Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

COVID-19 and liver damage: narrative review and proposed clinical protocol for critically ill pediatric patients

SARS-CoV-2 shares nearly 80% of its' genomic sequence with SARS-CoV and MERS-CoV, both viruses known to cause respiratory symptoms and liver impairment. The emergence of pediatric cases of multisystem inflammatory syndrome related to the SARS-CoV-2 infection (PIM-TS) has raised concerns over the issue of hepatic damage and liver enzyme elevation in the critically ill pediatric population with COVID-19. Some retrospective cohorts and case series have shown various degrees of ALT/AST elevation in SARS-CoV-2 infections. A limited number of liver histopathological studies are available that show focal hepatic periportal necrosis. This liver damage was associated with higher levels of inflammatory markers, C-reactive protein (CRP), and pro-calcitonin. Proposed pathophysiological mechanisms include an uncontrolled exacerbated inflammatory response, drug-induced liver injury, direct viral infection and damage to cholangiocytes, hypoxic-ischemic lesions, and micro-thrombosis in the liver. Based on the physiopathological characteristics described, our group proposes a clinical protocol for the surveillance, evaluation, management, and follow-up of critically ill pediatric COVID-19 patients with liver damage.

Opioid tapering and weaning protocols in pediatric critical care units: a systematic review

SUMMARY OBJECTIVE: Opioid abstinence syndrome is common in the pediatric intensive care environment because sedation is often needed during the children's treatment. There is no specific guideline regarding the management of these patients; and lately, methadone is an important drug for the prevention of abstinence symptoms during the weaning of opioids. This study gathers the available research to establish the initial dose of methadone, the rate of taper and tools to recognize this syndrome and act promptly. METHODS: A systematic review was made from data of four different databases. Forty-nine articles of observational and experimental studies were selected based on the inclusion criteria (critical pediatric patients in acute use of opioids) and exclusion criteria (previous chronic use of opioids, other medications). The data regarding specific themes were separated in sections: initial dose of methadone, use of protocols in clinical practice, abstinence scales and adjuvant drugs. RESULTS: The articles showed a great heterogeneity of ways to calculate the initial dose of methadone. The pediatric intensive care units of the study had different weaning protocols, with a lower incidence of abstinence when a pre-defined sequence of tapering was used. The Withdrawal Assessment Tool - 1 was the most used scale for tapering the opioids, with good sensitivity and specificity for signs and symptoms. CONCLUSION: There is still little evidence of other medications that can help prevent the abstinence syndrome of opioids. This study tries to promote a better practice during opioid weaning.

RESUMO OBJETIVO: A síndrome de abstinência de opioides é comum no ambiente de terapia intensiva pediátrica porque a sedação é frequentemente necessária durante o tratamento das crianças. Não existe uma diretriz específica sobre o manejo desse paciente e, ultimamente, a metadona tem sido uma droga importante para a prevenção dos sintomas de abstinência durante o desmame dos opioides. Este estudo reúne as pesquisas disponíveis para estabelecer a dose inicial de metadona, taxa de redução e ferramentas para reconhecer essa síndrome e agir prontamente. MÉTODOS: Uma revisão sistemática foi feita a partir de dados de quatro diferentes bases de dados. Quarenta e nove artigos, de estudos observacionais e experimentais, foram selecionados com base nos critérios de inclusão (pacientes críticos pediátricos em uso de opioides agudamente) e critérios de exclusão (uso crônico prévio de opioides, outros medicamentos). Os dados referentes a temas específicos foram separados em seções: dose inicial de metadona, uso de protocolos na prática clínica, escalas de abstinência e drogas adjuvantes. RESULTADOS: Os artigos mostraram uma grande heterogeneidade de formas de calcular a dose inicial de metadona. As unidades de terapia intensiva pediátrica do estudo apresentaram diferentes protocolos de desmame, com menor incidência de abstinência quando foi utilizada uma sequência predefinida de redução gradual. A Ferramenta de Avaliação de Retirada - 1 foi a escala mais utilizada durante a redução dos opioides, com boa sensibilidade e especificidade para sinais e sintomas. CONCLUSÃO: Ainda há poucas evidências de outros medicamentos que possam ajudar a prevenir a síndrome de abstinência dos opioides. Este estudo tenta promover uma prática melhor durante o desmame dos opioides.

Importance of the use of protocols for the management of analgesia and sedation in pediatric intensive care unit / Importância do uso de protocolos para manejo da analgesia e sedação em unidade de terapia intensiva pediátrica

Summary Introduction: Analgesia and sedation are essential elements in patient care in the intensive care unit (ICU), in order to promote the control of pain, anxiety and agitation, prevent the loss of devices, accidental extubation, and improve the synchrony of the patient with mechanical ventilation. However, excess of these medications leads to rise in morbidity and mortality. The ideal management will depend on the adoption of clinical and pharmacological measures, guided by scales and protocols. Objective: Literature review on the main aspects of analgesia and sedation, abstinence syndrome, and delirium in the pediatric intensive care unit, in order to show the importance of the use of protocols on the management of critically ill patients. Method: Articles published in the past 16 years on PubMed, Lilacs, and the Cochrane Library, with the terms analgesia, sedation, abstinence syndrome, mild sedation, daily interruption, and intensive care unit. Results: Seventy-six articles considered relevant were selected to describe the importance of using a protocol of sedation and analgesia. They recommended mild sedation and the use of assessment scales, daily interruptions, and spontaneous breathing test. These measures shorten the time of mechanical ventilation, as well as length of hospital stay, and help to control abstinence and delirium, without increasing the risk of morbidity and morbidity. Conclusion: Despite the lack of controlled and randomized clinical trials in the pediatric setting, the use of protocols, optimizing mild sedation, leads to decreased morbidity.

Resumo Introdução: analgesia e sedação são elementos necessários no cuidado do paciente em UTI, com o objetivo de promover controle de dor, angústia, agitação e evitar perda de dispositivos, extubação acidental e melhora da sincronia do paciente com a ventilação mecânica. No entanto, o excesso dessas medicações ocasiona um aumento de morbidades e mortalidade. O manejo ideal depende da adoção de medidas clínicas e farmacológicas, guiadas por escalas e protocolos. Objetivo: revisão da literatura sobre principais aspectos da analgesia e sedação, síndrome de abstinência e delirium em unidade de terapia intensiva pediátrica, mostrando a importância do uso de protocolos no manejo dos pacientes criticamente enfermos. Método: artigos publicados nos últimos 16 anos, nas plataformas PubMed, Lilacs e Cochrane Library, com os termos analgesia, sedação, síndrome de abstinência, nível leve de sedação, interrupção diária da sedação e unidade de terapia intensiva. Resultados: foram selecionados 76 artigos relevantes para descrever a importância da utilização do protocolo de sedação e analgesia, preconizando um nível leve de sedação, com uso de escalas de avaliação, interrupção diária e aplicação de teste de respiração espontânea. Essas medidas evidenciam uma diminuição no tempo de ventilação mecânica, no tempo de internação hospitalar, o controle da síndrome de abstinência e delirium, sem implicar em maior risco de morbimortalidade. Conclusão: apesar da falta de estudos controlados e randomizados em pediatria, o uso de protocolo, otimizando um nível leve de sedação, determina uma menor morbidade.