Extracellular hsp70 levels in children with septic shock.

OBJECTIVE: To determine whether hsp70 is elevated in the plasma of children with septic shock. DESIGN: Cohort study. SETTING: Two academic, tertiary pediatric intensive care units. PATIENTS: Ninety-four children admitted to the pediatric intensive care unit with septic shock and 24 control children undergoing elective surgical procedures. INTERVENTIONS: Venous or arterial blood sampling. MEASUREMENTS AND MAIN RESULTS: Children admitted to the pediatric intensive care unit with a diagnosis of septic shock were enrolled in the study following written informed consent. The control group consisted of healthy children undergoing elective surgical procedures. Blood samples from children in the septic shock or control groups were obtained within 24 hrs of admission to the pediatric intensive care unit or during the preoperative visit. Samples were collected, centrifuged, and stored at -70 degrees C. The hsp70 levels were measured using a commercially available enzyme-linked immunosorbent assay. Results were analyzed by Wilcoxon's rank sum test. Extracellular hsp70 levels in children with septic shock were significantly elevated compared with control patients (51.6 ng/mL vs. 8.1 ng/mL, respectively, p = .0004). CONCLUSIONS: Extracellular hsp70 levels are significantly elevated in children with septic shock compared with controls. Given the newly described cell signaling properties of hsp70, these data suggest that extracellular hsp70 may play a role in the host response during septic shock.     

Ferritin levels in children with severe sepsis and septic shock

AIM: To evaluate serum ferritin level in children with severe sepsis and septic shock and its association with mortality. METHOD: A cohort study of 36 children aged 1 month-16 years with severe sepsis or septic shock requiring intensive care was conducted. Serum ferritin levels were measured at the time of diagnosis of sepsis and a ferritin index (FI=observed serum ferritin divided by the upper limit of normal ferritin for age and gender) was calculated. RESULTS: The median age (range) of the children was 6 (2-100) months. Ferritin was <200 ng/mL in 13 children, 200-500 ng/mL in 11 children and >500 ng/mL in 12 children. The mortality associated with these groups was 23%, 9% and 58%, respectively. A ferritin>500 ng/mL was associated with a 3.2 (1.3-7.9) relative risk of death (p=0.01). FI of 1.7 was the best cutoff value for identifying those who died. In a logistic regression analysis, ferritin level and PRISM were independently associated with mortality. CONCLUSIONS: Ferritin is raised in children with septic shock and high ferritin level is associated with poorer outcome.     

Elevation of brain natriuretic peptide levels in children with septic shock

OBJECTIVES: 1) To compare brain natriuretic peptide levels in pediatric patients with septic shock with both children admitted to the pediatric intensive care unit without infection and with healthy subjects; and 2) to evaluate the correlation between brain natriuretic peptide with severity of illness and with myocardial dysfunction in children with septic shock. DESIGN:: Prospective, observational study. SETTING: Children's Hospital pediatric intensive care unit. PATIENTS: Children from age 2 wks to 18 yrs. Thirteen children with septic shock requiring inotropic support, 12 healthy controls, and five critically ill patients without infection or heart disease were evaluated. INTERVENTIONS: For patients with septic shock, brain natriuretic peptide was measured within 6 hrs of admission and throughout the pediatric intensive care unit course. Echocardiograms were performed within 12 hrs of admission and then repeated if the patient continued to require inotropic support. For controls, one measurement was performed. MEASUREMENTS AND MAIN RESULTS: Children with septic shock had an elevated (p < 0.0001) brain natriuretic peptide on admission (median 115 pg/mL [range 26-2960]) when compared with healthy (9 pg/mL [5-30]) and pediatric intensive care unit controls (10 pg/mL [5-30]). In patients with septic shock, brain natriuretic peptide at 12 hrs correlated directly with Pediatric Risk of Mortality III score (rs = .80, p = 0.002) and inversely with fractional shortening (rs = -.66, p = 0.014). In children with cold shock, brain natriuretic peptide at 12 hrs (718 pg/mL) [63-1530] was higher (p = 0.007) than in those with warm shock (208 pg/mL [20-366]). There was no pattern (p > 0.05) observed for brain natriuretic peptide over time. CONCLUSIONS: Brain natriuretic peptide measured early after admission is increased in children with septic shock, especially in those with cold shock. In addition, the level at 12 hrs correlates with both severity of illness and myocardial dysfunction. Brain natriuretic peptide may be useful in assessing myocardial dysfunction from septic shock, particularly in identifying children with cold shock. Further studies are warranted to determine whether this measurement will be helpful in guiding therapy in pediatric septic shock.     

Neurological injury markers in children with septic shock.

OBJECTIVE: To determine whether known serum markers of neurologic injury are increased in children with septic shock. DESIGN: Prospective, observational study. SETTING: Tertiary-care, pediatric intensive care unit. PATIENTS: Two cohorts of children (n = 24) with septic shock were prospectively enrolled within 24 hrs of their diagnosis. In cohort 1, serum markers (S100beta, neuron-specific enolase [NSE], and glial fibrillary acidic protein [GFAP]) were determined (n = 18). In cohort 2, in addition to serum markers, urine S100beta and GFAP were determined, and continuous electroencephalography (cEEG) was performed. Children who presented to the emergency room with a fever served as controls (n = 32). Children with known neurologic conditions were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum and urine were collected daily for up to 7 days or until pediatric intensive care unit discharge. Biomarker concentrations were determined by commercially available enzyme-linked immunosorbent assays. cEEG was performed on days 1, 2, 4, and 7 in a 16-channel montage for at least 6 hrs. Physical examinations did not reveal focal neurologic deficits. Children with septic shock demonstrated increased serum S100beta and NSE compared with controls (mean +/- SEM: 10.5 microg/L +/- 2.4 vs. .9 microg/L +/- .1, p < .001; 96.6 microg/L +/- 8.9 vs. 4.0 microg/L +/- 1.3, p < .001, respectively). Serum GFAP was detectable in five septic children and none of the controls. In cohort 2, urine of four patients demonstrated measurable S100beta levels, and GFAP was detected in one child (nonsurvivor). cEEG demonstrated moderate to severe encephalopathy in all children studied. CONCLUSIONS: Markers of neurologic injuries are increased in children with septic shock. This may indicate subclinical injuries that are either transient or permanent. Studies that correlate the long-term neurologic outcome of children with these markers are needed to identify children at risk for neurologic injuries from septic shock.     

Vasopressin infusion in children with catecholamine-resistant septic shock

Aim : To describe use of vasopressin infusion for catecholamine-refractory septic shock in children. Methods : We report successful use of vasopressin infusion in three children with septic shock, in whom hypotension and poor perfusion persisted despite use of multiple infusions of vasopressors and inotropes. Results : All three had a rapid improvement in hypotension and perfusion after starting vasopressin infusion, allowing tapering of other infusions. Two children recovered completely.

Conclusions

: Vasopressin appears to be useful in treatment of catecholamine-refractory septic shock in children.     

Adrenal status in children with septic shock using low-dose stimulation test.

OBJECTIVES: There is paucity of data on the magnitude of absolute or relative adrenal insufficiency in septic shock, especially in children. We conducted a prospective study to determine the prevalence of adrenal insufficiency in children with septic shock using a low-dose Synacthen (1 microg) stimulation test. DESIGN: Cross-sectional study. SETTING: Pediatric intensive care unit in a tertiary care hospital in northern India. PATIENTS: Children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed cortisol estimation at baseline and after low-dose Synacthen (1 microg) stimulation at 30 and 60 mins in children with fluid refractory septic shock admitted to our pediatric intensive care unit. Basal cortisol levels <7 microg/dL and peak cortisol level <18 microg/dL were used to define adrenal insufficiency. An increment of <9 microg/dL after stimulation was used to diagnose relative adrenal insufficiency. As there is lack of consensus on the cutoffs for defining relative adrenal insufficiency using the low-dose adrenocorticotropic hormone test, we evaluated different cutoff values (increment at 30 mins, increment at 60 mins, greater of the two increments) and evaluated their association with the incidence of catecholamine refractory shock and outcomes. Children with sepsis but without septic shock were sampled for baseline cortisol levels as a comparison. Thirty children (15 girls) with septic shock were included; median age (95% confidence interval) was 36.5 (9.39- 58.45) months. Median Pediatric Risk of Mortality score was 22.5 (14.13-24.87). Fifteen (50%) children survived. The median (95% confidence interval) cortisol values at baseline and 30 mins and 60 mins after stimulation were 71 (48.74-120.23) microg/dL, 78.1 (56.9-138.15) microg/dL, and 91 (56.17-166.44) microg/dL, respectively. The median baseline cortisol value in age- and gender-matched children with sepsis was 11.5 microg/dL. None of the children with septic shock fulfilled the criteria for absolute adrenal insufficiency. However, nine (30%) patients had relative adrenal insufficiency (increment in cortisol <9 microg/dL). Of these nine patients, five (56%) died; of the 21 patients with a greater increment in cortisol after stimulation, ten died (p = .69). Compared with patients in septic shock with normal adrenal reserve, those with relative adrenal insufficiency had a higher incidence of catecholamine refractory shock (p = .019) but no difference in mortality rate (p = .69). On the sensitivity and specificity analysis using various cutoffs of increment, the best discrimination for catecholamine refractory shock was obtained with a peak increment <6 microg/dL. CONCLUSIONS: Relative adrenal insufficiency is common in children with septic shock and is associated with catecholamine refractory shock.     

Thyroid function in children with sepsis and septic shock

AIM: A prospective study was conducted to determine thyroid hormone levels and their relationship to survival in children with septic shock and sepsis. METHODS: We estimated thyroid hormone levels (T3, T4, TSH, fT3 and fT4) in children with septic shock and compared with those in children with sepsis. RESULTS: Twenty-four children (13 boys) with septic shock and 25 children (14 boys) with sepsis were enrolled. The median T3, T4, fT3, fT4 and TSH (95% confidence interval) were 40 (40-40.23) ng/dL, 4.45 (1.9-6.03) microg/dL, 1.85 (1.2-2.37) pg/mL, 0.77 (0.57-0.95) ng/dL, 0.51 (0.26-1.15) microIU/mL, respectively in children with septic shock group compared with 130 (98.28-163.48) ng/dL, 9.3 (7.66-10.63) microg/dL, 3.2 (3-4.27) pg/mL, 1.3 (1.1-1.4) ng/dL, 2.85 (1.07-3.61) microIU/mL, respectively, in children with sepsis. Children with septic shock who died (n = 12) had higher TSH levels compared to those who survived (p = 0.04). There was no difference in hormone levels between children with catecholamine responsive and catecholamine resistant septic shock. CONCLUSION: Children with septic shock had lower levels of T3, T4, fT3, fT4 and TSH compared to those with sepsis. Findings of our study suggest that derangement of thyroid functions in children is not an important factor contributing to the severity of septic shock.     

感染性休克的循环评估

正确评估感染性休克患儿的循环状态是成功治疗的基础。临床工作中评估休克患儿循环状态的方法包括临床表现、血流动力学监测及反映组织氧合的检测指标。进行循环评估时应注意各项评估指标相结合,同时随病情进展进行动态监测。     

脓毒性休克患儿死亡危险因素分析

目的：探讨脓毒性休克患儿的死亡危险因素,以指导脓毒性休克患儿的治疗,降低死亡率。方法：对53例脓毒性休克患儿10项可能的危险因素先进行单因素分析,然后对单因素分析有显著意义的因素做多因素logistic回归分析。结果：单因素分析和logistic回归分析显示动脉血pH值<7.0、低血压、器官功能障碍数目≥3个、小儿危重病例评分<70分、未在休克后6 h内完成容量复苏、未在休克后1 h内使用有效抗生素、未合理应用血管活性药物为脓毒性休克患儿死亡的危险因素。结论：动脉血pH值<7.0、血压下降、器官功能障碍数目≥3个、小儿危重病例评分<70分的脓毒性休克患儿预后差、死亡率高。若在休克后1 h内能使用有效抗生素、6 h内能完成容量复苏、并能合理应用血管活性药物,则可提高脓毒性休克患儿的治愈率,降低死亡率。［中国当代儿科杂志,2009,11（4）：280-282］     

脓毒性休克患儿心肌酶及高密度脂蛋白胆固醇水平变化的临床意义

目的 探讨心肌酶及高密度脂蛋白胆固醇与小儿脓毒性休克病情严重程度及预后的关系.方法 2006年1月至2011年3月我科收治脓毒性休克患儿共52例,分为重度脓毒性休克组(27例)和轻度脓毒性休克组(25例).入院时检测脓毒性休克患儿的肌酸激酶同工酶(creatine kinase-MB,CK-MB)、α-羟丁酸脱氢酶(α-hydroxybutyrate dehydrogenase,α-HBDH)、乳酸脱氢酶(lacficdehydrogenase,LDH)及高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)含量,并与健康体检儿童(正常对照组)32例进行对比分析.轻、重度脓毒性休克组患儿于入院后第1、2、4、7、10、15天动态监测以上指标,同时密切观察脓毒性休克患儿的病情变化,记录死亡情况和治愈出院时间.结果 轻、重度感染性休克组患儿入院时血清CK-MB[ (32.084±4.595) U/L、(61.481±5.639) U/L]较对照组[(21.675±3.453) U/L]明显升高;α-HBDH/LDH(0.694±0.080、0.884±0.079)较对照组(0.443±0.065)明显升高;HDL-C[ (0.646±0.067) mmol/L、(0.310±0.124) mmol/L]较对照组[(1.012±0.156) mmol/L]明显降低,3组间比较差异有统计学意义(P均＜0.01).重度脓毒性休克组死亡5例,轻度组无死亡病例.重度脓毒性休克组患儿较轻度组在CK-MB恢复时间[(9.82±1.76)d vs (4.68±1.22)d]、α-HBDH/LDH恢复时间[(7.23±1.38)d vs (3.76±0.83)d]、HDL-C恢复时间[(12.14±2.21)d vs (6.48±1.33)d]及住院时间[(15.09±2.69)d vs (7.40±1.58)d]方面明显延长,两组比较差异均有统计学意义(P均＜0.01).结论脓毒性休克患儿血清CK-MB、α-HBDH/LDH越高,HDL-C越低,其病情越重,恢复时间越长,预后越差.     

Thyroid hormone levels and their relationship to survival in children with bacterial sepsis and septic shock

OBJECTIVES: Reported studies have showed alternations of thyroid hormones in critical illness mostly in adults and some in children. In this study, we aimed to measure thyroid hormone levels in children with sepsis and septic shock and investigate the relationship of these hormones with clinical state and survival. PATIENTS AND METHODS: Thyroid hormone levels of children with sepsis and septic shock, and age- and sex-matched controls were measured. RESULTS: There were 51 children in sepsis (group S), 21 children in septic shock (group SS) and 30 in the control (group C) group. Total triiodothyronine (TT3) levels were (nmol/l): 0.91 +/- 0.22, 0.64 +/- 0.23, 2.11 +/- 0.59; free triiodothyronine (FT3) (pmol/l): 0.027 +/- 0.006, 0.018 +/- 0.007, 0.049 +/- 0.010; total thyroxine (TT4) (nmol/l): 100.62 +/- 21.93, 65.79 +/- 19.35, 109.65 +/- 19.35; free thyroxine (FT4) (pmol/l): 18.06 +/- 3.87, 10.32 +/- 1.29, 19.35 +/- 3.87; and thyroid stimulating hormone (TSH) (mIU/ml): 5.0 +/- 2.0, 4.8 +/- 2.4, 5.2 +/- 3.0, in children with sepsis, septic shock, and controls, respectively. The TT3, FT3, TT4, and FT4 levels of group SS were significantly lower than those of groups S and C. The TT3 and FT3 levels of group S were lower than in group C, but there was no significant difference between TT4, and FT4 levels of groups S and C. TSH levels were slightly decreased in both sepsis and septic shock, but the difference was not significant. Eleven (21.6%) children with sepsis and 15 (71.4%) children with septic shock died (p < 0.001). The levels of TT3, FT3, TT4 and FT4 were markedly lower in non-survivors of groups S and SS compared to survivors (p < 0.001). CONCLUSIONS: These changes in the hypothalamo-pituitary-thyroidal axis may suggest a possible prognostic value of thyroid hormone levels in children with sepsis and septic shock. To the best of our knowledge, this report is the first study to compare thyroid hormone levels in a large number of patients with sepsis and septic shock with those in healthy controls in childhood.     

Myocardial cell injury is common in children with septic shock

Objective: To determine the prevalence of myocardial cell injury in children with septic shock by estimating the levels of biochemical markers of myocardial injury, troponin I (TnI) and creatine kinase MB (CK-MB).
Patients: Children aged 3 months to 16 years were admitted to paediatric intensive care unit (PICU) with septic shock. Children with sepsis without shock and children with hypovolaemic shock were enrolled as controls.
Measurements and Main Results: Serum TnI and CK-MB levels were measured at admission and serially at 24 h, 48 h and 96 h in children with septic shock, while baseline measurement of the same markers was taken from the controls. In total, 88% (15/18) of children with septic shock had elevated TnI levels compared with 25% (5/20) with sepsis and 6.7% (1/15) with hypovolaemic shock (p < 0.001). Serial TnI levels at admission, 24 h, 48 h and 96 h were higher in the nonsurvivors. There was a positive correlation between the baseline TnI levels and the predicted mortality using the paediatric index of mortality (PIM2) scores at admission (r = 0.51, p = 0.03).
Conclusion: A majority of children with septic shock have evidence of myocardial cell injury. The estimation of serum TnI levels may help in better prognostication of children with septic shock.     

血乳酸清除率在小儿脓毒性休克中的应用

血乳酸是反映全身组织灌注情况和细胞内是否缺氧的敏感标志物.近年来研究发现,脓毒性休克时血乳酸明显增高,当休克得到改善,血乳酸可很快下降.因此,测定体内乳酸的清除率可准确提示脓毒性休克的血流动力学改变情况并对其预后作出有效评估.该文就血乳酸清除率在小儿脓毒性休克中的研究进展作一概述.     

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??Abstract: Objective To investigate the related factors?? clinical features and prognosis of septic shock in children with acute leukemia. Methods Analyse the clinical features??therapeutic measures??effect and death risk factors of eighteen children with acute leukemia and septic shock in our hospital from Jan.1??2005 to Jun.1??2012. Result Male children 15 cases ??83.3%???? with a mean onset age of 9.8 years?? the average strong chemotherapy treatment of 6.5 times. All children’s neutrophile granulocyte count was lower than 0.5 × 109 / L??hypoalbuminemia occurred in 13 cases ??13/15??86.7%???? cardiac dysfunction in 12 cases ??66.7%???? pneumonia in 13 cases ??72.2%???? MODS in 7 cases ??38.9%??. Bacterial culture was gram negative ??G -?? bacillus in 9 cases??including pseudomonas aeruginosa??3 cases????gram positive??G +?? bacteria in 2 cases?? both were hemolytic staphylococcus. Among the 18 cases?? 1 gave up treatment?? 6 cases died?? 11 cases were cured?? and the mortality rate was 35.3%. Single factor analysis results showed that the use of sensitive antibiotics within 24 hours during fever in the shock-correction group and the death group had statistical significances?? as well as the occurrence of MODS in the process of shock rescue ??P??0.05??.Shock merger pneumonia?? cardiac dysfunction?? and refractory-relapsed patients had no statistical significance. Conclusion The older boys?? agranulocytosis?? multiple chemotherapy and hypoalbuminemia are high risk factors of septic shock. Gram negative bacilli is more in bacterial culture?? especially pseudomonas aeruginosa.Staphylococcus heamolyticus can’t be ignored. Patients with cardiac dysfunction are common?? but CK - MB doesn't increase or increase obviously?? Not using sensitive antibiotics within 24 hours since fever occurs and MODS are the high-risk factors causing death. Using sensitive antibiotics as soon as possible and supportting the organ function actively are important measures to reduce the death of children with septic shock.     

小儿脓毒性休克并发心脏损害的回顾性分析

目的探讨小儿脓毒性休克并发心脏损害的临床特点及心肌酶谱、心电图和超声心动图改变。方法对2003年1月～2006年6月在我院PICU接受监护治疗的38例脓毒性休克并发心脏损害患儿的临床资料及心肌酶谱、心电图和超声心动图检查结果作系统回顾性分析。结果本组患儿临床诊断心力衰竭16例,死亡20例。38例患儿肌酸激酶和肌酸激酶同工酶均超过正常参考值上限。作心电图检查的35例患儿中,ST-T改变16例,异位心律9例,传导阻滞4例。作超声检查的19例患儿中,心脏收缩和(或)舒张功能下降6例,整个室壁运动异常6例,节段性室壁运动异常3例,前间隔中段运动减弱1例,射血分数<50%5例,缩短分数<20%4例,心脏增大5例。结论小儿脓毒性休克可导致心肌酶学、心脏电生理、心脏功能及形态改变。     

Adrenocortical status in infants and children with sepsis and septic shock

BackgroundThe benefit from corticosteroids remains controversial in sepsis and septic shock and the presence of adrenal insufficiency (AI) has been proposed to justify steroid use.AimTo determine adrenal state and its relation with outcome in critical children admitted with sepsis to PICU of Cairo University, Children Hospital.MethodsThirty cases with sepsis and septic shock were studied. Cortisol levels (CL) were estimated at baseline and after high-dose short ACTH stimulation in those patients and in 30 matched controls. Absolute AI was defined as basal CL < 7 μg/dl and peak CL < 18 μg/dl. Relative AI was diagnosed if cortisol increment after stimulation is <9 μg/dl.ResultsOverall mortality of cases was 50%. The mean CL at baseline in cases was higher than that of controls (51.39 μg/dl vs. 12.83 μg/dl, p = 0.000). The mean CL 60 min after ACTH stimulation was higher than that of controls (73.38 μg/dl vs. 32.80 μg/dl, p = 0.000). The median of %rise in cases was lower than that of controls (45.3% vs. 151.7%). There was a positive correlation between basal and post-stimulation cortisol with number of system failure, inotropic support duration, mechanical ventilation days, and CO₂ level in blood. There was a negative correlation between basal and post stimulation cortisol with blood pH and HCO₃.ConclusionRAI is common with severe sepsis/septic shock. It is associated with more inotropic support and has higher mortality. Studies are warranted to determine whether corticosteroid therapy has a survival benefit in children with RAI and catecholamine resistant septic shock.     

血管活性药物评分与儿童脓毒性休克预后的关系

目的 探讨血管活性药物评分（VIS）与脓毒性休克患儿预后的关系。方法 以接受血管活性药物治疗的117例失代偿型脓毒性休克患儿为研究对象,根据预后分为死亡组（41例）和存活组（76例）,根据第1个24 h最大VIS （24 h VIS max）的临界点分为低VIS组（78例）和高VIS组（39例）。计算所有患儿24 h VIS max和第1个24 h VIS平均值（24 h VIS mean）,并对VIS与脓毒性休克预后的关系进行受试者工作特征曲线（ROC）分析。结果 死亡组24 h VIS max、24 h VIS mean、PRISMⅢ评分、血管活性药物使用前及24 h后的乳酸均明显高于存活组（P < 0.05）。24 h VIS max、24 h VIS mean、PRISMⅢ评分、血管活性药物使用前和24 h后的乳酸以及24 h后的pH对于脓毒性休克预后均具有一定的预测价值,但以24 h VIS max的曲线下面积（AUC）最大（P < 0.05）。高VIS组的死亡人数、PRISM Ⅲ评分、治疗前及治疗24 h后的乳酸均明显高于低VIS组（P < 0.05）。结论 血管活性药物评分与脓毒性休克患儿的病死率有关,血管活性药物评分越高,病情越危重,病死率越高。