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%.

Trait-specific effects of exogenous triiodothyronine on cytokine and behavioral responses to simulated systemic infection in male Siberian hamsters.

Seasonal changes in day length enhance and suppress immune function in a trait-specific manner. In Siberian hamsters (Phodopus sungorus) winter-like short days (SDs) increase blood leukocyte concentrations and adaptive T cell dependent immune responses, but attenuate innate inflammatory responses to simulated infections. Thyroid hormone (TH) signaling also changes seasonally and has been implicated in modulation of the reproductive axis by day length. Immunologically, TH administration in long days (LD) enhances adaptive immune responses in male Siberian hamsters, mimicking effects of SDs. This experiment tested the hypothesis that T3 is also sufficient to mimic the effects of SD on innate immune responses. Adult male hamsters housed in LDs were pretreated with triiodothyronine (T3; 1 µg, s.c.) or saline (VEH) daily for 6 weeks; additional positive controls were housed in SD and received VEH, after which cytokine, behavioral, and physiological responses to simulated bacterial infection (lipopolysaccharide; LPS) were evaluated. SD pretreatment inhibited proinflammatory cytokine mRNA expression (i.e. interleukin 1ß, nuclear factor kappa-light-chain-enhancer of activated B cells). In addition, the magnitude and persistence of anorexic and cachectic responses to LPS were also lower in SD hamsters, and LPS-induced inhibition of nest building behavior was absent in SD. T3 treatments failed to affect behavioral (food intake, nest building) or somatic (body mass) responses to LPS in LD hamsters, but one CNS cytokine response to LPS (e.g., hypothalamic TNFα) was augmented by T3. Together these data implicate thyroid hormone signaling in select aspects of innate immune responses to seasonal changes in day length.

Electro-acupuncture attenuates inflammatory responses and intraabdominal pressure in septic patients: A randomized controlled trial.

BACKGROUND: A pathological increase in intraabdominal pressure (IAP) and inflammatory responses have negative effects on splanchnic, respiratory, cardiovascular, renal, and neurological function in septic patients with intestinal dysfunction. Electro-acupuncture (EA) has been evidenced to have a bidirectional neuron-endocrine-immune system regulating effect in patients with intestinal dysfunction. The purpose of current study was to evaluate the effects of EA at "Zusanli" (ST36) and "Shangjuxu" (ST37) on inflammatory responses and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi. METHODS: Eighty-two septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi were randomly assigned to control group (n = 41) and EA group (n = 41). Patients in control group were given conventional therapies including fluid resuscitation, antiinfection, vasoactive agents, mechanical ventilation (MV), supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in EA group underwent 20-minutes of EA at ST36-ST37 twice a day for 5 days. At baseline, posttreatment 1, 3, and 7 days, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and IAP levels, were measured, respectively. And days on MV, length of stay in intensive care unit (ICU) and 28 days mortality were recorded. RESULTS: The serum levels of TNF-α and IL-1ß and IAP levels at posttreatment 1, 3, and 7 days were lower significantly in the EA group compared with the control group (mean [SD]; 61.03 [20.39] vs 79.28 [20.69]; P < .005, mean [SD]; 35.34 [18.75] vs 66.53 [30.43]; P < .005 and mean [SD]; 20.32 [11.30] vs 32.99 [20.62]; P = .001, respectively, TNF-α. Mean [SD]; 14.11 [5.21] vs 16.72 [5.59]; P = .032, mean [SD]; 9.02 [3.62] vs 12.10 [4.13]; P = .001 and mean [SD]; 5.11 [1.79] vs 8.19 [2.99]; P < .005, respectively, IL-1ß. Mean [SD]; 14.83 [5.58] vs 17.55 [3.37]; P = .009, mean [SD]; 11.20 [2.57] vs 14.85 [3.01]; P < .005 and mean [SD]; 8.62 [2.55] vs 11.25 [2.72]; P < .005, respectively, IAP). There were no significant differences in the duration of MV, length of stay in ICU, and 28d mortality between the groups. CONCLUSION: EA at ST36-ST37 attenuated inflammatory responses through reduction in serum levels of TNF-α and IL-1ß and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi.

[Cardiogenic shock : Current evidence]. / Kardiogener Schock : Aktuelle Evidenz.

This CME article addresses the pathophysiology, incidence, current survival outcome and treatment options for patients with cardiogenic shock as a complication of acute myocardial infarction. The shock spiral of left heart failure due to cardiac infarction, subsequent vasoconstriction and paradoxical vasodilation due to the systemic inflammation response syndrome (SIRS) is a vicious circle which must be interrupted. Treatment focuses on the evidence from randomized clinical trials and the current guideline recommendations. With respect to interventional and surgical treatment the question of culprit lesion vs. complete revascularization is still unsolved. For medicinal treatment acetylsalicylic acid (ASA) and heparin are more often supplemented with prasugrel and ticagrelor. In the case of inotropes, dobutamine remains the first-line treatment option and for vasopressors norepinephrine. The calcium sensitizer levosimendan has not provided the hoped for superiority over conventional treatment in randomized trials. The use of intra-aortic balloon pumps (IABP) is no longer recommended as circulatory support in acute heart failure (reduced to class III). The use of percutaneous implantable mechanical circulatory support devices has not shown a survival benefit in the few randomized trials carried out so far even when compared with IABP, due to increased bleeding complications.

Déficit de vitamina D y morbimortalidad en pacientes críticos pediátricos / Vitamin D deficiency and morbimortality in critically ill paediatric patients

Objetivos: Determinar la prevalencia y factores de riesgo del déficit de vitamina D (VDD) en una unidad de cuidados intensivos pediátricos (UCIP), así como su relación con la morbimortalidad durante el ingreso. Material y métodos: Estudio observacional prospectivo realizado en la UCIP de un hospital terciario en 2 fases: I: estudio de cohortes, y II: estudio de prevalencia. Se incluyó a 340 niños > 6 meses, excluyendo a aquellos con enfermedad renal crónica, trastornos paratiroideos y suplementación con vitamina D. Se realizó medición de 25-hidroxivitamina D total (25[OH]D) en las primeras 48 h del ingreso, parathormona (PTH), calcio, fósforo, gasometría venosa, hemograma, proteína C reactiva y procalcitonina. Se registraron datos sociodemográficos, características del episodio y complicaciones. Resultados: La prevalencia de VDD (< 20ng/ml) fue del 43,8%, con media de 22,28 (IC del 95%, 21,15-23,41) ng/ml. Los pacientes con déficit fueron de mayor edad (61 vs. 47 meses, p = 0,039), sus padres tenían un mayor nivel académico (36,5% vs. 20%, p = 0,016), ingresaron más frecuentemente en invierno y primavera, obtuvieron mayor puntuación PRISM-III (6,8 vs. 5,1, p = 0,037), mayor estancia (3 vs. 2 días, p = 0,001) y morbilidad (61,1% vs. 30,4%, p<0,001) que los pacientes con niveles suficientes (≥ 20ng/ml). Los pacientes fallecidos tuvieron niveles inferiores de 25(OH)D (14 ± 8,81ng/ml vs. 22,53 ± 10,53ng/ml, p = 0,012). La OR ajustada para la morbilidad fue 5,44 (IC del 95%, 2,5-11,6). Conclusiones: El VDD es frecuente en pacientes críticos pediátricos y está relacionado con la morbimortalidad en UCIP, aunque queda por esclarecer si se trata de una relación causal o es simplemente un marcador de gravedad en diferentes situaciones clínicas (AU)

Objectives: To determine the prevalence and risks factors of vitamin D deficiency, as well as its relationship with morbidity and mortality in a PICU. Material and methods An observational prospective study in a tertiary children's University Hospital PICU conducted in two phases: I: cohorts study, and II: prevalence study. The study included 340 critically ill children with ages comprising 6 months to 16 years old. Exclusion criteria: Chronic kidney disease, known parathyroid disorders, and vitamin D supplementation. Total 25-hydroxyvitamin D [25(OH)D] was measured in the first 48 hours of admission to a PICU. Parathormone, calcium, phosphate, blood gases, blood count, C-reactive protein, and procalcitonin were also analysed. A record was also made of demographic features, characteristics of the episode, and complications during the PICU stay. Results: The overall prevalence rate of vitamin D deficiency was 43.8%, with a mean of 22.28 (95% CI 21.15-23.41) ng/ml. Patients with vitamin D deficiency were older (61 vs 47 months, P=.039), had parents with a higher level of academic studies (36.5% vs 20%, P=.016), were admitted more often in winter and spring, had a higher PRISM-III (6.8 vs 5.1, P=.037), a longer PICU stay (3 vs 2 days, P=.001), and higher morbidity (61.1% vs 30.4%, P< 001) than the patients with sufficient levels of 25(OH)D. Patients who died had lower levels of 25(OH)D (14 ± 8.81ng/ml versus 22.53 ± 10.53ng/ml, P=.012). Adjusted OR for morbidity was 5.44 (95%CI; 2.5-11.6). Conclusions: Vitamin D deficiency is frequent in critically ill children, and it is related to both morbidity and mortality, although it remains unclear whether it is a causal relationship or it is simply a marker of severity in different clinical situations (AU)

Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery.

Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.

[What the surgeon needs to know about basic new concepts of inflammation and their therapeutic consequences: sanitation of inflammation is not a passive but rather an active process regulated by lipid mediators]. / Was der Chirurg über grundlegend neue Konzepte zur Entzündung und deren therapeutische Konsequenzen wissen sollte: Die Ausheilung der Entzündung ist kein passiver, sondern ein durch Lipidmediatoren regulierter aktiver Prozess.

The acute inflammatory response as a physiological programme that protects the organism against injurious pathogens is characterised by highly regulated actions of pro- and anti-inflammatory mediators. Intensive investigations during the last decades have led to the identification of these mediators and their complex interplay as well as the design and development of anti-inflammatory therapies. However, the resolution of acute inflammation has long been considered to be a passive process. In consequence, little was known about the mechanisms which guide acute inflammation either to complete resolution, repair of inflamed tissue and restoration of normal function or to a chronic inflammatory process characterised by persistent signs of inflammation, tissue damage and impaired function. Predominantly during the last decade the so-called specialised proresolving mediators (SPM) have been identified. These essential fatty acid-derived mediators - lipoxins, resolvins, protectins, and maresins - terminate the acute inflammatory responses and stimulate their complete resolution. SPM possess both anti-inflammatory and proresolving activities in that they inhibit pro-inflammatory cytokines, limit infiltration of neutrophils, enhance macrophage uptake, and finally stimulate their non-phlogistic activation and clearance of apoptotic neutrophils and microbial particles. It has been demonstrated in multiple animal models of human inflammatory diseases that, e.g., atherosclerosis, diabetes, and inflammatory bowel diseases are caused by a decreased synthesis and/or an impaired signal transduction of the proresolving mediators. Future studies are warranted to clarify whether these proresolving lipid mediators will participate in healing human inflammatory diseases and their complications.

Erythrocyte selenium concentration as a marker of selenium status.

BACKGROUND & AIMS: Plasma selenium concentration and glutathione peroxidase (GPx) activity are commonly used as markers of selenium nutritional status. However, plasma selenium concentrations fall independently of selenium status during the acute phase response and GPx is analytically problematic. The assay for erythrocyte selenium is robust and concentrations are unaffected by the systemic inflammatory response. This study was performed to investigate the validity of erythrocyte selenium measurement in assessing selenium status. METHODS: C-reactive protein (CRP), plasma and erythrocyte selenium concentrations and GPx activity were measured in 96 women from two regions of Malawi with low and high selenium dietary intakes. CRP and plasma and erythrocyte selenium was measured in 91 critically ill patients with a systemic inflammatory response. RESULTS & CONCLUSIONS: The median CRP value of all subjects from Malawi was 4.2 mg/L indicating no inflammation. The median CRP value for the critically ill patients was 126 mg/L indicating this group was inflamed. In the non-inflamed population there was a strong positive correlation (r = 0.95) between erythrocyte and plasma selenium and a strong positive correlation (r = 0.77) between erythrocyte selenium and erythrocyte GPx up to 6.10 nmol/g Hb after which maximal activity was reached. In the inflamed population, plasma selenium was low, erythrocyte selenium was normal and there was a weak correlation (r = 0.30) between selenium concentrations in plasma and erythrocytes. This demonstrates that plasma selenium is affected by the inflammatory response while erythrocyte selenium concentration is unaffected and can be used to reliably assess selenium status across a wide range of selenium intakes.

Immune-enhancing nutrition in surgical critical care.

Immune-enhancing nutrition, or "immunonutrition," refers to the use of specialized nutrients, including glutamine, alanine, omega-3 fatty acids, and others, that help regulate the body's response to illness and injury. Clinical studies have demonstrated some very specific benefits, including fewer infectious complications and shorter length of hospitalization, in certain populations including high-risk surgical patients, trauma victims, and the critically-ill. Nationally recognized guidelines support the use of immune-enhancing nutrition in high-risk patients.

Hepatic encephalopathy.

Hepatic encephalopathy is a serious and potentially fatal complication of both acute and chronic liver disease, arising as a result of hepatocellular failure, cirrhosis and/or portal-systemic shunting (Ferenci et al, 2002). It reflects a broad spectrum of neuropsychiatric abnormalities, encompassing a range of defects in psychomotor, locomotive, cognitive, emotional and behavioural functions (Prakash and Mullen, 2010). Hepatic encephalopathy is either overt or minimal. While overt hepatic encephalopathy can be diagnosed using bedside clinical tests, minimal hepatic encephalopathy is clinically invisible and requires psychometric testing to diagnose. The rising prevalence of end-stage viral hepatitis-related liver disease, coupled with the growing problem of alcoholic and non-alcoholic fatty liver disease, has significantly increased the burden of disease from cirrhosis (Mooney et al, 2007; Fleming et al, 2008), so recognition and appropriate management of the manifestations of decompensating cirrhosis (including hepatic encephalopathy) is essential. Hepatic encephalopathy has a substantial societal burden because of its impact on survival, quality of life and daily functioning, including an impaired ability to drive, leaving patients especially vulnerable to road traffic accidents (Ferenci et al, 2002; Prakash and Mullen, 2010).

Comparison of the effects of different intravenous fat emulsions in patients with systemic inflammatory response syndrome and sepsis.

BACKGROUND: In this study, the authors aimed to compare the effects that a medium- and long-chain triglyceride (MCT/LCT) fat infusion and a fish oil-based (ω-3) fat infusion for parenteral nutrition (PN) had on systemic inflammation, cytokine response, and hepatic steatosis in mixed intensive care unit (ICU) patients. METHODS: This was a single-center, placebo-controlled, randomized clinical trial in a university hospital. Four patient groups, including systemic inflammatory response syndrome (SIRS) and sepsis patients, were assigned to receive PN employing the MCT/LCT fat infusion or the fish oil-based fat infusion over 7 days. Blood biochemistry and liver steatosis were evaluated. RESULTS: Twenty sepsis and 20 SIRS patients were included in this study. There was no statistically significant difference in terms of biochemical values and Acute Physiology and Chronic Health Evaluation II scores between the different feeding groups. Sepsis groups who received MCT/LCT revealed higher grades of liver steatosis by ultrasound on days 7 and 10 (P < .05). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 values in sepsis group 1 (S1) were higher than in sepsis group (S2) on day 7, whereas IL-1 values were higher on days 3, 7, and 10 in group S1 than in group S2. Conversely, IL-10 values on days 3 and 7 were significantly higher in group S2. CONCLUSION: Fish oil-based fat emulsions might have anti-inflammatory and hepatoprotective effects in hyperinflammatory disease such as sepsis.

Tolerability and efficacy of a low-volume enteral supplement containing key nutrients in the critically ill.

BACKGROUND & AIMS: To compare early supplementation with antioxidants and glutamine using a low-volume enteral supplement containing key nutrients to an energy adjusted standard elementary diet and to investigate its effect on clinical efficacy and tolerability in critically ill patients with sepsis/SIRS. The primary endpoints were length of stay in the ICU and sufficient enteral feed. METHODS: This was a randomized, prospective, single-blind, controlled study in 58 critically ill patients (56.9% male, mean age 46.7 years, mean APACHE II score 21.6). They received either a low-volume enteral supplement containing key nutrients or a diluted standard nutrition solution. After 10 or 14 days inflammatory parameters, catecholamine need, and maximal enteral delivery were determined. RESULTS: Patients receiving a low-volume enteral supplement containing key nutrients did not reach sufficient enteral feed more often than controls (76 vs. 62%, respectively, p = 0.17). The difference in vitamin E and selenium uptake was higher in the treatment group than controls (12.4 vs. 3.7 and 54.7 vs. 16.3, respectively, p ≤ 0.011). Parameters such as fever, antibiotic treatment, artificial ventilation, and death were comparable. This was also true for days of ICU or hospital stay (33 ± 23 and 49 ± 34 days, respectively). CONCLUSIONS: The low-volume enteral supplement containing key nutrients was well tolerated and led to a better vitamin E and selenium supply. However, it did not affect length of ICU or hospital stay. Further studies are necessary to determine which disease-specific subgroups may benefit from this supplementation or which group may be harmed.

Selenio en los pacientes críticos con Respuesta Inflamatoria Sistémica / Selenium in critically ill patients with systemic inflammatory response

El Selenio es un micronutriente esencial para el hombre. Los estados de Respuesta Inflamatoria Sistémica (RIS) y Disfunción Orgánica Múltiple (DOM) tales como la sepsis severa, el trauma grave, la pancreatitis severa y quemaduras críticas se caracterizan por la existencia de estrés oxidativo. En este contexto, la depleción del estado nutricional de Selenio es una característica distintiva; la misma se traduce por una reducción de los niveles séricos de Selenio y de las diferentes selenoenzimas, en especial la Glutatión Peroxidasa y la Selenoproteína P. Estas selenoproteínas antioxidantes cumplen un rol protectivo frente a la lipoperoxidación de las membranas celulares participando además en el proceso de regulación de la respuesta inflamatoria. Ha sido demostrada la existencia de una correlación directa entre el grado de depleción de Selenio y la severidad de la enfermedad crítica. En los últimos años, numerosos estudios clínicos han investigado los efectos de la suplementación de Selenio en pacientes críticos con RIS -DOM. Esta estrategia terapéutica sería capaz de mejorar los resultados optimizando el pronóstico de la enfermedad crítica. En tal sentido, algunos pequeños estudios clínicos han demostrado una disminución del número de complicaciones infecciosas y de la estadía hospitalaria en los grupos de pacientes críticos suplementados con Selenio. Sin embargo, hasta el momento actual no existen datos concluyentes que permitan definitivamente afirmar la existencia de una reducción significativa de la mortalidad con el uso de Selenio en Terapia Intensiva. El objetivo del presente artículo de revisión es estudiar el metabolismo y estado nutricional del Selenio, evaluar el rol de las selenoenzimas durante la enfermedad crítica y repasar los estudios de suplementación de Selenio como estrategia antioxidante en Terapia Intensiva analizando por último la evidencia actual. Las recomendaciones actuales parecen sugerir el uso de altas dosis de Selenio parenteral. Sin embargo, recomendaciones definitivas sobre la suplementación de Selenio en pacientes críticos necesitan la realización de nuevos ensayos clínicos, randomizados, multicéntricos y doble ciego

Selenium is an essential micronutrient for humans. Critically ill patients with Systemic Inflammatory Response Syndrome (SIRS) and Multiple Organ Dysfunction (MOD) —such as severe sepsis, trauma, severe pancreatitis and critical burns— are exposed to severe oxidative stress. These patients exhibit decreased serum Selenium and selenoenzymes like Glutathione Peroxidase and Selenoprotein P. Selenoenzymes play a major role in protecting cells against lipid peroxidation and they are involved in the inflammatory response regulation. The degree of selenium deficiency correlates with disease severity and the incidence of mortality. In the past years, some clinical trials have studied Selenium supplementation effects in critical illness with SIRS-MOD. This therapeutic strategy could improve the outcome and prognosis in critically ill patients. Few small trials have demonstrated Selenium supplementation beneficial effects, reducing the rate of infectious complications and length of hospital stay. However, no clinical trials using Selenium supplementation in high doses have yet demonstrated significant improvement in mortality. The aims of this review are to evaluate: a) Selenium metabolism, b) the role of selenoenzymes during critical illness, c) clinical studies using Selenium alone or in combination with other antioxidants in critically ill patients and d) to analyze current parenteral Selenium replacement strategies and their results. Further multicentre, well designed randomized, double blind clinical trials about Selenium supplementation in critically ill patients with SIRS and MODS are required and appear to be attractive, necessary and challenging

Evolutive trophic phases of the systemic acute inflammatory response, oxygen use mechanisms and metamorphosis / Fases evolutivas tróficas de la respuesta inflamatoria aguda sistémica, mecanismos de utilización del oxígeno y metamorfosis

The physiopathological mechanisms involved in the systemic posttraumatic inflammatory response are studied. The successive phases of this inflammatory response are trophic mechanisms of increasing complexity. Moreover, evolutionary complications would give rise to the return to more primitive trophic mechanisms (AU)

Fases evolutivas tróficas de la respuesta inflamatoria aguda sistémica, mecanismos de utilización del oxígeno y metamorfosis. Se estudian los mecanismos fisiopatológicos implicados en la respuesta inflamatoria postraumática. Se considera que las sucesivas fases de esta respuesta inflamatoria constituyen mecanismos tróficos de complejidad creciente. Asimismo, las complicaciones evolutivas ocasionarían la regresión a mecanismos tróficos más primitivos (AU)

Parenteral nutrition with n-3 lipids in sepsis.

Dietary supplements of n-3 fatty acids have long been used to influence chronic inflammatory disorders. Recent studies with an immune-enhancing diet partly based on n-3 fatty acids report beneficial effects in patients with acute hyper-inflammatory diseases, such as the sepsis syndrome or adult respiratory distress syndrome (ARDS). The possible suppression of exaggerated leucocyte activity, the improvement of microcirculatory events, as well as the opportunity to administer intravenous lipids enriched in n-3 fatty acids signal the possibility of a combination of parenteral caloric support and pharmacological intervention. Using parenteral administration of fish oil-based lipids, a new rapid and highly effective anti-inflammatory agent may allow the option to alter the immune status in hyper-inflammatory diseases such as sepsis and ARDS.

Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock.

Oxidant-mediated reperfusion injury of the gut is a major contributor of the systemic inflammatory response in hemorrhagic shock. Recent studies have suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective mechanism against oxidant stress. We assessed whether HO-1 induction modulates the synthesis of tumor necrosis factor-alpha (TNF-alpha) in hemorrhagic shock. In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb) increased HO-1 mRNA expression in macrophages. This increased expression was associated with a decreased expression of TNF-alpha mRNA, as well as decreased plasma concentrations of TNF-alpha. These effects of Hb were reduced by the HO-1 inhibitor tin-protoporphyrin (Sn-PP 20 micromol/kg), while Sn-PP had no effect in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema, vascular injury, and increased mesenteric blood flow, and these effects were reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock, possibly through its antioxidant properties. Interventions that induce HO-1 may be beneficial in the treatment of shock states, leading to a reduced systemic inflammatory response.

[Pancreatitis and nutrition. Significance of the gastrointestinal tract and nutrition for septic complications]. / Pankreatitis und Ernährung. Bedeutung des Gastrointestinaltraktes und der Ernährung für die septischen Komplikationen.

Septic complications are an important factor for the morbidity and mortality of acute pancreatitis. The gut has been identified as a source of infection early in the course of the disease allowing intestinal bacteria to translocate into pancreatic necrosis and other organs. Bacterial translocation is promoted by an impaired intestinal mucosal barrier which can be attributed to the reduced oxygen and substrate supply of the intestine during the early systemic response to the pancreatic injury. A rat model of severe acute pancreatitis has been used to confirm the hypothesis that an impaired mucosal barrier can be stabilized by supplying certain nutritients, vitamins and trace elements. Following a discussion of the many aspects of bacterial translocation and gut derived sepsis, the role of the gut and nutrition for the development of septic complications in acute pancreatitis is summarized as follows: Early in the course of acute pancreatitis the gut is a target organ of the primary systemic inflammatory response (SIRS) to pancreatic injury. SIRS-induced gut barrier dysfunction promoting bacterial translocation makes the gut the motor for secondary (septic) complications. As a septic focus the gut becomes a target for therapeutic measures aimed at stabilizing the impaired gut barrier. Nutritive factors demonstrated to improve impaired gut barrier function include early enteral feeding and specific factors like glutamine which are essential for enterocytes and colonocytes in stress. Experimental data are presented to underline the significance of these nutritive factors and subsequent randomized multicenter trials performed to verify the positive experimental results are introduced. The effect of other nutritive factors (e.g. omega-3-fatty acids) has not yet been systemically investigated. Thus, experimental and clinical studies need to be performed for evaluating their effect on bacterial translocation and the disease course in acute pancreatitis.

Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats.

OBJECTIVE: To document the effects of propofol on the hemodynamic and inflammatory responses to endotoxemia in an animal model. DESIGN: Randomized, prospective laboratory study. SETTING: University experimental laboratory. SUBJECTS: Thirty-two male rats. INTERVENTIONS: The animals were randomly assigned to one of four groups: a) endotoxemia group (n = 8), which received intravenous Escherichia coli endotoxin (15 mg/kg over 2 mins); b) control group (n = 8), which was treated identically to the endotoxemia group except for the substitution of 0.9% saline for endotoxin; c) propofol group (n = 8), which was treated identically to the control group but also received propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after the injection of 0.9% saline; and d) propofol-endotoxemia group (n = 8), which was treated identically to the endotoxemia group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gases, and acid-base status were recorded and the blood propofol concentrations and plasma cytokine concentrations were measured during the 5-hr observation. Microscopic findings of lung tissue for each group were obtained at necropsy. The systolic arterial pressure and heart rate of the propofol-endotoxemia group were similar to those of the endotoxemia group. The increases in the plasma cytokine (tumor necrosis factor, interleukin-6, and interleukin-10) concentrations, in the base deficit, and in the infiltration of neutrophils in the air space or vessel walls of the lungs were attenuated in the propofol-endotoxemia group compared with the endotoxemia group. CONCLUSIONS: Propofol attenuated cytokine responses, base deficit, and activation of neutrophils to endotoxemia. These findings suggest that propofol may inhibit inflammatory response and prevent the development of metabolic acidosis during endotoxemia.