Síndrome Inflamatorio Sistémico Pediátrico Asociado a SARS-CoV-2 / Pediatric Systemic Inflammatory Syndrome Associated with SARS-CoV-2

La infección por SARS-CoV-2 es poco frecuente en niños, niñas y adolescentes, con manifestaciones clínicas leves o asintomáticos, pero desde abril del 2020, se han reportado niños gravemente enfermos en las zonas de mayor incidencia de infecciones por coronavirus, caracterizado por fiebre, síntomas gastrointestinales y marcadores de inflamación sistémica, compromiso cardiovascular importante (shock, disfunción miocárdica o miocarditis), con semejanzas a la Enfermedad de Kawasaki, tormenta de citoquinas y síndrome de activación macrofágica, denominado Síndrome Inflamatorio Multisistémico Pediátrico (PIMS/MIS-C). La patogénesis no se conoce exactamente, pero una respuesta inmune innata y adaptativa alterada asociada a autoinmunidad podría ser el mecanismo. Si bien no existe una guía terapéutica estandarizada, la mayoría de los pacientes reciben gamaglobulina intravenosa y corticoides sistémicos, y en algunos casos se requiere el uso inhibidores de interleuquinas. Se ha reportado una buena respuesta y mejoría en casi todos los niños, con una baja letalidad de 1,7-2%.

SARS-CoV-2 infection is rare in children and adolescents, with mild or asymptomatic clinical manifestations, but since April 2020, seriously ill children have been reported in areas with the highest incidence of coronavirus infections, characterized by fever, gastrointestinal symptoms and markers of systemic inflammation, significant cardiovascular compromise (shock, myocardial dysfunction or myocarditis), with similarities to Kawasaki disease, cytokine storm and macrophage activation syndrome, called Pediatric Multisystemic Inflammatory Syndrome (PIMS / MIS-C) ). The pathogenesis is not exactly known, but an altered innate and adaptive immune response associated with autoimmunity could be the mechanism. Although there is no standardized therapeutic guide, most patients receive intravenous gamma globulin and systemic corticosteroids, and in some cases the use of interleukin inhibitors is required. A good response and improvement has been reported in almost all children, with a low fatality rate of 1.7-2%.

Recomendación para la sospecha, manejo y seguimiento del compromiso cardiovascular en pacientes con Síndrome Inflamatorio Multisistémico en Pediatría asociado a COVID-19 (PIMS-TC). Declaración de Posición de la Sociedad Chilena de Pediatría (SOCHIPE) y Sociedad Chilena de Cardiología y Cirugía Cardiovascular (SOCHICAR) / Recommendation for the recognition, management and follow up of cardiovascular compromise in patients with Pediatric Multisystemic Inflammatory Syndrome associated with COVID-19 (PIMS-CT). Position statement of Chilean Scientific Societies

Desde la aparición de la pandemia por SARS-CoV-2, la población pediátrica ha sido menos afectada por la enfermedad tanto en frecuencia como en severidad. Sin embargo, desde abril de este año se han reportado casos de presentación y gravedad variables, caracterizados por fenómenos inflamato rios que afectan múltiples órganos, condición denominada Síndrome Inflamatorio Multisistémico Pediátrico (PIMS). La literatura describe frecuente compromiso cardíaco, hasta en un 80%. Este se caracteriza por injuria miocárdica con significativa elevación de biomarcadores: Troponinas séricas I/T, BNP o NT-ProBNP, unido a diversos grados de disfunción ventricular, pericarditis, valvulitis y arritmias. Además, se ha evidenciado la presencia de compromiso coronario el cual puede ocurrir hasta en un 23% de los casos, en un rango que va desde dilataciones hasta aneurismas. El seguimien to cardiológico hospitalizado y ambulatorio se ha sistematizado en base a los fenotipos clínicos de presentación: injuria miocárdica (miocarditis, valvulitis, pericarditis), shock (habitualmente de tipo "vasopléjico"), manifestaciones tipo Enfermedad de Kawasaki y aquellos casos PIMS que no cumplen con la clínica de los tres precedentes. Este último grupo es el que representa el mayor desafío en el cor to, mediano y seguimiento a largo plazo. Por esta razón se requiere un equipo multidisciplinario para su manejo. Considerando la alta frecuencia del compromiso cardíaco en el PIMS y la importancia de lograr un consenso en su manejo y seguimiento, se presentan estas recomendaciones según el estado actual del conocimiento de esta patología recientemente descrita.

Since the onset of the SARS-CoV-2 pandemic, the pediatric population has been less affected by the disease both in frequency and severity. However, since April cases of variable presentation and severity characterized by inflammatory phenomena that affect multiple organs have been reported, a condition called Multisystem Inflammatory Syndrome in Children (MIS-C). The literature has reported frequent cardiac involvement, up to 80%. This is characterized by myocardial injury with a significant increase of biomarkers such as serum troponins I and T, BNP, or NT-ProBNP coupled with varying degrees of ventricular dysfunction, pericarditis, valvulitis, and arrhythmias. Coronary compromise has also been described, which can occur in up to 23% of cases, and ranges from dila tations to aneurysms. Inpatient and outpatient cardiology follow-up has been systematized based on the clinical phenotypes such as myocardial injury (myocarditis, valvulitis, pericarditis), shock (usua lly vasoplegic), Kawasaki disease-type manifestations, and those MIS-C that do not comply with the clinic of the previous three. This last group represents the main challenge in the short-, medium- and long-term follow-up, therefore, it is necessary a multidisciplinary team for managing these patients. Considering the high frequency of cardiac compromise in MIS-C, and the importance of reaching a consensus regarding its management and follow-up, we present these recommendations according to the current state of knowledge regarding this recently described pathology.

Recomendaciones para el manejo inicial del síndrome inflamatorio multisistémico relacionado temporalmente con COVID-19, en niños y adolescentes / Recommendations for the initial management of multisystem inflammatory syndrome temporally related to COVID-19, in children and adolescents

El síndrome inflamatorio multisistémico en niños y adolescentes temporalmente relacionado con COVID-19 es una presentación clínica de la infección por SARS-CoV-2. Comparte algunas características con la enfermedad de Kawasaki, el shock tóxico, la sepsis, el síndrome de activación macrofágica y la miocarditis. Son escasas las publicaciones que abordan su manejo inicial, que tiene semejanzas con el propuesto para el shock séptico. Esta revisión analiza dicho abordaje basado en las características propias del síndrome inflamatorio multisistémico relacionado con COVID-19, de acuerdo con el paradigma de construcción de una "guía de práctica institucional", y sugiere estrategias de aproximación terapéutica, que incluyen detección temprana, estabilización, referencia, tratamiento específico y análisis de proceso

Multisystem inflammatory syndrome temporally related to COVID-19 in children and adolescents is a clinical presentation of SARS-CoV-2 infection. It shares some features with Kawasaki disease, toxic shock, sepsis, macrophage activation syndrome, and myocarditis. Few publications have addressed its initial management, which is similar to that proposed for septic shock. This review analyzes such approach based on the characteristics typical of multisystem inflammatory syndrome related to COVID-19 in accordance with the paradigm of an "institutional practice guideline" and suggests therapeutic approach strategies, including early detection, stabilization, referral, specific treatment, and process analysis.

SRIS y SDOM constructos asociados a sepsis / SRIS and SDOM constructs associated with sepsis

La sepsis es un síndrome de respuesta inflamatoria sistémica (SRIS) que se activa por infección. Por su parte, el síndrome de disfunción orgánica múltiple (SDOM) es el fallo de la función de órganos y sistemas críticos en pacientes que han desarrollado una SRIS. Debido a que SRIS y SDOM son consecuencias de una excesiva activación inflamatoria. El objetivo de este artículo es ofrecer una revisión sobre algunos aspectos fisiopatológicos del constructo SRIS / SDOM de origen infeccioso, utilizando a la colangitis aguda como un ejemplo de esta cadena de eventos.

Sepsis is a systemic inflammatory response syndrome (SIRS) that is triggered by infection. On the other hand, multiple organ dysfunction syndrome (MODS) is the failure of critical organ function in patients suffering from SIRS.Because SIRS and SDOM are consequences of excessive inflammatory activation. The aim of this article is to provide a review of some pathophysiological aspects of the SRIS / SDOM construct of infectious origin, using the acute cholangitis as an example of this chain of events.

Key Points for Curbing Cardiopulmonary Bypass Inflammation

PURPOSE: Cardiopulmonary bypass (CPB) procedures are thought to activate systemic inflammatory reaction syndrome (SIRS). Strategies to curb systemic inflammation have been previously described. However, none of them is adequate, since "curbing" the extent of the inflammatory response requires a multimodal approach. The aim of the present mini-review is to discuss the main key points about the main principles in cardiopulmonary bypass curbing inflammation. METHODS: No systematic literature search (MEDLINE) and extracted data from the accumulated experience of the authors. The preconceived idea of an association between severe inflammation and coagulation disorders is reviewed. Also, some fundamental concepts, CPB inflammatory biomarkers, the vasoplegic syndrome and the need forindividual CPB protocols for children, diabetes and old patients, are discussed. CONCLUSION: The ways in which surgical technique (atraumatic vein harvest, biocompatibility and shear resistance of the circuit, monitoring, minimizing organ ischemia, minimal cross-clamping trauma, and blood management) are thought to curb SIRS induced by CPB and affect positively the patient outcome.Improved patient outcomes are strongly associated with these modalities of care, more than single or combinatorial drug strategies (aprotinin, tranexamic acid, pentoxifylline) or CPB modalities (minicircuits, heparin-coated circuits, retrograde autologous prime).

Valor predictivo de la procalcitonina en niños con sospecha de sepsis / Predictive value of procalcitonin in children with suspected sepsis Abstract

Introducción: El uso de biomarcadores podría constituir una herramienta en el diagnóstico, pronóstico y estratificación en la sepsis. El objetivo fue analizar el valor de la procalcitonina (PCT), proteína C reactiva (PCR) y lactato en la predicción de shock séptico, mortalidad y en la estratificación en niños con sospecha de sepsis. Pacientes y método: Estudio prospectivo en 81 pacientes en los cuales se midió niveles plasmáticos de PCT, PCR y lactato al ingreso en la unidad de cuidados intensivos. Los pacientes se categorizaron en síndrome de respuesta inflamatoria sistémica, sepsis, sepsis grave y shock séptico. Resultados: Las concentraciones de la PCT (ng/mL) aumentaron significativamente de acuerdo a la gravedad de la sepsis: 0,36 (0-1,2) para síndrome de respuesta inflamatoria sistémica; 1,96 (0,4-3,5) para sepsis; 7,5 (3,9-11,1) en sepsis grave; y 58,9 (35,1-82,7) para shock séptico (p < 0,001). Comparada con la PCR y el lactato, el área bajo la curva ROC reveló un poder discriminativo favorable de la PCT para predecir shock séptico y mortalidad: 0,91 (IC95%: 0,83-0,97) y 0,80 (IC95%: 0,69-0,88), respectivamente. Conclusiones: A diferencia de la PCR y el lactato, la determinación de la PCT al ingreso en la unidad de cuidados intensivos es un buen predictor de shock séptico y mortalidad, y permite estratificar a los pacientes de acuerdo a la gravedad de la sepsis.

Introduction: The use of biomarkers could be a tool for diagnosis, prognosis and stratifying children with sepsis. Our main goal was to analyze the value of procalcitonin (PCT), C reactive protein (CRP) and lactate in predicting mortality, septic shock and the stratification in children with suspected sepsis Patients and method: Prospective study in 81 patients. Plasma levels of PCT, CRP and lactate were measured at admission in the pediatric intensive care unit. Patients were categorized into systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock. Results: Concentrations of PCT (ng/mL) increased significantly according to the severity of sepsis: 0.36 (0-1.2) for systemic inflammatory response syndrome; 1.96 (0.4-3.5) for sepsis; 7.5 (3.9-11.1) for severe sepsis; and 58.9 (35.1-82.7) for septic shock (P <.001). Compared to CRP and lactate, the area under the ROC curve revealed a good discriminative power of PCT to predict septic shock and mortality, 0.91 (95% CI: 0.83-0.97) and 0.80 (95% CI: 0.69-0.88), respectively. Conclusions: In contrast to CRP and lactate, the determination of PCT in pediatric intensive care unit admission is a good predictor of mortality and septic shock and can stratify patients according to severity of sepsis.

Retinol, β-carotene and oxidative stress in systemic inflammatory response syndrome / Retinol, β-caroteno e estresse oxidativo na síndrome da resposta inflamatória sistêmica.

Objective: patients suffering systemic inflammatory response syndrome (SIRS) constitute a group susceptible to elevated levels of oxidative stress. This study’s aim is to evaluate the state of oxidative stress and levels of serum retinol and β-carotene in these patients. Methods: forty-six patients were divided into 2 groups: those those without diet (G1; n=18) and those with enteral nutritional support (G2; n=28). Serum levels of retinol and total carotenoids were measured. C-reactive protein (CRP) levels and Apache scores were also calculated. Oxidative stress was estimated by measuring thiobarbituric acid reactive substance (TBARS) levels. Results: the patients’ median age was 66.9 (SD=19.3) years. Lower concentrations of retinol and carotenoids were found in 68.6 and 66.7% of G1, respectively. In G2, despite average vitamin A levels being 8078 + 4035, retinol and β-carotene were considered insufficient (31.2 and 33.4%, respectively). No difference was noted between the 2 groups, according to the variables studied, with the exception being PCR and β-carotene (p=0.002; p=0.01). Conclusion: the data presented in this study supports the need to establish/revise clinical practices in treating SIRS patients, in light of this micronutrient’s role in the immune system and antioxidant defense without it interfering with its toxicity. .

Objetivo: pacientes que apresentam a síndrome da resposta inflamatória sistêmica (SIRS) constituem um grupo suscetível a níveis elevados de estresse oxidativo. O objetivo do presente estudo é avaliar o estado de estresse oxidativo e os níveis séricos de retinol e β-caroteno nesses pacientes. Métodos: quarenta e seis pacientes foram divididos em dois grupos: aqueles sem dieta (G1; n = 18) e aqueles com suporte nutricional enteral (G2, n = 28). Foram investigadas as concentrações séricas de retinol e carotenoides totais, proteína C reativa, estresse oxidativo e escore Apache. O estresse oxidativo foi avaliado por dosagem da peroxidação lipídica e estimado por meio da dosagem de TBARS (substâncias reativas ao ácido tiobarbitúrico). Resultados: a média de idade dos pacientes foi de 66,9 (±19,3). Baixas concentrações de retinol e carotenoides foram encontradas em 68,6 e 66,7% do G1, respectivamente. No G2, a concentração sérica média de vitamina A foi de 8078 (± 4035), e o retinol e o β-caroteno apresentaram percentual de inadequação de 31,2 e 33,4%, respectivamente. Não foi observada nenhuma diferença entre os dois grupos, de acordo com as variáveis estudadas, com exceção do PCR e do β-caroteno (p=0,002; p=0,01). Conclusão: os dados apresentados neste estudo indicam a necessidade de estabelecer/rever práticas clínicas no tratamento de pacientes com SIRS, tendo em conta o papel desse micronutriente no sistema imunológico e na defesa antioxidante, sem que isso interfira na sua toxicidade. .

Proteína C Reactiva en la EPOC y su relación con la gravedad de la enfermedad, las exacerbaciones y las comorbilidades / C-Reactive protein levels in patients with chronic obstructive pulmonary disease

Background: Patients with chronic obstructive pulmonary disease (COPD) have elevated serum levels of ultrasensitive C reactive protein (CRPus). This raise may be related directly to COPD and its associated systemic inflammation or secondary to other factors such as smoking status, disease severity, acute exacerbations, or associated complications. Aim: To evaluate the potential causes of raised levels of CRPus in stable COPD patients. Patients and Methods: Cohorts of 133 mild-to-very severe COPD patients (41 current smokers), 31 never-smokers, and 33 current smoker controls were compared. Clinical assessments included body mass index (BMI), fat (FM) and fat-free mass (FFM) measurement by DEXA, forced expiratory volume in one second (FEV1), arterial oxygen tension (PaO2), six-minute walking test (SMWT), emphysema (EMPH) and right thigh muscle cross-sectional area (TMCSA), both quantified by high resolution computed tomography. Results: Serum CRPus levels were significantly higher in COPD patients than in controls (7 ± 4.2 and 3.7 ± 2.7 mg/L respectively; p < 0.0001). Being smoker did not influence CRPus levels. These levels were significantly correlated with FM (r = 0.30), BMI (r = 0.21), FEV1 (r = -0.21), number of acute exacerbations of the disease in the last year (r = 0.28), and PaO2 (r = -0.27). Using multivariate analysis FM, PaO2, and number of acute exacerbations of the disease in the last year had the strongest association with CRPus levels. Conclusions: CRPus is elevated in COPD patients, independent of smoking status. It is weakly associated with fat mass, arterial oxygen tension and frequency of exacerbations.

Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury.

Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns.

Efeito da sinvastatina em um modelo experimental de sepse Flora Magno de Jesus Oliveira / Effect of simvastatin in an experimental model of sepsis

A sepse é uma condição médica severa, caracterizada por uma resposta inflamatória sistêmica (designada por Síndrome da Resposta Inflamatória Sistêmica), que ocorre em vigência de um quadro infeccioso, podendo evoluir para disfunção múltipla dos órgãos e morte. Atualmente é a principal causa de morte nas Unidades de Terapia Intensiva em todo o mundo. Nos últimos anos, diversos medicamentos foram testados na prevenção e tratamento da sepse, com resultados pouco animadores. Estudos recentes mostraram que as estatinas (drogas hipolipemiantes amplamente utilizadas no tratamento de dislipidemias) foram capazes de reduzir a mortalidade em pacientes sépticos, bem como o risco do desenvolvimento de sepse severa. As estatinas atuam inibindo a 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA) redutase, enzima que catalisa a conversão da HMG-CoA em mevalonato, etapa limitante na biosíntese do colesterol. Além de agirem na diminuição do colesterol sérico, as estatinas estão emergindo como potentes inibidores de processos inflamatórios, ações conhecidas como efeitos pleiotrópicos. Neste estudo tivemos como principal objetivo a avaliação dos efeitos da sinvastatina em um modelo de ligadura e punção cecal (CLP), especificamente sobre a taxa de sobrevida e parâmetros inflamatórios, como migração celular, ativação celular, eliminação bacteriana e produção de óxido nítrico. Observamos que a sinvastatina foi capaz de causar uma tendência de melhora nas funções renais e hepáticas de animais submetidos ao CLP. Observamos também que 24 horas após a cirurgia houve aumento da migração celular para o peritôneo, ocorrendo uma tendência de reversão deste efeito após o tratamento com sinvastatina (2 mg/kg). Nossos resultados também mostraram que a sinvastatina foi capaz de reduzir os níveis de TNF-alfa, MIF, IL-6 e IL1beta. Nossos resultados mostraram um aumento significativo na produção de óxido nítrico no peritôneo de animais que receberam o tratamento com sinvastatina, o que pode estar relacionado com o resultado obtido na contagem de Unidades Formadoras de Colônias, da qual houve uma tendência de diminuição. O tratamento com sinvastatina ainda mostrou poder ser capaz de diminuir a produção de óxido nítrico na corrente sanguínea. Observamos, também, alteração na formação de corpúsculos lipídicos de células provenientes do lavado peritoneal de camundongos tratados com a droga, sendo este número menor nesses animais. E ainda, foi observado um efeito in vitro da droga sobre macrófagos peritoneais, havendo diminuição do CFU em todas as concentrações utilizadas. Nossos estudos, portanto, indicam que os efeitos da sinvastatina estão relacionados a determinantes da fisiopatologia da sepse, o que torna de grande importância a contínua avaliação de seus mecanismos de ação, para que possivelmente esta droga seja implementada como terapia adjuvante no tratamento da sepse.

Os leucócitos e a resposta inflamatória na lesão de isquemia-reperfusão / Leukocytes and the inflammatory response in ischemia-reperfusion injury

Os eventos de isquemia-reperfusão desencadeiam uma resposta inflamatória sistêmica que pode levar a lesões celulares e até falência de órgãos. Tais repercussões são notadas no pós-operatório de cirurgias, em especial, com o uso de circulação extracorpórea. Sabe-se, atualmente, que os leucócitos exercem importante papel neste processo. Assim, este estudo aborda o papel dos leucócitos na fisiopatologia das lesões de isquemia-reperfusão e a ativação das cascatas inflamatórias por esse processo e procura auxiliar na compreensão destes mecanismos assim como trazer contribuições acerca das abordagens terapêuticas que possam atenuá-los. Esta revisão bibliográfica retrospectiva foi realizada a partir de documentos científicos publicados nos últimos dez anos, em português e inglês, indexados em bases de dados internacionais Medline e SciELO e de textos clássicos relacionados. Os descritores pesquisados foram: isquemia-reperfusão, leucócitos, resposta inflamatória, circulação extracorpórea, efeitos adversos e apoptose.

The events of ischemia-reperfusion injury triggers a systemic inflammatory response and can lead to cellular injury and organ failure. Such effects are noted in the postoperative recovery, especially with the use of cardiopulmonary bypass. Nowadays, it is known that leukocytes play an important role in this process. Therefore, this study addresses the role of leukocytes in the physiopathology of ischemia-reperfusion injuries and activation of inflammatory cascades through this process and seek to help in the understanding of these mechanisms as well as to bring contributions on the therapeutic approaches that can mitigate them. This retrospective review was performed from indexed scientific papers published over the last ten years in Portuguese and English in international databases MEDLINE and SciELO and related classic texts. The descriptors investigated were: ischemia-reperfusion, leukocytes, inflammatory response, cardiopulmonary bypass, adverse effects and apoptosis.

Is persistent hypotension after transient cardiogenic shock associated with an inflammatory response?

We evaluated the recovery of cardiovascular function after transient cardiogenic shock. Cardiac tamponade was performed for 1 h and post-shock data were collected in 5 domestic large white female pigs (43 ± 5 kg) for 6 h. The control group (N = 5) was observed for 6 h after 1 h of resting. During 1 h of cardiac tamponade, experimental animals evolved a low perfusion status with a higher lactate level (8.0 ± 2.2 vs 1.9 ± 0.9 mEq/L), lower standard base excess (-7.3 ± 3.3 vs 2.0 ± 0.9 mEq/L), lower urinary output (0.9 ± 0.9 vs 3.0 ± 1.4 mL·kg-1·h-1), lower mixed venous saturation, higher ileum partial pressure of CO2-end tidal CO2 (EtCO2) gap and a lower cardiac index than the control group. Throughout the 6-h recovery phase after cardiac tamponade, tamponade animals developed significant tachycardia with preserved cardiac index, resulting in a lower left ventricular stroke work, suggesting possible myocardial dysfunction. Vascular dysfunction was present with persistent systemic hypotension as well as persistent pulmonary hypertension. In contrast, oliguria, hyperlactatemia and metabolic acidosis were corrected by the 6th hour. The inflammatory characteristics were an elevated core temperature and increased plasma levels of interleukin-6 in the tamponade group compared to the control group. We conclude that cardiovascular recovery after a transient and severe low flow systemic state was incomplete. Vascular dysfunction persisted up to 6 h after release of tamponade. These inflammatory characteristics may also indicate that inflammatory activation is a possible pathway involved in the pathogenesis of cardiogenic shock.

Circulação extracorpórea em adultos no século XXI: ciência, arte ou empirismo?: [revisão] / Adult cardiopulmonary bypass in the twentieth century: science, art or empiricism?: [review]

A presente revisão tem por objetivo ressaltar alguns aspectos pouco discutidos da circulação extracorpórea (CEC), levando-se em consideração fisiologia, fisiopatologia e algumas novas tecnologias de perfusão. Assim, alguns aspectos, até certo ponto filosóficos, motivaram a elaboração dessa revisão: a) Preservar e atualizar os conhecimentos do cirurgião sobre a CEC, pelo simples fato de manter a sua liderança pedagógica sobre a sua equipe; b) Questionar se pacientes idosos e diabéticos pelas suas características individuais, assim como adotado para crianças, talvez merecessem protocolos mais apropriados; c) Questionar a reação inflamatória sistêmica causada pela exposição do sangue à superfície não endotelizada do circuito de CEC diante da importância crescente do contato do sangue com a ferida cirúrgica; d) Em relação ao tratamento da síndrome vasoplégica, o azul de metileno continua sendo a melhor opção terapêutica, embora, muitas vezes não seja eficiente pela existência de uma "janela terapêutica" embasada na dinâmica da ação da guanilato ciclase (saturação e síntese "de novo") e; finalmente, e) Razão da escolha do título, ressaltando que, em seus moldes atuais, a CEC seria conseqüência do empirismo, arte, ou da ciência? A mensagem final vem com a convicção de que tanto o empirismo, a arte e a ciência são muito fortes em se tratando da CEC.

The aim of the present review is to highlight some less discussed aspects of the cardiopulmonary bypass (CPB), taking into consideration the physiology, physiopathology, and some new technologies of perfusion. Thus, some points, to a certain extent philosophical, have motivated this revision: a) To preserve and update the surgeon knowledge regarding CPB, even to keep his/her pedagogical leadership on his/her surgical team; b) To question if elderly and diabetic patients, as a result of their individual characteristics deserve more appropriate protocols similar to those adopted for children; c) One third aspect would be the questioning of the systemic inflammatory reaction caused by the blood exposure to CPB non-endothelized circuit surface, in face of the increasing importance of blood contact with the surgical wound; d) In relation to the treatment of the vasoplegic syndrome, methylene blue continues being the best therapeutical option, even so, many times are not efficient on account of a highly probable existence of a "therapeutical window" based on the guanylate cyclase dynamics of action (saturation and synthesis "de novo") and; finally, e) The reason of the title, highlighting that based on its current patterns, would the CPB be an outcome of empiricism, art, or science? The bottom line of this article carries the certainty of that as much as the empiricism, art, and science are highly related to CPB.

Alteraciones metabólicas asociadas a la sepsis: proteínas, lípidos y carbohidratos / Metabolic disorders associated with sepsis: proteins, lipids and carbohydrates

Para garantizar la función vital orgánica normalmente ofrecida por la absorción dietética es necesario disponer de un sustrato energético adecuado para mantener la homeostasis. Cuando los ingresos dietéticos no son adecuados, el organismo acude a fuentes alternativas de obtención de energía dadas por la gluconeogénesis, lipólisis y cetogénesis. A la interrupción de estas fuentes provisionales de sustratos de energía se asocia la sepsis. Se altera durante la sepsis la función de la vía glucolítica, cuya integridad es necesaria para utilizar adecuadamente la glucosa en la obtención de energía. Todas estas anomalías, unidas a las interrupciones de la maquinaria productora de energía intracelular (enzimas glucolíticas, gluconeogénesis y mitocondria) producen una reducción del adenosintrifosfato intracelular, cuestión que socava todas las funciones consumidoras de energía celular, incluyendo la formación de sustratos energéticos (gluconeogénesis fallida), producción antioxidante y homeostasis del calcio. Asimismo se conoce que el aumento de los niveles de calcio intracelular activa vías enzimáticas potencialmente destructivas, las cuales disminuyen más la función celular y logran provocar la muerte a este nivel. Puede así desempeñar la acumulación de calcio intracelular un importante rol en el progreso de la sepsis temprana a una disfunción múltiple de órganos, la causa más frecuente de mortalidad en las unidades de cuidados intensivos

Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Sepsis is a systemic inflammatory response commonly caused by bacterial infection. We demonstrated that the outcome of sepsis induced by cecal ligation and puncture (CLP) correlates with the severity of the neutrophil migration failure towards infectious focus. Failure appears to be due to a decrease in the rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil migration impairment is mediated by the circulating inflammatory cytokines, such as TNF-alpha and IL-8, which induce the nitric oxide (NO) production systemically. It is supported by the fact that intravenous administration of these cytokines reduces the neutrophil migration induced by different inflammatory stimuli, and in severe sepsis the circulating concentrations of the cytokines and chemokines are significantly increased. Moreover, the neutrophil migration failure and the reduction in the rolling/adhesion were not observed in iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was also observed that circulating neutrophils obtained from septic patients present failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in sepsis, failure of neutrophil migration is critical for the outcome and that NO is involved in the process.

Síndrome de respuesta inflamatoria sistémica / Syndrome of systemic inflammatory response

Se realizó una revisión bibliográfica sobre el síndrome de respuesta inflamatoria sistémica, se definieron conceptos esenciales para la comprensión de este síndrome. Se describieron de forma precisa y resumida, la fisiopatología actualizada que comprende el papel de los mediadores, la importancia del endotelio, los leucocitos y los radicales libres. Se expuso la hipótesis actual en la génesis del síndrome así como la vigilancia y el seguimiento de estos pacientes afectados