Characteristics and outcomes of autologous hematopoietic stem cell transplant recipients admitted to intensive care units: A multicenter study.

PURPOSE: Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission. METHODS: This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders. RESULTS: We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82-17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77-2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63-2.66) were not. CONCLUSIONS: In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.

Trends in clinical profiles, organ support use and outcomes of patients with cancer requiring unplanned ICU admission: a multicenter cohort study.

PURPOSE: To describe trends in outcomes of cancer patients with unplanned admissions to intensive-care units (ICU) according to cancer type, organ support use, and performance status (PS) over an 8-year period. METHODS: We retrospectively analyzed prospectively collected data from all cancer patients admitted to 92 medical-surgical ICUs from July/2011 to June/2019. We assessed trends in mortality through a Bayesian hierarchical model adjusted for relevant clinical confounders and whether there was a reduction in ICU length-of-stay (LOS) over time using a competing risk model. RESULTS: 32,096 patients (8.7% of all ICU admissions; solid tumors, 90%; hematological malignancies, 10%) were studied. Bed/days use by cancer patients increased up to more than 30% during the period. Overall adjusted mortality decreased by 9.2% [95% credible interval (CI), 13.1-5.6%]. The largest reductions in mortality occurred in patients without need for organ support (9.6%) and in those with need for mechanical ventilation (MV) only (11%). Smallest reductions occurred in patients requiring MV, vasopressors, and dialysis (3.9%) simultaneously. Survival gains over time decreased as PS worsened. Lung cancer patients had the lowest decrease in mortality. Each year was associated with a lower sub-hazard for ICU death [SHR 0.93 (0.91-0.94)] and a higher chance of being discharged alive from the ICU earlier [SHR 1.01 (1-1.01)]. CONCLUSION: Outcomes in critically ill cancer patients improved in the past 8 years, with reductions in both mortality and ICU LOS, suggesting improvements in overall care. However, outcomes remained poor in patients with lung cancer, requiring multiple organ support and compromised PS.

Aminoglycosides in Immunocompromised Critically Ill Patients With Bacterial Pneumonia and Septic Shock: A Post-Hoc Analysis of a Prospective Multicenter Multinational Cohort.

BACKGROUND: The routine use of empiric combination therapy with aminoglycosides during critical illness is associated with uncertain benefit and increased risk of acute kidney injury. This study aimed to assess the benefits of aminoglycosides in immunocompromised patients with suspected bacterial pneumonia and sepsis. METHODS: Secondary analysis of a prospective multicenter study. Adult immunocompromised patients with suspected bacterial pneumonia and sepsis or septic shock were included. Primary outcome was hospital mortality. Secondary outcomes were needed for renal replacement therapy (RRT). Mortality was also assessed in neutropenic patients and in those with confirmed bacterial pneumonia. Results were further analyzed in a cohort matched on risk of receiving aminoglycosides combination. RESULTS: Five hundred thirty-five patients were included in this analysis, of whom 187 (35%) received aminoglycosides in addition to another antibiotic effective against gram-negative bacteria. Overall hospital mortality was 59.6% (58.3% vs. 60.3% in patients receiving and not receiving combination therapy; P = 0.71). Lack of association between mortality and aminoglycosides was confirmed after adjustment for confounders and center effect (adjusted OR 1.14 [0.69-1.89]) and in a propensity matched cohort (adjusted OR = 0.89 [0.49-1.61]). No association was found between aminoglycosides and need for RRT (adjusted OR = 0.83 [0.49-1.39], P = 0.477), nor between aminoglycoside use and outcome in neutropenic patients or in patients with confirmed bacterial pneumonia (adjusted OR 0.66 [0.23-1.85] and 1.25 [0.61-2.57], respectively). CONCLUSION: Aminoglycoside combination therapy was not associated with hospital mortality or need for renal replacement therapy in immunocompromised patients with pulmonary sepsis.

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

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.

ICU staffing feature phenotypes and their relationship with patients' outcomes: an unsupervised machine learning analysis.

PURPOSE: To study whether ICU staffing features are associated with improved hospital mortality, ICU length of stay (LOS) and duration of mechanical ventilation (MV) using cluster analysis directed by machine learning. METHODS: The following variables were included in the analysis: average bed to nurse, physiotherapist and physician ratios, presence of 24/7 board-certified intensivists and dedicated pharmacists in the ICU, and nurse and physiotherapist autonomy scores. Clusters were defined using the partition around medoids method. We assessed the association between clusters and hospital mortality using logistic regression and with ICU LOS and MV duration using competing risk regression. RESULTS: Analysis included data from 129,680 patients admitted to 93 ICUs (2014-2015). Three clusters were identified. The features distinguishing between the clusters were: the presence of board-certified intensivists in the ICU 24/7 (present in Cluster 3), dedicated pharmacists (present in Clusters 2 and 3) and the extent of nurse autonomy (which increased from Clusters 1 to 3). The patients in Cluster 3 exhibited the best outcomes, with lower adjusted hospital mortality [odds ratio 0.92 (95% confidence interval (CI), 0.87-0.98)], shorter ICU LOS [subhazard ratio (SHR) for patients surviving to ICU discharge 1.24 (95% CI 1.22-1.26)] and shorter durations of MV [SHR for undergoing extubation 1.61(95% CI 1.54-1.69)]. Cluster 1 had the worst outcomes. CONCLUSION: Patients treated in ICUs combining 24/7 expert intensivist coverage, a dedicated pharmacist and nurses with greater autonomy had the best outcomes. All of these features represent achievable targets that should be considered by policy makers with an interest in promoting equal and optimal ICU care.

Association of frailty with short-term outcomes, organ support and resource use in critically ill patients.

PURPOSE: Frail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients' physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients. METHODS: Retrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses. RESULTS: The analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1-2) and 24,494 (18.9%) frail (MFI ≥ 3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89-3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54-0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased. CONCLUSIONS: Frailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support.

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

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

Effects of Organizational Characteristics on Outcomes and Resource Use in Patients With Cancer Admitted to Intensive Care Units.

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.

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

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

Síndrome de angústia respiratória aguda após Berlim / Acute respiratory distress syndrome after Berlin

As definições de Berlim tiveram o objetivo de aumentar a acurácia diagnóstica frente à Síndrome de Angústia Respiratória Aguda (SARA), principalmente no que diz respeito à sua estratificação de gravidade e ao seu prognóstico, progressivamente pior, associado a esta classificação. Esta distinção permitiu, inclusive que a abordagem terapêutica fosse aplicada de maneira mais oportuna e adequada, no momento da detecção da SARA grave, como, por exemplo, o uso da posição prona. Entretanto, ainda críticas existem sobre essas definições, que determinam incertezas relativas à reprodutibilidade, relacionada à estratégia ventilatória inicial pré diagnóstico, e à sua validade preditiva para letalidade. Portanto, essa revisão aborda esses questionamentos e apresenta possíveis melhorias futuras na sensibilidade e especificidade diagnósticas dessa síndrome de elevada letalidade em nosso país...

Berlin definition was intended to increase the diagnostic accuracy upon the Acute Respiratory Distress Syndrome (ARDS), particularly with regard to its stratification of severity and prognosis, progressively worse, associated with this classification. This distinction has allowed even that the therapeutic approach was applied in a more timely and adequate way at the time of detection of severe ARDS, such as, for instance, the use of the prone position. However, there is still criticism about these settings that determine uncertainties regarding the reproducibility, related to the initial ventilatory strategy before this diagnosis, and its predictive validity for mortality. Therefore, this review addresses these questions and presents possible future improvements in the diagnostic sensitivity and specificity of this highly lethal syndrome in our country...

Ventilator-associated pneumonia prevention by education and two combined bedside strategies.

OBJECTIVE: The objective of the study was to reduce the ventilator-associated pneumonia (VAP) incidence rates through a rational prevention program. DESIGN: The study was a non-controlled clinical trial with a set of interventions in mechanically ventilated patients from April 2006 until June 2008. Pneumonia rates were analyzed as time series and their mean risks of development were compared before and after the interventions with a non-concurrent cohort using the same time frame (January 2004-March 2006). SETTING: The study was conducted in a 14-bed medical intensive care unit of private general hospital in Rio de Janeiro, Brazil. PARTICIPANTS: The study included invasively ventilated patients (n = 224; intervention group) compared with 294 controls (historical cohort). INTERVENTIONS: An educational module about VAP prevention was introduced at the start of the trial (April 2006). A bundle checklist was used daily concomitantly with a standardized oral care in all patients afterwards. Main outcome measure The main outcome measure was reduction in VAP incidence rates. RESULTS: The observed mean rate before the intervention was 18.6 ± 7.8/1000 ventilator-days (95% CI 8.7-14.9), decreasing to 11.8 ± 7.8/1000 ventilator-days (95% CI 15.5-21.7) (P = 0.002) after the interventions. Under the adoption of non-informative prior distributions for the parameters of the proposed statistical model, there was a 70% posterior probability in favor of the hypothesis of risk reduction associated with the interventions, regardless their seasonality or secular trends. There was a 38% relative risk reduction. CONCLUSIONS: A reduction in VAP rates and on their risk after a set of preventive tools was observed. However, some other co-interventions not related to the primary interventions may have contributed to these results.

Estereologia do miocárdio em fetos humanos: estudo quantitativo das modificaçöes estruturais nos dois últimos trimestres de gestaçäo / Stereology of the Myocardium in Human Fetuses: Quantitative Study of the Structural Changes in the Last Two Trimesters of Gestation

Objetivo - Quantificar o miocárdio humano comparando o 2§ e 3§ trimestres gestacionais. Métodos - Fragmentos de miocárdio de 8 coraçöes de fetos humanos (sendo 4 do 2§ e 4 do 3§ trimestre) foram coletados e processados histologicamente. Quinze campos miocárdicos aleatórios de cada coraçäo foram quantificados para miócitos, tecido conjuntivo e vasos contando pontos-teste e intersecçöes . Resultados - As diferenças esterológicas para os miócitos, vasos e tecido conjuntivo, näo foram significantes comparando os 2 trimestres (p > 0,05). A densidade volumétrica foi: miócitos (núcleos inclusive) = 75,6// no 2§ trimestre e 67,7// no 3§ trimestre; vasos = 3,7// no 2§ trimestre e 6,4// no 3§ trimestre; tecido conjuntivo (substância intersticial excluindo os vasos) de 20,6 a 25,9// do 2§ para o 3§ trimestres, respectivamente. Entretanto, a diferença das densidades volumétricas dos núcleos dos miócitos foi significante (p=0,004) e indicou reduçäo do 2§ para o 3§ trimestres, de 15,2 para 8,1// respectivamente. Conclusäo - Esses resultados sugerem que há reduçäo gradativa da síntese protéica nos 2 últimos trimestres gestacionais, sem alteraçäo quantitativa importante na composiçäo do tecido cardíaco, provavelmente relacionada à simultânea diminuiçäo da multiplicaçäo celular miocárdica

Purpose - Quantitative study of the human myocardial comparing the2nd and 3rd trimesters of gestation. Methods - Fragments of the myocardium were collected from 8 fetal human hearts (4 from 2nd and 4 from 3rd trimesters) and prepared by histological methods. Fifteen random fields from each region were analyzed considering independently myocytes, connective tissue and vessels. Stereological determinations were possible by counting test-points and intersections on a multipurpose test lattice (M42). Results - Stereological differences between last 2 trimesters of gestation were not significant (p>0,05). The volume density was myocyte (including nucleus)=75.6% in 2nd trimester and 67.7% in 3rd trimester; vessels=3.7% in 2nd trimester and 6.4% in 3rd trimester; connective tissue (interstitial substance without vessels) = 20.6 to 25.9% for 2nd and 3rd trimesters respectively. However, considering the nuclei of the myocytes differences between last 2 trimesters were significant (p=0.004). The volume density of the nuclei had a reduction from 2nd to 3rd trimesters (from 15.2 to 8.1% respectively). Conclusion - This result suggests decreasing synthesis of proteins from nucleus of myocyte in the last 2 gestational trimesters, but without quantitative important changes in the cardiac tissue, probably in relation to the reduction of the myocardial cellular multiplication