Capillary refill time in febrile neutropenia / Tempo de enchimento capilar e neutropenia febril

Summary Introduction: Febrile neutropenia is a major cause of morbidity and mortality in patients presenting this condition following chemotherapy against several malignancies. Objective: To evaluate if capillary refill time (CRT) allows the prediction of poor clinical outcome with or without antibiotic dose escalation. Method: Capillary refill time was assessed in 50 patients with febrile neutropenia at its nadir after chemotherapy admitted to the emergency department at Hospital Universitário de Brasília. All patients included had a minimum average arterial blood pressure of 75 mmHg, O2/FiO2 saturation rate > 300, and 15 points in the Glasgow coma scale. Inclusion depended on at least three of the systemic inflammatory response syndrome (SIRS) criteria, suspected infection, and neutropenia after chemotherapy. Capillary refill time was calculated by pressing the index finger for 15 seconds, and then timing the return to the initial color. We studied whether there is a relationship between CRT and antibiotic escalation. The gold standard used to gravity was the level of lactate. Results: 31 patients had CRT ≥ 3 seconds, which it is associated with increased serum concentration of lactate (> 2 mmol/L; p<0.05). 32 patients underwent antibiotic escalation, which it is associated with CRT ≥ 3 seconds (p<0.01). Conclusion: CRT higher than three seconds was effective to predict antibiotic escalation.

Resumo Introdução: a neutropenia febril é uma das principais causas de morbimortalidade nos pacientes neutropênicos febris pós-quimioterapia para neoplasias diversas. Objetivo: avaliar se o tempo de enchimento capilar (TEC) é capaz de predizer pior desfecho clínico, pelo escalonamento ou não da antibioticoterapia. Método: foi pesquisado o TEC em 50 pacientes neutropênicos febris no nadir de pós-quimioterapia, que deram entrada no departamento de emergência do Hospital Universitário de Brasília. Todos os incluídos estavam com uma pressão arterial média mínima de 75 mmHg, relação saturação de O2/FiO2 > 300 e escala de coma de Glasgow de 15. Os critérios de inclusão foram pelo menos três da síndrome da resposta inflamatória sistêmica (SRIS), suspeita de infecção e neutropenia pós-quimioterapia. O TEC foi calculado através da pressão sobre o indicador por 15 segundos e cronometrado o tempo de retorno à cor inicial. Foi estudado se há relação entre valor encontrado no TEC e escalonamento de antibiótico. O padrão-ouro utilizado para gravidade foi o nível de lactato. Resultados: trinta e um pacientes tiveram o TEC ≥ 3 segundos, que se associou com o aumento da concentração de lactato (> 2 mmol/L; p<0,05). Trinta e dois pacientes tiveram escalonados seus antibióticos, que se associou com o TEC ≥ 3 segundos (p<0,01). Conclusão: o TEC maior que três segundos mostrou-se eficaz para predizer escalonamento de antibiótico.

Shock séptico en pediatría II. enfoque actual en el diagnóstico y tratamiento / Septic shock in pediatrics II. current concepts in diagnosis and treatment

Aunque los principios básicos para el diagnóstico y los pilares terapéuticos del niño con shock séptico se mantienen en el tiempo, es innegable que en las últimas décadas se han incorporado nuevos y trascendentes conceptos, siendo importante que el médico tratante en el Servicio de Urgencia tenga conocimiento a cabalidad de ellos. En la segunda parte de esta actualización se discuten las similitudes y diferencias entre la población infantil y adulta, la utilidad de las metas de reanimación metabólicas, como también el enfoque terapéutico inicial en el paciente séptico. Los conceptos más importantes revisados se refieren a las diferencias entre el niño y adulto con shock séptico, especialmente en la fisiopatología, clínica y tratamiento. Se recalca la importancia de expansión de la volemia y el uso de drogas vasoactivas si no hay respuesta a fluidos de reanimación. El manejo terapéutico debe estar orientado a la búsqueda de la normalización de metas macrohemodinámicas y de perfusión sistémica. Se deben evitar los errores más frecuentes de observar en el tratamiento inicial del paciente séptico. Esta entidad presenta una elevada incidencia y mortalidad, por lo cual el manejo precoz y agresivo es de máxima importancia en pediatría.

Although the basic concepts of diagnosis and therapy of the child with septic shock have remained similar over time, it is undeniable that in recent decades, new and important concepts have been added, and any treating physician either at the Emergency Department or Intensive Care Unit should be fully aware of them. This second part discusses the similarities and differences between pediatric and adult populations, the utility of metabolic resuscitation goals, as well as the initial therapeutic approach in septic patients. The most important concepts of this work make reference to the differences between children and adults with septic shock, specifically regarding to pathophysiology, clinical presentation and treatment. Volume expansion and vasoactive drugs are crucial if there is no response to fluid resuscitation. The therapeutic management should focus on finding the normalization of macrohemodynamic and systemic perfusion targets. Common observation mistakes in the initial treatment of septic patients should be avoided. This condition has a high incidence and mortality rate; therefore an early and aggressive treatment is essential.

La microcirculación en el paciente crítico: parte I: generalidades y fisiología en el paciente séptico / Microcirculation in the critically ill. Part I: Review and physiology of septic patients

Severe sepsis and septic shock involve circulatory, inflammatory and metabolic disorders eventually resulting in a disruption of cellular energy. Microcirculatory disturbances are common in septic patients. Microcir-culation is the primary site of oxygen and nutrients exchange to cells. Direct observation using Sidestream Dark Field (SDF) imaging has allowed direct visualization of microcirculatory failure in critically ill patients. Septic shock is characterized by weak or vulnerable microcirculatory units and heterogeneity of microcircula-tory flow. Multiple mechanisms may contribute to these alterations, including endothelial dysfunction, altered glycocalyx, impaired inter-cell communication and adhesion and rolling of white blood cells and platelets. Many therapeutic interventions routinely used in the treatment of critically ill patients seem to result in limited changes in microcirculatory perfusion, irrespective of systemic hemodynamics, due to the heterogeneous nature of these changes and the potentially involved mechanisms. Therefore, microcirculatory alterations and their presence in states of shock, especially in septic shock, can represent diagnostic and severity stratification tools and may be a target for therapeutic intervention (microcirculatory resuscitation), besides suggesting a prognostic role.

La sepsis grave y shock séptico involucran una compleja red de alteraciones circulatorias, inflamatorias y metabólicas que llevan finalmente a una disrupción energética celular. Las alteraciones microcirculatorias son frecuentes en el paciente séptico. La microcirculación corresponde al sitio anatómico-funcional donde ocurre el intercambio de oxígeno y nutrientes hacia la célula. Su observación directa mediante el uso de videomicroscopía como sidestream dark field (SDF) ha permitido la construcción de falla microcirculatoria como concepto clínico en el paciente crítico. En el shock séptico la existencia de unidades microcirculatorias débiles y la heterogeneidad del flujo microcirculatorio son características. Múltiples mecanismos contribuyen a estas alteraciones, incluyendo la disfunción endotelial, daño del glicocálix, alteración en la comunicación intercelular, adhesión y rotación de leucocitos y plaquetas. Diversas intervenciones terapéuticas empleadas rutinariamente en el tratamiento del paciente crítico parecen estar asociadas con cambios limitados en la perfusión de la microcirculación, con independencia de la hemodinamia sistémica, debido a la naturaleza heterogénea de estas alteraciones y los mecanismos potencialmente involucrados. Así, las alteraciones microcirculatorias y su persistencia en estados de shock, especialmente shock séptico, se pueden mostrar como una herramienta diagnóstica y de estratificación de gravedad, pudiendo ser un objetivo de intervención terapéutica (resucitación microcirculatoria) presentando a su vez un rol pronóstico.

Efeito da terapia farmacológica anti-hipertensiva sobre densidade capilar e função endotelial microcirculatória / Effect of pharmacological antihypertensive therapy on capillary density and microvascular endothelial function

Hipertensos têm rarefação capilar e disfunção endotelial microcirculatória, tornando-se mais vulneráveis a lesões em órgãos-alvo. O estudo buscou avaliar o efeito de seis meses de tratamento farmacológico sobre densidade capilar e reatividade microvascular a estímulos fisiológicos e farmacológicos em hipertensos de baixo risco cardiovascular. Secundariamente testou-se a existência de diversidade nas respostas a diferentes estratégias anti-hipertensivas. Foram recrutados 44 pacientes, com 46,7±1,3 anos e 20 normotensos com 48,0±1,6 anos. Avaliaram-se dados antropométricos e laboratoriais e dosaram-se no soro o fator de crescimento vascular endotelial (VEGF), receptor Flt-1 para VEGF e óxido nítrico (NO). A contagem capilar foi por microscopia intravital, captando-se imagens da microcirculação no dorso da falange do dedo médio e contando os capilares com programa específico. Repetia-se o procedimento após hiperemia reativa pós-oclusiva (HRPO) para avaliar o recrutamento capilar. A reatividade vascular foi testada por fluxometria Laser Doppler, iontoforese de acetilcolina (Ach), HRPO e hiperemia térmica local (HTL). Os pacientes foram distribuídos aleatoriamente para dois grupos de tratamento: succinato de metoprolol titulado a 100 mg diários ou olmesartana medoxomila titulada a 40 mg diários, empregando-se, se necessário, a hidroclorotiazida. Os controles seguiram o mesmo protocolo inicial e após seis meses todos os testes foram repetidos nos hipertensos. As variáveis clínicas e laboratoriais basais eram semelhantes em comparação aos controles e entre os dois grupos de tratamento. Após seis meses, havia pequenas diferenças entre os grupos na relação cintura-quadril e HDL. A densidade capilar antes do tratamento era significativamente menor que no grupo controle (71,3±1,5 vs 80,6±1,8 cap/mm2 p<0,001 e HRPO 71,7±1,5 vs 79,5±2,6 cap/mm2 p<0,05) e, com o tratamento, aumentou para 75,4±1,1 cap/mm2 (p<0,01) no estado basal e para 76,8±1,1 cap/mm2 à HRPO (p<0,05)...

Capillary rarefaction and microcirculatory endothelial dysfunction are hallmarks of hypertension, rendering patients vulnerable to target organ lesions. The study aimed at assessing the effect of a six-month treatment period upon capillary density and microvascular reactivity to physiological and pharmacological stimuli. In addition, two different treatment strategies were tested for possible differences between effects upon those variables. A total of 44 patients were recruited, mean age 46.7±1.3 years and 20 normotensive individuals served as controls, mean age 48.0±1.6 years. Anthropometrical and laboratory data were collected, as well as plasma levels of vascular endothelial growth factor (VEGF), its receptor Flt-1 and nitric oxide (NO). Capillary density was obtained by intra-vital microscopy of the dorsum of the middle phalanx before and after post-occlusive reactive hyperemia (PORH). Capillary loops were counted by a semi-automated software. Microvascular reactivity was tested by laser Doppler flowmetry (LDF), and the challenges consisted of acetylcholine iontophoresis, local thermal hyperemia (LTH) and PORH. Patients were randomly allocated to either one of two treatment arms: metoprolol succinate uptitrated to 100 mg daily or olmesartan medoxomil uptitrated to 40 mg daily, with addition of hydrochlorothiazide if necessary. Controls underwent the same initial protocol and all tests were repeated in patients after six months. Baseline clinical and laboratory parameters were similar between patients and controls and between the two treatment groups. After six months there were slight, although significant, differences between the two groups in waist/hip ratio and HDL-cholesterol. In the whole cohort, pretreatment capillary density was significantly reduced compared to controls (71.3±1.5 vs 80.6±1.8 cap/mm2 p<0.001 and PORH 71.7±1.5 vs 79.5±2.6 cap/mm2 p<0.05). After treatment it increased to 75.4±1.1 cap/mm2 (p<0.01) at rest and 76.8±1,1 cap/mm2...

Correlation of " in vivo" microcirculation and degeneration of the basal cells of the epithelium in lingual lichen planus.

Background: Oral lichen planus is an inflammatory chronic disease with an autimmune pathogenesis and unknown etiology that affects oral mucosa, with or without the involvement of the skin and other mucous membranes. The principal histological characteristics are the degeneration of the basal cell layer and the abnormal infiltration of inflammatory cells into the subepithelial layer of connective tissue. Objectives: This study is aimed to appraise if lingual lichen planus (LLP) is sustained by alteration of the oral microcirculation and if this abnormal vascularisation increases the degeneration of basal keratinocytes and the disruption of the basement membrane. Materials and Methods: Fifteen patients with a histological diagnosis of LLP with higher degree of degeneration of the basement membrane, fifteen LLP patients with lower degree of basement membrane (BM) degeneration and fifteen healthy patients were included in the study. The microcirculation of the left margin of the lingual mucosa of all the patients and subjects was analysed with the videocapillaroscopy. The following parameters were analyzed on each capillaroscopic image: c0 apillary loop length, loop diameter, and capillary density. The results obtained by videocapillaroscopy software were subjected to statistical analysis using Mann Whitney U-test (P < 0.001). Statistical analysis was performed using PAST software, v. 1.53. Results: Capillary density, loop length, and total diameter showed statistically significant differences between LLP patients with histologically lower degree of BM degeneration and healthy subjects and a meaningful significant difference between LLP patients with higher degree of BM degeneration. Conclusions: A remarkable increase in capillary density was showed by videocapillaroscopic exam. The increased value of the density could be associated with angiogenesis mechanism and it could be an indicator of the evolutionary condition of LLP. Videocapillaroscopy may be useful for the evaluation of the evolution or regression of the disease.

Microvascular reactivity in type 1 diabetics / Reatividade microvascular em diabéticos tipo 1

OBJECTIVE: To evaluate whether differences are present in microvascular response to the schemia induced by dynamic videocapillaroscopy (VCD), through analysis of the measured capillar transverse segment area (CTSA) in patients with type 1 diabetes mellitus (T1DM). METHODS: The vascular reactivity of the CTSA was studied by VCD, using a reactive hyperemia test in 61 volunteers, being 31 healthy controls without diabetes family history (Group 1) and 30 patients with T1DM without complications (Group 2). The images were captured every two seconds, during reperfusion after one minute induced ischaemia, and they were analyzed by the program Studio Version 8 and Motic Image Plus. The pre-ischemia capillary transverse segment (basal area, BA), the maximum strain post-ischemia (maximum area, MA), and time to achieve it (MAt) were measured during reperfusion, and the increased area percentage (Ap) was estimated. RESULTS: The mean differences between groups were evaluated by the t-test. The median comparisons between the groups were studied by the Mann-Whitney test. There was no difference in BA between the groups. The Ap was significantly lower among the diabetic patients, and there was a significant increase in the Mat among the patients of Group 2 when compared to Group 1. CONCLUSIONS: These data suggest that type 1 diabetes provokes earlier endothelial dysfunction, before the onset of clinically detectable degenerative complications. The outcomes from these alterations need further studies.

OBJETIVO: Avaliar se há diferença de resposta microcirculatória à isquemia induzida pela videocapilaroscopia dinâmica (VCD), por meio da análise de medida da área do segmento transverso capilar (ASTC) em pacientes com diabetes melito tipo 1 (DMT1). MÉTODOS: A reatividade vascular do ASTC foi estudada pela VCD usando o teste de hiperemia reativa em 61 voluntários, sendo 31 controles sadios sem história familiar de diabetes (Grupo 1) e 30 pacientes com DMT1, sem complicações (Grupo 2). As imagens foram capturadas a cada dois segundos, durante a reperfusão após um minuto de isquemia induzida, e analisadas pelo programa Studio Version 8 e Motic Image Plus. O segmento transverso pré-isquemia (área basal, AB), a área máxima pós-isquemia (área máxima, AM) e o tempo para alcançá-la foram medidos durante a reperfusão, e o percentual de incremento foi estimado. RESULTADOS: As principais diferenças entre os grupos foram avaliadas pelo teste t. As médias comparativas entre os grupos foram avaliadas pelo teste Mann-Whitney. Não houve diferença na área basal entre os dois grupos. O percentual de incremento foi significativamente menor entre os pacientes diabéticos e houve um aumento significativo no ASTC entre os pacientes do Grupo 2 quando comparados com o Grupo 1. CONCLUSÕES: Os dados sugerem que o diabetes tipo 1 provoca disfunção endotelial precoce, antes mesmo de complicações degenerativas serem detectadas clinicamente. Os fatores que levam a essas alterações necessitam de estudos adicionais.

Effects of buflomedil and pentoxifylline on hamster skin-flap microcirculation: prediction of flap viability using orthogonal polarization spectral imaging

OBJECTIVE: This study investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. METHOD: Twenty-four adult male Syrian golden hamsters were divided into three groups: a control (C, 0.1 ml 0.9 percent saline), buflomedil (B, 3 mg/kg/day), and pentoxifylline group (P, 14.5 mg/kg/day). Treatments administered intraperitoneally were initiated 1 hour before skin flap preparation and continued for 7 days post-operatively at 12-hour intervals. Preparations (skin flaps) were divided into 12 fields, which were organized into six bands. Functional capillary density (FCD, in mm/mm²), distance from the skin flap base to blood flow cessation (Dist with flow, in cm), percentage of viable skin (VA, in percent), and qualitative analysis of blood flow by orthogonal polarization spectral imaging were performed at 1 and 24 hours and on the seventh post-operative day. RESULT: Bands IV, V, and VI presented no flow independent of time. The functional capillary density group B was higher than that of groups C and P, primarily after 24 hours. All groups showed an increase in D with time but reached similar final distances (C = 2.73, B = 2.78 and P = 2.70 cm). Moreover, the percentage of viable areas remained at approximately 50 percent. The orthogonal polarization spectral imaging was useful to assess viability by counting fields with and without blood flow. CONCLUSIONS: Functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. Functional capillary density did not influence D or the percentage of VA, and the technique showed favorable potential to assess/predict the viability of skin flaps within 1 h after surgery.

Treatment of essential hypertension does not normalize capillary rarefaction

OBJECTIVES: To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS: We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS: Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm², p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm², p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm², p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1 percent. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS: Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.

Aspectos morfológicos dos capilares do sistema nervoso central: implicaçöes terapêuticas e fisiopatológicas / Central nervous system capillaries morphological aspects: therapeutic and physiopathologic implications

A barreira hematoencefálica (BHE) limita as trocas entre o SNC e o restante do organismo. Este conceito abrange consideraçöes sobre multiplos fatores que controlam as trocas bidirecionais que ocorrem entre sangue, cérebro e LCR. Sua funçäo é manter a estabilidade relativa da composiçäo química do cérebro e LCR, apesar das modificaçöes na composiçäo do sangue. A localizaçäo anatômica da BHE é o capilar do SNC e a estrutura responsável säo as zonas de oclusäo. Essa barreira näo é absoluta, exibindo uma certa seletividade, permitindo que algumas substâncias passem através dela mais prontamente do que outras. As características morfológicas particulares dos capilares do SNC e suas relaçöes com as BHE e BHL, assim como as propriedades que permitem maior permeabilidade a certas substâncias, inclusive medicamentos, säo discutidas