Risk Factors Associated with Intensive Care Admission in Children with Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome (MIS-C) in Latin America: A Multicenter Observational Study of the REKAMLATINA Network.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment.

The association between prolonged capillary refill time and microcirculation changes in children with sepsis.

BACKGROUNDS: In children with sepsis, circulatory shock and multi-organ failure remain major contributors to mortality. Prolonged capillary refill time (PCRT) is a clinical tool associated with disease severity and tissue hypoperfusion. Microcirculation assessment with videomicroscopy represents a promising candidate for assessing and improving hemodynamic management strategies in children with sepsis. Particularly when there is loss of coherence between the macro and microcirculation (hemodynamic incoherence). We sought to evaluate the association between PCRT and microcirculation changes in sepsis. METHODS: This was a prospective cohort study in children hospitalized with sepsis. Microcirculation was measured using sublingual video microscopy (capillary density and flow and perfused boundary region [PBR]-a parameter inversely proportional to vascular endothelial glycocalyx thickness), phalangeal tissue perfusion, and endothelial activation and glycocalyx injury biomarkers. The primary outcome was the association between PCRT and microcirculation changes. RESULTS: A total of 132 children with sepsis were included, with a median age of two years (IQR 0.6-12.2). PCRT was associated with increased glycocalyx degradation (PBR 2.21 vs. 2.08 microns; aOR 2.65, 95% CI 1.09-6.34; p = 0.02) and fewer 4-6 micron capillaries recruited (p = 0.03), with no changes in the percentage of capillary blood volume (p = 0.13). Patients with hemodynamic incoherence had more PBR abnormalities (78.4% vs. 60.8%; aOR 2.58, 95% CI 1.06-6.29; p = 0.03) and the persistence of these abnormalities after six hours was associated with higher mortality (16.5% vs. 6.1%; p < 0.01). Children with an elevated arterio-venous CO2 difference (DCO2) had an abnormal PBR (aOR 1.13, 95% CI 1.01-1.26; p = 0.03) and a lower density of small capillaries (p < 0.05). Prolonged capillary refill time predicted an abnormal PBR (AUROC 0.81, 95% CI 0.64-0.98; p = 0.03) and relative percentage of blood in the capillaries (AUROC 0.82, 95% CI 0.58-1.00; p = 0.03) on admission. A normal CRT at 24 h predicted a shorter hospital stay (aOR 0.96, 95% CI 0.94-0.99; p < 0.05). CONCLUSIONS: We found an association between PCRT and microcirculation changes in children with sepsis. These patients had fewer small capillaries recruited and more endothelial glycocalyx degradation. This leads to nonperfused capillaries, affecting oxygen delivery to the tissues. These disorders were associated with hemodynamic incoherence and worse clinical outcomes when the CRT continued to be abnormal 24 h after admission.

Association between mechanical ventilation parameters and mortality in children with respiratory failure on ECMO: a systematic review and meta-analysis.

Background: In refractory respiratory failure (RF), extracorporeal membrane oxygenation (ECMO) is a salvage therapy that seeks to reduce lung injury induced by mechanical ventilation. The parameters of optimal mechanical ventilation in children during ECMO are not known. Pulmonary ventilatory management during this therapy may impact mortality. The objective of this study was to evaluate the association between ventilatory parameters in children during ECMO therapy and in-hospital mortality. Methods: A systematic search of PubMed/MEDLINE, Embase, Cochrane, and Google Scholar from January 2013 until May 2022 (PROSPERO 450744), including studies in children with ECMO-supported RF assessing mechanical ventilation parameters, was conducted. Risk of bias was assessed using the Newcastle-Ottawa scale; heterogeneity, with absence <25% and high >75%, was assessed using I2. Sensitivity and subgroup analyses using the Mantel-Haenszel random-effects model were performed to explore the impact of methodological quality on effect size. Results: Six studies were included. The median age was 3.4 years (IQR: 3.2-4.2). Survival in the 28-day studies was 69%. Mechanical ventilation parameters associated with higher mortality were a very low tidal volume ventilation (<4 ml/kg; OR: 4.70; 95% CI: 2.91-7.59; p < 0.01; I2: 38%), high plateau pressure (mean Dif: -0.70 95% CI: -0.18, -0.22; p < 0.01), and high driving pressure (mean Dif: -0.96 95% CI: -1.83, -0.09: p = 0.03). The inspired fraction of oxygen (p = 0.09) and end-expiratory pressure (p = 0.69) were not associated with higher mortality. Patients who survived had less multiple organ failure (p < 0.01). Conclusion: The mechanical ventilation variables associated with higher mortality in children with ECMO-supported respiratory failure are high plateau pressures, high driving pressure and very low tidal volume ventilation. No association between mortality and other parameters of the mechanical ventilator, such as the inspired fraction of oxygen or end-expiratory pressure, was found. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023450744, PROSPERO 2023 (CRD42023450744).

Evaluation of the Renal Angina Index to Predict the Development of Acute Kidney Injury in Children With Sepsis Who Live in Middle-Income Countries.

OBJECTIVE: The renal angina index (RAI) provides a clinically feasible and applicable tool to identify critically ill children at risk of severe acute kidney injury (AKI) in high-income countries. Our objective was to evaluate the performance of the RAI as a predictor of the development of AKI in children with sepsis in a middle-income country and its association with unfavorable outcomes. METHODS: This is a retrospective cohort study in children with sepsis hospitalized in the pediatric intensive care unit (PICU) between January 2016 and January 2020. The RAI was calculated 12 hours after admission to predict the development of AKI and at 72 hours to explore its association with mortality, the need for renal support therapy, and PICU stay. RESULTS: We included 209 PICU patients with sepsis with a median age of 23 months (interquartile range, 7-60). We found that 41.1% of the cases (86/209) developed de novo AKI on the third day of admission (KDIGO 1, 24.9%; KDIGO 2, 12.9%; and KDIGO 3, 3.3%).Overall mortality was 8.1% (17/209), higher in patients with AKI (7.7% vs 0.5%, P < 0.01). The RAI on admission was able to predict the presence of AKI on day 3 (area under the curve (AUC), 0.87; sensitivity, 94.2%; specificity, 100%; P < 0.01), with a negative predictive value greater than 95%. An RAI greater than 8 at 72 hours was associated with a greater risk of mortality (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 2.0-3.2; P < 0.01), a need for renal support therapy (aOR, 2.9; 95% CI, 2.3-3.6; P < 0.01), and a PICU stay of more than 10 days (aOR, 1.54; 95% CI, 1.1-2.1; P < 0.01). CONCLUSIONS: The RAI on the day of admission is a reliable and accurate tool for predicting the risk of developing AKI on day 3, in critically ill children with sepsis in a limited resource context. A score greater than eight 72 hours after admission is associated with a higher risk of death, the need for renal support therapy, and PICU stay.

A Multicenter Study on the Clinical Characteristics and Outcomes Among Children With Moderate to Severe Abusive Head Trauma.

INTRODUCTION: We aimed to identify clinical characteristics, risk factors for diagnosis, and describe outcomes among children with AHT. METHODS: We performed an observational cohort study in tertiary care hospitals from 14 countries across Asia and Ibero-America. We included patients <5 years old who were admitted to participating pediatric intensive care units (PICUs) with moderate to severe traumatic brain injury (TBI). We performed descriptive analysis and multivariable logistic regression for risk factors of AHT. RESULTS: 47 (12%) out of 392 patients were diagnosed with AHT. Compared to those with accidental injuries, children with AHT were more frequently < 2 years old (42, 89.4% vs 133, 38.6%, p < 0.001), more likely to arrive by private transportation (25, 53.2%, vs 88, 25.7%, p < 0.001), but less likely to have multiple injuries (14, 29.8% vs 158, 45.8%, p = 0.038). The AHT group was more likely to suffer subdural hemorrhage (SDH) (39, 83.0% vs 89, 25.8%, p < 0.001), require antiepileptic medications (41, 87.2% vs 209, 60.6%, p < 0.001), and neurosurgical interventions (27, 57.40% vs 143, 41.40%, p = 0.038). Mortality, PICU length of stay, and functional outcomes at 3 months were similar in both groups. In the multivariable logistic regression, age <2 years old (aOR 8.44, 95%CI 3.07-23.2), presence of seizures (aOR 3.43, 95%CI 1.60-7.36), and presence of SDH (aOR 9.58, 95%CI 4.10-22.39) were independently associated with AHT. CONCLUSIONS: AHT diagnosis represented 12% of our TBI cohort. Overall, children with AHT required more neurosurgical interventions and the use of anti-epileptic medications. Children younger than 2 years and with SDH were independently associated with a diagnosis of AHT. TYPE OF STUDY: Observational cohort study. LEVEL OF EVIDENCE: III.

Association between fluid overload and mortality in children with sepsis: a systematic review and meta-analysis.

BACKGROUND: Sepsis is one of the main causes of morbidity and mortality worldwide. Fluid resuscitation is among the most common interventions and is associated with fluid overload (FO) in some patients. The objective of this systematic review and meta-analysis was to summarise the available evidence on the association between FO and morbimortality in children with sepsis. METHODS: A systematic search was carried out in PubMed/Medline, Embase, Cochrane and Google Scholar up to December 2022 (PROSPERO 408148), including studies in children with sepsis which reported more than 10% FO 24 hours after admission to intensive care. The risk of bias was assessed using the Newcastle-Ottawa scale. Heterogeneity was assessed using I2, considering it absent if <25% and high if >75%. A sensitivity analysis was run to explore the impact of the methodological quality on the size of the effect. Mantel-Haenszel's model of random effects was used for the analysis. The primary outcome was to determine the risk of mortality associated with FO and the secondary outcomes were the need for mechanical ventilation (MV), multiple organ dysfunction syndrome (MODS) and length of hospital stay associated with FO. RESULTS: A total of 9 studies (2312 patients) were included, all of which were observational. Children with FO had a higher mortality than patients without overload (46% vs 26%; OR 5.06; 95% CI 1.77 to 14.48; p<0.01). We found no association between %FO and the risk of MODS (OR: 0.97; 95% CI 0.13 to 7.12; p=0.98). Children with FO required MV more often (83% vs 47%; OR: 4.78; 95% CI 2.51 to 9.11; p<0.01) and had a longer hospital stay (8 days (RIQ 6.5-13.2) vs 7 days (RIQ 6.1-11.5); p<0.01). CONCLUSION: In children with sepsis, more than 10% FO 24 hours after intensive care admission is associated with higher mortality, the need for MV and length of hospital stay.

The association between hypoalbuminemia and microcirculation, endothelium, and glycocalyx disorders in children with sepsis.

OBJECTIVE: The objective of this study was to evaluate the association between serum albumin levels and microcirculation changes, glycocalyx degradation, and the clinical outcomes of interest. METHODS: Observational, prospective study in children with sepsis. The primary outcome was the association between hypoalbuminemia and microcirculation disorders, endothelial activation and glycocalyx degradation using a perfused boundary region (PBR) (abnormal >2.0 µm on sublingual video microscopy) or plasma biomarkers (syndecan-1, angiopoietin-2). RESULTS: A total of 125 patients with sepsis were included. The median age was 2.0 years (IQR 0.5-12.5). Children with hypoalbuminemia had more abnormal microcirculation with a higher PBR (2.16 µm [IQR 2.03-2.47] vs. 1.92 [1.76-2.28]; p = .01) and more 4-6 µm capillaries recruited (60% vs. 40%; p = .04). The low albumin group that had the worst PBR had the most 4-6 µm capillaries recruited (rho 0.29; p < .01), 48% higher Ang-2 (p = .04), worse annexin A5 (p = 0.03) and no syndecan-1 abnormalities (p = .21). Children with hypoalbuminemia and a greater percentage of blood volume in their capillaries needed mechanical ventilation more often (56.3% vs. 43.7%; aOR 2.01 95% CI 1.38-3.10: p < .01). CONCLUSIONS: In children with sepsis, an association was found between hypoalbuminemia and microcirculation changes, vascular permeability, and greater endothelial glycocalyx degradation.

A brief history of crystalloids: the origin of the controversy.

Fluid resuscitation with crystalloids has been used in humans for more than 100 years. In patients with trauma, sepsis or shock of any etiology, they can help modify the clinical course of the illness. However, these solutions are medications which are not side-effect free. Recently, they have been questioned in terms of quantity (fluid overload) and their composition. The most frequently used crystalloids, both in high and low-income countries, are 0.9% normal saline (NS) and Ringer's lactate. The first descriptions of the use of sodium and water solutions in humans date from the cholera epidemic which spread throughout Europe in 1831. The composition of the fluids used by medical pioneers at that time differs greatly from the 0.9% NS used routinely today. The term "physiological solution" referred to fluids which did not cause red blood cell hemolysis in amphibians in in vitro studies years later. 0.9% NS has an acid pH, a more than 40% higher chloride concentration than plasma and a strong ion difference of zero, leading many researchers to consider it an unbalanced solution. In many observational studies and clinical trials, this 0.9% NS composition has been associated with multiple microcirculation and immune response complications, acute kidney injury, and worse clinical outcomes. Ringer's lactate has less sodium than plasma, as well as other electrolytes which can cause problems in patients with traumatic brain injury. This review provides a brief summary of the most important historical aspects of the origin of the most frequently used intravenous crystalloids today.

Metagenomics by next-generation sequencing (mNGS) in the etiological characterization of neonatal and pediatric sepsis: A systematic review.

Introduction: Pediatric and neonatal sepsis is one of the main causes of mortality and morbidity in these age groups. Accurate and early etiological identification is essential for guiding antibiotic treatment, improving survival, and reducing complications and sequelae. Currently, the identification is based on culture-dependent methods, which has many limitations for its use in clinical practice, and obtaining its results is delayed. Next-generation sequencing enables rapid, accurate, and unbiased identification of multiple microorganisms in biological samples at the same time. The objective of this study was to characterize the etiology of neonatal and pediatric sepsis by metagenomic techniques. Methods: A systematic review of the literature was carried out using the PRISMA-2020 guide. Observational, descriptive, and case report studies on pediatric patients were included, with a diagnostic evaluation by clinical criteria of sepsis based on the systemic inflammatory response, in sterile and non-sterile biofluid samples. The risk of bias assessment of the observational studies was carried out with the STROBE-metagenomics instrument and the CARE checklist for case reports. Results and Discussion: Five studies with a total of 462 patients were included. Due to the data obtained from the studies, it was not possible to perform a quantitative synthesis (meta-analysis). Based on the data from the included studies, the result identified that mNGS improves the etiological identification in neonatal and pediatric sepsis, especially in the context of negative cultures and in the identification of unusual microorganisms (bacteria that are difficult to grow in culture, viruses, fungi, and parasites). The number of investigations is currently limited, and the studies are at high risk of bias. Further research using this technology would have the potential to improve the rational use of antibiotics.

In vitro comparison of marginal infiltration between a conventional resin and a bulk-fill resin, in the relocation of cervical margins technique / Comparación in vitro de la infiltración marginal entre una resina convencional y una resina bulk-fill, en la técnica de reubicación de márgenes cervicales

Introduction: Proximal lesions that exceed the cement enamel limit (ACE) under the gingival margin complicate impressions and the adhesive technique. Compare the magnitude of micro infiltration between conventional resin and bulk fill resin in the cervical margin relocation technique. Materials and Methods: 48 samples of human teeth re-ceived two preparations: occluso-mesial (OM) and occluso-distal (OD) under LAC; first they received the cervical margin relocation technique (RMC) with bulk fill and conventional resin; then restored with semi-direct resinous inlays. Sample analysis: immersion in 50% colloidal silver nitrate solution, 24 hours, 37°C and cut mesiodistally. Observed under a stereoscopic magnifying glass to assess dye penetration and digitally photographed, analyzed with "Image J" software. Results: Sample of 96 cavities in two groups of 48 units; control group restored with conventional resin with incremental technique and study group restored with bulk fill resin, mono-incremental technique. Probabilistic sampling. No statistically significant diffe-rences in percentage of microinfiltrated area between Filtek™ Z250™ and Filtek™ Bulk Fill™ (p-value= 0.68). Discussion: Various studies show that the presence of marginal microinfiltration exist independent of: restorative technique, consistency, adhesive mechanism and polyme-rization technique. The research carried out is no exception, observing a similar degree for both systems. Conclusions: Results allow us to conclude that conventi-onal resin and bulk fill resin did not show significant differences in microleakage percentages for the RMC technique. Outside the study framework, bulk fill resins would have comparative advantages; better behavior against light in depths greater than 2 mm, less sensitivity to the "C" factor, and less clinical time.

Introducción: Las lesiones proximales que superan el límite cemento esmalte (ACE) por debajo del margen gingival complican las impresiones y la técnica adhesiva. Comparar la magnitud de la microinfiltración entre la resina convencional y la resina de relleno en la técnica de reubicación del margen cervical. Materiales y Métodos: 48 muestras de dientes humanos recibieron dos preparaciones: ocluso-mesial (OM) y ocluso-distal (OD) bajo LAC, primero recibieron la técnica de reubicación del margen cervical (RMC) con relleno en bloque y resina convencional; luego restaurado con incrustaciones resinosas semidirectas. Análisis de la muestra: inmersión en solución de nitrato de plata coloidal al 50%, 24 horas, 37°C y corte mesiodistal. Observado bajo una lupa estereoscópica para evaluar la penetración del tinte y fotografiado digitalmente, analizado con el software "Image J". Resultados: Muestra de 96 cavidades en dos grupos de 48 unidades; grupo control restaurado con resina convencional con técnica incremental y grupo estudio restaurado con resina bulk fill, técnica mono-incremental. Muestreo probabilístico. No hubo diferencias estadísticamente significativas en el porcentaje de área microinfiltrada entre Filtek™ Z250™ y Filtek™ Bulk Fill™ (p-value = 0,68) Discusión: Diversos estudios evidencian presencia de microinfiltración marginal, independiente de técnica restauradora, consistencia, mecanismo adhesivo y técnica polimerizadora. La investigación realizada no es excepción, observándose grado similar para ambos sistemas. Conclusiones: Los resultados permiten concluir que resina convencional y resina bulk fill no presentaron diferencias significativas en porcentajes de microinfiltración para técnica RMC. Fuera del marco del estudio, resinas bulk fill tendrían ventajas comparativas; mejor comportamiento frente a la luz en profundidades superiores a 2 mm, menor sensibilidad al factor "C", y menor tiempo clínico.

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

OBJECTIVES: To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. DESIGN: A single-center prospective cohort study from January to December 2021. SETTING: Twelve medical-surgical PICU beds at a university hospital. PATIENTS: Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. CONCLUSIONS: Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. DESIGN: A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. MEASUREMENTS AND MAIN RESULTS: A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). CONCLUSION: Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.

Capillary refill time in sepsis: A useful and easily accessible tool for evaluating perfusion in children.

The international sepsis guidelines emphasize the importance of early identification along with the combined administration of fluids, antibiotics and vasopressors as essential steps in the treatment of septic shock in childhood. However, despite these recommendations, septic shock mortality continues to be very high, especially in countries with limited resources. Cardiovascular involvement is common and, in most cases, determines the outcomes. Early recognition of hemodynamic dysfunction, both in the macro and microcirculation, can help improve outcomes. Capillary refill time (CRT) is a useful, available and easily accessible tool at all levels of care. It is a clinical sign of capillary vasoconstriction due to an excessive sympathetic response which seeks to improve blood redistribution from the micro- to the macrocirculation. An important reason for functionally evaluating the microcirculation is that, in septic shock, the correction of macrocirculation variables is assumed to result in improved tissue perfusion. This has been termed "hemodynamic coherence." However, this coherence often does not occur in advanced stages of the disease. Capillary refill time is useful in guiding fluid resuscitation and identifying more seriously affected sepsis patients. Several factors can affect its measurement, which should preferably be standardized and performed on the upper extremities. In this review, we seek to clarify a few common questions regarding CRT and guide its correct use in patients with sepsis.

Kawasaki disease in Colombia: A systematic review and contrast with multisystem inflammatory syndrome in children associated with COVID-19

Introduction: Kawasaki disease (KD) is an acute vasculitis with multisystem involvement. Recently, the increasing incidence of a condition that closely resembles KD in many cases, named multisystem inflammatory syndrome in children (MIS-C), has set off alarms amid the current worldwide coronavirus disease-19 (COVID-19) pandemic. Hence, the aim is to conduct a systematic review of the literature about KD in Colombia and contrast it with COVID-19-related MIS-C. Materials and methods: A search was carried out in both international and Latin American electronic databases for publications concerning patients with KD in the Colombian population. Records were then screened by titles and/or abstracts, assessed for eligibility, and reviewed. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. The search included studies reporting MIS-C associated with COVID-19, and compared these patients with our findings of KD in Colombia. Results: Out of 36 publications retrieved, 17 were included, representing 120 individuals. Male to female ratio was 1.6, and most patients (90.4%) were aged 5 years or less. Among the main features of KD, fever was the most frequent (96.2% of the patients), while cervical lymphadenopathy was present in only 40.6%. Intravenous immunoglobulin was administered in 91.4% cases and 6.2% were resistant. Cardiac involvement was found in around 30%, and 20% had coronary artery lesions. Comparison between MIS-C associated with COVID-19 and KD in Colombia indicates that patients affected by MIS-C were older (72.2% of MIS-C patients > 5 years), had higher rates of cardiac involvement, and required critical care more often. Conclusions: Our findings of KD in Colombia are consistent with the available descriptions of KD in the scientific literature. Given the increasing rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in Colombia and Latin America, our study raises awareness about MIS-C in pediatric patients with COVID-19 and its relationship with KD.

Introducción: La enfermedad de Kawasaki (EK) es una vasculitis aguda con compromiso multisistémico. Recientemente, la incidencia creciente de una condición que se asemeja en forma considerable a la EK en muchos casos, denominada síndrome inflamatorio multisistémico (SIMS) en niños, ha encendido las alarmas en medio de la actual pandemia mundial de la enfermedad COVID-19. Por consiguiente, nos propusimos realizar una revisión sistemática de la literatura acerca de la EK en Colombia y contrastarla con el SIMS relacionado con COVID-19 en niños. Materiales y métodos: Buscamos publicaciones respecto a pacientes con EK en población colombiana, en bases de datos electrónicas tanto internacionales como latinoamericanas. Los registros hallados fueron tamizados por títulos o resúmenes, evaluados para elegibilidad y revisados. Se siguieron las guías Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Posteriormente, buscamos estudios que reportaran SIMS temporalmente asociado con COVID-19 en niños y comparamos estos pacientes con nuestros hallazgos de EK en Colombia. Resultados: De 36 publicaciones encontradas se incluyeron 17, las cuales representaron 120 individuos. La razón hombre a mujer fue de 1,6 y la mayoría de los pacientes (90,4%) tenía 5 anos o menos. Entre las principales características de EK, la fiebre fue la más frecuente (96,2%), mientras que la linfadenopatía cervical estuvo presente solo en el 40,6%. La inmunoglobulina intravenosa se administró en el 91,4% de los casos y 6,2% presentaron resistencia. Se encontró compromiso cardiaco en alrededor del 30% de los pacientes, en tanto que el 20% tuvo lesiones de arterias coronarias. La comparación entre las características clínicas de la EK y el SIMS asociado a COVID-19 mostró que los individuos afectados por el SIMS eran mayores (72,2% con SIMS tenían más de cinco anos), tuvieron mayores índices de compromiso cardiaco y requirieron cuidado crítico con mayor frecuencia. Conclusiones: Nuestros hallazgos de EK en Colombia son consistentes con las descripciones disponibles de esta enfermedad en la literatura científica. Debido al aumento de infección por SARS-CoV-2 en Colombia y Latinoamérica, nuestro estudio busca crear conciencia sobre el SIMS en pacientes pediátricos con COVID-19 y su relación con la EK.

Estrategia ventilatoria para el aclaramiento de dióxido de carbono en un lactante con hipercapnia incontrolable / Ventilatory strategy for carbon dioxide clearance in an infant with persistent hypercapnia / Estratégia ventilatória para depuração de dióxido de carbono em uma criança com hipercapnia incontrolável

Resumen Se presenta la experiencia de combinar la ventilación convencional y una técnica modificada de insuflación de gas paratraqueal para evitar complicaciones de la insuflación traqueal directa en un lactante con hipercapnia refractaria, quien ingresó con falla respiratoria aguda secundaria a neumonía multilobar. Al iniciar la ventilación mecánica presentó neumotórax, fístulas broncopleurales y acidemia hipercápnica refractaria a tratamiento convencional. Se inició insuflación de gas paratraqueal en ventilación convencional en modo de presión control, con 10 L/min de aire humidificado con una presión control máxima sostenida de 20 cmH2O. Tres horas después se observó una mejoría de la gasometría arterial y pasadas 72 horas se logró retirar el dispositivo paratraqueal sin complicaciones, con adecuada evolución clínica. Al no incluir un catéter intratraqueal se evitaron complicaciones conservando los mecanismos que mejoran la oxigenación e hipercapnia. La técnica presentada es prometedora; sin embargo, se deben realizar estudios con un mayor número de individuos.

Abstract The experience of combining conventional ventilation and a modified paratracheal gas insufflation technique to avoid complications is presented. An infant with acute respiratory failure secondary to multilobar pneumonia who after start off mechanical ventilation developed pneumothorax, bronchopleural fistulas, and persistent hypercapnic acidemia refractory to conventional ventilatory strategies. It was decided to initiate paratracheal gas insufflation in conventional ventilation in pressure control mode, with 10 L/min of humidified air with a maximum sustained control pressure of 20 cmH2O. Three hours after an improvement in arterial blood gas was recorded and after 72 hours the paratracheal device was removed without complications, with adequate clinical evolution. By not incorporate an intratracheal catheter some complications are avoided, preserving the mechanisms that improve oxygenation and CO2 elimination. Paratracheal gas insufflation is a promising technique, although more studies are required with a greater number of individuals.

Resumo Apresenta-se a experiência de combinar ventilação convencional e técnica modificada de insuflação de gás paratraqueal para evitar complicações da insuflação traqueal direta em uma criança com hipercapnia refratária que foi admitido com insuficiência respiratória aguda secundária a pneumonia multilobar. Ao iniciar ventilação mecânica, apresentou pneumotórax, fístulas broncopleurais e acidemia hipercápnica refratária ao tratamento convencional. A insuflação de gás paratraqueal foi iniciada em ventilação convencional no modo de controle de pressão, com 10 L/min de ar umidificado com pressão de controle máxima sustentada de 20 cmH2O. Três horas após, observou-se melhora da gasometria arterial e após 72 horas o dispositivo paratraqueal foi retirado sem intercorrências, com evolução clínica adequada. Ao não incluir um cateter intratraqueal, as complicações foram evitadas, preservando os mecanismos que melhoram a oxigenação e a hipercapnia. A técnica apresentada é promissora, porém, estudos com um número maior de indivíduos devem ser realizados.

Endothelial Damage in Sepsis: The Importance of Systems Biology.

The early diagnosis and appropriate stratification of sepsis continues to be one of the most important challenges in modern medicine. Single isolated biomarkers have not been enough to improve diagnostic and prognostic strategies and to progress toward therapeutic goals. The information generated by the human genome project has allowed a more holistic approach to the problem. The integration of genomics, transcriptomics, proteomics and metabolomics in sepsis has allowed us to progress in the knowledge of new pathways which are pathophysiologically involved in this disease. Thus, we have understood the importance of and complex interaction between the inflammatory response and the endothelium. Understanding the role of important parts of the microcirculation, such as the endothelial glycocalyx and its interaction with the inflammatory response, has provided early recognition elements for clinical practice that allow the rational use of traditional medical interventions in sepsis. This comprehensive approach, which differs from the classical mechanistic approach, uses systems biology to increase the diagnostic and prognostic spectrum of endothelial damage biomarkers in sepsis, and to provide information on new pathways involved in the pathophysiology of the disease. This, in turn, provides tools for perfecting traditional medical interventions, using them at the appropriate times according to the disease's pathophysiological context, while at the same time discovering new and improved therapeutic alternatives. We have the challenge of transferring this ideal scenario to our daily clinical practice to improve our patients' care. The purpose of this article is to provide a general description of the importance of systems biology in integrating the complex interaction between the endothelium and the inflammatory response in sepsis.

Latin American Consensus on the Management of Sepsis in Children: Sociedad Latinoamericana de Cuidados Intensivos Pediátricos [Latin American Pediatric Intensive Care Society] (SLACIP) Task Force: Executive Summary.

Objective: The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.

Association Between Unbalanced Solutions and Acute Kidney Injury During Fluid Resuscitation in Children With Sepsis.

OBJECTIVE: To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. DESIGN: An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. MEASUREMENTS AND MAIN RESULTS: Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis (P = 0.37), hyperchloremia (P = 0.11) and mortality (P = 0.25) between the 2 groups. CONCLUSION: In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.

Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with covid-19 in critically ill patients: an observational multicenter study (MISCO study).

BACKGROUND: The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes. METHODS: An observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C. RESULTS: There were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %). CONCLUSIONS: Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.

Consensus of the Respiratory Committee of the Latin American Society for Pediatric Intensive Care: Management of pediatric SARS-CoV-2. (SLACIP): COVID-19 Pediatric / Consenso del Comité Respiratorio Sociedad Latinoamericana Terapia Intensiva Pediátrica: Manejo SARS-CoV-2 pediátrico. (SLACIP): COVID-19 Pediátrico

Introduction The COVID-19 pandemic generated many controversies in the management of critically ill pediatric patients. The main ones were about ventilatory support, phenotypic differences between adults and children, and acute and subacute clinical forms. For this reason, the Respiratory Committee (RC) of the Latin American Society of Pediatric Intensive Care (SLACIP) generated a document to summarize the recommendations with the best evidence. The objective of these recommendations is to provide an update on issues related to pediatric COVID-19. Methods and Materials The Respiratory Committee created a group composed of 19 pediatric kinesiologists/physiotherapists and intensivists from 8 Latin American countries and defined on 3/27/20 the 15 most relevant topics, assigning 3 referents and 2 reviewers for each. The manuscripts went through 4 stages until their final version. The complete document was freely distributed on 22/05/20 and updated twice (07/08/20 and 02/09/21). For the current version there were 3 special collaborators. Result The material consists of a complete 94-page document and an executive summary. The topics included are case definition, epidemiology, clinical classification, subacute inflammatory syndrome, personal protective equipment, aerosolization situations (intubation, extubation, suctioning, sampling, filter replacement, cardiopulmonary resuscitation, early mobilization), high flow cannula support, invasive, non-invasive and high frequency mechanical ventilation, pharmacological treatment, laboratory and imaging. Conclusion The purpose of this document is to serve as a guide for nurses, kinesiologists/physiotherapists and physicians in the management of critically ill pediatric patients with COVID-19.

Introducción La pandemia por COVID-19 generó muchas controversias en el manejo de los pacientes pediátricos críticos. Las principales fueron sobre el soporte ventilatorio, las diferencias fenotípicas entre adultos y niños y las formas clínicas aguda y subaguda.Por esa razón el Comité Respiratorio (CR) de la Sociedad Latinoamericana de Cuidados Intensivos Pediátricos (SLACIP) generó un documento para resumir las recomendaciones con mayor evidencia. El objetivo de estas recomendaciones es brindar una actualización de temas relacionados a COVID-19 pediátrico.Métodos y Materiales El Comité Respiratorio creó un grupo compuesto por 19 kinesiólogos/fisioterapeutas y médicos intensivistas pediátricos de 8 países de Latinoamérica y definió el 27/03/20 los 15 temas más relevantes, asignando 3 referentes y 2 revisores por cada uno. Los manuscritos pasaron por 4 etapas hasta su versión final. El documento completo se distribuyó libremente el 22/05/20, actualizándose en dos oportunidades (07/08/20 y el 02/09/21). Para la versión actual se contó con 3 colaboradores especiales.Resultado El material se compone de un documento completo de 94 páginas y un resumen ejecutivo. Los temas incluidos son definición de caso, epidemiología, clasificación clínica, síndrome inflamatorio subagudo, equipos de protección personal, situaciones de aerosolización (intubación, extubación, aspiración, toma de muestras, recambio de filtros, reanimación cardiopulmonar, movilización temprana), soporte con cánula de alto flujo, ventilación mecánica invasiva, no invasiva y de alta frecuencia, tratamiento farmacológico, laboratorio e imágenes.Conclusión La elaboración de este documento ha tenido como fin servir de guía para enfermeros, kinesiólogos/fisioterapeutas y médicos en el manejo de pacientes pediátricos en estado crítico por COVID-19.