Predictive Accuracy of the Quick Sepsis-related Organ Failure Assessment Score in Brazil. A Prospective Multicenter Study.

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Quality Indicators of End-of-Life Care Among Privately Insured People With Cancer in Brazil.

PURPOSE: To examine quality indicators of end-of-life (EOL) care among privately insured people with cancer in Brazil. METHODS: We evaluated medical records linked to health insurance databank to study consecutive patients who died of cancer. We collected information about demographics, cancer type, and quality indicators of EOL care including emergency department (ED) visits, intensive care unit (ICU) admissions, chemotherapy use, medical imaging utilization, blood transfusions, home care support, days of inpatient care, and hospital deaths. RESULTS: We included 865 patients in the study. In the last 30 days of life, 62% visited the ED, 33% were admitted to the ICU, 24% received blood transfusions, and 51% underwent medical imaging. Only 1% had home care support in the last 60 days of life, and 29% used chemotherapy in the last 14 days of life. Patients had an average of 8 days of inpatient care and 52% died in the hospital. Patients with advanced cancer who used chemotherapy were more likely to visit the ED (78% vs 59%; P < .001), undergo medical imaging (67% vs 51%; P < .001), and die in the hospital (73% vs 50%; P = .03) than patients who did not use chemotherapy. In the multivariate analysis, chemotherapy use near death and advanced cancer were associated with ED visits and ICU admissions, respectively (odds ratio >1). CONCLUSION: Our study suggests that privately insured people with cancer receive poor quality EOL care in Brazil. Further research is needed to assess the impact of improvements in palliative care provision in this population.

Trends in Health-Care Utilization at the End of Life Among Patients With Hematologic Malignancies in a Middle-Income Country: Challenges and Opportunities in Brazil.

Patients with hematologic malignancies (HMs) often receive poor-quality end-of-life care. This study aimed to identify trends in end-of-life care among patients with HM in Brazil. We conducted a retrospective cohort study (2015-2018) of patients who died with HM, using electronic medical records linked to health insurance databank, to evaluate outcomes consistent with health-care resource utilization at the end of life. Among 111 patients with HM, in the last 30 days of life, we found high rates of emergency department visits (67%, n = 75), intensive care unit admissions (56%, n = 62), acute renal replacement therapy (10%, n = 11), blood transfusions (45%, n = 50), and medical imaging utilization (59%, n = 66). Patients received an average of 13 days of inpatient care and the majority of them died in the hospital (53%, n = 58). We also found that almost 40% of patients (38%, n = 42) used chemotherapy in the last 14 days of life. These patients were more likely to be male (64% vs 22%; P < .001), to receive blood transfusions (57% vs 38%; P = .05), and to die in the hospital (76% vs 39%; P = .009) than patients who did not use chemotherapy in the last 14 days of life. This study suggests that patients with HM have high rates of health-care utilization at the end of life in Brazil. Patients who used chemotherapy in the last 14 days of life were more likely to receive blood transfusions and to die in the hospital.

Prevalence and intensity of dyspnea, pain, and agitation among people dying with late stage dementia compared with people dying with advanced cancer: a single-center preliminary study in Brazil.

BACKGROUND: As death approaches, there may be similarities in terms of physical symptoms among dementia and cancer. This study aimed to estimate the prevalence and intensity of dyspnea, pain, and agitation among people dying with late stage dementia versus those dying with advanced cancer. Methods: A retrospective analysis, conducted in a post-acute care facility (PACF) in Rio de Janeiro, Brazil. We reviewed the electronic charts for the Edmonton Symptom Assessment System (ESAS) scores, from death backwards in time (3 days). METHODS: A retrospective analysis, conducted in a post-acute care facility (PACF) in Rio de Janeiro, Brazil. We reviewed the electronic charts for the Edmonton Symptom Assessment System (ESAS) scores, from death backwards in time (3 days). RESULTS: We included 57 patients who died with dementia and 54 patients who died with cancer. The prevalence of dyspnea (dementia: n=34, 60% vs. cancer: n=39, 72%; P=0.23), and agitation (dementia: n=7, 13% vs. cancer: n=14, 25%; P=0.17) were statically similar between the two groups. Pain was less common in dementia (dementia: n=19, 34% vs. cancer: n=31, 57%; P=0.02). There were no significant differences in the percentage of patients with moderate to severe dyspnea (dementia: n=28, 49% vs. cancer: n=33, 61%; P=0.28), and moderate to severe agitation (dementia: n=4, 7% vs. cancer: n=12, 23%; P=0.09). Dementia patients were less likely to experience moderate to severe pain than cancer patients (dementia: n=14, 25% vs. cancer: n=25, 46%; P=0.03). The diagnosis of cancer was independently associated with pain, severe symptoms, and the co-occurrence of dyspnea, pain, and agitation (odds ratio >1). CONCLUSIONS: People dying with dementia and those dying with cancer experienced similar rates of dyspnea, and agitation. However, pain was significantly more prevalent and intense among people dying with cancer.

Role of organisational factors on the 'weekend effect' in critically ill patients in Brazil: a retrospective cohort analysis.

INTRODUCTION: Higher mortality for patients admitted to intensive care units (ICUs) during the weekends has been occasionally reported with conflicting results that could be related to organisational factors. We investigated the effects of ICU organisational and staffing patterns on the potential association between weekend admission and outcomes in critically ill patients. METHODS: We included 59 614 patients admitted to 78 ICUs participating during 2013. We defined 'weekend admission' as any ICU admission from Friday 19:00 until Monday 07:00. We assessed the association between weekend admission with hospital mortality using a mixed logistic regression model controlling for both patient-level (illness severity, age, comorbidities, performance status and admission type) and ICU-level (decrease in nurse/bed ratio on weekend, full-time intensivist coverage, use of checklists on weekends and number of institutional protocols) confounders. We performed secondary analyses in the subgroup of scheduled surgical admissions. RESULTS: A total of 41 894 patients (70.3%) were admitted on weekdays and 17 720 patients (29.7%) on weekends. In univariable analysis, weekend admitted patients had higher ICU (10.9% vs 9.0%, P<0.001) and hospital (16.5% vs 13.5%, P<0.001) mortality. After adjusting for confounders, weekend admission was not associated with higher hospital mortality (OR 1.05, 95% CI 0.99 to 1.12, P=0.095). However, a 'weekend effect' was still observed in scheduled surgical admissions, as well as in ICUs not using checklists during the weekends. For unscheduled admissions, no 'weekend effect' was observed regardless of ICU's characteristics. For scheduled surgical admissions, a 'weekend effect' was present only in ICUs with a low number of implemented protocols and those with a reduction in the nurse/bed ratio and not applying checklists during weekends. CONCLUSIONS: ICU organisational factors, such as decreased nurse-to-patient ratio, absence of checklists and fewer standardised protocols, may explain, in part, increases in mortality in patients admitted to the ICU mortality on weekends.

Post-Acute Care Facility as a Discharge Destination for Patients in Need of Palliative Care in Brazil.

Patients with complex palliative care needs can experience delayed discharge, which causes an inappropriate occupancy of hospital beds. Post-acute care facilities (PACFs) have emerged as an alternative discharge destination for some of these patients. The aim of this study was to investigate the frequency of admissions and characteristics of palliative care patients discharged from hospitals to a PACF. We conducted a retrospective analysis of PACF admissions between 2014 and 2016 that were linked to hospital discharge reports and electronic health records, to gather information about hospital-to-PACF transitions. In total, 205 consecutive patients were discharged from 6 different hospitals to our PACF. Palliative care patients were involved in 32% (n = 67) of these discharges. The most common conditions were terminal cancer (n = 42, 63%), advanced dementia (n = 17, 25%), and stroke (n = 5, 8%). During acute hospital stays, patients with cancer had significant shorter lengths of stay (13 vs 99 days, P = .004), a lower use of intensive care services (2% vs 64%, P < .001) and mechanical ventilation (2% vs 40%, P < .001), when compared to noncancer patients. Approximately one-third of discharges from hospitals to a PACF involved a heterogeneous group of patients in need of palliative care. Further studies are necessary to understand the trajectory of posthospitalized patients with life-limiting illnesses and what factors influence their decision to choose a PACF as a discharge destination and place of death. We advocate that palliative care should be integrated into the portfolio of post-acute services.

Correlation of 6-min walk test with left ventricular function and quality of life in heart failure due to Chagas disease.

OBJECTIVES: To evaluate the correlation of the total distance walked during the six-minute walk test (6MWT) with left ventricular function and quality of life in patients with Chagas Disease (ChD) complicated by heart failure. METHODS: This is a cross-sectional study of adult patients with ChD and heart failure diagnosed based on Framingham criteria. 6MWT was performed following international guidelines. New York Heart Association functional class, brain natriuretic peptide (BNP) serum levels, echocardiographic parameters and quality of life (SF-36 and MLHFQ questionnaires) were determined and their correlation with the distance covered at the 6MWT was tested. RESULTS: Forty adult patients (19 male; 60 ± 12 years old) with ChD and heart failure were included in this study. The mean left ventricular ejection fraction was 35 ± 12%. Only two patients (5%) ceased walking before 6 min had elapsed. There were no cardiac events during the test. The average distance covered was 337 ± 105 metres. The distance covered presented a negative correlation with BNP (r = -0.37; P = 0.02), MLHFQ quality-of-life score (r = -0.54; P = 0.002), pulmonary artery systolic pressure (r = -0.42; P = 0.02) and the degree of diastolic dysfunction (r = -0.36; P = 0.03) and mitral regurgitation (r = -0.53; P = 0.0006) and positive correlation with several domains of the SF-36 questionnaire. CONCLUSIONS: The distance walked during the 6MWT correlates with BNP, quality of life and parameters of left ventricular diastolic function in ChD patients with heart failure. We propose this test to be adopted in endemic areas with limited resources to aid in the identification of patients who need referral for tertiary centres for further evaluation and treatment.

Thirty-day Readmission Rates in an HIV-infected Cohort From Rio de Janeiro, Brazil.

BACKGROUND: The 30-day readmission rate is an indicator of the quality of hospital care and transition to the outpatient setting. Recent studies suggest HIV infection might increase the risk of readmission although estimates of 30-day readmission rates are unavailable among HIV-infected individuals living in middle/low-income settings. Additionally, factors that may increase readmission risk in HIV-infected populations are poorly understood. METHODS: Thirty-day readmission rates were estimated for HIV-infected adults from the Instituto Nacional de Infectologia Evandro Chagas/Fiocruz cohort in Rio de Janeiro, Brazil, from January 2007 to December 2013. Cox regression models were used to evaluate factors associated with the risk of 30-day readmission. RESULTS: Between January 2007 and December 2013, 3991 patients were followed and 1861 hospitalizations were observed. The estimated 30-day readmission rate was 14% (95% confidence interval: 12.3 to 15.9). Attending a medical visit within 30 days after discharge (adjusted hazard ratio [aHR] = 0.73, P = 0.048) and being hospitalized in more recent calendar years (aHR = 0.89, P = 0.002) reduced the risk of 30-day readmission. In contrast, low CD4 counts (51-200 cells/mm³: aHR = 1.70, P = 0.024 and ≤ 50 cells/mm³: aHR = 2.05, P = 0.003), time since HIV infection diagnosis ≥10 years (aHR = 1.58, P = 0.058), and leaving hospital against medical advice (aHR = 2.67, P = 0.004) increased the risk of 30-day readmission. CONCLUSIONS: Patients with advanced HIV/AIDS are most at risk of readmission and should be targeted with prevention strategies to reduce this risk. Efforts to reduce discharge against medical advice and to promote early postdischarge medical visit would likely reduce 30-day readmission rates in our population.

The Challenge of Predicting Pressure Ulcers in Critically Ill Patients. A Multicenter Cohort Study.

RATIONALE: Pressure ulcers are preventable events. Critically ill patients are particularly vulnerable. The Braden scale has been used to identify hospitalized patients at high risk for the development of pressure ulcers; however, this predictive tool has not been adequately validated for critically ill patients. OBJECTIVES: We aimed to validate and improve the Braden scale for critically ill patients by adding clinical variables to the original scale. METHODS: We conducted a cohort study in 12 intensive care units (ICUs) within a network of hospitals in Brazil during 2013. We excluded patients who stayed less than 48 hours, patients with one or more pressure ulcers at admission, and those who developed a pressure ulcer within the first 48 hours. We evaluated the Braden scale and clinical variables through a competing risk analysis. Discrimination and calibration were evaluated using the Concordance index (C-index) and a calibration plot, respectively. We used bootstrapping to assess internal validation. MEASUREMENTS AND MAIN RESULTS: Our primary outcome was incident pressure ulcer within 30 days of ICU admission. We analyzed 9,605 patients and observed 157 pressure ulcers (rate of 3.33 pressure ulcers/1,000 patient-days). The majority of pressure ulcers were detected at stage I or II (28.7 and 66.2%, respectively). The Braden scale had good discrimination (C-index, 0.753; 95% confidence interval, 0.712-0.795), although its performance decreased for the most severely ill patients. We derived a modified predictive tool by adding eight clinical variables to the Braden scale: age, sex, diabetes mellitus, hematological malignancy, peripheral artery disease, hypotension at ICU admission, and need for mechanical ventilation or renal replacement therapy in the first 24 hours after ICU admission. The derived score had better discrimination and calibration than the original Braden scale. The best score cutoff was at least 6 points, with a sensitivity of 87% and a specificity of 71%. CONCLUSIONS: The original Braden scale measured at ICU admission is a valuable tool for pressure ulcer prediction, although it is not accurate for severely ill patients. To overcome the limitations of the original scale, we derived a modified score with better performance, which may identify high-risk ICU patients and support target interventions. External validation of the proposed clinical prediction score is needed.

Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study.

BACKGROUND: Tuberculosis is one of the leading causes of death from infectious diseases worldwide, mainly after the human immunodeficiency virus (HIV) epidemics. Patient with HIV-related illness are more likely to present with severe TB due to immunosuppression. Very few studies have explored HIV/TB co-infection in critically ill patients. The goal of this study was to analyze factors associated with long-term mortality in critically ill patient with HIV-related disease coinfected with TB. METHODS: We conducted a retrospective study in an infectious disease reference center in Brazil that included all patient with HIV-related illness admitted to the ICU with laboratory-confirmed tuberculosis from March 2007 until June 2012. Clinical and laboratory variables were analyzed based on six-month survival. RESULTS: Forty-four patients with HIV-related illness with a confirmed diagnosis of tuberculosis were analyzed. The six-month mortality was 52 % (23 patients). The main causes of admission were respiratory failure (41 %), severe sepsis/septic shock (32 %) and coma/torpor (14 %). The median time between HIV diagnosis and ICU admission was 5 (1-60) months, and 41 % of patients received their HIV infection diagnosis ≤ 30 days before admission. The median CD4 count was 72 (IQR: 23-136) cells/mm(3). The clinical presentation was pulmonary tuberculosis in 22 patients (50 %) and disseminated TB in 20 patients (45.5 %). No aspect of TB diagnosis or treatment was different between survivors and nonsurvivors. Neurological dysfunction was more prevalent among nonsurvivors (43 % vs. 14 %, p = 0.04). The nadir CD4 cell count lower than 50 cells/mm(3) was independently associated with Six-month mortality (hazard ratio 4.58 [1.64-12.74], p < 0.01), while HIV diagnosis less than three months after positive serology was protective (hazard ratio 0.27, CI 95 % [0.10-0.72], p = 0.01). CONCLUSION: The Six-month mortality of HIV critically ill patients with TB coinfection is high and strongly associated with the nadir CD4 cell count less than 50 cels/mm(3).

Organizational characteristics, outcomes, and resource use in 78 Brazilian intensive care units: the ORCHESTRA study.

PURPOSE: Detailed information on organization and process of care in intensive care units (ICU) in emerging countries is scarce. Here, we investigated the impact of organizational factors on the outcomes and resource use in a large sample of Brazilian ICUs. METHODS: Retrospective cohort study of 59,693 patients (medical admissions, 67 %) admitted to 78 ICUs during 2013. We retrieved patients' data from an ICU quality registry and surveyed ICUs regarding structure, organization, staffing patterns, and process of care. We used multilevel logistic regression analysis to identify factors associated with hospital mortality. Efficient resource use was assessed by estimating standardized resource use and mortality rates adjusted for the SAPS 3 score. RESULTS: ICUs were mostly medical-surgical (79 %) and located at private hospitals (86 %). Median nurse to bed ratio was 0.20 (IQR, 0.15-0.28) and board-certified intensivists were present 24/7 in 16 (21 %) of ICUs. Multidisciplinary rounds occurred in 67 (86 %) and daily checklists were used in 36 (46 %) ICUs. Most frequent protocols focused on sepsis management and prevention of healthcare-associated infections. Hospital mortality was 14.4 %. In multivariable analysis, the number of protocols was the only organizational characteristic associated with mortality [odds ratio = 0.944 (95 % CI 0.904-0.987)]. The effects of protocols were consistent across subgroups including surgical and medical patients as well as the SAPS 3 tertiles. We also observed a significant trend toward efficient resource use as the number of protocols increased. CONCLUSIONS: In emerging countries such as Brazil, organizational factors, including the implementation of protocols, are potential targets to improve patient outcomes and resource use in ICUs.

Effects of different levels of pressure support on intra-individual breath-to-breath variability.

BACKGROUND: Evidence exists that during pressure support ventilation (PSV), the addition of an extrinsic (ie, ventilator-generated) breath-to-breath variability (BBV) of breathing pattern improves respiratory function. If BBV is beneficial per se, choosing the PS level that maximizes it could be considered a valid strategy for conventional PSV. In this study, we evaluated the effect of different PS levels on intrinsic BBV in acutely ill, mechanically ventilated subjects to determine whether a significant relationship exists between PS level and BBV magnitude. METHODS: Fourteen invasively mechanically ventilated subjects were prospectively studied. PS was adjusted at 20 cm H2O and sequentially reduced to 15, 10, and 5 cm H2O. Arterial blood gas analysis and pressure at 0.1 s after the onset of inspiration (P0.1) were measured at each PS level. Airway and esophageal pressure and air flow were continuously recorded. Peak inspiratory flow, tidal volume (VT), breathing frequency, and pressure-time product (PTP) were calculated on a breath-by-breath basis. The breathing pattern variability was assessed by the coefficient of variation of the time series of VT, peak inspiratory flow, and breathing frequency from ∼ 60 consecutive breath cycles at each PS level. A general linear model for repeated measures was applied, with PS as an independent factor. A significance level of .05 was considered. RESULTS: Despite a large inter-individual difference in all measured variables (P < .001), the coefficient of variation was as low as 30%, and no significant differences in the coefficient of variation of peak inspiratory flow, breathing frequency, and VT between PS levels were observed (P > .15). Additionally, a significant increase in P0.1, PTP, and breathing frequency (P < .01) and a reduction in VT (P < .001) were observed with PS reduction. CONCLUSIONS: Despite a significant increase in spontaneous activity with PS reduction, BBV was not influenced by the PS level and was as low as 30% for all evaluated parameters.

The innate immune response in HIV/AIDS septic shock patients: a comparative study.

INTRODUCTION: In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients. METHODS: We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients. RESULTS: We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality. CONCLUSIONS: IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.

Changing sedative infusion from propofol to midazolam improves sublingual microcirculatory perfusion in patients with septic shock.

PURPOSE: The goal of this study was to explore possible microcirculatory alterations by changing sedative infusion from propofol to midazolam in patients with septic shock. MATERIALS AND METHODS: Patients (n=16) were sedated with propofol during the first 24 hours after intubation, then with midazolam, following a predefined algorithm. Systemic hemodynamics, perfusion parameters, and microcirculation were assessed at 2 time points: just before stopping propofol and 30 minutes after the start of midazolam infusion. Sublingual microcirculation was evaluated by sidestream dark-field imaging. RESULTS: The microvascular flow index and the proportion of perfused small vessels were greater when patients were on midazolam than when on propofol infusion (2.8 [2.4-2.9] vs 2.3 [1.9-2.6] and 96.4% [93.7%-97.6%] vs 92.7% [88.3%-94.7%], respectively; P<.005), and the flow heterogeneity index was greater with propofol than with midazolam use (0.49 [0.2-0.8] vs 0.19 [0.1-0.4], P<.05). There were no significant changes in systemic hemodynamics and perfusion parameters either during propofol use or during midazolam infusions. Data are presented as median (25th-75th percentiles). CONCLUSIONS: In this study, sublingual microcirculatory perfusion improved when the infusion was changed from propofol to midazolam in patients with septic shock. This observation could not be explained by changes in systemic hemodynamics.

Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5'-triphosphate synthase activity.

OBJECTIVE: Increasing evidence points to the role of mitochondrial dysfunction in the pathogenesis of sepsis. Previous data indicate that mitochondrial function is affected in monocytes from septic patients, but the underlying mechanisms and the impact of these changes on the patients' outcome are unknown. We aimed to determine the mechanisms involved in mitochondrial dysfunction in peripheral blood mononuclear cells from patients with septic shock. DESIGN: A cohort of patients with septic shock to study peripheral blood mononuclear cell mitochondrial respiration by high-resolution respirometry analyses and to compare with cells from control subjects. SETTING: Three intensive care units and an academic research laboratory. SUBJECTS: Twenty patients with septic shock and a control group composed of 18 postoperative patients without sepsis or shock. INTERVENTIONS: Ex vivo measurements of mitochondrial oxygen consumption were carried out in digitonin-permeabilized peripheral blood mononuclear cells from 20 patients with septic shock taken during the first 48 hrs after intensive care unit admission as well as in peripheral blood mononuclear cells from control subjects. Clinical parameters such as hospital outcome and sepsis severity were also analyzed and the relationship between these parameters and the oxygen consumption pattern was investigated. MEASUREMENTS AND MAIN RESULTS: We observed a significant reduction in the respiration specifically associated with adenosine-5'-triphosphate synthesis (state 3) compared with the control group (5.60 vs. 9.89 nmol O2/min/10(7) cells, respectively, p < .01). Reduction of state 3 respiration in patients with septic shock was seen with increased prevalence of organ failure (r = -0.46, p = .005). Nonsurviving patients with septic shock presented significantly lower adenosine diphosphate-stimulated respiration when compared with the control group (4.56 vs. 10.27 nmol O2/min/10(7) cells, respectively; p = .004). Finally, the presence of the functional F1Fo adenosine-5'-triphosphate synthase complex (0.51 vs. 1.00 ng oligo/mL/10(6) cells, p = .02), but not the adenine nucleotide translocator, was significantly lower in patients with septic shock compared with control cells. CONCLUSION: Mitochondrial dysfunction is present in immune cells from patients with septic shock and is characterized as a reduced respiration associated to adenosine-5'-triphosphate synthesis. The molecular basis of this phenotype involve a reduction of F1Fo adenosine-5'-triphosphate synthase activity, which may contribute to the energetic failure found in sepsis.

A central role for free heme in the pathogenesis of severe sepsis.

Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis. Free heme contributed to the pathogenesis of severe sepsis irrespective of pathogen load, revealing that it compromised host tolerance to infection. Development of lethal forms of severe sepsis after high-grade infection was associated with reduced serum concentrations of the heme sequestering protein hemopexin (HPX), whereas HPX administration after high-grade infection prevented tissue damage and lethality. Finally, the lethal outcome of septic shock in patients was also associated with reduced HPX serum concentrations. We propose that targeting free heme by HPX might be used therapeutically to treat severe sepsis.

An outbreak case of Clostridium difficile-associated diarrhea among elderly inpatients of an intensive care unit of a tertiary hospital in Rio de Janeiro, Brazil.

The aim of this study was to investigate Clostridium difficile-associated diarrhea (CDAD) in an intensive care unit (ICU) of a tertiary hospital in Rio de Janeiro, Brazil, and to characterize epidemiologically C. difficile strains obtained from an outbreak of CDAD. Within almost a 4-year surveillance period, CDAD incidence was determined for the first time in Brazil, and a 3-fold increase was observed in the average rate of CDAD, featuring an outbreak. About 80% of the patients were over 65 years. The main antibiotic that could be probably associated to CDAD was piperacillin/tazobactam. Four toxigenic strains were isolated, 3 from stools and 1 from environmental samples. They were all resistant to clindamycin and fluoroquinolones. Fingerprinting analysis revealed their distribution between 2 different polymerase chain reaction ribotypes, with one of them being exclusively found in Brazil. It was possible to detect cross-infection and environmental contamination in the ICU. Our results highlight the importance of a continuous CDAD surveillance in the hospitals, especially when a risk group is exposed.

Sepsis is a major determinant of outcome in critically ill HIV/AIDS patients.

INTRODUCTION: New challenges have arisen for the management of critically ill HIV/AIDS patients. Severe sepsis has emerged as a common cause of intensive care unit (ICU) admission for those living with HIV/AIDS. Contrastingly, HIV/AIDS patients have been systematically excluded from sepsis studies, limiting the understanding of the impact of sepsis in this population. We prospectively followed up critically ill HIV/AIDS patients to evaluate the main risk factors for hospital mortality and the impact of severe sepsis on the short- and long-term survival. METHODS: All consecutive HIV-infected patients admitted to the ICU of an infectious diseases research center, from June 2006 to May 2008, were included. Severity of illness, time since AIDS diagnosis, CD4 cell count, antiretroviral treatment, incidence of severe sepsis, and organ dysfunctions were registered. The 28-day, hospital, and 6-month outcomes were obtained for all patients. Cox proportional hazards regression analysis measured the effect of potential factors on 28-day and 6-month mortality. RESULTS: During the 2-year study period, 88 HIV/AIDS critically ill patients were admitted to the ICU. Seventy percent of patients had opportunist infections, median CD4 count was 75 cells/mm3, and 45% were receiving antiretroviral therapy. Location on a ward before ICU admission, cardiovascular and respiratory dysfunctions on the first day after admission, and the presence of severe sepsis/septic shock were associated with reduced 28-day and 6-month survival on a univariate analysis. After a multivariate analysis, severe sepsis determined the highest hazard ratio (HR) for 28-day (adjusted HR, 3.13; 95% CI, 1.21-8.07) and 6-month (adjusted HR, 3.35; 95% CI, 1.42-7.86) mortality. Severe sepsis occurred in 44 (50%) patients, mainly because of lower respiratory tract infections. The survival of septic and nonseptic patients was significantly different at 28-day and 6-month follow-up times (log-rank and Peto test, P < 0.001). CONCLUSIONS: Severe sepsis has emerged as a major cause of admission and mortality for hospitalized HIV/AIDS patients, significantly affecting short- and longer-term survival of critically ill HIV/AIDS patients.