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。     

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.     

PICU血液肿瘤患儿粒细胞减少症伴脓毒性休克的临床特点与预后

目的 探讨PICU住院的血液肿瘤患儿化疗后骨髓抑制期或再生障碍性贫血(骨髓增生低下)状态下粒细胞减少症并发脓毒性休克的临床特点及影响预后的因素.方法 对我院2002年1月至2008年5月PICU收治的40例血液肿瘤患儿粒细胞减少症并发脓毒性休克临床资料进行回顾性分析.结果 本组40例患儿,存活12例,死亡18例,放弃治疗10例,病死率60%(剔除放弃病例).在发生脓毒性休克时全部病例体温均显著升高(>38.5℃),C反应蛋白也明显升高.肺部感染是其主要病因(35%),其次为胃肠道感染(30%).本组血培养阳性结果 20例,其中革兰阴性杆菌14例(14/20,70%),铜绿假单胞菌为首位(8/14,57%).存活组与死亡组血糖、血浆白蛋白水平、血pH值、标准碱剩余、乳酸和小儿死亡危险评分比较,差异均有显著性(P<0.05).原发病缓解(或复发后缓解)与未缓解(或复发)患儿伴发脓毒性休克病死率分别为41%、85%,差异有显著性(P<0.05).脓毒性休克伴1个、2个、3个、3个以上器官功能不全,病死率分别为0、27%、89%、100%(剔除放弃病例),差异有显著性(P<0.05).结论 血液肿瘤化疗后骨髓抑制或骨髓增生低下的粒细胞减少症患儿并发脓毒性休克病死率高.高热是患儿主要临床表现;肺和胃肠道是脓毒症重要感染来源.革兰阴性杆菌(尤其是铜绿假单胞菌)是主要致病菌;在早期经验性抗感染治疗中,需加强对革兰阴性杆菌的治疗力度.C反应蛋白增高有利于早期判断脓毒症.患儿血糖、血浆白蛋白水平、血pH值、标准碱剩余、乳酸和小儿死亡危险评分与脓毒性休克死亡相关.积极治疗原发疾病,早期及正确治疗脓毒性休克能降低血液肿瘤骨髓抑制或增生低下的粒细胞减少症伴脓毒性休克患儿的病死率.     

不同呼气末正压对脓毒性休克合并急性呼吸窘迫综合征婴幼儿预后的影响

目的 评价不同呼气末正压(positive end-expiratory pressure,PEEP)对脓毒性休克合并急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)婴幼儿预后的影响.方法 将广西壮族自治区妇幼保健院PICU收治的60例脓毒性休克合并ARDS婴幼儿分为3组,每组20例,分别应用低、中、高三种水平PEEP(3、6、9 cmH2O,l cmH2O=0.098 kPa)进行呼吸机辅助通气,均采用压力控制机械通气模式,小潮气量(6 ～8 ml/kg)通气策略,同时根据美国危重病儿科高级生命支持协会2009年颁布的脓毒性休克指南指导液体复苏.监测3组患儿上机后6、24、48 h氧合指数(OI)、呼吸系统动态顺应性(Cdyn)、心脏指数(CI)的变化并统计每例患儿的液体入/出量,比较3组患儿机械通气时间、PICU住院时间及28 d病死率.结果 机械通气后6h开始,中、高PEEP组OI、Cdyn均明显好转,与低PEEP组比较差异均有统计学意义(P均＜0.01);中、低PEEP组CI明显高于高PEEP组,液体入量少于高PEEP组,差异均有统计学意义(P均＜0.01),3组液体出量比较差异无统计学意义(P＞0.05);中PEEP组呼吸机辅助通气时间[(5.40±0.61)d]、PICU住院时间[(7.00±0.61)d]均短于高、低PEEP两组[(6.23±0.90)d、(7.51±1.09)d;(8.23-±0.90)d、(9.14±1.21)d](P均＜0.01);3组患儿病死率比较差异无统计学意义(P＞0.05).结论 中PEEP能显著改善脓毒性休克合并ARDS患儿的肺功能,缩短机械通气时间,对血流动力学无严重不良影响.     

儿童严重脓毒症死亡危险因素分析

目的 探讨儿童严重脓毒症死亡危险因素,以利于疾病早期认识和诊断,改善预后,降低病死率.方法对69例严重脓毒症患儿,应用巢式病例对照研究方法 进行分析,以患儿入院日为研究起点,死亡或出院为终点.研究因素包括年龄、性别、基础疾病、感染部位、病原菌、临床征象、并发症和治疗措施方面共24个变量,作单因素分析,并采用Logistic回归进行多因素分析,计算OR及其95%CI.结果 69例患儿中死亡31例,病死率44.93%.基础疾病以血液系统恶性疾病最多.69例中并发急性呼吸窘迫综合征17例,并发脓毒性休克34例.脓毒症伴1、2、3及3个以上器官功能衰竭病死率分别为11.76%、36.00%、64.29%和84.62%.单因素分析显示.国内小儿危重病例评分(PCIS)、最初PICU死亡危险因索评分(PRISM)、7d内最高PRISM、血小板计数、血清乳酸值、休克和多脏器功能不全综合征(MODS)受累脏器数7个变量与儿童严重脓毒症的死亡有关.经逐步引入剔除法,建立Logistic回归模型,仍然与死亡有关的因素包括血小板计数、血清乳酸值、休克和MODS受累脏器数.结论 儿童严重脓毒症病死率高,血小板计数F降、血清乳酸增高、脓毒性休克和MODS是疾病死亡的危险因素.     

血小板计数对小儿肺炎炎症反应及病情严重程度的评价

目的探讨血小板计数在评判小儿肺炎炎症反应及病情严重程度方面的应用价值和意义。方法选取我院2013年7月至2015年7月收治的重症肺炎80例患儿作为研究对象,根据其表现将其分为全身炎症反应综合征( systemic inflammatory response syndrome, SIRS)组与非SIRS组,分别于入院后1d、3d和5d测定两组患儿的血小板含量,并测定其急性肺损伤、多器官功能障碍综合征与急性呼吸窘迫综合征的发生情况及其病死率。综合分析SIRS患儿中符合2项、3项和4项诊断标准时的血小板含量,急性呼吸窘迫综合征与急性肺损伤的发生情况及其病死率。结果 SIRS组和非SIRS组患儿的血小板数与入院时相比,差异具有统计学意义(P<0．05),对比分析两组患儿入院后1 d与3 d时的血小板含量,及3 d与5 d时的血小板含量,其生存组之间均差异不具有统计学意义(P>0．05),而死亡组之间则差异具有统计学意义(P<0．05)。生存组患儿与死亡组患儿的呼吸窘迫综合征发生情况分别是7．1%(4/56)与45．8%(11/24),差异具有统计学意义(χ2=33．3, P<0．05)。病死率分别为26．7%(16/60)与10．0%(2/20),差异具有统计学意义(χ2=3．48, P<0．05)。结论重症肺炎合并患有SIRS时,患儿的血小板含量会明显上升,这可能与重症肺炎病情发生恶化相关,随着SIRS病情加重,血小板则逐渐降低,所以血小板含量持续降低可能成为对重症肺炎患儿病情持续恶化的诊断标志之一。     

脓毒症致急性呼吸窘迫综合征的发病机制及乌司他丁的治疗作用

脓毒症是指由感染引起的全身炎症反应综合征,常导致脓毒性休克、多器官功能不全综合征,是儿童最常见的致死原因,是现代儿童危重病医学研究领域的热点和难点.严重脓毒症常并发急性呼吸窘迫综合征,是导致病情恶化及死亡的重要原因.本文就脓毒症所致急性呼吸窘迫综合征的发病机制及乌司他丁的治疗作用作一综述.     

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。     

急性呼吸窘迫综合征的诊断与治疗策略

急性呼吸窘迫综合征是在严重感染、休克、创伤、烧伤等疾病发生时,肺毛细血管和肺泡因炎症性损伤导致通透性增加,产生的急性高通透性肺水肿和进行性缺氧性呼吸衰竭.小儿急性呼吸窘迫综合征是儿科常见的危重症之一,病死率极高,早期诊断、早期合理治疗是降低其病死率的关键.     

侵袭性肺炎链球菌性疾病所致脓毒性休克患儿临床特点及预后分析

目的:了解儿童重症监护病房(PICU)内侵袭性肺炎链球菌性疾病(IPD)所致脓毒性休克患儿的临床特点及预后。方法:回顾性收集2013年1月至2019年8月首都医科大学附属北京儿童医院重症医学科及河南省儿童医院重症医学科收治的IPD所致脓毒性休克患儿的病历资料,分析其临床及预后特点。结果:共纳入患儿21例,年龄1.2(0.75,3.90)岁。入PICU时第二代小儿死亡指数(PIM-2)为(23.3±29.6)%,并基础疾病6例。感染部位主要为血液(20例)及颅内(15例)。18例患儿行药敏试验,其中对青霉素敏感9例,对头孢吡肟/头孢噻肟敏感分别为10例和11例,对美罗培南敏感10例,对万古霉素及利奈唑胺均敏感;病初及脓毒性休克前应用敏感抗生素者分别为7和13例。21例患儿乳酸水平为(6.1±4.6)mmol/L,其中10例经治疗休克纠正时间为(10.9±10.1)h。13/21例(61.9%)患儿休克后死亡时间为(14.6±12.2)h,10例死于枕骨大孔疝。死亡组患儿入PICU时PIM2[(37.1±30.3)%比(0.9±1.3)%]及并颅高压危象率[69.9%(9/13例)比25%(2/8例)]显著高于存活组,差异均有统计学意义(均P<0.05);但年龄、休克前有效抗生素使用率等差异均无统计学意义(均P>0.05)。4/8例存活患儿遗留严重颅脑后遗症。结论:IPD致脓毒性休克多见于5岁以下儿童,以血流和颅内感染最常见,对头孢菌素及碳青霉烯类耐药率高。化脓性脑膜炎者易并颅高压危象,致死致残率高,需早期识别并治疗。     

危重症患儿血乳酸水平与病情的关系

目的：探讨危重症患儿血乳酸水平与病情的关系。方法：回顾性分析2010年9月至2010年12月232例危重症患儿的临床资料。根据入院后患儿的血乳酸水平分为乳酸水平正常组（n=146）、高乳酸血症组（n=72）和乳酸酸中毒组（n=14）,比较3组危重症患儿循环功能、小儿危重病例评分及预后。结果：不同乳酸水平患儿间脓毒血症程度的比较差异有统计学意义（χ2=13.592,P<0.01）。乳酸酸中毒组脓毒症休克发生的比例（42.9%）较乳酸水平正常组（7.5%）、高乳酸血症组（11.1%）明显升高。不同乳酸水平患儿小儿危重病例评分也不同,3组比较差异有统计学意义（χ2 =12.854,P<0.05）。全血乳酸水平与小儿危重病例评分呈明显负相关（r=-0.405,P=0.002）。不同乳酸水平患儿预后亦不同（χ2=25.599,P<0.01）。乳酸酸中毒组的治愈率明显低于乳酸水平正常组（7.1% vs 23.3%,P<0.05）;乳酸酸中毒组的好转率亦明显低于乳酸水平正常组（28.6% vs 58.2%,P<0.05）,而其病死率（28.6%）明显高于乳酸水平正常组（5.5%）及高乳酸血症组（6.9%）,差异有统计学意义（P<0.05）。结论：患儿血乳酸水平越高,病情越危重,预后越差。     

Glucose level and risk of mortality in pediatric septic shock.

OBJECTIVE: To study the relationship between serum glucose level and mortality in children with septic shock. DESIGN: Prospective cohort study. SETTING: Twelve-bed pediatric intensive care unit at the Hospital S?o Lucas da PUCRS, Porto Alegre, Brazil. PATIENTS: All children admitted with septic shock refractory to fluid therapy over a period of 32 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum glucose levels were measured in all children during the study period, and the highest value was assessed in relation to outcome. Fifty-seven of 1,053 children admitted to the intensive care unit were enrolled in the study. The peak glucose level in those with septic shock was 214 +/- 98 mg/dL (mean +/- SD), and the mortality rate was 49.1% (28/57). In nonsurvivors, the peak glucose level was 262 +/- 110 mg/dL, which was higher (p < .01) than that found in survivors (167.8 +/- 55 mg/dL). The area under the receiver operator curve for peak glucose level and mortality rate was 0.754. The best peak glucose level for predicting death in children with sepsis was 178 mg/dL (sensitivity, 0.714; specificity, 0.724), and the relative risk of death in patients with peak glucose levels of > or =178 mg/dL was 2.59 (range, 1.37-4.88). CONCLUSION: In children with septic shock, a peak glucose level of >178 mg/dL is associated with an increased risk of death.     

Treatment in 2003 of septic shock in children in the first two hours (excluding newborns)]

Despite new understandings in pathophysiology, sepsis mortality remains high in children. Recently, it has been demonstrated that early goal directed therapy may decrease septic shock mortality. The aim of this paper is to propose practical clinical guidelines based on earlier consensus recommendations. Septic shock must be rapidly suspected and early recognized. Bases of treatment are maintenance of adequate oxygenation with use of artificial ventilation if necessary, larger and faster volume resuscitation than recommended before, empiric antibiotherapy and early use of vasopressive agents associated with corticosteroids in particular situations. Treatment efficacy must be regularly assessed during first hours of resuscitation. Taking into account pediatric particularities and results of adult studies, pediatricians who take care of children at beginning of septic shock may reasonably hope to decrease mortality if they keep in mind specific therapeutic goals.     

Pediatric acute lung injury

Among ventilated children, the incidence of acute lung injury (ALI) was 9%; of that latter group 80% developed the acute respiratory distress syndrome (ARDS). The population-based prevalence of pediatric ARDS was 5.5 cases/100.000 inhabitants. Underlying diseases in children were septic shock (34%), respiratory syncytial virus infections (16%), bacterial pneumonia (15%), near-drowning 9%, and others. Mortality ranged from18% to 27% for ALI (including ALI-non ARDS and ARDS) and from 29% to 50% for ARDS. Mortality was only 3%–11% in children with ALI-non ARDS. As risk factors, oxygenation indices and multi-organ failure have been identified. New insights into the pathophysiology (for example the interplay between intraalveolar coagulation/fibrinolysis and inflammation and the genetic polymorphism for the angiotensin-converting enzyme) offer new therapeutic options. Lung protective mechanical ventilation with optimal lung recruitment is the mainstay of supportive therapy. New therapeutic modalities refer to corticosteroid and surfactant treatment. Well-designed follow up studies are needed.     

Extracorporeal membrane oxygenation for refractory septic shock in children: one institution's experience.

OBJECTIVE: To report our institutional experience of venoarterial extracorporeal membrane oxygenation (ECMO) in children with septic shock and circulatory collapse. DESIGN: Retrospective case series. SETTING: Intensive care unit of a tertiary pediatric referral center. PATIENTS: Forty-five children with refractory septic shock who received venoarterial ECMO for hemodynamic support. INTERVENTIONS: Venoarterial ECMO. MEASUREMENTS AND MAIN RESULTS: We measured mean arterial pressure and inotropes before cannulation, ventilator settings, oxygenation, site and cause of infection, time on ECMO, complications of ECMO relating to the circuit or anticoagulation, survival to hospital discharge, and functional outcome assessment. Between July 1988 and October 2006, 441 children at our institution received extracorporeal life support for a variety of indications. Forty-five (10%) with septic shock received venoarterial ECMO specifically for hemodynamic support. Eighteen (40%) of these had suffered cardiac arrest and were receiving chest compressions immediately before cannulation. The median time spent on ECMO was 84 hrs (range, 32-135). There were mechanical problems with the ECMO circuit requiring intervention in 17 (38%) patients, such as oxygenator or pump head failure, clots in the circuit, or cannulae malposition. This caused no long-term harm in any but one of the patients, who died during a circuit change. Eleven patients (24%) had clinically apparent episodes of bleeding that required surgical intervention or blood transfusion. Twenty-one (47%) patients survived to hospital discharge. Atrioaortic cannulation through a sternotomy incision was associated with an improvement in survival to hospital discharge (73% of those with central cannulation survived vs. 44% without, p = .05). No survivors had severe disability at long-term follow-up. CONCLUSIONS: Extracorporeal membrane oxygenation can be safely used to resuscitate and support children with sepsis and refractory shock. Sepsis and multiorgan failure should not be considered a contraindication to ECMO. This study adds support to existing guidelines.     

Aggressive management of dengue shock syndrome may decrease mortality rate: a suggested protocol.

OBJECTIVES: Dengue shock syndrome is a leading cause of mortality among Indian children. In January 2000, we instituted a protocol for aggressive management of children with dengue shock syndrome. The objective of this study was to compare outcomes (duration of ventilation, pediatric intensive care unit stay, incidence of acute respiratory distress syndrome, and intensive care unit and hospital mortality) before and after the protocol. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit at a tertiary teaching hospital. PATIENTS: One hundred and fourteen patients admitted between July 1997 and December 1999 received standard therapy recommended by the World Health Organization (WHO) and were designated as the WHO guidelines group (W), whereas 96 patients admitted between January 2000 and December 2001 were treated by our protocol and designated as the protocol group (P). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patients in each group were equally matched in terms of age, Pediatric Risk of Mortality, and number with dengue hemorrhage fever grade IV, although the platelet counts were higher in the W group compared with the P group (geometric mean 42.2, confidence interval 36.9, 48.4 vs. geometric mean 36.7, confidence interval 33.3, 40.5, p < .05). Patients in the W group received less fluids in the first hour compared with the P group (median and interquartile range 20 mL/kg, 15 and 20 vs. 30 mL/kg, 20 and 60). Fluid was actively removed less often in the W group than the P group (6 of 111 vs. 45 of 96, p < .05). There was no difference in the need for ventilation or incidence of acute respiratory distress syndrome between groups, although among dengue hemorrhage fever grade IV patients, the number requiring ventilation (17 of 30 vs. 20 of 23, p < .05) and the incidence of acute respiratory distress syndrome (9 of 30 vs. 17 of 23, p < .05) were significantly greater in the W group compared with the P group. The duration of ventilation (1.5 +/- 1.7 vs. 4.2 +/- 2.9 days, p < .05) and length of intensive care unit stay (3.0 +/- 2.8 vs. 3.4 +/- 2.9 days, p < .05) were significantly less in the W group. The pediatric intensive care unit mortality (16.6% vs. 6.3%, p < .05) was significantly higher in the W group than in the P group. CONCLUSIONS: Patients with dengue shock syndrome are at high risk of mortality due to refractory shock and multiple organ failure. Survival was better for patients in the P group. Aggressive shock management and possibly the use of judicious fluid removal may decrease mortality rates in the severest forms of dengue shock syndrome.