Hemolytic-uremic syndrome: 24 years' experience of a pediatric nephrology unit / Síndrome hemolítico-urêmica: 24 anos de experiência de uma unidade de nefrologia pediátrica

Abstract Introduction: A better understanding of hemolytic-uremic syndrome (HUS) pathophysiology significantly changed its treatment and prognosis. The aim of this study is to characterize the clinical features, severity, management, and outcomes of HUS patients. Materials and Methods: Retrospective study of HUS patients admitted to a Pediatric Nephrology Unit between 1996 and 2020. Demographic and clinical data regarding etiology, severity, treatment strategies, and patient outcome were collected. Results: Twenty-nine patients with HUS were admitted to our unit, but four were excluded. Median age at diagnosis was two years (2 months - 17 years). Clinical manifestations included diarrhea, vomiting, oliguria, hypertension, and fever. During the acute phase, 14 patients (56%) required renal replacement therapy. Infectious etiology was identified in seven patients (five Escherichia coli and two Streptococcus pneumoniae). Since 2015, 2/7 patients were diagnosed with complement pathway dysregulation HUS and there were no cases of infectious etiology detected. Six of these patients received eculizumab. The global median follow-up was 6.5 years [3 months-19.8 years]. One patient died, seven had chronic kidney disease, four of whom underwent kidney transplantation, one relapsed, and seven had no sequelae. Conclusion: These results reflect the lack of infectious outbreaks in Portugal and the improvement on etiological identification since genetic testing was introduced. The majority of patients developed sequels and mortality was similar to that of other countries. HUS patients should be managed in centers with intensive care and pediatric nephrology with capacity for diagnosis, etiological investigation, and adequate treatment. Long-term follow-up is essential.

Resumo Introdução: Um melhor entendimento da fisiopatologia da síndrome hemolítico-urêmica (SHU) mudou significativamente seu tratamento e prognóstico. Este estudo teve como objetivo caracterizar condições clínicas, gravidade, manejo e desfechos de pacientes com SHU. Materiais e Métodos: Estudo retrospectivo de pacientes com SHU admitidos numa Unidade de Nefrologia Pediátrica entre 1996-2020. Foram coletados dados demográficos e clínicos sobre etiologia, gravidade, estratégias de tratamento, desfechos de pacientes. Resultados: 29 pacientes com SHU foram admitidos em nossa unidade, mas quatro foram excluídos. A idade mediana ao diagnóstico foi dois anos (2 meses-17 anos). Manifestações clínicas incluíram diarreia, vômitos, oligúria, hipertensão e febre. Durante a fase aguda, 14 pacientes (56%) necessitaram de terapia renal substitutiva. Identificou-se a etiologia infecciosa em sete pacientes (cinco Escherichia coli; dois Streptococcus pneumoniae). Desde 2015, 2/7 pacientes foram diagnosticados com SHU por desregulação da via do complemento e não foram detectados casos de etiologia infecciosa. Seis desses pacientes receberam eculizumab. A mediana global de acompanhamento foi 6,5 anos [3 meses-19,8 anos]. Um paciente faleceu, sete apresentaram doença renal crônica, sendo quatro submetidos a transplante renal, uma recidiva e sete sem sequelas. Conclusão: Estes resultados refletem a ausência de surtos infecciosos em Portugal e a melhoria na identificação etiológica desde que os testes genéticos foram introduzidos. A maioria dos pacientes desenvolveu sequelas e a mortalidade foi semelhante à de outros países. Pacientes com SHU devem ser manejados em centros com cuidados intensivos e nefrologia pediátrica com capacidade para diagnóstico, investigação etiológica e tratamento adequado. O acompanhamento alongo prazo é essencial.

Hemolytic-uremic syndrome: 24 years' experience of a pediatric nephrology unit.

INTRODUCTION: A better understanding of hemolytic-uremic syndrome (HUS) pathophysiology significantly changed its treatment and prognosis. The aim of this study is to characterize the clinical features, severity, management, and outcomes of HUS patients. MATERIALS AND METHODS: Retrospective study of HUS patients admitted to a Pediatric Nephrology Unit between 1996 and 2020. Demographic and clinical data regarding etiology, severity, treatment strategies, and patient outcome were collected. RESULTS: Twenty-nine patients with HUS were admitted to our unit, but four were excluded. Median age at diagnosis was two years (2 months - 17 years). Clinical manifestations included diarrhea, vomiting, oliguria, hypertension, and fever. During the acute phase, 14 patients (56%) required renal replacement therapy. Infectious etiology was identified in seven patients (five Escherichia coli and two Streptococcus pneumoniae). Since 2015, 2/7 patients were diagnosed with complement pathway dysregulation HUS and there were no cases of infectious etiology detected. Six of these patients received eculizumab. The global median follow-up was 6.5 years [3 months-19.8 years]. One patient died, seven had chronic kidney disease, four of whom underwent kidney transplantation, one relapsed, and seven had no sequelae. CONCLUSION: These results reflect the lack of infectious outbreaks in Portugal and the improvement on etiological identification since genetic testing was introduced. The majority of patients developed sequels and mortality was similar to that of other countries. HUS patients should be managed in centers with intensive care and pediatric nephrology with capacity for diagnosis, etiological investigation, and adequate treatment. Long-term follow-up is essential.

ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis.

PURPOSE: Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. METHODS: A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. RESULTS: 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations. CONCLUSIONS: Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance.

Inborn Errors of Metabolism in a Tertiary Pediatric Intensive Care Unit.

Few studies exist describing resources and care of pediatric patients with inborn errors of metabolism (IEM) admitted to pediatric intensive care unit (PICU). This study aims to characterize the PICU admissions of these patients to provide better diagnostic and therapeutic care in the future. Retrospective analysis of pediatric patients with IEM admitted to the PICU of a tertiary care center at a metabolic referral university hospital from 2009 to 2019 was included. Clinical information and demographic data were collected from PICU clinical records. During this period, 2% ( n = 88 admissions, from 65 children) out of 4,459 PICU admissions had clinical features of IEM. The median age was 3 years (range: 3 days-21 years) and 33 were male. Median age at diagnosis was 3 months; 23/65 patients with intoxication disorders, 21/65 with disorders of energy metabolism, 17/65 with disorders of complex molecules, and 4/65 with other metabolic diseases (congenital lipodystrophy, Menkes' disease, hyperammonemia without a diagnosis). From a total of 88 admissions, 62 were due to metabolic decompensation (infection-38, neonatal period decompensation-14, external accident-5, prolonged fasting-2, and therapeutic noncompliance-3) and 26 elective admissions after a scheduled surgery/elective procedure. The most frequent clinical presentations were respiratory failure (30/88) and neurological deterioration (26/88). Mechanical ventilation was required in 30 patients and parenteral nutrition in 6 patients. Extracorporeal removal therapy was required in 16 pediatric patients (12 with maple syrup urine disease and 4 with hyperammonemia) with a median duration of 19 hours. The median length of PICU stay was 3.6 days (3 hours-35 days). Eight patients died during the studied period (cerebral edema-2, massive hemorrhage-5, and malignant arrhythmia-1). Acute decompensation was the main cause of admission in PICU in these patients. The complexity of these diseases requires specialized human and technical resources, with an important impact on the recovery and survival of these patients.

Extracorporeal Membrane Oxygenation: The First 10 Years Experience of a Portuguese Pediatric Intensive Care Unit.

INTRODUCTION: In Portugal, extracorporeal membrane oxygenation (ECMO) is used in pediatric patients since 2010. The aim of this study was to describe the clinical characteristics of patients, indications, complications and mortality associated with the use of ECMO during the first 10-years of experience in the Pediatric Intensive Care Unit located in Centro Hospitalar Universitário Lisboa Norte. MATERIAL AND METHODS: Retrospective observational cohort study of all patients supported with ECMO in a Pediatric Intensive Care Unit, from the 1st of May 2010 up to 31st December 2019. RESULTS: Sixty-five patients were included: 37 neonatal (≤ 28 days of age) and 28 pediatric patients (> 28 days). In neonatal cases, congenital diaphragmatic hernia was the main reason for ECMO (40% of neonatal patients and 23% of total). Among pediatric patients, respiratory distress was the leading indication for ECMO (47% of total). The median length of ECMO support was 12 days. Clinical complications were more frequent than mechanical complications (65% vs 35%). Among clinical complications, access site bleeding was the most prevalent with 38% of cases. The overall patient survival was 68% at the time of discharge (65% for neonatal and 71% for pediatric cases), while the overall survival rate in Extracorporeal Life Support Organization registry was 61%. The number of ECMO runs has been increasing since 2011, even though in a non-linear way (three cases in 2010 to 11 cases in 2019). DISCUSSION: In the first 10 years we received patients from all over the country. Despite continuous technological developments, circuitrelated complications have a significant impact. The overall survival rate in the Pediatric Intensive Care Unit was not inferior to the one reported by the Extracorporeal Life Support Organization. CONCLUSION: The overall survival of our Pediatric Intensive Care Unit is not inferior to one reported by other international centers. Our experience showed the efficacy of the ECMO technique in a Portuguese centre.

Introdução: Em Portugal, a oxigenação por membrana extracorporal (ECMO) é utilizado em doentes pediátricos de forma consistente desde 2010. O nosso objetivo é descrever as características clínicas, indicações, complicações e sobrevivência associadas à utilização da ECMO nos primeiros 10 anos de experiência na nossa unidade. Material e Métodos: Estudo de coorte retrospetivo dos doentes tratados com ECMO na Unidade de Cuidados Intensivos Pediátricos do Hospital de Santa Maria, de 1 de maio de 2010 a 31 de dezembro de 2019. Resultados: Foram incluídos 65 doentes: 37 neonatais (≤ 28 dias de idade) e 28 pediátricos (> 28 dias). Nos neonatais, a hérnia diafragmática congénita foi a principal indicação (40% dos recém-nascidos e 23% do total). Relativamente aos doentes pediátricos, a insuficiência respiratória constituiu a principal indicação para ECMO (47% do total). A mediana de duração da técnica foi de 12 dias. As complicações clínicas foram mais frequentes do que as mecânicas (65% vs 35%). Entre as complicações clínicas, a hemorragia no local de acesso foi a mais frequente (38% dos casos). A sobrevivência global do total da amostra foi de 68% no momento da alta (65% nos neonatais e 71% nos pediátricos), enquanto que a sobrevivência descrita no registo da Extracorporeal Life Support Organization é de 61%. O número de casos de utilização de ECMO tem vindo a aumentar desde 2011, embora de forma não linear (três casos em 2010 para 11 casos em 2019). Discussão: Nos primeiros 10 anos de experiência em ECMO na Unidade de Cuidados Intensivos Pediátricos recebemos doentes oriundos de várias partes do país. Apesar da evolução tecnológica contínua, as complicações relacionadas com o circuito têm um impacto significativo. A taxa de sobrevida global no nosso centro não foi inferior à reportada no relatório da Extracorporeal Life Support Organization. Conclusão: A sobrevida global na Unidade de Cuidados Intensivos Pediátricos não é inferior à descrita no registo internacional. A nossa experiência demonstra a eficácia da ECMO num centro Português.

The Impact of Focused Cardiac Ultrasound Performed by Pediatric Intensivists: A Prospective Study.

OBJECTIVES: Focused cardiac ultrasound is an echocardiographic method used by medical intensivists for fast and reliable hemodynamic assessment. Prospective studies and guidelines have defined its role in adult critical care. Data regarding its use in pediatric critical care are scarce. This is the first prospective study that aims to evaluate its impact in this setting. METHODS: This is a single-center prospective study performed in a tertiary referral hospital pediatric intensive care unit (PICU). For a period of 6 months, when performing an echocardiogram, pediatric intensivists filled out a questionnaire that included the patient's clinical data and indication for the examination. The intensivists had to record both the clinical impression regarding that indication and therapeutic plan before and after the echocardiogram. All the patients with an echocardiogram performed by the pediatric intensive care unit medical staff were included. RESULTS: There were 80 echocardiograms performed on 35 patients during the study period. The most common patient diagnostic groups were respiratory infections (38%, n = 30) and septic shock (21%, n = 17). The main indication for the examination was assessment of intravascular volume status and left ventricular systolic function. After the echocardiogram, the clinical impression was maintained in 49% (n = 39) and changed in 44% (n = 35). There were new findings unrelated to the initial evaluation in 7% (n = 6). The planned treatment was maintained in 55% (n = 44) and changed in 45% (n = 36). CONCLUSIONS: The echocardiogram changed the clinical impression and therapeutic plan in almost half of the patients. These data show the value of focused cardiac ultrasound as a diagnostic and hemodynamic monitoring tool in pediatric intensive care and emphasize the importance of a rigorous training program.

[ECMO in Neonates with Congenital Diaphragmatic Hernia: The Experience of a Portuguese ECMO Referral Center]. / ECMO em Recém-nascidos com Hérnia Diafragmática Congénita: A Experiência de um Centro de Referência de ECMO em Portugal.

INTRODUCTION: The use of extracorporeal membrane oxygenation (ECMO) is considered by many authors as one of the most important technological advances in the care of newborns with congenital diaphragmatic hernia. The main objective of this study was to report the experience of a Portuguese ECMO center in the treatment of congenital diaphragmatic hernia. MATERIAL AND METHODS: Descriptive retrospective study of newborns with congenital diaphragmatic hernia requiring ECMO support in a Pediatric Intensive Care Unit from January 2012 to December 2019. Data collection using the Extracorporeal Life Support Organization registration and unit data base. RESULTS: Fourteen newborns were included, all with left congenital diaphragmatic hernia, in a total of 15 venoarterial ECMO cycles. The median gestational age was 38 weeks and the median birth weight was 2.950 kg. Surgical repair was performed before entry into ECMO in six, during in seven and after in one newborn. The average age at placement was 3.3 days and the median cycle duration was 16 days. Prior to ECMO, all newborns had severe hypoxemia and acidosis despite optimized ventilatory support, with nitric oxide and inotropic therapy. After 24 hours on ECMO, there was correction of acidosis, improvement of oxygenation and hemodynamic stability. All cycles presented mechanical complications, the most frequent being the presence of clots in the circuit. The most frequent physiological complications were hemorrhagic and embolic (three newborns suffered an ischemic stroke during the cycle). Five newborns (35.7%) died, all associated with complications (two strokes, two massive bleedings and one accidental decannulation). Chronic lung disease, poor weight gain and psychomotor developmental delay were the most frequent long-term morbidities. DISCUSSION: Despite technological advances in respiratory care and improved safety of the ECMO technique, the management of these newborns is complex and there are still several open questions, including the appropriate selection of patients, the best approach and time for surgical correction, and the treatment of pulmonary hypertension in the presence of persistent fetal shunts. CONCLUSION: Survival rate was higher than reported in 2017 Extracorporeal Life Support Organization report (64% versus 50%). Mechanical and hemorrhagic complications were very frequent.

Introdução: A utilização de oxigenação por membrana extracorporal (ECMO) é considerada por muitos autores como um dos maisimportantes avanços tecnológicos nos cuidados de recém-nascidos com hérnia diafragmática congénita. O principal objetivo deste estudo foi reportar a experiência de um centro de oxigenação por membrana extracorporal português no tratamento de hérnia diafragmática congénita.Material e Métodos: Estudo retrospetivo descritivo dos recém-nascidos com hérnia diafragmática congénita com necessidade de suporte de ECMO, numa unidade de Cuidados Intensivos Pediátricos de janeiro de 2012 a dezembro de 2019. Colheita de dados com recurso ao registo da Extracorporeal Life Support Organization e registo da unidade.Resultados: Incluídos 14 recém-nascidos, todos com hérnia diafragmática congénita esquerda, num total de 15 ciclos de ECMO veno-arterial. Mediana de idade gestacional de 38 semanas e de peso ao nascer de 2,950 kg. A correção cirúrgica foi realizada antes da entrada em ECMO em seis, durante em sete e após ciclo em um caso. A mediana de idade de colocação foi de 3,3 dias e a média de duração do ciclo foi de 16 dias. Previamente à ECMO, todos os recém-nascidos apresentavam hipoxemia e acidose grave apesar de suporte ventilatório otimizado, com terapêutica com oxido nítrico e inotrópicos. Após 24 horas em ECMO, verificou-se correção de acidose, melhoria de oxigenação e estado hemodinâmico. Todos os ciclos apresentaram complicações mecânicas, sendo a mais frequente a presença de coágulos no circuito. As complicações fisiológicas mais frequentes foram as hemorrágicas e embólicas (três recém-nascidos sofreram acidente vascular cerebral isquémico durante o ciclo). Cinco crianças (35,7%) morreram, estando todos os casos associados a complicações (duas com acidente vascular cerebral, duas com hemorragia maciça e uma descanulação acidental). A doença pulmonar crónica, má progressão ponderal e atraso do desenvolvimento psicomotor foram as morbilidades a longo prazo mais frequentes.Discussão: Apesar dos avanços tecnológicos nos cuidados respiratórios e melhoria da segurança da técnica ECMO, o manuseamento destes recém-nascidos é complexo e existem ainda várias questões em aberto, incluindo a selecção apropriada dos doentes, amelhor abordagem e tempo de correcção cirúrgica, e o tratamento da hipertensão pulmonar na presença de shunts fetais persistentes.Conclusão: A taxa de sobrevivência foi superior à reportada no relatório da Extracorporeal Life Support Organization de 2017 (64% vs 50%). As complicações mecânicas e hemorrágicas foram muito prevalentes.

Salicylate Intoxication in an Infant: A Case Report.

In children, the most common cause of an elevated anion gap (AG) with ketonemia, ketonuria, hyperglycemia, and glycosuria is diabetic ketoacidosis. However, when the clinical history is not clear, other causes must be considered. A 9-month-old girl was transferred to our pediatric intensive care unit (PICU) because of severe metabolic acidosis. On admission, she presented with Kussmaul breathing, tachycardia, irritability, and fever. Blood gasses revealed metabolic acidosis with superimposed respiratory alkalosis and elevated AG. Fluid replacement and bicarbonate for urine alkalinization were started. Ketonemia, acidic urine with glycosuria, ketonuria, and high blood glucose prompted an insulin infusion. Measurement of plasma salicylate confirmed toxic levels. When confronted, the parents admitted to accidentally preparing the child's bottle with water containing salicylic acid 1000 mg. Although the incidence of salicylate intoxication has declined, it remains an important cause of pediatric morbidity and mortality.

Sleep deprivation and accidental fall risk in children.

OBJECTIVES: To look for an association between sleep deprivation and risk of accidental falls (AF) in children. METHODS: A questionnaire was applied to two groups of children aged 1-14 years, encompassing children observed in an emergency room for AF (G1) and children attending health care visits (HV) (G2). Collected data included demographic characteristics, medical history, previous week's sleep pattern (PWSP), sleep duration and sleep pattern in the preceding 24 h, mechanism of fall, and injury severity. EXCLUSION CRITERIA: acute or chronic disease or exposure to drugs interfering with sleep. Statistical analyses included Fisher's exact test, Pearson Chi-square, Fisher-Freeman-Halton test, T and Mann-Whitney tests for independent samples, and multivariate logistic regression (α=5%). RESULTS: We obtained 1756 questionnaires in G1 and 277 in G2. Of those, 834 in G1 and 267 in G2 were analyzed. We found an increased risk of AF in boys (OR 1.6; 95% CI 1.2-2.4). After controlling for age, gender, summer holidays, parental education and profession, lack of naps and PWSP were associated with increased risk (OR 2.1; 95% CI 1.3-3.3 and OR 2.7; 95% CI 1.2-6.1). In 3-5 year-old children there was an association between AF and a shorter than usual sleep duration in the previous 24 h (p=0.02). CONCLUSIONS: To our knowledge, our study is the largest so far to assess the association between sleep deprivation and childhood injury. It evidences a protective effect of naps in children. Sleep duration of less than 8 h increases risk of AF. Pre-schoolers may be particularly susceptible to sleep deprivation.

[Subdural empyema due to gemella morbillorum as a complication of acute sinusitis]. / Empiema subdural a gemella morbillorum como complicação de sinusite aguda.

Subdural empyema is a life-threatening infection that may complicate acute sinusitis. The authors report the case of a previously healthy 10 year-old girl who presented with subdural empyema due to Gemella morbillorum after an untreated maxillary, ethmoidal and esphenoidal sinusitis. Despite immediate drainage of the empyema and underlying primary infection and treatment with broad spectrum antibiotics, she later developed frontal cerebritis and refractory intracranial hypertension, needing urgent decompressive craniectomy. She recovered gradually, maintaining to date slight right hemyparesis and aphasia. Even though it is considered a low virulence organism, G. morbillorum has been increasingly described in central nervous system infection. In this case, the prompt institution of broad spectrum antibiotics and surgical drainage, as well as the agressive treatment of complications, including decompressive craniectomy, were crucial to the patient's recovery.