Clearance and nutrition in neonatal continuous kidney replacement therapy using the Carpediem™ system.

BACKGROUND: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). METHODS: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal-Wallis analysis were performed using SAS version 9.4. RESULTS: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). CONCLUSIONS: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Enhancing Quality Control in Continuous Renal Replacement Therapy Through ICU Specialist Nursing Care Management Program.

Objective: This study aims to investigate the impact of a specialized intensive care unit (ICU) nursing quality control team management program on continuous renal replacement therapy (CRRT). Our goal is to provide insights for enhancing the clinical outcomes of CRRT and improving patient satisfaction. Methods: We conducted this study at The First People's Hospital of Linping District in Hangzhou, China, from January 2018 to December 2021. The study comprised 519 critically ill patients in need of CRRT. Among them, 265 patients received routine bedside care management for CRRT (control group), while 254 patients received specialized quality control management for CRRT (experimental group). We compared several key parameters between the two groups, including the unplanned downtime rate, average downtime duration, compliance with continuous treatment for >24 hours and scheduled downtime for 72 hours, daily hemodialysis cost per patient, duration of single filter usage, unplanned extubation rate, and incidence of catheter-associated bloodstream infections. Additionally, we assessed nursing satisfaction, blood biochemical markers, and coagulation indices for both groups. Results: Compared to the control group, the experimental group demonstrated a reduced occurrence of unplanned events, an increase in average downtime duration, greater compliance with continuous treatment (>24 hours) and scheduled downtime (72 hours), lower daily hemodialysis costs per patient, extended duration of single filter usage, reduced rates of unplanned extubation and catheter-related bloodstream infections. Furthermore, patients in the experimental group reported significantly higher nursing satisfaction. In terms of blood potassium, sodium, BUN, and SCr levels, the experimental group exhibited lower values compared to the control group. In the investigation of blood coagulation indices, the numerical values for patients in the experimental group were notably better than those in the control group. Conclusions: The ICU specialized nursing quality control team management program for continuous renal replacement therapy outperforms conventional nursing management.

Severe vitamin C deficiency associated with continuous renal replacement therapy: A case report.

Hypovitaminosis C is prevalent in critically ill patients. Continuous renal replacement therapy (CRRT) clears vitamin C, increasing the risk for vitamin C deficiency. However, recommendations for vitamin C supplementation in critically ill patients receiving CRRT vary widely, from 250 mg/day to 12 g/day. This case report describes a patient who developed a severe vitamin C deficiency after prolonged CRRT despite receiving ascorbic acid (450 mg/day) supplementation in her parenteral nutrition. This report summarizes recent research investigating vitamin C status in critically ill patients receiving CRRT, discusses the patient case, and provides recommendations for clinical practice. In critically ill patients receiving CRRT, the authors of this manuscript suggest providing at least 1000 mg/day of ascorbic acid to prevent vitamin C deficiency. Baseline vitamin C levels should be checked in patients who are malnourished and/or have other risk factors for vitamin C deficiency, and vitamin C levels should be monitored thereafter every 1-2 weeks.

Current status of nutritional provision and effects of nutritional support on the clinical outcomes of acute kidney injury requiring continuous renal replacement therapy in the surgical intensive care unit.

BACKGROUND AND OBJECTIVES: Patients with acute kidney injury requiring continuous renal replacement therapy are at high risk of malnutrition. Nutritional support is an important part of treatment for patients with critical illness admitted to the intensive care unit. We aimed to investigate the status of nutritional provision and the effects of nutritional support on clinical outcomes. METHODS AND STUDY DESIGN: Our institution's medical records (from January 1, 2020, to December 31, 2021) were analyzed in this retrospective cohort study. We included 43 patients aged >18 years who received continuous renal replacement therapy for acute kidney injury in the surgical intensive care unit. RESULTS: The demographic characteristics were similar between the survivor and non-survivor groups. The protein supply per body weight (0.88 ± 0.37 g/kg vs. 0.47 ± 0.53 g/kg, p = 0.029) and the proportion of patients who met the target protein level (58.9 ± 24.9% vs. 30.8 ± 34.9%, p = 0.022) were significantly higher in the survivor group. Approximately 79.1% of the patients had a high malnutrition risk with a modified Nutrition Risk in the Critically Ill score of ≥5. The lengths of hospital and intensive care unit stays were longer in the high nutritional risk group compared with that in the low nutritional risk group, but the result was not significant. CONCLUSIONS: The nutritional amount provided in patients with critical illness is significantly lesser than the recommended amount. Ensuring proper nutritional support can improve the clinical outcomes.

Efficacy and Safety of Citric Acid and Heparin Anticoagulation in Patients with Septic Acute Kidney Injury Undergoing Continuous Renal Replacement Therapy: A Meta-Analysis.

Objective: This meta-analysis compares the clinical efficacy and safety of citrate anticoagulation with heparin anticoagulation in continuous renal replacement therapy for acute kidney injury in sepsis. Methods: The experimental group underwent local anticoagulation with citrate, whereas the control group received systemic anticoagulation with heparin. Relevant data from randomized controlled trials (RCTs) meeting the inclusion criteria were independently extracted through computer searches of the China Journal Full Text Database (CNKI), Wanfang, and Vipul databases. Additionally, references to included literature were searched to expand the dataset. Extracted RCTs that met inclusion criteria underwent independent quality evaluation and cross-checking using the Cochrane systematic review method. Subsequently, a meta-analysis was conducted using Stata 12.0 software. Results: The analysis included seven studies involving a total of 652 patients. After treatment, renal function improvement was significantly more significant in the citrate group, while creatinine and urea nitrogen levels showed a more significant decrease in the heparin group, with statistically significant differences (WMD = -51.30, 95% CI = -68.54 ~ -34.06, P = .000 and WMD = 3.68, 95% CI = -4.52 ~ -2.85, P = .000). The filter lifespan in the citrate group was significantly longer than in the heparin group, with a statistically significant difference (WMD = 6.93, 95% CI = 6.30 ~ 7.55, P = .000). Adverse bleeding reactions were significantly less common in the citrate group compared to the heparin group, with a statistically significant difference (RR = 0.14, 95% CI = 0.06 ~ 0.32, P = .000). Conclusions: The results of this meta-analysis indicate that citrate anticoagulation is more effective than heparin anticoagulation in continuous renal replacement therapy for patients with acute kidney injury in sepsis. Citrate anticoagulation contributes to improved renal function and extended filter usage and reduces the incidence of adverse bleeding reactions.

Micronutrient Losses during Continuous Renal Replacement Therapy.

Acute kidney injury impacts the micronutrient status by various mechanisms including decreased enteral absorption, changes in redistribution, altered metabolism, and increased consumption. When renal replacement therapy (RRT) is applied, there are additional losses of vitamins, trace elements, and amino acids, and their derivatives due to diffusion or adhesion. Varied data exist regarding the degree of micronutrient losses and plasma concentrations in patients who receive RRT, and these differ by RRT modality, dose, duration, and type of micronutrient. Water-soluble vitamins, selenium, copper, and carnitine are among the most frequently reported depleted nutrients. The role of micronutrient supplementation in critically ill patients undergoing RRT and the optimal dose and mode of administration are yet to be determined.

Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy.

OBJECTIVES: Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT. METHODS: Patients were identified from an ongoing pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics, and were included if they had received at least two cefepime doses in the ICU and were on CKRT for at least 24 h. PK parameters were estimated using MwPharm++ with Bayesian estimation and a paediatric population PK model. Target attainment was assessed as time of free cefepime concentrations above minimum inhibitory concentration (fT > 1× or 4 × MIC). RESULTS: Seven patients were included in the study (ages 2 to 20 years). CKRT indications included liver failure (n = 1), renal failure (n = 4) and fluid overload (n = 2). Total effluent flow rates ranged from 1833 to 3115 (mean 2603) mL/1.73 m2/h, while clearance was 2.11-3.70 (mean 3.0) L/h/70 kg. Effluent flows were lower, but clearance and fT > MIC were similar to paediatric data published previously. Using Pseudomonas aeruginosa MIC breakpoints, all patients had 100% of dosing interval above MIC, but only one had 100% of dosing interval above 4× MIC. CONCLUSIONS: Since most patients failed to attain stringent targets of 100% fT > 4×  MIC, model-informed precision dosing may benefit such patients.

Ceftazidime Plasma Concentrations and Neurotoxicity: The Importance of Therapeutic Drug Monitoring in Patients Undergoing Different Modalities of Renal Replacement Therapy. A Grand Round.

ABSTRACT: Ceftazidime-avibactam (CTZ-AVM) is a novel cephalosporin/beta-lactamase inhibitor with broad-spectrum activity against multidrug-resistant Pseudomonas aeruginosa . Ceftazidime-induced neurotoxicity is a well-described adverse effect, particularly in patients with renal insufficiency. However, appropriate dosing of ceftazidime-avibactam in patients undergoing renal replacement therapy (RRT) is sparsely investigated, and therapeutic drug monitoring to guide dosing remains lacking. Furthermore, when dose adjustment for impaired renal function is based on CTZ-AVM product information, inferior cure rates have been obtained compared with those with the standard therapy for intra-abdominal infections. Maintaining an effective dose while avoiding toxicity in these patients is challenging. Here, the authors describe the case of a critically ill patient, undergoing 2 modalities of RRT, who developed ceftazidime-induced neurotoxicity as confirmed using ceftazidime therapeutic drug monitoring. This case illustrates a therapeutic drug monitoring-based approach for guiding ceftazidime-avibactam dosing in this context and in diagnosing the cause of neurological symptoms and signs.

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

A survey on nutritional management of critically ill children on continuous renal replacement therapy.

We conducted a survey of pediatric nephrologists to examine the knowledge and current practices of and identify challenges in the nutritional management of critically ill children during continuous renal replacement therapy (CRRT). Although it is known that there is a significant effect on nutrition during CRRT, there seems to be a lack of knowledge as well as variability in the practices of nutritional management in these patients, as indicated by our survey results. The heterogeneity of our survey results highlights the need to establish clinical practice guidelines and develop consensus around optimal nutritional management in pediatric patients requiring CRRT. The results as well as the known effects of CRRT on metabolism should be considered during the development of guidelines in critically ill children on CRRT. Our survey findings also highlight the need for further research in the assessment of nutrition, determination of energy needs and caloric dosing, specific nutrient needs, and management.

A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF).

PURPOSE: To explore pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) ceftazidime-avibactam for treating difficult-to-treat resistant Gram-negative (DTR-GN) infections in critical patients undergoing continuous venovenous haemodiafiltration (CVVHDF). MATERIALS AND METHODS: Patients treated with CI ceftazidime-avibactam for DTR-GN infections during CVVHDF were retrospectively assessed. Ceftazidime and avibactam concentrations were measured at steady-state and the free fraction (fCss) was calculated. Total clearance (CLtot) of both agents were calculated and the impact of CVVHDF intensity was assessed by linear regression. The joint PK/PD target of ceftazidime-avibactam was defined as optimal when both fCss/MIC≥4 for ceftazidime and fCss/CT > 1 for avibactam were achieved. Relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed. RESULTS: Eight patients with DTR-GN infections were retrieved. Median fCss were 84.5 (73.7-87.7 mg/L) for ceftazidime and 24.8 mg/L (20.7-25.8 mg/L) for avibactam. Median CLtot was 2.39 L/h (2.05-2.96 L/h) for ceftazidime and 2.56 L/h (2.12-2.98 L/h) for avibactam. Median CVVHDF dose was 38.6 mL/h/kg (35.9-40.0 mL/kg/h). CLtot were linearly correlated with CVVHDF dose (r = 0.53;p = 0.03, and r = 0.64;p = 0.006, respectively). The joint PK/PD targets were optimal granting microbiological eradication in all the assessable cases. CONCLUSION: CI administration of 1.25-2.5 g q8h ceftazidime-avibactam may allow prompt attainment and maintenance of optimal joint PK/PD targets during high-intensity CVVHDF.

Piperacillin-tazobactam dosing in anuric acute kidney injury patients receiving continuous renal replacement therapy.

INTRODUCTION: To determine appropriate dosing of piperacillin-tazobactam in critically ill patients receiving continuous renal replacement therapy (CRRT). METHODS: The databases of PubMed, Embase, and ScienceDirect were searched. We used the Medical Subject Headings of "piperacillin-tazobactam," "CRRT," and "pharmacokinetics" or related terms or synonym to identify the studies for reviews. A one-compartment pharmacokinetic model was conducted to predict piperacillin levels for the initial 48 h of therapy. The pharmacodynamic target was 50% of free drug level above the minimum inhibitory concentration (MIC) and 4 times of the MIC. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. RESULTS: Our simulation study reveals that the dosing regimen of piperacillin-tazobactam 12 g/day is appropriate for treating Pseudomonal infection with KDIGO recommended effluent rate of 25-35 mL/kg/h. The MIC values of each setting were an important factor to design piperacillin-tazobactam dosing regimens. CONCLUSION: The Monte Carlo simulation can be a useful tool to evaluate drug dosing in critically ill acute kidney injury patients receiving CRRT when limited pharmacokinetic data are a concern. Clinical validation of these results is needed.

Initiating Continuous Renal Replacement Therapy in Patients With Transurethral Resection of Prostate Syndrome: A Case Report.

With advances and developments in hysteroscopy, cystoscopy, transurethral resection of bladder tumor, and arthroscopy, transurethral resection of prostate (TURP) syndrome has been increasingly reported. TURP syndrome is often accompanied by severe hyponatremia, fluid overload, and a plasma hypotonic state, resulting in heart failure and pulmonary and cerebral edema. Conventional treatment methods, such as intravenous infusion of hyperosmotic saline, can rapidly reverse the downward trend of serum sodium levels in efforts to prevent and treat cerebral edema. However, this may not be suitable for patients with cardiac and renal insufficiency and may induce central pontine myelinolysis due to the possibility of worsening volume load and difficulty in controlling the correction rate of serum sodium. The patient described in this report presented with severe hyponatremia (sodium<100 mmol/L) combined with intraoperative pulmonary edema; his cardiac function and oxygenation status deteriorated after an intravenous infusion of 3% hypertonic saline. He underwent continuous renal replacement therapy (CRRT) to prevent the progression of multiple-organ edema and cardiac insufficiency. CRRT has demonstrated efficacy in the treatment of chronic hyponatremia in patients with renal failure, and can slowly and continuously correct water-electrolyte imbalance, acid-base imbalance, and volume overload. TURP syndrome with severe hyponatremia and pulmonary edema was diagnosed; accordingly, the patient was treated with 3% hypertonic saline, furosemide, and CRRT, without the development of overt neurological sequelae.

UHPLC-MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy.

BACKGROUND: Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples. METHODS: Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate. RESULTS: The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations. CONCLUSION: This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

Negative calcium balance despite normal plasma ionized calcium concentrations during citrate anticoagulated continuous venovenous hemofiltration (CVVH) in ICU patients.

BACKGROUND: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients. METHODS: This is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n = 324 in 42 patients) and a validation set (n = 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021. RESULTS: Calcium excretion (mmol/24 h) was - 1.2877 + 0.646*[Ca]blood,total * ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was - 1.0 ± 6.7 mmol/24 h, the mean absolute error was 4.8 ± 4.8 mmol/24 h. Calculated calcium excretion was 105.8 ± 19.3 mmol/24 h. Mean daily CVVH calcium balance was - 12.0 ± 20.0 mmol/24 h. Mean cumulative calcium balance ranged from - 3687 to 448 mmol. CONCLUSION: During citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH.

Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial.

BACKGROUND: A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA. METHODS: Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan-Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF. RESULTS: A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8-62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7-60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ±â€Š15.9 mL/h vs. 169.0 ±â€Š15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study. CONCLUSIONS: When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice. REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn, ChiCTR-IPR-17012629).

Meropenem Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children Receiving Continuous Renal Replacement Therapy.

BACKGROUND AND OBJECTIVE: We aimed to develop a meropenem population pharmacokinetic model in critically ill children receiving continuous renal replacement therapy and simulate dosing regimens to optimize patient exposure. METHODS: Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT>1-4×MIC). RESULTS: A total of 27 patients with a median age of 4 [interquartile range 0-11] years, a median body weight of 16 [range 7-35] kg receiving continuous renal replacement therapy were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (Qeff) produced significant effects on clearance (CL): [Formula: see text] and [Formula: see text], where Vpop and CLpop estimates were 32.5 L and 5.88 L/h, respectively, normalized to a 70-kg BW and median Qeff at 1200 mL/h. Using this final model and Monte Carlo simulations, for patients with Qeff over 1200 mL/h, meropenem continuous infusion was adequate in most cases to attain 100% fT>1-4xMIC. For bacterial infections with a low minimum inhibitory concentration (≤2 mg/L), meropenem intermitent administration was appropriate for patients weighing more than 20 kg with Qeff <500 mL/h and for patients weighing more than 10 kg with Qeff <100 mL/h. CONCLUSIONS: Meropenem exposure in critically ill children receiving continuous renal replacement therapy needs dosing adjustments to the minimum inhibitory concentration that take into account body weight and the continuous renal replacement therapy effluent flow rate.

Population Pharmacokinetic Meta-Analysis and Dosing Recommendation for Meropenem in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

The optimal dosing regimen for meropenem in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains undefined due to small studied sample sizes and uninformative pharmacokinetic (PK)/pharmacodynamic (PD) analyses in reported studies. The present study aimed to perform a population PK/PD meta-analysis of meropenem using available literature data to suggest the optimal treatment regimen. A total of 501 meropenem concentration measurements from 78 adult CRRT patients pooled from nine published studies were used to develop the population PK model for meropenem. PK/PD target (40% and 100% of the time with the unbound drug plasma concentration above the MIC) marker-based efficacy and risk of toxicity (trough concentrations of >45 mg/L) for short-term (30 min), prolonged (3 h), and continuous (24 h) infusion dosing strategies for meropenem were investigated. The impact of CRRT dose and identified covariates on the PD probability of target attainment (PTA) and predicted toxicity was also examined. Meropenem concentration data were adequately described by a two-compartment model with linear elimination. Trauma was identified as a pronounced modifier for endogenous clearance of meropenem. Simulations demonstrated that adequate PK/PD targets and low risk of toxicity could be achieved in non-trauma CRRT patients receiving meropenem regimens of 1 g every 6 h infused over 30 min, 1 g every 8 h infused over 3 h, and 2 to 4 g every 24 h infused over 24 h. The impact of CRRT dose (25 to 50 mL/kg/h) on PTA was clinically irrelevant, and continuous infusion of 3 to 4 g every 24 h was suitable for trauma CRRT patients (MICs of ≤0.5 mg/L). A population PK model was developed for meropenem in CRRT patients, and different dosing regimens were proposed for non-trauma and trauma CRRT patients.

Micronutrient deficiencies in critically ill patients receiving continuous renal replacement therapy.

BACKGROUND & AIMS: Continuous renal replacement therapy (CRRT) is essential to the management of acute kidney injury (AKI) in critical illness. Unfortunately, large quantities of micronutrients are shown to be lost in CRRT effluent. Current literature describes serum micronutrient values in CRRT patients to be below-reference range, yet seldom compares such values to other critically ill populations unexposed to CRRT. The aim of this study was to describe and compare the prevalence of micronutrient and carnitine deficiencies in critically ill patients at high malnutrition risk exposed to CRRT to a group of patient unexposed to CRRT. METHODS: A retrospective chart review was conducted at Duke University Hospital using the electronic medical record. The study group consisted of patients at high malnutrition risk requiring intensive care unit (ICU) admission from 01/01/2017-12/31/2018 with one or more of the following serum micronutrient levels checked: carnitine, copper, zinc, selenium, and vitamins B1, B6, B9, and C. Micronutrient deficiencies were defined as below the reference range and carnitine deficiencies were interpreted as an acyl to free carnitine ratio (ACFR) of >0.4. RESULTS: 106 ICU patients met inclusion criteria and 46% were exposed to CRRT. At least one micronutrient deficiency was reported in 90% of CRRT patients compared to 61% patients unexposed to CRRT (p = 0.002). A greater percentage of copper (p < 0.001) and carnitine (p < 0.001) deficiencies were found among patients exposed to CRRT, while more zinc deficiencies were noted among non-CRRT patients (p = 0.001). CONCLUSIONS: The vast majority of CRRT patients presented with micronutrient deficiencies. Clinicians should have a heightened awareness of the risk for serum copper, carnitine, and vitamin B6 deficiencies among CRRT patients. Further prospective and randomized-controlled trials are needed to better define this new category of malnutrition and test supplementation strategies to address and prevent these clinically-relevant deficiencies.