El tiempo de llene capilar prolongado es predictor de una saturación venosa central de oxígeno disminuida / A prolonged capillary refill is predictor of low central venous oxygen saturation

Introduction: Educational programs in pediatric life support endorse a capillary refill time > 2 s as an indicator of shock. In the emergency room, a barrier to the implementation of an early goal directed therapy, aiming at central venous oxygen saturation (ScvO2) ≥ 70% is the insertion of central venous catheter (CVC). Objective: To establish the predictive value of capillary refill time > 2 s to detect ScvO2 < 70% in children admitted to Intensive Care Units. Patients and Method: Prospective study. We included 48 children admitted in the first 24 hours in ICU with superior vena cava CVC. Simultaneously, we measured ScvO2 and capillary refill time in the heel of upper extremity or toe. Results: There were 75 paired measurements ScvO2 (75,9 ± 8,4%) and capillary refill capillary (1,9 ± 1,0 s). We found an inverse correlation between capillary refill time and ScvO2 (r - 0,58 ). The ROC curve analysis revealed an excellent ability for the capillary fill time > 2 s to predict ScvO2 < 70% (AUC 0,94) (95% CI 0,87-0,98). Conclusions: A prolonged capillary refill time > 2 s, is a predictor of ScvO2 < 70% in children admitted to ICU, which supports the current recommendations. This finding may be relevant in emergency units where the use of CVC is limited and ScvO2 is not available.

Introducción: Programas educativos de reanimación pediátrica establecen que un tiempo de llene capilar > 2 s es un indicador de shock. En unidades de emergencia, una barrera para la implementación de una reanimación precoz guiada por metas, teniendo como objetivo una saturación venosa central de oxígeno (ScvO2) ≥ 70%, es la inserción de un catéter venoso central (CVC). Objetivo: Determinar el valor predictivo de un tiempo de llene capilar > 2 s en la detección de ScvO2 < 70% en niños ingresados a la Unidad de Cuidados Intensivos. Pacientes y Método: Estudio prospectivo. Se incluyeron 48 niños ingresados en las primeras 24 h en UCI con CVC en la vena cava superior. De manera simultánea se determinaron ScvO2 y tiempo de llene capilar en talón o dedo de extremidad superior. Resultados: Se obtuvieron 75 mediciones pareadas de ScvO2 (75,9 ± 8,4%) y llene capilar (1,9 ± 1,0 s), observándose una correlación inversa entre llene capilar y ScvO2 (r = -0,58). El análisis de la curva ROC reveló una excelente capacidad del tiempo de llene capilar > 2 s para predecir una ScvO2 < 70% (AUC = 0,94, IC 95% = 0,87-0,98). Conclusiones: La prolongación del tiempo de llene capilar > 2 s es predictor de ScvO2 < 70% en niños críticamente enfermos. Este hallazgo apoya las recomendaciones actuales y podría ser relevante en unidades de emergencia donde el uso de CVC es limitado y la ScvO2 no está disponible.

Falta de concordância entre diferentes observadores e métodos na mensuração do tempo de reenchimento capilar em voluntários saudáveis: estudo observacional / Lack of agreement between different observers and methods in the measurement of capillary refill time in healthy volunteers: an observational study

Objetivo: As anomalias da perfusão periférica são manifestações importantes do choque, sendo o tempo de reenchimento capilar comumente utilizado em sua avaliação. Entretanto, a reprodutibilidade das mensurações do tempo de reenchimento capilar e sua correlação com outras variáveis da perfusão periférica não foram avaliadas de forma abrangente. Nosso objetivo foi determinar, em voluntários saudáveis, a concordância entre diferentes métodos e diferentes observadores na quantificação do tempo de reenchimento capilar, assim como sua correlação com outros marcadores da perfusão periférica. Métodos: Estudamos 63 voluntários saudáveis. Dois observadores mediram o tempo de reenchimento capilar por meio de dois métodos distintos: visão direta (TRCcronômetro) e vídeo-análise (TRCvídeo). Medimos também o índice de perfusão derivado de pletismografia de pulso e a temperatura da polpa digital (Tºperiférica). A concordância entre os observadores e os métodos foi avaliada utilizando o método de Bland-Altman. As correlações foram calculadas utilizando a correlação de Pearson. Valor de p<0,05 foi considerado significante. Resultados: Os limites de concordância de 95% entre ambos os observadores foram de 1,9 segundo para TRCcronômetro e 1,7 segundo para TRCvídeo. Os limites de concordância de 95% entre TRCcronômetro e TRCvídeo foram de 1,7 segundo para o Observador 1 e 2,3 segundos para o Observador 2. As mensurações do TRCcronômetro realizadas pelos dois observadores se correlacionaram com a Tºperiférica. As mensurações do TRCvídeo realizadas pelos dois observadores se correlacionaram com a Tºperiférica e o índice de perfusão. ...

Objective: Peripheral perfusion abnormalities are relevant manifestations of shock. Capillary refill time is commonly used for their evaluation. However, the reproducibility of capillary refill time measurements and their correlation with other variables of peripheral perfusion, have not been comprehensively evaluated. Our goal was to determine, in healthy volunteers, the agreement between different methods of capillary refill time quantification and different observers, as well as their correlation with other markers of peripheral perfusion. Methods: We studied 63 healthy volunteers. Two observers measured capillary refill time by means of two methods, direct view (CRTchronometer) and video analysis (CRTvideo). We also measured perfusion index (PI) derived from pulse plethysmography and finger pad temperature (Tºperipheral). The agreement between observers and methods was assessed using the Bland and Altman method. Correlations were calculated using Pearson's correlation. A p-value<0.05 was considered significant. Results: The 95% limits of agreement between the two observers were 1.9 sec for CRTchronometer and 1.7 sec for CRTvideo. The 95% limits of agreement between CRTchronometer and CRTvideo were 1.7 sec for observer 1 and 2.3 sec for observer 2. Measurements of CRTchronometer performed by the two observers were correlated with Tºperipheral. Measurements of CRTvideo performed by the two observers were correlated with Tºperipheral and perfusion index. Conclusion: In healthy volunteers, measurements of capillary refill time performed by either different observers or different methods showed poor agreement. Nevertheless, capillary refill time still reflected peripheral perfusion as shown by its correlation with objective variables of peripheral perfusion. .

La microcirculación en el paciente crítico: parte II: evaluación y microcirculación como objetivo terapéutico / Microcirculation in the critically ill patient: part II: evaluation and microcirculation as a therapeutic target

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. Su observación directa mediante el uso de vídeomicroscopia como sides-tream dark field (SDF) ha permitido la construcción de falla microcirculatoria como concepto clínico en el paciente crítico. 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.

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. Direct observation using sidestream dark field (SDF) videomicroscopy has enabled the construction of microcirculatory failure as a clinical concept in the critically ill patients. Many therapeutic interventions routinely used in the treatment of critically ill patients seem to be associated with limited changes in microcirculatory perfusion, irrespective of systemic hemodynamics, given the heterogeneous nature of these changes and the mechanisms potentially involved.

Efeitos macrovasculares, microvasculares e interação leucócito-endotélio, na endotoxemia experimental após o uso de Dobutamina com e sem ressuscitação volêmica / Macrovascular and microvascular effects and leukocyte-endothelial interaction in experimental endotoxemia after use of dobutamine with and without volume ressuscitation

Na sepse, o mecanismo desencadeador de morte é a disfunção múltipla de órgãos e sistemas. Com isso a microcirculação é considerada o motor na patogênese da sepse. A perfusão microcirculatória representa um dos principais objetivos para melhorar as taxas de sobrevida. Uma vez reconhecida a síndrome séptica, o protocolo clínico estabelece o uso de fluidoterapia com salina, de forma vigorosa na primeira hora e seguida de suporte inotrópico com Dobutamina. A partir daí foi levantada a hipótese das drogas β-agonistas serem relevantes na recuperação da microcirculação, antes mesmo de seu conhecido papel na recuperação do choque cardiogênico. Assim, estudar o papel da Dobutamina, um β-agonista, na resposta adrenérgica em situação de sepse se faz necessário e urgente e o entendimento de sua ação, associada à reposição volêmica, foi objeto deste estudo. Foram usados no presente estudo, 78 hamsters, induzida a endotoxemia com LPS (2mg/kg/de massa de peso corporal) e divididos em 9 grupos: controle (n=10), endotóxico(n=10), endotóxico tratados com Dobutamina na dose de 5 e 15 μg /kg/min (n=10), Isoproterenol(n=10), ressuscitação volêmica (n=10) e ressuscitação volêmica associada à Dobutamina 5 (n=10) e 15 μg/kg/min (n=4) e Isoproterenol (n=4). Foram comparados os resultados de recuperação da densidade capilar funcional ao longo do tempo entre os grupos, e obteve-se resultado estatisticamente significativo no grupo em que se usa Dobutamina de 5μg/kg/min associada à ressuscitação volêmica p< 0,05. Em conclusão este estudo mostra que o papel da ressuscitação volêmica é crucial na resposta da microcirculação para melhorar a densidade capilar funcional, que a velocidade da hemácia capilar tem relação direta com a melhora na perfusão tecidual e que a associação de recuperação volêmica com solução salina e Dobutamina na dose de 5 μg /kg /min melhora significativamente sua resposta e melhora a perfusão.

uring sepsis the mechanism responsible for death is multiple dysfunctions of organs and systems and therefore the microcirculation is considered the motor in the pathogenesis of sepsis and microcirculatory perfusion represents one of the main objectives to improve survival rate. Once one recognizes the septic syndrome, the clinical protocol establishes the use of fluid therapy with physiological saline, in a vigorous way, in the first hour followed by inotropic support with dobutamine. With these facts in mind, our hypothesis is that β-agonist drugs are relevant for microcirculatory recuperation, even before their role was known in the recuperation of cardiogenic shock. In this way, to study the role of dobutamine, a β-agonist, in the adrenergic response in sepsis is needed and urgent. The understanding of its action associated to volume resuscitation was the aim of our study. Seventy-eight male hamsters were used in our study, endotoxemia being induced with LPS (2 mg/kg body weight), divided in 9 groups: control (n=10), endotoxic (n=10), endotoxic treated with dobutamine in the concentrations of 5 and 15 μg/kg/min (n=10, each), isoproterenol (n=10), volume resuscitation associated to dobutamine 5 μg/kg/min (n=10), 15 μg/kg/min (n=4), isoproterenol (n=4) or not (n=10). The microcirculation was observed in the dorsal window chamber and the results compared the recuperation of function capillary density with time and the group treated with dobutamine 5 μg/kg/min associated to volume resuscitation showed a statistically significant improvement (p<0.05) of it. In conclusion, this study has shown that volume resuscitation plays a crucial role in the microcirculatory response in terms of improvement of functional capillary density, the velocity of red blood cells in the capillary has a direct relationship with the improvement of tissue perfusion and the association of volume resuscitation with physiological saline and dobutamine 5 μg/kg/min elicits ...

Moderate exercise training promotes adaptations in coronary blood flow and adenosine production in normotensive rats

OBJECTIVES: Aerobic exercise training prevents cardiovascular risks. Regular exercise promotes functional and structural adaptations that are associated with several cardiovascular benefits. The aim of this study is to investigate the effects of swimming training on coronary blood flow, adenosine production and cardiac capillaries in normotensive rats. METHODS: Wistar rats were randomly divided into two groups: control (C) and trained (T). An exercise protocol was performed for 10 weeks and 60 min/day with a tail overload of 5 percent bodyweight. Coronary blood flow was quantified with a color microsphere technique, and cardiac capillaries were quantified using light microscopy. Adenine nucleotide hydrolysis was evaluated by enzymatic activity, and protein expression was evaluated by western blot. The results are presented as the means ± SEMs (p<0.05). RESULTS: Exercise training increased the coronary blood flow and the myocardial capillary-to-fiber ratio. Moreover, the circulating and cardiac extracellular adenine nucleotide hydrolysis was higher in the trained rats than in the sedentary rats due to the increased activity and protein expression of enzymes, such as E-NTPDase and 59- nucleotidase. CONCLUSIONS: Swimming training increases coronary blood flow, number of cardiac capillaries, and adenine nucleotide hydrolysis. Increased adenosine production may be an important contributor to the enhanced coronary blood flow and angiogenesis that were observed in the exercise-trained rats; collectively, these results suggest improved myocardial perfusion.

Relações entre fase cefálica da digestão, consumo alimentar e reatividade microvascular de indivíduos saudáveis / Relations between cephalic phase of digestion, food consumption and microvascular reactivity in health people

A fase cefálica de secreção de insulina (FCSI) ocorre dentro da fase cefálica da digestão, em aproximadamente dez minutos entre a estimulação oro-sensorial pelo alimento e o início da absorção deste e determina um incremento rápido dos níveis basais de insulina. A FCSI parece ser importante para a tolerância normal à glicose. A hipótese deste estudo é de que a insulina secretada na fase cefálica da digestão teria ações direcionadas para o tecido microvascular, com conseqüente recrutamento capilar. Estudos recentes com indivíduos sadios têm mostrado a associação entre função microvascular e componentes dietéticos. Padrões alimentares saudáveis e intervenções nutricionais com alimentos específicos representam estratégias preventivas e terapêuticas não-farmacológicas para redução da inflamação e do risco metabólico e cardiovascular associados. O estudo de consumo alimentar inserido nesta pesquisa objetivou identificar associações entre componentes dietéticos e a função microvascular em indivíduos saudáveis. Após avaliação clínica e laboratorial, 39 voluntários saudáveis foram submetidos a dois exames de videocapilaroscopia do leito ungueal, com um intervalo de dez minutos entre os mesmos. Neste intervalo, conforme randomização, uma refeição com ótima apresentação e aroma foi apresentada (estímulo sendorial) ou não (controle). Coletas sangüíneas foram realizadas aos 3, 9 e 15 minutos após a apresentação do estímulo, para avaliação dos níveis de insulina e polipeptídeo pancreático (PP), marcadores bioquímicos da fase cefálica da digestão. Durante todo o exame, medidas de fluxo e vasomotricidade foram realizadas pela técnica de laser-Doppler fluxometria. Após o exame, foi realizada iontoforese transdérmica de insulina. Todos os participantes responderam a um questionário de freqüência alimentar (QFA), relativo ao hábito de consumo dietético dos últimos 12 meses. O estudo da resposta microvascular à fase cefálica comparou as diferenças de densidade capilar...

The cephalic phase of insulin secretion (CPIS) occurs within the cephalic phase of digestion, in approximately ten minutes between the oral-sensorial stimulation elicited by the food to be consumed and the beginning of its absorption. It determines a rapid increase in insulin levels. The CPIS is believed to be important for normal glucose tolerance. The hypothesis of this study is that insulin secreted during cephalic phase would also have actions targeting microvascular tissue, with resulting capillary recruitment. Recent studies with healthy subjects have shown an association between microvascular function and dietary factors. Healthy eating patterns and nutritional interventions with specific food items represent non-pharmacological preventive and therapeutic strategies for reducing inflammation and cardio-metabolic associated risk factors. The study of food intake included in this research aimed to identify associations between dietary intake and microvascular function in healthy subjects. After clinical and laboratorial assessment, 39 healthy men underwent two nailfold videocapillaroscopies, with an interval of 10 minutes between them. In this interval, according to radomization, they were subjected to a great-looking breakfast tray (CPIS group) or to nothing (control group). Blood samples were drawn at 3, 9 and 15 minutes after the stimulus presentation to assess insulin and pancreatic polypeptide (PP) levels, which are markers of cephalic phase of digestion. Throughout the exam, microflow and vasomotion were measured by laser-Doppler flowmetry. After the exam insulin iontophoresis was performed. All participants answered a food-frequency questionnaire (FFQ) regarding their dietary intake in the last 12 months. The assessment of microvascular response to CPIS compared differences in functional capillary density (FCD) and microflow in the CPIS and control groups, pre- and post-stimulus and their correlations with changes in insulin and PP...

Hemorheological changes in microcirculation: their mechanism and measurement technique.

Blood fluidity in the capillaries is affected significantly in diseases such as cardiac and brain infarcts, diabetic gangrene and many others. In view of the importance of physiology and pathology of capillary circulation, the hemorheological characteristics of the capillary blood flow are discussed in this article. Also, a new diagnosing technique for blood fluidity disorders is proposed. A computerized system for image analysis and determining blood rheological disorders for clinical and experimental use has also been discussed.

Blood flow regulation in the cerebral microvasculature with an arcadal network: a numerical simulation.

Blood flow regulation in the cerebral microvasculature with an arcadal network was investigated using a numerical simulation. A mathematical model for blood flow in the arcadal network, based on in vivo data of cat cerebral microvasculature and flow velocity was developed. The network model consists of 45 vessel segments and 25 branching points. To simulate microvascular response to blood flow, non-reactive (solid), cerebral arteriole-like, or skeletal muscle arteriole-like responses to wall shear stress were taken into account. Numerical calculation was carried out in the flow condition where the inlet (arterial) pressure was changed from 60 to 120 mmHg. Flow-rate in each efferent vessel and the mean flow-rate over all efferent vessels were evaluated for assessment of blood supply to the local area of cerebral tissue. The simulation demonstrated the wall shear stress-induced vasodilation in the arcadal network worked to maintain the blood flow at a constant level with pressure variable in a wide range. It is suggested that an individual microvessel (segment) should join in the regulatory process of flow, interacting with other microvessels (cooperative regulation).

Two alternative models concerning the perialveolar microcirculation in mammalian lungs

Despite the fact that the concept of sheet-flow in the pulmonary microcirculation of mammals was introduced more than three decades ago, the capillary circulatory model still prevails in the physiological literature. Since cardiac output is identical in the systemic and in pulmonary circulations, it is noteworthy that in the former, the resulting arterial pressure is five times higher than that of the latter, which means that the corresponding microcirculations must be radically different. The present study addresses this problem from both morphological and physiological perspectives.

Estudo comparativo do envelhecimento do sistema capilar dos músculos: diafragma e reto anterior do abdome em ratos. Futuro modelo para o estudo de atividade física? / A comparative study on the aging process of muscles' capillary system: diaphragm and rectus abdominis in rats. A future model for physical activity studies?

No presente estudo as alterações etárias no sistema capilar foram investigadas nos músculos diafragma e reto anterior do abdome em ratos de 1, 8 e 18 meses de idade. Os padrões de ativação destes músculos diferem em que o diafragma é regularmente mobilizado muitas vezes a cada minuto durante toda a vida do animal, enquanto o reto anterior do abdome, embora mobilizado na respiração seja ativado de maneira muito menos freqüente e regular. As fibras musculares foram pré-incubadas em pH 4,35 e fixadas pelo método de Padykula e Herman para estudar a atividade miofibrilar da ATP-ase, tornando possível a separação das fibras em três grupos: oxidativa lenta (I); glicolítica oxidativa rápida (IIA) e oxidativa rápida (IIB) e a identificação dos capilares ao redor das fibras no mesmo corte. A relação capilar/fibra e a densidade capilar foram obtidas. A análise da relação capilar/fibra e da área entre os dois tipos musculares mostrou padrões diferentes de desenvolvimento capilar, no envelhecimento, das fibras não fatigáveis (I e IIA) do músculo diafragma em comparação com o reto anterior do abdome. Estas diferenças etárias do diafragma e reto anterior do abdome poderiam estar relacionadas à contínua contração diafragmática e poderia vir a ser este um modelo natural de exercício permanente e envelhecimento muscular.

Capillary refill time in term neonates: bedside assessment.

Capillary refill time (CRT) is yet to be established as a specific clinical sign of peripheral circulation in neonates. This study was conducted to assess the influence of four body sites used for measurement, interobserver variability, sex, birth weight, age at assessment and room temperature on CRT recorded in healthy term neonates, at bedside. Two observers measured CRT in four different body sites (forehead, chest, palm and heel) of each of 155 healthy term neonates. Significant differences occurred between the mean CRT recorded by the two observers in forehead (mean +/- SD: 2.62 +/- 0.8 s and 1.88 +/- 0.57 s; p < 0.001), palm (2.99 +/- 0.61 s and 2.75 +/- 1.12 s; p < 0.05) and heel (3.08 +/- 0.79 s and 4.24 +/- 1.84 s; p < 0.001). Only CRT in chest (2.7 +/- 0.42 s and 2.62 +/- 0.74 s) produced no significant differences in the means with a statistically significant and clinically fair, but not strong, interobserver agreement (r = 0.4; p < 0.001). No significant associations occurred between CRT and sex or birth weight. The associations of chest CRT with age at assessment (r = -0.23; p < 0.01) and room temperature (r = 0.27; p < 0.01) were clinically not important. In conclusion, CRT in neonates needs to be validated further before it can be useful as a specific clinical sign of peripheral circulation.

Effect of growth on lung transfer factor and its components.

Measurement of lung transfer factor for CO (TLCO) and its constituent components, viz. diffusion capacity across alveolar capillary membrane (Dm) and instant pulmonary capillary blood volume (Vc) were undertaken in 120 healthy non-smoker males by single breath technique. All the three parameters (TLCO, Dm, Vc) showed direct negative correlation with age. While TLCO and Dm showed a significant direct positive correlation with height, there was no correlation between VC and height. The degree of correlation increased when both age and height were used together than either of them alone for prediction of TLCO120. The prediction formulae (TLCO120 = 3.8 + 21 H (m)-0.308 A) using both age and height has regression value (R) of 0.6479 (p < 0.001).

Effect of cold challenge on alveolar capillary blood volume in normal individuals.

The effect of immersion of both the hands and the feet in water at 10 degrees C on lung transfer factor for carbon monoxide (Tlco) and on pulmonary capillary blood volume (Vc) was investigated in 20 normal young adult males immediately, 60 min and 120 min after the end of the cold challenge. Vc was significantly reduced immediately and the reduction was aggravated at 60 min. Tlco was significantly reduced only at 60 min. All the values returned to baseline at 120 min. It is concluded that the cold-induced changes in Tlco and Vc are physiological responses and not unique to patients with Raynaud's phenomenon as suggested by some workers.

Applied aspects of theoretical analysis of pulmonary gas exchange.

This paper gives a summary of the theoretical analysis of the processes of gas exchange in the lungs. It brings out the effect of changes in the rate of equilibration of gases across the membrane due to a variety of factors. It brings out that the length of the capillary over which complete equilibration occurs is infinitesimally small, hence a diffusion defect is seldom a cause of hypoxaemia in disease unless the character of membrane changes like in interstitial fibrosis or pneumoconiosis. The increase in length of capillary for complete equilibrium is significant in hypoxia of high altitude and left ventricular failure causing dilatation of pulmonary capillaries.