Estudio de la sepsis pediátrica en el marco del estudio Envin-Helics : utilidad de los paquetes de medidas terapéuticas en el manejo de la sepsis grave y el shock séptico pediátricos

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 08-09-2022La sepsis es una entidad de gran importancia debido a su elevada incidencia y morbimortalidad. Las guías más recientes propuestas por la campaña Sobreviviendo a la Sepsis la definen como una disfunción orgánica con compromiso vital causada por una respuesta alterada del organismo frente a la infección. En los últimos años se ha insistido en mejorar las estrategias de diagnóstico precoz de la sepsis y en la búsqueda de paquetes de medidas terapéuticas para mejorar su pronóstico. El aumento de las infecciones relacionadas con la asistencia sanitaria y el aumento de los microorganismos multirresistentes suponen una dificultad adicional al manejo de los niños con sepsis en las Unidades de Cuidados Intensivos Pediátricos, debido a su rápida propagación y a que pueden producir un aumento de la morbimortalidad y del coste sanitario. Esto ha motivado el desarrollo de registros multicéntricos de vigilancia epidemiológica, como el ENVIN-HELICS pediátrico...Sepsis is a relevant disease in paediatrics due to its high incidence and associated morbidity and mortality, regardless of geographic location and socioeconomic status. The recent Surviving Sepsis Campaign guidelines define sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Recent research has been focused on improving early detection and the search for care bundles to improve sepsis prognosis.The increase in healthcare-related infections and the emergence of multi-drug resistant microorganisms pose an additional difficulty in the management of children with sepsis in Pediatric Intensive Care Units, due to their rapid spread and association with an increased morbidity, mortality, and healthcare costs. This has motivated the development of multicenter epidemiological surveillance registries, such as ENVIN-HELICS...Fac. de MedicinaTRUEunpu

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5–11.8) vs 3.4 years (IQR 0.4–9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5–8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients

Characteristics and management of patients with SARS‐CoV2 infection admitted to pediatric intensive care units: Data analysis of the Spanish national multicenter registry

Introduction The purpose of this study is to describe the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) disease characteristics and management in children admitted to the pediatric intensive care units (PICU). Methods The present study was based on a national multicentric prospective registry including PICU patients with SARS-CoV2 infection or symptoms of multisystem inflammatory syndrome in children (MIS-C). Results A total of 298 patients were admitted to 41 different Spanish PICUs. A total of 76% of them were previously healthy. The most frequent manifestation was MIS-C (69.8%). On admission, 59.4% of patients did not have respiratory distress, and only 17.4% needed conventional mechanical ventilation (MV). The need for MV was associated with age (incidence rate ratios [IRR] 1.21, p < .012), pediatric sequential organ failure assessment score (p-SOFA) Score (IRR 1.12, p = .001), and need for transfusion (IRR 4.5, p < .004) in MIS-C patients, and with vasoactive drug use (IRR 2.73, p = .022) and the diagnosis of acute respiratory distress syndrome (IRR 2.83, p = .018) in patients admitted for other reasons. During the first day of admission, 56% of patients met shock criteria and 50.7% needed vasoactive drugs. In MIS-C patients, their use was associated with higher p-SOFA score (IRR 1.06, p < .001) and with the diagnosis of shock (IRR 5.78, p < .001). In patients without MIS-C, it was associated with higher p-SOFA score (IRR 1.05, p = .022). The mortality rate was 3%, being lower in MIS-C patients compared to patients admitted for other reasons (0.5% vs. 9.4%, p < .001). It was also lower in previously healthy patients compared to patients with previous comorbidities (0.9% vs. 9.7%, p < .001). Conclusions Severe SARS-CoV2 infection is uncommon in the pediatric population. In our series, respiratory distress was rare, being MIS-C the most frequent cause of PICU admission related to SARS-CoV2. In most cases, the course of the disease was mild except in children with previous diseases.Instituto de Salud Carlos III (España)Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEpubAPC financiada por la UC

Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy

Objectives: Despite that piperacillin-tazobactam combination is commonly used in critically ill children, increasing evidence suggests that the current dosing schedules are not optimal for these patients. The aim of this work is to develop a population pharmacokinetic model for piperacillin to evaluate the efficacy of standard dosing in children with and without continuous kidney replacement therapy (CKRT) and to propose alternative dosing schemes maximizing target attainment. Methods: Four hundred twenty-nine piperacillin concentrations measured in different matrices, obtained from 32 critically ill children (19 without CKRT, 13 with CKRT) receiving 100 mg/kg of piperacillin/tazobactam every 8 hours (increased to 12 hours after the fourth dose) were modelled simultaneously using the population approach with NONMEM 7.4. The percentage of patients with 90% fT > MIC and target attainment (percentage of dosing interval above MIC) were estimated for different intermittent and continuous infusions in the studied population. Results: Piperacillin pharmacokinetic was best described with a two-compartment model. Renal, nonrenal, and hemofilter clearances were found to be influenced by the glomerular filtration rate, height (renal clearance), weight (nonrenal clearance), and filter surface (hemofilter clearance). Only seven (37%) children without CKRT and seven (54%) with CKRT achieved 90% fT > MIC with the current dosing schedule. Of the alternative regimens evaluated, a 24-hour continuous infusion of 200 mg/kg (CKRT) and 300 mg/kg (no CKRT) provided 100% fT > MIC (percent of time free drug remains above the minimum inhibitory concentration) (≤16 mg/L) and target attainments ≥90% across all evaluated MICs. Discussion: In children with and without CKRT, standard dosing failed to provide an adequate systemic exposure, while prolonged and continuous infusions showed an improved efficacy

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest

Abstract A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5–11.8) vs 3.4 years (IQR 0.4–9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5–8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients