Tomoko Fujii

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Background: The Sodium Bicarbonate for Metabolic Acidosis in the ICU (SODa-BIC) trial assessed the effect of sodium bicarbonate on Major Adverse Kidney Events at 30 days (MAKE30) in critically ill patients with metabolic acidosis. Although the trial demonstrated no significant difference in the primary outcome, the individual components showed differing magnitudes and directions of […] ABSTRACT Background: The Sodium Bicarbonate for Metabolic Acidosis in the ICU (SODa-BIC) trial assessed the effect of sodium bicarbonate on Major Adverse Kidney Events at 30 days (MAKE30) in critically ill patients with metabolic acidosis. Although the trial demonstrated no significant difference in the primary outcome, the individual components showed differing magnitudes and directions of […]

OBJECTIVE: Randomized trials evaluating the timing of renal replacement therapy (RRT) have informed current practice toward more conservative initiation strategies because of the lack of mortality benefit from early initiation. However, the optimal indications for RRT to offer lifesaving benefits remain uncertain. We aimed to estimate heterogeneous treatment effect of RRT and to identify patient groups associated with benefit or harm. DESIGN: Multicenter observational study. SETTING: A nationwide intensive care registry in Japan, Japanese Intensive Care Patient Database. Patients: Adult patients who were admitted to the ICUs from 2018 through 2023 were included, excluding those with end-stage kidney disease, early death, readmission, or normal renal function. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Exposure was RRT during the ICU stay. Hospital mortality was the primary outcome. After 1:1 propensity score matching to adjust for confounding, 18,794 patients (9,397 per group) were analyzed. On average, RRT was associated with higher hospital mortality (risk difference, 6.1% points [95% CI, 3.4–8.7]). However, our machine learning-based causal forest algorithm showed substantial heterogeneity of treatment effects heterogeneity of treatment effects (HTEs) (rank-weighted average treatment effect, –8.2 percentage points [95% CI, –9.7 to –6.7]). Patients characterized by elevated serum creatinine, reduced urine output, and elevated blood urea nitrogen levels showed potential mortality benefit from RRT, whereas relatively preserved renal function was more likely to be associated with harm. CONCLUSIONS: Although RRT was associated with an increased risk of hospital mortality overall, HTEs were identified in selected subgroups that may benefit from RRT. These findings support a data-driven approach to defining clinically applicable optimal RRT indications to guide more judicious use of RRT.

Continuous renal replacement therapy (CRRT) is commonly used for critically ill patients with acute kidney injury (AKI). Despite two decades of clinical research, the optimal CRRT dose remains uncertain. Early studies suggested benefits of high-intensity therapy; however, subsequent multicentre randomised clinical trials (RCTs) have demonstrated no survival advantage of effluent rates above 25 mL/kg/h, thereby establishing the current “standard dose” of 20–25 mL/kg/h recommended by guidelines. This narrative review synthesises current knowledge on the concept of CRRT dose, including physiologic principles of solute control, historical evolution of dosing strategies, distinctions between prescribed and delivered dose, and the potential adverse consequences of excessive clearance. Although standard dosing is based on achieving small-solute clearance, clinical practice varies widely, with some intensive care units (ICUs) delivering substantially lower doses, i.e., 13–16 mL/kg/h, without apparent harm. Excessive clearance increases the risk of hypophosphatemia, nutrient loss, altered drug exposure, and potentially delayed renal recovery, which are collectively described as dialytrauma. Experimental and clinical observations have renewed interest in permissive azotaemia, proposing that moderate urea levels may facilitate renal repair. In parallel, real-world data have revealed significant global heterogeneity and have suggested that the minimum effective dose may be lower than traditionally assumed. Three ongoing RCTs are evaluating whether lower-intensity regimens are feasible, safe, and beneficial. Accordingly, the debate has shifted from “high vs. standard” to “standard vs. low”. The results of the ongoing clinical trials will likely redefine optimal CRRT dosing and inform future international guidelines and clinical practice.

Background: Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations.Objective: This survey aims to assess current thromboprophylaxis preferences and willingness to participate in future randomized clinical trials (RCTs) on this topic.Method: We conducted an international online survey between February and May 2023 among intensive care unit (ICU) physicians, including 16 questions about preferences in relation to thromboprophylaxis and preferences on topics for a future RCT. The survey was distributed through the network of the Collaboration for Research in Intensive Care.Results: A total of 715 physicians from 170 ICUs in 23 countries contributed information, with a mean response rate of 36%. In most ICUs, both pharmacological (n = 166, 98%) and mechanical thromboprophylaxis (n = 143, 84%) were applied. A total of 36 pharmacological thromboprophylaxis regimens were reported. Use of low‐molecular‐weight heparin (LMWH) was most common (n = 149 ICUs, 87%), followed by subcutaneous unfractionated heparin (n = 44 ICUs, 26%). Seventy‐five percent of physicians indicated that they used enoxaparin 40 mg (4000 IU), dalteparin 5000 IU, or tinzaparin 4500 IU once daily, whereas 25% reported the use of 16 other LMWH type and dose combinations. Dose adjustment according to weight was common (78 ICUs, 46%). Participants perceived high variation in the application of thromboprophylaxis and were willing to consider an alternative LMWH type (n = 542, 76%) or dose (n = 538, 75%) in the context of an RCT.Conclusion: LMWH was the preferred agent for thromboprophylaxis in critically ill patients. There was considerable variation in the application of LMWH for prophylaxis, reflected by the use of different types, doses, and dosing strategies. Most physicians would be willing to participate in an RCT on thromboprophylaxis.Editorial comment: This survey demonstrates current patterns in implementation preferences for critically ill patients. While there is one approach and drug that is commonly preferred, these findings show that there is some variation in practice.