Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Epidemiology of Renal Replacement Therapy for Critically Ill Patients across Seven Health Jurisdictions.

INTRODUCTION: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. METHODS: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. RESULTS: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

Hospital Length of Stay and 30-Day Mortality Prediction in Stroke: A Machine Learning Analysis of 17,000 ICU Admissions in Brazil.

BACKGROUND: Hospital length of stay and mortality are associated with resource use and clinical severity, respectively, in patients admitted to the intensive care unit (ICU) with acute stroke. We proposed a structured data-driven methodology to develop length of stay and 30-day mortality prediction models in a large multicenter Brazilian ICU cohort. METHODS: We analyzed data from 130 ICUs from 43 Brazilian hospitals. All consecutive adult patients admitted with stroke (ischemic or nontraumatic hemorrhagic) to the ICU from January 2011 to December 2020 were included. Demographic data, comorbidities, acute disease characteristics, organ support, and laboratory data were retrospectively analyzed by a data-driven methodology, which included seven different types of machine learning models applied to training and test sets of data. The best performing models, based on discrimination and calibration measures, are reported as the main results. Outcomes were hospital length of stay and 30-day in-hospital mortality. RESULTS: Of 17,115 ICU admissions for stroke, 16,592 adult patients (13,258 ischemic and 3334 hemorrhagic) were analyzed; 4298 (26%) patients had a prolonged hospital length of stay (> 14 days), and 30-day mortality was 8% (n = 1392). Prolonged hospital length of stay was best predicted by the random forests model (Brier score = 0.17, area under the curve = 0.73, positive predictive value = 0.61, negative predictive value = 0.78). Mortality prediction also yielded the best discrimination and calibration through random forests (Brier score = 0.05, area under the curve = 0.90, positive predictive value = 0.66, negative predictive value = 0.94). Among the 20 strongest contributor variables in both models were (1) premorbid conditions (e.g., functional impairment), (2) multiple organ dysfunction parameters (e.g., hypotension, mechanical ventilation), and (3) acute neurological aspects of stroke (e.g., Glasgow coma scale score on admission, stroke type). CONCLUSIONS: Hospital length of stay and 30-day mortality of patients admitted to the ICU with stroke were accurately predicted through machine learning methods, even in the absence of stroke-specific data, such as the National Institutes of Health Stroke Scale score or neuroimaging findings. The proposed methods using general intensive care databases may be used for resource use allocation planning and performance assessment of ICUs treating stroke. More detailed acute neurological and management data, as well as long-term functional outcomes, may improve the accuracy and applicability of future machine-learning-based prediction algorithms.

Hydrazones in anion transporters: the detrimental effect of a second binding site.

Synthetic anion transporters can be developed using anion receptors that are able to bind the anion and stabilize it in the lipophilic interior of a bilayer membrane, and they usually contain functional groups with acidic NHs, such as ureas, thioureas and squaramides. To assess the suitability of acylhydrazones as a new functional group for the preparation of anion transporters, we have studied a family of thioureas functionalized with these and related functional groups. 1H NMR titrations and DFT calculations indicate that the thioureas bearing acylhydrazone groups behave as chloride receptors with two separate binding sites, of which the acylhydrazone binds weaker than the thiourea. Chloride transport studies show that the additional binding site has a detrimental effect on thiourea-based transporters, and this phenomenon is also observed for bis(thio)ureas with two separate binding sites. We propose that the presence of a second anion binding unit hinders the transport activity of the thiourea due to additional interactions with the phospholipids of the membrane. In agreement with this hypothesis, extensive molecular dynamics simulations suggest that the molecules will tend to be positioned in the water/lipid interface, driven by the interaction of the NHs of the thiourea and of the acylhydrazone groups with the POPC polar head groups and water molecules. Moreover, the interaction energies show that the poorest transporters have indeed the strongest interactions with the membrane phospholipids, inhibiting chloride transport. This detrimental effect of additional functional groups on transport activity should be considered when designing new ion transporters, unless these groups cooperatively promote anion recognition and transmembrane transport.

Systemic Severity and Organ Dysfunction in Subarachnoid Hemorrhage: A Large Retrospective Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Acute physiologic derangements and multiple organ dysfunction are common after subarachnoid hemorrhage. We aimed to evaluate the simplified acute physiology score 3 (SAPS-3) and the sequential organ failure assessment (SOFA) scores for the prediction of in-hospital mortality in a large multicenter cohort of SAH patients. METHODS: This was a retrospective analysis of prospectively collected data from 45 ICUs in Brazil, during 2014 and 2015. Patients admitted with non-traumatic subarachnoid hemorrhage (SAH) were included. Clinical and outcome data were retrieved from an electronic ICU quality registry. SAPS-3 and SOFA scores, without the neurological components (i.e., nSAPS-3 and nSOFA, respectively) were recorded, as well as the World Federation of Neurological Surgeons (WFNS) scale. We used multilevel logistic regression analysis to identify factors associated with in-hospital mortality. We evaluated performance using the area under the receiver operating characteristic curve (AUROC), as well as calibration belts and precision-recall plots. RESULTS: The study included 997 patients, from which 426 (43%) had poor clinical grade (WFNS 4 or 5) and in-hospital mortality was 34%. Median nSAPS-3 and nSOFA score at admission were 46 (IQR: 38-55) and 2 (0-5), respectively. Non-survivors were older, had higher nSAPS-3 and nSOFA, and more often poor grade. After adjustment for age, poor grade and withdrawal of life sustaining therapies, multivariable analysis identified nSAPS-3 and nSOFA score as independent clinical predictors of in-hospital mortality. The AUROC curve that included nSAPS-3 and nSOFA scores significantly improved the already good discrimination and calibration of age and WFNS to predict in-hospital mortality (AUROC: 0.89 for the full final model vs. 0.85 for age and WFNS; P < 0.0001). CONCLUSIONS: nSAPS-3 and nSOFA scores were independently associated with in-hospital mortality after SAH. The addition of these scores improved early prediction of hospital mortality in our cohort and should be integrated to other specific prognostic indices in the early assessment of SAH.

Proposal of new distribution coefficients (Kd) of potentially toxic elements in soils for improving environmental risk assessment in the State of São Paulo, southeastern Brazil.

Soil solid-solution distribution coefficients (Kd) are used in predictive environmental models to assess public health risks. This study was undertaken to determine Kd for potentially toxic elements (PTE) Cd, Co, Cr, Cu, Ni, Pb, and Zn in topsoil samples (0-20 cm) from 30 soils in the State of São Paulo, southeastern Brazil. Batch sorption experiments were carried out, and PTE concentrations in the equilibrium solution were determined by High Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICPMS). Sorption data was fitted to the Freundlich model. The Kd values were either obtained directly from the slope coefficients of C-type isotherms or derived from the slope of the straight line tangent to the non-linear L-type and H-type isotherms. Stepwise multiple regression models were used to estimate the Kd values through the combined effect of a number of soil attributes [pHH2O, effective cation exchange capacity (ECEC) and contents of clay, organic carbon, and Fe (oxy)hydroxides]. The smallest variation in Kd values was recorded for Cu (105-4598 L kg-1), Pb (121-7020 L kg-1), Ni (6-998 L kg-1), as variation across four orders of magnitude was observed for Cd (7-14,339 L kg-1), Co (2-34,473 L kg-1), and Cr (1-21,267 L kg-1). The Kd values for Zn were between 5 and 123,849 L kg-1. According to median values of Kd, PTE were sorbed in the following preferential order: Pb > Cu > Cd > Ni > Zn > Cr > Co. The Kd values were best predicted using metal-specific and highly significant (p < 0.001) linear regressions that included pHH2O, ECEC, and clay contents. The Kd values reported in this study are a novel result that can help minimize erroneous estimates and improve both environmental and public health risk assessments under humid tropical edaphoclimatic conditions.

Rapid differentiation of graft Citrus sinensis with and without Xylella fastidiosa infection by mass spectrometry.

RATIONALE: Xylella fastidiosa causes citrus variegated chlorosis (CVC) in sweet orange trees. A diagnostic method for detecting CVC before the symptoms appear, which would inform citrus producers in advance about when the plant should be removed from the orchard, is essential for reducing pesticide application costs. METHODS: Chemometrics was applied to high-performance liquid chromatography diode array detector (HPLC-DAD) data to evaluate the similarities and differences between the chromatographic profiles. A liquid chromatography/atmospheric pressure chemical ionization mass spectrometry selected reaction monitoring (LC/APCI-MS-SRM) method was developed to identify the major compounds and to determine their amounts in all samples. RESULTS: We evaluated the effect of this bacterium on the variation in the chemical profile in citrus plants. The organs of C. sinensis grafted on C. limonia were analyzed. Chemometrics was applied to the obtained data, and two major groups were differentiated. Flavonoids were observed in one group (leaves) and coumarins in the second (roots), both at higher concentrations in the plants with CVC symptoms than in those without the symptoms and those in the negative control. The rootstocks also interfered in the metabolism of the scion. CONCLUSIONS: The developed LC/APCI-MS-SRM method for detecting CVC before the symptoms appear is simple and accurate. It is inexpensive, and many samples can be screened per hour using 1 mg of leaves. Knowledge of the influence of the rootstock on the chemical profile of the graft is limited. This study demonstrates the effect of the rootstock in synthesizing flavonoids and increasing its content in all parts of the graft.

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

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

Influenza and associated co-infections in critically ill immunosuppressed patients.

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Influence of neutropenia on mortality of critically ill cancer patients: results of a meta-analysis on individual data.

BACKGROUND: The study objective was to assess the influence of neutropenia on outcome of critically ill cancer patients by meta-analysis of individual data. Secondary objectives were to assess the influence of neutropenia on outcome of critically ill patients in prespecified subgroups (according to underlying tumor, period of admission, need for mechanical ventilation and use of granulocyte colony stimulating factor (G-CSF)). METHODS: Data sources were PubMed and the Cochrane database. Study selection included articles focusing on critically ill cancer patients published in English and studies in humans from May 2005 to May 2015. For study selection, the study eligibility was assessed by two investigators. Individual data from selected studies were obtained from corresponding authors. RESULTS: Overall, 114 studies were identified and authors of 30 studies (26.3% of selected studies) agreed to participate in this study. Of the 7515 included patients, three were excluded due to a missing major variable (neutropenia or mortality) leading to analysis of 7512 patients, including 1702 neutropenic patients (22.6%). After adjustment for confounders, and taking study effect into account, neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = 0.03). When analyzed separately, neither admission period, underlying malignancy nor need for mechanical ventilation modified the prognostic influence of neutropenia on outcome. However, among patients for whom data on G-CSF administration were available (n = 1949; 25.9%), neutropenia was no longer associated with outcome in patients receiving G-CSF (OR 1.03; 95% CI 0.70-1.51; P = 0.90). CONCLUSION: Among 7512 critically ill cancer patients included in this systematic review, neutropenia was independently associated with poor outcome despite a meaningful survival. Neutropenia was no longer significantly associated with outcome in patients treated by G-CSF, which may suggest a beneficial effect of G-CSF in neutropenic critically ill cancer patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026347 . Date of registration: Sept 18 2015.

Background concentrations and quality reference values for some potentially toxic elements in soils of São Paulo State, Brazil.

Quality reference values (QRV) for potentially toxic elements (PTE) in soils are established as a tool for prevention and monitoring of soil pollution. These values should be periodically revised in order to ensure soil safety for agricultural purposes. Brazil is market leader for several commodities; therefore, the safety of Brazilian soils is of worldwide strategic importance. The objective of this study was to determine the natural background concentrations and the QRV for As, Ba, Cd, Cr, Ni, Pb, Se, and Zn by investigating 30 representative pedotypes in the São Paulo State, one of the most important agro-industry economy at worldwide level. Multivariate statistical analysis was applied to determine the sources of PTE and their variability. The mean natural background concentrations of PTE in the soils were generally lower to those reported in literature. QRV, calculated for each element as the 75th and 90th percentiles, were lower (75th for As, Cd, Pb, and Zn), similar (75th for Ba, Cr, and Se) or above (90th for Ba, Cr, and Se and 75-90th for Ni) those previously proposed by the Brazilian environmental protection agencies. The results indicate that 75th percentile may be too restrictive. The PTE in the investigated soils appear to have comes mainly from two primary natural sources: a prevalent one of geogenic and a secondary of pedogenic origin. These results confirm the predominant natural source of selected PTE in the investigated soils, thus sustaining the possibility of using the data set to develop QRV for the State of São Paulo.

Outcomes of subsyndromal delirium in ICU: a systematic review and meta-analysis.

BACKGROUND: Subsyndromal delirium (SSD) is a frequent condition and has been commonly described as an intermediate stage between delirium and normal cognition. However, the true frequency of SSD and its impact on clinically relevant outcomes in the intensive care unit (ICU) remains unclear. METHODS: We performed a systematic search in PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 October 2016 to identify publications that evaluated SSD in ICU patients. RESULTS: The six eligible studies were evaluated. SSD was present in 950 (36%) patients. Four studies evaluated only surgical patients. Four studies used the Intensive Care Delirium Screening Checklist (ICDSC) and two used the Confusion Assessment Method (CAM) score to diagnose SSD. The meta-analysis showed an increased hospital length of stay (LOS) in SSD patients (0.31, 0.12-0.51, p = 0.002; I 2 = 34%). Hospital mortality was described in two studies but it was not significant (hazard ratio 0.97, 0.61-1.55, p = 0.90 and 5% vs 9%, p = 0.05). The use of antipsychotics in SSD patients to prevent delirium was evaluated in two studies but it did not modify ICU LOS (6.5 (4-8) vs 7 (4-9) days, p = 0.66 and 2 (2-3) vs 3 (2-3) days, p = 0.517) or mortality (9 (26.5%) vs 7 (20.6%), p = 0.55). CONCLUSIONS: SSD occurs in one-third of the ICU patients and has limited impact on the outcomes. The current literature concerning SSD is composed of small-sample studies with methodological differences, impairing a clear conclusion about the association between SSD and progression to delirium or worse ICU clinical outcomes.

Acute kidney injury in hematological patients.

PURPOSE OF REVIEW: The present article reviews the recent literature on the main aspects of acute kidney injury (AKI) developing in patients with hematological malignancies admitted to ICU. RECENT FINDINGS: Up to two thirds of critically ill patients with hematological malignancies develop AKI. Current mortality rates range from 40 to 60% for most patients with hematological malignancies, except for recipients of allogeneic hematopoietic stem cell transplantation in whom outcomes remain very poor. Renal function recovery occurs in most patients with AKI, but is dependent on the underlying causes. AKI is usually multifactorial, resulting from causes common to other ICU patients and related to the underlying malignancy or its treatment. New targeted therapies and treatment strategies are potentially associated with AKI. Management of these patients requires a high degree of suspicion, close monitoring of metabolic parameters, and use of preventive strategies to limit risk of AKI or to mitigate its severity. SUMMARY: AKI is a frequent and severe complication in critically ill patients with hematological malignancies. As the clinical management is complex, close collaboration with hematologists is paramount.

Determinants of procedural pain intensity in the intensive care unit. The Europain® study.

RATIONALE: Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. OBJECTIVES: To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. METHODS: Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. MEASUREMENTS AND MAIN RESULTS: Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. CONCLUSIONS: Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

ICU severity of illness scores: APACHE, SAPS and MPM.

PURPOSE OF REVIEW: This review aims to evaluate the latest versions of the Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score and Mortality Probability Model scores, make comparisons and describe their strengths and limitations. Additionally, we provide critical analysis and recommendations for the use of these scoring systems in different scenarios. RECENT FINDINGS: The last generation of ICU scoring systems (Acute Physiology and Chronic Health Evaluation IV, Mortality Probability Model 0-III (MPM0-III) and Simplified Acute Physiology Score 3) was widely validated in different regions of the world and in distinct settings comprising general ICU patients as well as specific subgroups such as critically ill cancer patients, cardiovascular, surgical, acute kidney injury requiring renal replacement therapy and those in need of extra-corporeal membrane oxygen. Conflicting results are reported, and in general the scores presented a good discrimination despite a worse calibration as compared with the ones described in the original studies that generated them. Nonetheless, such calibration is often improved when customizations are performed both at ICU and region or country level. SUMMARY: ICU scoring systems provide a valuable framework to characterize patients' severity of illness for the evaluation of ICU performance, for quality improvement initiatives and for benchmarking purposes. However, to ensure the best accuracy, constant updates as well as regional customizations are required.

Inflammation biomarkers and delirium in critically ill patients.

INTRODUCTION: Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality. Septic patients with delirium may differ from a general critically ill population. The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and non-septic critically ill patients. METHODS: We performed a prospective cohort study in a 20-bed mixed intensive care unit (ICU) including 78 (delirium = 31; non-delirium = 47) consecutive patients admitted for more than 24 hours. At enrollment, patients were allocated to septic or non-septic groups according to internationally agreed criteria. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) during the first 72 hours of ICU admission. Blood samples were collected within 12 hours of enrollment for determination of tumor necrosis factor (TNF)-α, soluble TNF Receptor (STNFR)-1 and -2, interleukin (IL)-1ß, IL-6, IL-10 and adiponectin. RESULTS: Out of all analyzed biomarkers, only STNFR1 (P = 0.003), STNFR2 (P = 0.005), adiponectin (P = 0.005) and IL-1ß (P < 0.001) levels were higher in delirium patients. Adjusting for sepsis and sedation, these biomarkers were also independently associated with delirium occurrence. However, none of them were significant influenced by sepsis. CONCLUSIONS: STNFR1, STNFR2, adiponectin and IL-1ß were associated with delirium. Sepsis did not modify the relationship between the biomarkers and delirium occurrence.

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study.

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.

The Geriatric Patient: Frailty, Prehabilitation, and Postoperative Delirium.

Historically and for ease of classification, the geriatric patient has received a chronologic definition of a person 65 years and older. Chronologic age remains an independent risk of postoperative complications and adverse surgical outcomes. Frailty is an expression of an individual's biological age and as such a more reliable determination of their vulnerabilities or resilience to stress. The concept of prehabilitation has shown promise as a proactive approach to optimize a patient's functional, cognitive, nutritional, and emotional in preparation for surgical interventions. Postoperative delirium is the most common neuropsychological complication after surgery.