Ter Horst S, van Oosten J, Laros R
… +15 more, Sukkar B, van Everdink J, di Mauro A, Alawi A, de Vries W, Ter Voert M, Koliaki I, Slot A, van der Wiel D, Lu J, Colavolpe L, Blanca D, Bouma HR, Ter Maaten JC, Olgers TJ
J Crit Care
· 2026 Aug · PMID 41830860
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BACKGROUND: Initial fluid resuscitation is central to sepsis management, yet excessive fluids may exceed a patient's fluid tolerance, increasing the risk of fluid overload and organ dysfunction. The Venous Excess Ultraso...BACKGROUND: Initial fluid resuscitation is central to sepsis management, yet excessive fluids may exceed a patient's fluid tolerance, increasing the risk of fluid overload and organ dysfunction. The Venous Excess Ultrasound (VExUS) score allows noninvasive bedside assessment of venous congestion, but its prevalence and predictive value in the emergency department (ED) are unclear. METHODS: We analyzed prospectively collected data from the Acutelines data-biobank (University Medical Center Groningen, Netherlands). Adults with suspected sepsis requiring initial fluid resuscitation underwent VExUS assessments, including inferior vena cava and organ-specific Doppler measurements, within three hours of ED admission. The primary outcome was clinical fluid overload within 72 h, defined as positive fluid balance plus ≥10% weight gain, pulmonary edema on imaging, or loop diuretic use. Associations were analyzed using logistic and mixed-effects regression. RESULTS: Among 103 patients, 34 (33%) developed clinical fluid overload. At ED admission, 75% had VExUS grade 0, 22% grade 1, and 3% grade ≥ 2. At baseline, VExUS>0 and abnormal hepatic venous Doppler flow were associated with fluid overload within 72 h (aOR 3.66, 95% CI 1.23-11.55; p = 0.022 and 4.20, 95% CI 1.21-16.38; p = 0.028, respectively). In repeated-measures analyses, VExUS>0 and abnormal intrarenal venous Doppler flow were associated with next-day fluid overload. CONCLUSION: In patients with suspected sepsis, mild venous congestion was independently associated with clinical fluid overload within 72 h. Abnormal hepatic and intrarenal flow patterns may provide additional information on venous congestion. Early, serial VExUS assessments may detect fluid intolerance and support individualized fluid management.
Tang X, Du X, Fang Y
… +9 more, Jia Z, Gao Y, Liu H, Huang D, Ji Y, Liu J, Li Y, Xie K, Wang G
J Crit Care
· 2026 Aug · PMID 41818952
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BACKGROUND: Accurate nociception assessment in nonverbal, mechanically ventilated ICU patients remains a significant clinical challenge. This study evaluated the utility of the qNOX index, an EEG/EMG-derived metric, for...BACKGROUND: Accurate nociception assessment in nonverbal, mechanically ventilated ICU patients remains a significant clinical challenge. This study evaluated the utility of the qNOX index, an EEG/EMG-derived metric, for detecting nociceptive responses during routine ICU procedures (endotracheal suctioning and turning), compared to traditional measures such as the Bispectral Index (BIS). METHODS: In this prospective observational study, 102 mechanically ventilated patients were enrolled, with 323 pain assessments performed. Mean (qNOXm) and instantaneous (qNOXi) qNOX indices, alongside BIS and vital signs, were continuously recorded before, during, and after procedures. The Behavioral Pain Scale (BPS) was assessed at predefined time points. Primary outcomes included qNOX's discriminative ability (ROC analysis, AUC), correlation with BPS (Spearman's test), and predictive value (linear mixed-effects model analyses). Optimal thresholds were determined using the Youden index and restricted cubic spline (RCS) analysis. RESULTS: qNOX demonstrated numerically higher discriminatory performance compared to BIS, with higher specificity during suctioning (77.8% vs. 73.3%) and turning (80.6% vs. 64.5%). Area Under the Curve (AUC) values for qNOX were consistently greater across sedation levels (light sedation: 0.735-0.747 vs. BIS 0.610; deep sedation: 0.729-0.753 vs. BIS 0.698). qNOX correlated strongly with BPS (qNOXm: r = 0.53; qNOXi: r = 0.52; both P < 0.0001) and exhibited a nonlinear relationship (P < 0.001). Linear mixed-effects model analyses confirmed qNOX's predictive value, with each unit increase in qNOXi associated with a 11.2% rise in the odds of pain (OR: 1.112, 95% CI: 1.075-1.152). CONCLUSION: qNOX exhibits a significant correlation with the BPS during nociceptive procedures in mechanically ventilated ICU patients. These findings position qNOX as a promising, objective complementary tool for real-time nociception monitoring in critically ill patients who are deeply sedated, paralyzed, or neurologically impaired.
Ningxiang Q, Fahang Y, Feng L
… +7 more, Jing W, Xia Y, Xingguo W, Wei W, Xuefeng W, Xi P, Liang W
J Crit Care
· 2026 Aug · PMID 41806777
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OBJECTIVE: This study aimed to develop and validate machine learning (ML) models for predicting the prognosis of status epilepticus (SE) patients with multisystem complications. METHODS: We developed predictive models us...OBJECTIVE: This study aimed to develop and validate machine learning (ML) models for predicting the prognosis of status epilepticus (SE) patients with multisystem complications. METHODS: We developed predictive models using six ML algorithms: least absolute shrinkage and selection operator (LASSO) logistic regression, k-nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost). We systematically evaluated the prognostic performance of these models against established clinical scores. Specifically, we compared them with the Status Epilepticus Severity Score (STESS), the Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Imaging Abnormalities-Tracheal Intubation (ENDIT) score, and the Epidemiology-based Mortality Score in Status Epilepticus (EMSE). RESULTS: A total of 169 patients with SE were included in this study. In the test dataset, the areas under the curve (AUC) of the models were 0.660 for DT, 0.644 for RF, 0.663 for SVM, 0.689 for KNN, 0.825 for XGBoost, and 0.610 for LASSO logistic regression.The SHAP analysis revealed the top ten predictors contributing to the XGBoost model: hypoalbuminemia, nutritional risk score, age, ventilation duration, NCSE, GCS score, duration of impaired consciousness, creatinine level, APACHE II score, and CCI. CONCLUSION: Compared with the other models and scoring systems, XGBoost demonstrated superior predictive performance, suggesting its potential utility for the early identification of high-risk patients and timely clinical intervention. Hypoalbuminemia was identified as the most important prognostic factor, highlighting the critical role of systemic injury in determining adverse outcomes in SE patients treated within the neurocritical care setting.
Highsmith EA, Arellano D, Bash K
… +11 more, Bielewicz BJ, Dehne LM, Erich BJ, Fjeld K, Garcia I, Hatton C, Li M, Mores K, Sacha GL, Saldana S, Esteves AM
J Crit Care
· 2026 Aug · PMID 41780229
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OBJECTIVES: To summarize and provide clinical insights on the most impactful publications related to critical care pharmacotherapy in 2025. METHODS: A systematic search of PubMed/Medical Literature Analysis and Retrieval...OBJECTIVES: To summarize and provide clinical insights on the most impactful publications related to critical care pharmacotherapy in 2025. METHODS: A systematic search of PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE) was conducted between January 1, 2025 and October 5, 2025. Inclusion criteria consisted of randomized controlled trials with prospective study designs evaluating a critically ill adult patient population receiving pharmacotherapeutic interventions and reporting clinical endpoints. A multi-disciplinary and geographically diverse group of critical care clinicians was assembled and an a-priori defined three-round modified Delphi process was performed, with a focus on the publications determined to be the most impactful or novel. RESULTS: The systematic search yielded a total of 1609 articles for review and 1566 were excluded, leaving 43 articles to be included in the modified Delphi process. In each round, articles were scored based on their overall contribution to the literature and novelty with articles achieving a score at or above the median progressing to the next modified Delphi round. The six included articles are summarized. Article topics include alternative sedation options in mechanically ventilated patients, thrombolytic usage in acute ischemic strokes, management of coagulopathic bleeding following cardiac surgery, and use of corticosteroids in severe community-acquired pneumonia. CONCLUSIONS: This concise review identified, summarized, and offered insights on the most relevant critical care pharmacotherapy publications in the year 2025.
Ice S, Pellegrino B, Diab A
… +5 more, Parravani A, Poling M, Sakhuja A, Kashani K, Shawwa K
J Crit Care
· 2026 Aug · PMID 41780228
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BACKGROUND: Data on discontinuing continuous kidney replacement therapy (CKRT) in acute kidney injury (AKI) remain limited. We investigated whether a standardized approach improved successful CKRT discontinuation. METHOD...BACKGROUND: Data on discontinuing continuous kidney replacement therapy (CKRT) in acute kidney injury (AKI) remain limited. We investigated whether a standardized approach improved successful CKRT discontinuation. METHODS: This was a pilot prospective study of patients with AKI requiring CKRT in the intensive care unit between 7/2021-3/2024. In the intervention arm, a standardized form was completed daily to guide discontinuation of CKRT. Successful discontinuation was defined as being free from kidney replacement therapy for seven consecutive days. A 2-h creatinine clearance and cystatin C were done at the time of CKRT discontinuation in both arms. RESULTS: We screened 373 patients, 32 were included in the standard care and 35 in the intervention arm after satisfying the inclusion criteria. Patients in the intervention arm were more likely to be older (65 vs. 57 years) and require more norepinephrine (0 vs. 0.11 μg/kg/min) on the first day of CKRT compared to standard care. Among survivors at day 7 after CKRT discontinuation, successful discontinuation occurred in 16/23 (69.6%) in the standard care arm versus 19/26 (73.1%) in the intervention arm. When discontinuation was encouraged, CKRT was stopped in 26/35 (74%); when not encouraged, CKRT continued in 53/59 (90%). Performances of cystatin C alone or in combination with 2-h creatinine clearance in predicting successful discontinuation was fair. The best performance was observed in the intervention cohort, AUROC of 0.8 (95% CI, 0.57-0.99). CONCLUSION: A standardized approach did not improve the rate of successful CKRT discontinuation. Future studies are needed before biomarkers are used in decision-making.
Regaieg K, Alila I, Kallel M
… +2 more, Khaled A, Chapuis L
J Crit Care
· 2026 Aug · PMID 41775208
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Admission decisions to intensive care units (ICUs) are often presented as binary-patients either require intensive care or they do not. In daily practice, however, a substantial proportion of patients fall into an interm...Admission decisions to intensive care units (ICUs) are often presented as binary-patients either require intensive care or they do not. In daily practice, however, a substantial proportion of patients fall into an intermediate category in which admission is neither clearly indicated nor clearly inappropriate. This article describes and conceptualises this intermediate space as the ICU "gray zone". Within this gray zone, admission decisions depend not only on clinical severity, but also on contextual factors such as bed availability, staffing levels, team experience, organizational constraints, timing of decision-making, and patient preferences. Intensivists routinely face practical questions regarding postoperative admissions, pre-hospital referrals, inter-hospital transfers, or the use of time-limited trials of intensive care. These decisions are often conditional, reversible, and subject to reassessment as new information becomes available. The article highlights the ethical importance of proportionality of care, respect for patient autonomy, and the role of communication when ICU admission is not considered appropriate. Particular attention is paid to the impact of decision timing, including night shifts, weekends, and holiday periods, when uncertainty and resource limitations are greater. Finally, the COVID-19 pandemic is discussed as an illustrative example of the dynamic and seasonal nature of the ICU gray zone, revealing how admission thresholds evolve in response to system pressure. Recognising the ICU gray zone as an ethical concept helps make explicit the realities of critical care decision-making and supports more transparent, context-aware, and patient-centred admission practices.
Aissaoui Y, Belhadj A, Eddakya W
… +9 more, Bencharfa B, Bouchama A, Didi M, Elbaraka H, Fassiki N, Myatt I, Qamouss Y, Leone M, Abouqal R
J Crit Care
· 2026 Aug · PMID 41759300
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BACKGROUND: Cardiovascular dysfunction in sepsis is heterogeneous and contributes to poor outcomes. Hemodynamic phenotyping may delineate pathophysiologically distinct subgroups with implications for prognosis and indivi...BACKGROUND: Cardiovascular dysfunction in sepsis is heterogeneous and contributes to poor outcomes. Hemodynamic phenotyping may delineate pathophysiologically distinct subgroups with implications for prognosis and individualized management. No studies have evaluated such phenotypes in African intensive care units (ICUs). We aimed to explore cardiovascular phenotypes in patients with sepsis using clinical and echocardiographic variables. METHODS: We conducted a post-hoc exploratory analysis of two prospective ICU cohorts. Adults with sepsis and acute circulatory failure in whom fluid responsiveness was assessed were included. All patients underwent transthoracic echocardiography (TTE) within 24 h of ICU admission. Eight hemodynamic variables-heart rate (HR), diastolic arterial pressure (DABP), mean arterial pressure (MABP), left-ventricular ejection fraction (LVEF), LVOT velocity-time integral (VTI), lateral e', E/e', and tricuspid annular plane systolic excursion (TAPSE)-were standardized and clustered using k-means. Thirty-day ICU outcomes were evaluated with Kaplan-Meier curves and Cox models. RESULTS: Seventy-eight patients were analyzed. Three cardiovascular phenotypes emerged: (i) Hemodynamically optimized (n = 25): lower HR, near-normal MABP/DABP, higher VTI and LVEF; (ii) Vasoplegic (n = 27): low MABP/DABP with preserved systolic indices; and (iii) Myocardial depressed (n = 26): reduced VTI, LVEF, TAPSE, and lower e'. Thirty-day ICU mortality differed significantly across phenotypes (28% vs 59% vs 69%; p < 0.001). In the adjusted Cox model (reference = hemodynamically optimized), the Myocardial depressed phenotype had a higher hazard of ICU death (HR 2.90; 95% CI 1.24-6.79; p = 0.014). CONCLUSIONS: In this first echocardiography-informed phenotyping study from an African ICU, early cardiovascular phenotypes were identifiable and associated with distinct 30-day outcomes. TRIAL REGISTRATION: NCT05538637 and NCT06313671.
Akman TS, Akdemir NU, Colak OY
… +3 more, Isevi M, Kucuk AO, Ulger F
J Crit Care
· 2026 Aug · PMID 41759299
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PURPOSE: As the global climate crisis accelerates, reducing the environmental footprint of healthcare systems has become imperative. Intensive Care Units (ICUs) are among the most carbon-intensive hospital settings, yet...PURPOSE: As the global climate crisis accelerates, reducing the environmental footprint of healthcare systems has become imperative. Intensive Care Units (ICUs) are among the most carbon-intensive hospital settings, yet data from upper-middle-income countries remain limited. This national survey aimed to evaluate self-reported awareness, current practices, perceived barriers, and educational needs related to environmental sustainability within the Green ICU framework among ICU physicians in Turkey. METHODS: A nationwide, cross-sectional online survey was conducted between 15 May and 15 October 2025 among adult ICU physicians in Turkey. The 30-item questionnaire, developed based on current literature, assessed demographics, self-reported awareness of the Green ICU concept, institutional sustainability practices, perceived barriers, and future priorities. Descriptive statistics and chi-square tests were used to analyze associations between self-reported awareness and demographic and professional characteristics. RESULTS: A total of 325 physicians participated; 57.2% were female and 84.3% worked in university or training hospitals. Only 12.3% reported high self-reported awareness of the Green ICU concept, 1.8% had received formal training, and 89.7% expressed willingness to receive education. Structured Green ICU practices were reported by only 3.7% of respondents. Waste management was perceived as the most commonly implemented practice (92.9%), whereas energy-efficiency technologies were reported by 14.5% of respondents. The largest importance-implementation gaps were observed for energy-efficient devices, staff training, and eco-friendly cleaning products. Major perceived barriers included insufficient knowledge and training (84.3%), lack of staff support (60.6%), high costs (58.5%), and inadequate technological infrastructure (51.1%). Higher self-reported awareness was associated with older age, longer ICU experience, higher professional role, and institution type (all p < 0.01). CONCLUSIONS: Despite strong motivation among ICU physicians, Green ICU practices remain limited, reflecting educational, institutional, and infrastructural barriers. Expanding national coordination, strengthening institutional sustainability strategies, and implementing structured training programs may be important for narrowing the implementation gap and integrating environmental sustainability as a core component of high-quality intensive care.
Castro R, Retamal J, Hernández G
… +2 more, Kattan E, Pinsky MR
J Crit Care
· 2026 Jun · PMID 41747522
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The vascular waterfall (VW) concept describes a key mechanism of blood flow autoregulation, linking arterial critical closing pressure (Pcrit) to mean systemic filling pressure (Pmsf). This pressure gradient defines tiss...The vascular waterfall (VW) concept describes a key mechanism of blood flow autoregulation, linking arterial critical closing pressure (Pcrit) to mean systemic filling pressure (Pmsf). This pressure gradient defines tissue perfusion pressure (Pa - Pcrit) and supports a framework for interpreting circulatory dynamics and blood flow autoregulation in health and disease. This review explores the historical development, physiological foundations, clinical implications, and future directions of the VW model in critical care. Originating from Starling's resistor model, the VW arises when surrounding pressure, whether from vasomotor tone or interstitial forces, exceeds intraluminal arterial pressure, defining a Pcrit, causing flow to become independent of downstream pressure. In such conditions, Pcrit functions as the effective backpressure. The highly compliant capillary bed accommodates low inflow pressures, often 5-10 mmHg above Pmsf. Bedside techniques, such as inspiratory hold maneuvers, enable estimation of Pcrit and Pmsf as global circulatory parameters. In vasoplegia, such as sepsis, reduced vascular tone lowers Pcrit, often approaching Pmsf, which abolishes the VW and impairs autoregulation. Vasopressors may restore perfusion only if Pcrit increases more than Pmsf. Similarly, in pulmonary circulation, VW physiology helps explain how elevated alveolar and pleural pressures during mechanical ventilation, particularly with high PEEP, affect venous return and right ventricular load, with implications for ARDS management. Looking forward, non-invasive measurement of Pcrit, integration with continuous hemodynamic monitoring, and predictive modeling may enable real-time VW-guided therapy. By bridging macro- and microcirculatory physiology, the VW concept offers a promising basis for precision hemodynamic interventions in critically ill patients.
Spano S, Maeda A, Randhawa M
… +13 more, Hikasa Y, Pattamin N, Kitisin N, Nübel J, Caroli A, Eastwood G, Peck L, Young H, Hogan C, Bellomo R, Warrillow S, Neto AS, Chaba A
J Crit Care
· 2026 Jun · PMID 41747521
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In intensive care unit (ICU) patients receiving unfractionated heparin (UFH) infusion, activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-Xa) levels have limited correlation and significant discordance...In intensive care unit (ICU) patients receiving unfractionated heparin (UFH) infusion, activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-Xa) levels have limited correlation and significant discordance. We aimed to test whether thromboelastographic-derived citrated kaolin reaction time (CKR) and/or the difference (R-difference) and/or ratio (R-ratio) between CKR and heparinase-corrected CKR might help resolve such discordance METHODS: We obtained simultaneous triple-paired samples for aPTT, anti-Xa and thromboelastography (TEG) in ICU patients receiving UFH infusion. We assessed correlation between UFH dose and R-difference and concordance for therapeutic ranges between aPTT, anti-Xa, and CKR or R-difference or R-ratio. On multivariate analysis, we assessed factors associated with TEG R-based measurements RESULTS: We studied 136 samples from 24 patients with a median APACHE III score of 50 and median UFH dose of 14.6 [10.5, 18.3] units/kg/h. for each 1 unit/kg increase in UFH dose, the R-difference increased by 2 min (95% C.I. 0.23-3.7, p < 0.05) but the correlation was weak (R = 0.1). The Cohen's kappa coefficient for agreement was 0.39 for CKR-aPTT and 0.17 for CKR-anti-Xa. Similar results were seen for R-difference and R-ratio. When aPTT and anti-Xa were discordant for therapeutic ranges, TEG did not resolve discordance. On multivariate analysis, CKR, R-difference and R-ratio were independently positively associated with UFH dose but also with APACHE III score and, negatively, with iCa CONCLUSIONS: In ICU patients receiving UFH infusion, TEG R-based measurements have limited correlation and concordance with anti-Xa and aPTT for defined therapeutic ranges and do not help resolve their discordance.
Caicedo Ruiz JD, Aldana JL, Kattan E
… +6 more, Orozco N, García Gallardo G, Sánchez JIA, Diaztagle Fernández JJ, Mallat J, Ospina-Tascón GA
J Crit Care
· 2026 Jun · PMID 41734533
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Conventional modeling of cardiovascular function prioritizes the interplay between cardiac contractility and venous return curves as primary determinants of stroke volume. However, this approach does not capture the infl...Conventional modeling of cardiovascular function prioritizes the interplay between cardiac contractility and venous return curves as primary determinants of stroke volume. However, this approach does not capture the influence of arterial load in flow generation, thus hindering a more comprehensive understanding of macrovascular dynamics. Since both heart and arteries are elastic chambers with distinctive geometries housing blood volume, their coupling could be derived from pressure-volume curves, which ultimately denote time-varying elastance relationships. Accordingly, the left ventricular-arterial coupling (LVAC), represented by the ratio between arterial and ventricular elastances, could indirectly estimate the energy transmission from the heart to the proximal arterial tree, thus reflecting cardiovascular efficiency. Assessment of LVAC by combining bedside echocardiography and arterial pressure monitoring may improve the understanding of macrohemodynamics during shock conditions and might potentially help to evaluate the impact of cardiovascular therapies. Nevertheless, cardiovascular dysfunction in septic shock result from complex interactions and highly variable degrees of hypovolemia, pathological vasodilation, peripheral vascular decoupling, microvascular blood flow misdistribution, and heart-pump dysfunction, whereby optimizing LVAC during the resuscitation process would not necessarily reverse tissue hypoperfusion. This review provides an analysis of the components of LVAC, including the physiological fundamentals of arterial and ventricular elastances, explores its relationship with cardiovascular efficiency and energetics, synthesizes available data about LVAC assessment in septic shock, addresses some unresolved controversies, and proposes a conceptual framework for future research.