Purpose The Clinical Nursing Information System (CNIS) is a cornerstone of nursing informatics, yet its adaptability to the dynamic, context-dependent realities of clinical practice remains inadequately understood. Although existing research has quantitatively evaluated CNIS application outcomes, the ways nurses interact with the system and the adaptive strategies they develop have received insufficient attention. This study explored nurses’ lived experiences of CNIS use, examining how they perceive and respond to system functions, adapt their clinical workflows, and develop practical strategies when system design diverges from real-world patient care. Methods A qualitative study was conducted at a tertiary hospital, involving 22 purposively sampled participants (15 nurses, 7 nurse managers). Semi-structured interviews were analyzed using thematic analysis. Results Three themes emerged. (1) The system as a tool for rule embedding and enforcement: explicit efficiency gains in standardized care. Structured documentation reduced manual burden, prevented errors, and ensured full-process traceability. (2) The system as a cause of clinical context mismatch: hidden barriers in complex practice. The generic knowledge base was misaligned with specialty-specific needs; poor data integration forced nurses to revert to manual monitoring. (3) Adapting to the system: experience-based adjustments and workarounds. Junior nurses used the system’s structured framework as an operational guide, whereas senior nurses actively modified system-generated content based on clinical judgment; manual cross-checking, external notes, and unit-level conventions constituted invisible workarounds. Conclusions CNIS functions simultaneously as an enforcer of standardization and a barrier to contextualized care. Nurses’ workarounds, though essential for patient safety and care continuity, constitute an unquantified hidden workload and signal critical system deficiencies. Future development should move beyond expanding functionality toward a system-adaptation paradigm, using participatory design to integrate nurses’ experiential wisdom into flexible, context-responsive functions that support nursing quality and safety.
Purpose This study sought to develop a grounded theory that explains how emerging nurse leaders (ENLs) are prepared for and supported in assuming leadership responsibilities in clinical settings. Methods A Classical Grounded Theory design was employed. Between December 2020 and November 2022, in-depth individual interviews were conducted with 18 ENLs and 18 senior nurse leaders (SNLs) in a tertiary hospital in Singapore. Data were collected through open-ended interview questions and analyzed using constant comparative methods to generate a theoretical model grounded in participants’ experiences. Results Entrustment emerged as the core category that characterizes how ENLs cultivate leadership capability through the interrelated processes of responsibility, reflection, and relational affirmation. This developmental trajectory unfolded across three cyclical phases: Being positioned, Being exposed, and Being reshaped, each marking a shift in how leadership identity and confidence were negotiated. A concurrent process, withdrawing under pressure, was defined as a temporary withdrawal in response to emotional or contextual strain. Leadership growth occurred through repeated entrusted responsibility, relational support, experiential learning, and reflective recognition. Conclusion Leadership development among emerging nurse leaders is a trust-mediated, iterative process of being positioned, supported, and transformed. Intentional mentorship structures, relational affirmation, and emotional scaffolding are pivotal for sustaining emerging leadership capacity within clinical organizations.
Background:The ability of perfusion index (PI) for predicting fluid responsiveness has been extensively studied with conflicting results. This meta-analysis evaluated the value of variation of PI (ΔPI) for predicting fluid responsiveness in adult patients undergoing preload challenge tests. Methods:PubMed, Embase, and Cochrane Library were searched up to 20th July 2026. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUROC) were calculated. Q test and I2 statistics were used for study heterogeneity and publication bias was assessed by Deeks' funnel plot asymmetry test. Subgroup analysis was performed for the potential causes of heterogeneity arising from varied patient characteristics. Results:Overall, nine studies including 492 preload challenge tests were administered to 419 patients in this review, of whom 52% were fluid responsive. The cutoff values of ΔPI were increased between 1.024% and 33% or decreased between -7% and -40%. Pooled sensitivity and specificity were 0.79 (95% CI: 0.71-0.85) and 0.82 (95% CI: 0.75-0.87), respectively. DOR was 17 (95% CI: 10-30) and AUROC was 0.88 (95% CI: 0.85-0.90), indicating good diagnostic accuracy. Heterogeneity was low (I 2 = 28.95%, P = 0.124). Subgroup analysis showed that ΔPI performed consistently across ICU and operating room settings, regardless of preload challenge type, PI device, or ventilation status. Conclusions:Our meta-analysis suggests that ΔPI may serve as a promising adjunct non-invasive marker for predicting fluid responsiveness during preload challenge tests, but the current evidence base remains limited, heterogeneous, and at risk of bias.
Sepsis is a life-threatening syndrome characterized by a heterogeneous host response to infection that remains a major cause of mortality worldwide. Current clinical scoring systems capture organ dysfunction but fail to reflect the underlying biological diversity, limiting their utility for patient stratification and targeted therapy. This review provides a comprehensive overview of molecular biomarker approaches used to predict sepsis course and prognosis in adult patients, covering genetic, transcriptomic, proteomic, and integrative strategies up to May 2026. Here, we summarize findings from genetic association studies, along with analyses based on polygenic risk scores to aggregate genetic effects, Mendelian randomization, and rare-variant sequencing approaches. We also review transcriptomic and proteomic strategies for endotyping, and diagnostic and prognostic discrimination. Lastly, we discuss how multi-omics integration is emerging as a promising framework to assist in distinguishing causal therapeutic targets from non-causal biomarkers. We also address the challenges that still constrain clinical translation towards precision medicine.
PURPOSE:This study investigated how tooth loss relates to cognitive function among Chinese middle-aged and older adults, with particular attention to whether nutritional status, depressive symptoms, and social engagement serve as mediating factors in this relationship. METHOD:Data were drawn from the 2015 wave of the China Health and Retirement Longitudinal Study (CHARLS), comprising 4,386 individuals aged 45 and above. A binary measure of complete tooth loss served as the indicator for dental status. The analysis considered three mediators: the triglyceride-total cholesterol-body weight index (TCBI), depressive symptoms as evaluated by the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10), and a composite index of social engagement. Cognitive performance was quantified on a 0-21 scale encompassing two components: episodic memory and mental status. The R package lavaan was employed to build parallel multiple mediation models, with bootstrap procedures applied to evaluate indirect effects. RESULTS:A direct link was identified between tooth loss and diminished cognitive performance (β = 0.21, P < .001). Regarding the social engagement pathway, tooth loss predicted reduced engagement, which subsequently correlated with worse cognitive outcomes (β = 0.02, P < .010). For the nutritional pathway, tooth loss predicted lower TCBI values, which in turn were linked to diminished cognitive performance (β = 9.40 × 10-3, P < .001). The combined indirect pathways explained 14.2% of the overall effect (β = 3.40 × 10-2, P < .001). Although CESD-10-assessed depressive symptoms showed a correlation with cognitive function (r = .18, P < .001), they did not demonstrate a statistically significant mediating role (P = .125). CONCLUSION:Among Chinese middle-aged and older adults, tooth loss was linked to diminished cognitive performance. Both nutritional status and social engagement emerged as partial mediators of this relationship, while depressive symptoms failed to exhibit a noteworthy mediating influence. These results advocate for incorporating oral health care, nutritional evaluation, and social engagement facilitation into programs aimed at promoting cognitive well-being in aging individuals.
PURPOSE:This study aimed to explore the lived post-discharge experiences of medical aid recipients who received home-based medical aid services in Gangwon Province, South Korea, with particular attention to how they made sense of the transition from hospital to home and the meaning of service support in their everyday lives. METHODS:A hermeneutic phenomenological design was employed. Twelve medical aid recipients in Gangwon Province, South Korea, who had been discharged and received home-based services for at least three months, were purposively recruited. One or two semi-structured interviews were conducted with each participant, recorded, transcribed verbatim, and analyzed using interpretative phenomenological analysis. RESULTS:Analysis identified six themes: (1) Seeking survival in unfamiliar daily life after discharge and re-experiencing one's existence; (2) Restoring autonomy and achieving physical independence through home-based medical aid services; (3) Re-experiencing the warmth of relationships and recognition of existence through care; (4) Repeated disconnection and the re-encounter with the sense of being "alone"; (5) Longing for continuity and stability in care; and (6) Accepting changed life and reframing the self and the system. CONCLUSION:Home-based medical aid services helped vulnerable medical aid recipients sustain life at home by supporting daily independence, emotional reassurance, relational recognition, and participants' perceptions of quality of life. Nurses and case managers are central to ensuring continuity and stability of care, emphasizing the need for community-integrated approaches to reduce disparities and sustain life at home.
Background:Candidiasis remains a major global health challenge, with rising incidence and antifungal resistance complicating management. This multicenter survey aimed to describe diagnostic and therapeutic management practices of ICU physicians in France for high-risk invasive candidiasis cases, using randomized clinical case simulations distributed to French ICU physicians via email and academic congresses. Results:A total of 75 physicians completed 283 cases. Overall, clinical suspicion justified diagnostic investigation in 72.1% of cases. Key factors associated with the decision to test for invasive candidiasis included post-abdominal surgery (OR = 3.92; p = 0.002), central venous catheter (OR = 2.28; p = 0.04), parenteral nutrition (OR = 2; p = 0.027), prolonged antibiotic exposure (OR = 1.90; p = 0.041), and physician experience >10 years (OR = 2.79; p = 0.014). Echinocandins were the preferred first-line treatment (88.2%; n = 120/136). Their use was guided by clinical guidelines (78.3%), pharmacokinetic/pharmacodynamic profile (38.3%), SOFA score (29.2%), patient status (25.8%), and immunosuppression (20%). De-escalation to azoles upon documented mycological susceptibility occurred in 87.5% of cases initially treated with an echinocandin and 60.0% of cases initiated on amphotericin B, primarily after 5 days of treatment (51.2%; n = 64). Conclusions:Patient severity, immunosuppression, and catheter presence were the main factors guiding antifungal treatment decisions Management of confirmed invasive candidiasis was largely consensual among respondents, whereas empirical treatment decisions were heterogeneous. While conclusions are primarily reflective of practice patterns within specialized university hospital centers, the INSPIRE survey highlights the need for enhanced training, broader access to rapid diagnostics, and improved decision-support systems to better harmonize clinical practices.
Background:Prior corticosteroid use is linked to influenza-associated pulmonary aspergillosis (IAPA) in critically ill patients, yet the dose-response relationship remains unclear. Methods:In this multicenter emulated target trial across 48 ICUs in Central China (January 2023-June 2025), we included critically ill, non-neutropenic adults with influenza. Using inverse probability of treatment weighting (IPTW) and restricted cubic splines, we modeled the dose-response association between pre-ICU corticosteroid exposure and IAPA, identifying risk thresholds via segmented regression. Effect modification by pre-specified patient characteristics was further assessed. Results:Among 2763 patients (74.2% exposed to corticosteroids; median dose 35 mg dexamethasone-equivalent), 191 (6.9%) developed IAPA during their ICU stay. Pre-ICU corticosteroid exposure was independently associated with IAPA (weighted HR = 2.11; 95% CI 1.25-3.56). A non-linear, J-shaped dose-response relationship was identified (P < 0.001). Risk increased continuously, with a 50% increase at 43.4 mg and doubling at 51.4 mg, followed by a steep inflection point at 63.7 mg (95% CI 62.8-64.7). Higher SOFA scores (>7) significantly amplified per-dose risk (P < 0.001), lowering thresholds to 35.2 mg for 50% increase and 39.5 mg for doubling. Conclusions:Pre-ICU corticosteroid exposure is associated with a nonlinear, dose-dependent increase in IAPA risk. Cumulative doses approaching 40-50 mg warrant heightened vigilance, particularly in severely ill patients. These findings support individualized, dose-aware corticosteroid stewardship in severe influenza.
Background:No gold standard currently exists to evaluate fluid status during continuous renal replacement therapy (CRRT). We aimed to describe systemic venous congestion by using venous excess ultrasound (VExUS) and pulmonary congestion by lung ultrasound (LUS) in critically ill patients with acute kidney injury (AKI) who received CRRT. Methods:This was a single-centre prospective cohort study. Adult patients with AKI undergoing CRRT underwent serial ultrasound assessments on Day 1 and 3 by two independent operators. VExUS score and its individual components, including an inferior vena cava (IVC) diameter (≥2 cm), hepatic vein, portal vein, as well as intrarenal vein Doppler flow patterns, and 6-zone lung ultrasound (LUS) scores (ranged from 0 to 20 points), were collected. An exploratory modified VExUS (mVExUS) grading was derived by incorporating an IVC distensibility index (<18%) or collapsibility index (<50%). Venous congestion was defined as VExUS or mVExUS Grade ≥2. The primary descriptive outcome was the prevalence of venous congestion and serial LUS score changes. The principal clinical endpoint was the association between ultrasound parameters and 90-day mortality (NCT06254703). Results:Among 100 enrolled patients (median age 66 years, male 58%), baseline venous congestion was documented in 20% by VExUS score and 35% by mVExUS scores. The median LUS score was 4 (interquartile range 1-9). Baseline VExUS Grade 2-3 (Log rank p = 0.049) and mVExUS Grade 2-3 (Log rank p = 0.01) were associated with lower 90-day survival. In time-updated Cox models after adjustment for baseline Sequential Organ Failure Assessment score, hepatic vein Doppler Grade 2-3 (adjusted hazard ratio (aHR) 1.78; 95% confidence interval (CI) 1.05-3.01, p = 0.01) and higher LUS scores (aHR 1.04; 95% CI 1.001-1.08, p = 0.04) were independently associated with 90-day mortality. Unchanged or worsening LUS scores between Day 1 and Day 3 were associated with a significantly higher cumulative fluid balance compared to improved scores (p = 0.01). Conclusion:Systemic and pulmonary congestion assessed by multiorgan point-of-care ultrasound was associated with increased 90-day mortality in AKI patients receiving CRRT. Future studies should explore the utility of these tools in guiding individualised fluid management during CRRT.
Background:Ventilator-associated pneumonia (VAP) remains an important complication in mechanically ventilated patients in intensive care units (ICUs). Early subglottic microleakage may precede overt infection but remains difficult to detect at the bedside. Airway tracers and biochemical biomarkers have been proposed as bedside tools for detecting upstream microleakage and predicting downstream VAP, but their diagnostic value remains uncertain because studies differ in sampling matrices, thresholds, reference standards, and endpoints. Methods:Six databases were systematically searched from inception to 1 March 2026. Studies evaluating airway tracers or biomarkers in critically ill adults receiving invasive mechanical ventilation or with artificial airways were included under a dual-endpoint framework, comprising upstream microleakage or aspiration-related event detection and downstream VAP prediction. Study data were extracted, and risk of bias was assessed using the QUADAS-2 tool. For markers with sufficient clinical and methodological comparability, quantitative analyses included bivariate random-effects pooling, variance decomposition, stepwise sensitivity analyses, and Bayes' theorem-based post-test probability projection. Results:Sixteen studies were included. Blue-dye-based visual methods were summarized descriptively because the available studies represented distinct aspiration paradigms and did not meet the criteria for quantitative pooling. FEES-validated tracheostomy studies reported relatively high sensitivity for swallowing-related transglottic aspiration, whereas enteral-tracer or reflux-aspiration monitoring studies were limited by surrogate reference standards and/or low visual detectability for continuous, low-volume microleakage. One mechanically ventilated enteral-feeding cohort was retained as narrative evidence only because it did not provide a direct 2 × 2 diagnostic accuracy comparison of visual blue-dye detection against the microsphere reference standard. For VAP prediction, airway α-amylase showed a pooled sensitivity of 78.1%, specificity of 70.3%, and an area under the curve of 0.811. Conclusions:Current airway tracers and biomarkers do not appear suitable as standalone diagnostic triggers for VAP. However, airway α-amylase may have potential as a negative-predictive screening tool. Future research should standardize volumetric airway sampling and prospectively validate clinically actionable rule-out algorithms to support early antimicrobial de-escalation.
Background:Whether or not a direct tracheostomy without any prior weaning attempt is beneficial in patients intubated for Guillain-Barré syndrome (GBS) remains to be determined. Our objective was to determine whether direct tracheostomy results in earlier or later ventilator weaning compared to standard weaning. Methods:Multicenter, retrospective cohort study including all patients intubated for GBS over a 10-year period (2014-2023). We compared patients having undergone direct tracheostomy without any prior weaning attempt with those having undergone standard weaning (spontaneous-breathing trial or extubation attempt). We also compared direct tracheostomy with tracheostomy after weaning failure. The primary outcome was the proportion of patients alive and free from mechanical ventilation 28 days after weaning initiation. Results:Overall, 221 patients (45%) underwent direct tracheostomy and 273 (55%) standard weaning. Compared to patients with standard weaning, those with direct tracheostomy were less likely to be alive and free from mechanical ventilation at day 28 (43% vs. 83%, p < 0.001). Using G-computation to estimate the marginal causal effect of the weaning strategy, standard weaning was more effective than direct tracheostomy in reducing the risk of remaining under mechanical ventilation at day 28: -39.5% [95% Confidence Interval, -47.3% to -31.5%]. Even when compared to patients having undergone tracheostomy after weaning failure, those with direct tracheostomy were less likely to be alive and free from mechanical ventilation 28 days after the tracheostomy procedure. Interpretation:A direct tracheostomy without any prior weaning attempt might significantly delay the ventilator weaning process in patients intubated for GBS. Clinical Trial Registration:NCT07022028.
Background:While intensive care unit (ICU) capacity remains constrained, the number of older patients receiving resource-demanding ICU treatment continues to rise. Yet, long-term outcomes and post-critical illness frailty trajectories remain poorly characterized. We examined long-term mortality and frailty trajectories, and their associations with clinical characteristics and ICU treatment intensity. Methods:In this prospective, observational study across five Norwegian hospitals representing all health regions, we included patients aged ≥65 years who required invasive mechanical ventilation for ≥24 h. Frailty was assessed using the Clinical Frailty Scale (CFS) at baseline and at 3 and 12 months, categorized as robust (CFS 1-3), prefrail (CFS 4) and frail (CFS ≥ 5). Multiple regression models were used to examine associations between frailty trajectories and mortality, with baseline frailty, clinical characteristics and potentially modifiable aspects of ICU treatment. Results:346 patients were included. Mean age was 74 years (± 6), and 98 % lived at home before admission. The median ICU length of stay was 8 (IQR 9) days. Total mortality was 52 %, with most deaths occurring before hospital discharge. In the survivors, the prevalence of frailty increased from 23 % (79/346) at baseline, to 47 % (81/174) at three months. Between the three- and 12- month follow-up, CFS scores remained unchanged in 71 % (108/153), improved in 19 % (29/153) and deteriorated in 10 % (15/153). By 12 months 86 % (132/153) had returned home, though 32 % (49/153) required home care compared to 10 % pre-admission. Baseline CFS showed the strongest association with 12-month mortality (Risk Ratio 1.46, p < 0.001). Age (Risk Ratio 1.22, p < 0.001) and SOFA score on the first day after intubation (Risk Ratio 1.14, p < 0.01) were also significant predictors, whereas comorbidity was not. Conclusions:In elderly ICU-patients long-term frailty is deranged, and baseline CFS is closely associated with mortality. However, a small group of patients had a transitory decline in frailty at three months follow-up and then improved. Intervention studies targeting modifiable factors associated with long-term functional decline and mortality are warranted. Trial registration:ClinicalTrials.gov (NCT06012942).
CAR T-cell therapy carries significant risks, including ICANS. There is limited data on ICANS presentation and outcomes in patients admitted to ICU and it is still challenging to predict those who will have severe ICANS. This is a pre-planned substudy of an international, multicenter, observational cohort study of 241 CAR T-cell recipients for hematological malignancies, admitted to the ICU, focusing on those who developed ICANS. We aimed for a detailed description of symptoms and hierarchical clustering analysis was used to identify distinct patterns of neurological symptom presentation. ICANS was identified in 100 patients (41.5%), median age of 61 years. Most patients (93%) had non-Hodgkin lymphoma. Severe ICANS occurred in 38% of patients, associated with longer duration of symptoms (p = 0.02). On the whole cohort, the median duration of neurological symptoms was 5 (IQR 1-8) days and was also longer for patients with isolated ICANS (median of 16 days (IQR 11-24, p = 0.001)). Hierarchical clustering revealed four distinct clusters with minimal symptom overlap: Cluster 1: Mild or no symptoms, primarily confusion (11.2%); Cluster 2: High incidence of confusion (78.9%) and drowsiness (47.4%), with significant risks of seizures (42.1%) and coma (21.1%); Cluster 3: Predominantly tremor (75%) and attention deficit (37.5%); Cluster 4: High incidence of aphasia (70.3%), dysgraphia (37.8%), and disorientation (27%). The clustering of neurological symptoms was statistically significant (p < 0.001). This study provides a detailed characterization of ICANS, highlighting distinct patterns of neurological symptoms. These findings could inform clinicians, particularly regarding the risk and timing of ICU admission.
Acute kidney injury (AKI) is a common and harmful syndrome associated with sepsis. It is difficult to predict and has an adverse impact on both short- and long-term prognosis. Two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated for predicting moderate and severe AKI and improving the recognition of organ failure in critically ill patients with sepsis. We aimed to evaluate the performance of these markers for predicting sepsis-related AKI and its evolution in a cohort of patients admitted to the Emergency Department with infectious disease and high risk of sepsis. This single-centre, prospective, observational study included adult patients presenting to the Emergency Department (ED) with suspected infection. Patients were included in the study if they had a National Early Warning Score 2 (NEWS 2) of 3 or higher. Three blood samples were drawn during the first 24 h, and we defined AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. The first urine sample during ED stay was collected for urinary [TIMP-2]•[ IGFBP7] determination. Higher admission levels of urinary [TIMP-2]•[IGFBP7] were associated with the development of AKI moderate-severe within 24 h (adjusted Odds Ratio 1.24; 95% Confidence Interval 1.07-1.43; p < 0.01). The biomarker showed only modest overall discrimination (AUC 0.67). Still, predefined cut-offs revealed complementary diagnostic roles: low values (<0.3) may help exclude AKI with a negative predictive value of 0.86, whereas the highest values (>2.0) increase its likelihood. Creatinine trajectories and inflammatory profiles were largely similar across groups, except for elevations in IL-10 and IL-1RN in high-risk patients. In conclusion, urinary [TIMP-2]•[IGFBP7] measured on presentation to the ED had only moderate discrimination for sepsis-associated AKI. However, values (<0.3 units) could help to rule out the risk of developing AKI, while values >2.0 indicated high risk.
Background:Right ventricular (RV) injury is a frequent complication in patients with acute respiratory distress syndrome (ARDS), yet its prevalence and prognostic significance remain uncertain. The main objective of this systematic review and meta-analysis was to evaluate the association between RV injury and mortality in patients with ARDS. The secondary objectives were to determine the prevalence of RV injury and to assess the impact of both COVID-19 status and the definition of RV injury on mortality. Methods:From January 2013 to December 2024, we searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for all studies including adult patients with ARDS according to the Berlin definition, which reported mortality according to the presence or absence of RV injury. Results:Twenty-three studies including 3,977 patients with ARDS were analyzed. The pooled prevalence of RV injury was 30% (95% confidence intervals (CI) 23-38%), ranging from 6% to 56% across studies depending on the definition used, and did not differ between COVID-19 (33%, 95%CI 22-47%) and non-COVID-19 (25%, 95%CI 21-29 %) patients. RV injury was associated with increased ICU mortality in unadjusted analyses (random-effects odds ratio (OR) 2.49, 95%CI 1.81-3.42; I2 = 56%) and in adjusted analyses (aOR 2.37, 95%CI 1.24-4.51, I2 = 42%; adjusted hazard ratio (aHR) 2.64, 95%CI 1.60-4.37, I2 = 24%). This association remained consistent across subgroups based on COVID-19 status and RV injury definition, and across sensitivity analyses excluding patients receiving venovenous extracorporeal membrane oxygenation and low to moderate quality studies. Conclusions:RV injury is common in patients with ARDS and is consistently associated with increased mortality, irrespective of the definition used. Further studies enrolling consecutive patients, with standardized and repeated echocardiographic assessment of RV function, are needed to establish causal inference. Trial registration:CRD42024568063 and date of registration: 22/07/2024.
Background:Fluid overload is common in critically ill patients and is associated with worse outcomes. Diuretics are the mainstay of active fluid removal in patients with preserved renal function. The optimal diuretic strategy for fluid removal remains uncertain. Methods:We conducted a systematic review and Bayesian random-effects network meta-analysis of randomized controlled trials comparing two or more diuretic strategies for fluid removal in critically ill adults. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials via Ovid, as well as trial registries, from inception to November 20, 2025. Two reviewers independently extracted data and assessed risk of bias using ROBUST-RCT. Certainty of evidence was evaluated using the GRADE approach for network meta-analysis. Treatment effects were summarized as odds ratios (ORs) or mean differences (MDs) with 95% credible intervals (CrIs). Results:Twenty-six randomized controlled trials involving 1,652 participants were included. Evaluated interventions included bolus loop diuretics (19 studies), continuous loop infusion (15 studies), oral loop diuretics (5 studies), and loop diuretics combined with tolvaptan (8 studies), spironolactone (3 studies), thiazides (2 studies), acetazolamide (1 study), or triamterene (1 study). Compared with bolus loop diuretics, continuous loop infusion had an uncertain effect on mortality (OR 1.26; 95% CrI 0.62 to 2.55; very low certainty) and may increase ICU length of stay (MD 1.56 days; 95% CrI -0.02 to 3.16; low certainty). Tolvaptan monotherapy may reduce acute kidney injury compared with bolus or continuous loop diuretics (OR 0.12; 95% CrI 0.01 to 0.87; low certainty), although no studies evaluated its effect on the need for renal replacement therapy. For most other comparisons and outcomes, the certainty of evidence was low or very low. Conclusions:Available evidence comparing diuretic strategies for fluid removal during ICU-level care is limited, clinically heterogeneous, and derived largely from heart failure and post-cardiovascular surgery populations. Bolus loop diuretics were at least comparable to alternate diuretic strategies for patient important outcomes in critically ill adults, but this was based mostly on low or very low certainty evidence. Tolvaptan monotherapy may decrease acute kidney injury, but its effect on subsequent need for RRT and mortality remains uncertain.
Background:Utility of serum creatinine (SCr) and urine output (UO) is limited for real-time assessments of functional integrity and guiding kidney replacement therapy (KRT) decisions in acute kidney injury (AKI). Proenkephalin A 119-159 (PENK) may overcome these limitations. We evaluate PENK's use for AKI staging, assessment of residual kidney function during KRT, and assessment of liberation failure. Methods:Prospective, real-world study in 1,436 critically ill patients at Heidelberg University Hospital, including a subgroup of 138 patients receiving KRT for liberation analyses. Plasma PENK was measured from admission to discharge. AKI was defined by KDIGO criteria; biomarker kinetic, ROC analyses and binary logistic regression models were performed. KRT liberation was considered successful if no re-initiation occurred within >5 days. Results:Of 1,436 patients, 621 (43.2%) developed AKI. Acute KRT was required in 12.6%, 40.9% of whom were successfully liberated, 24.3% failed, and 31.5% underwent no liberation attempt (3.3% lost to follow up). PENK rose with AKI stages and, unlike SCr/UO, distinguished stage 3 AKI with versus without acute KRT requirements, and differentiated acute from chronic KRT patients even under ongoing KRT. From KRT start, mean PENK levels increased progressively whereas SCr decreased under treatment. Later, PENK declined around successful liberation, with lower values compared to cases with liberation failure. PENK was the strongest, independent predictor of KRT liberation failure, outperforming SCr. A PENK cut-off of ≥250 pmol/L provided >90% specificity for liberation failure. Combining PENK and UO, further improved risk stratification. Conclusions:PENK may reflect kidney integrity independent of KRT, enhance residual kidney function assessment, and may aid prediction of KRT liberation failure, warranting multicenter validation.
Venous congestion is an important pathophysiological mechanism impacting organ function in critically ill patients. However, congestion physiology is complex, can affect multiple organ systems, and is subject to change rapidly over time. Contemporary multimodal assessment integrates both traditional approaches and emerging technologies to refine our understanding and improve clinical evaluation of this dynamic process. In this review, we explore how combining various ultrasound assessments can enhance the evaluation of congestion in critically ill patients. Topics include diastolic function evaluation with echocardiography, the Venous Excess Ultrasound (VExUS) assessment, and lung ultrasound.
