High-flow nasal cannula and non-invasive mechanical ventilation in pediatric asthma exacerbation: two-year prospective observational study in intensive care / Cánula nasal de alto flujo y ventilación no invasiva en asma pediátrico grave: estudio observacional prospectivo de dos años de duración en cuidados intensivos

Abstract Background: Asthma is a common cause of admission to the pediatric intensive care unit (PICU). We described and analyzed the therapies applied to children admitted to a tertiary PICU because of asthma. Later, we evaluated high-flow nasal cannula (HFNC) use in these patients and compared their evolution and complications with those who received non-invasive ventilation. Methods: We conducted a prospective observational study (October 2017-October 2019). Collected data: epidemiological, clinical, respiratory support therapy needed, complementary tests, and PICU and hospital stay. Patients were divided into three groups: (1) only HFNC; (2) HFNC and non-invasive mechanical ventilation (NIMV); and (3) only NIMV. Results: Seventy-six patients were included (39 female). The median age was 2 years and 1 month. The median pulmonary score was 5. The median PICU stay was 3 days, and the hospital stay was 6 days. Children with HNFC only (56/76) had fewer PICU days (p = 0.025) and did not require NIMV (6/76). Children with HFNC had a higher oxygen saturation/fraction of inspired oxygen ratio ratio (p = 0.025) and lower PCO2 (p = 0.032). In the group receiving both therapies (14/76), NIMV was used first in all cases. No epidemiologic or clinical differences were found among groups. Conclusion: HFNC was a safe approach that did not increase the number of PICU or hospital days. On admission, normal initial blood gases and the absence of high oxygen requirements were useful in selecting responders to HFNC. Further randomized and multicenter clinical trials are needed to verify these data.

Resumen Introducción: El asma es una causa frecuente de ingreso en la unidad de cuidados intensivos pediátricos (UCIP). En este, cuadro el uso de cánula nasal de alto flujo (CNAF) se ha visto extendido. En este trabajo se describe el tratamiento global en la UCIP ante el ingreso por asma en un hospital monográfico pediátrico y se evalúa la respuesta al uso de la CNAF, comparando la evolución de los pacientes con aquellos que recibieron ventilación no invasiva (VNI). Métodos: Se llevó a cabo un estudio observacional prospectivo (de octubre del 2017 a octubre del 2019). Se describieron epidemiología, clínica, tratamiento y soporte respiratorio. Para la comparación se crearon tres grupos de pacientes: 1) solo CNAF; 2) CNAF y VNI; y 3) solo VNI. Resultados: Se incluyeron 76 pacientes. La mediana de edad fue de dos años y un mes; la mediana de índice pulmonar fue 5. La mediana de ingreso en UCIP fue de tres días y de ingreso hospitalario, seis días. Los niños con solo CNAF (56/76) mostraron menos días de UCIP (p = 0.025) y no requirieron VNI (6/76). También mostraron mayor SatO2/FiO2 (saturación de oxígeno/fracción de oxígeno inspirado) (p = 0.025) y menor nivel de PCO2 (presión parcial de CO2) (p = 0.032). La VNI se utilizó primero siempre en el grupo que recibió ambas modalidades (14/76). No se encontraron diferencias epidemiológicas o clínicas entre grupos. Conclusiones: En nuestra serie, el uso de CNAF no aumentó los días de ingreso en la UCIP ni de hospital. Tampoco requirió cambio a VNI. Al ingreso, una gasometría normal y bajo requerimiento de oxígeno permitieron seleccionar a los pacientes respondedores. Se necesitan más ensayos multicéntricos clínicos aleatorizados para verificar estos datos.

Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain.

INTRODUCTION: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. METHODS: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. RESULTS: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5-16.5). Two children died. CONCLUSIONS: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data.

PIMS-TS immunophenotype: description and comparison with healthy children, Kawasaki disease and severe viral and bacterial infections.

BACKGROUND: A new clinical syndrome named Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) has been described. This new disease is a leading cause of hospital and paediatric intensive care unit (PICU). It has been related to immunity dysregulation. METHODS: Prospective-retrospective observational study to describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS (from March 2020 to September 2020). The immunophenotype was done through the expression analysis of these proteins of mononuclear cells: CD64, CD18, CD11a and CD11b. They were compared with previous healthy controls and children admitted to PICU because of bacterial infection, viral infection and Kawasaki disease (KD). Two hundred and forty-seven children were studied: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 KD and 13 PIMS-TS. RESULTS: PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p = .000). Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression (p = .000). Also, CD11a and CD11b were highly expressed (p =,000). CONCLUSION: We observed a differential cell innate signature in PIMS-TS. These findings are consistent with a proinflammatory status (CD64 elevated expression) and lymphocyte trafficking to tissues (CD11a and CD11b). More studies should be carried out to confirm our results.

Prevalence of thrombotic complications in children with SARS-CoV-2.

Knowledge of thrombosis in children with SARS-CoV-2 is scarce. In this multicentre national cohort of children with SARS-CoV-2 involving 49 hospitals, 4 patients out of 537 infected children developed a thrombotic complication (prevalence of 0.7% (95% CI: 0.2% to 1.9%) out of the global cohort and 1.1% (95% CI: 0.3% to 2.8%) out of the hospitalised patients). We describe their characteristics and review other published paediatric cases. Three out of the four patients were adolescent girls, and only two cases had significant thrombotic risk factors. In this paediatric cohort, D-dimer value was not specific enough to predict thrombotic complications. Adolescence and previous thrombotic risk factors may be considered when initiating anticoagulant prophylaxis on children with SARS-CoV-2 disease (COVID-19).

Epidemiología del traumatismo craneoencefálico grave pediátrico: 15 años de experiencia en una unidad de politraumatismos infantil / Epidemiology of severe head injuries in children: 15 years' experience in a pediatric polytrauma unit

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sRAGE as severe acute bronchiolitis biomarker, prospective observational study.

INTRODUCTION AND OBJECTIVES: Acute bronchiolitis (AB) is the leading cause of hospitalization in infants and around 5% require intensive care treatment. Early identification of children diagnosed with AB at a high risk of severe progression is of great interest. The receptor for advanced glycation end products (RAGE), highly expressed in lung tissue, regulates immune responses and inflammation, and its soluble form, sRAGE, is believed to have an anti-inflammatory role. We hypothesized serum sRAGE might be a major determinant of AB severity and prognosis. This study was conducted to measure serum sRAGE in infants with severe AB and to assess its correlation with clinical severity, immediate complications, and outcome. METHODS: Single-center, prospective, observational study of hospitalized children with severe bronchiolitis admitted to the Pediatric Intensive Care Unit (PICU), from September 2015 to September 2016. RESULTS: A total of 52 children and 27 controls were included. The cases age ranged from 11 days to 21 months, resulting in a significant age difference with controls (11.85 vs 4.84 months, P < .01). Serum levels of sRAGE were lower but not significant in severe AB patients than in controls (1350.93 vs 1450.42 pg/mL; P = .399). No correlation was found between serum sRAGE and causative viruses, clinical symptoms, Wood-Downes score (a clinical severity score) on admission, respiratory support, or length of hospital stay. Serum sRAGE was also lower in the cases having had a previous respiratory disease (1463.84 vs 1072.43 pg/mL; P = .049). However, it was higher in patients with any lung consolidation on the chest X-ray (1584.79 vs 1131.62 pg/mL; P = .044) and weakly positively correlated with classical biomarkers (maximum C-reactive protein, +0.295, P = .034; maximum procalcitonin, +0.309; P = .029). CONCLUSION: This single-center study reveals that sRAGE couldn't predict AB severity or outcome in children hospitalized at PICU. Nevertheless, it significantly increased in the presence of any lung consolidation and had a positive correlation with classical biomarkers. The utility of sRAGE in this population could be probably elucidated with a better understanding of AGE-RAGE axis.

Utility of the transcranial doppler in the evaluation and follow-up of children with Sturge-Weber Syndrome.

INTRODUCTION: Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with typical clinical features including seizures, chronic hemiplegia, hemianopsia and intellectual impairment. Progressive clinical decline may be attributable, at least in part, to progressive venous ischemia. Transcranial Doppler (TCD) ultrasonography could be useful to monitor the degree of hemodynamic involvement and its progression. PURPOSE: To determine whether there is an association between the degree of asymmetry in TCD and intensity of clinical and radiological involvement and whether there is a correlation between clinical changes and changes in serial TCD. METHODS: In fourteen SWS pediatric patients and two "possible cases" (infants younger than two years old without previously known brain involvement, but with other typical signs of SWS) mean flow velocity in the middle cerebral arteries (MCA) was measured by TCD in both hemispheres. The percent difference between hemispheres (asymmetry) was calculated. Clinical and radiological severity was scored using scales. The correlation between TCD asymmetry and SWS clinical and radiological scores was analyzed at baseline, as well as the correlation between the changes in the different variables (TCD asymmetry, clinical and radiological cores) during evolution and in relation to the changes due to therapy. RESULTS: The percentage of MCA velocity asymmetry was positively correlated with the clinical severity score (p = 0.04), and with seizure frequency (p = 0.014). Throughout evolution, therapeutic and clinical changes were associated with noticeable changes in transcranial doppler asymmetry in some cases. CONCLUSIONS: TCD may provide a noninvasive method to assess the severity of blood flow abnormalities at baseline and a method to monitor children for progressive changes over time.

Children in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital.

OBJECTIVES: Spain has been one of the countries most severely affected by the coronavirus disease 2019. This study aims to describe a series of children admitted to a PICU due to coronavirus disease 2019 infection. DESIGN: Prospective observational study. SETTING: Tertiary hospital in Madrid, Spain. PATIENTS: Children admitted to the PICU with severe acute respiratory syndrome coronavirus 2 (severe acute respiratory syndrome coronavirus 2) infection, from March 1, 2020, to April 15, 2020. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: Epidemiologic data, previous clinical characteristics, support therapy needed, imaging tests, laboratory observations on admission, and pharmacologic therapy. Eleven children were admitted to the PICU, with suspected coronavirus disease 2019; the polymerase chain reaction test was positive in seven. The median age was 100.7 months (range, 0.5-162). Five were admitted from the emergency department and two from the ward. The Pediatric Sequential Organ Failure Assessment score was 3 (range, 0-9), and Pediatric Risk of Mortality II score was 4 (range, 0-16). All children were previously healthy except one (allogeneic hematopoietic stem cell transplantation). Respiratory symptoms and fever were prevalent. A chest radiograph led to a pneumonia diagnosis. Not all patients presented with lymphopenia on admission. D-Dimer and ferritin were elevated. All patients needed oxygen therapy through a nasal cannula; five patients received high-flow nasal cannula therapy, which was later substituted with noninvasive ventilation in four. Mechanical ventilation was necessary in two patients on the first day of PICU admission. Two children required mechanical ventilation and inotropic support. Tocilizumab was applied in two intubated children. Also, four children received heparin. No patients died. CONCLUSIONS: On the whole, the children were previously healthy and are more than 1 year old. Respiratory symptoms were the leading cause of PICU admission, making respiratory support the principal therapy. Patients requiring mechanical ventilation showed deterioration on the first day of admission. These children seemed to require close monitoring, and multicenter studies are necessary.

Retrospective Study in Children With Necrotizing Pneumonia: Nine Years of Intensive Care Experience.

BACKGROUND: Although necrotizing pneumonia (NN) is one of the most feared complications of community-acquired pneumonia, data in pediatric patients are scarce. The objective of this article is to describe children admitted to pediatric intensive care unit (PICU) because of NN. METHODS: Retrospective-prospective observational study in children admitted with NN to PICU (from January 1, 2010, to December 31, 2018). The data collected included information on disease epidemiology, PICU management, respiratory assistance and disease evolution. RESULTS: Fifty-one children were included, 42 of 51 had received 7-valent or 13-valent pneumococcal vaccine. Median age was 3.2 years (1.9-4.2), 15 of 51 had signs of sepsis at admission. Forty-nine patients presented pleural effusion with drainage in 46. The most common respiratory support modality was high-flow oxygen nasal cannula (17/51). Computed tomography was the gold standard for diagnosis. Etiologic diagnosis was obtained in 34 of 51, and pneumococcus was isolated in 29 of 34. In all of these cases, initial detection was made by capsular antigen in pleural fluid. Children with pneumococcal NN had fewer days of evolution prior to PICU admission (P = 0.041). Cefotaxime with clindamycin was used in 49 of 51. Surgery was necessary in 3 of 51 patients. After PICU discharge, only 5 of 51 were readmitted. There were deaths. CONCLUSIONS: In our study, the NN was mainly observed in children around 3 years old. The main causal agent was pneumococcus. The evolution towards NN appeared to be faster than in case of other etiologies. Surgery management was unusual. All children required prolonged admissions but had a full clinical recovery.

Pediatric Disseminated Lemierre Syndrome in 2 Infants: Not Too Young for an Ancient Disease.

The Lemierre syndrome is characterized by an oropharyngeal infection, thrombosis of the internal jugular vein, and multiple septic metastases. Fusobacterium necrophorum is a common cause of it. The incidence is 0.6 to 2.3 cases per million with a mortality rate of 4% to 18%. Its fast evolution and the possibility of severe complications require a high index of suspicion for its diagnosis. We present 2 infants with Lemierre syndrome. The younger case, a 6-month-old infant, was fully recovered. In the other side, and despite an aggressive therapy, an 18-month-old infant developed cerebral palsy. We also provide a short literature review with a focus on clinical presentation and differential diagnosis in order to initiate an early and adequate therapy.

Decompressive craniectomy in 14 children with severe head injury: clinical results with long-term follow-up and review of the literature.

BACKGROUND: Decompressive craniectomy (DC) is a controversial therapeutic measure used in patients with intractable intracranial hypertension after severe head injury. This study describes the morbidity and mortality of DC in 14 children with a mean follow-up of 3.2 years. We review published evidence from the past 10 years on the indications for DC in pediatric brain trauma. We also examine timing, surgical technique, and the results of this procedure. METHOD: We retrospectively reviewed patients who underwent DC from 2002 to 2010. Clinical data were collected at admission, as were data on the indication for craniectomy, timing, and surgical technique. Perioperative intracranial pressure (ICP), complications of craniectomy, and Glasgow Outcome Scale score at 2 years were recorded as outcome variables. RESULTS: Fourteen craniectomies were performed. The median presenting Glasgow Coma Scale score was 6.5 (range, 4-15). Ten patients were presented with anisocoria. In 13 patients, craniectomy initially decreased ICP to <25 mm Hg. Two patients (14%) had a poor prognosis on admission and died. The most frequent complications were hygroma (8 patients) and infections (3 patients). The mean Glasgow Outcome Scale score at the 2-year follow-up visit was 4.4 (range, 4-5). Behavioral and psychiatric abnormalities and poor academic performance were frequent (82%). CONCLUSIONS: DC reduces ICP in pediatric patients with traumatic brain injury. The mortality rate is low and long-term prognosis in survivors is good. Complications related to surgery are frequent. Wide craniectomy with duraplasty seems to be the most common technique. Defining the most appropriate indications and timing for DC in pediatric patients should be the objective of future prospective studies.