Trajectory pattern of serum urea nitrogen to creatinine ratio in acute kidney injury requiring continuous renal replacement therapy: A post hoc analysis of a retrospective multicenter cohort study.

Comment on "Trajectory pattern of serum urea nitrogen to creatinine ratio in acute kidney injury requiring continuous renal replacement therapy: A post hoc analysis of a retrospective multicenter cohort study".

Continuous renal replacement therapy (CRRT) is the preferred method of kidney support for critically ill children with severe acute kidney injury (AKI) or fluid overload (FO). The number of survivors after pediatric CRRT is increasing, but there are insufficient data describing the risk of developing chronic kidney disease (CKD) in these patients. A register-based study from a tertiary multidisciplinary hospital, 2008-2021. PICU patients 18 years or younger treated with CRRT due to AKI or FO at Karolinska University Hospital from 2008 to 2021 were included. Detailed PICU data from PICU survivors were combined with data from the Swedish National Patient Register aiming to investigate the long-term risk of CKD development. Secondary outcomes included risk of hypertension, end-stage renal disease and mortality. None. We identified and included 156 PICU survivors with a mean follow-up time of 6.4 years ( sd 3.2). CKD developed in 19 of 156 (12.2%) patients, resulting in an incidence of 18.9 (95% CI, 11.4-29.6) cases per 1000 person-years. Median time to CKD diagnosis was 11.5 months (interquartile range 3-62.5). Hypertension occurred in 17 of 156 patients (10.9%), and the composite outcome of CKD or hypertension in 28 of 156 patients (17.9%). The incidence of post-PICU mortality was 6 per 1000 person-years (95% CI, 2.2-13.1). In multivariable analysis, CRRT duration ( p = 0.02) and estimated glomerular filtration rate (eGFR) at hospital discharge ( p = 0.02) were associated with CKD development. We failed to identify an association between age at CRRT initiation or PICU illness and subsequent development of CKD. In our center in Sweden, 2008-2021, we found that a significant proportion of children surviving critical illness requiring CRRT are subsequently diagnosed with CKD or hypertension over time, demonstrating that rigorous follow-up of PICU patients undergoing CRRT is warranted.

Model-informed cefepime dosing in paediatric patients receiving continuous renal replacement therapy.

Adsorption within continuous renal replacement therapy (CRRT) circuits may reduce exposure to echinocandins. Because micafungin is highly protein bound, the behavior of its unbound fraction during CRRT remains difficult to characterize. We assessed unbound micafungin disappearance from a central compartment and late release/desorption in a protein-free in vitro CRRT model. Micafungin stability was assessed in a 5-L bag of Hemosol™ B0 over 8h. In the NeckEpur model, a 5-L protein-free central compartment was circulated at 200mL/min for 6h through either a polyacrylonitrile hemofilter (ST™150; post-dilution continuous veno-venous hemofiltration [CVVH], 2.5L/h) or a polysulfone hemofilter (AV™1000). For AV™1000, one run used CVVH (2.5L/h) and one used continuous veno-venous hemodiafiltration (CVVHDF; dialysis 1.5L/h plus filtration 1.0L/h). Initial micafungin concentrations in the central compartment were 2.18mg/L or approximately 6.8mg/L. Concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a lower limit of quantification (LLOQ) of 0.1mg/L. Apparent central-compartment clearance (Cl_CC), sieving coefficient (Sc), and extraction coefficient (EC) were used to describe disappearance from the circuit, filtration, and late release. Sensitivity analyses replaced values < LLOQ by LLOQ/2 or LLOQ/√2. Segmental sampling and within-filter mass balance were used descriptively to localize loss within the extracorporeal system. Micafungin was stable in Hemosol™ B0 over 8h (- 5.2 ± 0.5%). With ST™150 at 2.18mg/L, C_CC reached the LLOQ by 200min and was below the LLOQ thereafter; apparent Cl_CC was approximately 6L/h, effluent concentrations were not measurable, and limited late release was estimated over 120-200min. With ST™150 at approximately 6.8mg/L, elimination from the central compartment was 92 ± 4% at 6h (apparent Cl_CC 4.9 ± 0.2L/h), with within-filter contributions from measurable effluent removal (54 ± 6%) and non-effluent loss (46 ± 6%); small late release was compatible with negative EC values during 180-360min. For AV™1000, two exploratory runs-one CVVH and one CVVHDF-showed rapid disappearance from the central compartment, with C_CC below the LLOQ by 120min, no measurable effluent concentrations, and no negative EC values. Sensitivity analyses for values < LLOQ changed the numerical Cl_CC estimates but not the overall pattern. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. In this exploratory protein-free in vitro model, unbound micafungin rapidly disappeared from the CRRT circuit with both tested filter systems. ST™150 showed measurable effluent removal at higher concentrations and limited late release, whereas both exploratory AV™1000 runs showed rapid disappearance without detectable late release. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. These findings characterize unbound micafungin-circuit interactions under the tested conditions; their clinical translation will depend on in vivo protein binding and rebinding kinetics.

Continuous renal replacement therapy (CRRT) is a complex, high-risk life-sustaining intervention in intensive care units (ICUs). Despite its widespread use, understanding of how nurses navigate 'human-machine' interactions to develop professional competence remains limited. To describe the clinical experiences of critical care nurses in caring for patients receiving CRRT and to explore their professional growth trajectory from technical anxiety to autonomy. A descriptive qualitative study design was employed. Ten registered nurses with at least 1 year of ICU experience were recruited from a tertiary medical centre using purposeful sampling. Data from semi-structured interviews were analysed using inductive content analysis. The study was reported in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ). Methodological rigour was ensured using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. A dynamic growth trajectory from 'technical anxiety' to 'professional mastery' emerged, consisting of four core themes: (1) navigating uncertainty, (2) battling the machine, (3) beyond the numbers: developing clinical judgement and (4) the safety net of interprofessional collaboration. A critical turning point occurred when nurses integrated machine data with physiological responses to see the 'patient behind the machine'. Caring for patients on CRRT involves a complex psychological and professional maturation process. Through accumulated practice and interprofessional support, nurses overcome initial fears and develop 'technological competency as caring'. Healthcare institutions should implement simulation-based education focusing on clinical troubleshooting and establish robust interprofessional support systems to reduce cognitive load and foster professional resilience among nurses.

Erratum for Li et al., "Pharmacokinetics/pharmacodynamics of ceftazidime-avibactam in critically ill adult patients receiving continuous renal replacement therapy".

Aggressive joint pharmacokinetic/pharmacodynamic target attainment of TDM-guided continuous infusion meropenem-vaborbactam monotherapy: A valuable strategy for maximizing the microbiological outcome of documented KPC-producing Enterobacterales infections?

Background: Sepsis management in elderly populations presents unique challenges due to age-related physiological changes and comorbidities. Current guidelines remain conflicted regarding optimal antibiotic timing. We conducted a retrospective, multicenter study to evaluate the association between antibiotic administration timing and short-term and long-term outcomes in elderly sepsis patients. Methods: This retrospective cohort study analyzed data from the MIMIC-IV (v3.1) database. Patients were categorized into the early group (antibiotics initiated within 1 h) and the late group (antibiotics initiated >1 h after diagnosis). Further analyses were stratified by shock status (septic shock vs non-septic shock) and pathogen type (Gram-positive vs Gram-negative bacteria). Multivariable Cox regression assessed associations between antibiotic administration timing and 28-/180-/365-day hospital mortality. Restricted cubic spline models evaluated dose-response relationships. The primary outcome was 28-day hospital mortality. Secondary outcomes included 180-day and 365-day mortality rates, along with the incidence of continuous renal replacement therapy (CRRT) and mechanical ventilation requirements. Results: A total of 12,425 patients met the inclusion criteria from the MIMIC-IV database. The multivariable-adjusted analysis demonstrated that delayed antibiotics administration was significantly associated with a 35% increased risk of 28-day all-cause hospital mortality (HR = 1.35, 95% CI 1.22-1.52; P < 0.001), a 43% elevated 180-day hospital mortality risk (HR = 1.43, 95% CI 1.30-1.56; P < 0.001), and a 45% higher 365-day mortality risk (HR = 1.45, 95% CI 1.33-1.56; P < 0.001). Stratified analyses revealed mortality benefits persisted in non-shock patients (28-day HR = 1.31, P < 0.001) and Gram-positive infections (28-day HR = 1.63, P < 0.001), whereas no significant associations emerged in septic shock (28-day HR = 0.82, 95%CI 0.65-1.03; P = 0.081) or Gram-negative infections (HR = 1.04, 95%CI 0.87-1.24; P = 0.692). A linear relationship was observed between antibiotic delay and mortality (Nonlinear P = 0.88). Conclusions: Early antibiotic administration improves survival in elderly sepsis patients, particularly non-shock cases and Gram-positive infections. These insights advocate the importance of individualized selection based on patients' clinical context in critical care practice.

Effects of tocilizumab on neutrophil gelatinase-associated lipocalin following out-of-hospital cardiac arrest, and its prognostic value.

Chronic micro-inflammation in patients with end-stage renal disease (ESRD) is a significant driver of cardiovascular complications and diminished quality of life. While standard hemodialysis (SHD) effectively manages small-molecule clearance, its ability to remove medium-to-large uremic toxins-the primary catalysts of systemic inflammation-remains limited. This study aimed to evaluate the comparative clinical benefits of hemodiafiltration (HDF) and hemoperfusion (HDP) relative to SHD, specifically focusing on inflammatory control, dialysis adequacy, and patient safety. This was a 10-week, single-center, non-randomized prospective observational study evaluating 365 end-stage renal disease (ESRD) patients divided into three cohorts: standard hemodialysis (SHD, n = 145, thrice-weekly), online hemodiafiltration (HDF, n = 115, twice-weekly hemodialysis plus once-weekly HDF), and hemoperfusion (HDP, n = 105, twice-weekly hemodialysis plus once-monthly hemoperfusion). Primary endpoints were restricted to short-term surrogate outcomes, including shifts in serum inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)) and clearance adequacy indices (Kt/V, URR). Baseline characteristics were well-balanced across all three cohorts. Following 10 weeks of treatment, the HDF (84.2%) and HDP (77.1%) groups demonstrated significantly higher effective treatment rates (defined by clinical symptom improvement and biochemical stability, a composite of symptomatic improvement and biochemical stability) compared to the SHD group (61.4%; p < 0.05). Advanced modalities achieved increased association with biomarker reduction of middle-molecule toxins, with HDF showing the most profound reductions in IL-6, TNF-α, and CRP (p < 0.001). Dialysis adequacy was significantly improved in the HDF group, which showed the highest increases in dialysis adequacy. While the incidence of acute complications such as hypotension and muscle cramps did not differ significantly between groups, both HDF and HDP cohorts reported a notable reduction in post-dialysis fatigue compared to SHD (14% and 16% vs. 19%, respectively). However, HDF and HDP cohorts experienced lower incidences of cognitive dysfunction. Over a 10-week observation framework, advanced hybrid modalities (HDF and HDP) are independently associated with superior clearance of middle-to-large molecular uremic toxins and attenuated systemic inflammation compared to SHD. However, these short-term surrogate improvements did not translate into a statistically significant reduction in clinical adverse events or post-dialysis fatigue, indicating the need for long-term longitudinal evaluation.

Regional citrate anticoagulation (RCA) is standard in continuous renal replacement therapy (CRRT). Post-Filter ionized calcium (Post-Filter iCa) is the gold standard for monitoring anticoagulation efficacy, but it requires blood sampling. Effluent fluid iCa can be measured without blood sampling. This study assessed the correlation and agreement between Effluent Fluid iCa and Post-Filter iCa in critically ill patients undergoing RCA-CRRT. We conducted a prospective non-interventional study from June to November 2024 at West China Hospital of Sichuan University. Thirty-six critically ill patients receiving CVVHDF with RCA were enrolled, yielding 216 paired samples. Ionized calcium was measured in Pre-Filter, Post-Filter, and Effluent Fluid samples using a point-of-care analyzer. CRRT was performed using the Prismaflex system with ST150 filters and Oxiris tubing. Post-filter blood and effluent fluid samples were drawn simultaneously to ensure direct comparability. This study analyzed 216 paired samples from 36 critically ill patients on CVVHDF with RCA to assess the relationship between Post-Filter and Effluent Fluid ionized calcium. A moderate correlation was found (r = 0.551 [CI 0.45,0.64], p < 0.001). Bland-Altman analysis showed a mean difference of - 0.024 mmol/L (95% CI: -0.033 to - 0.015), with limits of agreement from - 0.153 (95% CI: -0.1682 to - 0.1378) to 0.105 mmol/L (95% CI: 0.0900 to 0.1204). Variance component analysis demonstrated that only 13.3% of variability (ICC = 0.134) was attributable to between-patient differences, while 86.7% reflected within-patient temporal variation. ICC for Post-Filter iCa reliability over time was 0.269, and for Effluent iCa was 0.146, indicating substantial dynamic changes. Agreement between methods was moderate at early time points (ICC 0.514-0.628 at 2-24h) but declined at 48-72h (ICC 0.424-0.435). Cluster analysis of serial calcium measurements identified three distinct profiles among 36 patients: a dominant cluster (66.7%, n = 24) with target-range levels; a high-calcium cluster (19.4%, n = 7), and a low-calcium cluster (13.9%, n = 5). Effluent Fluid iCa demonstrates moderate correlation with Post-Filter iCa but substantial within-patient variability limits its use as a direct substitute. While it may offer some supplementary information for tracking anticoagulation trends, it cannot replace Post-Filter sampling at present. Cluster analysis identified distinct calcium phenotypes associated with filter lifespan, though further multicenter validation would be needed to explore potential clinical utility.

The evolving landscape of acute kidney injury: research directions and changes in clinical practice.

Neonatal fluid management in extracorporeal life support (ECLS) is complex, with the goal of improving outcomes while preventing complications. This study evaluates the impact of early continuous renal replacement therapy (CRRT) on volume status, outcomes, and renal recovery in neonatal ECLS. A single-center retrospective review of neonates was performed (2007-2023, n =108). Routine early CRRT began in 2011, providing a natural cohort comparison between early (≤48 hours) and delayed/no CRRT. Early (70.4%) and delayed/no (29.6%) CRRT cohorts had similar ECLS indications, birthweights, and mortality. Time from cannulation to CRRT initiation was 4 hours (early CRRT) versus 4.4 days (delayed CRRT) (p < 0.001). Early CRRT was associated with significantly reduced median peak fluid balance (30% vs. 37%, p < 0.05) and earlier negative volume status, with 80% achieving negative fluid balance by day 3, compared with 53% in the delayed group (p = 0.030). In survivors, early CRRT had significantly shorter ECLS runs (5.1 vs. 8.6 days, p < 0.001) with fewer median extrarenal ECLS complications (1.0 vs. 3.0, p = 0.001). No differences were observed in renal recovery. Though the study design prohibits definitive conclusions, early CRRT initiation in neonatal ECLS was associated with improvement in early and peak fluid balance status and reduced ECLS duration and complications without differences in long-term renal outcomes.

The use of oXiris hemofilter in the initial continuous renal replacement therapy among patients with septic shock: A propensity score matched analysis.

Acute kidney injury (AKI) is among the most prevalent life-threatening complications in intensive care units (ICUs), with continuous renal replacement therapy (CRRT) being the primary mode of renal support for haemodynamically unstable patients. Despite the technical complexity of CRRT, formal training programmes for ICU nurses remain inconsistent across healthcare settings. This study explored the informal training experiences of critical care nurses managing dialysis-dependent patients in Al-Ahsa, Saudi Arabia. A qualitative descriptive design was employed, guided by reflexive thematic analysis as described by Braun and Clarke. Semi-structured in-depth interviews were conducted with 20 purposively sampled ICU nurses with direct CRRT management responsibilities across healthcare facilities affiliated with King Faisal University, Al-Ahsa. Data were analysed through six iterative phases of thematic analysis. Ethical approval was obtained from the Institutional Review Board of King Faisal University. Four overarching themes were generated: (1) "Figuring It Out on the Floor", nurses described learning CRRT management primarily through observation and immediate bedside practice; (2) "The Colleague Is the Textbook", experienced peers served as informal educators, transmitting practical knowledge through demonstration and narration; (3) "Anxiety Behind the Machine", nurses articulated persistent fear of error that gradually transformed into competence through repeated exposure; and (4) "Gaps the System Does Not See", participants identified a systemic absence of structured CRRT training and called for formalised competency frameworks. Critical care nurses in this setting rely heavily on informal, peer-mediated learning to acquire CRRT competencies in the absence of standardised institutional training. These findings highlight an urgent need for structured simulation-based CRRT education, written protocols, and competency assessment frameworks. Nursing leaders and ICU educators must recognise and address the informal learning burden carried by frontline nurses to safeguard patient safety and support workforce development. Not applicable.

IntroductionThere is a lack of data supporting rationale drug use with extracorporeal membrane oxygenation (ECMO). The aim of this study was to externally validate a previously developed population pharmacokinetic model of meropenem in neonatal ECMO and continuous renal replacement therapy.MethodsA total of twenty-eight neonates with a body weight of 3.81 (3.45-4.11) kg, median (interquartile) and a postnatal age of 3 (2-4) days were enrolled. One hundred plasma concentrations of meropenem were used for external validation by a published population pharmacokinetic analysis model using NONMEM V7.3.0 (ICON Development Solutions, Ellicott City, MD, USA) and PsN v3.4.2, both running in Pirana 2.9.0. Prediction error analyses, and NPDE diagnostics were performed to assess the model's extrapolative capability. Bayesian forecasting was conducted to determine the impact of prior concentration information on predictive performance.ResultsPopulation-based predictions showed minimal overall bias but limited accuracy, with substantial variability between predicted and observed concentrations and less than half of predictions falling within an acceptable deviation range. After incorporating one prior measured concentration through Bayesian forecasting, predictive performance improved markedly. Most predictions were then close to the values observed, and overall accuracy increased substantially.ConclusionsThe meropenem population pharmacokinetic model provides unbiased but imprecise population-level predictions and is therefore not suitable for a priori dosing in neonatal ECMO patients. Including just one prior concentration greatly improves prediction, supporting the use of this model for Bayesian, therapeutic drug monitoring-guided dosing of meropenem in this vulnerable population. (The study identification number is K 2026-0116).

Hepatic encephalopathy (HE) is a frequent and life-threatening neurological complication of acute liver failure (ALF) encountered in the intensive care unit and remains a major determinant of short-term mortality and long-term neurological outcomes. Increasing evidence indicates that HE in ALF is primarily driven by hyperammonemia, with synergistic contributions from systemic inflammation, cerebral hemodynamic dysregulation, metabolic failure, and osmotic imbalance. These interacting mechanisms promote astrocytic swelling, disruption of the blood-brain barrier, cerebral edema, and intracranial hypertension. In patients with ALF, early recognition of cerebral involvement and systematic exclusion of alternative causes of altered mental status are essential. Given the dynamic and heterogeneous neurological manifestations of HE, reliance on isolated clinical, biochemical, or radiological parameters is insufficient. Multimodal neuromonitoring-integrating neurological examination, ammonia kinetics, cerebral hemodynamic assessment, and neuroimaging-allows more accurate assessment of cerebral injury and supports timely, targeted intervention. This review summarizes current evidence on the pathophysiology of HE in ALF with a focus on mechanisms relevant to intensive care practice. We highlight evidence-based strategies for cerebral protection, including early and sustained control of hyperammonemia with continuous renal replacement therapy, optimization of cerebral perfusion and osmotic balance, selective use of plasma exchange, and structured neurocritical care. An integrated management framework is proposed to guide prognostication and inform timely decisions regarding advanced liver support and liver transplantation in the ICU setting.

An early initiation of continuous renal replacement therapy (CRRT) for ammonia reduction has shown a reduction in deaths due to cerebral edema (CE) in acute liver failure (ALF); however, there are no controlled trials assessing the same. We performed an open-label pilot randomized controlled trial (RCT) on ALF patients with CE. Patients underwent therapeutic plasma-exchange (PLEX) by centrifugal apheresis after initial resuscitation. Group 1 received CRRT initiation within the first 12 h, while Group 2, CRRT was initiated for PLEX non-responders. The primary endpoint was 28-day survival. Patients aged 28.11 ± 10.10 years, 56.67% viral, 69% hyperacute were randomized. At day 28, 46% died and 11% underwent liver transplant. There were a total of 31 protocol violations, significantly more in group 2 (55.6% vs. 13.3%; p < 0.001). On ITT and piece-wise exponential regression analysis, pre-emptive CRRT was associated with a significantly lower hazard of death during the first 7 days (2.2% vs. 17.8% Hazard ratio [HR] 0.12, 95% confidence interval [CI] 0.02-0.96) with comparable survival at 28-days. Notably, higher 28-day mortality was observed on PP analysis in group 2 (80% vs. 46%, HR 3.10, 95% CI 1.57-6.12) with a significantly higher reduction in ammonia and improvement in mean arterial pressure and lower number of sessions of TPE. Each hour delay in CRRT was associated with increased mortality (HR 1.01, 1.00-1.02). A pre-emptive initiation of CRRT in ALF patients is synergistic to TPE, reduces early deaths by rapid improvement in hemodynamics, ammonia and cerebral edema (NCT04991259).

The use of life-support therapies like extracorporeal membrane oxygenation (ECMO), mechanical circulatory systems (MCS), and continuous renal replacement therapy (CRRT) creates a complex and dynamic metabolic environment that profoundly challenges nutritional management for these critically ill patients. Current existing guideline recommendations are largely based on expert opinions and observational data. No specific guidelines exist for this population. This mini-review synthesizes the current, limited evidence on the pathophysiological and metabolic alterations induced by ECMO, MCS, and CRRT and provides pragmatic recommendations for nutritional assessment and delivery. The key challenges include dramatic nutrient fluxes in the case of CRRT, a possible hypermetabolic state exacerbated by ECMO, fluid overload constraints, and drug-nutrient interactions. Practical strategies are proposed for calorie-protein targeting, micronutrient repletion, and monitoring, emphasizing a 'start low, advance carefully' approach within a multidisciplinary framework.