioxidant potential (BAP), tumor necrosis factor (TNF) alpha, interleukin (IL)-6, and IL-10 were collected pre-CLP and at 1, 3, and 6 h post-CLP. TH and BAP levels at 1 h post-CLP were significantly higher in the CLP group than in the sham group. In the CLP group, TH decreased gradually and reached baseline levels by 6 h post-CLP, while BAP remained elevated. Linear correlations were identified between serum TH and BAP at 1 h post-CLP, serum TH and TNF-alpha at 1 h post-CLP, and BAP and IL-6 at 6 h post-CLP. Changes in and correlations between circulating oxidative and inflammatory state components in a neonatal sepsis model were clarified. This is the first study to reveal that the presence of oxidant/antioxidant imbalance in sepsis and septic shock changes during the disease course.