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Purpose To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Methods Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. Results HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients [less than or equal to] 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. Conclusion In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings., Author(s): Yahya Shehabi [sup.1] [sup.2], Ary Serpa Neto [sup.3] [sup.4] [sup.5] [sup.6], Belinda D. Howe [sup.3], Rinaldo Bellomo [sup.3] [sup.5] [sup.6], Yaseen M. Arabi [sup.7], Michael Bailey [sup.3] [sup.5], Frances [...]

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.

Purpose Liberal use of oxygen may contribute to secondary brain injury in patients with hypoxic-ischaemic encephalopathy (HIE). However, there are limited data on the effect of different oxygen regimens on survival and neurological disability in HIE patients. Methods We undertook a post-hoc analysis of the 166 patients with suspected HIE enrolled in a trial comparing conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary endpoint for the current analysis was death or unfavourable neurological outcome at day 180. Key secondary outcomes were day 180 mortality, and cause-specific mortality. Results Patients with HIE allocated to conservative oxygen spent less time in the ICU with an SpO.sub.2 [greater than or equal to] 97% (26 h [interquartile range (IQR) 13-45 vs. 35 h [IQR 19-70], absolute difference, 9 h; 95% CI - 21.4 to 3.4). A total of 43 of 78 patients (55.1%) assigned to conservative oxygen and 49 of 72 patients (68.1%) assigned to usual oxygen died or had an unfavourable neurological outcome at day 180; odds ratio 0.58; 95% CI 0.3-1.12; P = 0.1 adjusted odds ratio 0.54; 95% CI 0.23-1.26; P = 0.15. A total of 37 of 86 patients (43%) assigned to conservative oxygen and 46 of 78 (59%) assigned to usual oxygen had died by day 180; odds ratio 0.53; 95% CI 0.28-0.98; P = 0.04; adjusted odds ratio 0.56; 95% CI 0.25-1.23; P = 0.15. Cause-specific mortality was similar by treatment group. Conclusions Conservative oxygen therapy was not associated with a statistically significant reduction in death or unfavourable neurological outcomes at day 180. The potential for important benefit or harm from conservative oxygen therapy in HIE patients is not excluded by these data., Author(s): Paul Young [sup.1] [sup.2], Diane Mackle [sup.1], Rinaldo Bellomo [sup.3] [sup.4] [sup.5] [sup.6], Michael Bailey [sup.3] [sup.5], Richard Beasley [sup.1], Adam Deane [sup.5] [sup.6], Glenn Eastwood [sup.3] [sup.4], Simon [...]

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2) by near‐infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2), and, in some protocols, brain tissue PO2, by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2, rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg−1 min−1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose‐dependently decreased rSO2, but increased renal cortical and medullary PO2. Increasing blood haemoglobin concentration increased rSO2, but not renal PO2. We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation. [ABSTRACT FROM AUTHOR]

Introduction: Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy. Methods: We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization. Results: We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small "positive" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes. Conclusions: This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain. [ABSTRACT FROM AUTHOR]

Introduction: Continuous renal replacement therapy (CRRT) is common in the intensive care unit (ICU) but a high net ultrafiltration rate (UFNET) calculated with daily data may increase mortality. We aimed to study early UFNET practice using minute-by-minute CRRT machine recordings and to assess its association with admission diagnosis and mortality. Methods: We studied CRRT treatments in three adult ICUs over 7 years. We calculated early UFNET rates minute-by-minute and categorized UFNET into tertiles of mean UFNET in the first 72 h and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 h. Results: We studied 1,218 patients, 154,712 h, and 9,282,729 min of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46–1.57) mL/kg/h. Early UFNET tertiles were similar to, but somewhat higher than, previously reported values at 0.00–1.20 mL/kg/h, 1.21–1.93 mL/kg/h, and >1.93 mL/kg/h. UFNET values were similar whether evaluated at 24 or 72 h or for the entire duration of CRRT. There was, however, significant variation in UFNET practice by admission diagnosis: higher in respiratory diseases (pneumonia p = 0.01, other p < 0.0001) and cardiovascular disease (p = 0.005) but lower in cardiothoracic surgery (p = 0.04), renal (p = 0.0003) and toxicology-associated diagnoses (p = 0.01). Higher UFNET was associated with an increased hazard of death, HR 1.24 (1.13–1.37), independent of admission diagnosis, weight, age, sex, presence of end-stage kidney disease, and severity of illness. Conclusion: Early UFNET practice varies significantly by admission diagnosis. Higher early UFNET is independently associated with mortality. Impacts of UFNET on mortality may vary by admission diagnosis. Further work is required to elucidate the nature and mechanisms responsible for this association. [ABSTRACT FROM AUTHOR]

Introduction: Renal replacement therapy (RRT) is associated with hypotension. However, its impact on cardiac output (CO) is less understood. We aimed to describe current knowledge of CO monitoring and changes during RRT. Methods: We searched MEDLINE, Embase, and Cochrane from January 1, 2000, to January 31, 2023, using Covidence for studies of intermittent hemodialysis (IHD) and continuous RRT (CRRT) with at least three CO measurements during treatment. Two independent reviewers screened citations, and a third resolved disagreements. The findings did not allow meta-analysis and are presented descriptively. Results: We screened 3,285 articles and included 48 (37 during IHD, nine during CRRT, and two during both). Non-invasive devices (electrical conductivity techniques and finger cuff pulse contour) were the most common CO measurement techniques (21 studies). The median baseline cardiac index in IHD studies was 3 L/min/m2 (95% CI, 2.7–3.39). Among the 88 patient cohorts studied, a decrease in CO occurred in 63 (72%). In 16 cohorts, the decrease was severe (>25%). Changes in blood pressure (BP) were not concordant in extent or direction with changes in CO. The decrease in CO correlated weakly with ultrafiltration rate (r = −0.3, p = 0.05) and strongly with changes in systemic vascular resistance (SVR) (r = −0.6, p < 0.001). Conclusion: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in 1 of 5 patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR. [ABSTRACT FROM AUTHOR]