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Postoperative delirium (POD) contributes to severe outcomes such as death or development of dementia. Thus, it is desirable to identify vulnerable patients in advance during the perioperative phase. Previous studies mainly investigated risk factors for delirium during hospitalization and further used a linear logistic regression (LR) approach with time-invariant data. Studies have not investigated patients' fluctuating conditions to support POD precautions. In this single-center study, we aimed to predict POD in a recovery room setting with a non-linear machine learning (ML) technique using pre-, intra-, and postoperative data. The target variable POD was defined with the Nursing Screening Delirium Scale (Nu-DESC) ≥ 1. Feature selection was conducted based on robust univariate test statistics and L1 regularization. Non-linear multi-layer perceptron (MLP) as well as tree-based models were trained and evaluated-with the receiver operating characteristics curve (AUROC), the area under precision recall curve (AUPRC), and additional metrics-against LR and published models on bootstrapped testing data. The prevalence of POD was 8.2% in a sample of 73,181 surgeries performed between 2017 and 2020. Significant univariate impact factors were the preoperative ASA status (American Society of Anesthesiologists physical status classification system), the intraoperative amount of given remifentanil, and the postoperative Aldrete score. The best model used pre-, intra-, and postoperative data. The non-linear boosted trees model achieved a mean AUROC of 0.854 and a mean AUPRC of 0.418 outperforming linear LR, well as best applied and retrained baseline models. Overall, non-linear machine learning models using data from multiple perioperative time phases were superior to traditional ones in predicting POD in the recovery room. Class imbalance was seen as a main impediment for model application in clinical practice.
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BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients. METHODS: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient's maximum NRBC value during ICU stay was calculated and further specified according to Youden's method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed. RESULTS: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95-7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7-43.3] vs. 21 days [95% CI 18.2-23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2-8.5). CONCLUSIONS: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.
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The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital-Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 - 128], 133 days in the HighC group [95% CI: 124 - 141] and 144 days in the NoC group [95% CI: 121 - 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Enfermedad Crítica , Glucocorticoides , Mortalidad Hospitalaria , Humanos , Enfermedad Crítica/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , COVID-19/mortalidad , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , SARS-CoV-2/aislamiento & purificación , Anciano de 80 o más AñosRESUMEN
ABSTRACT: Background: Hemolysis is a frequent complication in patients with sepsis, ARDS, or extracorporeal membrane oxygenation (ECMO). Haptoglobin (Hp) can scavenge released cell-free hemoglobin (CFH). Hemolysis and low plasma concentrations of Hp may be independently associated with mortality in critically ill patients. Methods: This study used a retrospective analysis of 435 patients with ARDS and veno-venous ECMO therapy, admitted to a tertiary ARDS referral center (01/2007-12/2018). Hp depletion was defined as decrease in plasma Hp concentration <0.39 g/L within the first week after ECMO initiation. Patients with Hp depletion were compared to patients without Hp depletion. The primary endpoint was 28-day mortality. Secondary endpoints included organ dysfunction-free, renal replacement therapy-free, vasopressor-free, and ECMO-free composites. Results: Patients with Hp depletion (n = 269) had a significantly higher mortality 28 days after ECMO initiation compared to patients without Hp depletion (43.5% [95% CI 37.52-49.66] vs. 25.3% [19.03-32.74], P < 0.001). Furthermore, patients with Hp depletion had fewer organ dysfunction-free days (subdistribution hazard ratio [SHR] 0.35 [95% CI 0.25-0.50], P < 0.001), lower chances for successful weaning from renal replacement therapy (SHR 0.50 [0.32-0.79], P < 0.001), vasopressor therapy (SHR 0.39 [0.28-0.54], P < 0.001), and ECMO therapy (SHR 0.41 [0.30-0.57], P < 0.001) within 28 days after ECMO initiation. Patients with initial Hp <0.66 g/L had higher risks for Hp depletion than patients with initial Hp ≥0.66 g/L. Conclusion: Patients with Hp depletion within the first week of ECMO therapy might benefit from close monitoring of hemolysis with early detection and elimination of the underlying cause. They might be potential candidates for future Hp supplementation therapy to prevent overload of the CFH-scavenger system.
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Oxigenación por Membrana Extracorpórea , Haptoglobinas , Síndrome de Dificultad Respiratoria , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/mortalidad , Estudios Retrospectivos , Adulto , AncianoRESUMEN
COVID-19 is associated with various neurological symptoms. Serum neurofilament light chain (sNfL) is a robust marker for neuroaxonal injury. Recent studies have shown that elevated levels of sNfL are associated with unfavorable outcome in COVID-19 patients. However, neuroaxonal injury is rare in COVID-19, and renal dysfunction and hypoxia, both of which are known in severe COVID-19, can also increase sNfL levels. Thus, the meaning and mechanisms of sNfL elevation in COVID-19 patients remain unclear. We evaluated sNfL levels in 48 patients with COVID-19 (mean age = 63 years) and correlated them to clinical outcome, the form of oxygen therapy, and creatinine. Levels of sNfL were age adjusted and compared with normal values and z-scores. COVID-19 patients treated with nasal cannula had normal sNfL levels (mean sNfL = 19.6 pg/ml) as well as patients with high-flow treatment (mean sNfL = 40.8 pg/ml). Serum NfL levels were statistically significantly higher in COVID-19 patients treated with mechanical ventilation on intensive care unit (ICU) (mean sNfL = 195.7 pg/ml, p < 0.01). There was a strong correlation between sNfL elevation and unfavorable outcome in COVID-19 patients (p < 0.01). However, serum creatinine levels correlated directly and similarly with sNfL elevation and with unfavorable outcome in COVID-19 patients (p < 0.01). Additionally, multivariate analysis for serum creatinine and sNfL showed that both variables are jointly associated with clinical outcomes. Our results identify renal dysfunction as an important possible confounder for sNfL elevation in COVID-19. Thus, serum creatinine and renal dysfunction should be strongly considered in studies evaluating sNfL as a biomarker in COVID-19.
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COVID-19 , Enfermedades Renales , Esclerosis Múltiple , Humanos , Persona de Mediana Edad , Creatinina , Filamentos Intermedios , Biomarcadores , Riñón/fisiologíaRESUMEN
BACKGROUND: Corona Virus Disease 2019 (COVID-19) patients display risk factors for intensive care unit acquired weakness (ICUAW). The pandemic increased existing barriers to mobilisation. This study aimed to compare mobilisation practices in COVID-19 and non-COVID-19 patients. METHODS: This retrospective cohort study was conducted at Charité-Universitätsmedizin Berlin, Germany, including adult patients admitted to one of 16 ICUs between March 2018, and November 2021. The effect of COVID-19 on mobilisation level and frequency, early mobilisation (EM) and time to active sitting position (ASP) was analysed. Subgroup analysis on COVID-19 patients and the ICU type influencing mobilisation practices was performed. Mobilisation entries were converted into the ICU mobility scale (IMS) using supervised machine learning. The groups were matched using 1:1 propensity score matching. RESULTS: A total of 12,462 patients were included, receiving 59,415 mobilisations. After matching 611 COVID-19 and non-COVID-19 patients were analysed. They displayed no significant difference in mobilisation frequency (0.4 vs. 0.3, p = 0.7), maximum IMS (3 vs. 3; p = 0.17), EM (43.2% vs. 37.8%; p = 0.06) or time to ASP (HR 0.95; 95% CI: 0.82, 1.09; p = 0.44). Subgroup analysis showed that patients in surge ICUs, i.e., temporarily created ICUs for COVID-19 patients during the pandemic, more commonly received EM (53.9% vs. 39.8%; p = 0.03) and reached higher maximum IMS (4 vs. 3; p = 0.03) without difference in mobilisation frequency (0.5 vs. 0.3; p = 0.32) or time to ASP (HR 1.15; 95% CI: 0.85, 1.56; p = 0.36). CONCLUSION: COVID-19 did not hinder mobilisation. Those treated in surge ICUs were more likely to receive EM and reached higher mobilisation levels.
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COVID-19 , SARS-CoV-2 , Adulto , Humanos , Estudios Retrospectivos , Pandemias , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: Hemolysis is associated with increased mortality in patients with sepsis, ARDS, or therapy with extracorporeal membrane oxygenation (ECMO). To quantify a critical threshold of hemolysis in patients with ARDS and treatment with veno-venous ECMO, we aimed to identify cutoff values for cell-free hemoglobin (CFH) and haptoglobin (Hp) plasma concentrations associated with a significant increase in ICU mortality. METHODS: Patients with ARDS admitted to a tertiary ARDS referral center between 01/2007 and 12/2018 and treatment with veno-venous ECMO were included. Cutoff values for mean CFH (mCFH) and mean Hp (mHp) plasma concentrations dividing the cohort into groups with significantly different ICU mortalities were calculated and patient characteristics were compared. A multiple logistic regression model with stepwise backward variable selection was included. In addition, cutoff values for vulnerable relative timespans for the respective CFH and Hp concentrations were calculated. RESULTS: A quantitative cutoff value of 11 mg/dl for mCFH separated the cohort (n = 442) regarding ICU mortality (mCFH ≤ 11 mg/dl: 38%, [95%-CI: 32.22-43.93] (n = 277) vs. mCFH > 11 mg/dl: 70%, [61.99-76.47] (n = 165), p < 0.001). Analogously, a mHp cutoff value ≤ 0.39 g/l was associated with a significant increase in ICU mortality (mHp ≤ 0.39 g/l: 68.7%, [60.91-75.61] (n = 163) vs. mHp > 0.39 g/l: 38.7%, [33.01-44.72] (n = 279), p < 0.001). The independent association of ICU mortality with CFH and Hp cutoff values was confirmed by logistic regression adjusting for confounders (CFH Grouping: OR 3.77, [2.51-5.72], p < 0.001; Hp Grouping: OR 0.29, [0.19-0.43], p < 0.001). A significant increase in ICU mortality was observed when CFH plasma concentration exceeded the limit of 11 mg/dl on 13.3% of therapy days (≤ 13.3% of days with CFH > 11 mg/dl: 33%; [26.81-40.54] (n = 192) vs. > 13.3% of days with CFH > 11 mg/dl: 62%; [56.05-68.36] (n = 250), p < 0.001). Analogously, a mortality increase was detected when Hp plasma concentration remained ≤ 0.39 g/l for > 18.2% of therapy days (≤ 18.2% days with Hp ≤ 0.39 g/l: 27%; [19.80-35.14] (n = 138) vs. > 18.2% days with Hp ≤ 0.39 g/l: 60%; [54.43-65.70] (n = 304), p < 0.001). CONCLUSIONS: Moderate hemolysis with mCFH-levels as low as 11 mg/dl impacts mortality in patients with ARDS and therapy with veno-venous ECMO. Furthermore, a cumulative dose effect should be considered indicated by the relative therapy days with CFH-concentrations > 11 mg/dl. In addition, also Hp plasma concentrations need consideration when the injurious effect of elevated CFH is evaluated.
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BACKGROUND: Pleural effusions commonly occur in patients recovering from cardiac surgery; however, the impact on outcomes is not well characterized. The purpose of this study is to characterize the clinical outcomes of cardiac surgery patients with pleural effusion. METHODS: All patients undergoing cardiac surgery between 2006 and 2019 at a tertiary care university hospital were included in this observational, cross-sectional analysis using propensity matching. RESULTS: Of 11,037 patients that underwent cardiac surgery during the study period, 6461 (58.5%) had no pleural effusion (Group 0), 3322 (30.1%) had pleural effusion only (Group 1), and 1254 (11.4%) required at least one secondary drainage procedure after the index operation (Group 2). After propensity matching, the mortality of patients who underwent secondary drainage procedures was 6.1% higher than in Group 1 (p < 0.001). Intensive care unit (ICU) stay was longer for those with pleural effusions (18 [IQR 9-32] days in Group 2, 10 [IQR 6-17] days for Group 1, and 7 [IQR 4-11] days for Group 0, p < 0.001). Patients with pleural effusions had a higher incidence of hemodialysis (246 [20.0%] in Group 2, 137 [11.1%] in Group 1, 98 [7.98%] in Group 0), and a longer ventilation time in the ICU (57 [IQR 21.0-224.0] hours in Group 2, 25.0 [IQR 14.0-58.0] hours in Group 1, 16.0 [IQR 10.0-29.0] hours in Group 0). CONCLUSION: Pleural effusions, especially those that require a secondary drainage procedure during recovery, are associated with significantly worse outcomes including increased mortality, longer length of stay, and higher complication rates. These insights may be of great interest to scientists, clinicians, and industry leaders alike to foster research into innovative methods for preventing and treating pleural effusions with the aim of improving outcomes for patients recovering from cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos , Derrame Pleural , Humanos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Estudios Transversales , Periodo PosoperatorioRESUMEN
BACKGROUND: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. METHODS: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. RESULTS: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p ≤ 0.001) and early mobilisation (adjusted OR 0.83; 95% CI 0.76, 0.90; p ≤ 0.001), while a higher norepinephrine dose corresponded to a lower chance to be mobilised out-of-bed (adjusted OR 0.01; 95% CI 0.00, 0.04; p ≤ 0.001). Mobilisation with norepinephrine did not significantly affect mortality (p > 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 µg/kg/min norepinephrine for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation. CONCLUSIONS: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 µg/kg/min for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation.
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Enfermedad Crítica , Norepinefrina , Humanos , Enfermedad Crítica/terapia , Norepinefrina/farmacología , Norepinefrina/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Estudios ProspectivosRESUMEN
(1) Background: Acute respiratory distress syndrome (ARDS) is a rare complication in multiply injured patients. Due to the rarity of ARDS development after trauma, little is known about outcomes of patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. (2) Methods: This retrospective analysis included n = 1038 ARDS patients admitted to the ARDS center of Charité-Universitätsmedizin Berlin between 2007 and 2018. Patients with trauma-associated ARDS (n = 62) were compared to patients with non-trauma-associated ARDS (n = 976). In a secondary analysis, patients from the group with non-trauma-associated ARDS were 1:1 nearest neighbor matched to patients with trauma-associated ARDS. The primary outcomes were 28-day in-hospital mortality, 60-day in-hospital mortality, and overall in-hospital mortality. (3) Results: Overall in-hospital mortality in trauma-associated ARDS was 29.0% compared to 40.5% in all patients with non-trauma-associated ARDS (p = 0.074). The in-hospital mortality rate in matched patients with non-trauma-associated ARDS (33.9%) was comparable to the trauma-associated ARDS cohort (p = 0.701). Kaplan-Meier curves indicated time-sensitive variations in 28-day and 60-day in-hospital survival. (4) Conclusion: Mortality was not different in patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. Survival rate in the Kaplan-Meier curves stabilized after the critical initial phase and throughout the further 60-day period in patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. Since this divergence was less pronounced in the matched cohort, it may be related to the younger age, fewer comorbidities, and lower ARDS severity in patients with trauma-associated ARDS. Patients with trauma-associated ARDS remain a very different cohort compared to patients with non-trauma-associated ARDS. Therefore, the outcome comparison is limited, even after matching.
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BACKGROUND: Anticoagulation therapy with heparin is a frequent treatment in intensive care units and is monitored by activated partial thromboplastin clotting time (aPTT). It has been demonstrated that reaching an established anticoagulation target within 24 hours is associated with favorable outcomes. However, patients respond to heparin differently and reaching the anticoagulation target can be challenging. Machine learning algorithms may potentially support clinicians with improved dosing recommendations. OBJECTIVE: This study evaluates a range of machine learning algorithms on their capability of predicting the patients' response to heparin treatment. In this analysis, we apply, for the first time, a model that considers time series. METHODS: We extracted patient demographics, laboratory values, dialysis and extracorporeal membrane oxygenation treatments, and scores from the hospital information system. We predicted the numerical values of aPTT laboratory values 24 hours after continuous heparin infusion and evaluated 7 different machine learning models. The best-performing model was compared to recently published models on a classification task. We considered all data before and within the first 12 hours of continuous heparin infusion as features and predicted the aPTT value after 24 hours. RESULTS: The distribution of aPTT in our cohort of 5926 hospital admissions was highly skewed. Most patients showed aPTT values below 75 s, while some outliers showed much higher aPTT values. A recurrent neural network that consumes a time series of features showed the highest performance on the test set. CONCLUSIONS: A recurrent neural network that uses time series of features instead of only static and aggregated features showed the highest performance in predicting aPTT after heparin treatment.
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Memory consolidation is a continuous transformative process between encoding and retrieval of mental representations. Recent research has shown that neural activity immediately after encoding is particularly associated with later successful retrieval. It is currently unclear whether post-encoding neural activity makes a distinct and causal contribution to memory consolidation. Here, we investigated the role of the post-encoding period for consolidation of spatial memory in neurologically normal human subjects. We used the GABAA-ergic anesthetic propofol to transiently manipulate neural activity during the initial stage of spatial memory consolidation without affecting encoding or retrieval. A total of 52 participants undergoing minor surgery learned to navigate to a target in a five-armed maze derived from animal experiments. Participants completed learning either immediately prior to injection of propofol (early group) or more than 60 min before injection (late group). Four hours after anesthesia, participants were tested for memory-guided navigation. Our results show a selective impairment of navigation in the early group and near-normal performance in the late group. Analysis of navigational error patterns further suggested that propofol impaired distinct aspects of spatial representations, in particular sequences of path segments and spatial relationships between landmarks. We conclude that neural activity during the post-encoding period makes a causal and specific contribution to consolidation of representations underlying self-centered and world-centered memory-guided navigation. Distinct aspects of these representations are susceptible to GABAA-ergic modulation within a post-encoding time-window of less than 60 min, presumably reflecting associative processes that contribute to the formation of integrated spatial representations that guide future behavior.
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Consolidación de la Memoria , Propofol , Humanos , Animales , Memoria Espacial , Propofol/farmacología , Ácido gamma-AminobutíricoRESUMEN
BACKGROUND: The SARS-CoV-2 virus has been spreading in Germany since January 2020, with regional differences in incidence, morbidity, and mortality. Long-term exposure to air pollutants as nitrogen dioxide (NO2), nitrogen monoxide (NO), ozone (O3), and particulate matter (<10 µm PM10, <2.5 µm PM2.5) has a negative impact on respiratory functions. We analyze the association between long-term air pollution and the outcome of SARS-CoV-2 infections in Germany. METHODS: We conducted an observational study in Germany on county-level, investigating the association between long-term (2010-2019) air pollutant exposure (European Environment Agency, AirBase data set) and COVID-19 incidence, morbidity, and mortality rate during the first outbreak of SARS-CoV-2 (open source data Robert Koch Institute). We used negative binominal models, including adjustment for risk factors (age, sex, days since first COVID-19 case, population density, socio-economic and health parameters). RESULTS: After adjustment for risk factors in the tri-pollutant model (NO2, O3, PM2.5) an increase of 1 µg/m³ NO2 was associated with an increase of the need for intensive care due to COVID-19 by 4.2% (95% CI 1.011-1.074), and mechanical ventilation by 4.6% (95% CI 1.010-1.084). A tendency towards an association of NO2 with COVID-19 incidence was indicated, as the results were just outside of the defined statistical significance (+1.6% (95% CI 1.000-1.032)). Long-term annual mean NO2 level ranged from 4.6 µg/m³ to 32 µg/m³. CONCLUSIONS: Our results indicate that long-term NO2 exposure may have increased susceptibility for COVID-19 morbidity in Germany. The results demonstrate the need to reduce ambient air pollution to improve public health.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , COVID-19/epidemiología , Exposición a Riesgos Ambientales/análisis , Alemania/epidemiología , Humanos , Incidencia , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/toxicidad , Material Particulado/análisis , Material Particulado/toxicidad , SARS-CoV-2RESUMEN
To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19-related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)-related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18-58 d) versus 16 days (IQR, 19-39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6-28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9-27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7-25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival.
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BACKGROUND: Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI) in critically ill patients while the CFH-scavenger haptoglobin might play a protective role. We evaluated the association of CFH and haptoglobin with AKI in patients with an acute respiratory distress syndrome (ARDS) requiring therapy with VV ECMO. METHODS: Patients with CFH and haptoglobin measurements before initiation of ECMO therapy were identified from a cohort of 1044 ARDS patients and grouped into three CFH concentration groups using a risk stratification. The primary objective was to assess the association of CFH and haptoglobin with KDIGO stage 3 AKI. Further objectives included the identification of a target haptoglobin concentration to protect from CFH-associated AKI. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-three patients fulfilled the inclusion criteria. Of those, 154 patients (56.4%) had AKI at ECMO initiation. The incidence of AKI increased stepwise with increasing concentrations of CFH reaching a plateau at 15 mg/dl. Compared to patients with low [< 5 mg/dl] CFH concentrations, patients with moderate [5-14 mg/dl] and high [≥ 15 mg/dl] CFH concentrations had a three- and five-fold increased risk for AKI (adjusted odds ratio [OR] moderate vs. low, 2.69 [95% CI, 1.25-5.95], P = 0.012; and OR high vs. low, 5.47 [2.00-15.9], P = 0.001). Among patients with increased CFH concentrations, haptoglobin plasma levels were lower in patients with AKI compared to patients without AKI. A haptoglobin concentration greater than 2.7 g/l in the moderate and 2.4 g/l in the high CFH group was identified as clinical cutoff value to protect from CFH-associated AKI (sensitivity 89.5% [95% CI, 83-96] and 90.2% [80-97], respectively). CONCLUSIONS: In critically ill patients with ARDS requiring therapy with VV ECMO, an increased plasma concentration of CFH was identified as independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI and should be subject of future research.
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Lesión Renal Aguda , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Lesión Renal Aguda/etiología , Adulto , Enfermedad Crítica/terapia , Haptoglobinas , Hemoglobinas , Humanos , Síndrome de Dificultad Respiratoria/terapia , Estudios RetrospectivosRESUMEN
Packed red blood cells (PRBCs), stored for prolonged intervals, might contribute to adverse clinical outcomes in critically ill patients. In this study, short-term outcome after transfusion of PRBCs of two storage duration periods was analyzed in patients with Acute Respiratory Distress Syndrome (ARDS). Patients who received transfusions of PRBCs were identified from a cohort of 1044 ARDS patients. Patients were grouped according to the mean storage age of all transfused units. Patients transfused with PRBCs of a mean storage age ≤ 28 days were compared to patients transfused with PRBCs of a mean storage age > 28 days. The primary endpoint was 28-day mortality. Secondary endpoints included failure-free days composites. Two hundred and eighty-three patients were eligible for analysis. Patients in the short-term storage group had similar baseline characteristics and received a similar amount of PRBC units compared with patients in the long-term storage group (five units (IQR, 3-10) vs. four units (2-8), p = 0.14). The mean storage age in the short-term storage group was 20 (±5.4) days compared with 32 (±3.1) days in the long-term storage group (mean difference 12 days (95%-CI, 11-13)). There was no difference in 28-day mortality between the short-term storage group compared with the long-term storage group (hazard ratio, 1.36 (95%-CI, 0.84-2.21), p = 0.21). While there were no differences in ventilator-free, sedation-free, and vasopressor-free days composites, patients in the long-term storage group compared with patients in the short-term storage group had a 75% lower chance for successful weaning from renal replacement therapy (RRT) within 28 days after ARDS onset (subdistribution hazard ratio, 0.24 (95%-CI, 0.1-0.55), p < 0.001). Further analysis indicated that even a single PRBC unit stored for more than 28 days decreased the chance for successful weaning from RRT. Prolonged storage of PRBCs was not associated with a higher mortality in adults with ARDS. However, transfusion of long-term stored PRBCs was associated with prolonged dependence of RRT in critically ill patients with an ARDS.
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BACKGROUND: Etomidate is typically used as an induction agent in cardiac surgery because it has little impact on hemodynamics. It is a known suppressor of adrenocortical function and may increase the risk for post-operative infections, sepsis, and mortality. The aim of this study was to evaluate whether etomidate increases the risk of postoperative sepsis (primary outcome) and infections (secondary outcome) compared to propofol. METHODS: This was a retrospective before-after trial (IRB EA1/143/20) performed at a tertiary medical center in Berlin, Germany, between 10/2012 and 01/2015. Patients undergoing cardiac surgery were investigated within two observation intervals, during which etomidate and propofol were the sole induction agents. RESULTS: One-thousand, four-hundred, and sixty-two patients, and 622 matched pairs, after caliper propensity-score matching, were included in the final analysis. Sepsis rates did not differ in the matched cohort (etomidate: 11.5% vs. propofol: 8.2%, p = 0.052). Patients in the etomidate interval were more likely to develop hospital-acquired pneumonia (etomidate: 18.6% vs. propofol: 14.0%, p = 0.031). CONCLUSION: Our study showed that a single-dose of etomidate is not statistically associated with higher postoperative sepsis rates after cardiac surgery, but is associated with a higher incidence of hospital-acquired pneumonia. However, there is a notable trend towards a higher sepsis rate.
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BACKGROUND: In cases of hypertrophic obstructive cardiomyopathy (HOCM), the systolic anterior motion of the mitral valve apparatus results in an obstruction of the left ventricular outflow tract (LVOT), which is known as the SAM [systolic anterior motion] phenomenon. Hypothetically, a pathological obstruction of the LVOT of a different etiology would result in a comparable hemodynamic instability, which would be refractory to inotrope therapy, and may be detectable through echocardiography. CASE PRESENTATION: We observed a severely impaired left ventricular function due to a combination of a thrombotic LVOT obstruction and distinctive mitral regurgitation in a 56-year-old Caucasian, female patient after massive transfusion with aggressive procoagulant therapy. Initially, the patient had to be resuscitated due to cardiac arrest after a long-distance flight. The resuscitation attempts in combination with lysis therapy due to suspected pulmonary artery embolism were initially successful but resulted in traumatic liver injury, hemorrhagic shock and subsequent acute respiratory distress syndrome (ARDS). Oxygenation was stabilized with veno-venous extracorporeal membrane oxygenation (ECMO), but the hemodynamic situation deteriorated further. Transesophageal echocardiography (TEE) showed a massive, dynamic LVOT obstruction. Two thrombi were attached to the anterior leaflet of the mitral valve, resulting in a predominantly systolic obstruction. Unfortunately, the patient died of multiple-organ failure despite another round of lysis therapy and escalation of the ECMO circuit to a veno-venoarterial cannulation for hemodynamic support. CONCLUSION: Massive transfusion with aggressive procoagulant therapy resulted in mitral valve leaflet thrombosis with dynamic, predominantly systolic LVOT obstruction, comparable to the SAM phenomenon. The pathology was only detectable with a TEE investigation.
Asunto(s)
Cardiomiopatía Hipertrófica , Insuficiencia de la Válvula Mitral , Choque Hemorrágico , Obstrucción del Flujo Ventricular Externo , Femenino , Humanos , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Choque Hemorrágico/etiología , Choque Hemorrágico/terapia , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/etiología , Obstrucción del Flujo Ventricular Externo/terapiaRESUMEN
The Acute Respiratory Distress Syndrome (ARDS) is common in patients on the Intensive Care Unit and associated with significant mortality rates. In situations of severe respiratory insufficiency and failure of all possible conservative therapeutic approaches, veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a final option for temporary replacement of pulmonary function. ARDS as well as sepsis and VV ECMO treatment are all associated with intravascular hemolysis. The extent and relevance of intravascular hemolysis in the context of ARDS therapy is unclear. This systematic review aims to summarize the current evidence on the incidence and associated complications of intravascular hemolysis in adult patients with ARDS and treatment with VV ECMO. The databases MEDLINE, EMBASE and Web of Science were systematically searched and 19 publications fulfilled inclusion criteria. The incidence of hemolysis in patients with ARDS and treatment with VV ECMO ranged from 0 to 41% with survivors showing lower incidences and less severe hemolysis. A pump head thrombosis and high blood flows (≥3 l/min) as well as use of dual-lumen cannulas but not different pump models were associated with increased hemolysis. In conclusion, intravascular hemolysis in patients with ARDS and treatment with VV ECMO is a common and relevant complication that appears associated with increased mortality. Apart from ECMO hardware-settings, no additional possible causes for increased red cell breakdown such as disease severity, duration of ECMO therapy, or number and quality of red blood cell transfusions were investigated. Further research is needed to determine the origin and relevance of intravascular hemolysis in patients with ARDS and treatment with VV ECMO.