Search Results (197)

Background: Weaning from mechanical ventilation remains a complex and failure-prone process, with extubation failure rates reaching up to 30%. Conventional indices inadequately capture the multifactorial physiology underlying weaning failure. This study aimed to evaluate whether a multimodal ultrasound approach could improve the identification of mechanisms and prediction of extubation outcomes. Methods: In this prospective pilot observational study, adult mechanically ventilated patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) undergoing spontaneous breathing trials (SBT) were included. Multimodal ultrasound assessment—including transthoracic echocardiography (TTE), lung ultrasound (LUS), diaphragmatic ultrasound (DUS), and venous excess ultrasound (VExUS)—was performed at two predefined time points. Conventional respiratory mechanics parameters were recorded concurrently. The primary outcome was a composite of SBT failure (permanent weaning failure) or reintubation within 48 h. Results: A total of 27 patients were included, of whom 8 (29.6%) experienced extubation failure (5 permanent SBT failure, 3 post-extubation reintubation). Respiratory system compliance showed consistent associations with extubation failure across both ROC and regression analyses (AUC 0.806, 95% CI 0.611–1.000; cutoff ≤ 45 mL/cmH₂O; sensitivity 88%; specificity 74%; NPV 93%). Diaphragm excursion was significantly lower in the failure group (p = 0.042) and showed useful predictive performance (AUC 0.750, 95% CI 0.565–0.935; cutoff ≤ 24 mm; sensitivity 100%; specificity 58%; NPV 100%). Lung ultrasound, VExUS, and echocardiographic parameters did not demonstrate significant predictive value. Given the limited number of outcome events (n = 8) and events-per-variable ratio of 4.0 (EPV = 4.0), all multivariable findings are hypothesis-generating. Conclusions: In this prospective pilot study, respiratory system compliance and diaphragm excursion were associated with extubation failure in patients with preserved left ventricular function, while echocardiographic indices, LUS, and VExUS grading did not demonstrate significant predictive value. These hypothesis-generating findings suggest that impaired diaphragmatic function and reduced compliance may be more closely associated with weaning failure than cardiopulmonary congestion parameters. However, given the small sample size, low EPV, and single-centre design, all findings require validation in larger multicentre studies including patients with impaired systolic function. Full article

Background/Objectives: Weaning failure from mechanical ventilation affects 10–20% of critically ill patients. Cardiovascular dysfunction—particularly diastolic dysfunction with elevated left atrial pressure (LAP)—underlies up to 50–60% of failed spontaneous breathing trials (SBTs) and frequently remains undetected without targeted echocardiographic assessment. This narrative review synthesises current evidence on the echocardiographic evaluation of weaning failure, with emphasis on LAP estimation, right ventricular (RV) dysfunction, and the integration of lung and diaphragm ultrasound. Methods: A structured literature search of PubMed/MEDLINE and EMBASE was performed for publications from January 2000 to April 2026, supplemented by hand-searching of reference lists and current society guidelines. This article is reported as a narrative review; no formal systematic review protocol was registered. A qualitative synthesis emphasising pathophysiological mechanisms, echocardiographic phenotypes, and clinical applicability was performed. Results: Positive pressure ventilation with PEEP provides active LV afterload reduction; extubation abruptly removes this unloading and may precipitate acute filling pressure elevation in vulnerable patients. Multiparametric echocardiographic LAP assessment—integrating the E/e’ ratio, deceleration time, and pulmonary vein flow—supports pre-extubation risk stratification. The dynamic PEEP reduction test, although not yet standardised or multicentre-validated, may identify patients with load-dependent cardiac decompensation before extubation. RV dysfunction is present in 20–50% of ventilated patients and worsens weaning outcomes through ventricular interdependence. Complementary lung ultrasound B-line quantification and diaphragm thickening fraction assessment together support a phenotype-specific diagnostic approach. Conclusions: A structured multimodal ultrasound framework integrating echocardiography, lung ultrasound, and diaphragm ultrasound may support identification and targeted treatment of the dominant mechanism of weaning failure before extubation. Prospective multicentre validation of the integrated protocol as a whole remains a priority research need. Full article

Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of phrenic nerve stimulation (PNS) in mechanically ventilated adult patients. Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) up to 21 February 2026, without language restrictions. Two reviewers independently screened studies, extracted data, and evaluated the risk of bias using the Cochrane RoB 2 tool. The certainty of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled using fixed-effects or random-effects models according to heterogeneity. Results: Five RCTs involving 431 patients were included. PNS was associated with a higher weaning success rate (OR = 2.96, 95% CI: 1.04 to 8.40, p = 0.04), a shorter duration of mechanical ventilation (MD = −2.63, 95% CI: −3.90 to −1.35, p < 0.001), higher maximal inspiratory pressure (MD = 2.95, 95% CI: 1.10 to 4.79, p = 0.002), and higher diaphragm thickening fraction (MD = 15.67, 95% CI: 4.84 to 26.50, p = 0.005). No statistically significant differences were observed in ICU length of stay, rapid shallow breathing index, or tracheostomy rate. Noninvasive stimulation was generally tolerated in the included studies, whereas transvenous stimulation was associated with procedure-related serious adverse events. The certainty of evidence ranged from high to low across outcomes. Conclusions: PNS was associated with improved weaning outcomes and diaphragm function in mechanically ventilated patients. However, the evidence remains limited by the small number of RCTs, clinical heterogeneity, and uncertainty regarding long-term outcomes. Further large-scale, multicenter RCTs with standardized protocols are needed to assess the efficacy and safety of PNS. Full article

Background: The timing of tracheostomy in the intensive care unit (ICU) is debated because of its potential effects on comfort, sedation management, and ventilator weaning. Objective: To compare early (≤10 days) versus late (>10 days) tracheostomy with respect to discontinuation of sedation and invasive ventilation. Methods: Single-centre retrospective observational study. We included 52 consecutive ICU patients who underwent tracheostomy (January 2023–June 2025): 16 early and 36 late. Switching to dexmedetomidine was considered discontinuation of hypnotic sedation; transition to home mechanical ventilation (VAM) was considered discontinuation of invasive ventilation. Results: Sedation discontinuation occurred in 15/16 (93.8%) early vs. 35/36 (97.2%) late patients (p = 0.525). Discontinuation of invasive ventilation occurred in 12/16 (75.0%) early vs. 31/36 (86.1%) late patients (p = 0.431). Tracheostomy-to-sedation stop time: median 3 days [IQR 1–10] (overlapping between groups). Tracheostomy-to-ventilation stop time: median 17 days [IQR 10–27] (17 [11–33] early vs. 17 [10–25] late). ICU mortality: 3/16 (18.8%) vs. 6/36 (16.7%) (p = 1.00). Conclusions: In this retrospective cohort, no statistically significant differences emerged between early and late tracheostomy regarding discontinuation of sedation or invasive ventilation. However, given the retrospective design and small sample size, the study may have been underpowered to detect smaller but clinically relevant differences between groups. Prospective studies with larger sample sizes and severity-related variables may clarify any effects of timing. Full article

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the concept of “treatable traits” to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO₂) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it clinically relevant in selected situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994–2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation (IMV), and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with chronic obstructive pulmonary disease or obesity hypoventilation. For IMV, the effects depended on the presence and severity of acidosis and on its duration. Overall, PaCO₂ showed context-dependent clinical relevance, acting mainly as a prognostic or stratification marker and, in narrower settings, as a variable that may inform monitoring or support decisions. This review provides a pragmatic framework for interpreting PaCO₂ across respiratory support contexts and highlights the need for safe and clinically meaningful targets. Full article

Background: Failure of liberation from mechanical ventilation remains common despite successful spontaneous breathing trials (SBTs) and is associated with increased morbidity, prolonged ICU stay, and mortality. We aimed to evaluate the role of diaphragm and lung ultrasound for predicting composite liberation failure, including SBT failure and post-extubation failure, in adults. Methods: We conducted a systematic review with descriptive synthesis in accordance with PRISMA-DTA guidelines. The review protocol was developed a priori but was not prospectively registered. MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to 20 January 2026. Adult studies evaluating diaphragm ultrasound (diaphragm thickening fraction [DTF], diaphragmatic excursion [DE]) and/or lung ultrasound in patients undergoing SBTs were included. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results: Six studies (n = 430) were included. DTF demonstrated the most consistent association with liberation failure (AUC range 0.64–0.99; sensitivity 78–100%). DE showed a similar but less consistent association (AUC range 0.77–0.86). Elevated lung ultrasound scores—reflecting aeration loss from cardiogenic edema, acute respiratory distress syndrome (ARDS), atelectasis, or pneumonia—were associated with extubation failure. Conclusions: DTF shows potential clinical utility as an adjunct for predicting liberation outcomes. LUS offers complementary insight into aeration loss regardless of etiology. Standardization of measurement protocols and larger prospective studies are needed. Full article

Diaphragm dysfunction that leads to respiratory failure is a significant clinical consequence of sepsis-induced critical illness. Diaphragm muscle weakness contributes to morbidity and mortality in these individuals in part due to impaired mitochondrial function. Restoring normal mitochondrial biogenesis is associated with improved survival and physical function. Therefore, identifying reliable biomarkers of mitochondrial dysfunction in diaphragm muscle will allow for more focused and targeted interventions designed to improve the morbidity of critically ill patients. We used a rodent cecal-ligation and puncture (CLP) model to mimic a moderate grade of sepsis. The diaphragm muscle was harvested from adult mice 48 h following CLP (n = 6) or a sham CLP procedure (n = 6). Our primary finding was that moderate grade CLP increases expression of mitochondria-associated microRNA in the diaphragm. Correspondingly, genes associated with mitochondrial biogenesis decreased. Our study provides evidence for sepsis-mediated dysregulation of mitochondrial homeostasis. This may play a role in diaphragm muscle dysfunction, respiratory failure, and difficult weaning from mechanical ventilation in sepsis-induced critical illness. Full article

Background: Body mass index (BMI) is a common nutritional marker, but admission-only measurements present limitations. Early dynamic BMI changes may better reflect metabolic stress and fluid balance. However, the clinical significance of early BMI trajectory during critical illness remains poorly understood. This study evaluated the impact of early BMI trajectory on mortality and ventilator weaning in critically ill patients. Methods: This retrospective cohort study included 1355 adult patients (ICU stay ≥ 7 days) admitted to the medical ICU between 2019 and 2025. BMI trajectory was defined as the percentage change from admission to day 7 and was categorized into three groups: decrease (>5% reduction), stable (±5%), and increase (>5% gain). Multivariable Cox proportional hazard and logistic regression analyses were performed to evaluate the association between BMI trajectory and clinical outcomes. Results: Of the 1355 patients, 15.9%, 57.7%, and 26.4% were in the decrease, stable, and increase groups, respectively. The increase group demonstrated significantly higher hospital mortality (52.5%) than the decrease (41.9%) and stable (40.0%) groups (p = 0.001). Multivariable analysis revealed that an increasing BMI trajectory was independently associated with higher hospital mortality (HR 1.25, 95% CI 1.05–1.48). A decreasing BMI trajectory strongly predicted successful ventilator weaning (OR 2.76, 95% CI 1.81–4.21). Conclusions: Early BMI trajectory significantly predicted ICU outcomes. Increasing and decreasing BMI were associated with higher mortality and improved ventilator weaning, respectively. These findings suggest that BMI trajectory may be a simple surrogate marker of metabolic stress, nutritional status, and fluid balance during early critical illness. Full article

Background/Objectives: Survival after pediatric intensive care unit (PICU) admission has improved, yet many children experience post-intensive care syndrome in pediatrics (PICS-p), including persistent feeding difficulties that impair growth and quality of life. An intensive feeding program (IFP), also known as intensive interdisciplinary behavioral treatment (IIBT), reduces tube dependence and improves oral intake; however, outcomes in PICU survivors remain understudied. This study aimed to evaluate feeding outcomes in children with prior PICU admission who completed IIBT. Methods: This study was a retrospective case series of children (0–18 years) admitted to the HDVCH, Corewell Health, Grand Rapids, Michigan, who subsequently completed IIBT (from 2007 to 2024). Variables included demographics, PICU course (admission indication, complications, length of stay, ventilation, and nutrition status) and IIBT outcomes (feeding modality, oral skills, and malnutrition status). Feeding outcomes were compared pre- and post-IIBT. Results: Sixteen patients were included (62.5% female; mean age 1.44 ± 1.21 years). Primary PICU admission causes were post-operative recovery (68.8%) and acute respiratory failure (25%). PICU complications included acute respiratory failure (43.8%) and the need for respiratory support beyond baseline (62.5%). At PICU discharge, 75% remained tube-fed and 18.8% were malnourished. The mean time from PICU discharge to IIBT initiation was 641 ± 385 days. At IIBT baseline, 75% were tube-fed and all were non-self-feeders. Following IIBT completion (mean length of stay 4.8 ± 0.9 weeks), 58% of tube-fed patients achieved tube removal eligibility; 44% transitioned to partial or full self-feeding; problematic mealtime behaviors decreased (45.7% → 9.9%); oral acceptance improved (62% → 95%); and mouth clearance improved (59% → 96%). Malnutrition prevalence decreased (20% → 12%). Conclusions: Children with prior PICU admission demonstrated substantial feeding and behavioral improvement during IIBT participation, with over half achieving tube-weaning eligibility. The time from referral to program start reflects barriers that delay intervention. Full article

Background/Objectives: Ventilator weaning imposes profound hemodynamic stress, unmasking cardiopulmonary vulnerability. Since conventional predictors of post-tracheostomy weaning failure remain elusive, biomarker-driven risk stratification offers a translational approach. We evaluated the prognostic utility of admission N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an early triaging tool for weaning failure and explored its therapeutic implications alongside optimal tracheostomy timing. Methods: In this large-scale retrospective cohort study, we analyzed 707 critically ill patients who underwent tracheostomy in a medical intensive care unit. We investigated the association between baseline NT-proBNP levels—measured as a molecular surrogate of cardiovascular stress at ICU admission; echocardiographic parameters; and weaning outcomes. Multivariable logistic regression analysis was utilized to identify independent pathophysiological predictors associated with weaning failure. Results: Patients experiencing weaning failure exhibited significantly elevated admission NT-proBNP levels compared to those successfully weaned (3077.0 vs. 1410.0 pg/mL, p < 0.001). High admission NT-proBNP (>3271 pg/mL) was independently associated with an increased risk of weaning failure (adjusted odds ratio [aOR] 2.86, 95% confidence interval [CI] 1.81–4.53, p < 0.001). Conversely, an early clinical intervention—tracheostomy performed within 10 days of mechanical ventilation initiation—was associated with a significantly lower risk of weaning failure (aOR 0.55, 95% CI 0.35–0.87, p = 0.010). Furthermore, elevated biomarker levels strongly correlated with prolonged intensive care unit stays and higher 90-day mortality. Conclusions: Admission NT-proBNP serves as a powerful biomarker associated with cardiopulmonary vulnerability from the earliest stages of critical illness. Integrating this diagnostic biomarker with interventional strategies like optimal tracheostomy timing has significant prognostic implications. This biomarker-guided approach facilitates personalized risk stratification from ICU admission, potentially optimizing weaning pathways for mechanically ventilated patients. Full article

The evolution of non-invasive mechanical ventilation (NIV) from the iron lung of the 1950s to the use of sophisticated ventilators with mask apparatus has allowed for the optimal management of a wide range of respiratory disorders. NIV is now a mainstay in the management of acute, chronic and acute-on-chronic hypoxemic and hypercapnic respiratory failure from diverse etiologies. While NIV offers an effective approach to avoid invasive mechanical ventilation with its inherent risks of lung injury and sedation-related harms, it is a complex modality that requires a nuanced approach to management As the use of NIV has become ubiquitous, complex challenges are faced in the initiation, management and discontinuation of the treatment. We review complex clinical scenarios that present during liberation from non-invasive mechanical ventilation and an approach to successful weaning and liberation in these patient populations. Full article

Background: Malnutrition and sarcopenia are highly prevalent in intensive care settings and are associated with adverse clinical outcomes. Aim: The study aimed to evaluate the association between nutritional care, nutritional status, and patient outcomes in intensive care units. Methods: This prospective observational study at a Tunisian tertiary hospital investigated nutritional status and management of 100 intensive care unit patients, each of whom was followed for seven days after ICU admission. Malnutrition Risk was assessed by NUTRIC and MNA scores. The severity of disease was assessed using the APACHE II and SOFA scores. Malnutrition was diagnosed using body mass index and weight loss. Sarcopenia was assessed through grip strength, calf circumference, and psoas muscle area. Nutritional management was evaluated using calculations of caloric and protein intake. Clinical outcomes included the need for intubation, difficulty with oxygen weaning, healthcare-associated infections, and the development of pressure ulcers. Results: The participants had a mean age of 54.85 ± 17.25 years, with a slight male predominance (53 males, 47 females). Pre-existing metabolic conditions affected 80% of patients, including hypertension (40 patients), diabetes (36), and obesity (18). The primary reasons for admission were respiratory disorders (25%), infectious diseases (23%), and metabolic disorders (16%). The mean APACHE II score was 15.91 ± 6.84, and the mean NUTRIC score was 3 ± 1.66; 27% were classified as at high risk of malnutrition. The prevalence of malnutrition reached 50% (28% moderate, 22% severe). Only 31% received adequate caloric intake, while 84% had insufficient protein intake. Malnourished patients required intubation more frequently (50% versus 22.5%; p = 0.014), experienced greater difficulty with oxygen weaning (78.4% versus 48.6%; p = 0.008), and developed pressure ulcers more often (43.5% versus 6%; p < 0.001). Sarcopenic patients showed similar patterns for intubation (51.4% versus 18.9%, p = 0.003), oxygen weaning difficulty (77.5% versus 46.9%, p = 0.007), and pressure ulcers (39.2% versus 6.7%, p < 0.001). Conclusions: Malnutrition and sarcopenia are highly prevalent in intensive care patients and are associated with severe complications, including prolonged mechanical ventilation and pressure ulcer development. Inadequate nutritional support remains common despite known consequences. Early comprehensive nutritional assessment and appropriate management from admission are essential to improve outcomes in critically ill patients. Full article

Extremely preterm infants often require prolonged respiratory support due to lung immaturity and inflammation, placing them at high risk of lung injury and development of bronchopulmonary dysplasia (BPD). In many of these infants, systemic postnatal corticosteroids are used to reduce lung inflammation, facilitate mechanical ventilation (MV) weaning and extubation, and improve short-term pulmonary outcomes. However, despite decades of clinical use, substantial variation persists in timing, choice of agent and dosing. These inconsistencies reflect a lack of strong evidence and a limited understanding of the systemic and organ-specific effects of therapy for a highly heterogenous population usually exposed to this medication. This narrative review addresses these gaps by integrating current knowledge of the inflammatory and respiratory effects of postnatal corticosteroids in extremely preterm infants. We explore how corticosteroids modulate pulmonary inflammation, their effects on lung development, and how they affect key clinical outcomes such as extubation success and BPD severity. We also examine evolving approaches to corticosteroid administration and dosing, highlighting the importance of individualized strategies informed by developmental and disease-specific considerations. Comparative data from randomized controlled trials are reviewed, including the efficacy and side-effect profiles of commonly used regimens. Current evidence supports judicious use of late low-dose dexamethasone, while early prophylaxis with inhaled or intratracheal steroids remains experimental and is not routinely advised. In line with a physiology-driven approach, we also discuss emerging domain-specific monitoring tools that may enhance patient selection and optimize timing of intervention. By synthesizing mechanistic insights with clinical evidence, this review supports a more nuanced, individualized approach to postnatal corticosteroid therapy in extremely preterm infants, balancing therapeutic benefits with potential systemic trade-offs. Full article

Background: In critically ill patients, tracheostomy decisions are driven by heterogeneous and dynamic clinical trajectories, and no universally accepted scoring system exists to reliably predict tracheostomy requirement. An accurate and interpretable prediction model could help earlier decision-making and potentially reduce prolonged mechanical ventilation (MV) and failed weaning. Methods: In this retrospective study, data from 6507 mechanically ventilated intensive care unit (ICU) patients were analyzed using an electronic clinical decision support system; 1049 patients required tracheostomy and 5458 did not. The primary outcome was the prediction of tracheostomy occurrence during ICU stay based on invasive mechanical ventilation (IMV) parameters obtained within the first five days. The secondary outcome was the identification of the most influential parameters guiding tracheostomy decision-making during early IMV. Ten machine learning algorithms were developed using an 80/20 train–test split. Model performance was assessed using discrimination, calibration, and clinical performance metrics. Explainability was evaluated using SHapley Additive exPlanations (SHAP) analysis. Results: Among all models, Gradient Boosting demonstrated strong discrimination and calibration performance (AUROC 0.92, AUPRC 0.56, specificity 97%, F1 score 0.46, Brier score 0.078). In the Gradient Boosting model, feature importance analysis demonstrated that secretion count was the strongest predictor of tracheostomy requirement, accounting for 14.72% of the model’s predictive contribution. This was followed by lactate level (6.12%), arterial pH (3.74%), and peak airway pressure (3.57%). SHAP-based analyses consistently identified secretion count as the strongest predictor of tracheostomy requirement, followed by lactate level, Glasgow Coma Scale (GCS), and arterial pH. In addition, SHAP provided clinically interpretable insights into the direction and magnitude of the effects of individual predictors. Conclusions: Machine learning models integrating early-phase ventilatory and physiological data may enable clinically meaningful prediction of tracheostomy requirement. The combination of strong performance and explainability suggests potential utility as a decision-support tool in critically ill patients requiring prolonged MV. Full article

Introduction: Acute encephalitis is a severe neurological complication whose association with SARS-CoV-2 infection is increasingly recognized. However, the precise pathophysiological mechanisms remain incompletely understood. Understanding the factors contributing to central nervous system involvement in COVID-19 is crucial for guiding clinical management and improving patient outcomes. Methods: This single-center, retrospective cohort study analyzed data from 450 adult critically ill patients with RT-qPCR-confirmed SARS-CoV-2 infection admitted to our ICU between May 2021 and March 2023. All SARS-CoV-2-positive patients with suspected CNS involvement were included and categorized into encephalitis-positive (E+, n = 38) and encephalitis-negative (E−, n = 58) groups according to neurological examination, imaging, and lumbar puncture findings during ventilator weaning. Key patient characteristics, laboratory parameters at ICU admission (including SARS-CoV-2 Ct values and D-dimer levels), and clinical outcomes were analyzed with appropriate statistical methods, including ROC curve analysis and Cox regression. Results: Patients in the E+ group, compared with the E− group, were significantly older (mean 69 ± 15 vs. 61 ± 12 years, p = 0.006) and exhibited significantly lower median SARS-CoV-2 Ct values (23.7 vs. 27.0, p < 0.001) indicative of higher viral loads. The median D-dimer levels were also significantly elevated in the E+ group (4.6 vs. 1.1, p < 0.001). Other baseline characteristics and inflammatory markers were comparable between groups. Patients with encephalitis experienced significantly longer mechanical ventilation durations (median 19 vs. 14 days, p = 0.006) and ICU stays (median 21 vs. 15 days, p = 0.009) compared to those without encephalitis. No significant difference was observed in overall mortality between the groups (50.0% vs. 56.9%, p = 0.507). Multivariate analysis identified lower Ct values (HR: 1.9, p = 0.032) and higher D-dimer levels (HR: 2.9, p < 0.010) at ICU admission as independent risk factors for encephalitis development. Conclusions: Our findings indicated that higher SARS-CoV-2 viral loads (lower Ct values), older age, and higher D-dimer levels were significantly associated with a greater risk of COVID-19-associated encephalitis in critically ill patients. These markers might aid in identifying patients at high risk of neurological complications, thereby facilitating earlier monitoring and potentially improving patient management. Further prospective studies are warranted to fully elucidate the pathophysiological mechanisms underlying this association. Full article