Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock.

Background: The goal of fluid resuscitation and the use of inotropes in septic shock has traditionally focused on improving blood pressure and cardiac output, without considering the microcirculatory changes. Reaching macrocirculatory goals but with persistent microcirculatory abnormalities (hemodynamic incoherence) in septic shock has been associated with greater organ dysfunction and mortality. The objective of this study was to evaluate the microcirculation (flow and capillary density) and endothelial glycocalyx changes associated with the use of milrinone in children with septic shock, as well as their relationship with clinical variables and organ dysfunction. Methods: A prospective cohort study from February 2022 to January 2023 at a university hospital (Fundación Cardioinfantil-Instituto de Cardiología). Sublingual video microscopy was used to evaluate capillary density, microvascular flow rates and perfused boundary region (PBR-inverse parameter of glycocalyx thickness-abnormal if >2.0 microns). The primary outcome was the association between microcirculation and endothelial glycocalyx changes related to the use of milrinone. Results: A total of 140 children with a median age of two years [interquartile range (IQR) 0.58-12.1] were included. About 57.9% (81/140) of the patients received milrinone infusions. Twenty-four hours after receiving milrinone, the patients maintained functional capillary density (P<0.01) and capillary recruitment capacity (P=0.04) with no changes in capillary blood volume versus those who did not receive milrinone. Children under two years old who received milrinone had better 4-6-micron capillary density than older children [odds ratio (OR) 0.33; 95% confidence interval (95% CI): 0.12-0.89; P=0.02] and less endothelial glycocalyx degradation [adjusted OR (aOR) 0.34 95% CI: 0.11-0.99; P=0.04]. These changes persisted despite elevated ferritin (aOR 0.41; 95% CI: 0.18-0.93; P=0.03). Prolonged capillary refill and elevated lactate were correlated with microcirculation changes in both groups. The patients who died had the highest PBR levels (P=0.04). Conclusions: Children with septic shock who receive milrinone infusions have microcirculation changes compared with those who do not receive them. The group that received milrinone was found to maintain functional capillary density and capillary recruitment capacity and have less endothelial glycocalyx degradation 24 hours after administration. These changes were present despite the inflammatory response and were more significant in those under two years of age.

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.

Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study

Abstract Objective To describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. Method Multicenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. Results Fifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4−10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. -Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5-6.5). The median length of PICU stay was six days (IQR 5-11), and one death occurred (1.8%). Conclusions Most characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study.

OBJECTIVE: To describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. METHOD: Multicenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. RESULTS: Fifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4-10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. d-Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5-6.5). The median length of PICU stay was six days (IQR 5-11), and one death occurred (1.8%). CONCLUSIONS: Most characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

Neutrophil CD64 expression as an important diagnostic marker of infection and sepsis in hospital patients.

INTRODUCTION: Infection and sepsis are major health problems. Therefore, the need for improved diagnostic indicators, as well as for better therapeutic monitors in the treatment of infection, remains, since the current diagnostic tools have low specificity and passed through minimal changes in the last two decades. OBJECTIVE: The aim of this study was to establish the correlation of neutrophil CD64 with indicators of infection and sepsis. METHODS: We established the correlation of the neutrophil CD64 expression with the following variables: complete white blood count, band count, neutrophils, C-reactive protein (CRP), cultures, flags released by automated hematology analyzers and clinical groups. Accordingly clinical groups were divided into two: patients "without clinical or laboratory evidence of infection or inflammatory process" and "clinical or laboratory evidence of a systemic inflammatory response (SIRS) and systemic sepsis" based upon identification of organisms by culture. We analyzed 93 whole blood samples anticoagulated with K3EDTA of patients admitted in the Intensive Care Unit (ICU) of a community hospital. RESULTS: The expression CD64 was statistically significant with clinical groups, flags, and neutrophils and was not significantly correlated with total count of white blood cells and cultures. CONCLUSION: Our results indicate that high expression of CD64 is an indicator important in the diagnosis of infection and sepsis.

Leucemia mielomonocítica juvenil: relato de caso / Juvenile myelomonocytic leukaemia: case report

A leucemia mielomonocítica juvenil (LMMJ) é uma doença rara, que representa de 2 por centoa 3 por cento de todas as leucemias pediátricas. É uma doença clonal de células da linhagem mieloide, que apresenta características de mieloproliferação e de displasia. Os sinais e os sintomas são resultantes da infiltração de células monocíticas malignas em órgãos não hematopoéticos. Os sintomas mais comuns são febre, tosse, infecção, fraqueza, palidez, linfadenopatia, hepatoesplenomegalia, lesões cutâneas e manifestações hemorrágicas. Como a LMMJ exibe um curso clínico muito agressivo e responde pobremente à quimioterapia, o transplante de células-tronco hematopoéticas é a única modalidade terapêutica curativa. Neste estudo, relatamos o caso de um paciente do sexo masculino, com um ano e dez meses de idade, que compareceu na emergência do Hospital de Clínicas de Porto Alegre por apresentar febre, com diagnóstico prévio de mononucleose feito em outra Instituição. A apresentação clínica, em conjunto com os achados laboratoriais, permitiu o diagnóstico correto. O paciente foi tratado com quimioterapia e submetido a transplante de células-tronco hematopoéticas.

Juvenile myelomonocytic leukemia (JMML) is a rare hematopoietic malignancy, which accounts for 2 to 3 percent of all pediatric leukemia. JMML is a myeloproliferative disorder characterized by monoclonal overproduction of myeloid cells. The signs and symptoms are a result of the infiltration of monocytic cells into non-hematopoietic organs; the most common symptoms are fever, cough, infection, weakness, pallor, lymphadenopathy, hepatosplenomegaly, skin lesions and bleeding. JMML runs an aggressive clinical course and responds poorly to chemotherapy. Hematopoietic stem cell transplantation is the only curative treatment. We describe the case of a 22-month-old male child, who appeared in the emergency room of Hospital de Clínicas de Porto Alegre because of fever and with a previous diagnosis of mononucleosis made at another Institution. The clinical presentation together with laboratory findings allowed the correct diagnosis. The patient was treated with chemotherapy and underwent hematopoietic stem cell transplantation.