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1.  Patient-centered endpoints in trials of ICU sedation 
Critical Care  2014;18(5):536.
doi:10.1186/s13054-014-0536-7
PMCID: PMC4331382  PMID: 25672648
2.  Long-term mortality after critical care: what is the starting point? 
Critical Care  2013;17(5):191.
Mortality is still the most assessed outcome in the critically ill patient and is routinely used as the primary end-point in intervention trials, cohort studies, and benchmarking analysis. Despite this, interest in patient-centered prognosis after ICU discharge is increasing, and several studies report quality of life and long-term outcomes after critical illness. In a recent issue of Critical Care, Cuthbertson and colleagues reported interesting results from a cohort of 439 patients with sepsis, who showed high ongoing long-term mortality rates after severe sepsis, reaching 61% at 5 years (from a starting point of ICU admission). Follow-up may start at ICU admission, after ICU discharge, or after hospital discharge. Using ICU admission as a starting point will include patients with a wide range of illness severities and reasons for ICU admission. As a result, important consequences of the ICU, such as rehabilitation and reduced quality of life, may be diluted in an unselected population. ICU discharge is another frequently used starting point. ICU discharge is a marker of better outcome and reduced risk for acute deterioration, making this an interesting starting point for studying long-term mortality, need for ICU readmission, and critical illness rehabilitation. Finally, using hospital discharge as the starting point will include patients with the minimal requirements to sustain an adequate condition in a non-monitored environment but will add a ?survivors bias?; that is, patients who survive critical illness are a special group among the critically ill. In this commentary, we discuss the heterogeneity in long-term mortality from recent studies in critical care medicine ? heterogeneity that may be a consequence simply of changing the follow-up starting point ? and propose a standardized follow-up starting point for future studies according to the outcome of interest.
doi:10.1186/cc13024
PMCID: PMC4059375  PMID: 24073631
3.  In memoriam - Affonso Berardinelli Tarantino 
Jornal Brasileiro de Pneumologia  2014;40(5):453-454.
doi:10.1590/S1806-37132014000500001
PMCID: PMC4263326  PMID: 25410833
4.  Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study 
Critical Care  2014;18(4):R156.
Introduction
Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV).
Methods
A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality.
Results
A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality.
Conclusions
Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.
doi:10.1186/cc13995
PMCID: PMC4223597  PMID: 25047960
5.  Antiphospholipid antibodies in critically ill patients 
Antiphospholipid antibodies are responsible for a wide spectrum of clinical manifestations. Venous, arterial and microvascular thrombosis and severe catastrophic cases account for a large morbidly/mortality. Through the connection between the immune, inflammatory and hemostatic systems, it is possible that these antibodies may contribute to the development of organ dysfunction and are associated with poor short and long-term prognoses in critically ill patients. We performed a search of the PubMed/MedLine database for articles written during the period from January 2000 to February 2013 to evaluate the frequency of antiphospholipid antibodies in critically ill patients and their impact on the outcomes of these patients. Only eight original studies involving critically ill patients were found. However, the development of antiphospholipid antibodies in critically ill patients seems to be frequent, but more studies are necessary to clarify their pathogenic role and implications for clinical practice.
doi:10.5935/0103-507X.20140026
PMCID: PMC4103945  PMID: 25028953
Antibodies, antiphospholipid; Prognosis; Critical illness; Catastrophic illness; Multiple organ failure; Antiphospholipid syndrome; Intensive care units
6.  Incidence and diagnosis of ventilator-associated tracheobronchitis in the intensive care unit: an international online survey 
Critical Care  2014;18(1):R32.
Introduction
Several aspects of ventilator-associated tracheobronchitis (VAT)—including diagnostic criteria, overlap with ventilator-associated pneumonia (VAP), and appropriate treatment regimens—remain poorly defined. The objectives of this study were to survey reported practices in the clinical and microbiological diagnosis of VAT and to evaluate perceptions of the impact of VAT on patient outcomes.
Methods
We developed a questionnaire consisting of (a) characteristics of the respondent, the ICU, and hospital; (b) current clinical and microbiological diagnostic approach; (c) empirical antibiotic therapy; and (d) the perception of physicians regarding the clinical impact of VAT and its implications.
Results
A total of 288 ICUs from 16 different countries answered the survey: 147 (51%) from the Latin American (LA) group and 141 (49%) from Spain, Portugal, and France (SPF group). The majority of respondents (n = 228; 79.2%) reported making the diagnosis of VAT based on clinical and microbiological criteria, and 40 (13.9%) by clinical criteria alone. Approximately half (50.3%) of the respondents agreed that patients should receive antibiotics for the treatment of VAT. Out of all respondents, 269 (93.4%) assume that a VAT episode increases ICU length of stay, and this perception is greater in the LA group (97.3%) than in the SPF group (89.4%, P <0.05). Half of the physicians considered that VAT increases the risk of mortality, and this perception is again greater in the LA group (58.5% versus 41.1%, P <0.05).
Conclusions
Given the possible high incidence of VAT and the perception of its importance as a risk factor for VAP and mortality, a large multicenter international prospective study would be helpful to validate a consensual definition of VAT, determine its incidence, and delineate its impact on subsequent VAP occurrence.
doi:10.1186/cc13725
PMCID: PMC4057509  PMID: 24521533
7.  The Impact of Acute Brain Dysfunction in the Outcomes of Mechanically Ventilated Cancer Patients 
PLoS ONE  2014;9(1):e85332.
Introduction
Delirium and coma are a frequent source of morbidity for ICU patients. Several factors are associated with the prognosis of mechanically ventilated (MV) cancer patients, but no studies evaluated delirium and coma (acute brain dysfunction). The present study evaluated the frequency and impact of acute brain dysfunction on mortality.
Methods
The study was performed at National Cancer Institute, Rio de Janeiro, Brazil. We prospectively enrolled patients ventilated >48 h with a diagnosis of cancer. Acute brain dysfunction was assessed during the first 14 days of ICU using RASS/CAM-ICU. Patients were followed until hospital discharge. Univariate and multivariable analysis were performed to evaluate factors associated with hospital mortality.
Results
170 patients were included. 73% had solid tumors, age 65 [53–72 (median, IQR 25%–75%)] years. SAPS II score was 54[46–63] points and SOFA score was (7 [6]–[9]) points. Median duration of MV was 13 (6–21) days and ICU stay was 14 (7.5–22) days. ICU mortality was 54% and hospital mortality was 66%. Acute brain dysfunction was diagnosed in 161 patients (95%). Survivors had more delirium/coma-free days [4(1,5–6) vs 1(0–2), p<0.001]. In multivariable analysis the number of days of delirium/coma-free days were associated with better outcomes as they were independent predictors of lower hospital mortality [0.771 (0.681 to 0.873), p<0.001].
Conclusions
Acute brain dysfunction in MV cancer patients is frequent and independently associated with increased hospital mortality. Future studies should investigate means of preventing or mitigating acute brain dysfunction as they may have a significant impact on clinical outcomes.
doi:10.1371/journal.pone.0085332
PMCID: PMC3899009  PMID: 24465538
8.  Access to urban acute care services in high- vs. middle-income countries: an analysis of seven cities 
Intensive Care Medicine  2013;40(3):342-352.
Purpose
Cities are expanding rapidly in middle-income countries, but their supply of acute care services is unknown. We measured acute care services supply in seven cities of diverse economic background.
Methods
In a cross-sectional study, we compared cities from two high-income (Boston, USA and Paris, France), three upper-middle-income (Bogota, Colombia; Recife, Brazil; and Liaocheng, China), and two lower-middle-income (Chennai, India and Kumasi, Ghana) countries. We collected standardized data on hospital beds, intensive care unit beds, and ambulances. Where possible, information was collected from local authorities. We expressed results per population (from United Nations) and per acute illness deaths (from Global Burden of Disease project).
Results
Supply of hospital beds where intravenous fluids could be delivered varied fourfold from 72.4/100,000 population in Kumasi to 241.5/100,000 in Boston. Intensive care unit (ICU) bed supply varied more than 45-fold from 0.4/100,000 population in Kumasi to 18.8/100,000 in Boston. Ambulance supply varied more than 70-fold. The variation widened when supply was estimated relative to disease burden (e.g., ICU beds varied more than 65-fold from 0.06/100 deaths due to acute illnesses in Kumasi to 4.11/100 in Bogota; ambulance services varied more than 100-fold). Hospital bed per disease burden was associated with gross domestic product (GDP) (R2 = 0.88, p = 0.01), but ICU supply was not (R2 = 0.33, p = 0.18). No city provided all requested data, and only two had ICU data.
Conclusions
Urban acute care services vary substantially across economic regions, only partially due to differences in GDP. Cities were poor sources of information, which may hinder their future planning.
doi:10.1007/s00134-013-3174-7
PMCID: PMC3938845  PMID: 24337401
Urban population; Acute care services; Global burden of disease; Hospital beds; Intensive care beds; Ambulances
10.  Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study 
Critical Care  2013;17(2):R63.
Introduction
Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU).
Methods
In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure.
Results
Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30).
Conclusions
Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting.
Trial registration
ClinicalTrials.gov NCT01268410.
doi:10.1186/cc12594
PMCID: PMC3672504  PMID: 23557378
11.  Perceptions and practices regarding delirium, sedation and analgesia in critically ill patients: a narrative review 
A significant number of landmark studies have been published in the last decade that increase the current knowledge on sedation for critically ill patients. Therefore, many practices that were considered standard of care are now outdated. Oversedation has been shown to be hazardous, and light sedation and no-sedation protocols are associated with better patient outcomes. Delirium is increasingly recognized as a major form of acute brain dysfunction that is associated with higher mortality, longer duration of mechanical ventilation and longer lengths of stay in the intensive care unit and hospital. Despite all the available evidence, translating research into bedside care is a daunting task. International surveys have shown that practices such as sedation interruption and titration are performed only in the minority of cases. Implementing best practices is a major challenge that must also be addressed in the new guidelines. In this review, we summarize the findings of sedation and delirium research over the last years. We also discuss the gap between evidence and clinical practice and highlight ways to implement best practices at the bedside.
doi:10.5935/0103-507X.20130027
PMCID: PMC4031827  PMID: 23917981
Sedation; Delirium; Benzodiazepines; Propofol; Analgesics, opioid; Dexmedetomidine; Critical illness
13.  Use of biomarkers in sepsis: many questions, few answers 
doi:10.1590/S0103-507X2013000100001
PMCID: PMC4031864  PMID: 23887751
14.  CAM-ICU and ICDSC Agreement in Medical and Surgical ICU Patients Is Influenced by Disease Severity 
PLoS ONE  2012;7(11):e51010.
Introduction
Delirium is a prevalent condition in patients admitted to intensive care units (ICU) associated with worse outcomes. The principal aim of the present study was compare the agreement between two tools for delirium assessment in medical and surgical patients admitted to the ICU.
Methods
Consecutive adult surgical and medical patients admitted to the ICU for more than 24 hours between March 2009 and September 2010 were included. Delirium was evaluated twice a day using the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion Assessment Method adapted to the Intensive Care Unit (CAM-ICU). The kappa (k) and AC1 coefficients were calculated as a measure of agreement between the CAM-ICU and ICDSC.
Results
A total of 595 patients were enrolled in the study. There were 69 (12%) emergency surgical, 207 (35%) elective surgical and 319 (54%) medical patients. Delirium incidence evaluated by the ICDSC, but not by the CAM-ICU, was similar among the three groups. Overall agreement between CAM-ICU and ICDSC was moderate (k = 0.5) to substantial (AC1 = 0.71). In medical patients the agreement between the two instruments was moderate (k = 0.53) to substantial (AC1 = 0.76). The agreement between the two tools in emergency surgical patients was also moderate (k = 0.53) to substantial (AC1 = 0.68). In elective surgical patients the agreement between the two instruments was low (k = 0.42) to substantial (AC1 = 0.74).Agreement rates seemed to be influenced by disease severity. The agreement rate in the general ICU population with APACHE II = <14 was k = 0.57 and AC1 = 0.81, compared to k = 0.44 and AC1 = 0.59, in patients with more severe disease. This was even more different when the need for mechanical ventilation was used as a surrogate of disease severity.
Conclusions
The agreement rates between CAM-ICU and ICDSC may vary between different groups of ICU patients and seems to be affected by disease severity.
doi:10.1371/journal.pone.0051010
PMCID: PMC3511417  PMID: 23226448
15.  C-reactive protein in community-acquired sepsis: you can teach new tricks to an old dog 
Critical Care  2011;15(5):186.
Severe sepsis is a major challenge for clinicians caring for acutely ill patients. For many years, several biomarkers have been tested and proposed to improve the ability not only to diagnose but also to anticipate clinical response to antibiotics. Despite the availability of many sophisticated and novel biomarkers, current evidence demonstrates that C-reactive protein (CRP), a well-known and relatively inexpensive biomarker, is useful in the clinical setting. The sequential evaluation of plasma CRP concentrations in patients with severe sepsis and the interpretation of its patterns may allow assessments of individual prognosis and response to treatment.
doi:10.1186/cc10301
PMCID: PMC3334722  PMID: 21955725
16.  Biomarker-guided antibiotic therapy in adult critically ill patients: a critical review 
Biomarkers of infection, namely C-reactive protein and procalcitonin (PCT), are potentially useful in the diagnosis of infection as well as in the assessment of its response to antibiotic therapy. C-reactive protein variations overtime appears to have a good performance for the diagnosis of infection. Procalcitonin shows a better correlation with clinical severity. In addition, to overcome the worldwide problem of antibiotic overuse as well as misuse, biomarker guidance of antibiotic stewardship represents a promising new approach. In several randomized, controlled trials, including adult critically ill patients, PCT guidance was repeatedly associated with a decrease in the duration of antibiotic therapy. However, these trials present several limitations, namely high rate of patients’ exclusion, high rate of algorithm overruling, long duration of antibiotic therapy in the control group, disregard the effect of renal failure on PCT level, and above all a possible higher mortality and higher late organ failure in the PCT arm. In addition, some infections (e.g., endocarditis) as well as frequent nosocomial bacteria (e.g., Pseudomonas aeruginosa) are not suitable to be assessed by PCT algorithms. Therefore, the true value of PCT-guided algorithm of antibiotic stewardship in assisting the clinical decision-making process at the bedside remains uncertain. Future studies should take into account the issues identified in the present review.
doi:10.1186/2110-5820-2-32
PMCID: PMC3475044  PMID: 22824162
Antibiotic stewardship; Biomarkers; C-reactive protein; Infection; Procalcitonin; Sepsis
17.  The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies 
Critical Care  2012;16(4):R115.
Introduction
Delirium is a frequent form of acute brain dysfunction in critically ill patients, and several detection tools for it have been developed for use in the Intensive Care Unit (ICU). The objective of this study is to evaluate the current evidence on the accuracy of the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for the diagnosis of delirium in critically ill patients.
Methods
A systematic review was conducted to identify articles on the evaluation of the CAM-ICU and the ICDSC in ICU patients. A MEDLINE, SciELO, CINAHL and EMBASE databases search was performed for articles published in the English language, involving adult populations and comparing these diagnostic tools with the gold standard, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Results were summarized by meta-analysis. The QUADAS scale was used to assess the quality of the studies.
Results
Nine studies evaluating the CAM-ICU (including 969 patients) and four evaluating the ICDSC (n = 361 patients) were included in the final analysis. The pooled sensitivity of the CAM-ICU was 80.0% (95% confidence interval (CI): 77.1 to 82.6%), and the pooled specificity was 95.9% (95% CI: 94.8 to 96.8%). The diagnostic odds ratio was 103.2 (95% CI: 39.6 to 268.8). The pooled area under the summary receiver operating characteristic curve (AUC) was 0.97. The pooled sensitivity of the ICDSC was 74% (95% CI: 65.3 to 81.5%), and the pooled specificity was 81.9% (95% CI: 76.7 to 86.4%). The diagnostic odds ratio was 21.5 (95% CI: 8.51 to 54.4). The AUC was 0.89.
Conclusions
The CAM-ICU is an excellent diagnostic tool in critically ill ICU patients, whereas the ICDSC has moderate sensitivity and good specificity. The available data suggest that both CAM-ICU and the ICDSC can be used as a screening tool for the diagnosis of delirium in critically ill patients.
doi:10.1186/cc11407
PMCID: PMC3580690  PMID: 22759376
18.  Chest computed tomography findings in severe influenza pneumonia occurring in neutropenic cancer patients 
Clinics  2012;67(4):313-318.
OBJECTIVE:
To describe the chest computed tomography findings for severe influenza H1N1 infection in a series of hospitalized neutropenic cancer patients.
METHODS:
We performed a retrospective systematic analysis of chest computed tomography scans for eight hospitalized patients with fever, neutropenia, and confirmed diagnoses of influenza H1N1. The clinical data had been prospectively collected.
RESULTS:
Six of eight patients (75%) developed respiratory failure and required intensive care. Prolonged H1N1 shedding was observed in the three mechanically ventilated patients, and overall hospital mortality in our series was 25%. The most frequent computed tomography findings were ground-glass opacity (all patients), consolidation (7/8 cases), and airspace nodules (6/8 cases) that were frequently moderate or severe. Other parenchymal findings were not common. Five patients had features of pneumonia, two had computed tomography findings compatible with bronchitis and/or bronchiolitis, and one had tomographic signs of chronicity.
CONCLUSION:
In this series of neutropenic patients with severe influenza H1N1 infection, chest computed tomography demonstrated mainly moderate or severe parenchymatous disease, but bronchiolitis was not a common feature. These findings associated with febrile neutropenia should elicit a diagnosis of severe viral infection.
doi:10.6061/clinics/2012(04)03
PMCID: PMC3317247  PMID: 22522755
H1N1; Viral pneumonia; Neutropenia; Cancer; Computed tomography
19.  Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study 
Critical Care  2012;16(2):R53.
Introduction
Community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission remains a severe medical condition, presenting ICU mortality rates reaching 30%. The aim of this study was to assess the value of different patterns of C-reactive protein (CRP)-ratio response to antibiotic therapy in patients with severe CAP requiring ICU admission as an early maker of outcome.
Methods
In total, 191 patients with severe CAP were prospectively included and CRP was sampled every other day from D1 to D7 of antibiotic prescription. CRP-ratio was calculated in relation to D1 CRP concentration. Patients were classified according to an individual pattern of CRP-ratio response with the following criteria: fast response - when D5 CRP was less than or equal to 0.4 of D1 CRP concentration; slow response - when D5 CRP was > 0.4 and D7 less than or equal to 0.8 of D1 CRP concentration; nonresponse - when D7 CRP was > 0.8 of D1 CRP concentration. Comparison between ICU survivors and non-survivors was performed.
Results
CRP-ratio from D1 to D7 decreased faster in survivors than in non-survivors (p = 0.01). The ability of CRP-ratio by D5 to predict ICU outcome assessed by the area under the ROC curve was 0.73 (95% Confidence Interval, 0.64 - 0.82). By D5, a CRP concentration above 0.5 of the initial level was a marker of poor outcome (sensitivity 0.81, specificity 0.58, positive likelihood ratio 1.93, negative likelihood ratio 0.33). The time-dependent analysis of CRP-ratio of the three patterns (fast response n = 66; slow response n = 81; nonresponse n = 44) was significantly different between groups (p < 0.001). The ICU mortality rate was considerably different according to the patterns of CRP-ratio response: fast response 4.8%, slow response 17.3% and nonresponse 36.4% (p < 0.001).
Conclusions
In severe CAP, sequential evaluation of CRP-ratio was useful in the early identification of patients with poor outcome. The evaluation of CRP-ratio pattern of response to antibiotics during the first week of therapy was useful in the recognition of the individual clinical evolution.
doi:10.1186/cc11291
PMCID: PMC3681380  PMID: 22449513
20.  Corticosteroids in severe community-acquired pneumonia: the path we choose depends on where we want to get 
Critical Care  2011;15(2):137.
Severe community-acquired pneumonia is a major cause of admission to intensive care units and its mortality rates remain exceedingly high. In the search for adjunctive therapies, clinicians who were encouraged by available, though limited, evidence prescribed steroids in most patients with severe sepsis or septic shock, including those with community-acquired pneumonia. Current evidence demonstrates that, whereas corticosteroids should not be routinely employed as adjuvant therapy for severe community-acquired pneumonia, there is sufficient equipoise to continue studying the use of corticosteroids.
doi:10.1186/cc10099
PMCID: PMC3219358  PMID: 21457495
21.  The validity and reliability of the Portuguese versions of three tools used to diagnose delirium in critically ill patients 
Clinics  2011;66(11):1917-1922.
OBJECTIVES:
The objectives of this study are to compare the sensitivity and specificity of three diagnostic tools for delirium (the Intensive Care Delirium Screening Checklist, the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet) in a mixed population of critically ill patients, and to validate the Brazilian Portuguese Confusion Assessment Method for Intensive Care Units.
METHODS:
The study was conducted in four intensive care units in Brazil. Patients were screened for delirium by a psychiatrist or neurologist using the Diagnostic and Statistical Manual of Mental Disorders. Patients were subsequently screened by an intensivist using Portuguese translations of the three tools.
RESULTS:
One hundred and nineteen patients were evaluated and 38.6% were diagnosed with delirium by the reference rater. The Confusion Assessment Method for Intensive Care Units had a sensitivity of 72.5% and a specificity of 96.2%; the Confusion Assessment Method for Intensive Care Units Flowsheet had a sensitivity of 72.5% and a specificity of 96.2%; the Intensive Care Delirium Screening Checklist had a sensitivity of 96.0% and a specificity of 72.4%. There was strong agreement between the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet (kappa coefficient = 0.96).
CONCLUSION:
All three instruments are effective diagnostic tools in critically ill intensive care unit patients. In addition, the Brazilian Portuguese version of the Confusion Assessment Method for Intensive Care Units is a valid and reliable instrument for the assessment of delirium among critically ill patients.
doi:10.1590/S1807-59322011001100011
PMCID: PMC3203964  PMID: 22086522
CAM-ICU; ICDSC; CAM-ICU Flowsheet; Critical care; Delirium
22.  C-reactive protein in critically ill cancer patients with sepsis: influence of neutropenia 
Critical Care  2011;15(3):R129.
Introduction
Several biomarkers have been studied in febrile neutropenia. Our aim was to assess C-reactive protein (CRP) concentration in septic critically ill cancer patients and to compare those with and without neutropenia.
Methods
A secondary analysis of a matched case-control study conducted at an oncologic medical-surgical intensive care unit (ICU) was performed, segregating patients with severe sepsis/septic shock. The impact of neutropenia on CRP concentrations at admission and during the first week of ICU stay was assessed.
Results
A total of 154 critically ill septic cancer patients, 86 with neutropenia and 68 without, were included in the present study. At ICU admission, the CRP concentration of neutropenic patients was significantly higher than in non-neutropenic patients, 25.9 ± 11.2 mg/dL vs. 19.7 ± 11.4 mg/dL (P = 0.009). Among neutropenic patients, CRP concentrations at ICU admission were not influenced by the severity of neutropenia (< 100/mm3 vs. ≥ 100/mm3 neutrophils), 25.1 ± 11.6 mg/dL vs. 26.9 ± 10.9 mg/dL (P = 0.527). Time dependent analysis of CRP from Day 1 to Day 7 of antibiotic therapy showed an almost parallel decrease in both groups (P = 0.335), though CRP of neutropenic patients was, on average, always higher in comparison to that of non-neutropenic patients.
Conclusions
In septic critically ill cancer patients CRP concentrations are more elevated in those with neutropenia. However, the CRP course seems to be independent from the presence or absence of neutropenia.
doi:10.1186/cc10242
PMCID: PMC3218995  PMID: 21595932
23.  H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis 
PLoS ONE  2010;5(11):e14158.
Background
The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil.
Methods
We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir.
Results
A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples.
Conclusions
Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.
doi:10.1371/journal.pone.0014158
PMCID: PMC2994772  PMID: 21152402
24.  Delirium epidemiology in critical care (DECCA): an international study 
Critical Care  2010;14(6):R210.
Introduction
Delirium is a frequent source of morbidity in intensive care units (ICUs). Most data on its epidemiology is from single-center studies. Our aim was to conduct a multicenter study to evaluate the epidemiology of delirium in the ICU.
Methods
A 1-day point-prevalence study was undertaken in 104 ICUs from 11 countries in South and North America and Spain.
Results
In total, 975 patients were screened, and 497 fulfilled inclusion criteria and were enrolled (median age, 62 years; 52.5% men; 16.7% and 19.9% for ICU and hospital mortality); 64% were admitted to the ICU because of medical causes, and sepsis was the main diagnosis (n = 76; 15.3%). In total, 265 patients were sedated with the Richmond agitation and sedation scale (RASS) deeper than -3, and only 232 (46.6%) patients could be evaluated with the confusion-assessment method for the ICU. The prevalence of delirium was 32.3%. Compared with patients without delirium, those with the diagnosis of delirium had a greater severity of illness at admission, demonstrated by higher sequential organ-failure assessment (SOFA (P = 0.004)) and simplified acute physiology score 3 (SAPS3) scores (P < 0.0001). Delirium was associated with increased ICU (20% versus 5.7%; P = 0.002) and hospital mortality (24 versus 8.3%; P = 0.0017), and longer ICU (P < 0.0001) and hospital length of stay (LOS) (22 (11 to 40) versus 7 (4 to 18) days; P < 0.0001). Previous use of midazolam (P = 0.009) was more frequent in patients with delirium. On multivariate analysis, delirium was independently associated with increased ICU mortality (OR = 3.14 (1.26 to 7.86); CI, 95%) and hospital mortality (OR = 2.5 (1.1 to 5.7); CI, 95%).
Conclusions
In this 1-day international study, delirium was frequent and associated with increased mortality and ICU LOS. The main modifiable risk factors associated with the diagnosis of delirium were the use of invasive devices and sedatives (midazolam).
doi:10.1186/cc9333
PMCID: PMC3220001  PMID: 21092264

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