Search

Introduction: Fluid accumulation is associated with adverse outcomes in critically ill patients admitted to the intensive care unit (ICU). Fluid administration in the ICU may be a clinically relevant source of fluid accumulation in ICU patients. However, the extent is unknown, and no standard definition exists. We aim to provide epidemiological data on fluid accumulation, risk factors, use of fluid removal strategies, patient outcomes and describe current fluid administration practices in the ICU. Methods: We will conduct an international 14‐day inception cohort study including a minimum of 1000 acutely admitted adult ICU patients. Data will be collected from medical records and laboratory reports at baseline and daily from ICU admission to discharge with a maximum of 28 days. Follow‐up will be performed on day 90 after inclusion. The primary outcome is the number of patients with fluid accumulation. Secondary outcomes include the number of days with fluid accumulation, use of active fluid removal, days alive without life support at day 28, days alive and out of hospital day 90, and all‐cause mortality at day 90. Furthermore, we will assess risk factors for fluid accumulation and its association with 90‐day mortality and report on the types of fluid administration. Conclusion: This international inception cohort study will provide contemporary epidemiological data on fluid administration and fluid accumulation in adult ICU patients. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9‐bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. Methods: In this registry‐based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre‐cohort, with admissions prior to the change of transfusion strategy, and a post‐cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion‐related variables. Results: In total 5626 admissions were included in the analyses (pre‐cohort n = 4373, post‐cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre‐cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post‐cohort (p <.001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre‐cohort and 19% in the post‐cohort (p <.001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre‐ versus post‐cohort (90 [80–100] vs. 80 [72–90] g/L, p <.001 and 89 [82–96] g/L vs. 83 [79–94], p <.001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre‐cohort than in the post‐cohort (23% vs. 14%, p <.001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID‐19 demonstrated similar results. Conclusions: Implementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Reinforcement learning (RL) is a machine learning technique uniquely effective at sequential decision-making, which makes it potentially relevant to ICU treatment challenges. We set out to systematically review, assess level-of-readiness and meta-analyze the effect of RL on outcomes for critically ill patients. DATA SOURCES: A systematic search was performed in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection, Elsevier/SCOPUS and the Institute of Electrical and Electronics Engineers Xplore Digital Library from inception to March 25, 2022, with subsequent citation tracking. DATA EXTRACTION: Journal articles that used an RL technique in an ICU population and reported on patient health-related outcomes were included for full analysis. Conference papers were included for level-of-readiness assessment only. Descriptive statistics, characteristics of the models, outcome compared with clinician's policy and level-of-readiness were collected. RL-health risk of bias and applicability assessment was performed. DATA SYNTHESIS: A total of 1,033 articles were screened, of which 18 journal articles and 18 conference papers, were included. Thirty of those were prototyping or modeling articles and six were validation articles. All articles reported RL algorithms to outperform clinical decision-making by ICU professionals, but only in retrospective data. The modeling techniques for the state-space, action-space, reward function, RL model training, and evaluation varied widely. The risk of bias was high in all articles, mainly due to the evaluation procedure. CONCLUSION: In this first systematic review on the application of RL in intensive care medicine we found no studies that demonstrated improved patient outcomes from RL-based technologies. All studies reported that RL-agent policies outperformed clinician policies, but such assessments were all based on retrospective off-policy evaluation. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Malnutrition, hypercatabolism, and metabolic changes are well-established risk factors for delirium in critically ill patients. Although the exact mechanisms are not fully understood, there is mounting evidence suggesting that malnutrition can cause a variety of changes that contribute to delirium, such as electrolyte imbalances, immune dysfunction, and alterations in drug metabolism. Therefore, a comprehensive metabolic and malnutrition assessment, along with appropriate nutritional support, may help to prevent or ameliorate malnutrition, reduce hypercatabolism, and improve overall physiological function, ultimately lowering the risk of delirium. For this aim, bioelectrical impedance analysis can represent a valuable strategy. Further research into the underlying mechanisms and nutritional risk factors for delirium is crucial to developing more effective prevention strategies. Understanding these processes will allow clinicians to personalize treatment plans for individual patients, leading to improved outcomes and quality of life in the intensive-care-unit survivors. [ABSTRACT FROM AUTHOR]

Purpose: Inadequate piperacillin (PIP) exposure in intensive care unit (ICU) patients threatens therapeutic success. Model-informed precision dosing (MIPD) might be promising to individualize dosing; however, the transferability of published models to external populations is uncertain. This study aimed to externally evaluate the available PIP population pharmacokinetic (PopPK) models. Methods: A multicenter dataset of 561 ICU patients (11 centers/3654 concentrations) was used for the evaluation of 24 identified models. Model performance was investigated for a priori (A) predictions, i.e., considering dosing records and patient characteristics only, and for Bayesian forecasting, i.e., additionally including the first (B1) or first and second (B2) therapeutic drug monitoring (TDM) samples per patient. Median relative prediction error (MPE) [%] and median absolute relative prediction error (MAPE) [%] were calculated to quantify accuracy and precision. Results: The evaluation revealed a large inter-model variability (A: MPE − 135.6–78.3% and MAPE 35.7–135.6%). Integration of TDM data improved all model predictions (B1/B2 relative improvement vs. A: |MPE|median_all_models 45.1/67.5%; MAPEmedian_all_models 29/39%). The model by Kim et al. was identified to be most appropriate for the total dataset (A/B1/B2: MPE − 9.8/− 5.9/− 0.9%; MAPE 37/27.3/23.7%), Udy et al. performed best in patients receiving intermittent infusion, and Klastrup et al. best predicted patients receiving continuous infusion. Additional evaluations stratified by sex and renal replacement therapy revealed further promising models. Conclusion: The predictive performance of published PIP models in ICU patients varied considerably, highlighting the relevance of appropriate model selection for MIPD. Our differentiated external evaluation identified specific models suitable for clinical use, especially in combination with TDM. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, large numbers of elderly, multimorbid people required treatment in intensive care units. This study investigated how the inherent patient factors age and comorbidity burden affected the treatment strategy and the outcome achieved. Retrospective analysis of data from intensive care patients enrolled in the Lean European Open Survey on SARS-CoV2-Infected Patients (LEOSS) cohort found that a patient's age and comorbidity burden in fact influenced their mortality rate and the use of ventilation therapy. Evidence showed that advanced age and multimorbidity were associated with the restrictive use of invasive ventilation therapies, particularly ECMO. Geriatric patients with a high comorbidity burden were clustered in the sub-cohort of non-ventilated ICU patients characterized by a high mortality rate. The risk of death generally increased with older age and accumulating comorbidity burden. Here, the more aggressive an applied procedure, the younger the age in which a majority of patients died. Clearly, geriatric, multimorbid COVID-19 patients benefit less from invasive ventilation therapies. This implies the need for a holistic approach to therapy decisions, taking into account the patient's wishes. [ABSTRACT FROM AUTHOR]

Purpose: Central venous catheter (CVC)-related thrombosis (CRT) is a known complication in critically ill patients. However, its clinical significance remains unclear. The objective of the study was to evaluate the occurrence and evolution of CRT from CVC insertion to removal. Methods: A prospective multicenter study was conducted in 28 intensive care units (ICUs). Duplex ultrasound was performed daily from CVC insertion until at least 3 days after CVC removal or before patient discharge from the ICU to detect CRT and to follow its progression. CRT diameter and length were measured and diameter > 7 mm was considered extensive. Results: The study included 1262 patients. The incidence of CRT was 16.9% (95% confidence interval 14.8–18.9%). CRT was most commonly found in the internal jugular vein. The median time from CVC insertion to CRT onset was 4 (2–7) days, and 12% of CRTs occurred on the first day and 82% within 7 days of CVC insertion. CRT diameters > 5 mm and > 7 mm were found in 48% and 30% of thromboses. Over a 7-day follow-up, CRT diameter remained stable when the CVC was in place, whereas it gradually decreased after CVC removal. The ICU length of stay was longer in patients with CRT than in those without CRT, and the mortality was not different. Conclusion: CRT is a frequent complication. It can occur as soon as the CVC is placed and mostly during the first week following catheterization. Half of the thromboses are small but one-third are extensive. They are often non-progressive and may be resolved after CVC removal. [ABSTRACT FROM AUTHOR]

Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Influenza‐associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR‐confirmed influenza infection and treatment on intensive‐care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in‐hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. Results: One hundred fifty‐eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non‐IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1–67.2]) and days of mechanical ventilation (OR 1.1 [1.1–1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non‐IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU‐mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3–253.4]), influenza A (OR 3.3 [1.4–7.8]), and higher SAPS II score (OR 1.07 [1.05–1.10]) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA. [ABSTRACT FROM AUTHOR]

Superinfections with Aspergillus spp. in patients with Coronavirus disease 2019 (CAPA: COVID-19-associated pulmonary aspergillosis) are increasing. Dexamethasone has shown beneficial effects in critically ill COVID-19 patients. Whether dexamethasone increases the risk of CAPA has not been studied exclusively. Moreover, this retrospective study aimed to identify risk factors for a worse outcome in critically ill COVID-19 patients. Data from 231 critically ill COVID-19 patients with or without dexamethasone treatment from March 2020 and March 2021 were retrospectively analysed. Only 4/169 (6.5%) in the DEXA-group and 13/62 (7.7%) in the Non-DEXA group were diagnosed with probable CAPA (p = 0.749). Accordingly, dexamethasone was not identified as a risk factor for CAPA. Moreover, CAPA was not identified as an independent risk factor for death in multivariable analysis (p = 0.361). In contrast, elevated disease severity (as assessed by Sequential Organ Failure Assessment [SOFA]-score) and the need for organ support (kidney replacement therapy and extracorporeal membrane oxygenation [ECMO]) were significantly associated with a worse outcome. Therefore, COVID-19 treatment with dexamethasone did not increase the risk for CAPA. Moreover, adequately treated CAPA did not represent an independent risk factor for mortality. Accordingly, CAPA might reflect patients' severe disease state instead of directly influencing outcome. [ABSTRACT FROM AUTHOR]

Superinfections are a fundamental critical care problem, and their significance in severe COVID-19 cases needs to be determined. This study analyzed data from the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort focusing on intensive care patients. A retrospective analysis of patient data from 840 cases of COVID-19 with critical courses demonstrated that co-infections were frequently present and were primarily of nosocomial origin. Furthermore, our analysis showed that invasive therapy procedures accompanied an increased risk for healthcare-associated infections. Non-ventilated ICU patients were rarely affected by secondary infections. The risk of infection, however, increased even when non-invasive ventilation was used. A further, significant increase in infection rates was seen with the use of invasive ventilation and even more so with extracorporeal membrane oxygenation (ECMO) therapy. The marked differences among ICU techniques used for the treatment of COVID-19-induced respiratory failure in terms of secondary infection risk profile should be taken into account for the optimal management of critically ill COVID-19 patients, as well as for adequate antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Background: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream (BSI) and to determine the predictive value of biomarkers of inflammatory response on their ICU survival rates. Methods: A retrospective observational study that included critically ill COVID-19 patients treated during an 11-month period in a Croatian national COVID-19 hospital was performed. Clinical and diagnostic data were analyzed according to the origin of superinfection, and multivariate regression analysis was performed to determine the predictive values of biomarkers of inflammation on their survival rates. Results: 55.3% critically ill COVID-19 patients developed bacterial or fungal superinfections, and LRTI were most common, followed by BSI and UTI. Multidrug-resistant pathogens were the most common causes of LRTI and BSI, while Enterococcus faecalis was the most common pathogen causing UTI. Serum ferritin and neutrophil count were associated with decreased chances of survival in patients with LRTI, and patients with multidrug-resistant isolates had significantly higher mortality rates, coupled with longer ICU stays. Conclusion: The incidence of superinfections in critically ill COVID-19 patients was 55.3%, and multidrug-resistant pathogens were dominant. Elevated ferritin levels and neutrophilia at ICU admission were associated with increased ICU mortality in patients with positive LRTI. [ABSTRACT FROM AUTHOR]

Background: Capillary refill time (CRT) is a valuable tool for triage and to guide resuscitation. However, little is known about CRT kinetics after fluid infusion. Methods: We conducted a prospective observational study in a tertiary teaching hospital. First, we analyzed the intra-observer variability of CRT. Next, we monitored fingertip CRT in sepsis patients during volume expansion within the first 24 h of ICU admission. Fingertip CRT was measured every 2 min during 30 min following crystalloid infusion (500 mL over 15 min). Results: First, the accuracy of repetitive fingertip CRT measurements was evaluated on 40 critically ill patients. Reproducibility was excellent, with an intra-class correlation coefficient of 99.5% (CI 95% [99.3, 99.8]). A CRT variation larger than 0.2 s was considered as significant. Next, variations of CRT during volume expansion were evaluated on 29 septic patients; median SOFA score was 7 [5–9], median SAPS II was 57 [45–72], and ICU mortality rate was 24%. Twenty-three patients were responders as defined by a CRT decrease > 0.2 s at 30 min after volume expansion, and 6 were non-responders. Among responders, we observed that fingertip CRT quickly improved with a significant decrease at 6–8 min after start of crystalloid infusion, the maximal improvement being observed after 10–12 min (−0.7 [−0.3;−0.9] s) and maintained at 30 min. CRT variations significantly correlated with baseline CRT measurements (R = 0.39, P = 0.05). Conclusions: CRT quickly improved during volume expansion with a significant decrease 6–8 min after start of fluid infusion and a maximal drop at 10–12 min. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Some clinical and histological studies have reported that SARS-CoV-2 infection may damage the endothelium. However, the impact of this virus on endothelial function in vivo remains poorly characterized. In this single-center pilot observational study, we performed iontophoresis of acetylcholine coupled with Laser doppler to investigate microvascular endothelial reactivity in COVID-19 patients compared to patients with non-COVID-19 bacterial pneumonia (NCBP) patients. Results: During three consecutive months, 32 COVID-19 patients and 11 control NCBP patients with acute respiratory failure were included. The median age was 59 [50–68] and 69 [57–75] years in COVID-19 and NCBP groups, respectively (P = 0.11). There was no significant difference in comorbidities or medications between the two groups, except for body mass index, which was higher in COVID-19 patients. NCBP patients had a higher SAPS II score compared to COVID-19 patients (P < 0.0001), but SOFA score was not different between groups (P = 0.51). Global hemodynamic and peripheral tissue perfusion parameters were not different between groups. COVID-19 patients had significantly lower skin microvascular basal blood flow than NCBP patients (P = 0.02). In addition, endothelium-dependent microvascular reactivity was threefold lower in COVID-19 patients than NCBP patients (P = 0.008). Conclusions: Both baseline skin microvascular blood flow and skin endothelial-dependent microvascular reactivity were impaired in critically ill COVID-19 patients compared to NCBP patients, despite a lower disease severity score supporting a specific pathogenic role of SARS-CoV-2 on the endothelium. [ABSTRACT FROM AUTHOR]

PURPOSE: Critically ill elderly patients who suffer from Sars-CoV-2 disease are at high risk for organ failure. The modified MELD-XI score has not been evaluated for outcome prediction in these most vulnerable patients. METHODS: The Corona Virus disease (COVID19) in Very Elderly Intensive Care Patients study (COVIP, NCT04321265) prospectively recruited patients on intensive care units (ICU), who were = 70 years. Data were collected from March 2020 to February 2021. The MELD-XI score was calculated using the highest serum bilirubin and creatinine on ICU admission. Univariate and multivariable logistic regression analyses were performed to assess associations between the MELD-XI score and mortality. The primary outcome was 30-day-mortality, the secondary outcomes were ICU- and 3-month-mortality. RESULTS: In total, data from 2,993 patients were analyzed. Most patients had a MELD-XI <12 on admission (76%). The patients with MELD-XI = 12 had a significantly higher 30-day-, ICU- and 3-month-mortality (44%vs 64%, and 42%vs. 59%, and 57%vs. 76%, p < 0.001). After adjustment for multiple confounders, MELD-XI = 12 remained significantly associated with 30-day- (aOR 1.572, CI 1.268–1.949, p < 0.001), ICU-, and 3-month-mortality. CONCLUSION: In critically ill elderly intensive care patients with COVID-19, the MELD-XI score constitutes a valuable tool for an early outcome prediction. [ABSTRACT FROM AUTHOR]

Convalescent plasma (CP) containing antibodies derived from coronavirus disease 2019 (COVID-19) survivors has been proposed as a promising therapeutic option for severe COVID-19. In our intensive care unit (ICU), 55 patients (46 male, median age 61 years) with PCR-confirmed COVID-19 (35 = 63.6% on mechanical ventilation, 7 = 14.5% on high-flow nasal oxygen, 12 = 20% on non-invasive ventilation, 1 = 1.8% without respiratory support) were treated with high-titre CP (200 mL per dose, range 1–6 doses, median 3 doses per patient, minimum titre > 1:100, Wantai test). 139 COVID-19 patients treated in the same ICU who did not receive CP served as control group. In 27 patients, the effect of CP on the individual levels of SARS-CoV-2 IgG antibodies was assessed by ELISA in serum sample pairs collected before and after CP transfusion. The first CP dose was administered at a median of 8 days after symptom onset. 13 patients in the plasma cohort died (28-day mortality 24.1%), compared to 42 (30.2%) in the cohort who did not receive CP (p = 0.5, Pearson Chi-squared test). Out of the 27 individuals investigated for the presence of IgG antibodies, 8 did not have detectable IgG levels before the first CP transfusion. In this subpopulation, 3 patients (37.5%) died. Not a single confirmed adverse reaction to CP was noted. While adjunctive treatment with CP for severe and life-threatening COVID-19 was a very safe intervention, we did not observe any effect on mortality. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients.Methods: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians.Results: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)).Conclusion: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions.Trial Registration: NCT03134807 and NCT03370692 . [ABSTRACT FROM AUTHOR]

Abstract Background Hypoxic hepatitis (HH) is a type of acute hepatic injury that is histologically characterized by centrilobular liver cell necrosis and that is caused by insufficient oxygen delivery to the hepatocytes. Typical for HH is the sudden and significant increase of aspartate aminotransferase (AST) in response to cardiac, circulatory or respiratory failure. The aim of this study is to investigate its epidemiology, causes, evolution and outcome. Methods The screened population consisted of all adults admitted to the intensive care unit (ICU) at the Ghent University Hospital between January 1, 2007 and September 21, 2015. HH was defined as peak AST > 5 times the upper limit of normal (ULN) after exclusion of other causes of liver injury. Thirty-five variables were retrospectively collected and used in descriptive analysis, time series plots and Kaplan–Meier survival curves with multi-group log-rank tests. Results HH was observed in 4.0% of the ICU admissions at our center. The study cohort comprised 1116 patients. Causes of HH were cardiac failure (49.1%), septic shock (29.8%), hypovolemic shock (9.4%), acute respiratory failure (6.4%), acute on chronic respiratory failure (3.3%), pulmonary embolism (1.4%) and hyperthermia (0.5%). The 28-day mortality associated with HH was 45.0%. Mortality rates differed significantly (P = 0.007) among the causes, ranging from 33.3% in the hyperthermia subgroup to 52.9 and 56.2% in the septic shock and pulmonary embolism subgroups, respectively. The magnitude of AST increase was also significantly correlated (P 20× ULN, respectively. Conclusion This study surpasses by far the largest cohort of critically ill patients with HH. HH is more common than previously thought with an ICU incidence of 4.0%, and it is associated with a high all-cause mortality of 45.0% at 28 days. The main causes of HH are cardiac failure and septic shock, which include more than 3/4 of all episodes. Clinicians should search actively for any underlying hemodynamic or respiratory instability even in patients with moderately increased AST levels.

Neurological involvement is frequent in inherited metabolic disease of the intoxication type. Hyperammonemic coma related to these diseases may cause severe neurological sequelae. Early optimal treatment is mandatory combining metabolite scavengers (MS) and sometimes continuous veno-venous hemodialysis (CVVHD). We aimed to describe the therapeutic management of hyperammonemia in neonates upon diagnosis of their metabolic disease and to compare neonates managed with MS alone or with both MS and CVVHD. We conducted a retrospective study including all neonates admitted for initial hyperammonemia to the pediatric intensive care unit of a Reference Center of Inherited Metabolic Diseases, between 2001 and 2012. The study included 35 neonates. Before admission, MS were initiated for 11 neonates. At admission, the median ammonia levels were 391 μmol/L and were significantly lower in neonates who received MS before admission. At admission, ammonia levels were 644 μmol/L in dialyzed and 283 μmol/L in non-dialyzed neonates. The median time to reach a 50% decrease of the initial ammonia levels was significantly shorter in dialyzed neonates; however, the normalization of ammonia levels was similar between dialyzed and non-dialyzed neonates. Hemodynamic disorders were more frequent in dialyzed neonates. MS represent an effective treatment for hyperammonemia and should be available in all pediatric units to avoid the need for CVVHD. Although CVVHD enhances the kinetics of toxic metabolite decrease, it is associated with adverse hemodynamic effects. [ABSTRACT FROM AUTHOR]