Retrospective evaluation of therapeutic plasma exchange treatment in a pediatric intensive care unit: Single-center experience.

BACKGROUND: The aim of this study is to characterize the clinical indications, outcomes, and complications of therapeutic plasma exchange (TPE) in pediatric intensive care unit. METHODS: A retrospective study was conducted on critically ill patients who received TPE. A dataset of 672 treatments administered to 102 patients was analyzed. RESULTS: The most common indication for TPE was COVID-19-related clinical conditions, followed by sepsis (24.5%), neurological diseases (9.8%) and renal diseases (6.9%). None of our patients died due to TPE-related complications, and the most common complication during and after the TPE was hypotension (21.7%). CONCLUSION: Although TPE is riskier to provide to critically ill children, our experience indicates that it can be performed relatively safely in critically ill children with appropriate treatment indications. In particular, indications, onset time, number of sessions and other procedures should be standardized for the pediatric age group.

COVID-19 associated thrombotic microangiopathy.

A limited number of cases of thrombotic microangiopathy (TMA) have previously been reported in association with COVID-19. Our report describes two cases of TMA associated with COVID-19, one of which was successfully treated with eculizumab. The first case was a 23-month-old girl, and the second case was a 9-month-old boy. PCR tests for SARS-CoV-2 were positive in both cases, and laboratory results showed microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. No known aetiology for TMA was found in either case. Stool tests for Shigatoxin-producing Escherichia coli were negative. Coagulation tests, ADAMTS13 activity, serum complement levels, and homocysteine levels were all within the normal range. No known genetic mutation was found, including mutations of complement, diacylglycerol kinase epsilon, and cobalamin C. In the first case, eculizumab was administered due to persistent haemolysis and prolonged anuria. In conclusion, TMA may be associated with COVID-19 infection. Treatment with eculizumab may be beneficial in selected patients because of the potential activation of the complement system.

Why has plasma exchange failed in TRACK syndrome? Lessons from a new variant of the atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening form of thrombotic microangiopathy, associated with high mortality and morbidity. Most cases present with hemolytic anemia, thrombocytopenia, and renal insufficiency. However, it can have unusual multiple end-organ injuries including extrarenal organ and system involvements such as neurologic, cardiac, gastrointestinal, and respiratory systems. We describe a 4-year-old girl who developed aHUS due to the TSEN2 mutation and had cardiac involvement. She did not benefit from plasma exchange, as stated in previous cases. It should be kept in mind that therapeutic plasma exchange may not be beneficial in some cases of aHUS, especially due to genetic mutations.

A case of severe DRESS syndrome treated with therapeutic plasma exchange and intravenous immunoglobulin therapy.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in children is a rare adverse drug reaction with skin rash, fever, hematologic abnormalities, and multiorgan involvement. The diagnosis is difficult because of its various clinical presentations, nonetheless is extremely important due to the mortality rate. We describe a 14-year-old boy who developed hypersensitivity to either teicoplanin or meropenem therapy. After failing to improve with corticosteroids, he was successfully treated with therapeutic plasma exchange (TPE). TPE should be considered in the treatment with corticosteroid-resistant DRESS syndrome.

The role of treatment with plasma exchange therapy in two pediatric toxic epidermal necrolysis cases related to COVID-19.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions characterized by necrosis and detachment of the epidermis. Drugs and bacterial or viral infections are the most common causes of SJS/TEN. Although cases of SJS/TEN have been reported after hydroxychloroquine, vaccine (mRNA [Biontech], and inactivated vaccine [Sinovac]) administration and during the clinical course of active Coronavirus disease 2019 (COVID-19), limited data is indicating the COVID-19 disease as a triggering factor. Also, there are no pediatric cases of SJS/TEN associated with COVID-19 in the literature. Herein we reported two pediatric cases with a diagnosis of TEN related to COVID-19. Therapeutic plasma exchange therapy was applied to both of our patients. Although there are a few adult cases in the literature, our article is the first pediatric case report about patients diagnosed with TEN related to COVID-19 and successfully treated with plasma exchange.

Diagnostic and Prognostic Biomarkers of Coronavirus Disease 2019 in Children.

Predictors of early diagnosis and severe infection in children with coronavirus disease 2019 (COVID-19), which has killed more than 4 million people worldwide, have not been identified. However, some biomarkers, including cytokines and chemokines, are associated with the diagnosis, pathogenesis and severity of COVID-19 in adults. We examined whether such biomarkers can be used to predict the diagnosis and prognosis of COVID-19 in pediatric patients. Eighty-nine children were included in the study, comprising three patient groups of 69 patients (6 severe, 36 moderate and 27 mild) diagnosed with COVID-19 by real-time polymerase chain reaction observed for 2-216 months and clinical findings and 20 healthy children in the same age group. Hemogram, coagulation, inflammatory parameters and serum levels of 16 cytokines and chemokines were measured in blood samples and were analyzed and compared with clinical data. Interleukin 1-beta (IL-1ß), interleukin-12 (IL-12) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in the COVID-19 patients (p = 0.035, p = 0.006 and p < 0.001). Additionally, D-dimer and IP-10 levels were higher in the severe group (p = 0.043 for D-dimer, area under the curve = 0.743, p = 0.027 for IP-10). Lymphocytes, C-reactive protein and procalcitonin levels were not diagnostic or prognostic factors in pediatric patients (p = 0.304, p = 0.144 and p = 0.67). Increased IL-1ß, IL-12 and IP-10 levels in children with COVID-19 are indicators for early diagnosis, and D-dimer and IP-10 levels are predictive of disease severity. In children with COVID-19, these biomarkers can provide information on prognosis and enable early treatment.

COVID-19 in Turkey: A tertiary center experience.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a serious epidemic in our country and all over the world since December 2019 and has become a global health problem. The disease caused by the SARS-CoV-2 virus has been named as coronavirus disease 19 (COVID-19). METHODS: We report on the epidemiological and clinical features of 37 children diagnosed with COVID-19. RESULTS: The median age was of the children was 10 years and 57.1% were male. In addition, 78.3% of the children had a history of contact with adult patients who had been diagnosed with COVID-19, and 27.0% had coexisting medical conditions. We found that 40.5% of our patients had mild infection, while 32.4% had moderate infection, and 27.1% had developed severe or critical illness. The most common abnormal laboratory findings in our patients were decreased lymphocytes (45.9%) and increased D-dimer values (43.2%), while abnormal radiological findings were detected in 56.7% of the children. In addition, 64.8% of the children had received azithromycin, 59.4% had received oseltamivir, and hydroxychloroquine was used in combination with azithromycin in 35.1% of the children. Non-invasive mechanical ventilation was required in 27.0% of the children. CONCLUSIONS: Although COVID-19 infection is usually mild in children, severe illness can be seen in children with comorbidities, or even in children who were previously healthy.

Evaluation of Continuous Renal Replacement Therapy and Therapeutic Plasma Exchange, in Severe Sepsis or Septic Shock in Critically Ill Children.

Background and objective: Severe sepsis and septic shock are life-threatening organ dysfunctions and causes of death in critically ill patients. The therapeutic goal of the management of sepsis is restoring balance to the immune system and fluid balance. Continuous renal replacement therapy (CRRT) is recommended in septic patients, and it may improve outcomes in patients with severe sepsis or septic shock. Therapeutic plasma exchange (TPE) is another extracorporeal procedure that can improve organ function by decreasing inflammatory and anti-fibrinolytic mediators and correcting haemostasis by replenishing anticoagulant proteins. However, research about sepsis and CRRT and TPE in children has been insufficient and incomplete. Therefore, we investigated the reliability and efficacy of extracorporeal therapies in paediatric patients with severe sepsis or septic shock. Materials and methods: We performed a multicentre retrospective study using data from all patients aged <18 years who were admitted to two paediatric intensive care units. Demographic data and reason for hospitalization were recorded. In addition, vital signs, haemogram parameters, and biochemistry results were recorded at 0 h and after 24 h of CRRT. Patients were compared according to whether they underwent CRRT or TPE; mortality between the two treatment groups was also compared. Results: Between January 2014 and April 2019, 168 septic patients were enrolled in the present study. Of them, 47 (27.9%) patients underwent CRRT and 24 underwent TPE. In patients with severe sepsis, the requirement for CRRT was statistically associated with mortality (p < 0.001). In contrast, the requirement for TPE was not associated with mortality (p = 0.124). Conclusion: Our findings revealed that the requirement for CRRT in patients with severe sepsis is predictive of increased mortality. CRRT and TPE can be useful techniques in critically ill children with severe sepsis. However, our results did not show a decrease of mortality with CRRT and TPE.

Clinical characteristics of mechanically ventilated children in pediatric intensive care unit: A single-center study.

OBJECTIVE: Mechanical ventilation (MV) remains the most challenging and important issue in the field of pediatrics. It is a life-saving, invasive procedure that supports the cardiovascular and respiratory systems until the underlying disease is cured. The aim of this study was to evaluate the demographic profile, clinical aspects, indications and complications of MV, and outcome of the children in the pediatric intensive care unit (PICU) of a tertiary hospital in a developing country. METHODS: The demographic profile, clinical aspects, MV indications and complications, and outcomes of pediatric patients (0-18 years of age) who required MV in the Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital PICU from February 2022 to January 2023 were retrospectively reviewed. RESULTS: A total of 139 patients were analyzed, of whom 79 (56.8%) were males. The median age was 36 months (1-214). Respiratory diseases (38.8%) were the most common indication for MV. We observed a 19.4% mortality rate with a statistically significant association with sepsis (p=0.001). Compared to other diseases, a large number of sepsis patients were found to require a variety of critical care treatment modalities and prolonged respiratory support. CONCLUSION: Although MV is an indispensable treatment method in PICUs, it should not be forgotten that it carries the risk of morbidity and mortality in addition to the underlying disease. Therefore, the establishment of experienced teams in PICUs could make an important contribution to the prognosis of the patients.

The value of prognostic markers for pediatric trauma patients.

BACKGROUND: Despite the rapid development of pediatric intensive care medicine, there are still limited data in the literature regarding the follow-up of pediatric trauma patients in pediatric intensive care units (PICUs). In this study, we aim to evaluate our experience with children admitted and followed up with the diagnosis of trauma at our PICU. METHODS: We evaluated the retrospective data of 77 pediatric trauma patients who were admitted to the PICU at Sancaktepe Sehit Prof. Dr. IlhanVarank Training and Research Hospital from August 2020 to December 2022. The demographic data, clinical parameters and laboratory results were recorded. The primary outcome was the mortality in PICU. The performances of markers in predicting mortality were evaluated with receiver operating characteristic (ROC) curves. RESULTS: The median age of the patients was 70 (33-157) months, and the median duration of hospitalization in the PICU was 6 (2-11) d. Of the 77 patients, 9 died due to trauma (11,1%). Among the clinical parameters, Pediatric Risk of Mortality III (PRISM III) Score, inotrope requirement, extracorporeal treatment requirement, and mechanical ventilator requirement were significantly higher in non-survivors than in survivors. Among the laboratory parameters, procalcitonin (PCT), lactate/albumin ratio (LAR), neutrophil/lymphocyte ratio (NLR), and transfusion requirement were significantly higher in non-survivors than in survivors. CONCLUSION: In pediatric trauma patients, baseline PCT, LAR, and NLR values can be used to identify patients at risk for mortality.

Assessment of the Clinical Course of Human Rhinovirus/Enterovirus Infections in Pediatric Intensive Care.

BACKGROUND: This study aims to evaluate the clinical course of human rhinovirus/enterovirus (HRV/EV) infections in the pediatric intensive care unit. METHODS: The study was conducted as a multicenter, prospective observational study from September 2022 to December 2022. Cases with positive polymerase chain reaction testing for HRV/EV of nasopharyngeal swab samples within the first 24 hours of pediatric intensive care unit admission were recorded. There were 2 groups: 1-24 months and >24 months. RESULTS: A total of 75 cases (39 male) were included in the study. The median age for all cases was 21 months. The highest polymerase chain reaction positivity rates were observed in October (37.33%). Among the cases, 32 (42.67%) presented with bronchopneumonia/pneumonia, 24 (32%) presented with acute bronchiolitis/bronchitis and 7 (9.33%) presented with sepsis/septic shock. The frequency of pediatric acute respiratory distress syndrome was found to be 6.67%. In the age group of 1-24 months, mean lymphocyte and liver enzyme levels were higher, while in the age group of >24 months, mean hemoglobin and mean kidney function test levels were higher ( P ≤ 0.05). Continuous oxygen therapy was provided to 65.3% of the cases, noninvasive ventilation to 33.3%, high-flow nasal cannula-oxygen therapy to 32% and invasive mechanical ventilation to 16%. CONCLUSIONS: HRV/EV infections primarily affect the respiratory system and generally exhibit a clinical course with low mortality rates (1, 1.3%). In cases with underlying chronic diseases, more severe clinical conditions such as pediatric acute respiratory distress syndrome and septic shock may occur.

Mortality Risk Factors Among Critically Ill Children With Acute COVID-19 in PICUs: A Multicenter Study From Turkish Pediatric Critical COVID-19 and MIS-C Study Group.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the world has a large number of reported COVID-19 cases and deaths. Information on characteristics and mortality rate of pediatric intensive care unit (PICU) cases with COVID-19 remains limited. This study aims to identify the risk factors for mortality related to COVID-19 in children admitted to PICU. METHODS: A retrospective multicenter cohort study was conducted between March 2020 and April 2021 at 44 PICUs in Turkey. Children who were 1 month-18-year of age with confirmed COVID-19 admitted to PICU were included in the study. Children with multisystem inflammatory syndrome and asymptomatic for COVID-19 were excluded. RESULTS: Of 335 patients with COVID-19, the median age was 6.8 years (IQR: 1.2-14) and 180 (53.7 %) were male, 215 (64.2 %) had at least one comorbidity. Age and gender were not related to mortality. Among 335 patients, 166 (49.5%) received mechanical ventilation, 17 (5.1%) received renal replacement therapy and 44 (13.1 %) died. Children with medical complexity, congenital heart disease, immunosuppression and malignancy had significantly higher mortality. On multivariable logistic regression analysis, organ failure index [odds ratio (OR): 2.1, 95 confidence interval (CI): 1.55-2.85], and having congenital heart disease (OR: 2.65, 95 CI: 1.03-6.80), were associated with mortality. CONCLUSIONS: This study presents detailed data on clinical characteristics and outcomes of patients with COVID-19 admitted to PICU in the first pandemic year in Turkey. Our study shows that having congenital heart disease is associated with mortality. In addition, the high organ failure score in follow-up predict mortality.

Increased Severe Cases and New-Onset Type 1 Diabetes Among Children Presenting With Diabetic Ketoacidosis During First Year of COVID-19 Pandemic in Turkey.

Introduction: There have been some significant changes regarding healthcare utilization during the COVID-19 pandemic. Majority of the reports about the impact of the COVID-19 pandemic on diabetes care are from the first wave of the pandemic. We aim to evaluate the potential effects of the COVID-19 pandemic on the severity of diabetic ketoacidosis (DKA) and new onset Type 1 diabetes presenting with DKA, and also evaluate children with DKA and acute COVID-19 infection. Methods: This is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year. Results: The percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p < 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p < 0.0001) and also higher among children with new onset Type 1 diabetes (p < 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission. Discussion: The frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.

Clinical features and outcomes of 76 patients with COVID-19-related multi-system inflammatory syndrome in children.

OBJECTIVES: Multi-system inflammatory syndrome in children (MIS-C) is a less understood and a rare complication of coronavirus disease-2019 (COVID-19). Given the scarce data regarding this novel disease, we aimed to describe the clinical features and outcomes of our patients with MIS-C and to evaluate the associated factors for the pediatric intensive care unit (PICU) admission. METHODS: The MIS-C patients under 18 years old diagnosed and treated in three referral centers between July 2020 and March 2021 were included. Data of the patients were retrospectively obtained from their medical records. RESULTS: Overall, 76 subjects (24 females) with a mean age of 8.17 ± 4.42 years were enrolled. Twenty-seven (35.5%) patients were admitted to the PICUs. The two most common systemic involvement patterns were cardiac and gastrointestinal. There was only one lethal outcome in a patient with underlying acute lymphoblastic leukemia. Those with higher procalcitonin levels at admission were found to stay longer in the hospital (r = 0.254, p = 0.027). The risk of PICU admission increased with age (aOR: 1.277; 95% CI: 1.089-1.498; p = 0.003) and with decreased initial serum albumin levels (aOR: 0.105; 95% CI: 0.029-0.378; p = 0.001). CONCLUSION: Although there is a wide clinical variability among the patients with MIS-C, we suggest that those with older age and lower initial serum albumin levels merit close monitoring due to their higher risk for PICU admission. Key Points • Although there is a wide variability regarding the management process among clinicians, MIS-C is a rare, severe, less understood complication of COVID-19 that may cause rapid clinical deterioration in the patients. • Clinicians should be aware of this condition in children with persistent fever and a family history of COVID-19. • Older age and low serum albumin levels are the independent predictors for the pediatric intensive care unit admission among MIS-C patients.

Infections with Carbapenem-Resistant Gram-Negative Bacteria are a Serious Problem Among Critically Ill Children: A Single-Centre Retrospective Study.

Children in paediatric intensive care units (PICUs) are vulnerable to infections because invasive devices are frequently used during their admission. We aimed to determine the prevalence, associated factors, and prognosis of infections in our PICU. This retrospective study evaluated culture results from 477 paediatric patients who were treated in the PICU between January 2014 and March 2019. Ninety patients (18.9%) had bacterial infections, with gram-negative bacteria being the predominant infectious agents. Culture-positive patients were younger than culture-negative patients, and age was related to mortality and various clinical factors. Culture-positive bacterial infections in the PICU were associated with increased use of invasive mechanical ventilation (odds ratio(OR); 2.254), red blood cell (RBC) transfusions (OR:2.624), and inotropic drugs (OR:2.262). Carbapenem resistance was found in approximately one-third of gram-negative bacteria, and was most common in tracheal aspirate specimens and cases involving Klebsiella spp. Total parenteral nutrition was a significant risk factor (OR:5.870). Positive blood culture results were associated with poorer patient survival than other culture results. These findings indicate that infections, especially those involving carbapenem-resistant bacteria, are an important issue when treating critically ill children.

Can Nebulised Colistin Therapy Improve Outcomes in Critically Ill Children with Multi-Drug Resistant Gram-Negative Bacterial Pneumonia?

In the past decade, multidrug-resistant (MDR) gram-negative bacteria have become a major problem, especially for patients in intensive care units. Recently, colistin became the last resort therapy for MDR gram-negative bacteria infections. However, nebulised colistin use was limited to adult patients. Thus, we investigated the efficacy and safety of nebulised colistin treatment against MDR microorganisms in the paediatric intensive care unit (PICU). Data of all patients admitted for various critical illnesses (January 2016 to January 2019) were reviewed. Differences between groups (with and without a history of nebulised colistin) were compared. Of 330 patients, 23 (6.97%) used nebulised colistin. Significant relationships were found between nebulised colistin usage and several prognostic factors (inotropic drug use (p = 0.009), non-invasive mechanical ventilation (p ≤ 0.001), duration in PICU (p ≤ 0.001), and C-reactive protein level (p = 0.003)). The most common microorganism in tracheal aspirate and sputum cultures was Pseudomonas aeruginosa (13 patients). The most common underlying diagnosis was cystic fibrosis, noted in 6 patients. No serious nephrotoxicity and neurotoxicity occurred. This study showed that colistin can be safely used directly in the airway of critically ill children. However, nebulised colistin use did not have a positive effect on mortality and prognosis.