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Introduction: The FDA authorized the emergency use of enhanced hemoadsorption with oXiris in critically ill adult COVID patients with respiratory failure or severe disease to reduce inflammation. In this study, we evaluated critically ill adult COVID patients with acute kidney injury (AKI) who were exposed versus not exposed to enhanced hemoadsorption with oXiris during continuous renal replacement therapy (CRRT)., Methods: Retrospective cohort study of critically ill adult COVID patients with AKI requiring CRRT. Exposure to oXiris was defined as receiving oXiris for >12 cumulative hours and more than one-third of the time within the first 72 h of CRRT. Study outcomes included filter-specific performance metrics and clinical outcomes such as ventilator requirement, mortality, and dialysis dependence. Inverse probability treatment weighting was used to balance potential confounders in weighted regression models., Results: 14,043 h of CRRT corresponding to 85 critically ill adult patients were analyzed. Among these, 2,736 h corresponded to oXiris exposure (n = 25 patients) and 11,307 h to a standard CRRT filter (n = 60 patients). Transmembrane pressures (TMPs) increased rapidly and were overall higher with oXiris versus standard filter, but filter life (median of 36.3 vs. 33.1 h, p = 0.913, respectively) and filter/clotting alarms remained similar in both groups. In adjusted models, oXiris exposure was not independently associated with the composite of hospital mortality and dialysis dependence at discharge (OR 2.13, 95% CI: 0.98-4.82, p = 0.06), but it was associated with fewer ventilator (β = -15.02, 95% CI: -29.23 to -0.82, p = 0.04) and intensive care unit days (β = -14.74, 95% CI: -28.54 to -0.95, p = 0.04) in survivors., Discussion/conclusion: In critically ill adult COVID patients with AKI requiring CRRT, oXiris filters exhibited higher levels of TMP when compared to a standard CRRT filter, but no differences in filter life and filter/clotting alarm profiles were observed. The use of oXiris was not associated with improvement in clinical outcomes such as hospital mortality or dialysis dependence at discharge., (© 2023 S. Karger AG, Basel.)

Approximately 20% of patients with acute brain injury (ABI) also experience acute kidney injury (AKI), which worsens their outcomes. The metabolic and inflammatory changes associated with AKI likely contribute to prolonged brain injury and edema. As a result, recognizing its presence is important for effectively managing ABI and its sequelae. This review discusses the occurrence and effects of AKI in critically ill adults with neurological conditions, outlines potential mechanisms connecting AKI and ABI progression, and highlights AKI management principles. Tailored approaches include optimizing blood pressure, managing intracranial pressure, adjusting medication dosages, and assessing the type of administered fluids. Preventive measures include avoiding nephrotoxic drugs, improving hemodynamic and fluid balance, and addressing coexisting AKI syndromes. ABI patients undergoing renal replacement therapy (RRT) are more susceptible to neurological complications. RRT can negatively impact cerebral blood flow, intracranial pressure, and brain tissue oxygenation, with effects tied to specific RRT methods. Continuous RRT is favored for better hemodynamic stability and lower risk of dialysis disequilibrium syndrome. Potential RRT modifications for ABI patients include adjusted dialysate and blood flow rates, osmotherapy, and alternate anticoagulation methods. Future research should explore whether these strategies enhance outcomes and if using novel AKI biomarkers can mitigate AKI-related complications in ABI patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Continuous kidney replacement therapy (CKRT) is well entrenched as one of the dominant KRT modalities in modern critical care practice. Since its introduction four decades ago, there have been considerable innovations in CKRT machines that have improved precision, safety, and simplicity. CKRT is the preferred KRT modality for critically ill patients with hemodynamic instability. Early physical therapy and rehabilitation can be feasibly and safely provided to patients connected to CKRT, thus obviating concerns about immobility. Although randomized clinical trials have not shown a mortality difference when comparing CKRT and intermittent hemodialysis, CKRT allows precision delivery of solute and fluid removal that can be readily adjusted in the face of dynamic circumstances. Accumulated evidence from observational studies, although susceptible to bias, has shown that CKRT, when compared with intermittent hemodialysis, is associated with better short- and long-term kidney recovery and KRT independence. Critical care medicine encompasses a wide range of sick patients, and no single KRT modality is likely to ideally suit every patient in every context and for every condition. The provision of KRT represents a spectrum of modalities to which patients can flexibly transition in response to their evolving condition. As a vital tool for organ support in the intensive care unit, CKRT enables the personalization of KRT to meet the clinical demands of patients during the most severe phases of their illness., (Copyright © 2023 by the American Society of Nephrology.)

Accurate assessment of intravascular volume status in critically ill patients remains a very challenging task. Recent data have shown adverse outcomes in critically ill patients with either inadequate or overaggressive fluid therapy. Understanding the tools and techniques available for accurate volume assessment is imperative. This article discusses the concept of fluid responsiveness and reviews methods for assessing fluid responsiveness in critically ill patients., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Continuous RRT (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in patients who are critically ill with AKI in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population, such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk, and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized, or do not have solid evidence-based foundations. In this study, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to patients who are critically ill. Specific focus is on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation, and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves, and is on the basis of step-wise decisions made during the care of this patient, according to the specific patient's needs and the logistics available at the corresponding institution., Competing Interests: A. Tolwani reports a patent to 0.5% citrate solution issued, licensed, and with royalties paid. A. Tolwani, J.A. Neyra, and M. Thompson Bastin have provided consultations for Baxter Healthcare. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators., (Copyright © 2019 by the American Society of Nephrology.)

Acute kidney injury (AKI) is common in critically ill patients and associated with increased morbidity and mortality. With the increased use of renal replacement therapy (RRT) for severe AKI, the optimal time for initiation of RRT has become one of the most probed and debated topic in the field of nephrology and critical care. There appears to be an increased trend toward earlier initiation of RRT to avoid life-threatening complications associated with AKI. Despite the presence of a plethora of studies in this field, the lack of uniformity in study design, patient population types, definition of early and late initiation, modality of RRT, and results, the optimal time for starting RRT in AKI still remains unknown. The beneficial effects reported in observational studies have not been supported by clinical trials. Recently, 2 of the largest randomized control trials evaluating the timing of RRT in critically ill patients with AKI showed differing results. We provide an in-depth review of the available data on the timing of dialysis in patients with AKI.

Background and Objectives: Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT., Design, Setting, Participants, & Measurements: We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate., Results: Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion., Conclusions: Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT., (Copyright © 2016 by the American Society of Nephrology.)

Cefepime, ceftazidime, and piperacillin/tazobactam are commonly used beta-lactam antibiotics in the critical care setting. For critically ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic data are available to inform clinicians on the dosing of these agents. Monte Carlo simulations (MCS) can be used to guide drug dosing when pharmacokinetic trials are not feasible. For each antibiotic, MCS using previously published pharmacokinetic data derived from critically ill patients was used to evaluate multiple dosing regimens in 4 different prolonged intermittent renal replacement therapy effluent rates and prolonged intermittent renal replacement therapy duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis and hemofiltration modes). Antibiotic regimens were also modeled depending on whether drugs were administered during or well before prolonged intermittent renal replacement therapy therapy commenced. The probability of target attainment (PTA) was calculated using each antibiotic's pharmacodynamic target during the first 48 hours of therapy. Optimal doses were defined as the smallest daily dose achieving ≥90% probability of target attainment in all prolonged intermittent renal replacement therapy effluent and duration combinations. Cefepime 1 g every 6 hours following a 2 g loading dose, ceftazidime 2 g every 12 hours, and piperacillin/tazobactam 4.5 g every 6 hours attained the desired pharmacodynamic target in ≥90% of modeled prolonged intermittent renal replacement therapy patients. Alternatively, if an every 6-hours cefepime regimen is not desired, the cefepime 2 g pre-prolonged intermittent renal replacement therapy and 3 g post-prolonged intermittent renal replacement therapy regimen also met targets. For ceftazidime, 1 g every 6 hours or 3 g continuous infusion following a 2 g loading dose also met targets. These recommended doses provide simple regimens that are likely to achieve the pharmacodynamics target while yielding the least overall drug exposure, which should result in lower toxicity rates. These findings should be validated in the clinical setting., (© 2018, The American College of Clinical Pharmacology.)

Continuous renal replacement therapy (CRRT) is the preferred method for renal support in critically ill and hemodynamically unstable children in the pediatric intensive care unit (PICU) as it allows for gentle removal of fluids and solutes. The most frequent indications for CRRT include acute kidney injury (AKI) and fluid overload (FO) as well as non-renal indications such as removal of toxic metabolites in acute liver failure, inborn errors of metabolism, and intoxications and removal of inflammatory mediators in sepsis. AKI and/or FO are common in critically ill children and their presence is associated with worse outcomes. Therefore, early recognition of AKI and FO is important and timely transfer of patients who might require CRRT to a center with institutional expertise should be considered. Although CRRT has been increasingly used in the critical care setting, due to the lack of standardized recommendations, wide practice variations exist regarding the main aspects of CRRT application in critically ill children.     Conclusion: In this review, from the Critical Care Nephrology section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), we summarize the key aspects of CRRT delivery and highlight the importance of adequate follow up among AKI survivors which might be of relevance for the general pediatric community. What is Known: • CRRT is the preferred method of renal support in critically ill and hemodynamically unstable children in the PICU as it allows for gentle removal of fluids and solutes. • Although CRRT has become an important and integral part of modern pediatric critical care, wide practice variations exist in all aspects of CRRT. What is New: • Given the lack of literature on guidance for a general pediatrician on when to refer a child for CRRT, we recommend timely transfer to a center with institutional expertise in CRRT, as both worsening AKI and FO have been associated with increased mortality. • Adequate follow-up of PICU patients with AKI and CRRT is highlighted as recent findings demonstrate that these children are at increased risk for adverse long-term outcomes., (© 2023. The Author(s).)

Acute kidney injury (AKI) is associated with incremental risk for death and chronic kidney disease and represents a mounting clinical challenge for healthcare professionals. Renal replacement therapy (RRT) use in ICU settings is rising, likely in response to similar trends in AKI, taken together with an ageing population burdened by high prevalence of multi-morbidity and high illness acuity. Numerous features of RRT prescription and delivery are not standardized, nor are they supported from high-quality evidence derived from randomized trials. Despite the publication of rigorous clinical practice guidelines focused on RRT for AKI that are intended to optimize the quality and reliability of RRT in ICU settings, practice patterns and outcomes continue to show significant variability. In this concise review, we aim to summarize new knowledge and recent advances for the provision of RRT for critically ill patients with AKI.

Background and Objectives: AKI is frequent and is associated with poor outcomes. There is limited information on the epidemiology of AKI worldwide. This study compared patients with AKI in emerging and developed countries to determine the association of clinical factors and processes of care with outcomes., Design, Setting, Participants, & Measurements: This prospective observational study was conducted among intensive care unit patients from nine centers in developed countries and five centers in emerging countries. AKI was defined as an increase in creatinine of ≥0.3 mg/dl within 48 hours., Results: Between 2008 and 2012, 6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745 (58% of those with AKI) agreed to participate and had complete data. Patients in developed countries had more sepsis (52.1% versus 38.0%) and higher Acute Physiology and Chronic Health Evaluation (APACHE) scores (mean±SD, 61.1±27.5 versus 51.1±25.2); those from emerging countries had more CKD (54.3% versus 38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all P<0.05). Patients from developed countries were less often treated with dialysis (15.5% versus 30.2%; P<0.001) and started dialysis later after AKI diagnosis (2.0 [interquartile range, 0.75-5.0] days versus 0 [interquartile range, 0-5.0] days; P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis dependent at discharge. Independent risk factors associated with hospital mortality included older age, residence in an emerging country, use of vasopressors (emerging countries only), dialysis and mechanical ventilation, and higher APACHE score and cumulative fluid balance (developed countries only). A lower probability of renal recovery was associated with residence in an emerging country, higher APACHE score (emerging countries only) and dialysis, while mechanical ventilation was associated with renal recovery (developed countries only)., Conclusions: This study contrasts the clinical features and management of AKI and demonstrates worse outcomes in emerging than in developed countries. Differences in variations in care may explain these findings and should be considered in future trials., (Copyright © 2015 by the American Society of Nephrology.)

Objective: Acute kidney injury (AKI) is a highly morbid condition in critically ill patients that is associated with high mortality. Previous clinical studies have demonstrated the safety and efficacy of the Selective Cytopheretic Device (SCD) in the treatment of AKI requiring continuous renal replacement therapy in the intensive care unit (ICU)., Design, Setting, Patients: A randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy., Results: No significant difference in 60-day mortality was observed between the treated (27/69; 39%) and control patients (21/59; 36%, with six patients lost to follow up) in the intention to treat (ITT) analysis. Of the 19 SCD subjects (CRRT+SCD) and 31 control subjects (CRRT alone) who maintained a post-filter ionized calcium (iCa) level in the protocol's recommended range (≤ 0.4 mmol/L) for greater or equal to 90% of the therapy time, 60-day mortality was 16% (3/19) in the SCD group compared to 41% (11/27) in the CRRT alone group (p = 0.11). Dialysis dependency showed a borderline statistically significant difference between the SCD treated versus control CRRT alone patients maintained for ≥ 90% of the treatment in the protocol's recommended (r) iCa target range of ≤ 0.4 mmol/L with values of, 0% (0/16) and 25% (4/16), respectively (P = 0.10). When the riCa treated and control subgroups were compared for a composite index of 60 day mortality and dialysis dependency, the percentage of SCD treated subjects was 16% versus 58% in the control subjects (p<0.01). The incidence of serious adverse events did not differ between the treated (45/69; 65%) and control groups (40/65; 63%; p = 0·86)., Conclusion: SCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit., Trial Registration: ClinicalTrials.gov NCT01400893 http://clinicaltrials.gov/ct2/show/NCT01400893.

Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria (AKI UO). We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC) and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78). The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89), which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02) and PC levels independently predicted mortality/non-renal recovery (p=0.04). In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

Background: Patients with acute decompensated heart failure (ADHF) and cardiorenal syndrome (CRS) 1 have poor outcomes. Ultrafiltration (UF) is used to mechanically remove salt and water in ADHF patients with diuretic resistance. However, little is known about the outcomes of ADHF patients on inotropes and/or vasopressors who require continuous renal replacement therapy (CRRT) for both UF and solute clearance in severe acute kidney injury., Methods: We retrospectively analyzed 37 consecutive critically ill patients who were admitted for ADHF from 2005-13 and were on inotropes and/or vasopressors at the time of CRRT initiation. The primary outcome was in-hospital mortality., Results: In-hospital mortality rate was 62%. Median survival was 15.5 days after CRRT initiation, and 10 months following hospital discharge. When comparing renal and cardiovascular variables for survivors and non-survivors at baseline, admission and CRRT initiation, survivors were less likely to need vasopressors. After controlling for multiple predictors, vasopressor use remained associated with time to death (HR 9.9; 95% CI 2.3-43.3; P = 0.002). Patients with isolated right ventricular dysfunction had an in-hospital mortality of 45% compared with 69% in those with left ventricular dysfunction (P = 0.27). Age of >70 years was associated with 100% in-hospital mortality., Conclusions: Rescue therapy using CRRT in refractory CRS1 was associated with high in-hospital mortality, especially when vasopressors were used and when patient age exceeded 70 years. Additionally, survivors had a poor long-term prognosis.

Background: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT. Methods: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa. Results: Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function. Conclusions: Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing. [ABSTRACT FROM AUTHOR]

Introduction: There is an increasing use of point-of-care testing (POCT) devices for patients. These portable devices are preferred by healthcare personnel because they are quick and easy to use. The aim of this study was to investigate whether POCT devices can provide rapid and reliable blood gas measurements. Methods: Blood gas measurements were performed for 30 pediatric patients at the University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital using a POCT device and a fully automatic blood gas analyzer. Eleven parameters (pH, pCO2, pO2, sodium, potassium, calcium, glucose, lactate, hematocrit, cHCO3, and cSO2) were compared. The statistical analyses were performed using the NCSS software. To determine the correlation between the two methods, the intraclass correlation coefficient (ICC) was calculated, and Bland-Altman graphs were used. Results: The ICC demonstrated an almost strong correlation with pH (ICC=0.889), pCO2 (ICC=0.968), pO2 (ICC=0.981), sodium (ICC=0.799), potassium (ICC=0.968), calcium (ICC=0.909), glucose (ICC=0.967), cHCO3 (ICC=0.919) and cSO2(ICC=0.988) and moderate correlation with lactate (ICC=0.626) and hematocrit (ICC=0.491). All p-values were all <0.001 for all analytes. Conclusion: The POCT device was compared with a fully automatic blood gas analyzer. Unjustified postponement of analysis in patients with respiratory failure, shock, or electrolyte disorders can delay the application of appropriate treatment. Not only the benefits of an accurate POCT measurement but also the benefits of clinical practice and process changes should be taken into consideration. [ABSTRACT FROM AUTHOR]

Background Continuous renal replacement therapy (CRRT) is the most frequently used modality of renal replacement therapy (RRT) in critical care patients with acute kidney injury (AKI). Adequate CRRT delivery can be challenging, due to problems with circuit patency. To improve circuit patency, we developed a new CRRT protocol using continuous veno-venous hemodiafiltration (CVVHDF) with 3.0 mmol/l regional citrate anticoagulation (CVVHDF/RCA3.0) as our first choice RRT modality. Methods Retrospective comparison of efficacy and safety of a CVVHDF/RCA3.0 protocol with our former continuous veno-venous hemofiltration protocol with 2.2 regional citrate anticoagulation (CVVH/RCA2.2) in adult critically ill patients with AKI requiring CRRT between 25 April 2020 and 24 October 2021. Results In total, 56 patients (257 circuits) and 66 patients (290 circuits) were included in the CVVH/RCA2.2 and CVVHDF/RCA3.0 groups, respectively. Median circuit survival was significantly higher in patients treated with CVVHDF/RCA3.0 (39.6 (IQR 19.5–67.3) hours) compared to patients treated with CVVH/RCA2.2 (22.9 (IQR 11.3–48.6) hours) (P < .001). Higher body weight and higher convective flow were associated with a lower circuit survival. Metabolic control was similar, except for metabolic alkalosis that occurred less frequently during CVVHDF/RCA3.0 (19% of patients) compared to CVVH/RCA2.2 (46% of patients) (P = .006). Conclusions CRRT circuit survival was longer with CVVHDF/RCA3.0 compared to CVVH/RCA2.2. CRRT circuit survival was negatively associated with higher body weight and higher convective flow. [ABSTRACT FROM AUTHOR]

Up to 30% of patients undergoing cardiac surgery develop AKI, with 1% requiring RRT. AKI is an independent risk factor for morbidity and mortality. Postoperatively, even minimal changes in serum creatinine are associated with a substantial increase in mortality. No intervention has been definitely proven effective in reducing kidney injury. The successful prevention and management of AKI involves identifying patients at risk for AKI, recognizing subtle abnormalities in a timely manner, performing basic clinical assessments, and responding appropriately to data obtained. With that in mind, in this Attending Rounds, a woman with AKI in the setting of cardiac surgery is presented to highlight the use of history, physical exam, hemodynamic monitoring, laboratory data trends, and urine indices in establishing the correct diagnosis and appropriate management., (Copyright © 2014 by the American Society of Nephrology.)

Introduction: Regional citrate anticoagulation (RCA) is used as an anticoagulant for continuous renal replacement therapy (CRRT). A systemic calcium (Ca2+) infusion is required to replace Ca2+ lost in the effluent. The shortage of intravenous Ca2+ in the United States has limited RCA use. We describe a continuous veno-venous hemofiltration (CVVH) protocol with RCA using 2.2% anticoagulant citrate dextrose formula-A (ACD-A) and a commercial dialysate containing Ca2+ 1.5 mmol/l (N × Stage) as post-filter replacement fluid (RF), without need for Ca2+ infusion., Methods: We prospectively evaluated five patients on CRRT who had at least three episodes of filter clotting within 24 h. Patients were switched to CVVH using ACD-A infused pre-blood pump and titrated to achieve a post-filter ionized calcium (iCa2+) level <0.5 mmol/l. The Ca2+ -containing dialysate was delivered post-filter as RF., Results: Steady state mean serum chemistries were: Na+: 140.8 ± 2.3 meq/l, K+: 4.2 ± 0.4 meq/l, HCO3-: 30.9 ± 3.7 meq/l, pH: 7.42 ± 0.07, CO2: 47.9 ± 8.3 mmHg, total Ca2+: 8.08 ± 1.09 mg/dL. Post-filter iCa2+ ranged 0.27-0.36 mmol/l, and patient iCa2+ ranged 0.81-1.24 mmol/l. Mean post-filter RF rate: 3086 ± 164 ml/h, mean ACD-A rate: 298 ± 21 ml/h. Mean blood flow rate: 200 ± 17 ml/min, mean filtration fraction: 39.6 ± 7.2%. Mean effluent flow rate: 38.6 ± 6.7 ml/kg/h (range 28.7-55.8). Mean filter survival was 7 h without anticoagulation, compared to 42.6 h in the ACD-A group (p<0.0001)., Conclusions: In this pilot study, CVVH using ACD-A for RCA and a Ca2+ -containing RF was safely and effectively used without a continuous Ca2+ infusion. This protocol is a promising solution for maintaining effective CRRT when intravenous calcium is in short supply.

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field., (© 2023. The Author(s).)

Acute kidney injury (AKI) is characterized by deterioration in kidney function resulting in multisystem abnormalities. Much of the morbidity and mortality associated with AKI result from a systemic inflammatory response syndrome (SIRS). This study described herein is a prospective, single-arm, multicenter US study designed to evaluate the safety and efficacy of the Selective Cytopheretic Device (SCD) treatment on AKI requiring continuous renal replacement therapy (CRRT) in the ICU. The study enrolled 35 subjects. The mean age was 56.3±15. With regard to race, 71.4% of the subjects were Caucasian, 22.9% were Black, and 5.7% were Hispanic. Average SOFA score was 11.3±3.6. Death from any cause at Day 60 was 31.4%. Renal recovery, defined as dialysis independence, was observed in all of the surviving subjects at Day 60. The results of this pilot study indicate the potential for a substantial improvement in patient outcomes over standard of care therapy, which is associated with a greater than 50% 60-day mortality in the literature. The SCD warrants further study in scientifically sound, pivotal trial to demonstrate reasonable assurance of safety and effectiveness., (© 2012 Wiley Periodicals, Inc.)

In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI., (Published by Elsevier Inc.)

Normal acid-base homeostasis is severely challenged in the intensive care setting. In this review, we address acid-base disturbances, with a special focus on the use of continuous (rather than intermittent) extracorporeal technologies in critical ill patients with acute kidney injury. We consider hypercapnic acidosis and lactic acidosis as examples in which continuous modalities may have different roles and indications than the traditional intermittent approaches to renal replacement therapy. Hypercapnic acidosis develops as a consequence of alveolar hypoventilation. In this condition, correction of pH above 7.2 is not currently recommended, and may even abrogate the beneficial effects of hypercapnic acidosis on overall outcomes. Extracorporeal technologies support lung protection while maintaining overall patient homeostasis. Similarly, in lactic acidosis, current evidence does not support bicarbonate infusions to correct acidosis. The management of lactic acidosis should correct the underlying causative disturbances. Most often, lactic acidosis is a biomarker denoting unfavorable outcomes, rather than an intrinsic pathogenetic mechanism. Extracorporeal procedures may assist in the removal of pathogenic drugs or toxins, as well as partially correcting acidemia. Whether or not these approaches will permit normalization of systemic pH, and the impact of these approaches on patient outcomes, needs to be addressed with prospective controlled trials.

Background: Substantial efforts have been made toward defining the dose threshold of continuous renal replacement therapy (CRRT) associated with improved survival in critically ill patients with acute kidney injury. Published studies have used prescribed effluent rates, expressed as total effluent volume (TEV) per weight and unit time (mL/kg/h), as a surrogate for dose. The purpose of this study was to compare differences in CRRT dose based on prescribed effluent rate, measured TEV and direct measurement of urea and creatinine clearance., Methods: We analyzed data that had been prospectively collected on 200 patients enrolled in a randomized trial comparing survival with a prescribed effluent rate of 20 mL/kg/h (standard dose) to 35 mL/kg/h (high dose) using pre-dilution continuous venovenous hemodiafiltration (CVVHDF). Filters were changed every 72 h. Blood urea nitrogen (BUN), serum creatinine (SCr), effluent urea nitrogen (EUN) and effluent creatinine (ECr) were collected daily. Actual delivered dose was calculated as: (EUN/BUN)*TEV for urea and (ECr/SCr)*TEV for creatinine. Data were available for 165 patients., Results: In both groups, prescribed dose differed significantly from the measured TEV dose (P < 0.001). In the standard dose group, there was no difference between the measured TEV dose and actual delivered urea and creatinine clearances. However, in the high-dose group, measured TEV dose differed significantly from delivered urea clearance by 7.1% (P < 0.001) and creatinine clearance by 13.9% (P < 0.001)., Conclusions: Dose based on prescribed effluent rate or measured TEV is a poor substitute for actual CVVHDF creatinine and urea clearance.

Background and Objectives: Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions., Design, Setting, Participants, & Measurements: A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters., Results: Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h(-1), intraquartile range=0.052 h(-1)) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered., Conclusions: There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.

Purpose: Acute kidney injury in the pediatric intensive care unit (PICU) is associated with significant morbidity, with continued mortality greater than 50%. Previous studies have described an association between percentage of fluid overload (%FO) less than 20% and improved survival. We reviewed our continuous renal replacement therapy (CRRT) experience to evaluate for factors associated with mortality as well as secondary outcomes., Materials and Methods: This is a retrospective chart review of pediatric CRRT intensive care unit patients from January 2000 to September 2005., Results: Seventy-six admissions required CRRT during the study period. Overall survival was 55.3%. Median patient age was 5.8 years (range, 0-18.9). Median %FO at the time of CRRT initiation was 7.3% in survivors vs 22.3% in nonsurvivors (P = .0001). Presence of sepsis was significantly associated with mortality (P = .0001). All nonsurvivors had multiple organ dysfunction syndrome (MODS); only 69% of survivors had MODS (P = .0003). For survivors, there was a significant relationship between %FO and time to renal recovery (P = .0038). Greater %FO was also associated with significantly prolonged days of mechanical ventilation (P = .0180), PICU stay (P = .0425), and duration of hospitalization (P = .0123)., Conclusions: For patients with acute kidney injury who require CRRT, the presence of sepsis, MODS, and FO greater than 20% at the time of CRRT initiation are significantly associated with higher mortality. In addition, we report that duration of mechanical ventilation, PICU stay, hospitalization, and time to renal recovery were all significantly prolonged for survivors who had FO greater than 20%.

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury, particularly those with hemodynamic instability. Anticoagulation is necessary for effective delivery of CRRT, but this requirement can also present challenges, as many critically ill patients with sepsis and inflammation already have a higher risk of bleeding as well as clotting. Without anticoagulation, CRRT filter and circuit survival are diminished, and therapy becomes less helpful. Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods of anticoagulation have been investigated, including regional heparin/protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat). Each of these techniques has unique advantages and disadvantages, and anticoagulation for CRRT should be adapted to the patient's characteristics and institution's experience. Of the alternative methods, citrate anticoagulation is gaining wider acceptance with the development of simplified and safer protocols.

The effect of dosage of continuous venovenous hemodiafiltration (CVVHDF) on survival in patients with acute renal failure (ARF) is unknown. In this study, 200 critically ill patients with ARF were randomly assigned to receive CVVHDF with prefilter replacement fluid at an effluent rate of either 35 ml/kg per h (high dosage) or 20 ml/kg per h (standard dosage). The primary study outcome, survival to the earlier of either intensive care unit discharge or 30 d, was 49% in the high-dosage arm and 56% in the standard-dosage arm (odds ratio 0.75; 95% confidence interval 0.43 to 1.32; P = 0.32). Among hospital survivors, 69% of those in the high-dosage arm recovered renal function compared with 80% of those in the standard-dosage arm (P = 0.29); therefore, a difference in patient survival or renal recovery was not detected between patients receiving high-dosage or standard-dosage CVVHDF.

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.

Various definitions of acute kidney injury (AKI) exist, making comparisons among studies difficult. Despite this, significant changes have occurred in the epidemiology of AKI during the last decade. Recent studies, including PICARD and BEST, have examined the epidemiology of ICU-related AKI in the USA and worldwide, respectively, and found that AKI remains a major cause of morbidity and mortality. The incidence of AKI has increased, most likely due to a trend toward older, more severely and chronically ill patients admitted to the hospital. Sepsis and multi-organ system failure continue to be strongly associated with AKI, as well as pre-morbid chronic kidney disease. The proportion of patients with AKI requiring dialysis is high. The mortality of ICU-related AKI, although still very elevated, may be decreasing. Understanding these changes, in the context of standardized definitions, will be essential for the design of successful interventional studies., (Copyright (c) 2008 S. Karger AG, Basel.)

Sustained low-efficiency dialysis (SLED) is an increasingly popular form of renal replacement therapy for patients with renal failure in the intensive care unit. Advantages of SLED are efficient clearance of small solutes, good hemodynamic tolerability, flexible treatment schedules, and reduced costs. Studies comparing outcomes of SLED with those of other dialysis modalities are being performed.

Background: Although the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype. Methods: The systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle–Ottawa Quality Assessment Scale for observational studies. Results: A total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4–46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality. Conclusions: Evidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is prevalent in patients with acute stroke. Although AKI is linked to poor clinical outcomes, data about its incidence and effect on stroke outcomes is limited. Methods: This was a prospective observational study carried out at a single tertiary care center that analyzed the data of 204 consecutive subjects with acute ischemic stroke and intracerebral hemorrhage. Considering serum creatinine at admission as the baseline, AKI was defined as a rise in serum creatinine value of 0.3 mg/dl over 48 h or a percentage increase of at least 50% from baseline over 7 days during hospitalization. The primary outcome was to measure the prevalence of AKI in patients with acute stroke. Secondary outcome measures were all-cause mortality, duration of hospital stay, need for dialysis, and comparison of outcomes in ischemic and hemorrhagic stroke. For both the stroke subtypes, we employed a multivariate logistic regression model, with AKI and hospital mortality being the outcomes. Covariates included gender, age, ventilatory requirement, duration of hospital stay, and National Institutes of Health Stroke Scale score at admission. Results: There were 144 cases of ischemic stroke with 12 deaths (8.3%) and 60 cases of intracranial hemorrhage (ICH) with 22 deaths (36.7%). The mean age was 55 years, 72.6% were males, and AKI complicated 34% of ischemic stroke and 66.7% of ICH hospitalizations. AKI was linked to increased hospital mortality from ischemic stroke (odds ratio [OR] 27.21, 95% CI 3.39-218.13) and hemorrhagic stroke (OR 5.12, 95% CI 1.29-20.28) in multivariate analysis stratified by stroke type. Conclusions: AKI complicates stroke frequently and increases hospital mortality. Additional studies are required to assess if the association is causal and if remedies to prevent AKI would decrease mortality. [ABSTRACT FROM AUTHOR]

Background: Research into the acute kidney disease (AKD) after acute ischemic stroke (AIS) is rare, and how clinical features influence its prognosis remain unknown. We aim to employ interpretable machine learning (ML) models to study AIS and clarify its decision-making process in identifying the risk of mortality. Methods: We conducted a retrospective cohort study involving AIS patients from January 2020 to June 2021. Patient data were randomly divided into training and test sets. Eight ML algorithms were employed to construct predictive models for mortality. The performance of the best model was evaluated using various metrics. Furthermore, we created an artificial intelligence (AI)-driven web application that leveraged the top ten most crucial features for mortality prediction. Results: The study cohort consisted of 1633 AIS patients, among whom 257 (15.74%) developed subacute AKD, 173 (10.59%) experienced AKI recovery, and 65 (3.98%) met criteria for both AKI and AKD. The mortality rate stood at 4.84%. The LightGBM model displayed superior performance, boasting an AUROC of 0.96 for mortality prediction. The top five features linked to mortality were ACEI/ARE, renal function trajectories, neutrophil count, diuretics, and serum creatinine. Moreover, we designed a web application using the LightGBM model to estimate mortality risk. Conclusions: Complete renal function trajectories, including AKI and AKD, are vital for fitting mortality in AIS patients. An interpretable ML model effectively clarified its decision-making process for identifying AIS patients at risk of mortality. The AI-driven web application has the potential to contribute to the development of personalized early mortality prevention. Keypoints: What was known: Acute kidney disease (AKD) defines patients with acute kidney injury (AKI) or subacute loss of kidney function lasting for more than 7 days, which links well AKI to subsequent chronic kidney disease (CKD). Little is known about the risk and prognosis of AKD in acute ischemic stroke (AIS) patients. This study adds: Renal function trajectories, including both AKI and AKD, play a crucial role in predicting mortality in AIS patients. The LightGBM model elucidates decision processes by providing explanations at both global and local levels. The AI web application aids in reducing mortality rates and helps physicians make informed treatment decisions. Potential impact: Adding AKD as a definition for renal failure lasting > 7 days up to 90 days is of clinical importance in addition to the existing definitions for AKI and CKD. Research activities and clinical practice should also focus on AKD, which is far more accurate to predict prognosis especially mortality. [ABSTRACT FROM AUTHOR]

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8–34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe. [ABSTRACT FROM AUTHOR]

Obstacles to the widespread use of continuous renal replacement therapy (CRRT) include the need for anticoagulation, customized solutions, and complex protocols that carry an attendant risk for error, raise cost, and increase pharmacy and nursing workload. However, high solute clearance using CRRT with an effluent rate of 35 ml/kg per h has also recently been associated with improved survival in critically ill patients with acute renal failure. No published CRRT protocols using dilute regional citrate anticoagulation have achieved adequate metabolic control, effective anticoagulation, and high solute clearance in a practical, user-friendly, and economical manner. The safety and the efficacy of continuous venovenous hemodiafiltration at effluent rates of 35 ml/kg per h in critically ill acute renal failure patients were evaluated prospectively using a standardized bicarbonate-based dialysate; a systemic calcium infusion; and two separate trisodium citrate replacement solutions, a 0.67% solution and a 0.5% solution. All patients achieved adequate metabolic control, the desired effluent rate of 35 ml/kg per h, and high solute clearance. Use of the 0.67% citrate replacement solution resulted in mild alkalosis, whereas the 0.5% solution maintained appropriate acid-base balance. There was no difference in dialyzer survival between the 0.67 and 0.5% citrate groups (80 versus 82%; P = 0.60, Kaplan-Meier analysis). Dilute regional citrate as part of a CRRT protocol with a standard 25-mmol/L bicarbonate dialysate provides adequate metabolic control, high diffusive and convective clearance, and excellent dialyzer patency in a practical and cost-effective manner.