Diagnosis and treatment of pediatric septic shock in pediatric intensive care units from hospitals of different levels / 中华儿科杂志

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ2=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ2=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome / 中华儿科杂志

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

Survey on the application of external cardiopulmonary resuscitation in Chinese children with sudden cardiac arrest / 中华儿科杂志

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P>0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.

Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit / 中华儿科杂志

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Selection of blood purification for severe acute pancreatitis / 中国实用儿科杂志

Severe acute pancreatitis(SAP)is a severe inflammatory disease with persistent organ failure for more than 48 hours,resulting in a high mortality rate. The abnormal release of pancreatic enzyme and cytokines is accompanied by the occurrence and progress of SAP. Blood purification can not only continuously or intermittently remove excessive water and solutes from the body,but also regulate the balance of pro-inflammatory and anti-inflammatory factors,thus reducing organ function damage,which may be a new effective treatment method for SAP. At present,the application of blood purification for SAP is still controversial and still in the exploratory stage.

Myocardial protective effect of L-carnitine in children with hand, foot and mouth disease caused by Coxsackie A16 virus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms.</p><p><b>METHODS</b>A total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups.</p><p><b>RESULTS</b>There was no significant difference in treatment response between the L-carnitine group and the fructose group (P>0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P<0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P>0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P<0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P>0.05). SOD level was negatively correlated with aspartate aminotransferase, lactate dehydrogenase (LDH), CK, and creatine kinase-MB (CK-MB) (r=-0.437, -0.364, -0.397, and -0.519 respectively; P<0.05), and MDA level was positively correlated with LDH and CK-MB (r=0.382 and 0.411 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>L-carnitine exerts a good myocardial protective effect in children with HFMD caused by Coxsackie A16 virus, possibly by clearing oxygen radicals and inhibiting cardiomyocyte apoptosis.</p>

Paroxysmal muscle weakness, liver enlargement, and hypoglycemia in a boy / 中国当代儿科杂志

A boy aged 11 years was admitted due to intermittent weakness and difficulty in walking for 6 years, and hepatomegaly, glycopenia and unconsciousness for 4 years. The laboratory examinations showed severe metabolic acidosis, hypoglycemia, and abnormal liver function. CT scan showed marked liver enlargement with fat density shadow. The boy was given fluid infusion, correction of acidosis, intravenous injection of glucose, L-carnitine, compound vitamin B, and coenzyme Q10, but he was in a persistent coma and it was difficult to correct refractory metabolic acidosis and hypoglycemia. The boy died. Blood and urinary organic acid screening and gene detection confirmed that the boy had late-onset glutaric aciduria type II (GAIIc) caused by electron-transferring-flavoprotein dehydrogenase (ETFDH) gene defect. GAIIc is an inherited metabolic disease with a low incidence, resulting in a high misdiagnosis rate. GAIIc should be considered for children with recurrent weakness or reduced activity endurance, hypoglycemia, and marked liver enlargement with abnormal liver function. Urinary organic acid analysis and blood tandem mass spectrometry can help with the early diagnosis of GAIIc, and ETFDH gene analysis helps to make a confirmed diagnosis.

Oliguria and acute renal dysfunction in a six-month-old infant / 中国当代儿科杂志

The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

Risk factors for death in children with severe hand, foot and mouth disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the death risk factors in children with severe hand, foot and mouth disease (HFMD).</p><p><b>METHODS</b>A total of 164 children with severe HFMD between May 2010 and September 2012 were recruited and classified into death and survival groups according to their prognosis. The differences in general information, clinical signs and symptoms and laboratory examinations were compared between the two groups. The multivariate logistic regression analysis was used to identify death risk factors in children with severe HFMD.</p><p><b>RESULTS</b>There were significant differences in the incidences of atypical rash, persistent fever, dyspnea, pulmonary hemorrhage, heart rate increase, blood pressure abnormalities, cold sweat, capillary refill time>3 seconds and frequent seizures, and blood glucose, serum creatine kinase and serum lactate levels between the death and the survival groups (P<0.05). The multivariate logistic regression analysis showed three independent death risk factors for children with severe HFMD: pulmonary hemorrhage (OR=9.466, 95%CI: 1.786-21.256), abnormal blood pressure (OR=5.224, 95%CI: 1.012-28.985) and elevated serum lactate level (OR=2.154, 95%CI: 1.020-8.253).</p><p><b>CONCLUSIONS</b>Pulmonary hemorrhage, abnormal blood pressure and elevated serum lactate are major death risk factors for children with severe HFMD.</p>

Evaluation of adrenocortical function in children with severe and critical enterovirus 71 infection / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the adrenocortical function in children with severe and critical enterovirus 71 infection by using a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. And to at provide experimental basis for glucocorticoid in the treatment of hand-foot-and-mouth disease (HFMD).</p><p><b>METHOD</b>This was a prospective multi-center study which was carried out in PICUs of Beijing Children's Hospital, Zhengzhou Children's Hospital, Kaifeng Children's Hospital and Linyi People's Hospital in Shandong province. Children with severe and critical hand-foot-mouth disease admitted to PICUs of the four hospitals from June 2009 to April 2010 were enrolled in this study, and EV71 virus nucleic acid test and high-dose (250 µg) ACTH stimulation started at the same time. EV71 virus nucleic acid positive 51 cases were eventually enrolled in the study. Cortisol test was performed at baseline (T0) and after high-dose (250 µg) ACTH stimulation at 30 minutes (T30), 60 minutes (T60) in the first 6 hours after admission, but before glucocorticoid was given. The adrenocortical function was evaluated according to ΔTmax [ΔTmax=(T30, T60 maximum)-T0]. Diagnostic criteria of adrenal insufficiency (AI) is increment (ΔTmax)≤9 µg/dl.</p><p><b>RESULT</b>The incidence of AI in 51 cases was 52.94% (27/51). The incidence of AI in severe group was 44.74% (17/38), which was significantly higher in critical group 76.92% (10/13), P<0.05. Of the cases with a pediatric critical illness score (PCIS)≤70, 81.82% (9/11) had adrenal insufficiency, and it was 28.57% (4/14) when PCIS≥90. The incidence of AI was 75% (6/8) and 48.84% (21/43) in death and survivor group respectively, but there were no significant difference between the two groups (P>0.05). Baseline (T0) cortisol in death group was higher than survivor group (P<0.05).</p><p><b>CONCLUSION</b>AI may occur in children with enterovirus 71 infection. The critical enterovirus 71 infection had a high incidence of AI. AI may affect the prognosis of patients with severe and critical enterovirus 71 infection. Exogenous glucocorticoids administration may be considered when AI is identified or highly suspected. The timing, dosage and regimen of glucocorticoid are still unclear. Further animal experiments and clinical trials are needed.</p>