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- ItemSomente MetadadadosAbsolute and relative adrenal insufficiency in children with septic shock(Lippincott Williams & Wilkins, 2005-04-01) Pizarro, C. F.; Troster, E. J.; Damiani, D.; Carcillo, J. A.; Universidade Federal de São Paulo (UNIFESP)Objective: Corticosteroid replacement improves outcome in adults with relative adrenal insufficiency and catecholamine-resistant septic shock. We evaluated the relationship of absolute and relative adrenal insufficiency to catecholamine-resistant septic shock in children.Design. Prospective cohort study.Setting. University hospital pediatric intensive care unit in Brazil.Patients. Fifty-seven children with septic shock. Children with HIV infection, those with a history of adrenal insufficiency, and those submitted to any steroid therapy or etomidate within the week before diagnosis of septic shock were excluded.Interventions: None.Measurements and Main Results., A short corticotropin test (250 mu g) was performed, and cortisol levels were measured at baseline and 30 and 60 mins posttest. Adrenal insufficiency was defined by a response <= 9 mu g/dL. Absolute adrenal insufficiency was further defined by a baseline cortisol < 20 mu g/dL and relative adrenal insufficiency by a baseline cortisol > 20 mu g/dL. Absolute adrenal insufficiency was observed in 18% of children, all of whom had catecholamine-resistant shock. Relative adrenal insufficiency was observed in 26% of children, of whom 80% had catecholamine-resistant and 20% had dopamine/dobutamine-responsive shock. All children with fluid-responsive shock had a cortisol response > 9 mu g/dL. Children with adrenal insufficiency had an increased risk of catecholamine-resistant shock (relative risk, 1.88; 95% confidence interval, 1.26-2.79). However, mortality was independently predicted by chronic illness or multiple organ failure (p <.05), not adrenal insufficiency.Conclusions: Absolute and relative adrenal insufficiency is common in children with catecholamine-resistant shock and absent in children with fluid-responsive shock. Studies are warranted to determine whether corticosterold therapy has a survival benefit in children with relative adrenal insufficiency and catecholamine-resistant septic shock.
- ItemAcesso aberto (Open Access)Concentrações séricas de vitamina D e disfunção orgânica em pacientes com sepse grave e choque séptico(Universidade Federal de São Paulo (UNIFESP), 2016-06-30) Alves, Fernanda Sampaio [UNIFESP]; Machado, Flavia Ribeiro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Vitamin D is important to the immunomodulation and regulation of inflammatory response. Nevertheless, vitamin D deficiency is rarely taken into account in critically ill patients and its relation with worse outcomes is uncertain. We aimed to assess the baseline serum levels of vitamin D and its variation after the first 7days in septic and non- septic patients and to correlate them with the degree of organ dysfunction both at inclusion and after the first seven days. This was a prospective, observational study in critically ill patients ?18 years-old with severe sepsis or septic shock. We also included a control group paired by age and degree of organ dysfunction.. We determined serum vitamin D levels at baseline (D0) and after the seventh day (D7). Septic and non-septic patients were categorized according to the improvement of vitamin D levels. We consider severe deficiency values below 10 ng/mL, deficiency values between 10 and 20 ng/mL, insufficiency values between 20 and 30 ng/mL and sufficiency if they were ? 30 ng/mL. We also assess clinical and laboratory data to determine the Sequential Organ Failure Assessment score on D0 and D7 and its variation. We considered significant results at p < 0.05. We included 51 patients, 26 with sepsis and 25 controls. The prevalence of hypovitaminosis D was 98%, with no significant difference between septic and non-septic patients. There was no significant correlation between vitamin D at D0 and the Sequential Organ Failure Assessment score at D0 or its variation after 7 days., There was no correlation between the variation of vitamin D and the variation of organ dysfunction, neither in general population nor in septic patients. The baseline levels of vitamin D weakly correlated with D0 magnesium levels (r = 0.387). The improvement in vitamin D levels was higher in the sepsis group. Patients who improved classification of vitamin D also had improved the Sequential Organ Failure Assessment score at D7 (p = 0.013). In conclusion, the prevalence of vitamin D deficiency was high in critically ill patients, both septic and non-septic ones. Septic patients had a greater improvement in their vitamin D levels after 7th days as compared with the non-septic patients. Those critically ill patients who improved from their vitamin D deficiency also had a greater reduction in the intensity of organ dysfunction after 7 days.
- ItemSomente MetadadadosControversies of surviving sepsis campaign bundles: Should we use them?(Lippincott Williams & Wilkins, 2008-01-01) Machado, Flavia R. [UNIFESP]; Freitas, Flavio G. R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Latin Amer Sepsis InstSepsis accounts for a huge number of deaths in intensive care units all over the world. in 2002, Surviving Sepsis Campaign (SSC) was launched, targeting a mortality reduction of 25% in 5 years. Treatment guidelines were developed, published in 2004 and revised in 2007. An educational program was initiated based on bundles in which 11 of those guidelines were put together to facilitate their assimilation and use. More than 10,000 patients have been enrolled worldwide. However, the SSC and its bundles have been harshly criticized both because of an industry funding and by the presumed fragility of the studies from where they were based. in this review, the main arguments of the SSC critics are discussed and refuted, and the main controversial issues of the resuscitation and management bundles are analyzed, taking into account the new evidence in the literature.
- ItemSomente MetadadadosGENERATION of NITRIC OXIDE and REACTIVE OXYGEN SPECIES BY NEUTROPHILS and MONOCYTES FROM SEPTIC PATIENTS and ASSOCIATION WITH OUTCOMES(Lippincott Williams & Wilkins, 2012-07-01) Santos, Sidneia Sousa [UNIFESP]; Brunialti, Milena Karina Coló [UNIFESP]; Rigato, Otelo [UNIFESP]; Machado, Flavia Ribeiro [UNIFESP]; Silva, Eliezer [UNIFESP]; Salomao, Reinaldo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hosp Albert Einstein; Hosp Sirio LibanesIn this study, our aims were to evaluate the reactive oxygen species (ROS) and nitric oxide (NO) generation by monocytes and neutrophils from septic patients and to correlate their levels with clinical outcomes. Forty-nine septic patients and 19 healthy volunteers were enrolled in the study. the ROS and NO production was quantified in monocytes and neutrophils in whole blood by flow cytometry, constitutively, and after stimulation with Staphylococcus aureus and Pseudomonas aeruginosa. Nitric oxide production by monocytes was higher in septic patients compared with healthy volunteers for all conditions and by neutrophils at baseline, and ROS generation in monocytes and neutrophils was higher in septic patients than in healthy volunteers for all conditions. Nitric oxide production by monocytes and neutrophils was decreased at day 7 compared with that at admission (day 0) in survivors at baseline and after stimulation with S. aureus. Reactive oxygen species production by the monocytes and neutrophils was decreased in survivors at day 7 compared with day 0 under all conditions, except by neutrophils at baseline. No difference was found in NO and ROS generation by monocytes and neutrophils between day 7 and day 0 in nonsurvivors. Generation of NO and ROS by neutrophils and monocytes is increased in septic patients, and their persistence is associated with poor outcome.
- ItemSomente MetadadadosHow Can We Estimate Sepsis Incidence and Mortality?(Lippincott Williams & Wilkins, 2017) Nunes Gobatto, Andre Luiz; Maccagnan Pinheiro Besen, Bruno Adler; Azevedo, Luciano Cesar Pontes [UNIFESP]Sepsis is one of the oldest and complex syndromes in medicine that has been in debate for over two millennia. Valid and comparable data on the population burden of sepsis constitute an essential resource for guiding health policy and resource allocation. Despite current epidemiological data suggesting that the global burden of sepsis is huge, the knowledge of its incidence, prevalence, mortality, and case-fatality rates is subject to several flaws. The objective of this narrative review is to assess how sepsis incidence and mortality can be estimated, providing examples on how it has been done so far in medical literature and discussing its possible biases. Results of recent studies suggest that sepsis incidence rates are increasing consistently during the last decades. Although estimates might be biased, this probably reflects a real increase in incidence over time. Nevertheless, case fatality rates have decreased, which is a probable reflex of advances in critical care provision to this very sick population at high risk of death. This conclusion can only be drawn with a reasonable degree of certainty for high-income countries. Conversely, adequately designed studies from middle-and low-income countries are urgently needed. In these countries, sepsis incidence and case-fatality rates could be disproportionally higher due to health care provision constraints and ineffective preventive measures.
- ItemSomente MetadadadosIMPROVING MORTALITY in SEPSIS: ANALYSIS of CLINICAL TRIALS(Lippincott Williams & Wilkins, 2010-09-01) Machado, Flávia Ribeiro [UNIFESP]; Mazza, Bruno Franco [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Latin Amer Sepsis InstSepsis accounts for a huge number of deaths in intensive care units worldwide. Encouraging data from recent studies show that some interventions are able to reverse such a picture. Surviving Sepsis Campaign (SSC) bundles were built based on these interventions. Many studies were published analyzing the impact of sepsis protocol implementation on compliance, costs, and mortality, and the results are herein analyzed. Based on these studies, it is not clear if the reduction is secondary to improvement in the quality of care naturally associated with protocol implementation or to the improvement in compliance to strict goals. A high heterogeneity is present among institutions and countries, and the pitfalls for protocol implementation seem to depend on local characteristics. in the same way, the impact of interventions might be different according to each institution's epidemiological profile. Interventions not impacting in low-mortality-rate institutions can be important for places where mortality is high. in Brazil, mortality rates are very high, and the results of Brazilian SSC network are presented and discussed.
- ItemSomente MetadadadosMICROCIRCULATORY EVALUATION in SEPSIS: A DIFFICULT TASK(Lippincott Williams & Wilkins, 2010-09-01) Koh, Ivan H. J. [UNIFESP]; Díaz, José Luis Menchaca [UNIFESP]; Koh, Tarso H. [UNIFESP]; Souza, Ricardo L. [UNIFESP]; Shu, Christopher M. [UNIFESP]; Rogerio, Victor E. [UNIFESP]; Liberatore, Ana M. A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Microcirculatory dysfunction plays a pivotal role in the pathogenesis of severe sepsis and septic shock; hence, microcirculation blood flow monitoring has gained increasing attention. However, microcirculatory imaging is still investigational in human sepsis and has not yet been incorporated into routine clinical practice for several reasons, including the difficult interpretation of microcirculation imaging data, difficulty to draw a parallel between sublingual microcirculation imaging and organ microcirculation dysfunction, as well as the absence of microvessel dysfunction parameters defining sequential microcirculatory changes from the early to late stages of the disease, which could aid in the context of therapeutic approaches and of prognostic parameters. the purpose of this review was to bridge the experimental abdominal organ microvascular derangement kinetics and clinical aspects of microcirculatory findings in the early phase of severe sepsis/septic shock.
- ItemSomente MetadadadosSurviving sepsis campaign in Brazil(Lippincott Williams & Wilkins, 2008-01-01) Meira Teles, Jose Mario; Silva, Eliezer; Westphal, Glauco; Costa Filho, Rubens; Machado, Flavia Ribeiro [UNIFESP]; Hosp Portugues; Universidade de São Paulo (USP); Hosp Municipal Sao Jose; Hosp Procardiaco; Universidade Federal de São Paulo (UNIFESP)Severe sepsis and septic shock have long been a challenge in intensive care because of their common occurrence, high associated costs of care, and significant mortality. the Surviving Sepsis Campaign (SSC) was developed in an attempt to address clinical inertia in the adoption of evidence-based strategies. the campaign relies on worldwide support from professional societies and has gained consensus on the management of patients with severe sepsis. the guidelines have subsequently been deployed into two bundles, with each bundle component sharing a common relationship in time. the widespread adoption of such evidence-based practice in clinical care has been disappointingly slow despite the quantifiable benefits regarding mortality. in Brazil, a country of continental dimensions with a heterogeneous population and unequal access to health services, this reality is no different. From 2004 to 2007, four prospective studies were published describing the country's reality. in the multicenter Promoting Global Research Excellence in Severe Sepsis (PROGRESS) Study, the in-hospital mortality rate was higher in Brazil when compared with other countries: 56% against 30% in developed countries and 45% in other developing countries. During these 2.5 years of the campaign in Brazil, 43 hospitals have been receiving the necessary training to put in practice the recommended measures in all Brazilian regions, except for the North. the idea of the campaign is based on a 25% reduction in the relative risk of death from severe sepsis and septic shock within 5 years in the SSC-participating Brazilian hospitals. Ideally, the mortality rate should come to a 41.2% level subject to the 2009 deadline. This article aims to describe the actual scenario of the SSC implementation in Brazilian institutions and to report on some initiatives that have been used to overcome barriers.
- ItemSomente MetadadadosSurviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012(Lippincott Williams & Wilkins, 2013-02-01) Dellinger, R. Phillip; Levy, Mitchell M.; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M.; Sevransky, Jonathan E.; Sprung, Charles L.; Douglas, Ivor S.; Jaeschke, Roman; Osborn, Tiffany M.; Nunnally, Mark E.; Townsend, Sean R.; Reinhart, Konrad; Kleinpell, Ruth M.; Angus, Derek C.; Deutschman, Clifford S.; Machado, Flavia R. [UNIFESP]; Rubenfeld, Gordon D.; Webb, Steven A.; Beale, Richard J.; Vincent, Jean-Louis; Moreno, Rui; Surviving Sepsis Campaign Guidelin; Cooper Univ Hosp; Brown Univ; St George Hosp; Hop Raymond Poincare; Vivantes Klinikum Neukolln; Emory Univ Hosp; Hadassah Hebrew Univ; Denver Hlth Med Ctr; McMaster Univ; Barnes Jewish Hosp; Univ Chicago; Calif Pacific Med Ctr; Univ Jena; Rush Univ; Univ Pittsburgh; Univ Penn; Universidade Federal de São Paulo (UNIFESP); Sunnybrook Hlth Sci Ctr; Royal Perth Hosp; Guys & St Thomas Hosp Trust; Erasme Univ Hosp; Hosp Sao JoseObjective: To provide an update to the Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock, last published in 2008.Design: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. the entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development.Methods: the authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). the potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations.Results: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure >= 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao(2) /Fio(2) ratio of <= 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao(2) /Fio(2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose <= 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/ septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C).Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven absolute adrenal insufficiency (2C). Conclusions: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients. (Crit Care Med 2013; 41: 580-637)
- ItemSomente MetadadadosTLR signaling pathway in patients with sepsis(Lippincott Williams & Wilkins, 2008-01-01) Salomao, Reinaldo [UNIFESP]; Martins, Paulo Sergio [UNIFESP]; Brunialti, Milena Karina Coló [UNIFESP]; Fernandes, Maria da Luz [UNIFESP]; Martos, Leandro Silva Willish [UNIFESP]; Mendes, Marialice Erdelyi [UNIFESP]; Gomes, Natalia E. [UNIFESP]; Rigato, Otelo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The pathogenesis of sepsis involves complex interaction between the host and the infecting microorganism. Bacterial recognition and signaling are essential functions of the cells of innate immune systems and drive a coordinated immune response. One of the more intriguing aspects of sepsis is the fact that the protective and damaging host response are part of the same process, that is, the inflammatory response that is aimed to control the infectious process also underscores many of the pathophysiological events of sepsis. the discovery of Toll-like receptors (TLRs) in humans, and the early recognition of TLR-4 as the receptor that signals LPS bioactivity were major breakthroughs not only in the field of sepsis but also in immunology as a whole. in this article, we aimed to review TLR expression and signaling in the context of sepsis. the results obtained by our group show that TLR and other cellular surface receptors may be differently regulated on mononuclear cells and neutrophils, and that they are dynamically modulated across the stages of sepsis. Toll-like receptor signaling gene expression in mononuclear cells is decreased in more severe forms of the disease. in contrast, up-regulated genes are seen along the clinical spectrum of sepsis in neutrophils.
- ItemSomente MetadadadosToll-like receptor pathway signaling is differently regulated in neutrophils and peripheral mononuclear cells of patients with sepsis, severe sepsis, and septic shock(Lippincott Williams & Wilkins, 2009-01-01) Salomao, Reinaldo [UNIFESP]; Brunialti, Milena K. C. [UNIFESP]; Gomes, Natalia E. [UNIFESP]; Mendes, Marialice E. [UNIFESP]; Diaz, Ricardo Sobhie [UNIFESP]; Komninakis, Shirley [UNIFESP]; Machado, Flavia R. [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Rigato, Otelo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: Up- and down-regulation of inflammatory response was described in blood cells from septic patients, according to the stage of sepsis and the cells evaluated. This study aimed to evaluate the Toll-like receptor (TLR) signaling pathway gene expression in peripheral blood mononuclear cells (PBMC) and neutrophils in patients throughout the different stages of sepsis.Design: Prospective, observational study.Settings. Two emergency rooms and two intensive care units in one university and one teaching hospital.Patients and Controls., A total of 15 septic patients, five with sepsis, five with severe sepsis, and five with septic shock, in addition to five healthy volunteers were enrolled.Interventions: None.Measurements and Main Results: the Human-TLR Signaling Pathway, which comprises 84 genes related to TLR-mediated signal transduction, was evaluated by real time polymerase chain reaction in PBMC and neutrophils obtained from patients and controls. the fold change for each gene (2((-Delta Delta Ct))) was compared between the groups. Genes with fold changes greater than 2 and significant changes in Delta CT are reported as differently expressed. the told change ratios in PBMC gene expression between septic patients and healthy controls revealed a dynamic process according to the stage of sepsis, tending toward down-regulation of the TLR signaling pathway in PBMC in the more severe forms of the disease. However, the differential gene expression was restricted to five down-regulated genes in septic shock patients, which are found in the effector and downstream pathways. Neutrophils showed a different pattern of adaptation. Patients with sepsis, severe sepsis, and septic shock presented a broad gene upregulation, which included all functional groups evaluated and persisted throughout the stages of the disease.Conclusions: TLR-signaling pathway genes are differently regulated in PBMC and neutrophils of septic patients, and are dynamically modulated throughout the different stages of sepsis. (Grit Care Med 2009; 37:132-139)