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- ItemSomente MetadadadosABANDON the MOUSE RESEARCH SHIP? NOT JUST YET!(Lippincott Williams & Wilkins, 2014-06-01) Osuchowski, Marcin F.; Remick, Daniel G.; Lederer, James A.; Lang, Charles H.; Aasen, Ansgar O.; Aibiki, Mayuki; Azevedo, Luciano C.; Bahrami, Soheyl; Boros, Mihaly; Cooney, Robert; Cuzzocrea, Salvatore; Jiang, Yong; Junger, Wolfgang G.; Hirasawa, Hiroyuki; Hotchkiss, Richard S.; Li, Xiang-An; Radermacher, Peter; Redl, Heinz; Salomao, Reinaldo [UNIFESP]; Soebandrio, Amin; Thiemermann, Christoph; Vincent, Jean-Louis; Ward, Peter; Yao, Yong-Ming; Yu, Huang-Ping; Zingarelli, Basilia; Chaudry, Irshad H.; AUVA Res Ctr; Boston Univ; Brigham & Womens Hosp; Harvard Univ; Penn State Coll Med; Oslo Univ Hosp; Ehime Univ; Hosp Sirio Libanes; Univ Szeged; SUNY Upstate Med Univ; Univ Messina; Southern Med Univ Guangzhou; Beth Israel Deaconess Med Ctr; Chiba Univ; Washington Univ; Univ Kentucky; Ulm Med Univ Clin; Universidade Federal de São Paulo (UNIFESP); Univ Indonesia; Queen Mary Univ London; Univ Brussels; Univ Michigan; Chinese Peoples Liberat Army Gen Hosp; Chang Gung Mem Hosp; Cincinnati Childrens Hosp Med Ctr; Univ Alabama BirminghamMany preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. the underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. in conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. the scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.
- 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 MetadadadosEscherichia coli lipopolysaccharide impairs the calcium signaling pathway in mesangial cells: role of angiotensin II receptors(Soc Experimental Biology Medicine, 2010-06-01) Maquigussa, Edgar [UNIFESP]; Arnoni, Carine P. [UNIFESP]; Cristovam, Priscila C. [UNIFESP]; Oliveira, Andrea S. de [UNIFESP]; Higa, Elisa M. S. [UNIFESP]; Boim, Mirian A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Sepsis causes impaired vascular reactivity, hypotension and acute renal failure. the ability of the Escherichia coli endotoxin (lipopolysaccharide [LPS]) to impair agonist-induced contractility in mesangial cells, which contributes to LPS-induced renal dysfunction, was evaluated. Agonist-induced intracellular calcium ([Ca(2+)]i) mobilization was analyzed using angiotensin II (AngII). the effect of LPS on the levels of the renin-angiotensin system (RAS) components and the roles of vasodilatation-inducing molecules including AT2 receptor (AT2R) and nitric oxide (NO) in the cell reactivity were also evaluated. Confluent human mesangial cells (HMCs) were stimulated with LPS (0111-B4, 100 mu g/mL). AngII-induced [Ca(2+)]i mobilization was measured by fluorometric analysis using Fura-2AM in the absence and presence of an AT2R antagonist (PD123319). the mRNA and protein levels for angiotensinogen, renin, angiotensin-converting enzyme, AT1R and AT2R were analyzed by realtime reverse transcriptase-polymerase chain reaction and Western blot, respectively. NO production was measured by the chemiluminescence method in the culture media after 24, 48 and 72 h of LPS incubation. After 24 h, LPS-stimulated HMCs displayed lower basal [Ca(2+)]i and an impaired response to AngII-induced rise in [Ca(2+)]i. LPS significantly increased AT2R levels, but did not cause significant alterations of RAS components. PD123319 restored both basal and AngII-induced [Ca(2+)]i peak, suggesting an involvement of AT2R in these responses. the expected increase in NO production was significant only after 72 h of LPS incubation and it was unaffected by PD123319. Results showed that LPS reduced the reactivity of HMCs to AngII and suggest that the vasodilatation induced by AT2R is a potential mediator of this response through a pathway independent of NO.
- ItemSomente MetadadadosEscherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells(Nature Publishing Group, 2006-03-01) Almeida, W. S.; Maciel, T. T.; Di Marco, Giovana Seno [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Campos, Alexandre Holthausen [UNIFESP]; Schor, Nestor [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. the present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human mesangial cell (HMC) RAS. Quiescent HMC were incubated with vehicle or LPS (1-100 mu g/ml), and levels of angiotensin I and II (Ang I and II) and their metabolites were analyzed by high-performance liquid chromatography. in addition, angiotensin-converting enzyme (ACE) and renin activity were also investigated. Cell lysate and extracellular medium levels of Ang II were rapidly reduced (1 h) in a time- and concentration-dependent manner, reaching a significant -9 fold-change (P < 0.001) after 3 h of LPS incubation. Similar results were obtained for Ang I levels (-3 fold-change, P < 0.001). We ruled out Ang I and II degradation, as levels of their metabolic fragments were also significantly decreased by LPS. ACE activity was slightly increased following LPS incubation. On the other hand, renin activity was significantly inhibited, as Ang I concentration elevation following exogenous angiotensinogen administration was blunted by LPS (-60% vs vehicle, P < 0.001). Renin and angiotensinogen protein levels were not affected by LPS according to Western blot analysis. Taken together, these data demonstrate for the first time that LPS significantly downregulates HMC RAS through inhibition of renin or renin-like activity. These findings are potentially related to the development of and/or recovery from acute renal failure in the context of sepsis.
- 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 MetadadadosGraph Based Characterization of Microcirculation in Sepsis Using Sidestream Dark Field Imaging(Ieee, 2014-01-01) Zoghbi, J. M.; De-La-Cruz, L. T.; Galarreta, M. A. G. V.; Jackowski, Marcel P.; Vieira, J. C. F. [UNIFESP]; Liberatore, A. M. A. [UNIFESP]; Koh, Ivan H. J. [UNIFESP]; IEEE; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Real-time detection of sepsis on a video data is a new aboard technique that aids the septic patient and decreases the high mortality rate. the progressive impairment of the micro-circulation associated with increased systemic inflammatory response in sepsis has been considered the origin of the multiple organ dysfunction syndrome that often leads to death. However, despite the recognized importance of the microcirculatory dysfunction, analysis methods able to correlate the severity of sepsis with the degree of impairment of micro-hemodynamic captured by portable microscope Side-stream Dark Field Imaging (SDF) are rarely used. Hence, the classification of the severity of sepsis by analyzing the micro-circulatory dysfunction would be of great assistance in diagnosing severity and therapeutic management. in this context, the aim of this work is to propose a new computational methodology based on image processing to obtain graph metrics for determining the degree of micro-vascular and tissue commitment due to sepsis.
- 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 MetadadadosImpaired production of interferon-gamma and tumor necrosis factor-alpha but not of interleukin 10 in whole blood of patients with sepsis(Lippincott Williams & Wilkins, 2003-02-01) Rigato, Otelo [UNIFESP]; Salomão, Reinaldo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)It has been demonstrated that lipopolysaccharide (LPS)-induced cytokine response in patients with sepsis differ from the normal host, yet this has not been controlled for the presence of underlying disease. We studied the ability of LPS and killed gram-negative bacteria (GNB) to induce tumor necrosis factor (TNF)-alpha and interleukin (IL) 10, and of phytohemagglutinin (PHA) to induce interferon (IFN)-gamma, in whole blood from patients with sepsis (SP, n = 20), patients with matched underlying disease and without sepsis (control patients, n = 20), and healthy volunteers (HV, n = 20). LPS-induced TNF-alpha production was lower in SP (median = 638 pg/mL) compared with control patients (4060 pg/mL; P = 0.003), and control patients production was lower compared with HV (5329 pg/mL; P < 0.001). Pseudomonas aeruginosa-induced TNF-α production was lower in SP (1443 pg/mL) than in control patients (7319 pg/mL; P < 0.05), and was not different between control patients and HV (6612 pg/mL; P = 0.6). IFNgamma production was lower in SP (948 pg/mL) compared with control patients (5516 pg/mL; P < 0.001), and the control patients production was lowercompared with HV (11,282 pg/mL; P < 0.001). IL-10 production was not different among the three groups. Down-regulation of TNF-alpha production in patients with sepsis, although not restricted to them, was more pronounced with LPS than with GNB. Although the presence of underlying disease may be involved in the regulatory mechanisms of host response, the use of controls with matched underlying diseases provides strong evidence for the septic condition in the down-regulation of inflammatory response in patients with sepsis.
- ItemSomente MetadadadosLate-onset Bloodstream Infections in Hospitalized Term Infants(Lippincott Williams & Wilkins, 2014-09-01) Testoni, Daniela [UNIFESP]; Hayashi, Madoka; Cohen-Wolkowiez, Michael; Benjamin, Daniel K.; Lopes, Renato D.; Clark, Reese H.; Smith, P. Brian; Duke Clin Res Inst; Universidade Federal de São Paulo (UNIFESP); Duke Univ; Pediat Obstet Ctr Res & Educ; Clemson UnivBackground: the epidemiology and incidence of late-onset blood stream infections (BSIs) in premature infants have been described, but studies describing late-onset BSI in term infants are sparse. We sought to describe the pathogens, incidence, risk factors and mortality of late-onset BSI in hospitalized term infants.Methods: A cohort study was conducted of infants >= 37 weeks gestational age and <= 120 days of age discharged from Pediatrix Medical Group neonatal intensive care units from 1997 to 2010. We examined all cultures obtained from day of life 4-120 and used multivariable regression to assess risk factors for late-onset BSI.Results: We found a total of 206,019 infants cared for between day of life 4 and 120, and the incidence of late-onset BSI was 2.7/1000 admissions. We identified Gram-positive organisms in 64% of the cultures and -Gram-negative organisms in 26%. We found a decreased risk of late-onset BSI in infants with the following characteristics: small for gestational age, delivery by Cesarean, antenatal antibiotic use and discharged in the later years of the study. Late-onset BSI increased the risk of death after controlling for confounders [odds ratio 8.43 (95% confidence interval 4.42-16.07)].Conclusion: Our data highlight the importance of late-onset BSI in hospitalized term infants. We identified Gram-positive organisms as the most common pathogen, and late-onset BSI was an independent risk factor for death.
- ItemSomente MetadadadosMechanical Ventilation in Sepsis: A Reappraisal(Lippincott Williams & Wilkins, 2017) Zampieri, Fernando G.; Mazza, Bruno Franco [UNIFESP]Sepsis is the main cause of close to 70% of all cases of acute respiratory distress syndromes (ARDS). In addition, sepsis increases susceptibility to ventilator-induced lung injury. Therefore, the development of a ventilatory strategy that can achieve adequate oxygenation without injuring the lungs is highly sought after for patients with acute infection and represents an important therapeutic window to improve patient care. Suboptimal ventilatory settings cannot only harm the lung, but may also contribute to the cascade of organ failure in sepsis due to organ crosstalk. Despite the prominent role of sepsis as a cause for lung injury, most of the studies that addressed mechanical ventilation strategies in ARDS did not specifically assess sepsis-related ARDS patients. Consequently, most of the recommendations regarding mechanical ventilation in sepsis patients are derived from ARDS trials that included multiple clinical diagnoses. While there have been important improvements in general ventilatory management that should apply to all critically ill patients, sepsis-related lung injury might still have particularities that could influence bedside management. After revisiting the interplay between sepsis and ventilation-induced lung injury, this review will reappraise the evidence for the major components of the lung protective ventilation strategy, emphasizing the particularities of sepsis-related acute lung injury.
- ItemAcesso aberto (Open Access)Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?(Pioneer Bioscience Publ Co, 2016) Leite, Heitor Pons [UNIFESP]; Peixoto de Lima, Lucio Flavio [UNIFESP]Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named "metabolic resuscitation", would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to "mitochondrial resuscitation" are expected to increase driven by genomics and metabolomics.
- ItemSomente MetadadadosModulation of the renin-angiotensin-aldosterone system in sepsis: a new therapeutic approach?(Informa Healthcare, 2010-01-01) Salgado, Diamantino Ribeiro; Rocco, Jose Rodolfo; Silva, Eliezer [UNIFESP]; Vincent, Jean-Louis; Universidade Federal do Rio de Janeiro (UFRJ); Univ Libre Bruxelles; Albert Einstein Hosp; Universidade Federal de São Paulo (UNIFESP)Importance of the field: Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. the renin-angiotensin-aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting.Areas covered in this review. the role of RAAS activation in severe sepsis and septic shock, and the potential benefits (and risks) of using RAAS antagonists.What the reader will gain: Insight into RAAS function in severe sepsis and the potential for RAAS inhibitors to be used as an adjunctive therapy in patients with severe sepsis, with discussion of promising results from animal models of sepsis.Take home message: Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.
- ItemSomente MetadadadosPredictive value of pulse pressure variation for fluid responsiveness in septic patients using lung-protective ventilation strategies(Oxford Univ Press, 2013-03-01) Freitas, Flavio Geraldo Rezende [UNIFESP]; Bafi, Antonio Tonete [UNIFESP]; Nascente, A. P. M. [UNIFESP]; Assuncao, M. [UNIFESP]; Mazza, B. [UNIFESP]; Azevedo, L. C. P. [UNIFESP]; Machado, F. R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The applicability of pulse pressure variation (PP) to predict fluid responsiveness using lung-protective ventilation strategies is uncertain in clinical practice. We designed this study to evaluate the accuracy of this parameter in predicting the fluid responsiveness of septic patients ventilated with low tidal volumes (TV) (6 ml kg(1)).Forty patients after the resuscitation phase of severe sepsis and septic shock who were mechanically ventilated with 6 ml kg(1) were included. the PP was obtained automatically at baseline and after a standardized fluid challenge (7 ml kg(1)). Patients whose cardiac output increased by more than 15 were considered fluid responders. the predictive values of PP and static variables [right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP)] were evaluated through a receiver operating characteristic (ROC) curve analysis.Thirty-four patients had characteristics consistent with acute lung injury or acute respiratory distress syndrome and were ventilated with high levels of PEEP [median (inter-quartile range) 10.0 (10.013.5)]. Nineteen patients were considered fluid responders. the RAP and PAOP significantly increased, and PP significantly decreased after volume expansion. the PP performance [ROC curve area: 0.91 (0.821.0)] was better than that of the RAP [ROC curve area: 0.73 (0.590.90)] and pulmonary artery occlusion pressure [ROC curve area: 0.58 (0.400.76)]. the ROC curve analysis revealed that the best cut-off for PP was 6.5, with a sensitivity of 0.89, specificity of 0.90, positive predictive value of 0.89, and negative predictive value of 0.90.Automatized PP accurately predicted fluid responsiveness in septic patients ventilated with low TV.
- ItemSomente MetadadadosProcalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients(W B Saunders Co, 2004-04-01) Arkader, R.; Troster, E. J.; Abellan, D. M.; Lopes, M. R.; Raiz, R.; Carcillo, J. A.; Okay, T. S.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Univ PittsburghObjective: To determine the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) concentration after pediatric cardiac surgery with cardiopulmonary bypass.Design: Prospective, clinical cohort study.Setting: A fifteen-bed tertiary-care pediatric intensive care unit.Patients: Fourteen pediatric patients admitted for cardiac surgery.Measurements and Main Results: Serum PCT and CRP were measured before cardiopulmonary bypass (CPB); after CPB; and on the first, second, and third days after surgery by means of immunoluminometry and nephelometry, respectively. Reference values for systemic inflammatory response syndrome are 0.5 to 2.0 ng/mL for PCT and <5 mg/L for CRP. Baseline serum PCT and CRP concentrations were 0.24 +/- 0.13 ng/mL and 4.06 +/- 3.60 mg/L (median 25th percentile-75th percentile), respectively. PCT concentrations increased progressively from the end of CPB (0.62 +/- 0.30 ng/mL), peaked at 24 hours postoperatively (POD1) (0.77 +/- 0.49 ng/mL), and began to decrease at 48 hours or POD2 (0.35 +/- 0.21 ng/mL). CRP increased just after CPB (58.82 +/- 42.23 mg/L) and decreased after 72 hours (7.09 +/- 9.81 mg/L).Conclusion: An increment of both PCT and CRP was observed just after CPB. However, PCT values remained within reference values, whereas CRP concentrations increased significantly after CPB until the third day. These preliminary results suggest that PCT was more effective than CRP to monitor patients with SIRS and a favorable outcome. (C) 2004 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosProtective activity of the antilipopolysaccharide antibodies from human cord serum(Blackwell Publishing, 2006-08-01) Pontes, Gerlandia Neres; Massironi, Silvia Gomes; Arslanian, Christina; Friedlander-Del Nero, Dora Lisa; Sales Carneiro-Sampaio, Magda Maria; Nagao-Dias, Aparecida Tiemi [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Univ Fed CearaWe evaluated the ability of human maternal and cord serum antibodies to protect mice challenged with live Escherichia coli serotype O6:K2ac (E. coli O6). Mice received paired maternal or cord serum pools before a challenge with E. coli O6 to evaluate the mortality rate. All the pools were able to protect the animals challenged with bacteria except the test group from paired maternal and cord sera from preterm neonates containing less than 1.0 mg L-1 immunoglobulin G antibody levels. in liver, spleen and mesenteric lymph nodes from the control group (phosphate-buffered saline), more than 10(2) CFU mL(-1) bacteria were found at 30 min and more than 10(5) CFU mL(-1) after 120 min. the test group showed lower bacterial counts in the organs, and no bacteria in the mesenteric lymph nodes during the evaluated period. Tumor necrosis factor alpha and interleukin 6 were undetectable in serum from animals pretreated with paired maternal and cord serum pools from full-term neonates and pools from preterm neonates containing high antibody and avidity levels. Our findings suggest that placental transfer of antilipopolysaccharide O6 immunoglobulin G antibodies to neonates has a high capacity to prevent lethal infection with E. coli O6 in a mouse protection model and that the degree of protection is determined by the concentration and avidity of these IgG antibodies.
- ItemSomente MetadadadosRisk factors for death in children and adolescents with cancer and sepsis/septic shock(Lippincott Williams & Wilkins, 2008-07-01) Silva, Elenice Domingos da [UNIFESP]; Koch Nogueira, Paulo Cesar [UNIFESP]; Russo Zamataro, Tania Maria [UNIFESP]; Carvalho, Werther Brunow de [UNIFESP]; Petrilli, Antonio Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To assess risk factors for mortality in children and adolescents with cancer and sepsis/septic shock, admitted to intensive care unit.Patients and Methods: Retrospective Study of a cohort of cancer and sepsis/septic shock patients (n = 155) admitted to Oncological Pediatric Intensive Care Unit, between October 1998 and October 2001, with assessment of 12 potential risk factors for mortality by univariate analysis, followed by multivariable analysis.Results: Forty-seven out of 155 patients died (30.3%). In the present sample, after multivariable analysis, 3/12 variables proved to be statistically significant: respiratory infection [hazard ratio (HR) = 2.3 and 95% confidence interval (Cl) = 1.3-4.2], duration of granUlocytopenia (HR = 2.4 and 95% Cl = 1.2-4.9), and number of organ dysfunction (HR = 7.4 and 95% Cl = 2.6-21.3).Conclusions: Our data suggest that mortality in Oncological Pediatric Intensive Care Unit is high and the main factors involved in prognosis are number of dysfunctional organs, respiratory infections, and duration of granulocytopenia; the mortality rises 7.4 times for each dysfunctional organ. We believe that prospective and multicenter Studies are necessary to better characterize risk factors that are specific for cancer patients to produce a particular score to predict severity of complications and mortality of children with cancer.
- ItemAcesso aberto (Open Access)Sepse durante a gestação: relato de caso(Associação de Medicina Intensiva Brasileira - AMIB, 2007-06-01) Laks, Renato [UNIFESP]; Pedroso, José L. [UNIFESP]; Pinto, Juliana E. Marques [UNIFESP]; Góis, Aécio Flávio Teixeira de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)BACKGROUND AND OBJECTIVES: Sepsis during pregnancy is a rare complication. This potentially fatal disease often occurs due to maternal infectious and can lead to fetal loss. Therefore, any attempted treatment must be aimed at the mother s well being. As a matter of fact, there are few recent medical publications about sepsis in pregnancy. In spite of this, the treatment based on Surviving Sepsis Campaign seems suitable and practical. The aim of this article is making a case report highlighting a very well succeeded treatment of a pregnant woman with urinary sepsis. CASE REPORT: A 22 year old in her 27th week of pregnancy is hospitalized with pyelonefhritis. One day later, she begins presenting signs of sepsis and unresponsive hypoxemia, resulting in intubation. Afterwards, she evolved with persistent low blood pressure that was unresponsive to volume expansion and had to be put on vasopressor medication. She received intensive care support based on Surviving Sepsis Campaign. The patient evolved with an important improvement of her ventilatory stats and was extubated. After completing antibiotic treatment, she was discharged and delivered a healthy baby after 42 weeks pregnancy. CONCLUSIONS: Sepsis in pregnancy is a rare and potentially fatal complication. The main treatment is based on Surviving Sepsis Campaign. The patient had an outstanding improvement and overcame her condition after intensive care support.
- ItemSomente MetadadadosSepsis in Children: Global Implications of the World Health Assembly Resolution on Sepsis(Lippincott Williams & Wilkins, 2017) Kissoon, Niranjan; Reinhart, Konrad; Daniels, Ron; Machado, Machado Flavia R. [UNIFESP]; Schachter, Raymond D.; Finfer, SimonBackground: Sepsis, worldwide the leading cause of death in children, has now been recognized as the global health emergency it is. On May 26, 2017, the World Health Assembly, the decision-making body of the World Health Organization, adopted a resolution proposed by the Global Sepsis Alliance to improve the prevention, diagnosis, and management of sepsis. Objective: To discuss the implications of this resolution for children worldwide. Conclusions: The resolution highlights sepsis as a global threat and urges the 194 United Nations member states to take specific actions and implement appropriate measures to reduce its human and health economic burden. The resolution is a major step toward achieving the targets outlined by the Sustainable Developmental Goals for decreasing mortality in infants and children, but implementing it will require a concerted global effort.
- ItemSomente MetadadadosSepsis in Solid-Organ Transplant Patients(Lippincott Williams & Wilkins, 2017) Bafi, Antonio Tonete [UNIFESP]; Tomotani, Daniere Yurie Vieira [UNIFESP]; Freitas, Flavio Geraldo Rezende [UNIFESP]The growing population of solid organ transplant (SOT) recipients is at a significantly increased risk for developing infections. In some patients, the infection can lead to a dysregulated systemic inflammatory response with acute organ dysfunction. SOT recipients with sepsis tend to have less fever and leukocytosis instances. Moreover, they have diminished symptoms and attenuated clinical and radiologic findings. The current management of sepsis is similar to general patients. It relies mainly on early recognition and treatment, including appropriate administration of antibiotics and resuscitation with intravenous fluids and vasoactive drugs when needed. The infusion of fluids should be closely monitored because elevated central venous pressure levels and fluid overload can be particularly harmful. There is no consensus on how to manage immunosuppressive therapies during sepsis, although dose reduction or withdrawal is suggested to improve the host immunological response. There is compelling evidence suggesting that infections are associated with reduced allograft and patient survival. However, the traditional belief that SOT patients who develop sepsis have worse outcomes than non-transplanted patients has been challenged.