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.     

儿科脓毒性休克早期目标导向治疗：间歇上腔静脉氧饱和度监测技术与预后-前瞻性队列研究

目的评价间歇中心静脉氧饱和度监测法对脓毒性休克患儿预后的影响,因多数医院条件有限无法开展持续监测。设计前瞻性队列研究。场所三级教学医院的PICU。对象2010年11月至2012年10月间因难治性脓毒性休克收入我院PICU且年龄〈17岁的患儿。干预措施入组患儿行锁骨下／颈内静脉置管术。成功者为观察组（ScvO2组）,剩余患儿为对照组（非ScvO2组）。观察组于复苏开始后1、3、6h行间歇ScvO2监测以指导复苏治疗,对照组仅采用临床参数指导治疗。测量指标和主要结果主要预后指标为院内病死率及6h内实现治疗目标比率。共纳入120例患儿,其中ScvO2组63例,非ScvO2组57例。比较组间基本特征,包括器官功能障碍情况及死亡风险评分。ScvO2组患儿院内病死率显著低于非ScvO2组（33．3％ vs 54％;RR0．61;95％置信区间0．4,0．93;需治疗人数5;95％置信区间：3,27）。观察组患儿于开始6h内达到治疗终点比例（43％ vs 23％,P=0．02）及于ICU住院期间达到治疗终点比例（71％ vs 51％,P=0．02）高于对照组。观察组患儿平均器官功能障碍数目亦显著低于对照组（2 vs 3,P〈0．001）。结论应用间歇ScvO2监测技术指导早期目标导向治疗似可降低脓毒性休克患儿院内病死率并改善其器官功能障碍情况。     

南非PICU患儿脓毒症流行病学调查

目的报告南非PICU危重症患儿入PICU 24 h内脓毒症发病率以及脓毒症相关病死率。     

感染性休克的诊断治疗进展

感染性休克（septicshock，SS）也称脓毒性休克，是儿科常见危重症，其诊治一直是大家关注的热点。20世纪70年代，我国学者在救治暴发型流行性脑脊髓膜炎和中毒性痢疾患儿的工作中积累了丰富的经验，成功挽救了许多SS患儿的生命。但严重脓毒症在世界范围内依然是造成儿童死亡的重要原因。     

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。     

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。     

激素替代治疗在严重脓毒症和脓毒性休克中的应用

严重脓毒症时机体通过内分泌激素水平及免疫状态的改变来适应和对抗应激。过分强烈的应激状态将损害或耗竭机体的适应潜能,可导致严重后果。激素替代治疗是有利的治疗措施。循证医学证实,大剂量肾上腺糖皮质激素应用不但不能降低严重脓毒症患者病死率,反而增加感染机会,生理剂量肾上腺糖皮质激素在该症治疗上得到推崇;合理使用胰岛素,控制严重脓毒症患者血糖,补充甲状腺素可降低机体高分解状态。激素替代治疗将会在脓毒血症的治疗中发挥越来越重要的作用。     

早期连续血液净化治疗对儿童脓毒性休克预后的影响：前瞻性随机对照研究

目的 探讨早期连续血液净化（CBP）治疗对儿童脓毒性休克预后的影响。方法 前瞻性选择未达到6 h初期复苏目标和/或液体过负荷 > 10%的脓毒性休克患儿为研究对象,根据CBP治疗时间分为早期组（n=30）和常规组（n=28）。比较两组患儿的CBP开始时间、28 d病死率,两组治愈患儿的相关指标变化。结果 早期组CBP开始时间早于常规组（P < 0.05）。早期组治愈25例,常规组治愈22例,两组患儿28 d病死率比较差异无统计学意义（P > 0.05）。早期组治愈患儿的乳酸、尿量和液体过负荷纠正时间快于常规组治愈患儿（P < 0.05）。两组治愈患儿的初始T淋巴细胞亚群均明显降低,第7天复查均有升高,且早期组高于常规组（P < 0.05）。早期组治愈患儿的CBP治疗持续时间、机械通气时间、PICU住院时间均短于常规组治愈患儿（P < 0.05）。结论 对未达到6 h初期复苏目标和/或液体过负荷 > 10%的脓毒性休克患儿早期行CBP治疗,能够快速控制病情,缩短病程,加快免疫重建。     

连续血液净化治疗儿童脓毒性休克

目的观察连续血液净化(CBP)对儿童脓毒性休克的疗效并探讨其机理。方法用CBP的连续性静-静脉血液滤过模式治疗了9例脓毒性休克患儿,检测CBP治疗前及治疗中各时相点血气、生化、中分子物质浓度等指标及毛细血管再充盈时间(CRT)、血管活性药物用量、血压、尿量等临床症状、体征变化。结果9例脓毒性休克患儿体重3．1～14kg(平均8．3 kg±3．5kg),治疗时合并急性肾功能衰竭6例、急性呼吸窘迫综合征3例、细菌血培养阳性5例,全部需升压药维持血压。CBP治疗前pH7．14±0．23,BE(-11．3±4．25)mmol/L,MMS(3532±519)U/L,PO_2/FiO_2 188±33,CRT≥5s,尿量(0．85±0．52)ml/(kg·hr),肾上腺素用量(1．36±0．48)μg/(kg·min),多巴胺用量16．35±3．27μg/(kg·min)。CBP治疗24h后pH 7．38±0．16,BE(-0．28±1．37)mmol/L,MMS (2576±375)U/L,PO2/FiO_2 285±63,肾上腺素用量(0．08±0．04)μg/(kg·min),多巴胺用量(8．53±6．72)μg/(kg·min),CRT＜2s,治疗结束时尿量(2．9±1．6)ml/(kg·hr)。与CBP治疗前比均(P＜0．05)或(P＜0．01)差异有统计学意义。经过3～12d的治疗,2例死于MODS(肠套叠并肠坏死1例、大面积烫伤1例),1例肠扭转术后肠漏放弃治疗,6例治愈出院。结论CBP联合其他综合治疗可明显提高脓毒性休克患儿的氧合能力、纠正酸中毒、稳定血压、改善组织器官灌注、清除中分子物质,值得进一步研究和应用。     

儿童严重脓毒症连续性血液净化治疗时肾素-血管紧张素-醛固酮系统的变化

目的 探讨连续性血液净化(continuous blood purification,CBP)治疗严重脓毒症患儿时肾素-血管紧张素-醛固酮系统的变化.方法 前瞻性研究,对象为上海交通大学附属儿童医院PICU2012年6月至2014年5月收治的严重脓毒症患儿35例.监测中心静脉压、动脉血压及平均动脉压,在抗生素、液体治疗等常规治疗基础上,进行连续性静-静脉血液滤过透析或高容量血液滤过模式治疗.放射免疫法测定CBP治疗前及CBP治疗后24 h时的血浆肾素活性及血管紧张素Ⅱ、醛固酮水平;并以同时期、同年龄段25例健康体检儿童作为对照组.结果 35例严重脓毒症患儿CBP治疗前后和对照组儿童血中肾素活性分别为(2.11±1.93)μg/(L·h)、(1.27±1.56) μg/(L·h)和(0.37±0.22) μg/(L·h);血管紧张素Ⅱ分别为(426.78±332.37) ng/L、(364.40±325.51) ng/L和(41.70±10.81);醛固酮分别为(255.12±218.18) ng/L、(134.92±104.13) ng/L和(106.88±43.18) ng/L.严重脓毒症患儿肾素活性及血管紧张素Ⅱ、醛固酮水平较对照组明显升高,CBP治疗后明显减低,醛固酮降至对照组水平,差异均有统计学意义(P＜0.01,P＜0.05).35例患儿中,经治疗好转24例,死亡5例,放弃治疗6例.CBP治疗24 h后,脓毒症合并心血管功能障碍的26例患儿平均动脉压较治疗前显著上升(P＜0.01);多巴胺用量下降(P＜0.01).结论 严重脓毒症患儿肾素-血管紧张素-醛固酮系统反应水平明显升高;CBP治疗可降低严重脓毒症患儿血液中肾素活性及血管紧张素Ⅱ和醛固酮水平,但不加重或造成循环功能障碍.     

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.     

脓毒性休克患儿早期临床特点及预后相关因素分析

目的回顾性分析脓毒性休克患儿的早期临床特点及其预后相关危险因素。方法收集2016年1月至2018年11月首都儿科研究所附属儿童医院PICU收治的56例脓毒性休克患儿的临床资料。根据28 d预后情况,分为死亡组和存活组;根据患儿入PICU 24 h内最低小儿危重病例评分(PCIS),分为非危重组(>80分)、危重组(70~80分)及极危重组(<70分),分析比较各组患儿早期的临床特点。结果56例脓毒性休克患儿,平均年龄12.0(1.0,180.0)个月;原发病以呼吸系统感染(60.7%,34/56)为主,病原学以细菌(71.4%,40/56)为主。死亡21例,存活35例,总病死率37.5%;非危重组、危重组和极危重组病死率分别为12.5%(2/16)、16.7%(1/6)、52.9%(18/34)。死亡组与存活组患儿的年龄、性别、PICU住院时间、心率、1 h及24 h平均动脉压、是否使用机械通气及机械通气时间差异无统计学意义(P均>0.05);死亡组患儿的PCIS明显低于存活组,6 h及24 h血管活性药物评分(VIS)明显高于存活组,初始乳酸水平明显高于存活组,1 h、6 h及24 h内入液量明显高于存活组,差异均有统计学意义(P均<0.05)。极危重组患儿的6 h入液量与非危重组比较,差异有统计学意义(P<0.05)。单因素分析显示,PCIS、VIS6 h、VIS24 h、初始乳酸水平及24 h乳酸清除率、降钙素原、射血分数、6 h入液量水平及合并多器官功能障碍(MODS)与患儿死亡有关。多因素Logistic回归分析显示,PCIS、6 h入液量水平、早期乳酸水平及合并MODS是脓毒性休克患儿死亡的独立危险因素。受试者工作特征曲线分析显示,6 h液体入量、PCIS、初始乳酸及MODS预测脓毒性休克患儿死亡的曲线下面积分别是0.947、0.835、0.797、0.761。结论脓毒性休克患儿病死率高,PCIS评分、6 h内复苏液量、早期乳酸水平及合并MODS是患儿死亡的危险因素。     

儿童Wernicke's脑病1例并35例文献复习

目的 探讨儿童Wernicke's脑病临床特点以及诊断与治疗,提高对该病的认识.方法 总结1例以严重脓毒症为首发表现的儿童Wernicke's脑病的临床表现、诊断及治疗特点,并对国内外近10年报道的35例儿童病例进行文献复习.结果 包括本例患儿共36例,男22/36例,年龄2个月～16岁.除本例外均有基础疾病:喂养不当25/35例、长期呕吐5/35例、免疫抑制治疗4/35例、长期完全胃肠外营养(未添加维生素)3/35例以及神经性厌食1/35例;有典型临床"三联征(精神状态改变、眼部体征以及共济失调)"6/36例,其他临床表现:意识障碍24/36例、感染22/36例、神经病理征及肌张力改变18/36例、惊厥17/36例,发育迟缓4/36例、生长停滞2/36例.行脑脊液常规检测31/36例,异常7/31例(蛋白略增高);检测脑脊液乳酸水平4/36例,均增高;血清乳酸水平检测7/36例、6/7例增高;血清丙酮酸检测4/36例,均增高;硫胺索焦磷酸盐活力(TPPE)检测9/36例,均增高;血清硫胺素水平检测2/36例、1/2例降低;行颅脑CT检查20/36例,16/20例双基底节区低密度、1/20例弥漫性脑皮质萎缩;行颅脑MRI检查13/36例,均表现为双侧对称性乳头体、基底节区异常信号、7/13例还表现中脑被盖、中央导水管及Ⅲ、Ⅳ脑室周围白质区异常信号.诊断方法:在行颅脑MRI的13例中,根据MRI确立诊断12/13例、"三联征"+MRI确立3/13例、根据尸检1/13例;行TPPE和(或)乳酸测定11例中,确立诊断9/11例.初始治疗:33/36例经胃肠外补充硫胺素、1/36例给药方式不详、1/36例经口服给药、1/36例未补充;硫胺素剂量:29/35例每日100 mg、3/35例剂量不详、2/35例每日50 mg、1/35例每日600 mg.初始治疗后34/35例临床症状在24 h～1周内缓解,1/36例无反应死亡.存活34例中,19例接受随访,2～2.5个月内17/19例完全康复.结论 儿童Wernicke's脑病常无特异性临床表现,误诊率较高,颅脑MRI特征性表现为双侧乳头体、基底节区、中央导水管周围区等对称性异常信号.特征性颅脑MRI异常信号结合临床硫胺素治疗后快速反应有助于临床诊断.早期、及时补充大剂量硫胺素后,多数病例神经学异常可快速改善,预后良好.

Abstract：

Objective Wernicke's encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. The disorder is still greatly underdiagnosed in children because of either a relatively non-specific clinical presentation in some cases or unrecognized clinical setting The aim of this literature review was to provide knowledge of pediatric WE in an effort to assist in early diagnosis, thereby reducing the morbidity and mortality. Methods The clinical manifestations, characteristic magnetic resonance imaging ( MRI), diagnosis and treatment of one case and the other 35 cases reported in the last decade in children were summarized. Results Thirty-six cases (22 boys and 14 girls, 2-month to 16-year-old) were analyzed. All the other 35 cases except for our case had underlying diseases: improper feeding in 25/35 cases, long-time vomiting in 5/35 cases,immunosuppressive therapy in 4/35 cases, long-time total parenteral nutrition without multivitamin preparations supplementation in 3/35 cases and anorexia nervosa in 1/35 case. The classic triad ( mentalstatus changes, nystagmus and ophthalmoplegia, and ataxia) was seen in 6/36 cases. The other clinical manifestations included consciousness disturbance in 24/36 cases, infection in 22/36 cases, pathological reflex and muscular tension changes in 18/36 cases, convulsion in 17/36 cases, developmental delay in 4/36 cases and failure to thrive in 2/36 cases. Cerebrospinal fluid examination was performed in 31/36 cases,and a slightly raised protein concentration was seen in 7/31 cases. The cerebrospinal fluid lactate levels were detected in 4/36 cases ( all increased ), serum lactic acid levels in 7/36 cases ( 6/7 cases increased ),serum pyruvate in 4/36 cases ( all increased), thiamine pyrophosphate effect ( TPPE ) in 9/36 cases ( all increased), and serum thiamine in 2/36 cases (increased in 1/2 cases). The brain computed tomography (CT) scan was conducted in 20/36 cases and 16/20 cases showed abnormal hypodensity in bilateral basal ganglia, one case revealed diffuse cortical atrophy. The brain MR scan was conducted in 13/36 cases and all the 13 cases revealed symmetrical abnormal signal in bilateral mamillary body and basal ganglia, and 7/13 cases showed abnormal signals in the tegmentum of midbrain, cerebral aqueduct and white matter around the third and fourth ventricles. The diagnosis of WE was confirmed by MR in 12 cases, triad combined with MR in 3 cases, autopsy in 1 case among the 13 cases who underwent MR scan. The diagnosis of WE was confirmed by the TPPE and/or lactate levels in 9/11 cases. The initial thiamine was given by intravenous or intramuscular infusion in 33/36 cases, unknown method in 1 case, orally in 1 case and no thiamine was used in 1 case. The dosage of thiamine was 100 mg daily in 29/35 cases, unknown in 3/35 cases, 50 mg daily in 2/35 cases, 600 mg daily in 1/35 case. 34/35 patients' clinical symptoms improved during 24 hours to 1 week after initial treatment, and 1 case died due to no response to thiamine. Nineteen patients were followed up for 2-2. 5 months and 17 cases recovered completely. Conclusion Wernicke' s encephalopathy can be difficult to diagnose because of a relatively non-specific clinical presentation. The characteristic MRI findings and the dramatic response of neurological signs to parenteral thiamine will assist early clinical diagnosis.Early and timely thiamine supplementation could reverse the clinical features and improve the prognosis in most cases.     

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。     

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...     

Severe acute respiratory syndrome (SARS): chest radiographic features in children

Background Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children.Objective The goal of this study was to characterize the radiographic presentation of children with SARS.Materials and methods We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy.Results A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 °C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient.Conclusion In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.