Therapeutic plasma exchange in critically ill children: experience of the pediatric intensive care unit of two centers in Chile.

INTRODUCTION: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique used in a wide spectrum of diseases. We aim to review the indications, complications, and outcomes of critically ill children who received TPE and to compare a membrane versus centrifugal method in this cohort. METHODS: A retrospective observational study in two pediatric intensive care units in Chile during eight years (2011-2019) Results: A total of 36 patients underwent 167 TPE sessions (20 centrifugation and 16 membrane-based). The more frequent indications for TPE were autoimmune neurological diseases in 14 cases, renal diseases (9), and rheumatological disorders (5). 58 % of children received other immunomodulatory therapy. According to ASFA, 45 % of cases were I-II category, 50 % to III, and 5% not classified. Response to treatment was complete in 64 % (23/36) and partial in 33 % (12/36). Complications occurred in 17.4 % of sessions, and the most frequent was transient hypotension during the procedure. Overall survival at discharge from the PICU was 92 %. Patients who received TPE as a single therapy (n = 26) survived 96 %. The clinical outcomes between the two apheresis methods were similar. Survivors had a significantly lower PELOD score on admission (14.5 vs. 6.5, p = 0.004). CONCLUSIONS: TPE is mainly indicated as a rescue treatment in neurological autoimmune diseases refractory to conventional immunomodulatory treatment. Complications in critically ill children are mild and low. The outcome in children requiring TPE as a single therapy is good, and no differences were observed with centrifugation or membrane method.

Intercomunicación pulmón-riñón en el paciente crítico / Pulmonary-renal crosstalk in the critically ill patient

A pesar de los avances en el desarrollo de las terapias de reemplazo renal, la mortalidad de la falla renal aguda permanece elevada, especialmente, cuando se manifiesta simultáneamente con fallas orgánicas distantes, como es en el caso del síndrome de distrés respiratorio agudo. Se revisa la relación bidireccional deletérea entre pulmón y riñón, en el escenario de disfunción orgánica, la cual presenta aspectos clínicos relevantes de conocer. Se discuten los efectos renales del síndrome de distrés respiratorio agudo y del uso de la ventilación mecánica a presión positiva, siendo el daño inducido por este (ventilator induced lung injury) uno de los modelos utilizado frecuentemente para el estudio de la interacción pulmón-riñón. Se enfatiza el rol de la falla renal inducida por la ventilación mecánica (ventilator-induced kidney injury) en la patogenia de la falla renal aguda. Asimismo se analizan las repercusiones pulmonares de la falla renal aguda, reconociéndose que esta condición patológica induce un incremento en la permeabilidad vascular pulmonar, inflamación y alteración de los canales de sodio y agua del epitelio alveolar, entre otros efectos. Este modelo conceptual puede ser la base para el desarrollo de nuevas estrategias terapéuticas a utilizar en el paciente con síndrome de disfunción orgánica múltiple.

Despite advances in the development of renal replacement therapy, mortality of acute renal failure remains high, especially when occurring simultaneously with distant organic failure as it is in the case of the acute respiratory distress syndrome. In this update, birideccional deleterious relationship between lung and kidney on the setting of organ dysfunction is reviewed, which presents important clinical aspects of knowing. Specifically, the renal effects of acute respiratory distress syndrome and the use of positive-pressure mechanical ventilation are discussed, being ventilator induced lung injury one of the most common models for studying the lung-kidney crosstalk. The role of renal failure induced by mechanical ventilation (ventilator-induced kidney injury) in the pathogenesis of acute renal failure is emphasized. We also analyze the impact of the acute renal failure in the lung, recognizing an increase in pulmonary vascular permeability, inflammation, and alteration of sodium and water channels in the alveolar epithelial. This conceptual model can be the basis for the development of new therapeutic strategies to use in patients with multiple organ dysfunction syndrome.

[Pulmonary-renal crosstalk in the critically ill patient]. / Intercomunicación pulmón-riñón en el paciente crítico.

Despite advances in the development of renal replacement therapy, mortality of acute renal failure remains high, especially when occurring simultaneously with distant organic failure as it is in the case of the acute respiratory distress syndrome. In this update, birideccional deleterious relationship between lung and kidney on the setting of organ dysfunction is reviewed, which presents important clinical aspects of knowing. Specifically, the renal effects of acute respiratory distress syndrome and the use of positive-pressure mechanical ventilation are discussed, being ventilator induced lung injury one of the most common models for studying the lung-kidney crosstalk. The role of renal failure induced by mechanical ventilation (ventilator-induced kidney injury) in the pathogenesis of acute renal failure is emphasized. We also analyze the impact of the acute renal failure in the lung, recognizing an increase in pulmonary vascular permeability, inflammation, and alteration of sodium and water channels in the alveolar epithelial. This conceptual model can be the basis for the development of new therapeutic strategies to use in patients with multiple organ dysfunction syndrome.

[Septic shock in intensive care units. Current focus on treatment]. / Shock séptico en unidad de cuidados intensivos. Enfoque actual en el tratamiento.

Essential therapeutic principles in children with septic shock persist over time, although some new concepts have been recently incorporated, and fully awareness of pediatricians and intensivists is essential. Fluid resuscitation is a fundamental intervention, but the kind of ideal fluid has not been established yet, as each of these interventions has specific limitations and there is no evidence supportive of the superiority of one type of fluid. Should septic shock persists despite adequate fluid resuscitation, the use of inotropic medication and/or vasopressors is indicated. New vasoactive drugs can be used in refractory septic shock caused by vasopressors, and the use of hydrocortisone should be considered in children with suspected adrenal insufficiency, as it reduces the need for vasopressors. The indications for red blood cells transfusion or the optimal level of glycemia are still controversial, with no consensus on the threshold value for the use of these blood products or the initiation of insulin administration, respectively. Likewise, the use of high-volume hemofiltration is a controversial issue and further study is needed on the routine recommendation in the course of septic shock. Nutritional support is crucial, as malnutrition is a serious complication that should be properly prevented and treated. The aim of this paper is to provide update on the most recent advances as concerns the treatment of septic shock in the pediatric population.

[Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study]. / Predisposición genética y síndrome de distrés respiratorio agudo pediátrico: nuevas herramientas de estudio genético.

Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.

Shock séptico en unidad de cuidados intensivos: Enfoque actual en el tratamiento / Septic shock in intensive care units: Current focus on treatment

Los pilares terapéuticos del niño con shock séptico se mantienen en el tiempo, sin embargo, se han incorporado nuevos conceptos, siendo importante que el pediatra y el intensivista tengan conocimiento a cabalidad de ellos. La reanimación con fluidos es una intervención fundamental, no obstante, aún no se ha establecido un tipo de fluido ideal, presentando cada uno limitaciones específicas, no existiendo evidencia sobre la superioridad de un tipo de fluido. Si a pesar de una adecuada resucitación con fluidos persiste el shock, el inicio de inótropos y/o vasopresores está indicado. En caso de refractariedad al uso de vasopresores, nuevos fármacos vasoactivos pueden ser empleados y el uso de hidrocortisona debe considerarse en niños con sospecha de insuficiencia suprarrenal. Existe controversia respecto a la transfusión de glóbulos rojos o el nivel óptimo de glucemia, no existiendo consenso en el valor umbral para el uso de estos hemocomponentes o el inicio de insulina, respectivamente. Asimismo, la utilización de la hemofiltración de alto volumen (HFAV)aún permanece controversial, requiriendo mayores estudios para su recomendación en forma rutinaria en el curso de un shock séptico refractario. El soporte nutricional es primordial, ya que la desnutrición es una grave complicación que debe ser prevenida y tratada adecuadamente. El objetivo de la presente revisión es entregar una actualización en los más recientes avances en tratamiento del shock séptico en la población pediátrica.

Essential therapeutic principles in children with septic shock persist over time, although some new concepts have been recently incorporated, and fully awareness of pediatricians and intensivists is essential. Fluid resuscitation is a fundamental intervention, but the kind of ideal fluid has not been established yet, as each of these interventions has specific limitations and there is no evidence supportive of the superiority of one type of fluid. Should septic shock persists despite adequate fluid resuscitation, the use of inotropic medication and/or vasopressors is indicated. New vasoactive drugs can be used in refractory septic shock caused by vasopressors, and the use of hydrocortisone should be considered in children with suspected adrenal insufficiency, as it reduces the need for vasopressors. The indications for red blood cells transfusion or the optimal level of glycemia are still controversial, with no consensus on the threshold value for the use of these blood products or the initiation of insulin administration, respectively. Likewise, the use of high-volume hemofiltration is a controversial issue and further study is needed on the routine recommendation in the course of septic shock. Nutritional support is crucial, as malnutrition is a serious complication that should be properly prevented and treated. The aim of this paper is to provide update on the most recent advances as concerns the treatment of septic shock in the pediatric population.

Predisposición genética y síndrome de distrés respiratorio agudo pediátrico: nuevas herramientas de estudio genético / Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study

El síndrome de distrés respiratorio agudo (SDRA) es la forma más grave de falla respiratoria. Teóricamente, cualquier noxa pulmonar aguda puede resultar en un SDRA, pero solo un pequeño porcentaje de individuos desarrolla la enfermedad. Sobre este fundamento, factores genéticos han sido implicados en el riesgo de desarrollar SDRA. Basado en la fisiopatología de esta enfermedad, múltiples genes candidatos han sido evaluados como potenciales modificadores, tanto en pacientes como en modelos animales de SDRA. Datos experimentales y estudios clínicos recientes sugieren que variantes de genes implicados en procesos clave de daño tisular, celular y molecular pulmonar pueden influir en la predisposición y el pronóstico del SDRA. Sin embargo, la patogénesis del SDRA pediátrico es compleja y, en consecuencia, es posible anticipar que muchos genes pueden contribuir a ella. Variantes genéticas, tales como polimorfismos de nucleótido simple y variantes del número de copias, están probablemente asociadas con la predisposición al SDRA en niños con lesión pulmonar primaria. El estudio de asociación del genoma completo (GWAS, del inglés Genome-Wide Association Study) puede examinar estas variantes sin sesgos y ayudar a identificar nuevos genes fundamentales y vías patogénicas clave para futuros análisis. Esta aproximación también puede tener implicancias clínicas diagnósticas y terapéuticas, como predecir el riesgo del paciente o desarrollar un enfoque terapéutico personalizado para este grave síndrome.

Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.

[Ventilation strategies in the child with severe hypoxemic respiratory failure]. / Estrategias ventilatorias ante el niño con síndrome de distress respiratorio agudo e hipoxemia grave.

In this review, we assemble the fundamental concepts of the use of mechanical ventilation (MV) in children with acute respiratory failure (ARDS) and refractory hypoxemia. We also discusses topics of protective ventilation and recruitment potential, and specifically examine the options of ventilation and/or maneuvers designed to optimize the non-aerated lung tissue: alveolar recruitment maneuvers, positive end-expiratory pressure (PEEP) titulation, high frequency oscillatory ventilation (HFOV), airway pressure release ventilation (APRV), aimed at correcting the mismatch ventilation/perfusion (V/Q): use of prone position. The only pharmacological intervention analyzed is the use of neuromuscular blockers. In clinical practice, the protective MV concept involves using an individual adjustment of the PEEP and volume tidal (V(T)). Use of recruitment maneuvers and PEEP downward titration can improve lung function in patients with ARDS and severe hypoxemia. We must keep in mind HFOV instauration as early as possible in response to failure of MV. The use of early and prolonged prone can improve gas exchange in hopes of a better control of what caused the use of MV.

Fístula nefrobronquial en paciente pediátrico: caso clínico / Nephrobronchial fistula in pediatric patient. Case report

La fístula nefrobronquial es una complicación infrecuente de las infecciones renales, que ocurre habitualmente en pacientes adultos con pielonefritis xantogranulomatosa. Comunicamos el caso de una paciente de 12 años con antecedentes de mielomeningocele operado e infección urinaria recurrente, quien consultó con historia de cuatro semanas de fiebre, tos y disnea. Ingresó en shock séptico y presentó inundación de la vía aérea por pus, que le ocasionó episodio de asistolia. Mediante tomografía computarizada de abdomen, se diagnosticó extensa colección perirrenal izquierda. Se efectuó un drenaje percutáneo, que dio salida a pus y aire. TAC de tórax y abdomen mostró fístula transdiafragmática entre la base pulmonar izquierda y colección intraabdominal. Se realizó nefrectomía total. La paciente mostró mejoría progresiva poscirugía y regresión total de la sintomatología. Este infrecuente caso clínico en niños ilustra la importancia del diagnóstico precoz de infección urinaria en pacientes con patologías asociadas y de presentar un elevado índice de sospecha ante una complicación potencialmente letal

Nephrobronchial fistula is a rare complication of kidney infections, usually occurring in adult patients with xanthogranulomatous pyelonephritis and very occasionally in children. We reported a 12-year-old girl, with a history of myelomeningocele and recurrent urinary tract infection, who presented with a four-week fever, cough and dyspnea, developing septic shock and presenting flood of airway by pus which caused cardiac arrest. A diagnosis of left perirenal extensive collection was established by abdominal computed tomography (CT). The patient first had antibiotic therapy and percutaneous drainage was performed draining pus and air. Thoracic and abdominal CT scan was performed corroborating transdiaphragmatic fistula. Total nephrectomy was performed. The patient showed gradual improvement after surgery and total regression of symptoms. Pathologic examination concluded chronic pyelonephritis. This case report illustrates a rare complication in children, the importance of early diagnosis of urinary tract infection in patients with comorbidities and of exhibiting a high index of suspicion to a potentially lethal complication.

Shock séptico en la Unidad de Cuidados Intensivos: terapéutica avanzada, inmunoparálisis y genómica. Estado del arte / Septic shock in ICU: Advanced therapeutics, immunoparalysis and genomics. State of the art

En las últimas décadas, se han incorporado nuevos y trascendentes conceptos para el tratamiento avanzado del paciente en shock séptico. Se debe considerar el uso de terapia inmune en grupos seleccionados de pacientes. Las terapias de sustitución renal de carácter continuo son bien toleradas y su empleo precoz evita sobrecargas de fluidos. El uso de hemofiltración de alto volumen puede jugar un papel en el paciente séptico hiperdinámico. La plasmaféresis es útil en el paciente con disfunción multiorgánica. El empleo de soporte extracorpóreo se debe considerar en quienes presentan shock séptico refractario. La inmunoparálisis se ha asociado con infecciones nosocomiales y mortalidad tardía. La información obtenida de los marcadores genéticos puede permitir la búsqueda de una medicina basada en la genómica

New and important concepts have emerged for the advanced management of the child with septic shock in the recent decades. Attending physicians in the Pediatric intensive care unit must be fully aware of them to improve patient care in the critical care unit. It should be considered the use of immune therapy only in selected groups of patients. Continuous renal replacement therapies are well tolerated and their early use prevents deleterious fluid overload. Removal of inflammatory mediators by using high volume hemofiltration may play a role in hyperdynamic septic patients. The use of plasmapheresis is recommended in patients with thrombocytopenia-associated multiple organ failure. Extracorporeal support use should be considered in those with refractory septic shock despite goals directed therapy. The immunoparalysis has been associated with nosocomial infections and late mortality. The information from genetic markers may allow early intervention and preventive genomics-based medicine

Disfunción diafragmática inducida por ventilación mecánica / Ventilator-induced diaphragmatic dysfunction

The ventilator-induced diaphragmatic dysfunction is a group of disorders caused by the inactivity of the diaphragm muscle during controlled mechanical ventilation. From a structural point of view, the diaphragm subjected to mechanical ventilation undergoes an atrophy process, in which decreased synthesis and increased muscle protein degradation are observed. Recent research has identified different molecular signaling pathways that link both processes in the diaphragm, describing compelling evidence that shows that oxidative stress contributes to this phenomenon. Also, functional changes characterized by a reduction in stress and fatigue resistance, associated with an increase in the maximum shortening velocity are observed. The purpose of the present review is to analyze the impact of mechanical ventilation on the structure and function of the diaphragm muscle. Clinical implications and potential preventive steps are discussed. Since the duration of mechanical ventilation is the primary responsible for the absence of mechanical stimulation on the diaphragm, the use of ventilatory strategies for successful early weaning and early use of partial modalities should be the main pillars in the prevention of this condition.

La disfunción diafragmática inducida por ventilación mecánica consiste en un conjunto de alteraciones producidas por la inactividad del músculo diafragma durante la ventilación mecánica controlada. A nivel estructural, el diafragma sometido a ventilación mecánica experimenta un proceso de atrofia por desuso, en el que se observa una disminución de la síntesis y aumento en la degradación de proteínas musculares. Recientemente se han identificado diferentes rutas de señalización molecular que vinculan ambos procesos en el diafragma, existiendo evidencia fehaciente que el estrés oxidativo contribuye a este fenómeno. Concomitantemente, se han observado cambios funcionales caracterizados por una reducción de la fuerza y resistencia a la fatiga, asociado a un incremento en la velocidad máxima de acortamiento. El objetivo principal de esta revisión es analizar el impacto de la ventilación mecánica sobre la estructura y función del músculo diafragma. Además se discuten implicancias clínicas y potenciales intervenciones preventivas para esta emergente entidad. Dado que el tiempo de permanencia en ventilación mecánica controlada es el principal factor responsable de la ausencia de estímulo mecánico sobre el diafragma, el empleo de estrategias de destete ventilatorio precoz y el uso temprano de modalidades parciales, debieran constituir los pilares de su prevención.

[Septic shock in ICU: advanced therapeutics, immunoparalysis and genomics. State of the art]. / Shock séptico en la Unidad de Cuidados Intensivos: terapéutica avanzada, inmunoparálisis y genómica. Estado del arte.

New and important concepts have emerged for the advanced management of the child with septic shock in the recent decades. Attending physicians in the Pediatric intensive care unit must be fully aware of them to improve patient care in the critical care unit. It should be considered the use of immune therapy only in selected groups of patients. Continuous renal replacement therapies are well tolerated and their early use prevents deleterious fluid overload. Removal of inflammatory mediators by using high volume hemofiltration may play a role in hyperdynamic septic patients. The use of plasmapheresis is recommended in patients with thrombocytopenia-associated multiple organ failure. Extracorporeal support use should be considered in those with refractory septic shock despite goals directed therapy. The immunoparalysis has been associated with nosocomial infections and late mortality. The information from genetic markers may allow early intervention and preventive genomics-based medicine.

[Nephrobronchial fístula in pediatric patient: case report]. / Fístula nefrobronquial en paciente pediátrico: caso clínico.

Nephrobronchial fistula is a rare complication of kidney infections, usually occurring in adult patients with xanthogranulomatous pyelonephritis and very occasionally in children. We reported a 12-year-old girl, with a history of myelomeningocele and recurrent urinary tract infection, who presented with a four-week fever, cough and dyspnea, developing septic shock and presenting flood of airway by pus which caused cardiac arrest. A diagnosis of left perirenal extensive collection was established by abdominal computed tomography (CT). The patient first had antibiotic therapy and percutaneous drainage was performed draining pus and air. Thoracic and abdominal CT scan was performed corroborating transdiaphragmatic fistula. Total nephrectomy was performed. The patient showed gradual improvement after surgery and total regression of symptoms. Pathologic examination concluded chronic pyelonephritis. This case report illustrates a rare complication in children, the importance of early diagnosis of urinary tract infection in patients with comorbidities and of exhibiting a high index of suspicion to a potentially lethal complication.

[Ventilator-induced diaphragmatic dysfunction]. / Disfunción diafragmática inducida por ventilación mecánica.

The ventilator-induced diaphragmatic dysfunction is a group of disorders caused by the inactivity of the diaphragm muscle during controlled mechanical ventilation. From a structural point of view, the diaphragm subjected to mechanical ventilation undergoes an atrophy process, in which decreased synthesis and increased muscle protein degradation are observed. Recent research has identified different molecular signaling pathways that link both processes in the diaphragm, describing compelling evidence that shows that oxidative stress contributes to this phenomenon. Also, functional changes characterized by a reduction in stress and fatigue resistance, associated with an increase in the maximum shortening velocity are observed. The purpose of the present review is to analyze the impact of mechanical ventilation on the structure and function of the diaphragm muscle. Clinical implications and potential preventive steps are discussed. Since the duration of mechanical ventilation is the primary responsible for the absence of mechanical stimulation on the diaphragm, the use of ventilatory strategies for successful early weaning and early use of partial modalities should be the main pillars in the prevention of this condition.

Shock séptico en la Unidad de Cuidados Intensivos: terapéutica avanzada, inmunoparálisis y genómica. Estado del arte. / [Septic shock in ICU: advanced therapeutics, immunoparalysis and genomics. State of the art].

New and important concepts have emerged for the advanced management of the child with septic shock in the recent decades. Attending physicians in the Pediatric intensive care unit must be fully aware of them to improve patient care in the critical care unit. It should be considered the use of immune therapy only in selected groups of patients. Continuous renal replacement therapies are well tolerated and their early use prevents deleterious fluid overload. Removal of inflammatory mediators by using high volume hemofiltration may play a role in hyperdynamic septic patients. The use of plasmapheresis is recommended in patients with thrombocytopenia-associated multiple organ failure. Extracorporeal support use should be considered in those with refractory septic shock despite goals directed therapy. The immunoparalysis has been associated with nosocomial infections and late mortality. The information from genetic markers may allow early intervention and preventive genomics-based medicine.

Fístula nefrobronquial en paciente pediátrico: caso clínico. / [Nephrobronchial fístula in pediatric patient: case report].

Nephrobronchial fistula is a rare complication of kidney infections, usually occurring in adult patients with xanthogranulomatous pyelonephritis and very occasionally in children. We reported a 12-year-old girl, with a history of myelomeningocele and recurrent urinary tract infection, who presented with a four-week fever, cough and dyspnea, developing septic shock and presenting flood of airway by pus which caused cardiac arrest. A diagnosis of left perirenal extensive collection was established by abdominal computed tomography (CT). The patient first had antibiotic therapy and percutaneous drainage was performed draining pus and air. Thoracic and abdominal CT scan was performed corroborating transdiaphragmatic fistula. Total nephrectomy was performed. The patient showed gradual improvement after surgery and total regression of symptoms. Pathologic examination concluded chronic pyelonephritis. This case report illustrates a rare complication in children, the importance of early diagnosis of urinary tract infection in patients with comorbidities and of exhibiting a high index of suspicion to a potentially lethal complication.