Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade

Background@#Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. @*Methods@#This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, postcardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012–2016) and 2 (2017–2021). @*Results@#Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2.Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30–45%, P = 0.002).Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). @*Conclusion@#Pediatric ECMO demonstrated a steady increase in overall survival in Korea;however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

The impact of single dose intravenous dexamethasone as an adjunctive therapy for primary treatment on concentrations of inflammatory biomarkers in children with Kawasaki disease

Purpose@#This study was performed to investigate the impact of single dose dexamethasone as an adjunctive therapy for primary treatment on values of inflammatory markers in children with Kawasaki disease (KD). @*Methods@#We investigated inflammatory markers, including white blood cells, erythrocyte sedimentation rate, C-reactive protein (CRP), interleukin (IL)-6, and IL-10 in 42 children with complete KD who were hospitalized in the Kyungpook National University Children’s Hospital from March 2016 through April 2017. The children underwent primary treatment for KD with intravenous immunoglobulin (IVIG) and/or dexamethasone. They were divided into 2 groups according to the use of dexamethasone. To assess the change in values of inflammatory markers, the blood was drawn twice from each child; before and 24 hours after the administration of IVIG. @*Results@#Of the 42 study children, 18 and 24 were classified as the dexamethasone and control groups, respectively. No significant differences were found between the 2 groups in terms of the length of hospital stay, duration of fever, and time required for IVIG administration. In both groups, white blood cells, CRP, IL-6, and IL-10 significantly decreased after the primary therapy. The delta scores of CRP, IL-6, and IL-10 were higher in the dexamethasone group (P = 0.015, P = 0.001, and P = 0.002, respectively). No coronary artery abnormalities were found in both groups. @*Conclusion@#This study suggests an anti-inflammatory effect of single dose dexamethasone as an adjunctive therapy for primary treatment in children with KD without shortening the duration of fever and the length of hospital stay.

Analysis of PC20-FEF25%-75% and △FVC in the methacholine bronchial provocation test

Purpose@#Forced expiratory flow between 25% and 75% (FEF 25%-75%) is known to sensitively reflect bronchial obstruction. Methacholine challenge test (MCT) has shown varying reduction levels of forced vital capacity (FVC) with the reduction in forced expiratory volume in 1 second (FEV1) in asthma. The aim of this study was to evaluate the clinical implication of provocative concentration causing a 20% fall in FEF 25%-75%(PC 20-FEF 25%-75%) and the percentage fall in FVC at the PC 20 dose of methacholine (△FVC). @*Methods@#A total of 194 children who visited the hospital due to respiratory symptoms and underwent MCT were analyzed retrospectively. The patients were divided into 3 groups. Group I had both PC 20-FEV1 and PC 20-FEF 25%-75% above 16 mg/mL; group II had a PC 20-FEF 25%-75% that fell below 16 mg/mL but PC 20-FEV1 was 16 mg/mL or above; group III had a PC 20-FEV1and a PC 20-FEF 25%-75% that both fell below 16 mg/mL. @*Results@#In group II, PC 20-FEV1 was lower (P = 0.026) and the rate of change in FEV1 and FEF 25%-75% from baseline to 16 mg/mL of methacholine concentration was greater than in group I (both P< 0.001). Levels of PC 20-FEF 25%-75% were higher in group II compared to group III (P < 0.001). △FVC showed a correlation with PC 20-FEV1 (P < 0.001) only in the whole group. @*Conclusion@#In asthmatic children, PC 20-FEF 25%-75% may be associated with bronchial hyperresponsiveness. △FVC was not associated with other parameters in either group. For subjects with a positive finding of PC 20-FEF 25%-75% and a negative finding of MCT, the progression to asthma can be suspected.

Correlations of induced sputum eosinophils with blood allergic markers in pediatric asthma and eosinophilic bronchitis

Purpose@#Induced sputum eosinophil count is useful for the evaluation and diagnosis of asthma and eosinophilic bronchitis (EB).The aim of this study was to evaluate the correlation of induced sputum eosinophil count with various allergic indicators, including the peripheral blood eosinophil count, in pediatric asthma and EB. @*Methods@#From May 2014 to July 2018, 126 children visited Kyungpook National University Children’s Hospital, and underwent methacholine bronchial challenge test and sputum induction. Peripheral blood eosinophil counts, serum eosinophil cationic protein (ECP), serum total IgE, immunoCAP for inhalant allergens, and skin prick test were performed in the study subjects. @*Results@#In the asthma group, the eosinophil count of induced sputum correlated with peripheral blood eosinophils (r=0.279, P=0.043).The concordance rates of sputum and peripheral blood eosinophil count in the asthma and EB groups were 64.1% and 25.7%, respectively. The number of eosinophils in the sputum also correlated with serum total IgE, ECP, and specific IgE to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Aspergillus in the asthma group. @*Conclusion@#The number of eosinophils in the induced sputum correlated with peripheral blood in the asthma group. However, a third of subjects were discordant. Therefore, we need to keep in mind the possibility of discordance when predicting the degree of airway eosinophilic inflammation using the peripheral blood eosinophils. In EB, the number of induced sputum eosinophils did not correlate with the number of peripheral blood eosinophils, which may be attributed to the difference in mechanism. Further studies are warranted.

Diagnosis and management of Kawasaki disease

Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a common form of vasculitis in childhood. Among the recent trends in Kawasaki disease, it is notable that the prevalence rate is increasing, and the proportion of “incomplete” Kawasaki disease is also increasing. A delayed diagnosis with prolonged fever can cause complications, such as coronary artery aneurysm and decreased myocardial contractility. These complications might lead to significant morbidity and mortality. Kawasaki disease is diagnosed when the patient meets the principal criteria for clinical symptoms. Following the diagnostic criteria can prevent overdiagnosis but lead to missing of the incomplete form of the disease. Therefore, it is important to accurately understand Kawasaki disease. As the coronavirus disease 2019 (COVID-19) pandemic continues, concerns about a novel severe Kawasaki-like disease in children related to COVID-19 emerges. Indeed, there have been several reports of Kawasaki-like disease related to COVID-19 in children. Kawasaki disease is no longer rare and is often encountered at hospitals. This paper will provide useful and accurate information on Kawasaki disease.

Human Parechovirus: an Emerging Cause of Sepsis-Like Syndrome in Infants Aged under 3 Months

Purpose@#This study aimed to investigate the clinical characteristics of human parechovirus (HPeV) infection in sepsis-like syndrome in infants aged under 3 months. @*Methods@#Medical records of infants aged under 3 months with sepsis-like symptoms who were admitted between July 1, 2018 and August 31, 2018 were reviewed. A multiplex reverse transcription-polymerase chain reaction panel test was performed on the cerebrospinal fluid (CSF). Thirty-nine enrolled infants were categorized into three groups: 11 in group 1 (HPeV detected in the CSF), 13 in group 2 (enterovirus detected in the CSF), and 15 in group 3 (no virus detected in the CSF). @*Results@#Compared with groups 2 and 3, a higher proportion of group 1 had tachycardia, tachypnea, apnea, and hypotension (P<0.05). A significantly lower white blood cell (WBC) count was noted in group 1 than in groups 2 and 3 (5,622±2,355/μL, 9,397±2,282/μL, and 12,312±7,452/μL, respectively; P=0.005). The CSF WBC count was lower in group 1 than in groups 2 and 3 (0.9±1.7/μL, 85.1±163.6/μL, and 3.7±6.9/μL, respectively; P=0.068). The proportion of patients requiring inotrope support (36.6% vs. 0% and 6.6%), mechanical ventilation (18.1% vs. 0% and 0%), and high flow nasal cannula (45.4% vs. 15.3% and 6.6%) was higher in group 1 than in groups 2 and 3. All patients recovered completely without complications. @*Conclusions@#HPeV infection shows a severe clinical course and can cause a severe sepsis-like syndrome in infants aged under 3 months. Early diagnosis and proper treatment of HPeV infection are required.

Array Comparative Genomic Hybridization as the First-line Investigation for Neonates with Congenital Heart Disease: Experience in a Single Tertiary Center

BACKGROUND AND OBJECTIVES@#The purpose of the present study was to investigate the advantages and disadvantages of verifying genetic abnormalities using array comparative genomic hybridization (a-CGH) immediately after diagnosis of congenital heart disease (CHD).@*METHODS@#Among neonates under the age of 28 days who underwent echocardiography from January 1, 2014 to April 30, 2016, neonates whose chromosomal and genomic abnormalities were tested using a-CGH in cases of an abnormal finding on echocardiography were enrolled.@*RESULTS@#Of the 166 patients diagnosed with CHD, 81 underwent a-CGH and 11 patients (11/81, 13.5%) had abnormal findings on a-CGH. 22q11.2 deletion syndrome was the most common (4/11, 36.4%). On the first a-CGH, 4 patients were negative (4/81, 5%). Three of them were finally diagnosed with Williams syndrome using fluorescent in situ hybridization (FISH), 1 patient was diagnosed with Noonan syndrome through exome sequencing. All of them exhibited diffuse pulmonary artery branch hypoplasia, as well as increased velocity of blood flow, on repeated echocardiography. Five patients started rehabilitation therapy at mean 6 months old age in outpatient clinics and epilepsy was diagnosed in 2 patients. Parents of 2 patients (22q11.2 deletion syndrome and Patau syndrome) refused treatment due to the anticipated prognosis.@*CONCLUSIONS@#Screening tests for genetic abnormalities using a-CGH in neonates with CHD has the advantage of early diagnosis of genetic abnormality during the neonatal period in which there is no obvious symptom of genetic abnormality. However, there are disadvantages that some genetic abnormalities cannot be identified on a-CGH.

Array Comparative Genomic Hybridization as the First-line Investigation for Neonates with Congenital Heart Disease: Experience in a Single Tertiary Center

BACKGROUND AND OBJECTIVES: The purpose of the present study was to investigate the advantages and disadvantages of verifying genetic abnormalities using array comparative genomic hybridization (a-CGH) immediately after diagnosis of congenital heart disease (CHD). METHODS: Among neonates under the age of 28 days who underwent echocardiography from January 1, 2014 to April 30, 2016, neonates whose chromosomal and genomic abnormalities were tested using a-CGH in cases of an abnormal finding on echocardiography were enrolled. RESULTS: Of the 166 patients diagnosed with CHD, 81 underwent a-CGH and 11 patients (11/81, 13.5%) had abnormal findings on a-CGH. 22q11.2 deletion syndrome was the most common (4/11, 36.4%). On the first a-CGH, 4 patients were negative (4/81, 5%). Three of them were finally diagnosed with Williams syndrome using fluorescent in situ hybridization (FISH), 1 patient was diagnosed with Noonan syndrome through exome sequencing. All of them exhibited diffuse pulmonary artery branch hypoplasia, as well as increased velocity of blood flow, on repeated echocardiography. Five patients started rehabilitation therapy at mean 6 months old age in outpatient clinics and epilepsy was diagnosed in 2 patients. Parents of 2 patients (22q11.2 deletion syndrome and Patau syndrome) refused treatment due to the anticipated prognosis. CONCLUSIONS: Screening tests for genetic abnormalities using a-CGH in neonates with CHD has the advantage of early diagnosis of genetic abnormality during the neonatal period in which there is no obvious symptom of genetic abnormality. However, there are disadvantages that some genetic abnormalities cannot be identified on a-CGH.

The change of QRS duration after pulmonary valve replacement in patients with repaired tetralogy of Fallot and pulmonary regurgitation / 소아과

PURPOSE: This study aimed to analyze changes in QRS duration and cardiothoracic ratio (CTR) following pulmonary valve replacement (PVR) in patients with tetralogy of Fallot (TOF). METHODS: Children and adolescents who had previously undergone total repair for TOF (n=67; median age, 16 years) who required elective PVR for pulmonary regurgitation and/or right ventricular out tract obstruction were included in this study. The QRS duration and CTR were measured pre- and postoperatively and postoperative changes were evaluated. RESULTS: Following PVR, the CTR significantly decreased (pre-PVR 57.2%±6.2%, post-PVR 53.8%±5.5%, P=0.002). The postoperative QRS duration showed a tendency to decrease (pre-PVR 162.7±26.4 msec, post-PVR 156.4±24.4 msec, P=0.124). QRS duration was greater than 180 msec in 6 patients prior to PVR. Of these, 5 patients showed a decrease in QRS duration following PVR; QRS duration was less than 180 msec in 2 patients, and QRS duration remained greater than 180 msec in 3 patients, including 2 patients with diffuse postoperative right ventricular outflow tract hypokinesis. Six patients had coexisting arrhythmias before PVR; 2 patients, atrial tachycardia; 3 patients, premature ventricular contraction; and 1 patient, premature atrial contraction. None of the patients presented with arrhythmia following PVR. CONCLUSION: The CTR and QRS duration reduced following PVR. However, QRS duration may not decrease below 180 msec after PVR, particularly in patients with right ventricular outflow tract hypokinesis. The CTR and ECG may provide additional clinical information on changes in right ventricular volume and/or pressure in these patients.

Outcome of neonatal palliative procedure for pulmonary atresia with ventricular septal defect or tetralogy of Fallot with severe pulmonary stenosis: experience in a single tertiary center / 소아과

PURPOSE: The present study aimed to evaluate progression and prognosis according to the palliation method used in neonates and early infants aged 3 months or younger who were diagnosed with pulmonary atresia with ventricular septal defect (PA VSD) or tetralogy of Fallot (TOF) with severe pulmonary stenosis (PS) in a single tertiary hospital over a period of 12 years. METHODS: Twenty with PA VSD and 9 with TOF and severe PS needed initial palliation. Reintervention after initial palliation, complete repair, and progress were reviewed retrospectively. RESULTS: Among 29 patients, 14 patients underwent right ventricle to pulmonary artery (RV-PA) connection, 11 palliative BT shunt, 2 central shunt, and 2 ductal stent insertion. Median age at the initial palliation was 13 days (1–98 days). Additional procedure for pulmonary blood flow was required in 5 patients; 4 additional BT shunt operations and 1 RV-PA connection. There were 2 early deaths among patients with RV-PA connection, one from RV failure and the other from severe infection. Finally, 25 patients (86%) had a complete repair. Median age of total correction was 12 months (range, 2–31 months). At last follow-up, 2 patients had required reintervention after total correction; 1 conduit replacement and 1 right ventricular outflow tract (RVOT) patch enlargements. CONCLUSION: For initial palliation of patients with PA VSD or TOF with severe PS, not only shunt operation but also RV-PA connection approach can provide an acceptable outcome. To select the most proper surgical strategy, we recommend thorough evaluation of cardiac anomalies such as RVOT and PA morphologies and consideration of the patient's condition.

Two patients with Mycoplasma pneumoniae pneumonia progressing to acute respiratory distress syndrome

Mycoplasma pneumoniae pneumonia is one of the most prevalent community-acquired pneumonias in pediatric patients. It commonly presents with mild respiratory symptoms and is well controlled by macrolide antibiotics. Rarely, it can progress to acute respiratory distress syndrome (ARDS) despite appropriate antibiotic therapy, and systemic corticosteroids and quinolone antibiotics are required. We recently treated 2 patients who presented with M. pneumoniae pneumonia with ARDS. Case 1: A 17-year-old girl was admitted with pneumonia that showed no response to antibiotics and progressed to ARDS, which required initiation of mechanical ventilation therapy. The patient was negative for M. pneumoniae IgM; but positive for, M. pneumoniae. After treatment with methylprednisolone and levofloxacin, rapid improvement was observed in both clinical manifestations and chest radiographic findings. Two days after discontinuing a 5-day methylprednisolone treatment regimen, she developed fever, and investigations revealed an elevated C-reactive protein level; this necessitated additional methylprednisolone treatment. Subsequently, she showed complete recovery with no sequelae. Case 2: A 14-year-old girl was admitted with M. pneumoniae pneumonia with ARDS that required mechanical ventilation therapy. She showed a IgM titers against M. pneumoniae of 1:320. After treatment with antibiotics and methylprednisolone, she recovered and was discharged at 48 admission days; however, mild dyspnea persisted. The chest computed tomography showed multiple bronchiectasis areas. After 15 days, because of aggravated dyspnea, she was readmitted and adminis-tered methylprednisolone pulse therapy. Despite 3 courses of methylprednisolone pulse therapy, she still showed mild dyspnea.

Comparison of Infective Endocarditis between Children and Adults with Congenital Heart Disease: A 16-Year, Single Tertiary Care Center Review

PURPOSE: This study aimed to evaluate and compare the characteristics of infective endocarditis (IE) between children and adults with congenital heart disease (CHD) at a single tertiary care center. METHODS: In this retrospective medical record review, we extracted the demographic characteristics, diagnostic variables, and outcomes of patients diagnosed with IE and CHD between 2000 and 2016. RESULTS: We identified a total of 14 pediatric patients (nine male; median age at diagnosis, 3 years). Of the 14 patients, six had a history of previous open heart surgery, while four had undergone tetralogy of Fallot repair, with transannular patch or Rastelli procedure. Among the 10 children with positive blood cultures, the most common isolated organism was Staphylococcus spp. (8/10, 80%). Eleven adult patients had IE and CHD. Among the adult patients, only four were diagnosed with CHD before IE, and ventricular septal defect was the most common CHD. The most common isolated organism was Streptococcus spp. (6/11, 55%). Compared with adult patients, pediatric patients had a higher incidence of previously diagnosed CHD (P=0.001), with Staphylococcus spp. as the causative organism (P =0.027). The median duration between the onset of symptoms and diagnosis of IE was 9 days in children and 42 days in adults (P=0.012). CONCLUSIONS: Significant differences with regard to the diagnosis and progress of IE were observed between children and adults. Ageadjusted and systematic reassessment may be necessary for the diagnosis and management of IE.

Sleep Problems and Daytime Sleepiness in Children with Nocturnal Enuresis

PURPOSE: Nocturnal enuresis (NE) is one of the most common problems in childhood. NE has a multifactorial etiology and is influenced by sleep and arousal mechanisms. The aim of the present study was to prospectively evaluate sleep problems and patterns in children with NE compared with normal healthy controls. METHODS: Twenty-eight children with NE and 16 healthy controls were included in the study. To evaluate sleep habits and disturbances, parents and children filled out a questionnaire that included items about sleep patterns and sleep-related behaviors prior to treatment for NE. Demographic factors and other data were compared for the two groups based on the responses to the sleep questionnaire. RESULTS: Night awakening, sleepwalking, and periodic limb movements were more prevalent in children with NE, but symptoms of sleep-disordered breathing were not increased in this group. There were statistically significant differences in periodic limb movements and daytime sleepiness between the two groups. CONCLUSION: Children with NE seemed to have more sleep problems such as night awakening, sleepwalking, and periodic limb movements. In addition, a higher level of daytime sleepiness and hyperactivity in patients with NE suggested a relationship between NE and sleep disorders.

Influence of the Head Posture on Central Venous Catheter Position during Right Subclavian Catheterization / 대한마취과학회지

BACKGROUND: Confirmation of central venous catheter position with chest X-ray is recommended, but frequently omitted in clinical practice. It was suggested that the head posture during right subclavian catheterization affects the incidence of catheter malposition in infants. We evaluated the influence of the head posture on catheter position during right subclavian catheterization in adults. METHODS: Two-hundred and seventy four patients scheduled for thoracic or neuro-surgery requiring central venous catheterization were enrolled. Patients were divided into 3 groups depending on the head posture during catheter insertion: the neutral group (n = 109), the turn away group (n = 72), and the turn toward group (n = 93). The catheter position was confirmed with postoperative chest X-ray. RESULTS: Central venous catheterization was failed in 5 patients. There were no differences in the incidence of catheter malposition and the complications among the 3 groups. CONCLUSIONS: The head posture during right subclavian catheterization did not affect catheter malposition and immediate complication rates.

The Limited Immune Modulatory Effect of Early Escharectomy on Adhesion Molecules in Major Burn Patients / 대한마취과학회지

BACKGROUND: Early escharectomy has been shown to improve the survival rates and the treatment outcomes of major burn patients. However, its exact mechanism, especially in terms of the human immune system, has not been fully elucidated. This observational study, which placed a focus on adhesion molecules, was conducted to assess changes of soluble intercelluar adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin in major burn patients undergoing early eschar excision. METHODS: Seventeen ASA physical status II or III adult major burn patients, admitted for plastic and reconstructive surgery for burn wound care, were initially recruited. When early escharectomy was scheduled, a series of blood samples were obtained four times at 72 and 24 hours preop and 24 and 72 hours postop, respectively. Changing levels of sICAM-1, sVCAM-1, and E-selectin were measured using quantitative sandwich immunoassay techniques. RESULTS: All patients suffered from major burns. Early escharectomy does not appear to have any significant impact on the levels of sICAM-1 and sVCAM-1. On the other hand, E-selectin levels showed a significant decrease after escharectomy. CONCLUSIONS: Major burn injury certainly induces a systemic inflammatory response. Adhesion molecules behave in such a way that escharectomy has a limited immunomodulatory effect in major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn related inflammation.