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Continuous renal replacement therapies (CRRTs) and sequential extracorporeal blood purification (EBP) therapies can be used in patients with severe COVID‐19 disease to support kidney failure and restore immune homeostasis. EBP prescription should be based on the patient's clinical needs and frequently re‐evaluated during the intensive care unit (ICU) stay. Personalization of treatment at the bedside plays a fundamental role for patient recovery. This aim can be simplified by using both clinical and molecular data collected from a patient‐individualized web registry. In this case report, we describe how we apply a sequential approach to EBP therapies following the rapid evolution of a critically ill COVID‐19 patient with acute kidney injury. We show patient strategies and outcomes using bedside data from a registry‐based method for the routine use of EBP. We explain the choice of specific hemofilter prescription, also focusing on dose and anticoagulation strategies. We describe the difficulties, uncertainties, and mistakes made during EBP prescription. Furthermore, we discuss the causes and workable solutions that can be adopted by the ICU physician for a better EBP prescription, considering the current lack of well‐recognized indications. Trial Registration: ClinicalTrials.gov identifier: NCT03807414 [ABSTRACT FROM AUTHOR]

Background: To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods: Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. Results: Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. Conclusion: For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies. [ABSTRACT FROM AUTHOR]

Introduction: An inverse relationship exists between vancomycin serum concentrations and the intensity of continuous renal replacement therapy (CRRT), reflected through the dialysate flow rate (DFR). There remains a lack of evidence to guide initial vancomycin dosing in the setting of high‐intensity CRRT (i.e., DFR >30 mL/kg/h). Additionally, recommendations for pharmacokinetic monitoring of vancomycin have transitioned from a trough‐based to area under the curve (AUC)‐based dosing strategy to optimize efficacy and safety. Therefore, an improved understanding of the impact of CRRT intensity on AUC/MIC (minimum inhibitory concentration) has the potential to enhance vancomycin dosing in this patient population. Objectives: The goal of this study is to evaluate current vancomycin dosing strategies and achievement of pharmacokinetic targets in patients on high‐intensity CRRT. Methods: This was a single‐center, retrospective cohort study of adult critically ill patients admitted to Houston Methodist Hospital between May 2019 and October 2021 and received vancomycin therapy while on high‐intensity CRRT. High‐intensity CRRT was defined by a DFR that was both ≥3 L/h and >30 mL/kg/h. Depending on the initial vancomycin dosing strategy, patients were stratified into either the traditional (15 mg/kg/day) or enhanced (≥15 mg/kg/day) dosing group. The primary outcome was the percent of patients who attained steady‐state AUC24/MIC ≥400 mg*h/L at the first obtained vancomycin level in the enhanced group compared with the traditional group. Results: A total of 125 patients were included in the final analysis, 56 in the traditional and 69 in the enhanced dosing group. The primary end point occurred in 74% and 54% of patients in the enhanced and traditional dosing groups, respectively (p = 0.029). Therapeutic vancomycin trough levels (10–20 μg/mL) were more commonly achieved in the enhanced dosing group compared with the traditional dosing group (66.7% vs. 45%, p = 0.013). As DFR rose, increasingly higher doses of vancomycin, up to 27 mg/kg/day, were required to achieve the therapeutic targets. Conclusion: This is the first study to evaluate the influence of variable CRRT intensities on vancomycin AUC/MIC. Our findings suggest that vancomycin doses of ≥15 mg/kg/day are needed to achieve early therapeutic targets in patients on high‐intensity CRRT. [ABSTRACT FROM AUTHOR]

Introduction: Hyponatremia is a common electrolyte disturbance in critically ill patients. Management of intensive care unit patients with concurrent hyponatremia and renal failure requiring dialysis is challenging especially with regional citrate anticoagulation, which may cause excessive rise of serum [Na+]. We described the first and successful modified continuous veno‐venous hemodialysis (CVVHD) regimen using regional citrate anticoagulation. Method: A mathematical model was developed to predict serum [Na+] change during CVVHD. Our in‐house CVVHD regimen using regional citrate anticoagulation was modified to slow down the rise of serum [Na+] by both modifying the dialysate solution and modifying the circuit. Result: Five out of six patients had gradual serum [Na+] correction not exceeding the daily limit. None of them developed osmotic demyelination syndrome. Conclusion: We concluded that regional citrate anticoagulation, with proper modification, is safe and effective for patients with concomitant renal failure requiring hemodialysis. [ABSTRACT FROM AUTHOR]

When 18 F-FDG PET/CT is used to diagnose cardiovascular inflammation or infection, it is important to differentiate between pathologic and physiologic 18 F-FDG myocardial uptake. Several methods to suppress physiologic 18 F-FDG myocardial uptake have been reported, all based on the principle of promoting free fatty acid metabolism over glucose metabolism. However, despite rigorous implementation of these protocols, there is variation in successful myocardial glucose suppression. Sometimes this variation can be explained by specific patient conditions or treatment regimes. Here, we describe a patient on continuous venovenous hemodialysis with 18 F-FDG myocardial uptake despite adequate preparation., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Drug-induced rhabdomyolysis has become increasingly prevalent due to the rising use of medications such as statins, antidepressants, and antipsychotics. These can lead to muscle cell destruction and the release of myoglobin, potentially causing kidney damage. Recent advancements include the use of CytoSorb hemoadsorption as a promising therapy to remove myoglobin and other potentially toxic substances from the bloodstream. A 47-year-old male with a complex medical history presented with weakness, pain, and dizziness. Lab results indicated severe rhabdomyolysis, most likely of medication-induced etiology. He developed acute kidney injury (AKI) and underwent continuous venovenous hemodialysis (CVVHD) combined with CytoSorb hemoadsorption. Despite initial stabilization, rhabdomyolysis parameters surged, necessitating the use of an additional high-flux filter with enhanced middle molecule clearance. CytoSorb therapy was administered for nine consecutive sessions, resulting in decreased creatine kinase (CK) and myoglobin levels. Due to persistent kidney injury, the patient required permanent dialysis and was transferred to a kidney disease center. This case highlights the complexity and severity of drug-induced rhabdomyolysis with hemoadsorption playing a pivotal role in reducing myoglobin levels and improving the patient's condition. Combining hemoadsorption and filters with enhanced middle molecule clearance holds even more promise for improved myoglobin removal., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Sebastian Hafner et al. Case Reports in Critical Care published by John Wiley & Sons Ltd.)

Abstract Background Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking. Methods Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. Results A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45–94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI. Conclusions Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT. Trial registration EudraCT, 2012–005617-39. Registered on 7 August 2013.

Background: To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations.Methods: Apixaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for apixaban were estimated via noncompartmental analysis. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was utilized to provide dosing estimations for flow rates from 0.5-5 L/h.Results: Mean adsorption to the HF1400 and M150 filters differed significantly at 38 and 13%, respectively, while mean (± standard deviation, SD) percent protein binding was 70.81 ± 0.01%. Effect of CVVH point of dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 2.5-7.5 mg twice daily (BID) may be needed for flow rates ranging from 0.5-5 L/h, respectively.Conclusion: For CRRT flow rates most commonly employed in clinical practice, the standard labeled 5 mg BID dose of apixaban is predicted to achieve target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies. [ABSTRACT FROM AUTHOR]

Purpose of this study is to find the difference among dosage of CRRT based on effluent rate prescription and actual delivered effluent rate by monitoring records of dialysis. Study Design: Prospective observational cohort study. Setting: King Fahad Hospital Medina Saudi Arabia. Period: 1st June 2016 to 31st December 2016. Material & Methods: Two hundred acute kidney injury patients admitted in ICU on CRRT at rate of 20ml/kg using pre-filter continuous venovenous hemodia-filtration (CVVHDF), among (AKI) patients prescribed doses were compared with the actual dose with in the duration of 24 hours to find out difference between prescribed and actual dose. Results: Findings of our study shows that. Mean average dose of dialysis delivered per day was only 16 hours which is 21% of prescription of pre-dilution CVVHDF. Patients were receiving 14ml/Kg of continues renal replacement therapy (CRRT) with the lack of 21% dilution correction factor. The average number of hours/day on continuous renal replacement therapy was 14.1±2.41, with a mean flow rate of 1.36±0.31 L/h (averaged over 24 h). The delivered doses were significantly lowered then the prescribed doses with (P < 0.001). 30% of doses was missing during CRRT among patients with acute kidney diseases admitted in ICU at king Fahad hospital Saudi Arabia (P-value <0.001). Conclusions: We concluded that during dialysis patients did not received the prescribed dose in comparison to actual delivered dose which effects the survival of critical ill patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

An 18-year-old woman presented to the emergency department. She had ingested 43 extended-release tablets of carbamazepine 400 mg. Although the patient had high carbamazepine plasma levels and classified as severe intoxication, her clinical symptoms were less severe than expected. With the combination of hemodialysis and continuous venovenous hemodialysis in addition to usual care, including multiple-dose activated charcoal, a fast decrease (within 3 days) in carbamazepine plasma levels to levels in the therapeutic range was achieved. Only one session of hemodialysis was performed because the clinical status of the patient stabilized. In retrospect, the patient did not suffer severe toxicological symptoms from carbamazepine. Therefore, continuous venovenous hemodialysis could have been discontinued earlier. On the other hand, the fast decrease in carbamazepine plasma levels during extracorporeal treatment may have prevented the development of severe or rebound toxicological symptoms. This case report adds evidence to the successful management of carbamazepine intoxication using hemodialysis followed by continuous venovenous hemodialysis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Aim The objective of this population pharmacokinetic (PK) analysis was to provide guidance for the dosing interval of daptomycin in patients undergoing continuous renal replacement therapy (CRRT). Methods A previously published population PK model for daptomycin was updated with data from patients undergoing continuous veno-venous haemodialysis (CVVHD; n = 9) and continuous veno-venous haemodiafiltration (CVVHDF; n = 8). Model-based simulations were performed to compare the 24 h AUC, Cmax and Cmin of daptomycin following various dosing regimens (4, 6, 8, 10, and 12 mg kg−1 every [Q] 24 h and Q48 h), with the safety and efficacy exposure references for Staphylococcus aureus bacteraemia/right-sided infective endocarditis. Results The previously developed daptomycin structural population PK model could reasonably describe data from the patients on CRRT. The clearance in patients undergoing CVVHDF and CVVHD was estimated at 0.53 and 0.94 l h−1, respectively, as compared with 0.75 l h−1 in patients with creatinine clearance (CrCl) ≥ 30 ml min−1. Daptomycin Q24 h dosing in patients undergoing CRRT resulted in optimal exposure for efficacy, with AUC comparable to that in patients with CrCl ≥ 30 ml min−1. In contrast, Q48 h dosing was associated with considerably lower AUC24-48h in all patients for doses up to 12 mg kg−1 and is therefore inappropriate. Conclusions Q24 h dosing of daptomycin up to 12 mg kg−1 provides comparable drug exposure in patients on CVVHD and in those with CrCl ≥ 30 ml min−1. Daily daptomycin use up to 8 mg kg−1 doses are appropriate for patients on CVVHDF, but higher doses may increase the risk of toxicity. [ABSTRACT FROM AUTHOR]

Background: The CARdiorenal PEDIatric EMergency (CARPEDIEM) machine was originally designed to perform only continuous venovenous hemofiltration (CVVH) in neonatal and pediatric patients. In some cases, adequate convective clearance may not be reached because of a limited blood flow. In such conditions, the application of diffusive clearance [continuous venovenous hemodialysis (CVVHD)] would help optimize blood purification. In this study, the CARPEDIEM™ machine was modified to enable the circulation of dialysis through the filter allowing testing of the performance of CARPEDIEM™ machine in CVVHD. Methods: Three different polyethersulfone hemodialyzers (surface area = 0.1 m, 0.2 m, and 0.35 m, respectively) were tested in vitro with a scheduled combination of plasma flow rates (Qp = 10-20-30 ml/min) and dialysis fluid flow rate (Qd = 5-10-15 ml/min). Three sessions were performed in co-current and one in counter-current configuration (as control) for each filter size. Clearance was measured from the blood and dialysate sides and results with mass balance error greater than 5 % were discarded. Results: Urea and creatinine clearances for each plasma/dialysate combination are reported: clearance increase progressively for every filter proportionally to plasma flow rates. Similarly, clearances increase progressively with dialysate flow rates at a given plasma flow. The clearance curve tends to present a steep increase for small increases in plasma flow in the range below 10 ml/min, while the curve tends to plateau for values averaging 30 ml/min. As expected, the plateau is reached earlier with the smaller filter showing the effect of membrane surface-area limitation. At every plasma flow, the effect of dialysate flow increase is evident and well defined, showing that saturation of effluent was not achieved completely in any of the experimental conditions explored. No differences ( p > 0.05 for all values) were obtained in experiments using whole blood instead of plasma or using co-current versus counter-current dialysate flow configuration. Conclusions: Although plasma flow and filter surface give an important contribution to the level of clearance urea and creatinine, it appears evident that dialysate flow plays an essential role in the blood purification process, justifying the use of CVVHD versus CVVH in case of high dialysis dose requirement and/or limited blood flow rate. [ABSTRACT FROM AUTHOR]

Objective: Describe the rate of compliance with institutional antimicrobial dosing guidelines in patients on concomitant continuous venovenous hemodialysis (CVVHD). Methods: This single-center retrospective chart review evaluated adult patients receiving concomitant intravenous antimicrobials and CVVHD for at least 24 hours over a 2-month period. Results: A total of 42 patients, 76 antimicrobial courses, and 208 study days (24 hours of concomitant therapy) were evaluated. Overall, antimicrobials were dosed according to the institutional guidelines on 162 (78%) of 208 study days. All nonconcordant doses were below recommendations. The recommended dose was never received prior to antibiotic or CVVHD discontinuation in 22% of the cases. In cases where antimicrobials were initiated when the patient was already on CVVHD, 74% of the initial doses met guideline criteria. Pharmacist recommendation was associated with increased dosing compliance (94% vs 73% of study days, P = .001). During transition from CVVHD to intermittent hemodialysis (IHD), only 62% of antimicrobial doses were decreased by the first IHD day. Conclusions: Antimicrobial dosing in patients on CVVHD was below institutional guideline recommendations in many cases. Pharmacist recommendation was associated with compliance. Centers should evaluate their own compliance rate with institutional guideline recommendations for CVVHD and implement initiatives to improve dosing practices. [ABSTRACT FROM AUTHOR]

Some of ICU patients with Acute Renal Failure (ARF) require dialysis. Conventional or intermittent hemodialysis (HD) may cause hypotension and insufficient loss of fluids and toxins from blood. Peritoneal dialysis also my cause peritonitis and has lower efficiency than HD. We did continuous Venovenous Hemodialysis (CVVHD) for three ICU patients with ARF in Saint-Zahra Medical Center for the first time in our country. Method and Material: With a polysulfone membrane, blood pump, peritoneal dialysis solution, heparin, and a fix nurse, HD was done for 12-24 hours. Results: 1) Urea clearance was 18-50 ml/h. 2) Ultrafiltration was 160-1000 ml/h. 3) With dialysis, hemorrhage, coagulation disorder, and oxygenation recovered. 4) All of patients developed hyperglycemia and hypothermia. 5) All of patients died (two with septicemia and one with hypotension). Conclusion: In the absence of hemodialysis or peritoneal dialysis, CVVHD with present preliminary equipments is suitable and can excrete more toxins and fluids.

Purpose: Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT. Materials and Methods: A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected. Results: The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime. Conclusion: RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Study Objective To investigate oseltamivir and oseltamivir carboxylate pharmacokinetics in critically ill patients who were receiving continuous venovenous hemodialysis ( CVVHD) and/or extracorporeal membrane oxygenation ( ECMO). Design Prospective, open-label, pharmacokinetic study. Setting Intensive care units of an academic medical center. Patients Thirteen critically ill patients aged 13 years or older with suspected or confirmed H1N1 influenza who had a prescription for oseltamivir and were concurrently receiving CVVHD and/or ECMO between October 2009 and January 2010. Intervention Oseltamivir 150 mg was administered nasogastrically or nasoenterically every 12 hours. Blood samples were collected at baseline and at 1, 2, 4, 6, 8, 10, and 12 hours after administration of the fourth oseltamivir dose or subsequent doses. In patients receiving CVVHD, effluent also was collected at the same time points. Urine was collected throughout the 12-hour dosing interval. Measurements and Main Results Eight patients received CVVHD only, four patients received both CVVHD and ECMO, and one patient received ECMO only. Pharmacokinetic parameters for the patient who received only ECMO were not reported. The median maximum plasma concentration and area under the plasma concentration-time curve for the 12-hour dosing interval (AUC0-12) for the remaining 12 patients were 83.4 ng/ml and 216 ng•hour/ml, respectively, for oseltamivir and 2000 ng/ml and 21,500 ng•hour/ml, respectively, for oseltamivir carboxylate. Mean clearance due to CVVHD was 33.8 ml/minute for oseltamivir and 50.2 ml/minute for oseltamivir carboxylate. For patients who received ECMO, no substantial differences between pre- and post- ECMO oxygenator plasma concentrations were found for oseltamivir or oseltamivir carboxylate. Conclusion Although the optimal pharmacokinetic-pharmacodynamic targets for oseltamivir carboxylate remain unclear, in the patients receiving CVVHD with or without ECMO, a regimen of oseltamivir 150 mg every 12 hours yielded a median oseltamivir carboxylate AUC0-12 considerably higher than would be expected in non-critically ill patients receiving the same dosage regimen. [ABSTRACT FROM AUTHOR]

Background. Newborns with inborn errors of metabolism often present with hyperammonaemic coma, requiring prompt diagnosis and specific medical therapy, nutritional support and efficient toxin removal. Little information regarding the efficacy and safety of continuous venovenous haemodialysis (CVVHD) as an option for extracorporal ammonia detoxification in children is available. Methods. Twenty-one patients with hyperammonaemia [19 neonates (mean age 4.1 ± 2.4 days) and two children 1 and 7 years of age, respectively] were admitted to our hospital for dialysis between 1996 and 2008. Seventeen children (15 neonates), received CVVHD. Four neonates received continuous peritoneal dialysis (CPD). All started medical treatment with sodium benzoate, L-arginine hydrochloride and carnitine as well as protein-restricted parenteral diets with high caloric intake before dialysis. Results. Plasma ammonia levels (range 464–7267 µg/dl before dialysis and 27–3317 µg/dl after dialysis) were significantly reduced by 50% within 4.7 ± 2.5 h with CVVHD compared with 13.5 ± 6.2 h with CPD (P < 0.0001). Plasma ammonia levels <200 µg/dl critical range were achieved within 22.4 ± 18.1 h in CVVHD patients compared with 35.0 ± 24.1 h with CPD. Depending on the weight and blood pressure stability of the patients, mean blood flow velocities of 9.8 ± 3.4 ml/kg/min and mean dialysate flow rates of 3925 ± 2398 ml/min/1.73 m2 were employed. Blood and dialysate flows significantly correlated with ammonia clearance and decay of ammonia in vivo. Because of the severe underlying disease, 18% of CVVHD patients died compared with 50% undergoing CPD. In total, 82% of CVVHD patients survived the first 6 months after dialysis. Among these, 43% were without sequelae, 43% developed moderate mental retardation, and two (14%) developed severe mental retardation. Conclusion. CVVHD effectively and quickly eliminates plasma ammonia. To optimize long-term mental outcome, rapid identification and appropriate treatment of the underlying disease as well as starting dialysis early are of enormous therapeutic value. [ABSTRACT FROM AUTHOR]

The clinical effect of beta-lactam antibiotics depends on the time of drug concentration above the minimal inhibitory concentration (MIC) for a susceptible bacterium. Continuous infusion (CI) of ß-lactams such as meropenem may therefore be a more rational approach than intermittent bolus injections (IB). The aim of this study was to test whether CI of meropenem achieves effective drug concentrations comparable to IB in patients treated by continuous renal replacement therapy (CRRT). Prospective, randomised cross-over study. Twelve-bed medical intensive care unit (ICU). Six ICU patients were randomised to receive either meropenem 1 g IB every 12 h or a 0.5 g i.v. loading dose followed by 2 g i.v. CI over 24 h. After 2 days, regimens were crossed over. Meropenem pharmacokinetics were determined on days 2 and 4. Peak serum concentration [median (25% and 75% quartiles)] after short infusion of 1 g meropenem were 62.8 (51.4; 85.0) mg/l, trough levels at 12 h were 8.1 (4.5; 18.7) mg/l, and serum half-life was 5.3 (5.1; 7.0) h. Steady-state concentrations during CI were 18.6 (13.3; 24.5) mg/l. The AUCs during either treatment were comparable and determined as 233 (202; 254) mg/l*h (IB) and 227 (182; 283) mg/l*h (CI), respectively. Four hours after IB, drug concentrations dropped below CI steady-state concentrations. Appropriate antibacterial concentrations of meropenem in patients with CRRT are easily achievable with CI. CI may be an effective alternative dosing regimen to IB. A prospective comparison of the clinical efficacy of the two dosage regimens is warranted. [ABSTRACT FROM AUTHOR]

: ObjectivesThis study investigated outcomes in patients with cardiogenic shock and severe renal dysfunction treated with ventricular assist devices (VAD) as a bridge to cardiac transplantation.: BackgroundPrevious reports have documented poor survival in patients with cardiogenic shock and severe renal dysfunction treated with VAD.: MethodsWe surveyed 215 consecutive patients who received a VAD from 1992 to 2000 and selected patients who had a serum creatinine ≥3.0 mg/dl at the time of VAD placement. Demographic, laboratory, and clinical outcome data were collected.: ResultsEighteen patients met the inclusion criteria. Mean serum creatinine at the time of VAD placement was 4.0 ± 0.7 mg/dl (range 3.0 to 5.2 mg/dl). Seven patients required temporary renal support with continuous venovenous hemodialysis (CVVHD). Eleven patients underwent cardiac transplantation. At six months post-transplantation, mean serum creatinine was 2.0 ± 0.6 mg/dl (range 1.3 to 3.5 mg/dl). None of the transplanted patients required subsequent renal support. Seven patients died with a VAD before transplantation. Three died early (<1 month) after VAD placement, and all three required CVVHD until death. Four patients survived for >1 month after VAD placement; all four had resolution of renal dysfunction with mean serum creatinine of 1.9 ± 1.2 mg/dl (range 0.8 to 3.6 mg/dl) without the need for renal support. Overall 30-day and six-month survival after VAD placement, survival to transplantation, and survival one year post-transplantation were similar to patients without severe renal dysfunction.: ConclusionsContemporary use of VAD leads to resolution of severe renal dysfunction in most cardiogenic shock patients and comparable long-term outcomes to patients without renal dysfunction. [Copyright &y& Elsevier]

Objectives: Evaluate the risk of accumulation of midazolam and conjugated 1-hydroxy-midazolam in high-risk ICU patients treated by continuous veno-venous haemofiltration.Study design: A prospective pharmocokinetic and clinical evaluation in 11 patients, with hepatic and renal failure.Methods: Midazolam and metabolites were dosed in plasma and ultrafiltration liquid by chromatography. Sedation was assessed by a simplified Ramsay score (EDS) with 4 levels.Results: The mean duration of continuous infusion was 11 ± 6 days. Peak plasma levels were over 150 ng ml–1 during the first 3 days, but normalized after that, only by drug adjustment based on scoring and clinical observation. There was no progressive accumulation of OH-midazolam, in spite of high levels (>1000 ng ml–1). The Sieving coefficient (S) was 0,11 ± 0,10 and 0,44 ± 0,15 for midazolam and conjugated OH-midazolam respectively. A significant clearance (9.6 ± 1.9 ml min–1) was observed for the conjugated products. T 1/2β was 11 h and was correlated with the mean time of recovery. A significant correlation was found between sedation score and both midazolam (r = 0.47) and OH-midazolam (r = 0.32).Conclusion: OH-midazolam risk of accumulation and significant clearance by haemodiafiltration should be taken into account in the drug adjustment in patients treated by continuous veno-venous haemofiltration. [Copyright &y& Elsevier]

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Background: Extracorporeal circulation, such as cardiopulmonary bypass and hemodialysis, has been associated with an activation of the immune system. Continuous veno venous hemodiafiltration (CVVHD) is used in critically ill septic patients. During CVVHD, cytokines are excreted in ultrafiltrate. When the membranes, used in CVVHD, are incubated with leukocytes in vitro a slight production of cytokines is observed. Due to the underlying disease it is difficult to investigate the effect of CVVHD in septic patients. We therefore studied the separate effect of CVVHD on the chemotaxis of granulocytes, the proliferation of lymphocytes and the release of IL-8 and IL-10 in healthy pigs compared to an endotoxin and a control group.Methods: Thirty-one pigs were anesthetized and mechanically ventilated. CVVHD was performed in 10 pigs. Eleven pigs received an infusion of Escherichia coli endotoxin 30 microg/kg, and 10 pigs served as a control group. The chemotaxis of granulocytes was measured in an assay chamber, and the cytokines IL-8 and IL-10 with an enzyme-linked immunosorbent assay. The adhesion molecules CD18 and CD62 on lymphocytes were measured using monoclonal antibodies, and the lymphocyte proliferation was measured without stimulation and in response to mitogens.Results: CVVHD was accompanied by lymphocytopenia and increased spontaneous lymphoproliferative response, but no change in adhesion molecules on lymphocytes or cytokine levels in plasma, and no decrease in the chemotaxis of granulocytes. Following endotoxin we observed a pronounced lymphocytopenia and an increased secretion of IL-8 and IL-10, a decrease in the expression of CD18 on lymphocytes and in the stimulated lymphocyte proliferation and in the chemotaxis of granulocytes.Conclusion: CVVHD does not, in contrast to endotoxin-induced sepsis, influence chemotaxis of granulocytes, the production of IL-8 and IL-10 or the proliferation of lymphocytes. [ABSTRACT FROM AUTHOR]

Objective: Extracorporeal circulation, such as cardiopulmonary bypass and haemodialysis, has been associated with an activation of the immune system, especially the granulocytes. Continuous veno-venous haemodiafiltration (CVVHD) is used in critically ill septic patients. During CVVHD cytokines are excreted in the ultrafiltrate. But when the membranes used in CVVHD are cultured with granulocytes, the granulocytes are slightly activated. This effect is potentiated by endotoxin. We therefore, in vivo, compared the effect on granulocyte activation of CVVHD with an endotoxin group and a control group.Methods: Thirty-one pigs were anaesthetized and mechanically ventilated. In ten pigs CVVHD was performed. Eleven pigs received an infusion of Escherichia coli endotoxin 30 mu/kg(-1) and ten pigs served as a control group. The adhesion molecules CD18 and CD62L were measured using monoclonal antibodies. The oxidative burst activity was assayed as superoxide dismutase-inhibitory reduction of cytochrome c. The number of granulocytes in peripheral blood and in the lungs and liver were counted.Results: The infusion of endotoxin was followed by granulocytopenia, reduced oxidative burst activity, increased expression of CD18 and decreased expression of CD62L on granulocytes. Accumulation of granulocytes in liver and lung tissue was also noted in this group. CVVHD was only associated with a non-significant decrease in CD62L expression on granulocytes. It did not affect any of the other measured immunological parameters.Conclusion: In contrast to endotoxin-induced sepsis, the granulocytes were not activated during CVVHD. [ABSTRACT FROM AUTHOR]

The history of continuous renal replacement therapy (CRRT) is marked by technological advances linked to improvements in the knowledge of the mechanisms and kinetics of extracorporeal removal of solutes, and the pathophysiology of acute kidney injury (AKI) and other critical illnesses. In the present article, we review the main steps in the history of CRRT, from the discovery of continuous arteriovenous hemofiltration to its evolution into the current treatments and its early use in the treatment of AKI, to the novel sequential extracorporeal therapy. Beyond the technological advances, we describe the development of new medical specialties and a shared nomenclature to support clinicians and researchers in the broad and still evolving field of CRRT. [ABSTRACT FROM AUTHOR]

Background.Certain inborn errors of metabolism become manifest during the neonatal period by acute accumulation of neurotoxic metabolites leading to coma and death or irreversible neurological damage. Outcome critically depends on the immediate elimination of the accumulated neurotoxins. Recent technological progress provides improved tools to optimize the efficacy of neonatal dialysis. [ABSTRACT FROM PUBLISHER]

Abstract: We present the case of a 24-year-old-female patient, who made an attempt to autolysis with valproic acid, benzodiazepines and neuroleptic. The valproic acid plasma level was very high (1437μg/mL), confirming it was a severe intoxication. She presents an acute encephalopathy with prolonged status epilepticus, a lactic metabolic acidosis and hematologic disorders such as bicytopenia. Treatment including L-carnintine and continuous veno-venous haemodialysis (CVVHD) was rapidly introduced to prevent the occurrence of cerebral oedema. The evolution was favourable despite the occurrence of a nosocomial ventilation acute lung injury. The patient had motor sequelae of cranial nerves following status epilepticus extended, which disappeared spontaneously after several days. [Copyright &y& Elsevier]

COVID-19 often leads to acute respiratory distress syndrome complicated by acute kidney injury (AKI). The indications for renal replacement therapy for these patients are those commonly accepted to treat AKI. We describe a continuous veno-venous haemodialysis (CVVHD) protocol for AKI, which aims to provide the best treatment according to the particular patient's and medical personnels' needs in biohazard settings with limited human and technological resources. We designed a CVVHD protocol with a high cut-off (HCO) filter in regional citrate anticoagulation (RCA). The HCO filter in diffusion determines the enhanced cytokines clearance with less filter clotting due to a lower filtration fraction. In our hospital, at the beginning of the pandemic outbreak, we treated seven COVID-19 patients with AKI stage 2 and 3 and recorded the circuit lifespan and the number of interventions on monitors. CVVHD in RCA appears to be safe, effective and easy to be performed in a biohazard scenario using lower blood flows and less bag changes with fluid savings, a biohazard reduction and sparing of resources. Although the data come from a very small cohort, our protocol seems related to a low mortality. [ABSTRACT FROM AUTHOR]

We report the case of a 37-year-old woman that developed severe hypercalcemia due to a parathyroid gland mass. After the initial medical treatment, only a minimal reduction of calcemia was observed and her clinical condition worsened; thus, she required continuous renal replacement therapy (CRRT) that resulted in the normalization of calcium serum level. She then underwent a left thyroid lobectomy with exeresis of the associated parathyroid glands; the histological diagnosis revealed a giant parathyroid adenoma (GPA). CRRT, initially recommended only in case of severe refractory hypercalcemia poorly responsive to pharmacological approaches, is now being evaluated in the first line treatment of life-threatening cases, with or without associated acute kidney injury (AKI)., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Continuous arterio-venous haemofiltration (CAVH), continuous veno-venous haemofiltration (CVVH), continuous arterio-venous haemodialysis (CAVHD) and continuous veno-venous haemodialysis (CVVHD) are increasingly used in patients with acute renal failure (ARF). The elimination rate of fluconazole varies considerably depending on the procedure used. (In Germany, fluconazole is approved for the treatment of life-threatening fungal infections caused by Candida spp. and Cryptococcus neoformans at a dosage of up to 800 mg day-1.) The elimination rate of fluconazole by CVVHD depends on the combined dialysate/ultrafiltrate flow rate, but is much higher than achieved with CVVH and intermittent dialysis, with a fluconazole clearance in patients with CVVHD 2 l h-1 exceeding the values of healthy persons. To achieve therapeutic plasma levels during continuous renal replacement therapy, the same loading dose as in patients without renal failure should be administered, followed by a maintenance dose that is adjusted for anuric patients by multiplying by a factor that takes into account the extracorporeal elimination of the absorbed dose (CAVH, CVVH×2.2, ultrafiltrate flow 0.5 l h-1; CAVHD, CVVHD×3.8, combined dialysate/ultrafiltrate flow 1.5 l h-1). Despite the broad therapeutic margin of fluconazole, drug monitoring is recommended to achieve therapeutic drug levels in life-threatening indications because there have been only a few investigations of this, all involving relatively low dosages (up to 200 mg day-1). [ABSTRACT FROM AUTHOR]

Background: Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking.Methods: Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT.Results: A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45-94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI.Conclusions: Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT.Trial Registration: EudraCT, 2012-005617-39 . Registered on 7 August 2013. [ABSTRACT FROM AUTHOR]