Diagnóstico e conduta de sepse em crianças de hospital de referência de 2016 e 2017 / Diagnosis and management of sepsis in children from a referral hospital in 2016 and 2017

A sepse é definida pela presença de disfunção orgânica ameaçadora à vida secundária a resposta desregulada do organismo a determinada infecção(SINGER et al,2016). Atualmente, os critérios para seu diagnóstico, estabelecidos no Sepse-3(2016) e Sepse-4(2017), dependem da pontuação de dois ou mais pontos no escore SOFA (Sequential Organ Failure Assessment), que leva em consideração os quadros respiratórios, coagulativo, hepático, cardiovascular, renal e do sistema nervoso central do paciente. Esses quadros são avaliados através de marcadores clínicos e laboratoriais, respectivamente o coeficiente entre a pressão parcial de oxigênio (PaO2) sobre a fração inspirada de oxigênio (FiO2), contagem de plaquetas, bilirrubina, creatinina ou débito urinário e escala de coma de Glasgow (SINGER et al,2016).Nos neonatos os parâmetros são diferentes devido a suas diferenças fisiológicas, nesses casos o diagnóstico é dado pela presença de taquipneia, taquicardia, instabilidade térmica,hipotensão na ausência de desidratação e alterações nas contagens de glóbulos brancos(BIBI et al, 2012). Apesar desses critérios não serem completamente aceitos na comunidade científica(CARNEIRO;GOMES;POVOA,2017), seu uso na prática hospitalar parece apresentar maiores benefícios na acurácia diagnóstica quando comparados aos critérios antecessores (BESEN et al,2016) razão pela qual será o critério adotado nesta pesquisa.Em relação ao choque séptico, trata-se de uma evolução do quadro, na qual anormalidades graves circulatórias, celulares e metabólicas estão associadas com maior risco de mortalidade(MARTIN, 2016), sendo seu diagnóstico em crianças problemático pois o choque em si tende a ocorrer muito antes do início da hipotensão, sendo esta indicativa de choque descompensado. Assim,o choque séptico deve ser caracterizado prioritariamente pela taquicardia (que pode estar ausente em pacientes com hipotermia) com redução da perfusão periférica ou oligúria (GOLDSTEIN; GIROIR;RANDOLPH, 2005).No atendimento clínico deve-se atentar aos sinais de complicações da sepse, como: presença de delirium e alterações nos reflexos, pois podem acusar comprometimento neurológico, o tempo de preenchimento vascular, indicativo de choque séptico, e manchas brancas na pele, que pode ser preditivo de choque séptico, pois indica hipoperfusão (POSTELNICU; EVANS, 2017).Achados clínicos presentes na sepse podem contemplar petéquias e púrpuras, quando houver instabilidade hemodinâmica, febre, tosse, e hipoxemia em casos de leucocitose e infiltrados pulmonares, ou abdome distendido timpânico com febre e leucocitose, associado a perfuração intestinal (GOLDSTEIN; GIROIR; RANDOLPH, 2005).Para a confirmação da sepse deve-se fazer a hemocultura, porém devido à necessidade de uma ação rápida pode-se utilizar outros exames complementares que ajudam a confirmar a sepse como:hemograma completo com contagem de plaquetas, PCR, procalcitonina e citocinas (EDWARDS;BAKER, 2004).O hemograma é utilizado para avaliar quantidade de linfócitos e neutrófilos, entretanto o hemograma é mais útil para excluir a possibilidade de sepse do que para confirmar a mesma (POLIN, 2012).O PCR encontra-se aumentado em reações inflamatórias como a sepse, é um exame altamente sensível porém pouco específico, os níveis de PCR podem ser utilizados para acompanhar a eficiência da terapia antibiótica (MUKHERJEE et al., 2015).A procalcitonina é liberada em resposta a toxinas bacterianas, diversos estudos mostraram que ela pode ser utilizada para detectar infecções bacterianas graves em crianças febris (MANIACI et al., 2008),As taxas de mortalidade por sepse são influenciadas por diversos fatores, tais como o quadro clínico na admissão, o agente etiológico envolvido na doença, presença ou não de choque séptico,presença ou não de disfunção de mais de dois órgãos e a presença de comorbidade. Dos fatores de risco para óbito por sepse destaca-se a presença de complicações durante a internação e envolvimento de dois ou mais órgãos pela infecção, isto demonstra a importância de uma terapêutica precoce no prognóstico do paciente aplicando antibióticos de forma empírica tomando como base as bactérias de maior prevalência na região (PEDRO; MORCILLO; BARACAT, 2015).Portanto, pretende-se avaliar as condições de admissão e desfecho de internamento das crianças com sepse, analisando a influência de fatores como a forma de diagnóstico, o tempo de permanência hospitalar,a admissão em UTI e tratamento empregado no prognóstico do paciente visando estabelecer fatores que contribuíram e prejudicaram a evolução do paciente séptico

Tempo de permanência de crianças diagnosticadas com sepse em UTI e estudo dos dispositivos usados nesses pacientes. / Length of stay of children diagnosed with sepsis in ICU and study of the devices used in these patients.

A sepse é definida pela presença de disfunção orgânica ameaçadora à vida secundária a resposta desregulada do organismo a determinada infecção. Caso não haja um tratamento adequado da sepse inicialmente pode haver evolução para choque séptico. Pacientes com sepse geralmente requerem internação na unidade de terapia intensiva (UTI). Através desse estudo conclui-se que o óbito causado por sepse bem como a taxa de incidência da doença pode ocorrer em pacientes mais jovens. Além de 100% dos óbitos terem ocorrido no grupo de recém-nascidos, a incidência da doença é drasticamente mais prevalente em crianças mais jovens: 67% dos pacientes eram recém nascidos e apenas 31% era lactente e 1% era pré-escolar

Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil.

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

BACKGROUND: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. METHODS: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. FINDINGS: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages

Initial Description of the Presumed Congenital Zika Syndrome.

OBJECTIVES: To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. METHODS: We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. RESULTS: About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. CONCLUSIONS: Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. POLICY IMPLICATIONS: Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require

Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika