Romero-García N, Robba C, Ruiz-Pacheco A
… +8 more, Pascual-González M, Beltran-Piles C, Devís-Peiró A, Martí-Cervera JF, Premraj L, Cinotti R, Taccone FS, Badenes R
BACKGROUND: Carbon dioxide is a key determinant of cerebral blood flow and is needed to prevent secondary damage in neurocritical care; however, optimal targets across the heterogeneous spectrum of acute brain injury (AB...BACKGROUND: Carbon dioxide is a key determinant of cerebral blood flow and is needed to prevent secondary damage in neurocritical care; however, optimal targets across the heterogeneous spectrum of acute brain injury (ABI) remain to be elucidated. The aim of this study was to evaluate the association between arterial hypocapnia and mortality and neurological outcomes in adult patients with ABI. METHODS: Six electronic databases were systematically searched from inception to January 2025. Observational and randomized controlled trials comparing exposure to hypocapnia, defined as an arterial partial pressure of carbon dioxide (PaCO) lower than 35 mmHg, and no-hypocapnia in adult patients with ABI-related conditions (including traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, central nervous system infections, brain tumors, and post-cardiac arrest encephalopathy) were included. Random-effects meta-analyses were conducted using the restricted maximum likelihood (REML) method to pool unadjusted odds ratios (ORs). The primary outcome was all-cause mortality, and the secondary outcome was the occurrence of poor neurological outcomes defined using validated scales. Prespecified subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. RESULTS: A total of 8,637 records were identified after duplicate removal, of which 37 studies met inclusion criteria for the systematic review. Twenty-seven studies (51,373 patients) were included for mortality outcomes, and thirteen studies (3,814 patients) were included for neurological outcomes. Hypocapnia was associated with higher odds of mortality in adult patients with ABI (OR 1.29, 95% CI 1.05-1.59). Subgroup analyses demonstrated variability across ABI types, with stronger associations observed in subarachnoid hemorrhage and ischemic stroke populations. Hypocapnia was also associated with increased odds of poor neurological outcomes (OR 2.09, 95% CI 1.24-3.54), particularly in the traumatic brain injury population. Subgroup analyses suggested that the association with neurological outcomes was more consistent in studies defining exposure as severe hypocapnia (PaCO<32 mmHg). CONCLUSIONS: Arterial hypocapnia was associated with increased mortality and poor neurological outcomes in adults with acute brain injury, although the evidence is predominantly observational and limited randomized data are available. These findings underscore the need for cautious, individualized PaCO management and further high-quality prospective research.
Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a complex and invasive intervention used increasingly in the management of severe respiratory failure. Once established, the management of prolonged V-V ECMO...Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a complex and invasive intervention used increasingly in the management of severe respiratory failure. Once established, the management of prolonged V-V ECMO support involves balancing priorities of lung protection, prevention of pulmonary complications, sedation weaning and safe reduction in ECMO support. These occur variably as the pulmonary pathology resolves and ECMO support is reduced. Evidence based strategies to assist clinicians during prolonged V-V ECMO support are lacking, with the majority of literature focussing on ventilation strategies following ECMO initiation and the criteria for separation from V-V ECMO once liberation is considered safe. Practice is largely clinician and institution dependent with significant heterogeneity. There are numerous questions which remain unanswered regarding the prioritisation and strategies for safe V-V ECMO weaning. This review aimed to provide a novel conceptual framework to assist clinicians by dividing prolonged V-V ECMO support into six phases: ultra-lung-protective, lung protective, transition to spontaneous breathing, liberation trial, decannulation and post decannulation support. We reviewed existing literature and identified knowledge gaps for future research.
BACKGROUND: Vasopressor responsiveness in septic shock is typically assessed using static metrics that cannot capture temporal hemodynamic evolution. The Blood Pressure Response Index (BPRI = mean arterial pressure / Vas...BACKGROUND: Vasopressor responsiveness in septic shock is typically assessed using static metrics that cannot capture temporal hemodynamic evolution. The Blood Pressure Response Index (BPRI = mean arterial pressure / Vasoactive-Inotropic Score) integrates hemodynamic response and treatment intensity into a single metric, but its longitudinal trajectory patterns remain unexplored. METHODS: We applied latent class mixed models to BPRI trajectories during the first 48 h of vasopressor therapy in 4,389 septic shock patients from MIMIC-IV (development cohort). External validation was performed via parameter transport to 1,240 eICU-CRD patients. The prognostic significance of trajectory phenotypes was assessed using multivariable logistic and Cox regression with a three-level adjustment framework, restricted mean survival time analysis, and incremental predictive value assessment beyond conventional severity scores. RESULTS: Six distinct hemodynamic phenotypes were identified with ICU mortality ranging from 21.9% (C3 Responders) to 54.5% (C2 Non-Responders). Parameter transport validation showed preserved class separation and prognostic gradient (average posterior probability 0.960) in eICU-CRD. After full multivariable adjustment, C2 (OR 3.67, 95% CI 2.76-4.86) and C1 (OR 2.68, 95% CI 2.08-3.46) remained independently associated with ICU mortality. Restricted mean survival time analysis showed the largest adjusted losses for C2 (- 2.56 days at τ = 14 days) with minimal attenuation from unadjusted estimates, suggesting an association that persisted after comprehensive adjustment. Adding trajectory classification to severity scores yielded statistically significant incremental discrimination (ΔAUC + 0.020, P < 0.001), while static BPRI added no further information. CONCLUSIONS: BPRI trajectory analysis identifies six hemodynamic phenotypes in septic shock that are validated in an independent external database, are independently associated with mortality, and capture temporal hemodynamic response patterns missed by static assessments. These phenotypes may facilitate risk stratification and enrichment strategies for clinical trials targeting vasopressor-dependent patients.
BACKGROUND: Lung-protective ventilation in acute respiratory distress syndrome (ARDS) can lead to hypercapnia, an independent risk factor for increased mortality. Extracorporeal CO removal (ECCOR) enables further reducti...BACKGROUND: Lung-protective ventilation in acute respiratory distress syndrome (ARDS) can lead to hypercapnia, an independent risk factor for increased mortality. Extracorporeal CO removal (ECCOR) 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 ECCOR (miECCOR) implemented via a renal replacement therapy (RRT) platform in patients with mild-to-moderate ARDS and refractory hypercapnia. METHODS: In this prospective single-center observational study, 20 ICU patients with persistent hypercapnia despite escalated ventilation received either standalone miECCOR (n = 11) or miECCOR combined with continuous RRT (n = 9). As a primary outcome, efficacy of miECCOR 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 miECCOR. RESULTS: miECCOR led to a rapid and sustained reduction in PaCO levels from 71.4 mm Hg to 51.6 mm Hg within 24 h. This was accompanied by normalization of pH, and the median CO clearance rate was 64.5 mL/min. Driving pressure decreased significantly from 22 cm HO to 15 cm HO by day 5, while oxygenation remained stable. The standalone miECCOR treatment group demonstrated faster CO 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. CONCLUSIONS: miECCOR 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 miECCOR on clinical outcomes.
Calvo-Barceló M, Irvine FB, Tierney N
… +13 more, Ayyar S, Devine T, Panoulas V, Montegudo-Vela M, Gil FR, Caballero CH, Poveda Pinedo ID, Bautista J, Van Schoor J, Hall D, Pinto S, Galiatsou E, Rosenberg A
Wicky PH, Petit ÉM, Bordet F
… +7 more, Aebischer É, Dupré C, Rousseau AF, Bodet-Contentin L, Federici L, Thiery G, SRLF’s Patients and Relatives Working Group
BACKGROUND: Pneumonia is the leading cause of sepsis. This study aimed to compare the predictive accuracy for 28-day mortality between Sequential Organ Failure Assessment (SOFA)-2 score and SOFA score in pneumonia-associ...BACKGROUND: Pneumonia is the leading cause of sepsis. This study aimed to compare the predictive accuracy for 28-day mortality between Sequential Organ Failure Assessment (SOFA)-2 score and SOFA score in pneumonia-associated sepsis, and to develop and externally validate a composite model incorporating SOFA-2 with key clinical variables. METHODS: This retrospective cohort study analyzed data from MIMIC-IV (n = 7,150) and externally validated using an Intensive Care Unit (ICU) cohort from Shandong Provincial Hospital (n = 301). Adults meeting Sepsis-3 criteria with pneumonia as the infection source were included. The primary outcome was 28-day all-cause mortality. Multivariable Cox regression, time-dependent AUC analysis, and decision curve analysis were performed. The SOFA-2 composite model was developed and evaluated. RESULTS: In the MIMIC‑IV cohort, the 28‑day all-cause mortality was 28.1%. Multivariable analysis indicated that the SOFA‑2 score was an independent predictor of 28‑day mortality. The Area Under the Curve (AUC) curves of SOFA‑2 and SOFA overlapped substantially, with no significant difference in predictive performance (day 1: 0.78 vs. 0.79; day 28: 0.61 vs. 0.62). A composite SOFA‑2 model significantly improved predictive performance (day‑1 AUC = 0.87). MaxStat analysis identified an optimal risk‑stratification cutoff of 11 for SOFA‑2; patients in the high‑score group (> 11) had significantly lower 28‑day survival than those in the low‑score group (p < 0.001). Subgroup analysis demonstrated that the association between SOFA‑2 and prognosis remained consistent across different characteristic subgroups. External validation further confirmed the independent prognostic value and risk‑stratification ability of SOFA‑2. CONCLUSIONS: In patients with pneumonia‑associated sepsis, the SOFA‑2 score exhibited a predictive performance for 28‑day mortality risk similar to that of the conventional SOFA score. Although its standalone use did not show superiority, integrating SOFA‑2 with key clinical variables into a composite model significantly enhanced predictive accuracy.
Liufu R, Fu XY, Shi XQ
… +12 more, Shen F, Wu Y, Cao M, Wang YF, Peng JM, Jiang W, Hu XY, Wang YY, Weng L, Zhou X, Du B, China Critical Care Clinical Trials Group (CCCCTG)
OBJECTIVE: The revised Sequential Organ Failure Assessment (SOFA-2) score was recently developed to update definitions of acute organ dysfunction in intensive care units (ICU). This study aimed to evaluate performance be...OBJECTIVE: The revised Sequential Organ Failure Assessment (SOFA-2) score was recently developed to update definitions of acute organ dysfunction in intensive care units (ICU). This study aimed to evaluate performance between SOFA-1 and SOFA-2 definition for sepsis identification in patients with suspected infection. METHODS: We analyzed 24,510 patients with suspected infection in Chinese multicenter cohort and validated in the MIMIC-IV database. Patients were divided into four categories based on concordance between SOFA versions: SOFA-1(-)/SOFA-2(-), SOFA-1(+)/SOFA-2(+), SOFA-1(-)/SOFA-2(+), and SOFA-1(+)/SOFA-2(-). Kaplan-Meier analyses and cox proportional hazards models assessed the associations with in-hospital mortality. RESULTS: Most patients met sepsis criteria under both SOFA versions (18,179/24,510; 74.2%[95% confidential interval (CI), 73.6%-74.7%]), while 9.9% (95% CI, 9.53%-10.2%) were classified as SOFA-1(+)/SOFA-2(-), 5.5% (95% CI, 5.2%-5.8%) as SOFA-1(-)/SOFA-2(+), and 10.2% (95% CI, 9.8%-10.6%) as SOFA-1(-)/SOFA-2(-). Patients in SOFA-1(-)/SOFA-2(+) group were younger, more often male, higher rates of pneumonia, gastrointestinal infection, and neurologic infection. Superior discrimination for in-hospital mortality was observed in SOFA-2 [area under the receiver operating characteristic curve (AUROC) 0.746; 95% confidence interval (CI) 0.737-0.756] compared with SOFA-1 (0.679; 95% CI 0.668-0.689). In-hospital mortality was markedly higher in SOFA-2 (+) groups [2.9% in SOFA-1(-)/SOFA-2(-), 3.3% in SOFA-1(+)/SOFA-2(-), 10.6% in SOFA-1(-)/SOFA-2(+), and 14.3% in SOFA-1(+)/SOFA-2(+); p < 0.001]. Compared with SOFA-1(-)/SOFA-2(-), the hazard ratios for in-hospital mortality were 0.99 (95% CI, 0.72-1.36) for SOFA-1(+)/SOFA-2(-), 3.52 (95% CI, 2.66-4.67) for SOFA-1(-)/SOFA-2(+), and 4.44 (95% CI, 3.52-5.60) for SOFA-1(+)/SOFA-2(+). These patterns were consistent in sensitivity analyses. CONCLUSION: SOFA-2-based sepsis identified a clinically meaningful higher-risk subgroup, with consistent results across sensitivity analyses. Nevertheless, cohort-specific differences emphasize the need for cautious interpretation and further validation in diverse clinical settings.