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Background: High cortisol levels are frequent in patients with severe infections. However, the predictive value of total cortisol and of the presence of critical illness-related corticosteroid insufficiency (CIRCI) in severe community-acquired pneumonia (CAP) remains to be thoroughly evaluated. The aim of this study was to investigate the predictive value of adrenal response in patients with severe CAP admitted to the ICU.Methods: Baseline and postcorticotropin cortisol levels C-reactive protein (CRP), d-dimer, clinical variables, sequential organ failure assessment (SOFA), APACHE (acute physiology and chronic health evaluation) II, and CURB-65 (confusion, urea nitrogen, respiratory rate, BP, age > or = 65 years) scores were measured in the first 24 h. Results are shown as median (interquartile range [IQR]). The major outcome measure was hospital mortality.Results: Seventy-two patients with severe CAP admitted to the ICU were evaluated. Baseline cortisol levels were 18.1 microg/dL (IQR, 14.4 to 26.7 microg/dL), and the difference between baseline and postcorticotropin cortisol after 250 microg of corticotropin was 19 microg/dL (IQR, 12.8 to 27 microg/dL). Baseline cortisol levels presented positive correlations with scores of disease severity, including CURB-65, APACHE II, and SOFA (p < 0.05). Cortisol levels in nonsurvivors were higher than in survivors. CIRCI was diagnosed in 29 patients (40.8%). In univariate analysis, baseline cortisol, CURB-65, and APACHE II were predictors of death. The discriminative ability of baseline cortisol (area under receiver operating characteristic curve, 0.77; 95% confidence interval, 0.65 to 0.90; best cutoff for cortisol, 25.7 microg/dL) for in-hospital mortality was better than APACHE II, CURB-65, SOFA, d-dimer, or CRP.Conclusions: Baseline cortisol levels are better predictors of severity and outcome in severe CAP than postcorticotropin cortisol or routinely measured laboratory parameters or scores as APACHE II, SOFA, and CURB-65. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether intensive care unit (ICU) outcomes for patients not affected by coronavirus disease 2019 (COVID-19) worsened during the COVID-19 pandemic., Methods: Retrospective cohort study including prospectively collected information of patients admitted to 165 ICUs in a hospital network in Brazil between 2011 and 2020. Association between admission in 2020 and worse hospital outcomes was performed using different techniques, including assessment of changes in illness severity of admitted patients, a variable life-adjusted display of mortality during 2020, a multivariate mixed regression model with admission year as both fixed effect and random slope adjusted for SAPS 3 score, an analysis of trends in performance using standardized mortality ratio (SMR) and standardized resource use (SRU), and perturbation analysis., Results: A total of 644,644 admissions were considered. After excluding readmissions and patients with COVID-19, 514,219 patients were available for analysis. Non-COVID-19 patients admitted in 2020 had slightly lower age and SAPS 3 score but a higher mortality (6.4%) when compared with previous years (2019: 5.6%; 2018: 6.1%). Variable-adjusted life display (VLAD) in 2020 increased but started to decrease as the number of COVID-19 cases increased; this trend reversed as number of COVID cases reduced but recurred on the second wave. After logistic regression, being admitted in 2020 was associated with higher mortality when compared to previous years from 2016 and 2019. Individual ICUs standardized mortality ratio also increased during 2020 (higher SMR) while resource use remained constant, suggesting worsening performance. A perturbation analysis further confirmed changes in ICU outcomes for non-COVID-19 patients., Conclusion: Hospital outcomes of non-COVID-19 critically ill patients worsened during the pandemic in 2020, possibly resulting in an increased number of deaths in critically ill non-COVID patients., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Daily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group., Methods and Analysis: A multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units., Ethics and Dissemination: The study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient's enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit., Trial Registration Number: NCT03920501; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS)., Materials and Methods: Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models., Results: The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone., Conclusion: After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Background: Survival benefit from low tidal volume (V T ) ventilation (LTVV) has been demonstrated for patients with acute respiratory distress syndrome (ARDS), and patients not having ARDS could also benefit from this strategy. Organizational factors may play a role on adherence to LTVV. The present study aimed to identify organizational factors with an independent association with adherence to LTVV., Methods: Secondary analysis of the database of a multicenter two-phase study (prospective cohort followed by a cluster-randomized trial) performed in 118 Brazilian intensive care units. Patients under mechanical ventilation at day 2 were included. LTVV was defined as a V T  ≤ 8 ml/kg PBW on the second day of ventilation. Data on the type and number of beds of the hospital, teaching status, nursing, respiratory therapists and physician staffing, use of structured checklist, and presence of protocols were tested. A multivariable mixed-effect model was used to assess the association between organizational factors and adherence to LTVV., Results: The study included 5719 patients; 3340 (58%) patients received LTVV. A greater number of hospital beds (absolute difference 7.43% [95% confidence interval 0.61-14.24%]; p = 0.038), use of structured checklist during multidisciplinary rounds (5.10% [0.55-9.81%]; p = 0.030), and presence of at least one nurse per 10 patients during all shifts (17.24% [0.85-33.60%]; p = 0.045) were the only three factors that had an independent association with adherence to LTVV., Conclusions: Number of hospital beds, use of a structured checklist during multidisciplinary rounds, and nurse staffing are organizational factors associated with adherence to LTVV. These findings shed light on organizational factors that may improve ventilation in critically ill patients.

Background: Although light sedation levels are associated with several beneficial outcomes for critically ill patients on mechanical ventilation, the majority of patients are still deeply sedated. Organizational factors may play a role on adherence to light sedation levels. We aimed to identify organizational factors associated with a moderate to light sedation target on the first 48 h of mechanical ventilation, as well as the association between early achievement of within-target sedation and mortality., Methods: This study is a secondary analysis of a multicenter two-phase study (prospective cohort followed by a cluster-randomized controlled trial) performed in 118 Brazilian ICUs. We included all critically ill patients who were on mechanical ventilation 48 h after ICU admission. A moderate to light level of sedation or being alert and calm (i.e., the Richmond Agitation-Sedation Scale of - 3 to 0) was the target for all patients on mechanical ventilation during the study period. We collected data on the type of hospital (public, private, profit and private, nonprofit), hospital teaching status, nursing and physician staffing, and presence of sedation, analgesia, and weaning protocols. We used multivariate random-effects regression with ICU and study phase as random-effects and correction for patients' Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment. We also performed a mediation analysis to explore whether sedation level was just a mediator of the association between organizational factors and mortality., Results: We included 5719 patients. Only 1710 (29.9%) were on target sedation levels on day 2. Board-certified intensivists on the morning and afternoon shifts were associated with an adequate sedation level on day 2 (OR = 2.43; CI 95%, 1.09-5.38). Target sedation levels were associated with reduced hospital mortality (OR = 0.63; CI 95%, 0.55-0.72). Mediation analysis also suggested such an association, but did not suggest a relationship between the physician staffing model and hospital mortality., Conclusions: Board-certified intensivists on morning and afternoon shifts were associated with an increased number of patients achieving lighter sedation goals. These findings reinforce the importance of organizational factors, such as intensivists' presence, as a modifiable quality improvement target.

Objectives: The Society of Critical Care Medicine recommends routine delirium monitoring, based on data in critically ill patients without primary neurologic injury. We sought to answer whether there are valid and reliable tools to monitor delirium in neurocritically ill patients and whether delirium is associated with relevant clinical outcomes (e.g., survival, length of stay, functional independence, cognition) in this population., Data Sources: We systematically reviewed Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed., Study Selection and Data Extraction: Inclusion criteria allowed any study design investigating delirium monitoring in neurocritically ill patients (e.g., neurotrauma, ischemic, and/or hemorrhagic stroke) of any age. We extracted data relevant to delirium tool sensitivity, specificity, negative predictive value, positive predictive value, interrater reliability, and associated clinical outcomes., Data Synthesis: Among seven prospective cohort studies and a total of 1,173 patients, delirium was assessed in neurocritically patients using validated delirium tools after considering primary neurologic diagnoses and associated complications, finding a pooled prevalence rate of 12-43%. When able to compare against a common reference standard, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the test characteristics showed a sensitivity of 62-76%, specificity of 74-98%, positive predictive value of 63-91%, negative predictive value of 70-94%, and reliability kappa of 0.64-0.94. Among four studies reporting multivariable analyses, delirium in neurocritically patients was associated with increased hospital length of stay (n = 3) and ICU length of stay (n = 1), as well as worse functional independence (n = 1) and cognition (n = 2), but not survival., Conclusions: These data from studies of neurocritically ill patients demonstrate that patients with primary neurologic diagnoses can meet diagnostic criteria for delirium and that delirious features may predict relevant untoward clinical outcomes. There is a need for ongoing investigations regarding delirium in these complicated neurocritically ill patients.

Objectives: To evaluate the effect of an extended visitation model compared with a restricted visitation model on the occurrence of delirium among ICU patients., Design: Prospective single-center before and after study., Setting: Thirty-one-bed medical-surgical ICU., Patients: All patients greater than or equal to 18 years old with expected length of stay greater than or equal to 24 hours consecutively admitted to the ICU from May 2015 to November 2015., Interventions: Change of visitation policy from a restricted visitation model (4.5 hr/d) to an extended visitation model (12 hr/d)., Measurements and Main Results: Two hundred eighty-six patients were enrolled (141 restricted visitation model, 145 extended visitation model). The primary outcome was the cumulative incidence of delirium, assessed bid using the confusion assessment method for the ICU. Predefined secondary outcomes included duration of delirium/coma; any ICU-acquired infection; ICU-acquired bloodstream infection, pneumonia, and urinary tract infection; all-cause ICU mortality; and length of ICU stay. The median duration of visits increased from 133 minutes (interquartile range, 97.7-162.0) in restricted visitation model to 245 minutes (interquartile range, 175.0-272.0) in extended visitation model (p < 0.001). Fourteen patients (9.6%) developed delirium in extended visitation model compared with 29 (20.5%) in restricted visitation model (adjusted relative risk, 0.50; 95% CI, 0.26-0.95). In comparison with restricted visitation model patients, extended visitation model patients had shorter length of delirium/coma (1.5 d [interquartile range, 1.0-3.0] vs 3.0 d [interquartile range, 2.5-5.0]; p = 0.03) and ICU stay (3.0 d [interquartile range, 2.0-4.0] vs 4.0 d [interquartile range, 2.0-6.0]; p = 0.04). The rate of ICU-acquired infections and all-cause ICU mortality did not differ significantly between the two study groups., Conclusions: In this medical-surgical ICU, an extended visitation model was associated with reduced occurrence of delirium and shorter length of delirium/coma and ICU stay.

Purpose: To assess the impact of performance status (PS) impairment 1 week before hospital admission on the outcomes in patients admitted to intensive care units (ICU)., Methods: Retrospective cohort study in 59,693 patients (medical admissions, 67 %) admitted to 78 ICUs during 2013. We classified PS impairment according to the Eastern Cooperative Oncology Group (ECOG) scale in absent/minor (PS = 0-1), moderate (PS = 2) or severe (PS = 3-4). We used univariate and multivariate logistic regression analyses to investigate the association between PS impairment and hospital mortality., Results: PS impairment was moderate in 17.3 % and severe in 6.9 % of patients. The hospital mortality was 14.4 %. Overall, the worse the PS, the higher the ICU and hospital mortality and length of stay. In addition, patients with worse PS were less frequently discharged home. PS impairment was associated with worse outcomes in all SAPS 3, Charlson Comorbidity Index and age quartiles as well as according to the admission type. Adjusting for other relevant clinical characteristics, PS impairment was associated with higher hospital mortality (odds-ratio (OR) = 1.96 (95 % CI 1.63-2.35), for moderate and OR = 4.22 (3.32-5.35), for severe impairment). The effects of PS on the outcome were particularly relevant in the medium range of severity-of-illness. These results were consistent in the subgroup analyses. However, adding PS impairment to the SAPS 3 score improved only slightly its discriminative capability., Conclusion: PS impairment was associated with worse outcomes independently of other markers of chronic health status, particularly for patients in the medium range of severity of illness.

For decades, corticosteroids are proposed as adjuvant therapies for severe infections. Despite mounting evidence from randomized controlled trials, there is still an intense debate regarding the role of systemic low-dose corticosteroids as a part of the treatment of septic shock. In the present article, we review the current literature and detail aspects on the pathophysiologic rationale, the current evidence, actual practice, and future directions on this topic.

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., Competing Interests: The authors have declared that no competing interests exist.

Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis., Competing Interests: None.

Purpose: To investigate the impact of organizational characteristics and processes of care on hospital mortality and resource use in patients with cancer admitted to intensive care units (ICUs)., Patients and Methods: We performed a retrospective cohort study of 9,946 patients with cancer (solid, n = 8,956; hematologic, n = 990) admitted to 70 ICUs (51 located in general hospitals and 19 in cancer centers) during 2013. We retrieved patients' clinical and outcome data from an electronic ICU quality registry. We surveyed ICUs regarding structure, organization, staffing patterns, and processes of care. We used mixed multivariable logistic regression analysis to identify characteristics associated with hospital mortality and efficient resource use in the ICU., Results: Median number of patients with cancer per center was 110 (interquartile range, 58 to 154), corresponding to 17.9% of all ICU admissions. ICU and hospital mortality rates were 15.9% and 25.4%, respectively. After adjusting for relevant patient characteristics, presence of clinical pharmacists in the ICU (odds ratio [OR], 0.67; 95% CI, 0.49 to 0.90), number of protocols (OR, 0.92; 95% CI, 0.87 to 0.98), and daily meetings between oncologists and intensivists for care planning (OR, 0.69; 95% CI, 0.52 to 0.91) were associated with lower mortality. Implementation of protocols (OR, 1.52; 95% CI, 1.11 to 2.07) and meetings between oncologists and intensivists (OR, 4.70; 95% CI, 1.15 to 19.22) were also independently associated with more efficient resource use. Neither admission to ICUs in cancer centers compared with general hospitals nor annual case volume had an impact on mortality or resource use., Conclusion: Organizational aspects, namely the implementation of protocols and presence of clinical pharmacists in the ICU, and close collaboration between oncologists and ICU teams are targets to improve mortality and resource use in critically ill patients with cancer., (© 2016 by American Society of Clinical Oncology.)

Importance: The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain., Objective: To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults., Design, Setting, and Participants: This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase., Interventions: Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care., Main Outcomes and Measures: In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients' severity and the ICU's baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events., Results: A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line-associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions)., Conclusions and Relevance: Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality., Trial Registration: clinicaltrials.gov Identifier: NCT01785966.

Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit (ICU) admissions with high mortality. Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial. Heterogeneity of published data regarding study design, population demographics, severity of illness, dosing, type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions. However, it is reasonable to admit that, as it was not found any advantage of corticosteroid therapy in so diverse conditions, such beneficial effects do not exist at all. Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies. Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay. Finally, it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection. Thus its current use in severe influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.

Several observational studies as well as experimental data suggest that the use of macrolides is associated with better outcomes in patients with severe pneumonia. In severe community acquired pneumonia (SCAP), data demonstrate a benefit of combination therapy, including a beta-lactam plus a macrolide or floroquinolone, at least in the subgroup of patients with critical disease. Such combination seems to have a more significant impact in those with increased disease severity, particularly in those presenting with shock. In addition, data suggest that not all combinations are the same, and SCAP patients receiving combination therapy with macrolides have lower mortality than patients receiving combination with fluoroquinolones. Better results could be associated with a potential immunomodulatory effect of macrolides as well as inhibition to bacterial growth and virulence factors expression (e.g. Streptococcus pneumoniae pneumolysin). Additionally, recent studies try to incorporate these drugs to our therapeutic options in patients with other sepsis causes (e.g. nosocomial pneumonia) and pathogens (e.g. Pseudomonas aeruginosa). In this review, we will assess these issues, discussing the available evidence on macrolides use and highlighting potential research questions to be assessed on this field.

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.

Objective: To conduct a multinational survey of intensive care unit professionals to determine the practices on delirium assessment and management, in addition to their perceptions and attitudes toward the evaluation and impact of delirium in patients requiring noninvasive ventilation., Methods: An electronic questionnaire was created to evaluate the profiles of the respondents and their related intensive care units, the systematic delirium assessment and management and the respondents' perceptions and attitudes regarding delirium in patients requiring noninvasive ventilation. The questionnaire was distributed to the cooperative network for research of the Associação de Medicina Intensiva Brasileira (AMIB-Net) mailing list and to researchers in different centers in Latin America and Europe., Results: Four hundred thirty-six questionnaires were available for analysis; the majority of the questionnaires were from Brazil (61.9%), followed by Turkey (8.7%) and Italy (4.8%). Approximately 61% of the respondents reported no delirium assessment in the intensive care unit, and 31% evaluated delirium in patients under noninvasive ventilation. The Confusion Assessment Method for the intensive care unit was the most reported validated diagnostic tool (66.9%). Concerning the indication of noninvasive ventilation in patients already presenting with delirium, 16.3% of respondents never allow the use of noninvasive ventilation in this clinical context., Conclusion: This survey provides data that strongly reemphasizes poor efforts toward delirium assessment and management in the intensive care unit setting, especially regarding patients requiring noninvasive ventilation.

Rationale: Sepsis is a major cause of mortality among critically ill patients with cancer. Information about clinical outcomes and factors associated with increased risk of death in these patients is necessary to help physicians recognize those patients who are most likely to benefit from ICU therapy and identify possible targets for intervention., Objectives: In this study, we evaluated cancer patients with sepsis chosen from a multicenter prospective study to characterize their clinical characteristics and to identify independent risk factors associated with hospital mortality., Methods: Subgroup analysis of a multicenter prospective cohort study conducted in 28 Brazilian intensive care units (ICUs) to evaluate adult cancer patients with severe sepsis and septic shock. We used logistic regression to identify variables associated with hospital mortality., Measurements and Main Results: Of the 717 patients admitted to the participating ICUs, 268 (37%) had severe sepsis (n = 142, 53%) or septic shock (n = 126, 47%). These patients comprised the population of the present study. The mean score on the third version of the Simplified Acute Physiology Score was 62.9 ± 17.7 points, and the median Sequential Organ Failure Assessment score was 9 (7-12) points. The most frequent sites of infection were the lungs (48%), intraabdominal region (25%), bloodstream as primary infection (19%), and urinary tract (17%). Half of the patients had microbiologically proven infections, and Gram-negative bacteria were the most common pathogens causing sepsis (31%). ICU and hospital mortality rates were 42% and 56%, respectively. In multivariable analysis, the number of acute organ dysfunctions (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87), hematological malignancies (OR, 2.57; 95% CI, 1.05-6.27), performance status 2-4 (OR, 2.53; 95% CI, 1.44-4.43), and polymicrobial infections (OR, 3.74; 95% CI, 1.52-9.21) were associated with hospital mortality., Conclusions: Sepsis is a common cause of critical illness in patients with cancer and remains associated with high mortality. Variables related to underlying malignancy, sepsis severity, and characteristics of infection are associated with a grim prognosis.

Purpose: The purpose of the study is to determine if pharmacologic approaches are effective in prevention and treatment of delirium in critically ill patients., Materials and Methods: We performed a systematic search to identify publications (from January 1980 to September 2014) that evaluated the pharmacologic interventions to treat or prevent delirium in intensive care unit (ICU) patients., Results: From 2646 citations, 15 studies on prevention (6729 patients) and 7 studies on treatment (1784 patients) were selected and analyzed. Among studies that evaluated surgical patients, the pharmacologic interventions were associated with a reduction in delirium prevalence, ICU length of stay, and duration of mechanical ventilation, but with high heterogeneity (respectively, I(2) = 81%, P = .0013; I(2) = 97%, P < .001; and I(2) = 97%). Considering treatment studies, only 1 demonstrated a significant decrease in ICU length of stay using dexmedetomidine compared to haloperidol (Relative Risk, 0.62 [1.29-0.06]; I(2) = 97%), and only 1 found a shorter time to resolution of delirium using quetiapine (1.0 [confidence interval, 0.5-3.0] vs 4.5 [confidence interval, 2.0-7.0] days; P = .001)., Conclusion: The use of antipsychotics for surgical ICU patients and dexmedetomidine for mechanically ventilated patients as a preventive strategy may reduce the prevalence of delirium in the ICU. None of the studied agents that were used for delirium treatment improved major clinical outcome, including mortality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To determine the relation between delirium in critically ill patients and their outcomes in the short term (in the intensive care unit and in hospital) and after discharge from hospital., Design: Systematic review and meta-analysis of published studies., Data Sources: PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 January 2015., Eligibility Criteria for Selection Studies: Reports were eligible for inclusion if they were prospective observational cohorts or clinical trials of adults in intensive care units who were assessed with a validated delirium screening or rating system, and if the association was measured between delirium and at least one of four clinical endpoints (death during admission, length of stay, duration of mechanical ventilation, and any outcome after hospital discharge). Studies were excluded if they primarily enrolled patients with a neurological disorder or patients admitted to intensive care after cardiac surgery or organ/tissue transplantation, or centered on sedation management or alcohol or substance withdrawal. Data were extracted on characteristics of studies, populations sampled, identification of delirium, and outcomes. Random effects models and meta-regression analyses were used to pool data from individual studies., Results: Delirium was identified in 5280 of 16,595 (31.8%) critically ill patients reported in 42 studies. When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; P<0.001) as well as longer durations of mechanical ventilation and lengths of stay in the intensive care unit and in hospital (standard mean differences 1.79 (95% confidence interval 0.31 to 3.27; P<0.001), 1.38 (0.99 to 1.77; P<0.001), and 0.97 (0.61 to 1.33; P<0.001), respectively). Available studies indicated an association between delirium and cognitive impairment after discharge., Conclusions: Nearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge., (© Salluh et al 2015.)

Background: The Checklist During Multidisciplinary Visits for Reduction of Mortality in Intensive Care Units (Checklist- ICU) trial is a pragmatic, two-arm, cluster-randomised trial involving 118 intensive care units in Brazil, with the primary objective of determining if a multifaceted qualityimprovement intervention with a daily checklist, definition of daily care goals during multidisciplinary daily rounds and clinician prompts can reduce inhospital mortality., Objective: To describe our trial statistical analysis plan (SAP)., Methods: This is an ongoing trial conducted in two phases. In the preparatory observational phase, we collect three sets of baseline data: ICU characteristics; patient characteristics, processes of care and outcomes; and completed safety attitudes questionnaires (SAQs). In the randomised phase, ICUs are assigned to the experimental or control arms and we collect patient data and repeat the SAQ., Results: Our SAP includes the prespecified model for the primary and secondary outcome analyses, which account for the cluster-randomised design and availability of baseline data. We also detail the multiple mediation models that we will use to assess our secondary hypothesis (that the effect of the intervention on inhospital mortality is mediated not only through care processes targeted by the checklist, but also through changes in safety culture). We describe our approach to sensitivity and subgroup analyses and missing data., Conclusion: We report our SAP before closing our study database and starting analysis. We anticipate that this should prevent analysis bias and enhance the utility of results.

Introduction: The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients., Methods: We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality., Results: A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment., Conclusions: In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo., Trial Registration: Clinicaltrials.gov NCT00604214 . Registered 24 January 2008.

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.

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.