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The cardiovascular system plays a key role in sepsis, and septic myocardial depression is a common finding associated with increased morbidity and mortality. Myocardial depression during sepsis is not clearly defined, but it can perhaps be best described as a global (systolic and diastolic) dysfunction of both the left and right sides of the heart. The pathogenesis of septic myocardial depression involves a complex mix of systemic (hemodynamic) factors and genetic, molecular, metabolic, and structural alterations. Pulmonary artery catheterization and modern echo-Doppler techniques are important diagnostic tools in this setting. There are no specific therapies for septic myocardial depression, and the cornerstone of management is control of the underlying infectious process (adequate antibiotic therapy, removal of the source) and hemodynamic stabilization (fluids, vasopressor and inotropic agents). In this review, we will summarize the pathogenesis, diagnosis, and treatment of myocardial depression in sepsis. Additional studies are needed in order to improve diagnosis and identify therapeutic targets in septic myocardial dysfunction.

IntroductionIn critically ill patients, individualised strategies for red blood cell transfusion (RBCT) are lacking. The objective of this study is to demonstrate the potential advantages of employing an individualised transfusion strategy compared with a restrictive approach, in unselected intensive care unit (ICU) patients.MethodsThis will be a randomised, multicentre, international trial. Two open-label parallel groups will be compared with an allocation ratio of 1:1. The trial is designed to investigate the superiority of the individualised intervention group compared with the standard intervention group. The study will be performed in four mixed academic ICU located in two different countries. In the individualised group, prescription of RCBT is restricted to patients who present haemoglobin (Hb) ≤9.0 g/dL and oxygen extraction ratio (O2ER) ≥ 30%, for a minimum Hb value of ≤6.0 g/dL. In the control group, prescription of RBCT is guided by thresholds proposed by recent guidelines, regardless of O2ER values.Ethics and disseminationThis trial is approved by the Comitato Etico Area Vasta Centro della Regione Emilia-Romagna (protocol number 350/2023/Sper/AOUFe/PRBCT, date of approval 18/05/2023) and ethic boards at all participating sites. Our results will be published and shared with relevant organisations and healthcare professionals.Trial registration numberClinicaltrials.gov NCT06102590

Lung transplantation is a life-saving procedure for end-stage lung diseases. Size matching is critical in the donor-recipient selection process. This retrospective study analyzed 146 patients who underwent lung transplantation between 2013 and 2023. Patients who required graft resizing were assigned to the sizing group (S), non-resizing cases to the non-sizing group (NS). The primary goal was to identify predictive factors for graft resizing. Secondary endpoints included ischemia time, ventilation time, primary graft dysfunction (PGD) and hospital stay. The S group was further stratified on baseline parameters to assess differences in outcomes. Recipient height and single transplants were higher in the NS group. Donor-recipient height ratio was the only predictor for resizing (p = 0.02). Postoperative outcomes and overall survival were similar between the groups. In Group S, male patients showed higher rates of acute kidney injury (AKI) and chronic rejection, the former being associated also with anatomical resections; patients older than 50 experienced higher rates of PGD. Graft resizing is a feasible strategy for addressing size mismatch, but it is associated with increased risks of PGD and AKI, particularly in older male recipients and those undergoing anatomical resections. These findings highlight the importance of careful preoperative donor-recipient size matching.

Background and objectives: In older and frail patients, in-hospital cardiac arrest (IHCA) is associated with high mortality. Early warning scores such as the National Early Warning Score 2 (NEWS2) are widely used to detect clinical deterioration, but their predictive accuracy in frail populations remains uncertain. This study aimed to assess whether integrating frailty measures with NEWS2 could better describe elderly IHCA patients. Materials and Methods: We conducted a single-center, retrospective observational study in adult and frail patients (≥18 years) admitted to medical and surgical wards of the University Hospital of Siena who experienced IHCA between January 2022 and January 2024. Data on demographics, such as last NEWS2 before IHCA, Clinical Frailty Scale (CFS), Barthel Index (BI), and Charlson Comorbidity Index (CCI) were retrospectively collected and analyzed. Patients were stratified into three categories, according to NEWS2: Stable (A), Potentially Unstable or Unstable (B), and Critical (C). Results: Seventy patients were analyzed (mean age 76.9 ± 11.0 years; 56% male). The mean pre-IHCA NEWS2 score was 6.0 ± 3.5, with 41% of patients classified as NEWS2-C, 48% classified as NEWS2-B, and 11% classified as NEWS2-A. The NEWS2-A category showed higher BI and lower CFS than NEWS2-B and NEWS2-C (p < 0.01), while CCI and age did not significantly differ. Conclusions: The association of NEWS2 with frailty scores could identify some elderly patients with limited pre-arrest physiological derangements but high frailty who suffered from IHCA. These findings provide descriptive insights that may inform monitoring strategies for “at-risk” elderly patients to help prevent IHCA.

Few data are available regarding hypoxic hepatitis (HH) and acute liver failure (ALF) in patients resuscitated from cardiac arrest (CA). The aim of this study was to describe the occurrence of these complications and their association with outcome. All adult patients admitted to the Department of Intensive Care following CA were considered for inclusion in this retrospective study. Exclusion criteria were early death (<24 hours) or missing biological data. We retrieved data concerning CA characteristics and markers of liver function. ALF was defined as a bilirubin >1.2 mg/dL and an international normalized ratio ≥1.5. HH was defined as an aminotransferase level >1000 IU/L. Neurological outcome was assessed at 3 months and an unfavourable neurological outcome was defined as a Cerebral Performance Categories (CPC) score of 3-5. A total of 374 patients (age 62 [52-74] years; 242 male) were included. ALF developed in 208 patients (56%) and HH in 27 (7%); 24 patients developed both conditions. Patients with HH had higher mortality (89% vs. 51% vs. 45%, respectively) and greater rates of unfavourable neurological outcome (93% vs. 60% vs. 59%, respectively) compared to those with ALF without HH (n = 184) and those without ALF or HH (n = 163; p = 0.03). Unwitnessed arrest, non-shockable initial rhythm, lack of bystander cardiopulmonary resuscitation, high adrenaline doses and the development of acute kidney injury were independent predictors of unfavourable neurological outcome; HH (OR: 16.276 [95% CIs: 2.625-81.345; p = 0.003), but not ALF, was also a significant risk-factor for unfavourable outcome. Although ALF occurs frequently after CA, HH is a rare complication. Only HH is significantly associated with poor neurological outcome in this setting.

Background Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome. Methods Retrospective analysis of all patients undergoing venous–venous (V–V) or venous–arterial (V–A) ECMO with a concomitant EEG recording (April 2009–December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge. Results A total of 139 patients (54 [41–62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno–arterial (V–A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25–16.74]; p  = 0.02) and a suppressed background (OR 10.08 [1.24–82.20]; p  = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories. Conclusions In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.

Background Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. Methods This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. Results Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7–22). Median DTF within 24 h since the start of weaning was 28% (IQR 22–39%), RASS score (− 2 vs − 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO 2 /FiO 2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 10 27 ; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO 2 /FiO 2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). Conclusions DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

BackgroundVariation of inferior vena cava (IVC) is used to predict fluid-responsiveness, but the IVC visualization with standard sagittal approach (SC, subcostal) cannot be always achieved. In such cases, coronal trans-hepatic (TH) window may offer an alternative, but the interchangeability of IVC measurements in SC and TH is not fully established. Furthermore, artificial intelligence (AI) with automated border detection may be of clinical value but it needs validation.MethodsProspective observational validation study in mechanically ventilated patients with pressure-controlled mode. Primary outcome was the IVC distensibility (IVC-DI) in SC and TH imaging, with measurements taken both in M-Mode or with AI software. We calculated mean bias, limits of agreement (LoA), and intra-class correlation (ICC) coefficient.ResultsThirty-three patients were included. Feasibility rate was 87.9% and 81.8% for SC and TH visualization, respectively. Comparing imaging from the same anatomical site acquired with different modalities (M-Mode vs AI), we found the following IVC-DI differences: (1) SC: mean bias − 3.1%, LoA [− 20.1; 13.9], ICC = 0.65; (2) TH: mean bias − 2.0%, LoA [− 19.3; 15.4], ICC = 0.65. When comparing the results obtained from the same modality but from different sites (SC vs TH), IVC-DI differences were: (3) M-Mode: mean bias 1.1%, LoA [− 6.9; 9.1], ICC = 0.54; (4) AI: mean bias 2.0%, LoA [− 25.7; 29.7], ICC = 0.32.ConclusionsIn patients mechanically ventilated, AI software shows good accuracy (modest overestimation) and moderate correlation as compared to M-mode assessment of IVC-DI, both for SC and TH windows. However, precision seems suboptimal with wide LoA. The comparison of M-Mode or AI between different sites yields similar results but with weaker correlation. Trial registration Reference protocol: 53/2022/PO, approved on 21/03/2022

SARS-CoV2-induced direct cytopathic effects against type II pneumocytes are suspected to play a role in mediating and perpetuating lung damage. The aim of this study was to evaluate serum KL-6 behavior in COVID-19 patients to investigate its potential role in predicting clinical course. Sixty patients (median age IQR, 65 (52–69), 43 males), hospitalized for COVID-19 at Siena COVID Unit University Hospital, were prospectively enrolled. Twenty-six patients were selected (median age IQR, 63 (55–71), 16 males); all of them underwent follow-up evaluations, including clinical, radiological, functional, and serum KL-6 assessments, after 6 (t1) and 9 (t2) months from hospital discharge. At t0, KL-6 concentrations were significantly higher than those at t1 (760 (311–1218) vs. 309 (210–408) p = 0.0208) and t2 (760 (311–1218) vs 324 (279–458), p = 0.0365). At t0, KL-6 concentrations were increased in patients with fibrotic lung alterations than in non-fibrotic group (755 (370–1023) vs. 305 (225–608), p = 0.0225). Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 levels showed good accuracy in discriminating patients with fibrotic sequelae radiologically documented (AUC 85%, p = 0.0404). KL-6 concentrations in patients with fibrotic involvement were significantly reduced at t1 (755 (370–1023) vs. 290 (197–521), p = 0.0366) and t2 (755 (370–1023) vs. 318 (173–435), p = 0.0490). Serum concentrations of KL-6 in hospitalized COVID-19 patients may contribute to identify severe patients requiring mechanical ventilation and to predict those who will develop pulmonary fibrotic sequelae in the follow-up.

Central venous pressure (CVP) has long been a cornerstone of hemodynamic monitoring, traditionally interpreted as a surrogate of intravascular volume and cardiac preload. Current evidence demonstrates that CVP has limited value as a standalone marker of preload and fluid responsiveness (FR), and its role as a fixed target for fluid resuscitation has progressively declined. This narrative review retraces the evolution of CVP interpretation, from its physiological foundations to its role in contemporary clinical practice. While early resuscitation strategies relied on predefined CVP thresholds, this approach has been abandoned. Despite these limitations, CVP remains widely used due to its simplicity and historical familiarity and modern perspectives instead emphasize its role as a marker of venous congestion. In this context, CVP retains clinical utility when used for waveform interpretation, assessment of venous congestion, and, most importantly, as part of an integrated, multimodal hemodynamic monitoring strategy.