Extreme obesity and outcomes in critically ill patients.
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ABSTRACT: Recent literature suggests that obese critically ill patients do not have worse outcomes than patients who are normal weight. However, outcomes in extreme obesity (BMI ≥ 40 kg/m(2)) are unclear. We sought to determine the association between extreme obesity and ICU outcomes.We analyzed data from a multicenter international observational study of ICU nutrition practices that occurred in 355 ICUs in 33 countries from 2007 to 2009. Included patients were mechanically ventilated adults ≥ 18 years old who remained in the ICU for > 72 h. Using generalized estimating equations and Cox proportional hazard modeling with clustering by ICU and adjusting for potential confounders, we compared extremely obese to normal-weight patients in terms of duration of mechanical ventilation (DMV), ICU length of stay (LOS), hospital LOS, and 60-day mortality.Of the 8,813 patients included in this analysis, 3,490 were normal weight (BMI 18.5-24.9 kg/m(2)), 348 had BMI 40 to 49.9 kg/m(2), 118 had BMI 50 to 59.9 kg/m(2), and 58 had BMI ≥ 60 kg/m(2). Unadjusted analyses suggested that extremely obese critically ill patients have improved mortality (OR for death, 0.77; 95% CI, 0.62-0.94), but this association was not significant after adjustment for confounders. However, an adjusted analysis of survivors found that extremely obese patients have a longer DMV and ICU LOS, with the most obese patients (BMI ≥ 60 kg/m(2)) also having longer hospital LOS.During critical illness, extreme obesity is not associated with a worse survival advantage compared with normal weight. However, among survivors, BMI ≥ 40 kg/m(2) is associated with longer time on mechanical ventilation and in the ICU. These results may have prognostic implications for extremely obese critically ill patients.
Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Project description:BackgroundA high body mass index (BMI) has been associated with decreased mortality in critically ill patients. This association may, in part, relate to the impact of BMI on glycemia. We aimed to study the relationship between BMI, glycemia and hospital mortality.MethodsWe included all patients with a recorded BMI from four large international clinical databases (n = 259,177). We investigated the unadjusted association of BMI with average glucose levels, mortality and hypoglycemia rate. We applied multivariate analysis to investigate the impact of BMI on hypoglycemia rate, after adjusting for glycemia-relevant treatments (insulin, dextrose, corticosteroids, enteral and parenteral nutrition) and key physiological parameters (previous blood glucose level, blood lactate, shock state, SOFA score).ResultsWe analyzed 5,544,366 glucose measurements. On unadjusted analysis, increasing BMI was associated with increasing glucose levels (average increase of 5 and 10 mg/dL for the 25-30, 30-35 kg/m2 BMI groups compared to normal BMI (18.5-25 kg/m2) patients). Despite greater hyperglycemia, increasing BMI was associated with lower hospital mortality (average decrease of 2% and 3.25% for the 25-30, 30-35 kg/m2 groups compared to normal BMI patients) and lower hypoglycemia rate (average decrease of 2.5% and 3.5% for the 25-30, 30-35 kg/m2 groups compared to normal BMI patients). Increasing BMI was significantly independently associated with reduced hypoglycemia rate, with odds ratio (OR) 0.72 and 0.65, respectively (95% CIs 0.67-0.77 and 0.60-0.71, both p < 0.001) when compared with normal BMI. Low BMI patients showed greater hypoglycemia rate, with OR 1.6 (CI 1.43-1.79, p < 0.001). The association of high BMI and decreased mortality did not apply to diabetic patients. Although diabetic patients had higher rates of hypoglycemia overall and higher glucose variability (p < 0.001), they also had a reduced risk of hypoglycemia with higher BMI levels (p < 0.001).ConclusionsIncreasing BMI is independently associated with decreased risk of hypoglycemia. It is also associated with increasing hyperglycemia and yet with lower mortality. Lower risk of hypoglycemia might contribute to decreased mortality and might partly explain the obesity paradox. These associations, however, were markedly modified by the presence of diabetes.
Project description:Some prior studies have shown that elevated mean central venous pressure in certain patient populations and disease processes may lead to poor prognosis. However, these studies failed to generalize the concept of elevated central venous pressure (ECVP) load to all patients in critical care settings because of the limited cases and exclusive cohorts. The aim of the study was to investigate the association between elevated central venous pressure and outcomes in critical care.We performed a retrospective analysis on a single-center public database (MIMIC) of more than 9000 patients and more than 500,000 records of central venous pressure measurement. We evaluated the association between mean central venous pressure level and 28-day mortality after intensive care unit admission. The secondary outcomes were duration of mechanical ventilation, vasoactive drug use, laboratory results related to organ dysfunction and length of intensive care unit hospitalization. Accordingly, we proposed the concept of ECVP10 (the time sum of CVP above 10 mmHg) and investigated its association with outcome.There were 1645 deaths at 28 days after admission. Compared with the lowest quartile of mean central venous pressure [mean (SD) 7.4 (1.9) mmHg], the highest quartile [17.4 (4.1) mmHg] was associated with a 33.6% (95% CI 1.117-1.599) higher adjusted risk of death. Poor secondary outcomes were also associated with higher quartiles of elevated mean central venous pressure. After stratification by mean central venous pressure, elevated duration of central venous pressure above 10 mmHg was significantly higher in the non-survival group than in the survival group.Elevated central venous pressure level correlated with poor outcomes and prolonged treatment in critical care settings. Level and duration of elevated central venous pressure should be both evaluated to establish its cause and apply appropriate treatment.
Project description:Objective: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill ICU patients positive for COVID19 vs. those negative for COVID19 to better understand the COVID19 associated host response. Design: Transcriptome profiling of buffy coat cells via ribonucleic acid sequencing (RNAseq) at the time of admission to the ICU. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Interventions: None. Measurement and Main Results: Age- and sex-matched ICU patients that were either COVID19+ (PCR positive, 2 genes) or COVID19- (PCR negative) were enrolled. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia compared to COVID19- patients. Further, the mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signaling, and protein SUMOylation/ubiquitination. Conclusions: COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients. Identification of this profile provides guidance for future targeted studies exploring novel prognostic/therapeutic aspects of COVID19.
Project description:IntroductionCancer 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 methodsSecondary analysis of two prospective cohorts of cancer patients admitted to ICUs. We used multivariable logistic regression to identify variables associated with hospital mortality.ResultsOut 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.ConclusionsThe 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.
Project description:Rationale: Recent studies have revealed that, in critically ill patients, lung microbiota are altered and correlate with alveolar inflammation. The clinical significance of altered lung bacteria in critical illness is unknown.Objectives: To determine if clinical outcomes of critically ill patients are predicted by features of the lung microbiome at the time of admission.Methods: We performed a prospective, observational cohort study in an ICU at a university hospital. Lung microbiota were quantified and characterized using droplet digital PCR and bacterial 16S ribosomal RNA gene quantification and sequencing. Primary predictors were the bacterial burden, community diversity, and community composition of lung microbiota. The primary outcome was ventilator-free days, determined at 28 days after admission.Measurements and Main Results: Lungs of 91 critically ill patients were sampled using miniature BAL within 24 hours of ICU admission. Patients with increased lung bacterial burden had fewer ventilator-free days (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88), which remained significant when the analysis was controlled for pneumonia and severity of illness. The community composition of lung bacteria predicted ventilator-free days (P = 0.003), driven by the presence of gut-associated bacteria (e.g., species of the Lachnospiraceae and Enterobacteriaceae families). Detection of gut-associated bacteria was also associated with the presence of acute respiratory distress syndrome.Conclusions: Key features of the lung microbiome (bacterial burden and enrichment with gut-associated bacteria) predict outcomes in critically ill patients. The lung microbiome is an understudied source of clinical variation in critical illness and represents a novel therapeutic target for the prevention and treatment of acute respiratory failure.
Project description:BackgroundCritically ill patients with obesity (PwO) have anthropometric characteristics that can be associated with different nutritional-metabolic requirements than other critically ill patients. However, recommendations regarding nutrition delivery in PwO are not clearly established among the different published clinical practice guidelines (CPGs). Our main aim was to evaluate the impact of energy and protein intake in critically ill PwO.MethodsA multicenter (n = 37) prospective observational study was performed. Adult patients requiring medical nutrition therapy (MNT) were included, and PwO (BMI ≥ 30 Kg·m-2) were analyzed. Demographic data, comorbidities, nutritional status, and the average caloric and protein delivery administered in the first 14 days, including complications and outcomes, were recorded in a database. Patients were classified and analyzed based on the adequacy of energy and protein intake according to CPG recommendations.Results525 patients were included, of whom 150 (28.6%) had obesity. The energy delivery was considered inadequate (<11 Kcal/Kg/d) in 30.7% (n = 46) and adequate (≥11 Kcal/Kg/d) in 69.3% (n = 104) of cases. PwO who received adequate energy delivery had greater use of the parenteral route and longer mean hospital stays (28.6 ± 26.1 vs. 39.3 ± 28.1; p = 0.01) but lower ICU mortality (32.6% vs. 16.5%; p = 0.02). Protein delivery was inadequate (<0.8 g/Kg/d) in 63.3% (n = 95), insufficient (0.8-1.2 g/Kg/d) in 31.33% (n = 47), and adequate (≥1.2 g/Kg/d) in only 5.4% (n = 8) of patients. PwO with inadequate protein delivery-compared with insufficient delivery-had higher use of the parenteral route and lower mortality in the ICU (25.5% vs. 14.9%; p = 0.02). Multivariate analysis revealed that PwO who received adequate energy delivery (hazard ratio [HR]: 0.398; 95% confidence interval [CI]: 0.180-0.882; p = 0.023) had better survival, while patients with insufficient protein delivery (HR: 0.404; CI 95%: 0.171-0.955; p = 0.038) had better survival than those with inadequate delivery.ConclusionPwO can frequently receive inadequate energy and protein delivery from MNT during an ICU stay, which may impact the short-term mortality of these critically ill patients. It is emerging to develop strategies to optimize MNT delivery in these patients, which may improve their outcomes. NCT Registry: 03634943.
Project description:The relationship between body mass index and pressure ulcers in critically ill patients is controversial. We aimed to investigate the association between body mass index and pressure ulcers by analysing data from the Medical Information Mart for Intensive Care IV (version 2.0) database. Eligible data (21 835 cases) were extracted from the database (2008-2019). The association between body mass index and pressure ulcers in critically ill patients was investigated by adjusting multivariate trend analysis, restricted cubic spline analysis, and segmented linear models. Subgroup analyses and sensitivity analyses were used to ensure the stability of the results. Trend analysis and restricted cubic spline analysis showed an approximate U-shaped correlation between body mass index and the occurrence of pressure ulcers in critically ill patients, with the risk of pressure ulcers decreasing rapidly with increasing body mass index (8.6% decrease per unit) after adjusting for relevant factors; the trend reached its minimum at a body mass index of 27.5 kg/m2, followed by a slow increase in the risk of pressure ulcers with increasing body mass index (1.4% increase per unit). Among the subgroups, the highest overall risk of pressure ulcers and the risk of severe pressure ulcers were significantly higher in the underweight group than in the other subgroups, and the risk associated with the overweight group was the lowest. There is a U-shaped association between body mass index and pressure ulcers in critically ill patients, and being underweight and obese both increase the risk of pressure ulcers. The risk is highest among underweight patients and lowest among overweight patients (but not patients of normal weight), necessitating targeted prevention strategies for critically ill patients with different body mass indexes.
Project description:Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients. Even patients who are normoglycemic can develop hyperglycemia in response to acute metabolic stress. An expanding body of literature describes the benefits of normalizing hyperglycemia with insulin therapy in hospitalized patients. As a result, both the American Diabetes Association and the American College of Endocrinology have developed guidelines for optimal control of hyperglycemia, specifically targeting critically ill, hospitalized patients. Conventional blood glucose values of 140-180 mg/dL are considered desirable and safely achievable in most patients. More aggressive control to <110 mg/dL remains controversial, but has shown benefits in certain patients, such as those in surgical intensive care. Intravenous infusion is often used for initial insulin administration, which can then be transitioned to subcutaneous insulin therapy in those patients who require continued insulin maintenance. This article reviews the data establishing the link between hyperglycemia and its risks of morbidity and mortality, and describes strategies that have proven effective in maintaining glycemic control in high-risk hospitalized patients.