Delanote, Valentine; Heylen, Jannes; Lauwers, Hanne Moon; Jacobs, Cato; Maessen, Lenn; Debaveye, Yves; Frederiks, Pascal; Hermans, Greet; Maertens, Johan; Meersseman, Philippe; Peetermans, Marijke; Vanderbeke, Lore; Van Wijngaerden, Eric; Wilmer, Alexander; Lagrou, Katrien; Wauters, Joost; Feys, Simon
doi: 10.1186/s13054-025-05830-9pmid: 41508132
ObjectivesInfluenza- and COVID-19-associated pulmonary aspergillosis (IAPA and CAPA respectively) are associated with increased mortality in critically ill patients. We evaluated whether longitudinal bronchoalveolar lavage (BAL) galactomannan (GM) dynamics predict clinical outcomes in these patients.MethodsIn a retrospective cohort (2009–2024) at a tertiary care ICU in Belgium, 180 adult patients with probable/proven IAPA (n = 68) or CAPA (n = 112) requiring mechanical ventilation were included. A total of 698 BAL samples were analysed. GM optical density values were modelled using linear mixed-effects models (10- and 30-day follow-up windows), with outcome measures at 30 and 90 days. Bayesian joint models linked longitudinal GM trends with time-to-death, adjusting for age, Charlson Comorbidity Index (CCI) and immunosuppression. Associations between Aspergillus culture results dynamics and mortality were also assessed.ResultsIn general, BAL GM values declined significantly over days after diagnosis of aspergillosis, with steeper reductions in survivors (interaction p < 0.05). Joint models revealed each unit increase in GM over time corresponded to a 19% higher hazard of death at both 30 (aHR 1.19, p = 0.02) and 90 days (aHR 1.19, p = 0.007) after ICU admission. Persistent BAL culture positivity also correlated with worse outcomes.ConclusionsIn this large virus-associated pulmonary aspergillosis cohort, BAL GM kinetics emerged as a potential prognostic biomarker. Early and sustained increases in BAL GM values identify patients at increased risk of mortality.
Kryvenko, Vitalii; Husain-Syed, Faeq; Schnell, Elisa; Oruqaj, Gani; Morty, Rory E.; Herold, Susanne; Hecker, Matthias; Tello, Khodr; Seeger, Werner; Vadász, István
doi: 10.1186/s13054-026-06062-1pmid: 42057044
BackgroundLung-protective ventilation in acute respiratory distress syndrome (ARDS) can lead to hypercapnia, an independent risk factor for increased mortality. Extracorporeal CO2 removal (ECCO2R) enables further reduction of ventilator intensity, but its routine use is limited due to safety concerns. In the current study, we evaluated the feasibility, efficacy, and safety of minimally invasive ECCO2R (miECCO2R) implemented via a renal replacement therapy (RRT) platform in patients with mild-to-moderate ARDS and refractory hypercapnia.MethodsIn this prospective single-center observational study, 20 ICU patients with persistent hypercapnia despite escalated ventilation received either standalone miECCO2R (n = 11) or miECCO2R combined with continuous RRT (n = 9). As a primary outcome, efficacy of miECCO2R was assessed. Moreover, ventilator parameters, disease severity, renal function, and adverse events were evaluated as secondary outcome parameters over a time-course of five days upon initiation of miECCO2R.ResultsmiECCO2R led to a rapid and sustained reduction in PaCO2 levels from 71.4 mm Hg to 51.6 mm Hg within 24 h. This was accompanied by normalization of pH, and the median CO2 clearance rate was 64.5 mL/min. Driving pressure decreased significantly from 22 cm H2O to 15 cm H2O by day 5, while oxygenation remained stable. The standalone miECCO2R treatment group demonstrated faster CO2 reduction, probably due to higher blood flow rates. There were no severe adverse events related to either the device or the therapy. Circuit clotting was managed by system exchange, without clinical consequences for the patients. Platelet counts declined moderately, but no major bleeding complications occurred.ConclusionsmiECCO2R delivered via an RRT platform appears to be a safe and effective method of controlling hypercapnia and facilitating lung-protective ventilation in patients with ARDS. These findings need to be supported by further randomized controlled trials that can more definitely demonstrate the impact of miECCO2R on clinical outcomes.
Alzmmam, Abdulrahman Ibrahim; Alghanem, Reema Fahad; Alshahrani, Asma; Aljawaied, Raneem; Alolayqi, Faisal Sulaiman; Alanazi, Salem Khalaf; Alanazi, Lafi; Alkawabah, Ghaida; Zaeri, Nawal Ali; Alrabghi, Khawlah; Alshemali, Zainab; Alsaeedi, Alawi S.
doi: 10.1186/s13054-026-05858-5pmid: 41578281
BackgroundOptimal pain and sedation management in intensive care unit (ICU) remains challenging. While opioids and benzodiazepines are widely used, their adverse effects highlight the need for alternative or adjunctive strategies. Ketamine, with its analgesic and opioid-sparing has been proposed as an adjuvant. However, current evidence regarding its efficacy in ICU patients, particularly within the surgical population, remains inconclusive. We evaluated whether continuous low-dose ketamine infusion in postoperative surgical ICU patients reduces opioid consumption and improves pain intensity, and whether it affects opioid-related adverse events and key ICU recovery outcomes.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing continuous postoperative ketamine infusion versus non-ketamine based infusion for analgesia & sedation in patients admitted to the surgical ICU. Literature searches were performed in PubMed, Cochrane Central, and ClinicalTrials.gov from inception until July 2025. The primary endpoints were cumulative opioid consumption in the first 24–48 h (standardized to IV morphine equivalents where applicable) and rest pain intensity at prespecified early postoperative timepoints. Secondary endpoints included PONV, psychotomimetic events (e.g., hallucinations), and ICU recovery outcomes (e.g., ICU length of stay and duration of mechanical ventilation) when reported. We performed random-effects meta-analyses and assessed certainty using GRADE.ResultsNine RCTs comprising 666 patients were included. Ketamine significantly reduced opioid consumption at 24 h in adults (mean difference [MD] − 5.77 mg morphine equivalents; 95% CI − 6.32 to − 5.23; p < 0.0001), although the reduction at 48 h and in pediatric subgroups was not statistically significant. Pain scores at 12, 24, and 48 h were comparable between the groups. Ketamine did not significantly shorten the mechanical ventilation time (MD − 0.84 h; 95% CI − 1.93 to 0.24) or ICU length of stay (MD − 0.97 h; 95% CI − 1.95 to 0.02). However, ketamine use was associated with a lower incidence of PONV (RR 0.59; 95% CI 0.36–0.98; p = 0.0399). Psychotomimetic adverse events were infrequent and not significantly increased. GRADE evidence was moderate for opioids in adults at 24 h and low to very low for the remaining outcomes.ConclusionsIn postoperative surgical ICU patients, continuous low-dose ketamine infusion provides modest opioid sparing and is associated with lower PONV, without clear improvements in pain scores or ICU recovery outcomes. Large-scale trials with different dosing protocols are needed to explore the optimal role of ketamine beyond analgesia and PONV reduction.
Lim, Oliver; Ling, Ryan Ruiyang; Mak, Vivien; Lim, Shir Lynn; Ramanathan, Kollengode; Orosz, Judit; Pound, Gemma; Jones, Daryl; Subramaniam, Ashwin
doi: 10.1186/s13054-026-05880-7pmid: 41761217
BackgroundCardiac arrest in the intensive care unit (ICU-CA) is distinct from other in-hospital cardiac arrests, involving critically ill patients in monitored settings. Its prevalence and outcomes remain unclear. This systematic review and meta-analysis aimed to fill this evidence gap and identify areas for future research to improve outcomes in this patient population.MethodsWe searched MEDLINE, Embase and Scopus databases from inception until 26 November 2025 for studies reporting on ICU-CA in adults. We performed random effects meta-analyses with the generalised linear mixed model. We used the Joanna Briggs Institute Checklist to assess risk of bias and the GRADE approach to assess the certainty of evidence. The primary outcome was the prevalence of patients with ICU-CA; secondary outcomes included ICU and in-hospital mortality. We performed subgroup analyses based on geographical region (continent), study source (registry vs. non-registry), and COVID-19 status (infected vs. non-infected).ResultsWe included 35 observational studies including 36 cohorts in the meta-analysis. The pooled proportion of ICU-CA was 3.23% (95% CI: 2.08–4.98, moderate certainty). The proportion of ICU-CA was significantly higher (p < 0.001) in patients with COVID-19 (10.6%, 95%-CI: 5.4–19.7) compared with non-COVID-19 cohorts (2.3%, 95%-CI: 1.5–3.5). Pooled ICU mortality was 74.0% (95%-CI: 63.7–82.1, moderate certainty) and in-hospital mortality was 82.0% (95%-CI: 75.9–86.9, high certainty). Meta-regression found that proportion of shockable rhythm was inversely associated with ICU mortality, but not in-hospital mortality.ConclusionCardiac arrest in the ICU was associated with poor survival, with a higher prevalence in patients with COVID-19. Future studies should focus on peri-arrest characteristics to guide prognostication and management of individuals who experience ICU-CA.
Jansen, Gerrit; Varghese, Lydia Johnson Kolaparambil; Brand-Saberi, Beate; Falk, Cornelius Christopher; Feth, Maximilian; Förster, Eckart; Gelashvili, Tamar; Genzwürker, Harald; Hoyer, Annika; Ihlenfeld, Marcel; Pooth, Jan-Steffen; Thomasseck, Amy; Trenkel, Justin; Tiesmeier, Jens
Puggioni, Angelo; Nembrini, Sara; Esposito, Teresa; Giovanniello, Andrea; Cappellano, Giuseppe; Raineri, Davide; Burgener, Alessia; Scotti, Lorenza; Grossini, Elena; Rolla, Roberta; Cammarota, Gianmaria; Manfredi, Marcello; Chiocchetti, Annalisa; Vaschetto, Rosanna; ,
Bishop, Maya S.; Lane, Darius J. R.; Ayton, Scott ; May, Clive N.; Plummer, Mark P.; Lankadeva, Yugeesh R.
doi: 10.1186/s13054-025-05831-8pmid: 41485064
Sepsis remains the leading cause of death in intensive care units globally, with catecholamine-resistant shock posing a persistent therapeutic challenge. Norepinephrine is the primary vasopressor used to treat hypotension in sepsis, but its efficacy is often limited by multifactorial loss of pressor responsiveness, including adrenergic receptor desensitisation, excess nitric oxide, systemic inflammation, and endothelial injury. Ascorbate (vitamin C) has emerged as a potential adjunct therapy because it supports endothelial function, reduces oxidative stress, activates the immune system and enhances endogenous vasopressor synthesis. Despite restoration of systemic hemodynamics with fluids and vasopressors, the frontal cortex remains particularly vulnerable to microcirculatory ischemia and hypoxia, contributing to sepsis-associated encephalopathy through hypoperfusion, hypoxia, hyperthermia, oxidative stress, neuroinflammation, and mitochondrial dysfunction, ultimately leading to neuronal injury and delirium. Plasma levels of ascorbate are profoundly depleted in sepsis and correlate with disease severity. Cerebral cortical neurons actively concentrate ascorbate at levels up to 250-fold higher than plasma, underscoring its importance in maintaining redox homeostasis and metabolism in the brain. While the conventional intravenous vitamin C formulation, ascorbic acid, has been associated with harm in clinical trials, emerging preclinical and early clinical data suggest that intravenous sodium ascorbate, a pH–neutral formulation of vitamin C, may restore noradrenaline sensitivity and re-establish frontal cortical microvascular perfusion and oxygenation. This review discusses the mechanistic rationale and therapeutic potential of sodium ascorbate in sepsis, including its ability to cross the blood-brain barrier. By stabilising cardiovascular and cerebrovascular function, sodium ascorbate may represent a promising adjunctive therapy to improve the management of sepsis.
Showing 1 to 10 of 280 Articles
BackgroundThis study evaluates the effects of the new supraglottic airway-device laryngeal tube evo (LT®evo) versus that of tracheal intubation (TI) concerning the target parameters of ventilation therapy during mechanical chest compressions in intra-arrest-ventilation with biphasic-positive-airway-pressure-ventilation.MethodsThis prospective randomized crossover study involving Thiel-embalmed human body donors, compares TI with LT®evo using biphasic-positive-airway-pressure-ventilation during mechanical cardiopulmonary resuscitation. Each body donor underwent ventilation with both airway-devices in randomized order. Ventilatory parameters were recorded at ventilator flow sensors. Primary endpoint was expiratory tidal volume (VTe), secondary endpoints included expiratory tidal volume per kg ideal body weight (VTe/kgIBW); delta tidal volume (ideal-VTe; ΔVT); leakage volume (VLeak); peak (PPeak), mean (PMean), plateau (PPlat) pressures; and respiratory rates.ResultsFive body donors were included. Linear regression analyses with random intercepts revealed lower VTe (-295.7 ± 8 ml; 95%CI:-339.2 to -252.2); p < 0.0001), VTe/kgIBW (-5.0 ml/kg; 95%:-5.7 to -4.2; p < 0.0001), PPeak (-19.0mbar; 95%CI:-23.1 to -14.9; p < 0.0001) and PMean (-2mbar; 95%CI:-3.2 to -0.8 ;p = 0.001) but higher ∆VT (296.0 ml; 95%CI:252.5 to 339.4; p < 0.0001) and VLeak (52.7%; 95%CI:41.6 to 63.7; p < 0.0001) for LT®evo. While all tracheal-intubated body donors (100%) were successfully ventilated with biphasic-positive-airway-pressure-ventilation (VTe/kgIBW > 2 ml/kg), only one of five body donors (20%) could be ventilated via LT®evo.ConclusionIn this body donor model of biphasic-positive-airway-pressure-ventilation during mechanical cardiopulmonary resuscitation, TI provided higher VTe and lower leakage than LT®evo did. LT®evo ventilation frequently failed to achieve tidal volumes above the estimated dead space. These findings suggest that LT®evo may be poorly suited for intra-arrest ventilation using biphasic-positive-airway-pressure-ventilation during mechanical cardiopulmonary resuscitation. When the LT®evo is used in this setting, a synchronous 30:2 ventilation strategy may represent a safer alternative.Trial registrationGerman Clinical Trials Register; unique identifier: DRKS00037836; registration date: September 09, 2025.