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.

Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery.

BACKGROUND: Postoperative acute kidney injury (PO-AKI) is a frequent complication after surgery. Various tools have been proposed to identify patients at high risk for AKI, including preoperative serum creatinine or estimated glomerular filtration rate (eGFR), urinary cell cycle arrest, and tubular damage biomarkers; however, none of these can appropriately assess AKI risk before surgery. Renal functional reserve (RFR) screened by the Doppler-derived intraparenchymal renal resistive index variation (IRRIV) test has been proposed to identify patients at risk for AKI before a kidney insult. IRRIV test has been developed in healthy individuals and previously investigated in cardiac surgery patients. This study aims to evaluate the value of the IRRIV test in identifying PO-AKI among patients undergoing robotic abdominal surgery in the Trendelenburg position for pelvic oncological disease. METHODS: We performed a prospective, double-blinded, observational study. Preoperative baseline renal function and RFR were assessed in 53 patients with baseline eGFR >60 mL/min/1.73 m2, undergoing robotic surgery in the Trendelenburg position for pelvic oncological disease. The capability of Doppler-derived RFR in predicting PO-AKI was investigated with the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Approximately 15.1% of patients developed AKI within the first 3 postoperative days. Thirty-one (58.5%) patients had a physiologic delta-RRI (ie, ≥0.05), while 22 (41.5%) patients did not. The ROC-AUC for PO-AKI was 0.85 (95% confidence interval [CI], 0.74-0.97; P = .007) for serum creatinine, 0.84 (95% CI, 0.71-0.96; P = .006) for eGFR, and 0.84 (95% CI, 0.78-0.91; P = .017) for delta-RRI. When combined with eGFR, the ROC-AUC for delta-RRI was 0.95 (95% CI, 0.9-1). CONCLUSIONS: Our findings show that the preoperative assessment of Doppler-derived RFR combined with baseline renal function improves the capability of identifying patients at high risk for PO-AKI with eGFR >60 mL/min/1.73 m2 after robotic abdominal surgery in Trendelenburg position for pelvic oncological disease.

Sampling from Extracorporeal Circuit: A Step Forward for Dose Monitoring in Continuous Renal Replacement Therapy.

INTRODUCTION: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines. However, samples must be collected simultaneously from the extracorporeal circuit ports, with the same suction flow at an unknown rate. METHODS: The proposed study takes the first step toward identifying the technical factors that should be considered in determining the optimal suction rate to collect samples from the extracorporeal circuit to measure the extracorporeal clearance for a specific solute. RESULTS: The results obtained identify the low suction rate (i.e., 1 mL/min) as an ideal parameter for an adequate sampling method. Low velocities do not perturb the external circulation system and ensure stability prevailing pressures in the circuit. Higher velocities can be performed only with blood flows above 120 mL/min preferably in conditions of appropriate filtration fraction. DISCUSSION/CONCLUSIONS: The specific value of aspiration flow rate must be proportioned to the prescription of CRRT treatments set by the clinician.

The Effect of Positive Pressure Ventilation on Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: An Observational Study.

INTRODUCTION: Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS. METHODS: This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected. RESULTS: A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively. CONCLUSIONS: In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function.

Sequential Extracorporeal Blood Purification Is Associated with Prolonged Survival among ICU Patients with COVID-19 and Confirmed Bacterial Superinfection.

INTRODUCTION: This study investigates the impact of sequential extracorporeal treatments with oXiris® or CytoSorb® plus Seraph-100® on the clinical and laboratory parameters of critically ill COVID-19 patients with bacterial superinfection. METHODS: Patients admitted to the intensive care unit with COVID-19, bacterial superinfection, and undergoing blood purification (BP) were enrolled in this prospective, single-center, observational study. "standard BP" with oXiris® or CytoSorb® were used in 35 COVID-19 patients with bacterial infection. Seraph-100® was added in 33 patients when available serially in the same oXiris® circuit or as sequential treatment with CytoSorb® as a sequential BP. RESULTS: A significant reduction in SOFA score 3 days after treatment was observed in patients undergoing sequential BP (11.3 vs. 8.17, p < 0.01) compared to those undergoing "standard BP" (11.0 vs. 10.3, p > 0.05). The difference between the observed and expected mortality rate based on APACHE IV was greater in the sequential BP group (42.4% vs. 81.7%, p < 0.001) than the "standard BP" (74.2% vs. 81.7%, p > 0.05). Patients treated with sequential BP had a longer survival than those treated with "standard BP" (22.4 vs. 18.7 months; p < 0.001). CONCLUSIONS: The sequential approach may enhance the positive effect of BP on organ dysfunction among critically ill patients with COVID-19 and bacterial superinfection.

Standardization of Nomenclature for the Mechanisms and Materials Utilized for Extracorporeal Blood Purification.

In order to develop a standardized nomenclature for the mechanisms and materials utilized during extracorporeal blood purification, a consensus expert conference was convened in November 2022. Standardized nomenclature serves as a common language for reporting research findings, new device development, and education. It is also critically important to support patient safety, allow comparisons between techniques, materials, and devices, and be essential for defining and naming innovative technologies and classifying devices for regulatory approval. The multidisciplinary conference developed detailed descriptions of the performance characteristics of devices (membranes, filters, and sorbents), solute and fluid transport mechanisms, flow parameters, and methods of treatment evaluation. In addition, nomenclature for adsorptive blood purification techniques was proposed. This report summarizes these activities and highlights the need for standardization of nomenclature in the future to harmonize research, education, and innovation in extracorporeal blood purification therapies.

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study.

BACKGROUND: Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects. METHODS: The prospective "Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation" study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations. RESULTS: The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI - 1.4, - 1.7] vs. - 3.3 [95% CI - 4.4, - 2.2] ml/min/1.73 m2) and 12 months (- 2.7 [95% CI - 4.2, - 1.2] vs - 10.2 [95% CI - 11.3, - 9.1] ml/min/1.73 m2; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (- 8.0 [95% CI - 14.1, - 1.9] vs. - 18.6 [95% CI - 23.3, - 14.0] ml/min/1.73 m2; p = 0.008). A dose-response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression. CONCLUSIONS: A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells. Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).

Ultrasonographic Intraparenchymal Renal Resistive Index Variation for Assessing Renal Functional Reserve in Patients Scheduled for Cardiac Surgery: A Pilot Study.

INTRODUCTION: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication in patients undergoing cardiac surgery. Preoperative renal functional reserve (RFR) has been demonstrated to be highly predictive of CSA-AKI. We have previously demonstrated that intraparenchymal renal resistive index variation (IRRIV) measured by ultrasound (US) can identify the presence of RFR in healthy individuals. This study aimed (1) to examine the correlation between the US IRRIV test and RFR measured through the protein loading test in patients undergoing elective cardiac surgery and (2) to determine the value of the 2 methods for predicting occurrence of AKI or subclinical AKI after cardiac surgery. METHODS: Consecutive patients scheduled for cardiac surgery were enrolled for this pilot study. The protein loading test and the IRRIV test were performed in all patients 2 days before cardiac surgery. Correlation between IRRIV and RFR was tested using Pearson correlation analysis. Association between presence of RFR and positive IRRIV test, presence of RFR and AKI and subclinical AKI, and positive IRRIV test and AKI and subclinical AKI was evaluated using logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the values of IRRIV for predicting RFR, RFR for predicting AKI and subclinical AKI, and IRRIV for predicting AKI and subclinical AKI. RESULTS: Among the 31 patients enrolled, significant association was found between IRRIV and RFR (r = 0.81; 95% CI: 0.63-0.90; p < 0.01). The association between RFR and IRRIV was described in 27/31 (87.1%) patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IRRIV test were 100, 84, 60, and 100%, respectively. In ROC curve analysis, the area under the curve (AUC) was 0.80 (95% CI: 0.64-0.96). After cardiac surgery, 1/31 (3.2%) patient had AKI and 12/31 (38.7%) had subclinical AKI. RFR predicted subclinical AKI (odds ratio [OR] = 0.93; 95% CI: 0.87-0.98; p = 0.02). The sensitivity, specificity, PPV, and NPV of the RFR were 61, 88.8, 80, and 76%, respectively; the AUC was 0.75 (95% CI: 0.59-0.91). IRRIV predicts subclinical AKI (OR = 0.79; 95% CI: 0.67-0.93; p = 0.005). The sensitivity, specificity, PPV, and NPV of the IRRIV test were 46.1, 100, 100, and 72%, respectively; the AUC was 0.73 (95% CI: 0.58-0.87). CONCLUSION: This pilot study suggests that a positive IRRIV test can significantly predict the presence of RFR in patients scheduled for cardiac surgery. RFR measured by the protein loading test or by the US IRRIV test can predict the occurrence of subclinical postoperative AKI. The findings of this study need to be confirmed in large patient cohorts.

Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation. With this work, we evaluated the longitudinal changes of systemic inflammatory markers in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) haemofilter. METHODS: We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing haemofilter (CAH) according to local practice; we visualize longitudinal results of biochemical, inflammatory, blood gas, and vital sign parameters focussing on systemic levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. RESULTS: All patients were treated with ≥1 cycle extracorporeal continuous venovenous haemofiltration (CVVH) with CAH; of these, 30 severe patients received CVVH-CAH within 4-12 h of admission after recognizing a hyper-inflammatory state. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and were placed on EBP during hospitalization. The treatment was associated with a reduction of ferritin, CRP, fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3%. CONCLUSION: EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.

A Role of Circuit Clotting and Strategies to Prevent It during Blood Purification Therapy with oXiris Membrane: An Observational Multicenter Study.

INTRODUCTION: Membrane fouling is a significant complication potentially reducing clinical effects of extracorporeal blood purification (EBP) in critically ill septic patients with acute kidney injury. Although fascinating, the effect of heparin coating in preventing membrane fouling is currently unknown. This multicenter prospective study aims to preliminary describe the incidence, associated factors, and clinical consequences of premature circuit clotting in a cohort of adult critically ill septic patients treated with EBP using a high biocompatible heparin-coated hemodiafilter characterized by advanced adsorption properties. METHODS: This study was a retrospective analysis of prospectively entered data in the oXirisNet Registry; overall, 97 septic patients undergoing EBP with oXiris between May 2019 and March 2020 were enrolled in this study. Patients were divided into two groups according to the occurrence of filter clotting (premature vs. nonpremature). Logistic regression analysis was used to identify factors associated with premature circuit clotting. RESULTS: Premature clotting occurred in 18 (18.6%) patients. Results of the multivariate logistic regression analysis demonstrated that hematocrit (p = 0.02, odds ratio [OR] 1.15 [1.05; 1.30]), serum procalcitonin (PCT) (p = 0.03, OR 1.1 [1.05; 1.2]), and anticoagulation strategy (p = 0.05 at Wald's test) were independent predictors of circuit clotting. Systemic anticoagulation (p = 0.02, OR 0.03 [0.01; 0.52]) and regional citrate anticoagulation (p = 0.10, OR 0.23 [0.04; 1.50]) were both protective factors if compared to no-anticoagulation strategy. Patients with nonpremature circuit clotting showed more rapid recovery from hemodynamic instability, pulmonary hypo-oxygenation, and electrolyte disorders and greater improvement of inflammatory markers and SOFA scores. CONCLUSION: Although in this study the incidence of premature circuit clotting was relatively low (18.6%) compared to previously reported values (54%), membrane clotting in adult critically ill septic patients could cause clinically relevant interferences with treatment performances. Prevention of clotting should be based on avoiding higher patients' hematocrit, high serum PCT, and no-anticoagulation strategy which resulted as independent predictors of circuit clotting.

The Impact of Fast Microbiology in Intensive Care Units in the Era of Antibiotic Resistance: An Observational Retrospective Study.

The increasing prevalence of multi-drug-resistant bacteria responsible for bloodstream infections (BSIs) makes therapeutic choices progressively more complex. Fast microbiology quickly detects the presence of pathogens and clinically relevant determinants of antibiotic resistance, offering the potential for early administration of antibiotics. In this retrospective observational study, we comparatively evaluated the performances of FilmArray and the current standard method using blood samples collected from intensive care unit (ICU) patients with suspected BSI. A full agreement with the standard was observed in 97/102 samples (95.1 ± 4.2%), a mismatch in 3/102 samples (2.9 ± 3.2%) and detection failure in 2/102 cases (1.96 ± 2.7%). Statistical analysis demonstrated a near-perfect/perfect level of agreement between the two methods, with an overall degree of agreement of 95%. The high performance demonstrated by the FilmArray could allow a "watch and wait" approach helping clinicians in decision-making processes related to choice and initiation of the antimicrobial therapy, thus avoiding ineffective and excessive use of drugs.

Molecular Mechanisms and Biomarkers Associated with Chemotherapy-Induced AKI.

Acute kidney injury (AKI) is a life-threatening condition characterized by a rapid and transient decrease in kidney function. AKI is part of an array of conditions collectively defined as acute kidney diseases (AKD). In AKD, persistent kidney damage and dysfunction lead to chronic kidney disease (CKD) over time. A variety of insults can trigger AKI; however, chemotherapy-associated nephrotoxicity is increasingly recognized as a significant side effect of chemotherapy. New biomarkers are urgently needed to identify patients at high risk of developing chemotherapy-associated nephrotoxicity and subsequent AKI. However, a lack of understanding of cellular mechanisms that trigger chemotherapy-related nephrotoxicity has hindered the identification of effective biomarkers to date. In this review, we aim to (1) describe the known and potential mechanisms related to chemotherapy-induced AKI; (2) summarize the available biomarkers for early AKI detection, and (3) raise awareness of chemotherapy-induced AKI.

Methods for dose quantification in continuous renal replacement therapy: Toward a more precise approach.

Periodic dose assessment is quintessential for dynamic dose adjustment and quality control of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI). The flows-based methods to estimate dose are easy and reproducible methods to quantify (estimate) CRRT dose at the bedside. In particular, quantification of effluent flow and, mainly, the current dose (adjusted for dialysate, replacement, blood flows, and net ultrafiltration) is routinely used in clinical practice. Unfortunately, these methods are critically influenced by several external unpredictable factors; the estimated dose often overestimates the real biological delivered dose quantified through the measurement of urea clearance (the current effective delivered dose). Although the current effective delivered dose is undoubtedly more precise than the flows-based dose estimation in quantifying CRRT efficacy, some limitations are reported for the urea-based measurement of dose. This article aims to describe the standard of practice for dose quantification in critically ill patients with AKI undergoing CRRT in the intensive care unit. Pitfalls of current methods will be underlined, along with solutions potentially applicable to obtain more precise results in terms of (a) adequate marker solutes that should be used in accordance with the clinical scenario, (b) correct sampling procedures depending on the chosen indicator of transmembrane removal, (c) formulas for calculations, and (d) quality controls and benchmark indicators.

Hemodynamic Instability during Acute Kidney Injury and Acute Renal Replacement Therapy: Pathophysiology and Clinical Implications.

Hemodynamic instability associated with acute renal replacement therapy (aRRT, HIRRT) and/or with acute kidney injury (AKI) is frequently observed in the intensive care unit; it affects patients' renal recovery, and negatively impacts short- and long-term mortality. A thorough understanding of mechanisms underlying HIRRT and AKI-related hemodynamic instability may allow the physician in adopting adequate strategies to prevent their occurrence and reduce their negative consequences. The aim of this review is to summarize the main alterations occurring in patients with AKI and/or requiring aRRT of those homeostatic mechanisms which regulate hemodynamics and oxygen delivery. In particular, a pathophysiological approach has been used to describe the maladaptive interactions between cardiac output and systemic vascular resistance occurring in these patients and leading to hemodynamic instability. Finally, the potential positive effects of aRRT on these pathophysiological mechanisms and on restoring hemodynamic stability have been described.

Family Care Rituals in the ICU to Reduce Symptoms of Post-Traumatic Stress Disorder in Family Members-A Multicenter, Multinational, Before-and-After Intervention Trial.

OBJECTIVES: To assess the feasibility and efficacy of implementing "Family Care Rituals" as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members. DESIGN: Prospective, before-and-after intervention evaluation. SETTING: Two U.S. academic medical ICU's, and one Italian academic medical/surgical ICU. SUBJECTS: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission. INTERVENTIONS: A novel intervention titled "Family Care Rituals" during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay. MEASUREMENTS AND MAIN RESULTS: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge. CONCLUSIONS: Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients.

Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study.

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.

The golden hour of polymyxin B hemoperfusion in endotoxic shock: The basis for sequential extracorporeal therapy in sepsis.

Endotoxin is recognized as a major trigger of the immune response leading to pro- and anti-inflammatory cytokine release, activation of the coagulation cascade, vasoplegic shock, and multiple organ dysfunction syndrome. A beneficial effect could be achieved through extracorporeal adsorption of circulating endotoxins in the blood as adjunctive treatment for unresponsive endotoxic shock. However, the precise clinical indication for its initiation is widely debated in the literature. Similar to the source control, microbiological cultures and antibiotics administration, endotoxin activity assay evaluation at regular intervals, and the targeted use of PMX-B hemoperfusion could be lifesaving and adequate within the golden hour for the diagnosis and treatment of endotoxic shock.

Use of Fluoride as a Marker Solute to Quantify the Current Effective Delivered Dose in Continuous Renal Replacement Therapy: An "in vitro" Study.

BACKGROUND: The current effective delivered dose is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the current effective delivered dose using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. METHODS: We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. RESULTS: In CVVH, the median SC values were 1.06 (1.02-1.07) and 1.02 (1.01-1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01-31.31) mL/kg/h and 30.30 (29-31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96-1.02) and 1 (0.95-1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52-31.32) mL/kg/h and 31.16 (30-31.75) mL/kg/h (discrepancy of -2.97%), respectively. CONCLUSION: Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the current effective delivered dose during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.

Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis.

BACKGROUND: The "END-of-Life ScorING-System" (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients. MATERIALS AND METHODS: Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient's ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis. RESULTS: Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort. CONCLUSIONS: ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.

Intraoperative core temperature monitoring: accuracy and precision of zero-heat flux heated controlled servo sensor compared with esophageal temperature during major surgery; the ESOSPOT study.

Monitoring of intraoperative core temperature is strongly recommended to reduce the risk of perioperative thermic imbalance and related complications. The zero-heat-flux sensor (3M Bair Hugger Temperature monitoring system, ZHF), measures core temperature in a non-invasive manner. This study was aimed at comparing accuracy and precision of the ZHF sensor compared to the esophageal thermometer. Patients scheduled for major elective abdominal or urologic surgery were considered eligible for enrollment. Core body temperature was measured using both an esophageal probe (TESO) and a ZHF sensor (TZHF) every 15 min from induction until the end of general anaesthesia. A Bland-Altman plot for repeated measures was performed. The proportion of measurements within ± 0.5 °C was estimated; from a clinical point of view, a proportion greater than 90% was considered sufficiently accurate. Lin's concordance correlation coefficient (CCC) for repeated measures were calculated. To evaluate association between the two methods, a generalized estimating equation (GEE) simple linear regression model, was elaborated. A GEE multiple regression model was also performed in order to adjust the estimate of the association between measurements from surgical and patient's features. Ninety-nine patients were enrolled. Bland-Altman plot bias was 0.005 °C with upper and lower limits of agreement for repeated measures of 0.50 °C and - 0.49 °C. The percentage of measurements within 0.5 °C of the reference value was 97.98% (95% confidence interval 92.89-99.75%), indicating a clinically sufficient agreement between the two methods. This was also confirmed by a CCC for repeated measures of 0.89 (95% CI 0.80 to 0.94). The GEE simple regression model (slope value of 0.77) was not significantly influenced by any patient or surgical variables. According to GEE multiple regression model results, the explored patient- and surgery-related variables did not influence the association between methods. ZHF sensor has shown a clinically acceptable accuracy and precision for body core temperature monitoring during elective major surgery. CLINICAL TRIALS: Clinical trial number: NCT03820232.