Acute kidney injury predicts mortality in very elderly critically-ill patients.

BACKGROUND: The increasing admissions of very elderly patients to intensive care units (ICUs) over recent decades highlight a growing need for understanding acute kidney injury (AKI) in this population. Although these individuals are potentially at high risk for AKI and adverse outcomes, data on AKI in this population is scarce. This study investigates the AKI incidence and outcomes of critically-ill patients aging at least 90 years. METHODS: This retrospective cohort study conducted at the Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Germany (2008-2020), investigates AKI incidence and outcomes between 2008 and 2020 in critically-ill patients aged ≥ 90 years. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using creatinine dynamics and/or urine output. Primary endpoint was overall mortality after 1 year. Secondary endpoints were in-hospital mortality, length of ICU and hospital stay. RESULTS: During the study period 92,958 critically-ill patients were treated and 1108 were ≥ 90 years. Of these, 1054 patients had available creatinine values and were included in the present study. AKI occurred in 24.4%, mostly classified as mild (17.5%). AKI was independently associated with a significant increase in overall mortality (HR 1.21, 95 %-CI: 1.01-1.46), in-hospital mortality (OR 2, 1.41-2.85), length of ICU (+2.8 days, 2.3-3.3) and hospital stay (+2.3 days, 0.9-3.7). Severity escalated these effects, but even mild AKI showed significance. Introducing urine-based criteria increased incidence but compromised mortality prediction. CONCLUSIONS: AKI is a frequent complication in very elderly critically-ill patients. Occurrence of AKI at any stage was associated with increased mortality. Predictive ability applied to AKI defined by creatinine but not urine output. Careful attention of creatinine dynamics is essential in very elderly ICU-patients.

Kidney Doppler Ultrasonography in Critical Care Nephrology.

Color pulsed-wave Doppler ultrasound (CPWD-US) emerges as a pivotal tool in intensive care units (ICUs) for diagnosing acute kidney injury (AKI) swiftly and non-invasively. Its bedside accessibility allows for rapid assessments, making it a primary imaging modality for AKI characterization. Furthermore, CPWD-US serves as a guiding instrument for key diagnostic-interventional procedures such as renal needle biopsy and percutaneous nephrostomy, while also facilitating therapy response monitoring and AKI progression tracking. This review shifts focus towards the integration of renal ultrasound into ICU workflows, offering contemporary insights into its utilization through a diagnostic-standard-oriented approach. By presenting a flow chart, this review aims to provide practical guidance on the appropriate use of point-of-care ultrasound (POC-US) in critical care scenarios, enhancing diagnostic precision, patient management, and safety, albeit amidst a backdrop of limited evidence regarding long-term outcomes.

Renal implications of pneumoperitoneum in laparoscopic surgery: mechanisms, risk factors, and preventive strategies.

Pneumoperitoneum, which is established for laparoscopic surgery, has systemic implications on the renal system and may contribute to acute kidney injury or postoperative renal dysfunction. Specifically, when the pressure exceeds 10 mmHg, pneumoperitoneum decreases renal blood flow, leading to renal dysfunction and temporary oliguria. The renal effects of pneumoperitoneum stem from both the direct effects of increased intra-abdominal pressure and indirect factors such as carbon dioxide absorption, neuroendocrine influences, and tissue damage resulting from oxidative stress. While pneumoperitoneum can exacerbate renal dysfunction in patients with pre-existing kidney issues, preserving the function of the remaining kidney is crucial in certain procedures such as laparoscopic live donor nephrectomy. However, available evidence on the effects of pneumoperitoneum on renal function is limited and of moderate quality. This review focuses on exploring the pathophysiological hypotheses underlying kidney damage, mechanisms leading to oliguria and kidney damage, and fluid management strategies for surgical patients during pneumoperitoneum.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23.

BACKGROUND: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS: A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS: The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS: Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

The Future of Artificial Intelligence Using Images and Clinical Assessment for Difficult Airway Management.

Artificial intelligence (AI) algorithms, particularly deep learning, are automatic and sophisticated methods that recognize complex patterns in imaging data providing high qualitative assessments. Several machine-learning and deep-learning models using imaging techniques have been recently developed and validated to predict difficult airways. Despite advances in AI modeling. In this review article, we describe the advantages of using AI models. We explore how these methods could impact clinical practice. Finally, we discuss predictive modeling for difficult laryngoscopy using machine-learning and the future approach with intelligent intubation devices.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Bioimpedance-assessed muscle wasting and its relation to nutritional intake during the first week of ICU: a pre-planned secondary analysis of Nutriti Study.

BACKGROUND: Muscle mass evaluation in ICU is crucial since its loss is related with long term complications, including physical impairment. However, quantifying muscle wasting with available bedside tools (ultrasound and bioimpedance analysis) must be more primarily understood. Bioimpedance analysis (BIA) provides estimates of muscle mass and phase angle (PA). The primary aim of this study was to evaluate muscle mass changes with bioimpedance analysis during the first 7 days after ICU admission. Secondary aims searched for correlations between muscular loss and caloric and protein debt. METHODS: Patients with an expected ICU-stay ≥ 72 h and the need for artificial nutritional support were evaluated for study inclusion. BIA evaluation of muscle mass and phase angle were performed at ICU admission and after 7 days. Considering the difference between ideal caloric and protein targets, with adequate nutritional macronutrients delivered, we calculated the caloric and protein debt. We analyzed the potential correlation between caloric and protein debt and changes in muscle mass and phase angle. RESULTS: 72 patients from September 1st to October 30th, 2019 and from August 1st to October 30th, 2021 were included in the final statistical analysis. Median age was 68 [59-77] years, mainly men (72%) admitted due to respiratory failure (25%), and requiring invasive mechanical ventilation for 7 [4-10] days. Median ICU stay was 8 [6-12] days. Bioimpedance data at ICU admission and after 7 days showed that MM and PA resulted significantly reduced after 7 days of critically illness, 34.3 kg vs 30.6 kg (p < 0.0001) and 4.90° vs 4.35° (p = 0.0004) respectively. Mean muscle loss was 3.84 ± 6.7 kg, accounting for 8.4% [1-14] MM reduction. Correlation between caloric debt (r = 0.14, p = 0.13) and protein debt (r = 0.18, p = 0.13) with change in MM was absent. Similarly, no correlation was found between caloric debt (r = -0.057, p = 0.631) and protein debt (r = -0.095, p = 0.424) with changes in PA. CONCLUSIONS: bioimpedance analysis demonstrated that muscle mass and phase angle were significantly lower after 7 days in ICU. The total amount of calories and proteins does not correlate with changes in muscle mass and phase angle.

Crosstalk Between the Nervous System and Systemic Organs in Acute Brain Injury.

Organ crosstalk is a complex biological communication between distal organs mediated via cellular, soluble, and neurohormonal actions, based on a two-way pathway. The communication between the central nervous system and peripheral organs involves nerves, endocrine, and immunity systems as well as the emotional and cognitive centers of the brain. Particularly, acute brain injury is complicated by neuroinflammation and neurodegeneration causing multiorgan inflammation, microbial dysbiosis, gastrointestinal dysfunction and dysmotility, liver dysfunction, acute kidney injury, and cardiac dysfunction. Organ crosstalk has become increasingly popular, although the information is still limited. The present narrative review provides an update on the crosstalk between the nervous system and systemic organs after acute brain injury. Future research might help to target this pathophysiological process, preventing the progression toward multiorgan dysfunction in critically ill patients with brain injury.

Ten good reasons to consider gastrointestinal function after acute brain injury.

The brain-gut axis represents a bidirectional communication linking brain function with the gastrointestinal (GI) system. This interaction comprises a top-down communication from the brain to the gut, and a bottom-up communication from the gut to the brain, including neural, endocrine, immune, and humoral signaling. Acute brain injury (ABI) can lead to systemic complications including GI dysfunction. Techniques for monitoring GI function are currently few, neglected, and many under investigation. The use of ultrasound could provide a measure of gastric emptying, bowel peristalsis, bowel diameter, bowel wall thickness and tissue perfusion. Despite novel biomarkers represent a limitation in clinical practice, intra-abdominal pressure (IAP) is easy-to-use and measurable at bedside. Increased IAP can be both cause and consequence of GI dysfunction, and it can influence cerebral perfusion pressure and intracranial pressure via physiological mechanisms. Here, we address ten good reasons to consider GI function in patients with ABI, highlighting the importance of its assessment in neurocritical care.

Medium cut-off dialyzer for middle molecular uremic toxins in AKI and chronic dialysis.

Uremic toxins accumulate in patients affected by renal failure and can deposit in different organs, including the kidneys and heart. Given their physicochemical characteristics, uremic toxins can contribute to organ dysfunction due to several pathobiological actions at cellular and molecular levels. Several uremic compounds have been described in serum and plasma from patients with acute kidney injury (AKI) and kidney failure; they are usually classified based on their molecular size and protein-binding properties. In this scenario, new dialytic approaches have been proposed in the last few years with the aim of improving uremic toxin removal. Recent studies which focused on the use of medium cut-off membranes in patients on chronic hemodialysis have shown a discrete ability to remove ß2-microglobulin and other middle molecules, such as kappa and lambda free light chains, complement factor D and α1-microglobulin. However, current evidence is mainly based on the impact on short-term outcomes and, consequently, longer observational studies are necessary to confirm the efficacy and safety of the medium cut-off dialyzer. Here we present the state-of-the-art on the clinical application of medium cut-off membranes in AKI and chronic dialysis patients.

Clinical Characteristics of Spinal versus General Anaesthesia in Older Patients Undergoing Hip Fracture Repair Surgery in Jordan: A Multicentre Study.

BACKGROUND: The primary aim of this study was to examine the clinical characteristics and outcomes of older patients who underwent hip fracture repair surgery. The secondary aims were to assess the predictors of the choice of spinal or general anaesthesia and to explore the risk factors for all-cause mortality. METHODS: This three-tertiary centres study was conducted at a tertiary care centre in Jordan. Clinical data include previous fracture history; medication details; comorbidities; surgical approach; and postoperative pain management. RESULTS: Overall, 1084 patients who underwent hip fracture repair were included in this study. The mean age of patients was 78 years, and 55.2% were women. Twenty-four were treated with bisphosphonates before the fracture, whereas 30 were in steroid therapy. Overall, 61.8% of patients underwent spinal anaesthesia, whereas 38.2% underwent general anaesthesia. Spinal anaesthesia group had a lower prevalence of cardiovascular accidents (16.3% vs. 22.3%, p = 0.014) and Alzheimer's (3.4% vs. 1.4%, p = 0.049) than the general anaesthesia group. In the spinal anaesthesia group, postoperative opioid administration (p = 0.025) and postoperative blood transfusion (p = 0.011) occurred more frequently than general anaesthesia group. In hospital, 30-day and all-cause mortality were comparable between both groups. Diabetes mellitus (HR = 2.6; 95%CI = 1.5-4.4; p = 0.001); cemented hip hemiarthroplasty (HR = 2.4; 95%CI = 1.1-5.1; p = 0.025); deep venous thrombosis/pulmonary embolism (HR = 5.0; 95%CI = 1.2-12.9; p = 0.001); and readmission within 1 month from surgery (HR = 3.6; 95%CI = 2.0-6.3; p < 0.001) were all significant predictors of mortality. CONCLUSIONS: This study provides insights into the outcomes and factors associated with different anaesthesia types in hip fracture repair surgery. The anaesthesia type does not affect all-cause mortality in patients undergoing hip fracture repair.

Early acute kidney injury and transition to renal replacement therapy in critically ill patients with SARS-CoV-2 requiring veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring veno-venous extracorporeal membrane oxygenation (vv-ECMO) are at risk for acute kidney injury (AKI). Currently, the incidence of AKI and progression to kidney replacement therapy (RRT) in critically ill patients with vv-ECMO for severe COVID-19 and implications on outcome are still unclear. METHODS: Retrospective analysis at the University Medical Center Hamburg-Eppendorf (Germany) between March 1st, 2020 and July 31st, 2021. Demographics, clinical parameters, AKI, type of organ support, length of ICU stay, mortality and severity scores were assessed. RESULTS: Ninety-one critically ill patients with SARS-CoV-2 requiring ECMO were included. The median age of the study population was 57 (IQR 49-64) years and 67% (n = 61) were male. The median SAPS II and SOFA Score on admission were 40 (34-46) and 12 (10-14) points, respectively. We observed that 45% (n = 41) developed early-AKI, 38% (n = 35) late-AKI and 16% (n = 15) no AKI during the ICU stay. Overall, 70% (n = 64) of patients required RRT during the ICU stay, 93% with early-AKI and 74% with late-AKI. Risk factors for early-AKI were younger age (OR 0.94, 95% CI 0.90-0.99, p = 0.02) and SAPS II (OR 1.12, 95% CI 1.06-1.19, p < 0.001). Patients with and without RRT were comparable regarding baseline characteristics. SAPS II (41 vs. 37 points, p < 0.05) and SOFA score (13 vs. 12 points, p < 0.05) on admission were significantly higher in patients receiving RRT. The median duration of ICU (36 vs. 28 days, p = 0.27) stay was longer in patients with RRT. An ICU mortality rate in patients with RRT in 69% (n = 44) and in patients without RRT of 56% (n = 27) was observed (p = 0.23). CONCLUSION: Critically ill patients with severe SARS-CoV-2 related ARDS requiring vv-ECMO are at high risk of early acute kidney injury. Early-AKI is associated with age and severity of illness, and presents with high need for RRT. Mortality in patients with RRT was comparable to patients without RRT.

Update on persistent acute kidney injury in critical illnesses.

Acute kidney injury (AKI) affects about half of patients admitted to the intensive care unit (ICU), and worsens their short- and long-term outcomes. Apparently self-limiting AKI episodes initiate a progression toward chronic kidney disease (CKD) through cellular and molecular mechanisms that are yet to be explained. In particular, persistent AKI, defined in 2016 by the Acute Dialysis Quality Initiative as an AKI which lasts more than 48 h from its onset, has been correlated with higher morbidity and mortality, and with a higher progression to acute kidney disease (AKD) and CKD than transient AKI (i.e. AKI with a reversal within 48 h). This classification has been also used in the setting of solid organ transplantation, demonstrating similar outcomes. Due to its incidence and poor prognosis and because prompt interventions seem to change its course, persistent AKI should be recognized early and followed-up also after its recovery. However, while AKI and CKD are well-described syndromes, persistent AKI and AKD are relatively new entities. The purpose of this review is to highlight the key phases of persistent AKI in ICU patients in terms of both clinical and mechanistic features in order to offer to clinicians and researchers an updated basis from which to start improving patients' care and direct future research.

Nutritional support and prevention of post-intensive care syndrome: the Italian SIAARTI survey.

BACKGROUND: Malnutrition and muscle wasting are common in ICU patients and predict adverse patient-centered outcomes. The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) conducted a nationwide survey to identify the nutritional practices in the Italian ICUs and to plan future, training interventions to improve the national clinical practice. METHODS: Nationwide online survey, involving Italian ICUs, developed by experts affiliated with SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected over a period of three months (October 1 to December 31, 2022) during 2022. RESULTS: One hundred full responses from participating ICUs were collected. The number of beds is < 10 in most ICUs and > 20 in 11 ICUs. Most ICUs (87%) are mixed, cardiac (5%), neurosurgical (4%), or pediatric ICUs (1%). Although the nutritional program is widely prescribed based on the patients' general evaluation, 52 ICUs (52%) do not perform nutritional risk evaluation at admission in case of > 24-h stay. Daily caloric intake is mainly based on the 25 kcal/kg equation; otherwise, the Harris-Benedict formula is mostly used, whereas indirect calorimetry is less used. Most clinicians apply a personalized nutritional approach to organ failure. Most ICUs have a nutritional management protocol, and enteral nutrition (EN) is frequently started within 2 days from admission, while supplemental parenteral nutrition is used when EN is insufficient by most clinicians. The EN administered seems to correspond to that prescribed, but it is stopped if the gastric residual gastric is > 300-500 ml in most ICUs. CONCLUSION: Prescription, route, and mode of administration of nutritional support seem to be in line with international recommendations, while suggestions on the tools for assessing the nutritional risk and monitoring efficacy and complications seem far less followed. Future national clinical studies are necessary to investigate the optimal nutritional and metabolic management of critically ill patients and the correspondence with the results of this survey on actual practices.

Endotoxin removal therapy with Polymyxin B immobilized fiber column: a single center experience from EUPHAS2 registry.

Although the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might play a critical role in the clinical course of a specific subphenotype of septic shock (endotoxic shock). In light of this view, since 2019, we have introduced in our clinical practice a diagnostic-therapeutic flowchart to select patients that can benefit the most from the treatment proposed. In addition, we reported in this study our experience of PMX-HA in a cohort of critically ill patients admitted to our intensive care unit (ICU). We analyzed a single centre, retrospective, observational web-based database (extracted from the EUPHAS2 registry) of critically ill patients admitted to the ICU between January 2016 and May 2021 who were affected by endotoxic shock. Patients were divided according to the diagnostic-therapeutic flowchart in two groups: Pre-Flowchart (Pre-F) and Post-Flowchart (Post-F). From January 2016 to May 2021, 61 patients were treated with PMX-HA out of 531 patients diagnosed with septic shock and of these, fifty patients (82%) developed AKI during their ICU stay. The most common source of infection was secondary peritonitis (36%), followed by community-acquired pneumonia (29%). Fifty-five (90%) out of 61 patients received a second PMX-HA treatment, with a statistically significant difference between the two groups (78% of the Pre-F vs. 100% of the Post-F group, p = 0.005). In both groups, between T0 and T120, the Endotoxin Activity Assay (EAA) decreased, while the SOFA score, mean arterial pressure (MAP), and Vasoactive Inotropic Score (VIS) improved with no statistically significant difference. Furthermore, when performing a propensity score matching analysis to compare mortality between the two groups, statistically significant lower ICU and 90-day mortalities were observed in the Post-F group [p = 0.016]. Although in this experienced centre data registry, PMX-HA was associated with organ function recovery, hemodynamic improvement, and current EAA level reduction in critically ill patients with endotoxic shock. Following propensity score-matched analysis, ICU mortality and 90-day mortalities were lower in the diagnostic-therapeutic flowchart group when considering two temporal groups based on strict patient selection criteria and timing to achieve PMX. Further Randomised Control Trials focused on centre selection, adequate training and a flowchart of action when assessing extracorporeal blood purification use should be performed.

Endotoxin activity trend and multi-organ dysfunction in critically ill patients with septic shock, who received Polymyxin-B hemadsorption: A multicenter, prospective, observational study.

BACKGROUND: The baseline endotoxin activity (EAT0) may predict the outcome of critically ill septic patients who receive Polymyxin-B hemadsorption (PMX-HA), however, the clinical implications of specific EA trends remain unknown. METHODS: Subgroup analysis of the prospective, multicenter, observational study EUPHAS2. We included 50 critically ill patients with septic shock and EAT0 ≥ 0.6, who received PMX-HA. The primary outcome of the study was the EA and SOFA score progression from T0 to 120 h afterwards (T120). Secondary outcomes included the EA and SOFA score progression in whom had EA at 48 h (EAT48) < 0.6 (EA responders, EA-R) versus who had not (EA non-responders, EA-NR). RESULTS: Septic shock was mainly caused by 27 abdominal (54%) and 17 pulmonary (34%) infections, predominantly due to Gram negative bacteria (39 patients, 78%). The SAPS II score was 67.5 [52.8-82.3] and predicted a mortality rate of 75%. Between T0 and T120, the EA decreased (p < 0.001), while the SOFA score and the Inotropic Score (IS) improved (p < 0.001). In comparison with EA-NR (18 patients, 47%), the EA-R group (23 patients, 53%) showed faster IS improvement and lower requirement of continuous renal replacement therapy (CRRT) during the ICU stay. Overall hospital mortality occurred in 18 patients (36%). CONCLUSIONS: In critically ill patients with septic shock and EAT0 ≥ 0.6 who received PMX-HA, EA decreased and SOFA score improved over 120 h. In whom high EA resolved within 48 h, IS improvement was faster and CRRT requirement was lower compared with patients with EAT48 ≥ 0.6.

The Cytotoxic Effect of Septic Plasma on Healthy RBCs: Is Eryptosis a New Mechanism for Sepsis?

Sepsis is a life-threatening multiple-organ dysfunction induced by infection and is one of the leading causes of mortality and critical illness worldwide. The pathogenesis of sepsis involves the alteration of several biochemical pathways such as immune response, coagulation, dysfunction of endothelium and tissue damage through cellular death and/or apoptosis. Recently, in vitro and in vivo studies reported changes in the morphology and in the shape of human red blood cells (RBCs) causing erythrocyte death (eryptosis) during sepsis. Characteristics of eryptosis include cell shrinkage, membrane blebbing, and surface exposure to phosphatidylserine (PS), which attract macrophages. The aim of this study was to evaluate the in vitro induction of eryptosis on healthy RBCs exposed to septic plasma at different time points. Furthermore, we preliminary investigated the in vivo levels of eryptosis in septic patients and its relationship with Endotoxin Activity Assay (EAA), mortality and other biological markers of inflammation and oxidative stress. We enrolled 16 septic patients and 16 healthy subjects (no systemic inflammation in the last 3 months) as a control group. At diagnosis, we measured Interleukin-6 (IL-6) and Myeloperoxidase (MPO). For in vitro study, healthy RBCs were exposed to the plasma of septic patients and CTR for 15 min, 1, 2, 4 and 24 h. Morphological markers of death and eryptosis were evaluated by flow cytometric analyses. The cytotoxic effect of septic plasma on RBCs was studied in vitro at 15 min, 1, 2, 4 and 24 h. Healthy RBCs incubated with plasma from septic patients went through significant morphological changes and eryptosis compared to those exposed to plasma from the control group at all time points (all, p < 0.001). IL-6 and MPO levels were significantly higher in septic patients than in controls (both, p < 0.001). The percentage of AnnexinV-binding RBCs was significantly higher in septic patients with EAA level ≥0.60 (positive EAA: 32.4%, IQR 27.6-36.2) compared to septic patients with EAA level <0.60 (negative EAA: 14.7%, IQR 5.7-30.7) (p = 0.04). Significant correlations were observed between eryptosis and EAA levels (Spearman rho2 = 0.50, p < 0.05), IL-6 (Spearman rho2 = 0.61, p < 0.05) and MPO (Spearman rho2 = 0.70, p < 0.05). In conclusion, we observed a quick and great cytotoxic effect of septic plasma on healthy RBCs and a strong correlation with other biomarkers of severity of sepsis. Based on these results, we confirmed the pathological role of eryptosis in sepsis and we hypothesized its use as a biomarker of sepsis, potentially helping physicians to face important treatment decisions.