Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways.

Insulin-like growth factor-1 (IGF-1) plays critical roles in the development of the central nervous system (CNS), including the retina, regulating cell proliferation, differentiation, and survival. Here, we investigated the role of IGF-1 on retinal cell proliferation using primary cultures from rat neural retina. Our data show that IGF-1 stimulates retinal cell proliferation and regulates the expression of neurotrophic factors, such as interleukin-4 and brain-derived neurotrophic factor. In addition, our results indicates that IGF-1-induced retinal cell proliferation requires activation of multiple signaling pathways, including phosphatidylinositol 3-kinase, protein kinase Src, phospholipase-C, protein kinase C delta, and mitogen-activated protein kinase pathways. We further show that activation of matrix metalloproteinases and epidermal growth factor receptor is also necessary for IGF-1 enhancing retinal cell proliferation. Overall, these results unveil potential mechanisms by which IGF-1 ensures retinal cell proliferation and support the notion that manipulation of IGF-1 signaling may be beneficial in CNS disorders associated with abnormal cell proliferation.

Interleukin-4 activates divergent cell-intrinsic signals to regulate retinal cell proliferation induced by classical growth factors.

In the developing retina, precise coordination of cell proliferation, differentiation, and survival is essential for proper retinal maturation and function. We have previously reported evidence that interleukin-4 (IL-4) plays critical roles in neuronal differentiation and survival during retinal development. However, little is known about the role of IL-4 on retinal cell proliferation. In the current study, we investigated if IL-4 regulates cell proliferation induced by epidermal growth factor (EGF) and by fibroblast growth factor 2 (FGF2) in primary retinal cell cultures obtained from newborn rats. First, we show that EGF and FGF2 act as mitogens for glial cells, increasing proliferation of these cells in the retina. EGF- and FGF2-induced mitogenesis requires activation of distinct cell-intrinsic signals. In retinal cells exposed to FGF2, IL-4 downregulates p53 levels (a protein whose activation induces cell-cycle arrest) and increases mitogenic responsiveness to FGF2 through activation of protein kinase A (PKA) pathway. Conversely, in retinal cells exposed to EGF, IL-4 downregulates cyclin D1 levels (a protein required for cell-cycle progression), upregulates p53 levels, and decreases mitogenic responsiveness to EGF. The inhibitory effect induced by IL-4 on retinal cells exposed to EGF requires activation of Janus kinase 3 (JAK3), but not activation of PKA. Based on previous and current findings, we propose that IL-4 serves as a node of signal divergence, modulating multiple cell-intrinsic signals (e.g., cyclin D1, p53, JAK3, and PKA) and mitogenic responsiveness to cell-extrinsic signals (e.g., FGF2 and EGF) to control cell proliferation, differentiation, and survival during retinal development.

Factors leading to increased operational costs in a public hospital in São Paulo, Brazil / Fatores determinantes para o aumento dos custos operacionais em um hospital público de São Paulo, Brasil

Objectives: To quantify the operational costs of a municipal public hospital in the city of São Paulo (Brazil) and to identify factors that led to cost increases during the year of 2016 using the absorption method. Methods: This was a retrospective study conducted between January and December of 2016 at Vila Santa Catarina Municipal Hospital, a public tertiary hospital in São Paulo, Brazil. Results: We identified and analyzed a total of 8702 inpatient data. Average day cost per patient was US$ 949, with a median of US$ 1,825, and a total operating cost of US$ 48,743,847. Transplant patients showed the highest median costs, while pregnant women had the lowest median costs, 69.9% of the 8,702 hospitalized patients was above the mean cost of US$ 3,068 registered for 2016. Age was associated with a 6.6% increase in cost for each one-year increase in age, while the cost associated with female patients was 1.1 times that of men. Patients who died in the hospital were 8 times more likely to cost more than patients who were discharged from the hospital. Oncology, transplant, and clinical-surgical patients had 18.8 times the cost of patients in the maternity unit, respectively. Conclusion: We identify the operating costs of the Vila Santa Catarina Municipal Hospital, where the average cost for the operation of the unit was US$ 133.179. The cost per patient was US$ 1,825.91. We also concluded as to the second objective that the cost increase factors were age and death.

Objetivos: Quantificar os custos operacionais de um hospital público municipal da cidade de São Paulo (Brasil) e identificar fatores determinantes no aumento de custos durante o ano de 2016. Métodos: Estudo retrospectivo realizado entre janeiro e dezembro de 2016 no Hospital Municipal Vila Santa Catarina, um hospital público terciário em São Paulo, Brasil. Resultados: Identificamos e analisamos um total de 8.702 dados de pacientes internados. O custo médio paciente-dia foi de US$ 949, com mediana de US$ 1.825 e um custo operacional de US$ 48.743.847. O transplante teve os maiores custos médios, enquanto as gestantes apresentaram os menores, 69,9% dos 8.702 pacientes hospitalizados estavam acima do custo médio de US $ 3.068 registrado em 2016. A idade foi associada a um aumento de 6,6% no custo para cada aumento de um ano na idade, enquanto o custo associado ao sexo feminino pacientes foi 1,1 vez maior do que os homens. Os pacientes que morreram no hospital tiveram uma probabilidade 8 vezes maior de custar mais do que os pacientes que receberam alta do hospital. Pacientes oncológicos, transplantes e clínico-cirúrgicos apresentaram 18,8 vezes o custo dos pacientes na maternidade, respectivamente. Conclusão: Identificamos os custos operacionais do Hospital Municipal de Vila Santa Catarina, onde o custo médio para a operação da unidade foi de US$ 133.179. O custo por paciente foi de US$ 1.825,91. Também concluímos quanto ao segundo objetivo que os fatores de aumento de custo foram idade e morte.

Quality improvement model (IHI) as a strategy to implement a sepsis protocol in a public hospital in Brazil.

A major challenge for hospitals in low-income and middle-income countries is to improve management of patients diagnosed with sepsis. The objective of the present study was to evaluate the Institute for Healthcare Improvement (IHI) Model as a strategy to implement a managed sepsis protocol aimed at reducing sepsis mortality. We performed a longitudinal, prospective, non-randomised study using PDSA cycles for translating and implementing improvement actions and tools. Baseline case mortality/case fatality data were collected, and compliance rates were evaluated according to the Surviving Sepsis Campaign guidelines (3-hour care-bundle). Sepsis multidisciplinary work teams were designated and were responsible to develop Driver Diagrams and implement process changes in the intensive care unit, wards and emergency department. Satisfaction levels of healthcare professionals were assessed (balance variables). The study was carried out in a public quaternary hospital, in São Paulo city, Brazil (Hospital Municipal da Vila Santa Catarina). The number of patients with sepsis studied was 416 who were followed over a 15-month period. The data analyses were carried out by statistical process control. Case fatality rates were kept below a prespecified target of 25% (15.9%) during the period. Satisfaction level of the participating staff was high (95.2%) and 71% of participants reported no work overload. The IHI model was found to be a feasible and useful strategy for implementing a sepsis management clinical protocol.

Inducing Brain Cooling Without Core Temperature Reduction in Pigs Using a Novel Nasopharyngeal Method: An Effectiveness and Safety Study.

BACKGROUND: Acute brain lesions constitute an alarming public health concern. Neuroprotective therapies have been implemented to stabilize, prevent, or reduce brain lesions, thus improving neurological outcomes and survival rates. Hypothermia is the most effective approach, mainly attributed to the reduction in cellular metabolic activity. Whole-body cooling is currently implemented by healthcare professionals; however, adverse events are frequent, limiting the potential benefits of therapeutic hypothermia. Therefore, selective methods have been developed to reduce adverse events while delivering neuroprotection. Nasopharyngeal approaches are the safest and most effective methods currently considered. Our primary objective was to determine the effects of a novel nasopharyngeal catheter on the brain temperature of pigs. METHODS: In this prospective, non-randomized, interventional experimental trial, 10 crossbred pigs underwent nasopharyngeal cooling for 60 min followed by 15 min of rewarming. Nasopharyngeal catheters were inserted into the left nostril and properly positioned at the nasopharyngeal cavity. RESULTS: Nasopharyngeal cooling was associated with a decrease in brain temperature, which was more significant in the left cerebral hemisphere (p = 0.01). There was a reduction of 1.47 ± 0.86 °C in the first 5 min (p < 0.001), 2.45 ± 1.03 °C within 10 min (p < 0.001), and 4.45 ± 1.36 °C after 1 h (p < 0.001). The brain-core gradient was 4.57 ± 0.87 °C (p < 0.001). Rectal, esophageal, and pulmonary artery temperatures and brain and systemic hemodynamic parameters, remained stable during the procedure. Following brain cooling, values of oxygen partial pressure in brain tissue significantly decreased. No mucosal lesions were detected during nasal, pharyngeal, or oral inspection after nasopharyngeal catheter removal. CONCLUSIONS: In this study, a novel nasopharyngeal cooling catheter effectively induced and maintained exclusive brain cooling when combined with effective counter-warming methods. Exclusive brain cooling was safe with no device-related local or systemic complications and may be desired in selected patient populations.

Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial.

BACKGROUND: Transfusion of blood components prior to invasive procedures in cirrhosis patients is high and associated with adverse events. OBJECTIVES: We compared three transfusion strategies prior to central venous catheterization in cirrhosis patients. PATIENTS/METHODS: Single center randomized trial that included critically ill cirrhosis patients with indication for central venous line in a tertiary private hospital in Brazil. INTERVENTIONS: Restrictive protocol, thromboelastometry-guided protocol, or usual care (based on coagulogram). The primary endpoint was the proportion of patients transfused with any blood component (ie, fresh frozen plasma, platelets, or cryoprecipitate). The secondary endpoints included incidence of bleeding and transfusion-related adverse events. RESULTS: A total of 57 patients (19 per group; 64.9% male; mean age, 53.4 ± 11.3 years) were enrolled. Prior to catheterization, 3/19 (15.8%) in the restrictive arm, 13/19 (68.4%) in the thromboelastometry-guided arm, and 14/19 (73.7%) in the coagulogram-guided arm received blood transfusion (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01-0.45; P = .002 for restrictive versus coagulogram-guided arm; OR, 0.09; 95% CI, 0.01-0.56; P = .006 for restrictive versus thromboelastometry-guided arm; and OR, 0.77; 95% CI, 0.14-4.15; P = .931 for thromboelastometry-guided versus coagulogram-guided arm). The restrictive protocol was cost saving. No difference in bleeding, length of stay, mortality, and transfusion-related adverse events was found. CONCLUSIONS: The use of a restrictive strategy is associated with a reduction in transfusion prior to central venous catheterization and costs in critically ill cirrhosis patients. No effect on bleeding was found among the groups.

Assessment of the peripheral microcirculation in patients with and without shock: a pilot study on different methods.

Microvascular dysfunction has been associated with adverse outcomes in critically ill patients, and the current concept of hemodynamic incoherence has gained attention. Our objective was to perform a comprehensive analysis of microcirculatory perfusion parameters and to investigate the best variables that could discriminate patients with and without circulatory shock during early intensive care unit (ICU) admission. This prospective observational study comprised a sample of 40 adult patients with and without circulatory shock (n = 20, each) admitted to the ICU within 24 h. Peripheral clinical [capillary refill time (CRT), peripheral perfusion index (PPI), skin-temperature gradient (Tskin-diff)] and laboratory [arterial lactate and base excess (BE)] perfusion parameters, in addition to near-infrared spectroscopy (NIRS)-derived variables were simultaneously assessed. While lactate, BE, CRT, PPI and Tskin-diff did not differ significantly between the groups, shock patients had lower baseline tissue oxygen saturation (StO2) [81 (76-83) % vs. 86 (76-90) %, p = 0.044], lower StO2min [50 (47-57) % vs. 55 (53-65)  %, p = 0.038] and lower StO2max [87 (80-92) % vs. 93 (90-95) %, p = 0.017] than patients without shock. Additionally, dynamic NIRS variables [recovery time (r = 0.56, p = 0.010), descending slope (r = - 0.44, p = 0.05) and ascending slope (r = - 0.54, p = 0.014)] and not static variable [baseline StO2 (r = - 0.24, p = 0.28)] exhibited a significant correlation with the administered dose of norepinephrine. In our study with critically ill patients assessed within the first twenty-four hours of ICU admission, among the perfusion parameters, only NIRS-derived parameters could discriminate patients with and without shock.

IGF-1 and IGF-1R modulate the effects of IL-4 on retinal ganglion cells survival: The involvement of M1 muscarinic receptor.

Trophic factors are involved in different cellular responses. Previously we demonstrated that IL-4 treatment induces an increase in retinal ganglion cell survival (RGCS) and regulates cholinergic differentiation of retinal cells in vitro. Data from literature show that IGF-1 also promotes RGCS, an effect mediated by PI-3K/AKT pathway. The aim of this study was to investigate the role of IGF-1 and IGF-1R on RGCS mediated by IL-4 treatment and the role of M1 acetylcholine receptors in this effect. Here we show that the effect of IL-4 on RGCS depends on IGF-1 and IGF-1R activation, the PI-3K/AKT and NFkB intracellular pathways and depends on M1 mAChRs activation. IGF-1 increases the levels of M1 mAChRs in 15min, 45min, 24 h and 48 h in mixed retinal cells culture, modulates the levels of IL-4, pIGF-1R, IGF-1R. IL-4 modulates IGF-1, pIGF-1R and IGF-1R levels in different time intervals. These results put in evidence a crosstalk between IL-4 and IGF-1 and a role of M1 mAChRs, IGF-1 and IGF-1R in RGCS mediated by IL-4.

Efficiency in the operational process: reduction of incorrect entries and guarantee of compliance in the rendering of accounts.

OBJECTIVE: To verify the impact of the Lean Six Sigma methodology in reducing incorrect entries of non-appropriated revenues and expenses. METHODS: Process for the review and application of the Lean Six Sigma methodology between December 2015 and September 2016, in a high-complexity general hospital in the city of São Paulo (SP). RESULTS: A total of 3,756,814 (100%) entries were audited between December 2015 and September 2016. The Sigma level evolved over the course of the process and increased from 3.44 Sigma in December 2015 to 5.92 Sigma in September 2016. Entries classified as non-appropriated revenues and expenses were brought down to 0% at the end of the study. CONCLUSION: The use of the Lean Six Sigma methodology was efficient in reducing incorrect entries, calculating costs, ensuring compliance in rendering of accounts and accurately determining cost-outcome ratios.

Thromboelastometry profile in critically ill patients: A single-center, retrospective, observational study.

BACKGROUND: Transfusion therapy is associated with increased morbidity, mortality and costs. Conventional coagulation tests (CCT) are weak bleeding predictors, poorly reflecting coagulation in vivo. Thromboelastometry (ROTEM) provides early identification of coagulation disorders and can guide transfusion therapy by goals, reducing blood components transfusion. OBJECTIVE: The aim of this study is to describe coagulation profile of critically ill patients using ROTEM and evaluate the association between CCT and thromboelastometry. METHODS: This is a retrospective, observational study conducted in medical-surgical intensive care unit (ICU). Adult patients (≥18 years) admitted to ICU between November 2012 and December 2014, in whom ROTEM analyses were performed for bleeding management were included in this study. The first ROTEM and CCT after ICU admission were recorded simultaneously. Additionally, we collected data on blood components transfusion and hemostatic agents immediately after laboratory tests results. RESULTS: The study included 531 patients. Most ROTEM tests showed normal coagulation profile [INTEM (54.8%), EXTEM (54.1%) and FIBTEM (53.3%)] with divergent results in relation to CCT: low platelet count (51.8% in INTEM and 55.9% in EXTEM); prolonged aPTT (69.9% in INTEM and 63.7% in EXTEM) and higher INR (23.8% in INTEM and 27.4% in EXTEM). However 16,7% of patients with normocoagulability in ROTEM received platelet concentrates and 10% fresh frozen plasma. CONCLUSION: The predominant ROTEM profile observed in this sample of critically ill patients was normal. In contrast, CCT suggested coagulopathy leading to a possibly unnecessary allogenic blood component transfusion. ROTEM test may avoid inappropriate allogeneic blood products transfusion in these patients.

Efficiency in the operational process: reduction of incorrect entries and guarantee of compliance in the rendering of accounts / Eficiência no processo operacional: redução dos lançamentos incorretos e garantia de compliance na prestação de contas

ABSTRACT Objective To verify the impact of the Lean Six Sigma methodology in reducing incorrect entries of non-appropriated revenues and expenses. Methods Process for the review and application of the Lean Six Sigma methodology between December 2015 and September 2016, in a high-complexity general hospital in the city of São Paulo (SP). Results A total of 3,756,814 (100%) entries were audited between December 2015 and September 2016. The Sigma level evolved over the course of the process and increased from 3.44 Sigma in December 2015 to 5.92 Sigma in September 2016. Entries classified as non-appropriated revenues and expenses were brought down to 0% at the end of the study. Conclusion The use of the Lean Six Sigma methodology was efficient in reducing incorrect entries, calculating costs, ensuring compliance in rendering of accounts and accurately determining cost-outcome ratios.

RESUMO Objetivo Verificar o impacto da metodologia Lean Seis Sigma na redução de lançamentos incorretos de receitas e despesas não apropriadas. Métodos Processo de revisão e aplicação de metodologia Lean Seis Sigma, no período de dezembro de 2015 e setembro de 2016, em um hospital geral de alta complexidade da cidade de São Paulo (SP). Resultados Foram auditados 3.756.814 (100%) lançamentos durante os meses de dezembro de 2015 e setembro de 2016. O nível Sigma foi demonstrado na evolução do processo e aumentou de 3,44 Sigma, em dezembro de 2015, para 5,92 Sigma, em setembro de 2016. Os lançamentos classificados como receitas e despesas não apropriadas chegaram a 0% ao término do estudo. Conclusão O uso da metodologia Lean Seis Sigma foi eficiente na redução de lançamentos incorretos, na apuração correta de custos, na garantia de compliance na prestação de contas e na acurácia no projeto de custos e desfechos.

Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution's Main Source of Income Influence the Results? An Analysis of 21,103 Patients.

OBJECTIVE: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions' main source of income (public or private). DESIGN: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014. SETTINGS: Brazilian public and private institutions. PATIENTS: Patients with sepsis admitted in the participant institutions. INTERVENTIONS: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle. MEASUREMENTS AND MAIN RESULTS: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods. CONCLUSION: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial.

BACKGROUND: Liver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far. The aim of this study is to compare three transfusion strategies (routine coagulation test-guided - ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis. METHODS/DESIGN: Design and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. INCLUSION CRITERIA: adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis. DISCUSSION: This study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly reduce transfusion of blood products in this population, leading to a reduction in costs and transfusion-related adverse reactions. In this manner, this trial will add evidence in favor of reducing empirical transfusion in severely ill patients with coagulopathy. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02311985 . Retrospectively registered on 3 December 2014.

Vasodilators in Septic Shock Resuscitation: A Clinical Perspective.

Microcirculatory abnormalities have been shown to be frequent in patients with septic shock despite "normalization" of systemic hemodynamics. Several studies have explored the impact of vasodilator therapy (prostacyclin, inhaled nitric oxide, topic acetylcholine, and nitroglycerin) on microcirculation and tissue perfusion, with contradictory findings.In this narrative review, we briefly present the pathophysiological aspects of microcirculatory dysfunction, and depict the evidence supporting the use of vasodilators and other therapeutic interventions (fluid administration, blood transfusion, vasopressors, and dobutamine) aiming to improve the microcirculatory flow in septic shock patients.

Outcomes in Critically Ill Patients with Cancer-Related Complications.

INTRODUCTION: Cancer patients are at risk for severe complications related to the underlying malignancy or its treatment and, therefore, usually require admission to intensive care units (ICU). Here, we evaluated the clinical characteristics and outcomes in this subgroup of patients. MATERIALS AND METHODS: Secondary analysis of two prospective cohorts of cancer patients admitted to ICUs. We used multivariable logistic regression to identify variables associated with hospital mortality. RESULTS: Out of 2,028 patients, 456 (23%) had cancer-related complications. Compared to those without cancer-related complications, they more frequently had worse performance status (PS) (57% vs 36% with PS≥2), active malignancy (95% vs 58%), need for vasopressors (45% vs 34%), mechanical ventilation (70% vs 51%) and dialysis (12% vs 8%) (P<0.001 for all analyses). ICU (47% vs. 27%) and hospital (63% vs. 38%) mortality rates were also higher in patients with cancer-related complications (P<0.001). Chemo/radiation therapy-induced toxicity (6%), venous thromboembolism (5%), respiratory failure (4%), gastrointestinal involvement (3%) and vena cava syndrome (VCS) (2%) were the most frequent cancer-related complications. In multivariable analysis, the presence of cancer-related complications per se was not associated with mortality [odds ratio (OR) = 1.25 (95% confidence interval, 0.94-1.66), P = 0.131]. However, among the individual cancer-related complications, VCS [OR = 3.79 (1.11-12.92), P = 0.033], gastrointestinal involvement [OR = 3.05 (1.57-5.91), P = <0.001] and respiratory failure [OR = 1.96(1.04-3.71), P = 0.038] were independently associated with in-hospital mortality. CONCLUSIONS: The prognostic impact of cancer-related complications was variable. Although some complications were associated with worse outcomes, the presence of an acute cancer-related complication per se should not guide decisions to admit a patient to ICU.

Georeferencing of deaths from sepsis in the city of São Paulo

Abstract Objective The aim of the present study was to obtain information about deaths due to sepsis in São Paulo from 2004 to 2009 and their relationship with geographical distribution. Methods Causes of death, both main and secondary, were defined according to the codes of the International Classification of Disease version 10 (ICD-10) contained in the database. Sepsis, septic shock, multiple organ failure, pneumonia, urinary tract infection, peritonitis and other intraabdominal infections, skin and soft tissue infections (including surgical wound infection) and meningitis were considered as immediate cause of death or as the condition leading to the immediate cause of death related or associated to sepsis. Results In the analyzed period, there was a 15.3% increase in the absolute number of deaths from sepsis in São Paulo. The mean number of deaths during this period was 28,472 ± 1566. Most deaths due to sepsis and sepsis-related diseases over the studied period occurred in a hospital or health care facility, showing that most of the patients received medical care during the event that led to death. We observed a significant concentration of deaths in the most populous regions, tending more toward the center of the city. Conclusions Georeferencing data from death certificates or other sources can be a powerful tool to uncover regional epidemiological differences between populations. Our study revealed an even distribution of sepsis all over the inhabited areas of São Paulo.

Georeferencing of deaths from sepsis in the city of São Paulo.

OBJECTIVE: The aim of the present study was to obtain information about deaths due to sepsis in São Paulo from 2004 to 2009 and their relationship with geographical distribution. METHODS: Causes of death, both main and secondary, were defined according to the codes of the International Classification of Disease version 10 (ICD-10) contained in the database. Sepsis, septic shock, multiple organ failure, pneumonia, urinary tract infection, peritonitis and other intraabdominal infections, skin and soft tissue infections (including surgical wound infection) and meningitis were considered as immediate cause of death or as the condition leading to the immediate cause of death related or associated to sepsis. RESULTS: In the analyzed period, there was a 15.3% increase in the absolute number of deaths from sepsis in São Paulo. The mean number of deaths during this period was 28,472±1566. Most deaths due to sepsis and sepsis-related diseases over the studied period occurred in a hospital or health care facility, showing that most of the patients received medical care during the event that led to death. We observed a significant concentration of deaths in the most populous regions, tending more toward the center of the city. CONCLUSIONS: Georeferencing data from death certificates or other sources can be a powerful tool to uncover regional epidemiological differences between populations. Our study revealed an even distribution of sepsis all over the inhabited areas of São Paulo.

Performance of noninvasive ventilation in acute respiratory failure in critically ill patients: a prospective, observational, cohort study.

BACKGROUND: Noninvasive ventilation (NIV) is used in critically ill patients with acute respiratory failure (ARF) to avoid endotracheal intubation. However, the impact of NIV use on ARF patient's outcomes is still unclear. Our objectives were to evaluate the rate of NIV failure in hypoxemic patients with an arterial carbon dioxide partial pressure (PaCO2) < 45 mmHg or ≥ 45 mmHg at ICU admission, the predictors of NIV failure, ICU and hospital length of stay and 28-day mortality. METHODS: Prospective single center cohort study. All consecutive patients admitted to a mixed ICU during a three-month period who received NIV, except for palliative care purposes, were included in this study. Demographic data, APACHE II score, cause of ARF, number of patients that received NIV, incidence of NIV failure, length of ICU, hospital stay and mortality rate were compared between NIV failure and success groups. RESULTS: Eighty-five from 462 patients (18.4 %) received NIV and 26/85 (30.6 %) required invasive mechanical ventilation. NIV failure patients were comparatively younger (67 ± 21 vs. 77 ± 14 years; p = 0.031), had lower arterial bicarbonate (p = 0.005), lower PaCO2 levels (p = 0.032), higher arterial lactate levels (p = 0.046) and APACHE II score (p = 0.034) compared to NIV success patients. NIV failure occurred in 25.0 % of patients with PaCO2 ≥ 45 mmHg and in 33.3 % of patients with PaCO2 < 45 mmHg (p = 0.435). NIV failure was associated with an increased risk of in-hospital death (OR 4.64, 95 % CI 1.52 to 14.18; p = 0.007) and length [median (IQR)] of ICU [12 days (8-31) vs. 2 days (1-4); p < 0.001] and hospital [30 (19-42) vs. 15 (9-33) days; p = 0.010] stay. Predictors of NIV failure included age (OR 0.96, 95 % CI 0.93 to 0.99; p = 0.007) and APACHE II score (OR 1.13, 95 % CI 1.02 to 1.25; p = 0.018). CONCLUSION: NIV failure was associated with an increased risk of in-hospital death, ICU and hospital stay and was not affected by baseline PaCO2 levels. Patients that failed were comparatively younger and had higher APACHE II score, suggesting the need for a careful selection of patients that might benefit from NIV. A well-designed study on the impact of a short monitored NIV trial on outcomes is needed.

Smart Care™ versus respiratory physiotherapy-driven manual weaning for critically ill adult patients: a randomized controlled trial.

INTRODUCTION: A recent meta-analysis showed that weaning with SmartCare™ (Dräger, Lübeck, Germany) significantly decreased weaning time in critically ill patients. However, its utility compared with respiratory physiotherapist-protocolized weaning is still a matter of debate. We hypothesized that weaning with SmartCare™ would be as effective as respiratory physiotherapy-driven weaning in critically ill patients. METHODS: Adult critically ill patients mechanically ventilated for more than 24 hours in the adult intensive care unit of the Albert Einstein Hospital, São Paulo, Brazil, were randomly assigned to be weaned either by progressive discontinuation of pressure support ventilation (PSV) with SmartCare™. Demographic data, respiratory function parameters, level of PSV, tidal volume (VT), positive end-expiratory pressure (PEEP), inspired oxygen fraction (FIO2), peripheral oxygen saturation (SpO2), end-tidal carbon dioxide concentration (EtCO2) and airway occlusion pressure at 0.1 second (P0.1) were recorded at the beginning of the weaning process and before extubation. Mechanical ventilation time, weaning duration and rate of extubation failure were compared. RESULTS: Seventy patients were enrolled 35 in each group. There was no difference between the two groups concerning age, sex or diagnosis at study entry. There was no difference in maximal inspiratory pressure, maximal expiratory pressure, forced vital capacity or rapid shallow breathing index at the beginning of the weaning trial. PEEP, VT, FIO2, SpO2, respiratory rate, EtCO2 and P0.1 were similar between the two groups, but PSV was not (median: 8 vs. 10 cmH2O; p =0.007). When the patients were ready for extubation, PSV (8 vs. 5 cmH2O; p =0.015) and PEEP (8 vs. 5 cmH2O; p <0.001) were significantly higher in the respiratory physiotherapy-driven weaning group. Total duration of mechanical ventilation (3.5 [2.0-7.3] days vs. 4.1 [2.7-7.1] days; p =0.467) and extubation failure (2 vs. 2; p =1.00) were similar between the two groups. Weaning duration was shorter in the respiratory physiotherapy-driven weaning group (60 [50-80] minutes vs. 110 [80-130] minutes; p <0.001). CONCLUSION: A respiratory physiotherapy-driven weaning protocol can decrease weaning time compared with an automatic system, as it takes into account individual weaning difficulties. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02122016 . Date of Registration: 27 August 2013.

Current concepts on hemodynamic support and therapy in septic shock / Conceitos atuais sobre suporte hemodinâmico e terapia em choque séptico

ABSTRACTSevere sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

RESUMOA sepse grave e o choque séptico são um grande desafio para a assistência médica. Grande parte da melhoria na taxa de mortalidade associada ao choque séptico está relacionada ao reconhecimento precoce em combinação com a reposição volêmica oportuna e a administração adequada de antibióticos. Os principais objetivos da reanimação do choque séptico incluem reposição intravascular, manutenção adequada da pressão de perfusão e fornecimento de oxigênio para os tecidos. Para atingir esses objetivos, a avaliação da responsividade do volume e das intervenções complementares (vasopressores, inotrópicos e transfusão de sangue) pode ser necessária. Este artigo é uma revisão da literatura para identificar as evidências disponíveis do suporte hemodinâmico inicial aos pacientes com choque séptico admitidos em sala de emergência ou unidade de terapia intensiva e as principais intervenções disponíveis para atingir essas metas, com foco em terapia com reposição de líquidos e vasopressores, transfusão de sangue e administração de inotrópicos.