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A 72-year-old female presented to the emergency room (ER) of Fatmawati Hospital with pneumonia and ketosis. After 12 h, her level of consciousness (LoC) decreased and she developed shortness of breath. In the ICU, antibiotics and supportive therapies were administered. After several hours, the need for vasopressors increased. Laboratory results showed severe lymphopenia, increased neutrophil to lymphocyte ratio (NLR) and D-Dimer levels. Septic shock and decreased LoC with severe immunoparalysis can be caused by intracranial process. A brain CT scan revealed massive ischemic stroke. Measures were taken to reduce intracranial pressure. Continuous Renal Replacement Therapy (CRRT) was performed for blood purification and immunomodulation. Vasopressor requirements decreased, her absolute lymphocyte increased and her NLR decreased. Diuresis and fluid balance were improved. She was subsequently discharged to the ICU. In this patient, massive ischemic stroke induced immunoparalysis, which manifested as lymphopenia and increased susceptibility to infection. Severe lymphopenia can be used as an early marker of ischemic stroke with signs of sepsis. [ABSTRACT FROM AUTHOR]

Sepsis is an uncontrolled immunological host reaction to infection that causes organ dysfunction. Mortality related to sepsis-associated acute kidney injury (SA-AKI) is 30%−60%. A 62−year-old woman presented to emergency room (ER) of Fatmawati Hospital with decreased consciousness for one day. Complaints of productive cough, fever, and shortness of breath were noted. We found hypotension with cold extremities, fever, tachycardia, and labored breathing. Her SOFA score was 12, blood glucose level was very high, urine production was less than 0.5 ml/kg/h in 6 h, high creatinine level (1.69 mg/dL), fluid balance +643 ml/6 h, and chest X-ray showing bilateral infiltrates. The patient was intubated to reduce work of breathing and stabilize hemodynamics. Management of the sepsis bundle was initiated by administration of vasopressors despite adequate fluid intake and two broad-spectrum antibiotics (meropenem and levofloxacin). On the second day, continuous renal replacement therapy (CRRT) was performed due to oliguria and worsened AKI caused by septic shock. After 48 h of CRRT, the patient clinically improved. The patient was extubated successfully on the fifth day of treatment. [ABSTRACT FROM AUTHOR]

Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid–base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required. Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient's bleeding risk. Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the impact of citrate on hemodynamic responses and secondary outcomes, including the filter life span, metabolic complications, and levels of inflammatory cytokines, in critically ill patients who required CRRT compared with those who underwent the heparin-free method. This prospective, multicenter, open-label randomized trial compared regional citrate anticoagulation (RCA) with a heparin-free protocol in severe acute kidney injury (AKI) patients who received continuous venovenous hemodiafiltration (CVVHDF) in the postdilution mode. We measured hemodynamic changes using the FloTrac Sensor/EV1000™ Clinical Platform at certain time points after starting CRRT (0, 6, 12, 24, 48, and 72 h.). The levels of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10 and TNF-ɑ) were measured on days 1 and 3. Forty-one patients were recruited and randomized into the heparin (n = 20) and citrate groups (n = 21). The cardiac performances were not significantly different between the 2 groups at any time point. The inflammatory cytokines declined similarly in both treatment arms. The maximum filter survival time was insignificantly longer in the RCA group than in the heparin-free group (44.64 ± 26.56 h. vs p = 0.693 in citrate and heparin free group). No serious side effects were observed for either treatment arm, even in the group of liver dysfunction patients. RCA did not affect hemodynamic changes during CRRT. Inflammatory cytokines decreased similarly in both treatment arms.The filter life span was longer in the citrate group. RCA is a valid alternative to traditional anticoagulation and results in stable hemodynamic parameters. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery. Study Design: Multicenter, prospective living registry. Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded. Exposure: CKRT for more than 24 hours. Outcomes: Hospital mortality, kidney recovery, and health care resource utilization. Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively. Results: Patients’ characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P

For patients on extracorporeal membrane oxygenation (ECMO) who require renal replacement therapy (RRT), dialysis can be achieved through a dedicated hemodialysis (HD) catheter or direct connection to the ECMO circuit. The relative effect of each on filtration efficacy is not known. We conducted a retrospective single-center analysis of patients on ECMO who required CRRT. We examined the outcomes of blood biomarkers and transmembrane filter pressures, comparing sessions by attachment approach. All analyses were clustered by patient. Of the 33 patients (7 ECMO access and 23 HD catheter access) that met the inclusion criteria, there were a total of 493 CRRT sessions (93 ECMO access and 400 HD catheter access). At the end of the first 12 h of CRRT therapy, the ECMO group had a greater rate of decline in serum BUN than the HD catheter access group (2.5 mg/dl (SD 11) vs. 2 mg/dl (SD 6), p = 0.035). Additionally, the platelet level was significantly higher in the ECMO group compared to the HD catheter access group after 72 h (94.5 k/uL (SD 41) vs. 71 k/uL (SD 29), p = 0.008). Utilizing the ECMO circuit as direct venous access for CRRT was associated with some improved filtration proximal outcomes. [ABSTRACT FROM AUTHOR]

For reducing the high mortality rate of severe acute kidney injury (AKI) patients initiating continuous renal replacement therapy (CRRT), diagnosing sepsis and predicting prognosis are essential. However, with reduced renal function, biomarkers for diagnosing sepsis and predicting prognosis are unclear. This study aimed to assess whether C-reactive protein (CRP), procalcitonin, and presepsin could be used to diagnose sepsis and predict mortality in patients with impaired renal function initiating CRRT. This was a single-center, retrospective study involving 127 patients who initiated CRRT. Patients were divided into sepsis and non-sepsis groups according to the SEPSIS-3 criteria. Of the 127 patients, 90 were in the sepsis group and 37 were in the non-sepsis group. Cox regression analysis was performed to determine the association between the biomarkers (CRP, procalcitonin, and presepsin) and survival. CRP and procalcitonin were superior to presepsin for diagnosing sepsis. Presepsin was closely related to the estimated glomerular filtration rate (eGFR) (r = −0.251, p = 0.004). These biomarkers were also evaluated as prognostic markers. Procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher all-cause mortality using Kaplan–Meier curve analysis. (log-rank test p = 0.017 and p = 0.014, respectively). In addition, procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher mortality in univariate Cox proportional hazards model analysis. In conclusion, a higher lactic acid, sequential organ failure assessment score, eGFR, and a lower albumin level have prognostic value to predict mortality in patients with sepsis initiating CRRT. Moreover, among these biomarkers, procalcitonin and CRP are significant factors for predicting the survival of AKI patients with sepsis-initiating CRRT. [ABSTRACT FROM AUTHOR]

Background and objectives: Amino acid (AA) loss is a prevalent unwanted effect of continuous renal replacement therapy (CRRT) in critical care patients, determined both by the machine set-up and individual characteristics. The aim of this study was to evaluate the bioelectrical impedance analysis-derived fat-free mass index (FFMI) effect on amino acid loss. Materials and methods: This was a prospective, observational, single sample study of critical care patients upon initiation of CRRT. AA loss during a 24 h period was estimated. Conventional determinants of AA loss (type and dose of CRRT, concentration of AA) and FFMI were entered into the multivariate regression analysis to determine the individual predictive value. Results: Fifty-two patients were included in the study. The average age was 66.06 ± 13.60 years; most patients had a high mortality risk with APAHCE II values of 22.92 ± 8.15 and SOFA values of 12.11 ± 3.60. Mean AA loss in 24 h was 14.73 ± 9.83 g. There was a significant correlation between the lost AA and FFMI (R = 0.445, B = 0.445 CI95%: 0.541–1.793 p = 0.02). Multivariate regression analysis revealed the independent predictors of lost AA to be the systemic concentration of AA (B = 6.99 95% CI:4.96–9.04 p = 0.001), dose of CRRT (B = 0.48 95% CI:0.27–0.70 p < 0.001) and FFMI (B = 0.91 95% CI:0.42–1.41 p < 0.001). The type of CRRT was eliminated in the final model due to co-linearity with the dose of CRRT. Conclusions: A substantial amount of AA is lost during CRRT. The amount lost is increased by the conventional factors as well as by higher FFMI. Insights from our study highlight the FFMI as a novel research object during CRRT, both when prescribing the dosage and evaluating the nutritional support needed. [ABSTRACT FROM AUTHOR]

Treating chronic hyponatremia by continuous renal replacement therapy (CRRT) is challenging because the gradient between a replacement fluid's [sodium] and a patient's serum sodium can be steep, risking too rapid of a correction rate with possible consequences. Besides CRRT, other gains and losses of sodium‐ and potassium‐containing solutions, like intravenous fluid and urine output, affect the correction of serum sodium over time, known as osmotherapy. The way these fluids interact and contribute to the sodium/potassium/water balance can be parsed as a mixing problem. As Na/K/H2O are added, mixed in the body, and drained via CRRT, the net balance of solutes must be related to the change in serum sodium, expressible as a differential equation. Its solution has many variables, one of which is the sodium correction rate, but all variables can be evaluated by a root‐finding technique. The mixing paradigm is proved to replicate the established equations of osmotherapy, as in the special case of a steady volume. The flexibility to solve for any variable broadens our treatment options. If the pre‐filter replacement fluid cannot be diluted, then we can compensate by calculating the CRRT blood flow rate needed. Or we can deduce the infusion rate of dextrose 5% water, post‐filter, to appropriately slow the rise in serum sodium. In conclusion, the mixing model is a generalizable and practical tool to analyze patient scenarios of greater complexity than before, to help doctors customize a CRRT prescription to safely and effectively reach the serum sodium target. [ABSTRACT FROM AUTHOR]

Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction. [ABSTRACT FROM AUTHOR]

The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%–70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19's pathophysiological impact. [ABSTRACT FROM AUTHOR]

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Background and Aim: There is limited data on natural course and interventions in stage‐3 acute kidney injury (AKI‐3) in patients with acute‐on‐chronic liver failure (ACLF). We studied the factors of AKI‐3 reversal and outcomes of dialysis in ACLF patients. Methods: Consecutive patients with ACLF were prospectively enrolled (n = 1022) and variables determining AKI and its outcomes were analysed. Results: At 1 month, 337 (33%) patients had AKI‐3, of which, 131 had AKI‐3 at enrolment and 206 developed AKI‐3 during hospital stay. Of patients with AKI‐3 at enrolment, 18% showed terlipressin response, 21% had AKI resolution and 59% required dialysis. High MELD (≥35) (model 1), serum bilirubin (≥23 mg/dL) (model 2) and AARC score (≥11) (model 3) were independent risk factors for dialysis. Dialysis was associated with worse survival in all AKI patients but improved outcomes in patients with AKI‐3 (p =.022, HR 0.69 [0.50–0.95]). Post‐mortem kidney biopsies (n = 61) revealed cholemic nephropathy (CN) in 54%, acute tubular necrosis (ATN) in 31%, and a combination (CN and ATN) in 15%. Serum bilirubin was significantly higher in patients with CN, CN and ATN compared with ATN respectively ([30.8 ± 12.2] vs. [26.7 ± 12.0] vs. [18.5 ± 9.8]; p =.002). Conclusion: AKI‐3 rapidly increases from 13% to 33% within 30 days in ACLF patients. Histopathological data suggested cholemic nephropathy as the predominant cause which correlated with high bilirubin levels. AKI‐3 resolves in only one in five patients. Patients with AARC grade 3 and MELD >35 demand need for early dialysis in AKI‐3 for improved outcomes. [ABSTRACT FROM AUTHOR]

Objective: We retrospectively analyzed risk factors on in-hospital mortality in CRRT-therapy patients with open cardiac surgery (CS)-induced acute kidney injury (AKI), to provide the clinical basis for predicting and lowering the in-hospital mortality after CS. Methods: 84 CS-AKI patients with CRRT were divided into survival and death groups according to discharge status, and the perioperative data were analyzed with R version 4.0.2. Results: There were significant differences between the two groups, including: urea nitrogen, Sequential Organ Failure Assessment (SOFA) score and vasoactive-inotropic score (VIS) on the first day after operation; VIS just before CRRT; SOFA score and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, severe infection and MODS after operation; and the interval between AKI and CRRT. Univariate logistic regression analysis showed that SOFA score and VIS on the first day after operation; VIS just before CRRT; VIS and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, infection and multiple organ dysfunction syndrome (MODS) after operation; bootstrap resampling analysis showed that SOFA score and VIS 24 h after CRRT, as well as the incidence of bleeding after operation were the independent risk factors. Conclusion: Maintaining stable hemodynamics and active prevention of bleeding are expected to decrease the in-hospital mortality. [ABSTRACT FROM AUTHOR]

Background: Cefiderocol is a novel parenteral siderophore cephalosporin, demonstrating enhanced activity against multidrug-resistant (MDR) Gram-negative bacteria and difficult-to-treat Acinetobacter baumannii (DTR-AB). Plasma-free trough concentration (fCtrough) over the minimum inhibitory concentration (MIC) was reported as the best pharmacokinetic parameter to describe the microbiological efficacy of cefiderocol. Materials and methods: We retrospectively described the pharmacokinetic and pharmacodynamic profile of three critically ill patients admitted to the intensive care unit, receiving cefiderocol under compassionate use to treat severe DTR-AB infections while undergoing continuous venovenous haemofiltration. Cefiderocol was administrated at a dosage of 2 g every 8 h infused over 3 h. Therapeutic drug monitoring (TDM) was assessed at the steady state. Cthrough was evaluated by assuming a plasma protein binding of 58.0%. The fCmin/MIC was calculated assuming a cefiderocol MIC equal to the PK-PD breakpoint of susceptibility ≤ 2. The association between the PK/PD parameters and microbiological outcome was assessed. Results: fCtrough/MIC were >12 in 2 patients and 2.9 in the 1 who rapidly recovered from renal failure. Microbiological cure occurred in 3/3 of patients. None of the 3 patients died within 30 days. Conclusions: A cefiderocol dosage of 2 g q8 h in critically ill patients with AKI undergoing CVVH may bring about a very high plasma concentration, corresponding to essentially 100% free time over the MIC for DTR-AB. [ABSTRACT FROM AUTHOR]

Abstract Background Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT02486614

Background: Acute kidney injury (AKI) remains a common sequela of sepsis necessitating use of continuous renal replacement therapy (CRRT). In the setting of AKI, renally adjusted antimicrobials (eg, β-lactams) are dose reduced to prevent toxicity; however, the extracorporeal clearance of CRRT may lead to subtherapeutic exposures of dose reduced antimicrobials. The present study sought to evaluate the time to dose adjustment to CRRT appropriate doses of antimicrobials after initiation of CRRT. Methods: A retrospective cohort study of patients on CRRT and anti-pseudomonal β-lactams was conducted. CRRT was conducted as continuous veno-venous hemodialysis (CVVHD) per institutional standards. Baseline characteristics were collected including dialysate flow rate. The primary outcome was time to CRRT appropriate dose adjustment. Secondary outcomes included the pharmacist shift (ie, day, evening, or night shift) that CRRT was ordered and initiated. Continuous data were reported as median (IQR). Results: Forty-four patients were included in the analysis. The median dialysate flow rate was 2.3 L/hour (2, 3.1). Of included patients, 75% received cefepime therapy while 25% received meropenem. The median time to CRRT appropriate dosing was 13 hours (6, 20). CRRT was most commonly ordered during day shift (68%) but not started until evening (59%). The observed delay in appropriate dose adjustment may predispose patients to suboptimal antimicrobial exposure and subsequently therapeutic failure. CRRT was often ordered during the day shift but not initiated until evening which led to identification of potential procedural improvements. Conclusions: These data led to the initiation of a pharmacy in basket consult to alert pharmacists in real time of CRRT orders so that once CRRT was started, doses could be appropriately adjusted. Future studies to assess the impact of this process change on both time to appropriate dose and clinical outcomes are warranted. [ABSTRACT FROM AUTHOR]

Sha He, Zeneng Cheng, Feifan Xie Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, People’s Republic of ChinaCorrespondence: Zeneng Cheng; Feifan XieDivision of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Tongzipo Road 172, Changsha, 410013, People’s Republic of ChinaTel/Fax +86 731 8265 0446Email chengzn@csu.edu.cn; feifan.xie@csu.edu.cnPurpose: Appropriate gentamicin dosing in continuous renal replacement therapy (CRRT) patients remains undefined. This study aimed to develop a population pharmacokinetic (PK) model of gentamicin in CRRT patients and to infer the optimal dosing regimen for gentamicin.Methods: Fourteen CRRT patients dosed with gentamicin were included to establish a population PK model to characterize the variabilities and influential covariates of gentamicin. The pharmacokinetic/pharmacodynamic (PK/PD) target attainment and risk of toxicity for different combinations of gentamicin regimens (3– 7 mg/kg q24h) and CRRT effluent doses (30– 50 mL/h/kg) were evaluated by Monte Carlo simulation. The probability of target attainment (PTA) was determined for the PK/PD indices of the ratio of drug peak concentration/minimum inhibitory concentration (Cmax/MIC > 10) and the ratio of area under the drug concentration–time curve/MIC over 24 h (AUC0-24h/MIC > 100), and the risk of toxicity was estimated by drug trough concentration thresholds (1 and 2 mg/L).Results: A one-compartment model adequately described the PK characteristics of gentamicin. Covariates including body weight, age, gender, and CRRT modality did not influence the PK parameters of gentamicin based on our dataset. All studied gentamicin regimens failed to achieve satisfactory PTAs for pathogens with an MIC ≥ 2 mg/L. A good balance of PK/PD target attainment and risk of toxicity (> 2 mg/L) was achieved under 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose for an MIC ≤ 1 mg/L. CRRT dose intensity had a significant impact on the target attainment of AUC0-24h/MIC > 100 and risk of toxicity.Conclusion: A combination of 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose might be considered as a starting treatment option for CRRT patients, and drug monitoring is required to manage toxicity.Keywords: gentamicin, CRRT, population pharmacokinetics, critically ill

Abstract Treating chronic hyponatremia by continuous renal replacement therapy (CRRT) is challenging because the gradient between a replacement fluid's [sodium] and a patient's serum sodium can be steep, risking too rapid of a correction rate with possible consequences. Besides CRRT, other gains and losses of sodium‐ and potassium‐containing solutions, like intravenous fluid and urine output, affect the correction of serum sodium over time, known as osmotherapy. The way these fluids interact and contribute to the sodium/potassium/water balance can be parsed as a mixing problem. As Na/K/H2O are added, mixed in the body, and drained via CRRT, the net balance of solutes must be related to the change in serum sodium, expressible as a differential equation. Its solution has many variables, one of which is the sodium correction rate, but all variables can be evaluated by a root‐finding technique. The mixing paradigm is proved to replicate the established equations of osmotherapy, as in the special case of a steady volume. The flexibility to solve for any variable broadens our treatment options. If the pre‐filter replacement fluid cannot be diluted, then we can compensate by calculating the CRRT blood flow rate needed. Or we can deduce the infusion rate of dextrose 5% water, post‐filter, to appropriately slow the rise in serum sodium. In conclusion, the mixing model is a generalizable and practical tool to analyze patient scenarios of greater complexity than before, to help doctors customize a CRRT prescription to safely and effectively reach the serum sodium target.

Introduction: Evidence shows that continuous renal replacement therapy (CRRT) and hemodialysis may be effective in the treatment of Coronavirus disease-2019 (COVID-19). This study aimed to compare the effects of CRRT and hemodialysis on complications, vital signs, and laboratory parameters in patients with COVID-19. Materials and Methods: This cross-sectional study was performed on 113 patients with COVID-19 who underwent hemoperfusion in Kosar Hospital of Semnan city (Iran) between 2020 and 2021. The patients were divided into two groups, the CRRT hemoperfusion group (n=49) and the hemodialysis group (n=64). A checklist was used for collecting data, which included demographic variables, history of underlying diseases, vital signs, laboratory parameters, complications, and various outcomes, which were extracted through interviews with patients or companions and in medical records. IBM Statistical Package for the Social Sciences Statistics for Windows version 26 was used for data analysis. Results: The time from hemoperfusion to hospital discharge (3.84±4.51 vs. 5.92±4.16 day), duration of intubation (0.33±0.94 vs. 1.84±3.42), death after hemoperfusion (64.06 vs. 26.5%), situational instability (21.9 vs. 8.2%), and death during hemoperfusion (14.1 vs. 0%) were significantly lower in the CRRT group than in the hemodialysis group (p

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. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal membrane oxygenation (ECMO) and Continuous renal replacement therapy (CRRT) are treatments for critically ill patients with respiratory failure and acute kidney injury. However, no reliable factors have been identified to predict survival in patients treated with both ECMO and CRRT. The aim of this study was to identify prognostic factors for discharging intensive care unit (ICU) patients who required CRRT during ECMO. Methods: We retrospectively analyzed data from patients who required CRRT in addition to the ECMO, between April 2015 and March 2018. The patients were divided into two groups: patients who survived and patients who died during ICU hospitalization. We determined their demographic and clinical characteristics, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, Simplified Acute Physiology Score II (SAPS II) scores, and sequential organ failure assessment (SOFA) scores. Further, we assessed whether these characteristics differed between individuals who did or did not survive the ICU hospitalization. Results: We found that the APACHE II and SAPS II scores differed significantly between both ECMO and CRRT treated patients who did or did not survive hospitalization. Further, intracranial hemorrhage during ECMO and CRRT therapy was associated with lower survival rate. Conclusions: Using APACHE II and SAPS II scores might be helpful in making treatment decisions for patients treated with ECMO and CRRT. Intracranial hemorrhage could be a poor prognostic factor. Our findings indicate the potential utility of APACHE II and SAPS II scores to predict mortality in patients treated with both ECMO and CRRT. [ABSTRACT FROM AUTHOR]

Keywords: AKI; CRRT; G6PD; High-dose vitamin; No adverse effects; Other side effects; Safe; Septic shock; Vitamin inducing AKI EN AKI CRRT G6PD High-dose vitamin No adverse effects Other side effects Safe Septic shock Vitamin inducing AKI 1199 1202 4 09/05/22 20220901 NES 220901 The article is related to the article available at https://doi.org/10.1007/s40262-022-01142-1. Conclusions Whereas the conclusions drawn by Chen et al. add to our knowledge of high-dose IVC, they are not applicable in patients with G6PD deficiency, in those with AKI receiving CRRT, and in patients with septic shock. While low doses of vitamin C can treat methemoglobinemia in patients with G6PD deficiency, high doses of vitamin C can induce this pathology [[8]]. [Extracted from the article]

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus, need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90% and 95% and 80% and 90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing deceased donor transplants in Asian countries, living donations in Western countries, auxiliary liver transplants, and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cefiderocol is the first antibiotic with effluent flow rate-based dosing recommendations outlined in the product label for patients receiving continuous renal replacement therapy (CRRT). We aimed to investigate the population pharmacokinetics of cefiderocol among patients receiving CRRT and validate these dosing recommendations., Methods: A multicenter, prospective cefiderocol pharmacokinetic study among intensive care unit patients receiving CRRT was conducted (2022-2023). Blood sampling was performed at steady-state and cefiderocol concentrations were assayed by validated liquid chromatography-tandem mass spectrometry. Population pharmacokinetic analyses were conducted in Pmetrics using R software. The free time above the minimum inhibitory concentration ( f T > MIC) and total daily area under the concentration time curve (AUC daily ) were calculated., Results: Fourteen patients with effluent flow rates ranging from 2.1 to 5.1 L/h were enrolled. Cefiderocol concentrations best fitted a 2-compartment model. Mean ± standard deviation (SD) parameter estimates for clearance, central compartment volume, and intercompartment transfer constants (k 12 and k 21 ) were 3.5 ± 1.5 L/hour, 10.7 ± 8.4 L, 3.9 ± 1.8 hours -1 , and 2.2 ± 2.2 hours -1 , respectively. With simulations based on product label dosing recommendations, all patients achieved 100% f T > MIC up to MIC 8 mg/L with an AUC daily (mean ± SD) of 1444 ± 423 mg × hour/L. Cefiderocol was well tolerated among the 14 patients., Conclusions: The current package insert dosing recommendations resulted in pharmacodynamically optimized cefiderocol exposures. Cefiderocol concentrations exceeded relevant MIC breakpoints in all patients at each effluent flow rate, and AUC daily was within the range observed in patients in the phase 3 clinical trials, suggestive of a safe and therapeutic drug profile., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: This study aimed to assess the clinical impact of oXiris-continuous hemofiltration adsorption on patients with septic shock and their prognosis., Design: A retrospective study., Participants: Septic shock patients., Interventions: The oXiris group underwent hemofiltration adsorption using oXiris hemofilters and septic shock standard treatment, while the control group received septic shock standard treatment., Main Variables of Interest: The changes in inflammatory indicators and short-term mortality rate were evaluated. Propensity score matching (PSM) was conducted based on the 1:2 ratio between the oXiris and control groups to account for any baseline data differences., Results: Results showed that after 24 h, 48 h, and 72 h of treatment, PCT, IL-6, and hs-CRP levels in the oXiris group were significantly lower than those in the control group (P < 0.05). However, there were no significant differences in norepinephrine equivalents and organ function status (APACHE II score, SOFA score, Lac) between the two groups at the same time points. The 72-h mortality rate (21.88% vs. 34.04%) and the 7-day mortality rate (28.12% vs. 44.68%) were lower in the oXiris group compared to the control group, but not statistically significant. The 28-day mortality rate did not show a significant difference between the two groups (53.19% vs. 56.25%)., Conclusions: oXiris continuous hemofiltration adsorption technology may reduce the levels of inflammatory factors in patients with septic shock; however, it does not appear to enhance organ function or improve the 28-day mortality rate in these patients., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Background: Acute kidney injury patients on continuous renal replacement therapy are subjected to alterations in metabolism, which in turn are associated with worse clinical outcome and mortality. The aim of this study is to determine which metabolism indicators can be used as independent predictors of 30 days intensive care unit (ICU) mortality., Methods: This was a prospective observational study on critical care patients on renal replacement therapy. Integrated approach of metabolism evaluation was used, combining the energy expenditure measured by indirect calorimetry, bioelectrical impedance provided fat free mass index (FFMI), amino acid and glucose concentrations. ICU mortality was defined as all cause 30 days mortality. Regression analysis was conducted to determine the conventional and metabolism associated predictors of mortality., Results: The study was conducted between the 2021 March and 2022 October. 60 high mortality risk patients (APACHE II of 22.98 ± 7.87, 97% on vasopressors, 100% on mechanical ventilation) were included during the period of the study. The rate of 30 days ICU mortality was 50% (n = 30). Differences across survivors and non-survivors in metabolic predictors were noted in energy expenditure (kcal/kg/day) (19.79 ± 5.55 vs 10.04 ± 3.97 p = 0.013), amino acid concentrations (mmol/L) (2.40 ± 1.06 vs 1.87 ± 0.90 p = 0.040) and glucose concentrations (mmol/L) (7.89 ± 1.90 vs 10.04 ± 3.97 p = 0.010). No differences were noted in FFMI (23.38 ± 4.25 vs 21.95 ± 3.08 p = 0.158). In the final linear regression analysis model, lower energy expenditure (exp(B) = 0.852 CI95%: 0.741-0.979 p = 0.024) and higher glucose (exp(B) = 1.360 CI95%: 1.013-1.824 p = 0.041) remained as independent predictors of the higher mortality., Conclusion: The results of the study imply strong association between the metabolic alterations and ICU outcome. Our findings suggest that lower systemic amino acid concentration, lower energy expenditure and higher systemic glucose concentration are predictive of 30 days ICU mortality., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Meticulous antimicrobial management is essential among critically ill patients with acute kidney injury, particularly if renal replacement therapy is needed. Many factors affect drug removal in patients undergoing continuous renal replacement therapy CRRT. In this study, we aimed to compare current databases that are frequently used to adjust CRRT dosages of antimicrobial drugs with the gold standard. The dosage recommendations from various databases for antimicrobial drugs eliminated by CRRT were investigated. The book 'Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys' was chosen as the gold standard. There were variations in the databases. Micromedex, UpToDate, and Sanford had similar rates to the gold standard of 45%, 35%, and 30%, respectively. The Micromedex database shows the most similar results to the gold standard source. In addition, a consensus was reached as a result of the expert panel meetings established to discuss the different antimicrobial dose recommendations of the databases.

Background: Acute kidney injury (AKI) and the need for Continuous Renal Replacement Therapy (CRRT) are critically important health concerns. This study analyzes global and regional Internet search queries to understand public attention in AKI and CRRT over time., Methods: We used Google Trends™ to analyze search queries for AKI and CRRT from January 2004 to March 2024. The study examined global trends and detailed insights from the United States, including state-by-state breakdowns. We identified patterns, peaks of attention, and temporal trends in public attention, comparing regional variations across the US and top-ranking countries worldwide., Results: Global attention in AKI peaked in October 2022, with Portugal, Zambia, and Spain showing the highest regional attention. Within the United States, peak attention was in February 2008. Tennessee, Pennsylvania, and West Virginia were the top states that paid attention to AKI. Attention in CRRT peaked globally in March 2024. South Korea, Saudi Arabia, and Bahrain have led the global attention to CRRT. In the United States, peak attention was in April 2020. West Virginia, Tennessee, and Kentucky showed the highest state-specific attention in CRRT., Conclusions: This study reveals significant temporal and geographical variations in online search patterns for AKI and CRRT, suggesting evolving public attention to these critical health issues. This knowledge can guide the development of targeted public health initiatives, enhance medical education efforts, and help healthcare systems tailor their approach to improving awareness and outcomes in kidney health across diverse populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Thongprayoon, Wathanavasin, Suppadungsuk, Sheikh, Abdelgadir, Miao, Mao, Craici, Qureshi, Kashani and Cheungpasitporn.)

Purpose: The clinical efficacy and safety of ertapenem use in patients undergoing renal replacement therapies (RRT) are not well-documented. Therefore, we aimed to investigate the safety and efficacy of ertapenem in patients with sepsis secondary to Enterobacterales who are undergoing RRT., Methods: A retrospective cohort study was conducted on patients who met the inclusion criteria at our hospital between May 2015 and December 2021. The primary endpoint was 30-day mortality. Secondary endpoints included clinical cure, microbiologic cure, recurrence rate, and incidence of seizures., Results: During the study period, 158 patients met the inclusion criteria. Of these, 86 were male (54.4%), the mean age was 66.4 ± 13.8 years, and the mean weight was 77 ± 22.4 kg. The most common diagnosis was bacteremia in 48 (30.4%) subjects, followed by urinary tract infection in 39 (24.7%) subjects, and pneumonia in 35 (22.2%) patients. The most isolated pathogens were Escherichia coli , followed by Klebsiella species. The median ertapenem dose was 0.5 g intravenously (IV) daily in those who received intermittent hemodialysis (IHD) and 1 g IV daily for those who received continuous veno-venous hemofiltration (CVVH). The 30-day mortality rate was 24%, the clinical cure rate was 89.2%, the microbiologic cure rate was 82%, the 30-day recurrence rate was 41.1%, and the incidence of seizures was 2.5%. Multivariate logistic regression analysis indicated that age (OR 1.04 [95% CI: 1.003-1.075]), being critically ill at therapy initiation (OR 2.9 [95% CI: 1.1-7.5]), and Enterobacterales other than Klebsiella species and Escherichia coli (OR 3.8 [95% CI: 1.1-12.5]) were significant independent risk factors associated with mortality in this population. Ertapenem dose was not associated with mortality., Conclusion: Our findings suggest that the commonly used doses of ertapenem in patients undergoing IHD and CVVH are clinically effective but may pose a higher risk of seizures. A comprehensive pharmacokinetic study is needed to determine the most effective and safe dose for this population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract Background Previous studies reported that patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) after cardiac surgery were at a higher risk of postoperative mortality. However, the impact of AKI and CRRT on long-term mortality has not yet been identified. Therefore, we investigated whether postoperative AKI requiring CRRT was associated with one-year all-cause mortality after coronary artery bypass grafting (CABG). Methods For this population-based cohort study, we analyzed data from the National Health Insurance Service database in South Korea. The cohort included all adult patients diagnosed with ischemic heart disease who underwent isolated CABG between January 2012 and December 2017. Results A total of 15,115 patients were included in the analysis, and 214 patients (1.4%) required CRRT for AKI after CABG during hospitalization. They received CRRT at 3.1 ± 8.5 days after CABG, for 3.1 ± 7.8 days. On multivariable Cox regression, the risk of 1-year all-cause mortality in patients who underwent CRRT was 7.69-fold higher. Additionally, on multivariable Cox regression, the 30-day and 90-day mortality after CABG in patients who underwent CRRT were 18.20-fold and 20.21-fold higher than the normal value, respectively. Newly diagnosed chronic kidney disease (CKD) requiring renal replacement therapy (RRT) 1 year after CABG in patients who underwent CRRT was 2.50-fold higher. In the generalized log-linear Poisson model, the length of hospital stay (LOS) in patients who underwent CRRT was 5% longer. Conclusions This population-based cohort study showed that postoperative AKI requiring CRRT was associated with a higher 1-year all-cause mortality after CABG. Furthermore, it was associated with a higher rate of 30-day and 90-day mortality, longer LOS, and higher rate of CKD requiring RRT 1 year after CABG. Our results suggest that CRRT-associated AKI after CABG may be associated with an increased risk of mortality; hence, there should be interventions in these patients after hospital discharge.

Abstract Background The appropriate dosing of imipenem for critically ill AKI patients undergoing CRRT remains scarce. Purpose This study aimed to (1) gather the available published pharmacokinetic studies conducted in septic patients receiving continuous renal replacement therapy (CRRT) and (2) to define the optimal imipenem dosing regimens in these populations via Monte Carlo simulations. Methods The databases of PubMed, Embase, and ScienceDirect were searched from inception to May 2020. We used the Medical Subject Headings of “Imipenem,” “CRRT,” and “pharmacokinetics” or related terms or synonym to identify the studies for systematic reviews. A one-compartment pharmacokinetic model was conducted to predict imipenem levels for the initial 48 h of therapy. The pharmacodynamic target was 40% of free drug level above 4 times of the MIC (40% fT > 4 MIC). The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Results Eleven articles were identified and included for our systematic review. The necessary pharmacokinetic parameters such as the volume of distribution and the CRRT clearance were mentioned in 100 and 90.9%, respectively. None of the current studies reported the complete necessary parameters. A regimen of 750 mg q 6 h was the optimal dose for the predilution-CVVH and CVVHD modality with two effluent rates (25 and 35 mL/kg/h) for the pharmacodynamic target of 40% fT > 4MIC. Conclusions None of the current studies showed the complete necessary pharmacokinetic parameters for drug dosing. Pharmacodynamic target significantly contributed to imipenem dosing regimens in these patients. Different effluent rates and types of CRRT had minimal impact on dosing regimens. Clinical validation of the recommendation is necessary.

An extracorporeal blood purification method called continuous renal replacement therapy uses a porous hollow-fiber polymeric membrane that is exposed to prolonged contact with blood. In that condition, like with any other submerged filtration membrane, the hemofilter loses its properties over time and use resulting in a rapid decline in flux. The most significant reason for this loss is the formation of a biofilm. Protein, blood cells and bacterial cells attach to the membrane surface in complex and fluctuating processes. Anticoagulation allows for longer patency of vascular access and a longer lifespan of the membrane. Other preventive measures include the modification of the membrane itself. In this article, we focused on the role of nanoadditives in the mitigation of biofouling. Nanoparticles such as graphene, carbon nanotubes, and silica effectively change surface properties towards more hydrophilic, affect pore size and distribution, decrease protein adsorption and damage bacteria cells. As a result, membranes modified with nanoparticles show better flow parameters, longer lifespan and increased hemocompatibility.

Previous publications regarding perioperative renal replacement therapy (RRT) have focused on the general care of the RRT-dependent patient and provided a broad overview of the various RRT modalities. The goal of this review article is to provide anesthesiologists with specific practical information regarding the possible intraoperative advantages and limitations of each modality, mandatory equipment to institute intraoperative therapy, and background knowledge necessary to communicate effectively with nephrologists and/or support staff regarding the intraoperative RRT goals. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) and chronic kidney disease (CKD) previously have been associated with in-hospital and long-term mortality of patients undergoing support with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Patient selection criteria and survival prediction scores for VA-ECMO often include AKI or CKD, but exclude patients requiring renal replacement therapy (RRT). The need for RRT in ECMO patients is associated with increased intensive unit care and in-hospital mortality. The effect RRT has on mortality beyond hospital survival is not well-reported. The authors hypothesized that the timing of initiation (pre-ECMO v during ECMO) of RRT can have a significant impact on short- and long-term mortality. The authors categorized patients into 3 groups: those receiving RRT before initiation of ECMO, those initiated on RRT while on ECMO, and those who did not need RRT while on ECMO. The authors compared survival to decannulation, 30 days and 1 year between the 3 groups. A multivariate survival analysis also was conducted. This was a single center retrospective review of all patients receiving VA-ECMO. A total of 347 adult VA-ECMO extracorporeal membrane oxygenation patients. None, retrospective. The authors' cohort included 347 total patients, 39 required RRT before ECMO, 139 while on ECMO, and 169 did not require RRT while on ECMO. If RRT was initiated before ECMO, survival to decannulation was 48.72%, 46.6% if RRT was initiated on ECMO, and 73.96% for patients who did not need RRT while on ECMO. One-year survival was 25.64%, 23.74%, and 46.75%, respectively. There was no significant difference in survival between patients initiated on RRT before ECMO and those who required RRT while on ECMO. The authors demonstrated that the need for RRT before or while on ECMO has reduced short- and long-term survival when compared with those who did not need RRT while on ECMO. The authors believe that RRT is a marker for severe multiorgan failure and that, despite the benefits of RRT, high mortality will occur. This lack of mortality difference between patients previously on RRT and those newly requiring RRT may help clinicians in deciding to initiate ECMO for patients previously on RRT. Further investigation into complication rates between the groups is required. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple organ dysfunction syndrome is the leading cause of death in pediatric intensive care units and can be very critical when combined with shock and disseminated intravascular coagulation (DIC). Currently, there is no effective treatment. We developed a new hemodiafiltration (HDF) method called plasma HDF (PHDF) that uses fresh frozen plasma as replacement fluid and investigated the safety and efficacy of this treatment. Methods We enrolled critically ill children with (1) a Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score ≥ 14, (2) a Japanese Ministry of Health and Welfare (JMHW) DIC score ≥ 7, (3) a vasoactive inotropic score (VIS) ≥ 10, and (4) a serum total protein concentration ≤ 5.0 g/dL. PHDF was performed for 5 h and then switched to continuous HDF. The primary endpoint was the 28-day mortality rate. Secondary endpoints included assessment of vital signs, blood test data, and fluid balance from PHDF start to day 7. Results Nine patients (four males and five females) between 3 days and 40 months of age, weighing 2.1–13 kg, met the inclusion criteria. Although the median PMR was 0.94 (0.71–0.96), the 28-day mortality rate was 22.2% (2/9). One hour after the start of PHDF, there was an increase in mean arterial pressure and central venous pressure and a decrease in heart rate; by day 7, there was a significant decrease in the PELOD-2 score, the JMHW DIC score, and the VIS. Hypoproteinemia also improved the day after PHDF. Water balance was able to remain negative after day 2. Conclusions PHDF was found to be effective in the treatment of DIC and circulatory failure by supplementing coagulation and antithrombotic factors as well as by raising colloid osmotic pressure to increase circulating blood volume. PHDF has been shown to be a safe and useful treatment for critically ill children and has the potential to improve 28-day survival.

Purpose: Colistin is still a therapeutic cornerstone against multidrug-resistant gram-negative bacteria (MDRGN), mostly when other antibiotics do not gain adequate activity on these strains. In the present study, we evaluated in a cohort of burn patients the relationship between colistin therapy, survival and requirement of renal replacement therapy (CRRT). Patients and Methods: Retrospective study of 133 burn patients treated with iv colistimethate sodium (loading dose 9.0 × 106 IU, maintenance dose 4.5 × 106 IU BID) and 35 treated with other antibiotics for MDRGN infection including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae between January 2008 and December 2017. Multivariate analysis with logistic regression was used to determine the effect of the predictors such as age, total body surface area (TBSA), third-degree burn areas, Revised Baux score, Charlson comorbidity score, length of stay, colistin dose and duration of treatment, mechanical ventilation, and need of CRRT on in-hospital mortality. To investigate the relationship between colistin and renal function, we focused on survivor patients as the completion of the therapeutic course of colistin represented the basic requirement to analyze its impact on the kidney. Results: Out of 133 colistin- and 35 other antibiotics-treated patients, 83 (62.4%) and 31 (88.6%) survived, and 53 (39.8%) and 3 (9.7%) required CRRT, respectively. The severity of burns, as well as CRRT requirement and mortality, was significantly higher in colistin-treated patients than in other antibiotics-treated patients. Age and TBSA% were the significant predictors of mortality. Out of 83 colistin-treated survivors, 19 (22.9%) required CRRT (9 before and 10 after the start of colistin), and 64 (77.1%) had a normal renal function. No difference about the colistin dose and baseline characteristics, but the revised Baux score was found between the 9 patients requiring CRRT before the colistin course and the 10 patients after. Similarly, among the 64 patients not undergoing CRRT, no difference was found between the patients treated with the cumulative dose of colistin < 99.0 × 106 IU (n = 33, median daily dose of 4.0 × 106 IU) and > 99.0 × 106 IU (n = 31, median daily dose of 9.0 × 106 IU) about the baseline characteristics and the daily median plasma creatinine over 24 days of therapy. Conclusion: Colistin therapy was associated with more severe burns, mortality, and CRRT requirement. A short course therapy, at appropriate cumulative dosage, can lead to clinical success without a significant association with severe renal impairment. [ABSTRACT FROM AUTHOR]

High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p =.02), amelioration of SIRS (84% vs. 26%; P =.02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P =.02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P =.001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P =.04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. ClinicalTrial.gov (identifier: NCT02718079) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results: At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions: Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT02486614 [ABSTRACT FROM AUTHOR]

Background: Polymyxin B has become the last choice for patient with carbapenem-resistant bacterial infection. However, the optimal dosing of polymyxin B in critically ill children receiving continuous renal replacement therapy (CRRT) remains unclear. Case Presentation: Two cases of critically ill pediatric patients (7 years old) with acute kidney injury requiring continuous renal replacement (CRRT) received polymyxin B treatment due to carbapenem-resistant organism bloodstream infections. Therapeutic drug monitoring (TDM) of polymyxin B was carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS). The average steady-state plasma concentration (Css,avg) of 2–4 mg/L was set as the target level. Initial polymyxin B dose was 1 mg/kg every 12 h, and the Css,avg at 4–5th dosing were 1.76 and 1.06 mg/L for patient 1 and patient 2, respectively. TDM-guided polymyxin B dose was escalated to 2 mg/kg every 12 h for both patients, resulting in the Css,avg of 2.60 and 1.73 mg/L, and the infection was controlled subsequently. Css,avg of polymyxin B with the same dosing regimens and infusion length were different during CRRT and after termination of CRRT for both patients (2.60 mg/L vs. 4.94 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 1; and 1.73 mg/L vs. 3.53 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 2). The estimation of drug exposure (estimated by AUCss,12h at the same dose) during CRRT and cessation of CRRT showed that 45% and 51% of polymyxin B was cleared during CRRT. Conclusion: Our study showed high clearance of polymyxin B through CRRT, and supplanted dosing of polymyxin B is necessary in pediatric patients undergoing CRRT. [ABSTRACT FROM AUTHOR]

Background Outpatient dialysis is standardized with several evidence-based measures of adequacy and quality that providers aim to meet while providing treatment. By contrast, in the intensive care unit (ICU) there are different types of prolonged and continuous renal replacement therapies (PIRRT and CRRT, respectively) with varied strategies for addressing patient care and a dearth of nationally accepted quality parameters. To eventually describe appropriate quality measures for ICU-related renal replacement therapy (RRT), we first aimed to capture the variety and prevalence of basic strategies and equipment utilized in the ICUs of Veteran Affairs (VA) medical facilities with inpatient hemodialysis capabilities. Methods Via email to the dialysis directors of all VA facilities that provided inpatient hemodialysis during 2018, we requested survey participation regarding aspects of RRT in VA ICUs. Questions centered around the mode of therapy, equipment, solutions, prescription authority, nursing, anticoagulation, antimicrobial dosing, and access. Results Seventy-six centers completed the questionnaire, achieving a response rate of 87.4%. Fifty-five centers reported using PIRRT or CRRT in addition to intermittent hemodialysis. Of these centers, 42 reported being specifically CRRT-capable. Over half of respondents had the capabilities to perform PIRRT. Twelve centers (21.8%) were equipped to use slow low efficient dialysis (SLED) alone. Therapy was largely prescribed by nephrologists (94.4% of centers). Conclusions Within the VA system, ICU-related RRT practice is quite varied. Variation in processes of care, prescription authority, nursing care coordination, medication management, and safety practices present opportunities for developing cross-cutting measures of quality of intensive care RRT that are agnostic of modality choice.

Background: Polymyxin B has become the last choice for patient with carbapenem-resistant bacterial infection. However, the optimal dosing of polymyxin B in critically ill children receiving continuous renal replacement therapy (CRRT) remains unclear.Case Presentation: Two cases of critically ill pediatric patients (7 years old) with acute kidney injury requiring continuous renal replacement (CRRT) received polymyxin B treatment due to carbapenem-resistant organism bloodstream infections. Therapeutic drug monitoring (TDM) of polymyxin B was carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS). The average steady-state plasma concentration (Css,avg) of 2–4 mg/L was set as the target level. Initial polymyxin B dose was 1 mg/kg every 12 h, and the Css,avg at 4–5th dosing were 1.76 and 1.06 mg/L for patient 1 and patient 2, respectively. TDM-guided polymyxin B dose was escalated to 2 mg/kg every 12 h for both patients, resulting in the Css,avg of 2.60 and 1.73 mg/L, and the infection was controlled subsequently. Css,avg of polymyxin B with the same dosing regimens and infusion length were different during CRRT and after termination of CRRT for both patients (2.60 mg/L vs. 4.94 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 1; and 1.73 mg/L vs. 3.53 mg/L with 2 mg/kg every 12 h in 2 h infusion for patient 2). The estimation of drug exposure (estimated by AUCss,12h at the same dose) during CRRT and cessation of CRRT showed that 45% and 51% of polymyxin B was cleared during CRRT.Conclusion: Our study showed high clearance of polymyxin B through CRRT, and supplanted dosing of polymyxin B is necessary in pediatric patients undergoing CRRT.

Introduction: The optimal modality for renal replacement therapy (RRT) in patients venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. This study aimed to compare outcomes between continuous renal replacement therapy (CRRT) and peritoneal dialysis (PD) in VA-ECMO patients., Methods: This single-center retrospective study included VA-ECMO patients who developed AKI and subsequently required CRRT or PD. Data on patient demographics, comorbidities, clinical characteristics, RRT modality, and outcomes were collected. The primary outcome was in-hospital mortality, with secondary outcomes including length of stays, RRT durations, and complications associated with RRT., Results: A total of 43 patients were included (72.1% male, mean age 58.2 ± 15.7 years). Of these, 21 received CRRT and 22 received PD during ECMO therapy. In-hospital mortality rates did not significantly differ between CRRT and PD groups (80.9% vs 90.9%, p = 0.35). However, PD was associated with a higher incidence of catheter-related complications, including malposition (31.8% vs 4.7%, p = 0.046), infection (22.7% vs 4.7%, p = 0.19), and bleeding (18.2% vs 9.5%, p = 0.66), respectively., Conclusion: Among patients receiving VA-ECMO-supported RRT, our study revealed comparable in-hospital mortality rates between CRRT and PD, although PD was associated with a higher incidence of catheter-related complications., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

[Creatinine] was proved to change in the opposite direction of the kinetic GFR (GFRK), but does the [creatinine] also change in the opposite direction of the volume rate? If volume is administered and the [creatinine] actually goes up, then the two changes move in the same direction and their ratio is positive, paradoxically. The equation that describes [creatinine] as a function of time was differentiated with respect to the volume rate. This partial first derivative has a global maximum that can be positive under definable conditions. Knowing what makes the maximum positive informs when the derivative will be positive over some continuous domain of volume rate inputs. The first derivative versus volume rate curve has a maximum and a minimum point depending on the GFRK. If GFRK is below a calculable value, then the curve's minimum vanishes, letting it descend to ‐∞ and not allowing the derivative to ever be positive. If GFRK lies between a lower and a higher calculable value, then the curve's maximum vanishes, letting the derivative diverge to +∞, though the clinical scenario is unrealistic. If GFRK is above the higher calculable value, then the curve's absolute maximum can become positive by decreasing the creatinine generation rate or increasing the initial [creatinine]. The derivative is potentially positive under these clinically realizable circumstances. The combination of parameters above can align in septic patients (low creatinine generation rate) with kidney failure (high initial [creatinine]) who are put on continuous dialysis (high GFRK). If a first derivative is positive, removing more volume can improve the [creatinine] and, dismayingly, giving more volume can worsen the [creatinine]. This paradox is explained by a covert interplay between the ambient [creatinine] and GFRK that excretes creatinine faster than its volume of distribution declines. [ABSTRACT FROM AUTHOR]

Introduction: Though cost-effectiveness analyses (CEAs) have evaluated continuous renal replacement therapy (RRTs) and intermittent RRTs in acute kidney injury (AKI) patients; it is yet to establish which RRT technique is most cost-effective. We systematically reviewed the current evidence from CEAs of CRRT versus IRRT in patients with AKI.Areas Covered: PubMed, EMBASE, and Cochrane databases searched for CEAs comparing two RRTs. Overall, seven CEAs, two from Brazil and one from US, Canada, Colombia, Belgium, and Argentina were included. Five CEAs used Markov model, three reported following CHEERS, none accounted indirect costs. Time horizon varied from 1-year-lifetime. Marginal QALY gain with CRRT compared to IRRT was reported across CEAs. Older CEAs found CRRT to be costlier and not cost-effective than IRRT (ICER 2019 US$: 152,671$/QALY); latest CEAs (industry-sponsored) reported CRRT to be cost-saving versus IRRT (-117,614$/QALY). Risk of mortality, dialysis dependence, and incidence of renal recovery were the key drivers of cost-effectiveness.Expert Opinion: CEAs of RRTs for AKI show conflicting findings with secular trends. Latest CEAs suggested CRRT to be cost-effective versus IRRT with dialysis dependence rate as major driver of cost-effectiveness. Future CEAs, preferably non-industry sponsored, may account for indirect costs to improve the generalizability of CEAs. [ABSTRACT FROM AUTHOR]