A Comparison of Mortality From Sepsis in Brazil and England: The Impact of Heterogeneity in General and Sepsis-Specific Patient Characteristics.

OBJECTIVES: To test whether differences in both general and sepsis-specific patient characteristics explain the observed differences in sepsis mortality between countries, using two national critical care (ICU) databases. DESIGN: Cohort study. SETTING: We analyzed 62 and 164 ICUs in Brazil and England, respectively. PATIENTS: Twenty-two-thousand four-hundred twenty-six adult ICU admissions from January 2013 to December 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After harmonizing relevant variables, we merged the first ICU episode of adult medical admissions from Brazil (ORganizational CHaractEeriSTics in cRitical cAre study) and England (Intensive Care National Audit & Research Centre Case Mix Programme). Sepsis-3 definition was used, and the primary outcome was hospital mortality. We used multilevel logistic regression models to evaluate the impact of country (Brazil vs England) on mortality, after adjustment for general (age, sex, comorbidities, functional status, admission source, time to admission) and sepsis-specific (site of infection, organ dysfunction type and number) patient characteristics. Of medical ICU admissions, 13.2% (4,505/34,150) in Brazil and 30.7% (17,921/58,316) in England met the sepsis definition. The Brazil cohort was older, had greater prevalence of severe comorbidities and dependency compared with England. Respiratory was the most common infection site in both countries. The most common organ dysfunction was cardiovascular in Brazil (41.2%) and respiratory in England (85.8%). Crude hospital mortality was similar (Brazil 41.4% vs England 39.3%; odds ratio, 1.12 [0.98-1.30]). After adjusting for general patient characteristics, there was an important change in the point-estimate of the odds ratio (0.88 [0.75-1.02]). However, after adjusting for sepsis-specific patient characteristics, the direction of effect reversed again with Brazil having higher risk-adjusted mortality (odds ratio, 1.22 [1.05-1.43]). CONCLUSIONS: Patients with sepsis admitted to ICUs in Brazil and England have important differences in general and sepsis-specific characteristics, from source of admission to organ dysfunctions. We show that comparing crude mortality from sepsis patients admitted to the ICU between countries, as currently performed, is not reliable and that the adjustment for both general and sepsis-specific patient characteristics is essential for valid international comparisons of mortality amongst sepsis patients admitted to critical care units.

Patterns of C-reactive protein ratio response to antibiotics in pediatric sepsis: A prospective cohort study.

PURPOSE: Evaluate sequential C-reactive protein (CRP) measurements and patterns of CRP-ratio response to antibiotic therapy during first 7days in Pediatric Intensive Care Unit (PICU) of septic children. METHODS: Prospective, cohort study of children (1month-12years) admitted at 3 PICUs, with diagnosis of sepsis with <72h course. CRP-ratio was calculated in relation to D0_CRP value. Children were classified according to an individual pattern of CRP-ratio response: fast - CRP_D4 of therapy was <0.4 of D0_CRP; slow - continuous but slow decrease of CRP; non - CRP remained ≥0.8 of D0_CRP; biphasic - initial CRP decrease to levels <0.8 of D0_CRP followed by secondary rise ≥0.8. RESULTS: 103 septic children (age-median: 2yrs; 54% male) were prospectively included (infection focus: 65% respiratory, 12.5% central nervous system). Overall PICU mortality was 11.7%. 102 children could be classified according to a predefined CRP-ratio response pattern. Time-dependent analysis of CRP-ratio and CRP course of the different patterns were significantly different. Besides, PICU mortality rate was significantly different according CRP-ratio response patterns: fast response 4.5%; slow response 5.8%; non-response 29.4%; biphasic response 42.8%. CONCLUSIONS: In pediatric sepsis, CRP-ratio serial evaluation was useful in early identification of patients with poor outcome.

Patterns of C-reactive protein ratio predicts outcomes in healthcare-associated pneumonia in critically ill patients with cancer.

PURPOSE: Describe the patterns of C-reactive protein relative changes in response to antibiotic therapy in critically ill cancer patients with healthcare-associated pneumonia (HCAP) and its ability to predict outcome. METHODS: Secondary analysis of a prospective cohort of critically ill cancer patients with HCAP. CRP was sampled every other day from D0 to D6 of antibiotic therapy. Patients were classified according to an individual pattern of CRP-ratio response: fast - CRP at D4 of therapy was <0.4 of D0 CRP; slow - a continuous but slow decrease of CRP; non - CRP remained ≥0.8 of D0 CRP; biphasic - initial CRP decrease to levels <0.8 of the D0 CRP followed by a secondary rise ≥0.8. RESULTS: 129 patients were included and septic shock was present in 74% and invasive mechanical ventilation was used in 73%. Intensive care unit (ICU) and hospital mortality rates were 47% and 64%, respectively. By D4, both CRP and CRP-ratio of survivors were significantly lower than in nonsurvivors (p<0.001 and p=0.004, respectively). Both time-dependent analysis of CRP-ratio of the four previously defined patterns (p<0.001) as ICU mortality were consistently different [fast 12.9%, slow 43.2%, biphasic 66.7% and non 71.8% (p<0.001)]. CONCLUSION: CRP-ratio was useful in the early prediction of poor outcomes in cancer patients with HCAP.

Personalized treatment of severe pneumonia in cancer patients.

Patients with cancer are at increased risk for sepsis as a consequence of immunosuppression. The hospital mortality remains elevated and it could be attributed to antibiotic failure because of the presence of multiresistant pathogens. Once the patient is critically ill, the use of the American Thoracic Society/Infectious Diseases Society of America classification does not seem very useful in the assessment of outcomes and the choice of antimicrobials. In critically ill patients, the characteristics of clinical response to antibiotics are usually inaccurate and occur late in the course of disease. So, the sequential evaluation of C-reactive protein-ratio is useful in the early identification of patients with antibiotic failure. To achieve safe and efficient antimicrobial therapy, we proposed an algorithm that may aid clinicians in their decision-making process.

Clinical outcomes and microbiological characteristics of severe pneumonia in cancer patients: a prospective cohort study.

INTRODUCTION: Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia. METHODS: Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected. RESULTS: There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92-15.84)], the use of invasive MV [OR 12.74 (3.60-45.07)] and poor Performance Status [OR 3.00 (1.07-8.42)] were associated with increased hospital mortality. CONCLUSIONS: Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population.

Antiphospholipid antibodies in critically ill patients with cancer: a prospective cohort study.

PURPOSE: The purpose of this study is to evaluate the prevalence and the prognostic impact of antiphospholipid antibodies (aPL) in critically ill cancer patients. METHODS: This is a prospective cohort study in adult patients admitted to the intensive care unit for more than 48 hours at a cancer center. Clinical and laboratory data including coagulation parameters were obtained. Cox proportional hazard models were used to identify predictors of 6-month mortality. RESULTS: Ninety-five (solid tumor, 79%; hematologic malignancies, 21%) patients were included, and aPL were identified in 74% of them. Median Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment scores were 51 (37-65) and 5 (2-8) points, respectively. The most frequent aPL were lupus anticoagulant (61%) and anti-ß2 glicoprotein I (32%). Vascular complications occurred in 18% of patients and were comparable between aPL+ and aPL- patients. Sepsis and need for renal replacement therapy were more frequent in aPL+ patients. Hospital and 6-month mortality rates were 44% and 56%, respectively. Higher Sequential Organ Failure Assessment scores (each point) (hazard ratios [HR]=2.83 [95% confidence interval, 1.59-5.00]), medical admissions (HR=2.66 [1.34-5.27]), and d-dimer more than 500 ng/dL (HR=1.89 (1.04-3.44]) were independently associated with mortality. After adjusting for these covariates, aPL status was not associated with outcomes (HR=1.22 [0.60-2.47]). CONCLUSIONS: Lupus anticoagulants were frequent in critically ill cancer patients. However, they were not associated with medium-term survival in these patients.

Critically ill patients with cancer and sepsis: clinical course and prognostic factors.

PURPOSE: The purposes of this study were to evaluate the clinical course and to identify independent predictors of mortality in patients with cancer with sepsis. MATERIALS AND METHODS: This is a secondary analysis of a prospective cohort study conducted at an oncological medical-surgical intensive care unit. Logistic regression was used to identify predictors of hospital mortality. RESULTS: A total of 563 patients (77% solid tumor, 23% hematologic malignancies) were included over a 55-month period. The most frequent sites of infection were the lung, abdomen, and urinary tract; 91% patients had severe sepsis/septic shock. Gram-negative bacteria were responsible for more than half of the episodes of infection; 38% of patients had polymicrobial infections. Intensive care unit, hospital, and 6-month mortality rates were 51%, 65%, and 72%, respectively. In multivariate analyses, sepsis in the context of medical complications; active disease; compromised performance status; presence of 3 to 4 systemic inflammatory response syndrome criteria; and the presence of respiratory, renal, and cardiovascular failures were associated with increased mortality. Adjusting for other covariates, patients with non-urinary tract infections, mostly represented by patients with pneumonia and abdominal infections, had worse outcomes. CONCLUSIONS: Sepsis remains a frequent complication in patients with cancer and associated with high mortality. Our results can be of help to assist intensivists in clinical decisions and to improve characterization and risk stratification in these patients.

The impact of coagulation parameters on the outcomes of patients with severe community-acquired pneumonia requiring intensive care unit admission.

INTRODUCTION: Coagulation abnormalities are frequent in patients with severe infections. However, the predictive value of d-dimer and of the presence of associated coagulation derangements in severe community-acquired pneumonia (CAP) remains to be thoroughly evaluated. The aim of this study was to investigate the predictive value of coagulation parameters in patients with severe CAP admitted to the intensive care unit. METHODS: d-Dimer, antithrombin, International Society of Thrombosis and Hemostasis score, clinical variables, Sequential Organ Failure Assessment (SOFA), The Acute Physiology and Chronic Health Evaluation II (APACHE II) and the CURB-65 score were measured in the first 24 hours. Results are shown as median (25%-75% interquartile range). The main outcome measure was hospital mortality. RESULTS: Ninety patients with severe CAP admitted to the intensive care unit were evaluated. Overall hospital mortality was 15.5%. d-Dimer levels in nonsurvivors were higher than those in survivors. In the univariate analysis, d-dimer, SOFA, and APACHE II scores were predictors of death. The discriminative ability of d-dimer (area under receiver operating curve = 0.75 [95% confidence interval, 0.64-0.83]; best cutoff for d-dimer was 1798 ng/mL) for in-hospital mortality was comparable with APACHE II and SOFA and better than C-reactive protein. Moreover, the addition of d-dimer to APACHE II or SOFA score increased the discriminative ability of both scores (area under the receiver operating curve = 0.82 [0.72-0.89] and 0.84 [0.75-0.91], respectively). CONCLUSIONS: d-Dimer levels are good predictors of outcome in severe CAP and may augment the predictive ability of scoring systems as APACHE II and SOFA.