Oosterveld T, Paulus MC, Hess B
… +13 more, Häbel H, Johansson Å, Mürner N, Blaser AR, Fetterplace K, Ridley EJ, Tatucu-Babet OA, van Zanten ARH, Wanecek M, Wittholz K, Deane A, Rooyackers O, Sundström Rehal M
BACKGROUND: Metabolic alterations are a fundamental part of critical illness, but changes during prolonged ICU stay are inadequately understood. This study aimed to describe longitudinal trends in energy expenditure and...BACKGROUND: Metabolic alterations are a fundamental part of critical illness, but changes during prolonged ICU stay are inadequately understood. This study aimed to describe longitudinal trends in energy expenditure and substrate utilisation in persistent critical illness, defined as an ICU stay of ≥ 10 days. METHODS: This prospective, observational, multicentre study was conducted from 2022 to 2024 at five European and two Australian ICUs. The primary outcome was the change in energy expenditure over time. Adult patients with ≥ 1 indirect calorimetry and length of stay ≥ 10 days were included. Clinical parameters, markers of inflammation and protein catabolism were collected at each measurement. Longitudinal trends were analysed using mixed-effects models with restricted cubic splines. Latent class analysis was performed with identical covariates. RESULTS: 433 patients with 1194 measurements were included. The mean age was 56 years, and 70% were male. An initial increase in energy expenditure, peaking around day 10, and subsequent decline were found (p < 0.001), remaining significant after adjustment for sex, age, CRP, FiO2, presence of fever, BMI, renal replacement therapy, administered protein as fixed effects and patient and site as random effects (p = 0.001, conditional R² = 0.76). The association between the respiratory quotient and time was non-significant (p = 0.067). The urea: creatinine ratio increased over the first 10 days (p < 0.001). Latent class analysis identified three trajectories of energy expenditure: hypo-, normo-, and hypermetabolism (entropy 0.63). CONCLUSIONS: Mean energy expenditure follows a biphasic pattern during prolonged ICU stay, with the inflection point coinciding with the empirical onset of persistent critical illness. Further research is required to validate potential metabolic subgroups and explore their biological correlates in this population. TRIAL REGISTRATION: The study, including the statistical analysis plan, was prospectively registered at clinicaltrials.gov (NCT05124860, registered 2021-11-15).
BACKGROUND: Severe Covid-19 has been associated with acute cardiovascular complications, but data on long-term cardiovascular outcomes after critical care are limited. This study aimed to evaluate the risk of atheroscler...BACKGROUND: Severe Covid-19 has been associated with acute cardiovascular complications, but data on long-term cardiovascular outcomes after critical care are limited. This study aimed to evaluate the risk of atherosclerotic cardiovascular disease (ASCVD) within three years following severe COVID-19 requiring intensive care. METHODS: This nationwide, population-based matched cohort study included adults with confirmed COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and were discharged alive from the hospital between March 1, 2020, and June 8, 2021, identified from the Swedish Intensive Care Registry. After a 1:4 propensity score match including age, sex, district of residence, comorbidities and socioeconomic factors - cases and controls were compared regarding cardiovascular outcomes during a three-year follow-up. The primary outcome was ASCVD events occurring more than 30 days after discharge from the ICU and secondary outcomes included hospitalization for heart failure, atrial fibrillation, and all-cause mortality. RESULTS: After propensity score matching, 16,530 individuals (3,350 cases and 13,180 controls) were included. The median age was 61 years, and 71% were male. Compared with controls, cases had an increased risk for ASCVD [subdistribution hazard ratio (sHR) 1.42 (95% CI 1.26-1.60)], hospitalization with atrial fibrillation [sHR 1.85 (95% CI 1.64-2.10)] and heart failure [sHR 1.81 (95% CI 1.57-2.09)]. All-cause mortality [hazard ratio (HR) 1.48 (95% CI 1.26-1.74)] was also significantly more frequent among cases. CONCLUSION: Among ICU-treated survivors of severe COVID-19, the risk of ASCVD, heart failure, atrial fibrillation, and all-cause mortality was increased during three years of follow-up compared with the matched population-based controls, with associations strongest during the first year of follow-up [period-specific estimates are provided in the Supplementary].
Kreitmann L, Rouzé A, Luyt CE
… +10 more, Razazi K, Fartoukh M, Bruneel F, Gouzien L, Maxime V, Le Terrier C, Zahar JR, Béhal H, Nseir S, COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators
BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a serious complication of severe SARS-CoV-2 pneumonia in critically ill patients requiring invasive mechanical ventilation (IMV). Several host...BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a serious complication of severe SARS-CoV-2 pneumonia in critically ill patients requiring invasive mechanical ventilation (IMV). Several host- and treatment-related risk factors have been identified, but the role of environmental factors-particularly ICU room air pressure-remains underexplored. METHODS: We conducted an ancillary analysis of the COVID-ICU study, a prospective multicenter cohort of COVID-19 patients admitted to ICUs in France, Belgium and Switzerland during the first wave of the pandemic. Our analysis included 1233 mechanically ventilated patients. We compared the cumulative incidence of probable invasive pulmonary aspergillosis (IPA), defined according to the 2024 Invasive-Fungal-Diseases-in-Adult-Patients-in-ICU (FUNDICU) consensus criteria, between patients isolated in negative-pressure rooms and those housed in neutral-pressure rooms. Secondary outcomes included the incidence of putative IPA, the incidence of putative IPA or Aspergillus colonization (both defined according to the AspICU algorithm), and the association between probable IPA occurrence and clinical outcomes. RESULTS: Probable IPA occurred significantly less frequently in patients isolated in negative-pressure rooms, compared to those in neutral-pressure rooms (2.0% vs. 4.8%; adjusted cause-specific hazard ratio [cHR] 0.44, 95%CI 0.21-0.90, p = 0.024). No significant between-group difference was observed in the incidence of putative IPA alone or in combination with Aspergillus colonization (1.3% vs. 2.1%, adjusted cHR 0.65, 95% CI 0.23-1.77, p = 0.4 and 3.3% vs. 5.8%, adjusted cHR 0.66, 95% CI 0.30-1.42, p = 0.29, respectively). The occurrence of probable IPA was associated with longer IMV duration and ICU length-of-stay (adjusted HR 0.45, 95% CI 0.27-0.76, p = 0.002 and 0.59, 95% CI 0.38-0.91, p = 0.017, respectively). CONCLUSION: In this large multicenter cohort of mechanically ventilated COVID-19 patients, isolation in negative-pressure ICU rooms was associated with a lower incidence of probable IPA, but the small event rate and potential confounders indicate this finding needs to be replicated and validated by other studies.
The recent guideline from the American Heart Association on acute pulmonary embolism provides an updated framework for diagnosis, risk stratification, and management. Computed tomography pulmonary angiography remains the...The recent guideline from the American Heart Association on acute pulmonary embolism provides an updated framework for diagnosis, risk stratification, and management. Computed tomography pulmonary angiography remains the reference standard for confirming pulmonary embolism. However, in critically ill patients with hemodynamic or respiratory instability, transport for definitive imaging may be unsafe or impractical. In this context, bedside evaluation becomes central to early decision-making. Point-of-care ultrasound (POCUS), particularly when performed as a multi-organ assessment integrating cardiac, pulmonary, and venous ultrasound, can rapidly identify signs of right ventricular dysfunction, detect thrombus in transit, and exclude alternative life-threatening causes of shock. Emerging evidence suggests that multi-organ POCUS has high diagnostic performance in critically ill patients with suspected pulmonary embolism. In unstable patients, bedside ultrasound may therefore provide clinically actionable information to support timely therapeutic decisions when definitive imaging is not immediately feasible.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving form of cardiopulmonary support for patients with severe refractory cardiopulmonary disease. It is a resource-intensive intervention requiring speci...BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving form of cardiopulmonary support for patients with severe refractory cardiopulmonary disease. It is a resource-intensive intervention requiring specialised equipment and personnel, with significant associated costs. This study aimed to determine the costs of care for patients who received ECMO in Australia and New Zealand, and to determine the impact of ECMO-related complications on costs. METHODS: A prospective observational clinical registry analysis was performed using data from 1,345 patients commenced on ECMO in Australia and New Zealand between 2019 and 2022. Per patient resource use was costed based on data from hospital admission to hospital discharge. Key outcomes were mean total patient cost and costs associated with complications. Costs were reported in 2022 Australian Dollars. RESULTS: Mean costs and daily ECMO costs varied significantly between ECMO modes. While total costs for venovenous (VV) ECMO was significantly more expensive (mean $287,264, standard deviation [SD] $251,193) than venoarterial (VA) ECMO (mean $215,128, SD $162,418) and extracorporeal cardiopulmonary resuscitation (ECPR) (mean $121,274, SD $131,893), daily costs while receiving ECMO were least costly for VV ECMO. Complications occurred in 57% of patients. Cost incrementally increased with number of complications. Mean costs were significantly higher in patients with infection (mean $292,197, SD $217,806) compared to those without (mean $161,674, SD $165,175). Key cost drivers were intensive care and hospital length of stay, and ECMO-related procedure costs. CONCLUSIONS: ECMO costs were high, with venovenous ECMO being most expensive due to an increased length of stay. Total patient cost increased with additional ECMO complications. Accurate ECMO costs and complications data can enable informed health budgeting and identification of areas for clinical improvement. (Trial registration: NCT03793257).
Rodrigues EAP, Pacheco EC, Nakamura MAM
… +21 more, Dos Santos ACC, de Melo JL, Plens GM, Alcala GC, Victor M, Xin Y, Cereda M, Gomes S, Lee HJ, Ribeiro BM, Ianotti RM, Freitas-Filho O, Alves-Jr JL, Berra L, Morais CCA, Bertacchini L, Mlček M, Souza R, Borges JB, Costa ELV, Amato MBP
BACKGROUND: Timely detection of pulmonary embolism (PE) is crucial, particularly in critical settings where rapid confirmation or exclusion is required and computerized tomography pulmonary angiography (CTPA) poses safet...BACKGROUND: Timely detection of pulmonary embolism (PE) is crucial, particularly in critical settings where rapid confirmation or exclusion is required and computerized tomography pulmonary angiography (CTPA) poses safety challenges. We assessed the experimental and clinical accuracy of electrical impedance tomography (EIT)-ventilation-perfusion (V̇/Q̇) maps and a novel wasted-ventilation index for detecting PE. METHODS: Ten piglets underwent EIT-V̇/Q̇ mapping before and after proximal or distal pulmonary artery occlusions. EIT-perfusion maps were validated against dynamic contrast-enhanced CT (DCE-CT) and quantitative clot-burden analysis from whole-lung CTPA. To assess specificity, models of non-occlusive perfusion impairment were added (6 piglets). The wasted-ventilation index was refined across 114 piglet conditions (66 PE) and subsequently validated in 66 patients with acute respiratory failure (257 exams) and 10 patients with chronic thromboembolic disease (31 exams), totaling 288 EIT-exams. RESULTS: Strong positive correlations between estimates of regional perfusion obtained by EIT vs. DCE-CT or CTPA were found. Agreement showed mean bias of - 3.04 ± 3.02% between EIT and DCE-CT, and + 3.45 ± 2.81% between EIT and CTPA. The wasted-ventilation index performed with AUC = 0.989 in animals (P < 0.0001; sensitivity 96%, specificity 94%) and AUC = 0.923 in patients (P < 0.001; sensitivity 81%, specificity 94%). The index consistently decreased after thrombolysis. CONCLUSIONS: The novel wasted-ventilation index showed high accuracy in detecting pulmonary arterial occlusions of varying severity, distinguishing them from other perfusion problems. Its agreement with CTPA, DCE-CT, and reference methods supports EIT-V̇/Q̇ mapping as a reliable diagnostic aid when conventional imaging is unfeasible or risky.
Escolà-Rodríguez A, Sandoval E, Rigo-Bonnin R
… +11 more, Téllez Santoyo A, Herrera S, Hernández Meneses M, Carramiñana A, Sainz de Medrano JI, Brunet Serra M, Moisés J, Roca C, Castro P, Soy Muner D, Bastida C
BACKGROUND: Antimicrobial pharmacokinetics (PK) in patients receiving extracorporeal membrane oxygenation (ECMO) remains poorly defined. Drug sequestration within the ECMO circuit has been reported; however, existing evi...BACKGROUND: Antimicrobial pharmacokinetics (PK) in patients receiving extracorporeal membrane oxygenation (ECMO) remains poorly defined. Drug sequestration within the ECMO circuit has been reported; however, existing evidence is primarily based on ex vivo studies and small clinical series, resulting in conflicting findings with limited clinical applicability. This study aimed to characterize antimicrobial sequestration within different ECMO circuit components and to describe the PK of meropenem, piperacillin/tazobactam, linezolid, and ceftaroline in critically ill patients receiving ECMO support. METHODS: We conducted a prospective, single-center observational study in critically ill patients receiving ECMO (veno-venous (VV) or veno-arterial (VA)) and treated with meropenem, piperacillin/tazobactam, linezolid, or ceftaroline. Serial blood samples were collected simultaneously from the patient's arterial line and from pre- and post-membrane oxygenator sampling sites. Non-compartmental analysis was used to derive PK measures, and concentration differences across sampling sites were analyzed to estimate circuit-related drug sequestration. Antimicrobial target attainment was assessed according to established PKPD targets. RESULTS: A total of 237 samples from 8 patients (4 VV, 4 VA) were analyzed. Limited, component-specific sequestration was observed in the membrane oxygenator for meropenem (9.28% ± 21.6%, p = 0.046) and ceftaroline (14.6% ± 17.5%, p = 0.010), for linezolid it was also identified (10.1% ± 12.3%, p = 0.005), but in tubing and connectors. Piperacillin/tazobactam showed negligible retention. However, when considering the ECMO circuit as a whole, no statistically significant reductions in systemic concentrations were observed for any antimicrobial. PK measures were generally consistent across sampling sites. In 20% of treatments, predefined PKPD efficacy targets were not achieved. CONCLUSIONS: Antimicrobial sequestration within the ECMO circuit is detectable and drug- and component-specific. However, overall impact on systemic antimicrobial exposure appears limited. Inadequate PKPD target attainment in a subset of antimicrobial treatments likely reflects the marked PK variability of critical illness rather than ECMO-related drug loss alone. These exploratory results support the use of therapeutic drug monitoring to individualize antimicrobial therapy in ECMO-supported patients and the need to conduct further population PK studies to better characterize determinants of antimicrobial exposure and to clarify the clinical relevance of circuit-related drug sequestration.
BACKGROUND: Most Artificial Intelligence prognostic models in intensive care are trained and validated on a single source, limiting their reliability in external settings. This study evaluated generalizability and specia...BACKGROUND: Most Artificial Intelligence prognostic models in intensive care are trained and validated on a single source, limiting their reliability in external settings. This study evaluated generalizability and specialization for ICU mortality and remaining length of stay (RLoS) prediction across international databases, and explored multi-source strategies to mitigate the performance cost of external deployment. METHODS: Using the Temporal Pointwise Convolution (TPC) architecture, we conducted external validation across four harmonized BlendedICU databases (eICU-CRD, MIMIC-IV, AmsterdamUMCdb, HiRID), extracting nearly 20,000 unique patients from each. Four training configurations were compared: single-source training on AmsterdamUMC (N = 3,574) or MIMIC-IV (N = 10,915), data pooling, and transfer learning (both N = 14,489). Performance was assessed using AUROC and AUPRC for mortality, MAPE for RLoS, and a composite metric (Mcomposite). RESULTS: Internal validation consistently overestimated external performance, with MAPE increasing by up to 51.8% and AUROC dropping by up to 13.8% on external databases. Site-specific features such as drug exposure acted as "shortcuts" degrading portability. Data pooling emerged as the superior strategy, achieving the best generalization (Mcomposite improvement up to 8.0% over single-source models) while matching or outperforming transfer learning for specialization - particularly for RLoS (MAPE 84.49 vs. 89.24, non-overlapping confidence intervals). CONCLUSION: Single-source training compromises clinical applicability. Data pooling across harmonized international cohorts is the most effective strategy for both generalization and specialization, supporting a "Data-Centric AI" approach. We advocate for the democratization of local ICU datasets and open-source customizable models to empower independent clinical validation.
BACKGROUND: Patient factors determining the benefit of prone positioning remain uncertain, resulting in the maneuver being applied indiscriminately among those with moderate-severe ARDS. We aimed to assess if baseline re...BACKGROUND: Patient factors determining the benefit of prone positioning remain uncertain, resulting in the maneuver being applied indiscriminately among those with moderate-severe ARDS. We aimed to assess if baseline respiratory system elastance (Ers), or "stiffness", determines the treatment effect of prone positioning on mortality. METHODS: Bayesian logistic regression modeling of the PROSEVA Trial was used to estimate the posterior probability of prone positioning effect moderation by baseline Ers on 90-day mortality in patients with moderate-severe ARDS. As a secondary aim, we tested whether the absolute change in driving pressure of the respiratory system (∆DPrs ) in response to prone positioning predicted 90-day mortality, using logistic regression. RESULTS: The treatment effect of prone positioning on mortality did not meaningfully vary with baseline Ers (posterior probability of benefit OR < 0.95 = 52%; interaction OR 0.94, 90% credible interval, CrI, 0.74-1.20). Higher baseline Ers was associated with greater improvements in DPrs at the end of the first prone session (β= -3.3, 95% confidence interval (CI) -4.09, -2.49; p = < 0.001). However, this response was not associated with mortality benefit in adjusted models (OR 1.14, 95% CI 0.96, 1.37; p = 0.14). CONCLUSIONS: The effect of prone positioning on mortality did not vary with Ers in the PROSEVA trial. Similarly, prone positioning-induced improvement in DPrs was not predictive of mortality in this cohort of passively ventilated ARDS patients.
BACKGROUND: Survivors of pediatric intensive care often experience prolonged morbidity, but recovery trajectories and features associated with impairment in general PICU populations remain uncertain. We aimed to explore...BACKGROUND: Survivors of pediatric intensive care often experience prolonged morbidity, but recovery trajectories and features associated with impairment in general PICU populations remain uncertain. We aimed to explore the trajectory of health-related quality of life (HRQoL) and fatigue in critically ill children over the first year following PICU discharge, and to identify baseline and PICU factors associated with worse outcomes. METHODS: OCEANIC is a multicenter prospective cohort study across 10 English PICUs. Children aged 1 month-17 years with PICU stay ≥ 48 h were enrolled (2019-2022) and followed for 12-months (to 2023). HRQoL (PedsQL™ 4.0 Acute Versions) and fatigue (PedsQL™ Multidimensional Fatigue) were assessed at baseline (pre‑admission), PICU discharge, and 1, 3, 6 and 12 -months. We used Random Forest models with SHapley Additive exPlanations (SHAP) to identify features associated with below‑baseline HRQoL at each timepoint. RESULTS: Of 326 children enrolled, 220 had ≥ 3 HRQoL assessments. Mean PedsQL fell from 73.3 (SD 20.99) at baseline to 54.3 (SD 23.52) at discharge, then rose to 62.9 (1-month, SD 21.73) and 67.1 (3-months, SD 20.38), stabilizing thereafter (70.4 (SD 21.34) at 6-months; 69.8 (SD 22.46) at 12-months; p < 0.001 across time). At discharge, 71.8% were below their baseline HRQoL. Among 12‑month respondents, 58.1% remained below their baseline. Physical and school functioning showed persistent impairment, with cognitive functioning returning to baseline by 1-month. Fatigue largely normalized by 6-months. Higher baseline HRQoL and older age were consistently influential features with worse HRQoL, with physiological/illness markers important features across timepoints. CONCLUSION: At 12-months, 58% of responding children remained below their pre-PICU baseline HRQoL, with persistent impairment most evident in physical and school functioning. Modelling identifies population-level subgroups of children characterized by higher baseline or lower discharge HRQoL, older age, and prolonged PICU exposure who may warrant closer multidisciplinary follow‑up after PICU discharge. TRIAL REGISTRATION: ISRCTN28072812 14/02/2020.
BACKGROUND: Prone positioning improves survival in patients with ARDS; however, no consensus exists on how to define a positive response to this intervention. We conducted a systematic review and meta-analysis to map exi...BACKGROUND: Prone positioning improves survival in patients with ARDS; however, no consensus exists on how to define a positive response to this intervention. We conducted a systematic review and meta-analysis to map existing definitions of response to prone position in invasively ventilated patients with ARDS and to quantify their pooled proportion across existing body of evidence. We also evaluated the association between responsiveness to prone position and mortality. METHODS: We surveyed PubMed, Embase, and Cochrane Central Register of Controlled Trials databases from inception to July 2025. For the primary outcome (proportion of responders), pooled estimates were calculated using a random-effects model with logit transformation of individual study proportions. For the secondary outcome, we performed a pairwise meta-analysis to estimate pooled odds ratios for mortality. RESULTS: Oxygenation response, defined as a change of PaO/FiO from the supine to the prone position, was adopted as definition by 53 non-randomized studies. The pooled proportion of responders was estimated as 68% (95% C.I. 63-72%). Twenty-one studies assessed responsiveness using physiological variables other than, or in addition to, oxygenation, including carbon dioxide clearance, respiratory mechanics, or ventilation-perfusion matching. Using these alternative definitions, the pooled proportion of responders ranged from 45% to 53%. Of the 26 studies providing unadjusted mortality data in responders and non-responders, 11 (42%) reported a reduced risk of mortality in the responder cohort. A sensitivity analysis restricted to the five studies at serious risk of bias showed a reduced unadjusted risk of mortality in responders (OR 0.41, 95% CI 0.25-0.68; I² = 78%). CONCLUSIONS: Definitions of responsiveness to prone positioning are highly heterogeneous across the literature, and the reported proportion of responders varies widely depending on the definition adopted. High risk of bias, residual confounding and substantial between-study heterogeneity, limit robust conclusions regarding the association between physiological responsiveness to prone positioning and survival. PROSPERO REGISTRATION: CRD420251104725.
Neves Briard J, English SW, Fergusson DA
… +19 more, Dhanani S, Lauzier F, Turgeon AF, Ball I, Darvesh S, Titova P, Lebrasseur M, Couillard P, Kramer A, D'Aragon F, Hannouche M, Burns KEA, Boyd JG, Binnie A, Wang HT, Shemie S, Shankar JJS, Chassé M, INDex Investigators and The Canadian Critical Care Trials Group
PURPOSE: In comatose patients at risk of death by neurologic criteria (DNC), spinal-mediated movements (SMM) and movements of unclear neuroanatomic origin (MUO) are occasionally challenging to discriminate from cerebral-...PURPOSE: In comatose patients at risk of death by neurologic criteria (DNC), spinal-mediated movements (SMM) and movements of unclear neuroanatomic origin (MUO) are occasionally challenging to discriminate from cerebral-mediated movements. Our objectives were to assess the respective prevalence and semiology of SMM and of MUO in this population and to estimate the associations between these movements with cerebral blood flow and perfusion. METHODS: In this prospective cohort study conducted in 15 intensive care units across Canada, we enrolled consecutive, brain-injured adults with an unconfounded Glasgow Coma Scale score of 3. Physicians conducted standardized DNC clinical evaluation, and participants underwent a brain CT-perfusion scan with CT-angiography reconstructions within a 2-h delay. We assessed the prevalence and semiology of SMM and MUO with descriptive statistics. We estimated the associations between SMM and MUO with cerebral blood flow and brain perfusion using generalized linear mixed models with a logit link function, age and sex as covariates, and random intercepts for study sites. RESULTS: We included 282 participants with a median [IQR] age of 60 [47-69] years. The respective prevalence of SMM and MUO were 27% (95% CI: 22-32%) and 12% (95% CI: 9-16%). SMM and MUO were not associated with the presence of cerebral blood flow on CT-angiography (aOR for SMM: 1.14, 95% CI: 0.63-2.05; aOR for MUO: 1.36, 95% CI: 0.61-3.01) or brain perfusion on CT-perfusion (aOR for SMM: 1.44, 95% CI: 0.77-2.68; aOR for MUO: 1.75, 95% CI: 0.77-3.97). Findings were similar in the subgroup of 204 patients fulfilling clinical criteria for DNC. CONCLUSIONS: SMM and MUO are common among comatose patients at risk of DNC. Their prevalence is similar among alive comatose patients and patients fulfilling clinical criteria for DNC. These movements are not associated with cerebral blood flow on CT-angiography or brain perfusion on CT-perfusion. TRIAL REGISTRATION: Registered on ClinicalTrials.gov: NCT03098511 on March 27, 2017.
Rajsic S, Argudo E, Hofheinz SMB
… +12 more, Martínez MM, Delgado A, Wulczyňská S, Breitkopf R, Putzer G, Rubin J, Mendonca M, Antonini MV, Swol J, Belliato M, Bělohlávek J, EuroELSO ECPR Working Group on Ethics and Organ Donation
Extracorporeal cardiopulmonary resuscitation (ECPR) offers a life-saving option for select patients with refractory cardiac arrest, yet a substantial proportion suffer devastating neurological injury and die despite extr...Extracorporeal cardiopulmonary resuscitation (ECPR) offers a life-saving option for select patients with refractory cardiac arrest, yet a substantial proportion suffer devastating neurological injury and die despite extracorporeal support. In this context, organ donation may emerge as a potential downstream pathway, introducing complex ethical tensions at the intersection of life-sustaining treatment, end-of-life care, and organ preservation. This narrative review examines the ethical challenges associated with organ donation following ECPR, with particular attention to the transition from resuscitative intent to donation-oriented care. We discuss the clinical and ethical challenges of ECPR programs related to patient autonomy, informed consent, conflicts of interest, and equity of access in both adult and paediatric populations. Building on core principles of biomedical ethics, we propose a structured ethical model to guide clinicians and institutions navigating these scenarios. Central elements include strict separation between resuscitative and donation-related decision-making, transparent prognostication, robust safeguards around treatment intent, and early integration of ethics consultation and structured communication processes. We extend the prior evidence by offering ECPR-specific considerations, including concrete governance triggers, bedside tools, the integration of paediatric perspectives, and the translation of ethical principles into operational guidance. By defining clear ethical boundaries and governance mechanisms, this review aims to support the responsible integration of organ donation pathways following ECPR, while preserving public trust and reaffirming the primacy of patient-centred care.
BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) requires balancing thrombotic and bleeding risks, yet early coagulation dynamics may differ between venovenous (VV) and venoarterial (VA) supp...BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) requires balancing thrombotic and bleeding risks, yet early coagulation dynamics may differ between venovenous (VV) and venoarterial (VA) support. This study prospectively characterized standard coagulation tests and viscoelastic profiles during the first 48 h of ECMO and related these to early bleeding and transfusion need. METHODS: Multicenter, prospective cohort in four Belgian ICUs (03/2021-01/2023; NCT04912336). Adults initiated on VV- or VA-ECMO were enrolled immediately before cannulation and sampled at inclusion, + 2 h, + 24 h, and + 48 h. Laboratory tests (aPTT, PT/INR, fibrinogen, platelets, anti-Xa, D-dimer, AT), ROTEM, bleeding (BARC, GUSTO), and transfusions were recorded. RESULTS: Forty-three patients were included (23 VV, 20 VA). At inclusion, platelet counts were higher in VV than in VA (median 292 vs. 145·10/L). Thrombocytopenia was present at enrollment in 30% and developed in 56% during the first 48 h (mild 14%, moderate 35%, severe 7%); both modes showed significant platelet decline (p < 0.001). Fibrinogen remained higher in VV, whereas VA exhibited lower fibrinogen and higher INR and aPTT at all time points; anti-Xa was higher at baseline in VA and declined over 48 h. CRP was higher in VV but rose in VA after initiation. ROTEM showed initial hypocoagulability in VA (prolonged CT/CFT, reduced A10/MCF) that normalized by 48 h; while VV remained hypercoagulable. Early bleeding occurred in 37% by BARC ≥ 2 (VA 55% vs. VV 22%) and 21% by GUSTO moderate/severe (VA 35% vs. VV 9%); between-group differences were nonsignificant. Transfusion occurred in 58%; no fresh frozen plasma was given to VV patients (significantly fewer than VA). One-year survival was 87% for VV and 60% for VA. CONCLUSIONS: Early hemostatic profiles differed markedly between patients requiring ECMO for circulatory failure and those supported for isolated respiratory failure. VA-ECMO showed lower platelet counts and a more hypocoagulable profile early after initiation that partially improved within 48 h, whereas VV-ECMO remained relatively hypercoagulable. These findings support the importance of individualized hemostatic monitoring and anticoagulation management.
Benítez-Cano A, Sancho-Araiz A, Carazo J
… +13 more, Ramos I, Sánchez-Font A, Chalela R, López-Palacio M, García-Prieto FF, Navarrete-Rouco ME, Juanes-Borrego AM, Gómez-Junyent J, Horcajada JP, Adalia R, Roberts J, Sorlí L, Luque S
BACKGROUND: Ceftolozane/tazobactam (TOL/TAZ) and ceftazidime-avibactam (CAZ/AVI) are increasingly used to treat pneumonia caused by multidrug-resistant Gram-negative bacilli. However, data on intrapulmonary penetration t...BACKGROUND: Ceftolozane/tazobactam (TOL/TAZ) and ceftazidime-avibactam (CAZ/AVI) are increasingly used to treat pneumonia caused by multidrug-resistant Gram-negative bacilli. However, data on intrapulmonary penetration to confirm dosing adequacy are limited. Therefore, the aim of this study was to compare epithelial lining fluid (ELF) penetration and pharmacokinetic/pharmacodynamic (PK/PD) target attainment of TOL/TAZ versus CAZ/AVI administered by continuous infusion (CI) in critically ill patients with nosocomial pneumonia. METHODS: Single-center, open-label, randomized pharmacokinetic (PK) study. Thirty patients were randomized 1:1 to receive 6 g/3 g of TOL/TAZ or 6 g/1.5 g of CAZ/AVI administered by CI. A population PK model was constructed using plasma and ELF concentrations. Lung penetration was estimated based on the ratio AUC/AUC. Simulations were performed to estimate the probability of attaining predefined joint ELF PK/PD target defined as free concentration 100% fT> minimum inhibitory concentration (MIC) for the β-lactam component and 100% fT> concentration threshold (CT) for the β-lactamase inhibitors, among relevant MIC scenarios. Three different dosing regimens (low, standard and high) were evaluated for each combination. RESULTS: A total of 298 plasma and 58 ELF samples were analyzed. The median [IQR] age, body mass index, and creatinine clearance were 77 [9.8] years, 26.48 [5.5] kg/m², and 76.0 [96.0] mL/min, respectively. Median intrapulmonary penetration was 0.66 [0.32] for ceftolozane, 0.41 [0.30] for ceftazidime 0.44 [0.05] for tazobactam and 0.44 [0.46] for avibactam. Under the prespecified ELF PK/PD target, standard dosing achieved adequate target attainment for both combinations. Simulations showed that all CAZ/AVI regimens achieved high ELF target attainment under conservative inhibitor threshold assumptions (assuming ceftazidime MIC = 8 mg/L and avibactam C =1 mg/L), whereas for TOL/TAZ (assuming ceftolozane MIC = 4 mg/L and tazobactam C 2 mg/L) at least the standard-dose regimen was required. More aggressive target scenarios reduced the probability of target attainment, particularly for inhibitor thresholds of 4 mg/L and for Enterobacterales-oriented joint targets. CONCLUSIONS: In critically ill adults with nosocomial pneumonia receiving TOL/TAZ or CAZ/AVI by CI, standard doses achieved ELF exposures consistent with dual PK/PD target attainment against all susceptible isolates. Interindividual variability and the risk of plasma overexposure support individualized dosing and consideration of therapeutic drug monitoring. TRIAL REGISTRATION: The trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT No. 2021-006908-32). Registered 10 February 2022; https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-006908-32/ES .
Jacobs R, Schneider A, Hoste E
… +26 more, Verbrugghe W, Bagshaw S, Bell M, Boer W, Bouchard J, Broman M, Crawford B, David S, Di Mario F, Joannes-Boyau O, Joannidis M, Joseph C, Merrill KA, Ostermann M, Palevsky P, Papez K, Prowle J, Rewa O, Ricci Z, Shin S, Szamosfalvi B, Tolwani A, Villa G, Volbeda M, Rimmelé T, Jorens PG
BACKGROUND: Regional citrate anticoagulation (RCA) is recommended by guidelines over systemic heparinization for continuous renal replacement therapy (CRRT). However, its use in patients with impaired citrate metabolism...BACKGROUND: Regional citrate anticoagulation (RCA) is recommended by guidelines over systemic heparinization for continuous renal replacement therapy (CRRT). However, its use in patients with impaired citrate metabolism poses specific challenges and standardized guidance for managing RCA-related metabolic complications remains lacking. METHODS: A modified Delphi study was conducted according to a predefined protocol and reported in adherence with the CREDES (Conducting and REporting of DElphi Studies) checklist. The international expert panel comprised 29 clinicians and researchers from Europe, United States and Canada, with recognized expertise in RCA for CRRT in critically ill patients. Three iterative survey rounds were conducted to obtain agreement with proposed statements. RESULTS: Twenty-three experts completed all Delphi rounds, achieving consensus on twenty-two statements. RCA was considered feasible in patients with liver dysfunction, severe shock, or hyperlactatemia, with close monitoring and citrate dosing adjustment. Citrate accumulation can be prevented and managed using a stepwise approach, focused on reducing citrate delivery and discontinuing RCA in cases of overt accumulation. Metabolic alkalosis and electrolyte disturbances were identified as relevant but manageable complications, underscoring the need for individualizing CRRT settings. CONCLUSION: These consensus statements support the use of RCA during CRRT in critically ill patients with impaired citrate metabolism and provide practical guidance for monitoring and management of metabolic complications. However they reflect expert opinion, especially for questions with limited data and low-level evidence.