Introduction In critically ill patients, accurate measurements of glomerular filtration rate (GFR) are challenging and commonly used GFR estimation equations based on a single serum creatinine measurement perform poorly. In this study, we evaluated mannitol as a clearance marker for measuring GFR in intensive care unit (ICU) patients. Multi-sample plasma clearance of the radiocontrast agent, iohexol, served as the reference method. Methods Twenty ICU patients received simultaneous bolus injections of mannitol and iohexol. Blood samples for marker concentrations were collected over five hours. Marker concentrations were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For both markers, GFR was assessed by the Bröchner-Mortensen multi-sample calculation model. In addition, plasma clearance for mannitol was assessed by the one-sample Jacobsson equation, for samples taken 4 and 5 h after the bolus injection. Agreement between clearance methods was assessed by the Bland-Altman method and accuracy of mannitol by calculating P30 and P10. Results The bias between mannitol and iohexol clearances was 2.9 ± 9.3 ml/min/1.73 m2, corresponding to 6% of the reference value, with an error of 39%. The accuracy for mannitol clearance vs. the reference method was 85% (P30) and 60% (P10), respectively. The corresponding values for bias, error, P30 and P10 for the one-sample plasma clearance of mannitol at 5 h, were: 0.9 ± 8.0 ml/min/1.73 m2, 32%, 84% and 68%, respectively. Conclusions In critically ill patients, plasma clearance of mannitol showed acceptable agreement with iohexol clearance, for both multi-and single-sample measurements.
The optimal sequence for weaning norepinephrine and vasopressin in recovering septic shock patients remains unresolved despite thirteen comparative studies enrolling over 2500 patients. A striking paradox defines this literature: both available randomized trials suggest weaning norepinephrine first produces more hypotension, while the observational evidence consistently suggests the opposite. We argue this contradiction is methodological rather than biological, arising from three interacting confounds no study has adequately addressed: hypotension definitions that conflate clinician dose-escalation behavior with patient hemodynamic events; failure to distinguish weaning sequence from the method of vasopressin withdrawal (abrupt versus titrated); and uncontrolled corticosteroid use that modifies vasopressor pharmacology through the V3-ACTH-cortisol axis. We propose a pharmacological framework built on the distinct half-lives, receptor biology, and hemodynamic roles of norepinephrine and vasopressin that suggests specific predictions about which patients may be at greatest risk from each withdrawal approach. We also identify a subgroup, patients with reduced left ventricular function, where directional evidence from two independent datasets suggests potential benefit with vasopressin-first weaning, though prospective validation is required. We propose a 2 × 2 factorial trial addressing sequence and method simultaneously, and note that the recently registered WAVES trial (NCT07067866) will provide complementary evidence on withdrawal method that would strengthen the rationale for such a design.
BACKGROUND:Diagnosing acute respiratory failure (ARF) in patients with hematologic malignancies is complex and prognostically critical. We hypothesized that immune dysfunction driven by disease and treatments determines ARF etiologies and outcomes. METHODS:This post-hoc analysis of a prospective multicenter cohort included patients with hematological malignancies admitted to ICU with hypoxemic ARF. Immune dysfunctions were classified as phagocytic, humoral, or cellular. Associations between malignancies, immune profiles, treatments, and ARF causes were assessed by multivariate logistic regression. Unsupervised hierarchical clustering identified immune-phenotypic subgroups. RESULTS:Among 708 patients, the most frequent malignancies were acute myeloid leukemia (AML, 29.5%), non-Hodgkin lymphoma (25.6%), and myeloma (21.3%). Immune dysfunctions were frequent: humoral (71.5%), cellular (57.9%), and phagocytic (55.5%). Main ARF etiologies were bacterial pneumonia (40.4%), viral infections (18.8%), and invasive fungal infections (16.8%), while 12.7% remained undiagnosed. Phagocytic dysfunction was associated with bacterial (OR 1.60, p = 0.026) and infiltrative causes (OR 2.17, p = 0.007). Humoral dysfunction was linked to viral infections (OR 1.83, p = 0.014), and cellular dysfunction to viral infections (OR 1.70, p = 0.01) and Pneumocystis jirovecii pneumonia (PJP) (OR 2.33, p = 0.03). AML was associated with infiltrative ARF (OR 2.63, p = 0.009) but negatively with influenza (OR 0.34, p = 0.002) and PJP (OR 0.15, p = 0.009). Lymphomas were linked to pleural effusion (OR 4.31, p < 0.001), airway obstruction (OR 4.30, p = 0.009), and aspiration pneumonia (OR 2.58, p = 0.042). Corticosteroids correlated with undiagnosed ARF (OR 2.07, p = 0.03), and neutropenia with Gram-negative (OR 2.42, p < 0.001) and fungal infections (OR 1.73, p = 0.050). Cluster 1 (myeloid infiltration/uncertainty) had 53% mortality, Cluster 2 (mixed immunosuppression) 49%, and Cluster 3 (chronic lymphoid diseases) 39%. CONCLUSION:Immune dysfunction strongly influences ARF patterns and prognosis. Immune-guided diagnostic strategies could improve early etiological identification and outcomes in high-risk patients with hematological malignancies.
BACKGROUND:Patients who undergo tandem extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) have a high risk of metabolic disturbances, malnutrition, and fluid imbalances. ECMO/CRRT tandem therapy is becoming more prevalent in use; however, there are limited evidence-based guidelines for optimizing nutritional management. In this review, we examine the current literature on nutritional strategies for tandem ECMO and CRRT patients and provisional, consensus-informed clinical practice points to support individualized nutritional interventions. METHODS:We present a literature review with provisional, consensus-informed clinical practice points using a modified Delphi process. A literature search was conducted in PubMed and included studies discussing ECMO, CRRT, or tandem nutritional support in all age groups. Data extraction was standardized, and risk bias was assessed using the Newcastle-Ottawa Scale. Statements were considered clinically relevant practice points if more than 70% of respondents assigned them a rating of 3 or higher on a 5-point Likert scale. Statements identified as needing additional evidence were categorized as recommendations for future research. RESULTS:The review identified key areas critical for nutritional management in ECMO/CRRT patients: (1) early malnutrition assessment within 48 h of ICU admission, (2) individualized energy and protein requirement estimations accounting for device-specific challenges, (3) aggressive fluid and electrolyte monitoring, (4) preference for early enteral nutrition with parenteral nutrition as a safe alternative when needed, (5) early timing of nutrition initiation, (6) heightened protein targets (2-2.5 g/kg/day for adults; 3-3.5 g/kg/day for pediatrics), (7) careful carbohydrate and lipid administration to avoid metabolic complications, and (8) proactive replacement of vitamins and trace elements lost through CRRT. These recommendations are summarized in clinical practice points for bedside implementation. CONCLUSIONS:This review presents a structured set of provisional, expert consensus-informed clinical practice points for the nutritional management of patients undergoing tandem ECMO/CRRT therapy. While numerous studies address nutrition in the context of either ECMO or CRRT, none were found to specifically examine nutritional strategies in patients receiving both therapies simultaneously. This gap significantly limits the direct applicability of existing evidence to patients on ECMO and CRRT. Nevertheless, the review highlights the critical role of optimized nutritional interventions in improving outcomes, including survival and complication rates, in these critically ill patients. The findings underscore the urgent need for targeted research to validate these preliminary recommendations and to establish evidence-based nutritional goals for this complex and vulnerable population. REGISTRATION:PROSPERO ID: CRD420250651962.
BACKGROUND:Accurate core temperature management is fundamental to intensive care unit (ICU) practice, yet the dynamic reliability of less-invasive surrogate metrics during critical illness remains under-investigated. This study evaluated the accuracy and potential confounders of esophageal, bladder, and tympanic thermometry against intravascular temperature. METHODS:A prospective longitudinal study was conducted in 22 ICU patients receiving concurrently multi-site core temperature monitoring. High-resolution temperature and hemodynamic data were extracted over up to 72 h. Absolute agreement and dynamic trending were assessed using Bland-Altman and four-quadrant analyses, with confounders evaluated via Spearman correlation matrices. RESULTS:Among 833 paired measurements, esophageal thermometry demonstrated near-perfect agreement with intravascular temperature (bias 0.11 °C; 95% limits of agreement [LoA] -0.19 to 0.41 °C; Lin's concordance correlation coefficient [CCC] = 0.957). In contrast, bladder and tympanic modalities showed wider 95% LoAs (-0.32 to 0.82 °C and -0.62 to 0.55 °C, respectively) and context-dependent reliability. During targeted temperature management (TTM), bladder temperature exhibited marked thermal lag (trending concordance rate, 50.2%), driven by cardiac output, where decreased cardiac output increased delays between core and bladder temperature during cooling and re-warming (r = -0.42, P < 0.05). Tympanic thermometry errors were independent of hemodynamic parameters, showing no correlation with cardiac index (r = 0.08, P = 0.218) or norepinephrine dosage (r = 0.13, P = 0.052). CONCLUSIONS:Esophageal thermometry is a highly reliable non-invasive surrogate for intravascular temperature. Conversely, bladder thermometry is susceptible to flow-dependent thermal inertia during shock and TTM. Meanwhile, tympanic measurements exhibit wide, hemodynamically-independent variability, rendering them unreliable for continuous monitoring.
BACKGROUND:Angiotensin II is increasingly used as an adjunctive vasopressor in septic shock, but the clinical significance and determinants of early hemodynamic response remain incompletely understood. METHODS:We performed a retrospective cohort study of adults with bloodstream infection-associated septic shock treated with angiotensin II between 2019 and 2025. Early hemodynamic response was quantified as the proportional reduction in background norepinephrine-equivalent dose (NED) 3 h after angiotensin II initiation and analyzed as a continuous variable. The primary outcome was 30-day mortality. Multivariable logistic regression and 3-h landmark Cox proportional hazards models were used to evaluate associations between response magnitude and mortality. RESULTS:A total of 320 patients met inclusion criteria, of whom 207 (64.7%) were male and the mean age was 63.7 years (SD 14.7). Greater proportional reductions in NED at 3 h were independently associated with lower 30-day mortality (adjusted OR per 10% reduction, 0.83; 95% CI 0.76-0.90; p < 0.001), with similar findings in 3-h landmark Cox modeling (adjusted HR per 10% reduction, 0.89; 95% CI 0.85-0.92; p < 0.001). Findings were consistent when response was modeled using absolute reductions in NED and when angiotensin II was incorporated into total vasopressor burden. CONCLUSIONS:Greater reductions in vasopressor requirements following angiotensin II initiation were strongly associated with improved survival in bloodstream infection-associated septic shock. This relationship was best characterized as a continuous physiologic gradient, with progressively larger reductions in norepinephrine-equivalent dose associated with lower mortality rather than a discrete threshold effect.
OBJECTIVE:To evaluate whether serial diaphragmatic excursion (DE) and diaphragmatic thickening fraction (DTF) are associated with subsequent tracheal intubation during high-flow nasal cannula (HFNC) therapy and whether they add information beyond the ROX index. DESIGN:Prospective, single-center, repeated-measures cohort study. SETTING:Intensive care unit. PATIENTS:Consecutive adults with acute hypoxemic respiratory failure receiving HFNC. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Right-sided diaphragm ultrasound was performed at HFNC initiation and 1, 3, 6, 9, and 12 h. The primary outcome was intubation within 48 h of HFNC initiation. At T1-T5 landmarks, current DE, DTF, and ROX were used to estimate remaining intubation risk through 48 h using pooled logistic regression with patient-clustered robust standard errors. Next-window prediction was a sensitivity analysis. Among 270 patients, 64 (23.7%) were intubated; 1491 ultrasound assessments yielded 1221 person-period records. After adjustment for age and APACHE II, each 1-SD increase in DTF (35.7 percentage points) was associated with higher intubation odds (OR, 1.50; 95% CI, 1.29-1.74; P < 0.001), whereas DE was not. ROX remained the stronger bedside marker. Adding DTF to ROX improved apparent AUC from 0.707 to 0.736 (delta AUC, 0.029; cluster-bootstrap 95% CI, 0.009-0.055); adding DE provided little improvement. Next-window results were directionally consistent. CONCLUSIONS:Serially measured DTF, but not DE, was associated with subsequent intubation risk. DTF may complement, but should not replace, ROX and clinical assessment.
Unmeasured anions are commonly detected in critically ill patients, yet their nature remains unclear. We examined whether endothelial glycocalyx degradation may be related to this unexplained anionic burden through release of polyanionic heparan sulfate fragments. In a prospective subanalysis embedded in a randomized trial of cardiopulmonary bypass priming, 34 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were studied. A total of 150 serial measurements of strong ion gap, heparan sulfate, and syndecan-1 were obtained at five timepoints from post-induction to the first 24 h of intensive care unit admission. In mixed-effects models accounting for repeated measurements and timepoint effects, strong ion gap was associated with heparan sulfate (β = 0.20, 95%CI 0.06-0.33; p = 0.005), but not syndecan-1. These findings suggest that glycocalyx-derived heparan sulfate may be related to persistent unmeasured anions extending from cardiopulmonary bypass into the subsequent intensive care unit admission, a period characterized by acute inflammation and volume loading. The absence of an association with syndecan-1 suggests a specific association to circulating polyanionic glycosaminoglycans rather than all glycocalyx degradation products. These findings are hypothesis-generating and suggest a possible relationship between circulating glycocalyx degradation and a persistent strong ion gap in critically ill patients, although comprehensive gap fractionation is required to quantify the contribution of heparan sulfate and determine whether it can be modified by resuscitation strategy.
BACKGROUND:Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma, that can lead to life-threatening complications requiring intensive care unit (ICU) admission. This study aimed to describe the clinical characteristics, WM-specific complications, and outcomes of WM patients admitted to the ICU. METHODS:We conducted a multicenter retrospective study in 6 French ICUs including all patients with WM admitted between 2010 and 2024. The primary outcome was ICU mortality, analyzed using Ridge logistic regression. One-year mortality and associated risk factors were also assessed after ICU admission. RESULTS:A total of 151 patients with WM were admitted to the ICU over the 14-year period. ICU mortality was 20% (n = 30), with infections being the leading cause of death. The main reason for admission was acute respiratory failure, and nearly half of the patients presented with sepsis at admission. The most WM-specific complications included hyperviscosity syndrome (n = 29, 19%) and other IgM-related vascular complications (n = 27, 18%). In Ridge logistic regression, a higher SOFA score (β = 0.099) and autoimmune haemolytic anemia (β = 0.058) were most strongly associated with ICU mortality, whereas, hyperviscosity syndrome (β = -0.045) showed the strongest negative association. The one-year mortality rate was 40% (n = 58) and remission at one year was achieved in 47% (n = 56) of treated patients. CONCLUSION:This is the first large retrospective cohort of critically ill patients with WM. SOFA score and autoimmune cytopenias were most strongly associated with ICU mortality, highlighting the importance of both disease-specific complications and baseline severity, and supporting the need for tailored prognostic tools and individualized management strategies.
BACKGROUND:The IntelliSync+ [IS+] algorithm provides closed-loop synchronization by continuously analyzing airway pressure and flow waveforms in real time to optimize inspiratory and expiratory cycling. This study evaluated the efficacy of IS+ compared with conventional physician-tailored synchronization during noninvasive ventilation [NIV] in spontaneously breathing adult patients with ARF. METHODS:This multicenter, prospective, randomized controlled, single-blind crossover trial was conducted between March 2024 and May 2025 in two tertiary hospitals. Adult patients receiving NIV for ARF were randomized to start with either conventional synchronization or IS+. Each mode was applied for 30 min, separated by a 15-min washout period. The primary outcome was the Asynchrony Index [AI], defined as the number of asynchronous events per 100 breaths. RESULTS:Compared with conventional synchronization, IS+ significantly reduced the total AI [11.8 (7.9-22.4) vs. 25.5 (12.1-35.3) events/100 breaths, p < 0.001], as well as both major and minor asynchrony indices [8.3 (4.5-16.4) vs. 17.6 (7.5-25.6), p < 0.001; 3.4 (1.5-5.4) vs. 7.6 (3.4-13.6), p < 0.001, respectively]. Dyspnea scores were significantly reduced during IS+ [3 ± 1 vs. 5 ± 1, p = 0.0001], indicating improved comfort. CONCLUSIONS:Closed-loop synchronization using IS+ significantly improved patient-ventilator interaction and comfort during NIV in adults with acute respiratory failure with no adverse events observed during the study period. This study demonstrates that synchrony during NIV can be enhanced using a closed-loop algorithm alone, solely through real-time waveform analysis, without the need for additional invasive monitoring. Clinical Trials ID: NCT06357780.
INTRODUCTION:Venoarterial extracorporeal membrane oxygenation (V-A ECMO) is frequently combined with intra-aortic balloon pump (IABP) support in patients with refractory cardiogenic shock. Although IABP may reduce V-A ECMO-related afterload, its effect on cerebral perfusion remains uncertain. We aimed to assess the impact of IABP support on middle cerebral artery (MCA) blood flow velocity measured by transcranial Doppler ultrasonography in patients receiving V-A ECMO. METHODS:We conducted a retrospective study in our tertiary intensive care unit between November 2021 and May 2022. Adults receiving femoro-femoral V-A ECMO with concomitant IABP support were screened. Patients with documented transcranial Doppler monitoring parameters were included. MCA blood flow velocities and systemic hemodynamic variables were compared between IABP standby mode and active IABP support at a 1:1 assist ratio. RESULTS:Among 88 screened patients, 21 were included. IABP support was associated with lower peak systolic and pre-ejection arterial pressures, whereas mean arterial pressure remained unchanged. MCA systolic and late diastolic flow velocities decreased during IABP support, while early diastolic velocity increased. Overall, MCA mean flow velocity was significantly lower during IABP support than during standby mode (42 [39-55] vs. 59 [48-64] cm·s-1, p < 0.001). Higher unassisted pulse pressure and greater reduction in late diastolic flow velocity were associated with a larger decrease in MCA mean flow velocity during IABP support. CONCLUSION:In patients receiving V-A ECMO, IABP support was associated with reduced MCA mean flow velocity despite unchanged mean arterial pressure, a TCD pattern consistent with a net decrease in cerebral blood flow, potentially related to IABP-induced changes in arterial waveform and cerebral hemodynamics.
PURPOSE:Blood cultures are often obtained during central venous catheter (CVC) insertion in intensive care units (ICUs), but contamination risk has not been fully evaluated while accounting for patient-level and short-term clinical factors. MATERIALS AND METHODS:We conducted a single-centre retrospective study of all blood culture sets obtained in an eight-bed adult ICU between June 2023 and June 2025. We compared contamination rates between cultures obtained from the CVC hub during insertion and those obtained from other sites. A self-controlled, same-day within-patient paired analysis was performed to reduce confounding. RESULTS:Among 1,196 blood culture sets from 316 patients and 331 ICU admissions, the primary analysis included 102 same-day matched pairs from 88 ICU admissions involving 86 patients. In this self-controlled, same-day within-patient analysis, CVC-insertion hub cultures were associated with higher odds of contamination than comparator cultures (OR 2.58, 95% CI 1.21-5.51). The finding was consistent after restriction to arterial-line comparator cultures and in analyses using 7- and 14-day within-patient matching windows. CONCLUSION:Blood cultures obtained from the CVC hub during insertion were associated with an increased risk of contamination. These cultures should be interpreted with caution, and alternative sampling sites may be preferable when feasible.
INTRODUCTION:Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS:We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS:We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS:This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.
BACKGROUND:The healthcare sector's environmental impact is mostly caused by hospital care, with Intensive Care Units (ICUs) being a significant source of pollution. The Dutch Green ICU network shares sustainability interventions and best practices on its online platform, supporting ICUs in making their ICUs more sustainable. However, it remains uncertain which measures are actually implemented by ICUs in the Netherlands. Our objective is to investigate which sustainability interventions of The Green ICU network have been implemented in Dutch ICUs. METHODS:A questionnaire (in Dutch) was sent to 72 ICUs in the Netherlands in May 2024 and contained 24 questions encompassing all sustainability interventions identified by The Green ICU. The interventions were divided into seven thematic areas. The ICU size was also measured, as the number of beds. The data analysis included frequency counts of the interventions and qualitative analyse of the given open answers. RESULTS:In total, 46 ICUs (64%) have opened the questionnaire, of whom 28 ICUs (response rate 39%) rated all sustainability interventions. This article provides detailed information on the implementation frequency of 85 sustainability interventions. One of the most commonly implemented interventions is: 'Establishing a green team' (implemented by 100% of responding ICUs). One of the least commonly implemented interventions is: 'Use NaCl 0,9% instead of ultrasound gel' (0%). CONCLUSIONS:This survey facilitates the identification of implemented sustainability actions and focus-areas in Dutch ICUs. A national platform that shares sustainable interventions can help drive the shift towards a green healthcare system.
BACKGROUND:SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS:Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS:Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS:Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.
