Programs and processes for advancing pediatric acute kidney support therapy in hospitalized and critically ill children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a pediatric population, we summarize here the current state of knowledge in paKST programs and technology, identify key knowledge gaps in the field, and propose a framework for current best practices and future research in paKST.

Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration.

Cefiderocol is a broad-spectrum cephalosporin antibiotic and is indicated in patients with difficult-to-treat Gram-negative bacterial infections. Cefiderocol is applied as a 2-4-times daily prolonged 3-h infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (MIC). However, limited information on cefiderocol as CI has been assessed. We present a case of a critically ill 37-year-old woman with continuous venovenous haemofiltration (CVVH) treated with a CI of cefiderocol for multidrug-resistant Pseudomonas aeruginosa. She received 4 g per 24 h, in accordance with the recommendations for the total daily dose during CVVH with an effluent flow rate of 2.1-3 L/h. We evaluated intraperitoneal, plasma arterial pre- and postfilter and ultrafiltrate (urine) total cefiderocol concentrations and discussed the pharmacokinetics in respect to the CVVH settings. The predicted unbound plasma concentrations during CI resulted in 6.8-9.5-fold higher concentrations than the adopted MIC of 2 mg/L for cefiderocol against P. aeruginosa. The optimal time of the unbound concentration >MIC target of cefiderocol was met during the sampling period, suggesting adequate exposure during the total treatment period. The obtained intraperitoneal concentration indicated adequate cefiderocol exposure at the site of infection. Continuous infusion of 4 g cefiderocol per 24 h led to sufficient plasma concentrations in our anuric critically ill patient treated with CVVH. This case is supportive to the use of cefiderocol as continuous infusion.

One-Year Survival for Adult Venoarterial Extracorporeal Membrane Oxygenation Patients Requiring Renal-Replacement Therapy.

OBJECTIVES: 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. DESIGN: 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. SETTING: This was a single center retrospective review of all patients receiving VA-ECMO. PARTICIPANTS: A total of 347 adult VA-ECMO extracorporeal membrane oxygenation patients. INTERVENTIONS: None, retrospective. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report.

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as 'probable' on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.

Filter clotting with continuous renal replacement therapy in COVID-19.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.

Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial.

BACKGROUND: Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. METHODS: Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325-0.4 mmol/L vs. 0.2-0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). RESULTS: 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs - 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was - 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th-75th percentile 140-384) to 162 (111-265) pg/ml (p = 0.002); oxPTH from 192 (124-353) to 154 pg/ml (87-231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. CONCLUSIONS: A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.

Pharmacokinetics and dialytic clearance of apixaban during in vitro continuous renal replacement therapy.

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.

Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group.

BACKGROUND: The cumbersome program and the shortage of commercial solution hindered the regular application of regional citrate anticoagulation (RCA). It is urgent to simplify the protocol using only commercial preparations. The aim of this study was to explore the feasibility and efficacy of the modified protocol for continuous veno-venous hemofiltration (CVVH) in unselected critically ill patients. METHODS: A prospective cohort study was conducted in 66 patients who received a new protocol combining fixed citrate concentration with modified algorithm for supplements (i.e., fixed protocol), and compared the efficacy, safety and convenience for this group to a historical control group with a traditional protocol (n = 64), where citrate was titrated according to the circuit ionized calcium concentration (i.e., titrated protocol). The convenience was defined as the demand for monitoring test and dose adjustment of any supplement. RESULTS: The filter lifespan was 63.2 ± 16.1 h in the fixed group and 51.9 ± 17.7 h in the titrated group, respectively. Kaplan-Meier survival analysis demonstrated longer circuit lifetime for fixed group (log-rank, p = 0.026). The incidence of circuit clotting was lower in the fixed protocol (15.2% vs. 29.7% in the titrated protocol, p = 0.047). Moreover, compared with the titrated group, patients with fixed protocol had less demand for monitoring test and dose adjustment of any supplement (the number of times per person per day) (3.3 [IQR 2.3-4.5] vs. 5.7 [IQR 3.3-6.9], p = 0.001 and 1.9 [IQR 0.5-2.7] vs. 6.3 [IQR 4.2-7.9], p < 0.001; respectively). No new onset bleeding complications occurred in all patients. The overall incidence of suspected citrate accumulation was 4.6% and there was no difference between the two groups (p = 0.969), yet a lower rate of metabolic alkalosis was found in the fixed group (3.0% vs. 14.1%, p = 0.024). CONCLUSIONS: Our modified fixed citrate concentration protocol is feasible, safe and effective to enhance the circuit lifespan and the convenience of implementation while maintaining a similar safety when compared to the traditional protocol. Using only commercial preparations may be helpful for widespread application of RCA. TRIAL REGISTRATION: Clinicaltrials.gov. NCT02663960 . Registered 26 January 2016.

ECMO as a Platform for Rapid Ammonia Removal in a Neonate with Multienzyme Urea Cycle Disorder.

Since the initial deployment of neonatal extracorporeal membrane oxygenation (ECMO) for respiratory failure, the use of ECMO in this population has diversified. We present a term female infant with carbamoyl phosphate synthetase 1 and partial N-acetylglutamate synthase deficiencies who developed severe hyperammonemia refractory to medical management requiring venoarterial ECMO-driven continuous veno-venous hemodiafiltration for ammonia detoxification. This case report illustrates a subpopulation where neonatal ECMO may improve survival and neurodevelopmental outcomes. To our knowledge, this is the first reported case of a urea cycle defect arising from two proximal enzyme deficiencies. Also, this is one of the few reported patients with UCD associated with peak ammonia levels >2,000 µmol/L who survived to hospital discharge after the successful use of ECMO for ammonia reduction. This case will add to the existing scant literature supporting the use of ECMO as a platform for rapid removal of serum ammonia.

Non-tunneled versus tunneled dialysis catheters for acute kidney injury requiring renal replacement therapy: a prospective cohort study.

BACKGROUND: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is associated with high morbidity, mortality and resource utilization. The type of vascular access placed for AKI-RRT is an important decision, for which there is a lack of evidence-based guidelines. METHODS: We conducted a prospective cohort study over a 16-month period with 154 patients initiated on AKI-RRT via either a non-tunneled dialysis catheter (NTDC) or a tunneled dialysis catheter (TDC) at an academic hospital. We compared differences in renal replacement delivery and mechanical and infectious outcomes between NTDCs and TDCs. RESULTS: Patients who received TDCs had significantly better RRT delivery, both with continuous venovenous hemofiltration (CVVH) and intermittent hemodialysis (IHD), compared to patients who received NTDCs; these findings were confirmed after multivariable adjustment for AKI-specific disease severity score, history of chronic kidney disease, renal consult team, and AKI cause. In CVVH and IHD, the median venous and arterial blood flow pressures were significantly higher with TDCs compared to NTDCs (p < 0.001). Additionally for CVVH, the median number of interruptions per catheter was higher with NTDCs compared to TDCs (Rate Ratio (RR) 2.7; p < 0.001), and for IHD, a higher median blood flow was seen with TDCs (p < 0.001). There were a significantly higher number of mechanical complications with NTDCs (RR 13.6 p = 0.001). No significant difference was observed between TDCs and NTDCs for positive blood cultures per catheter. CONCLUSIONS: Compared to NTDCs, TDCs for patients with AKI-RRT had improved RRT delivery and fewer mechanical complications. Initial TDC placement for AKI-RRT should be considered when not clinically contraindicated given the potential for improved RRT delivery and outcomes.

A service evaluation comparing CVVH an CVVHD in minimising circuit failure.

BACKGROUND: A significant problem during continuous renal replacement therapy is premature circuit failure, affecting efficacy and molecular clearance. Techniques to improve circuit failure are anticoagulation, access site and modality. A modality change was introduced, moving from continuous veno-venous haemofiltration to continuous veno-venous haemodiafiltration as a result of existing issues with failing circuit times and failure rates. AIM: The aim of this service evaluation was to ascertain if the use of continuous veno-venous haemodiafiltration compared to continuous veno-venous haemofiltration had affected failed circuit survival times and rates. METHODS: A service evaluation was chosen because the focus was to ascertain what effect a practice change had had on a particular service. The service evaluation was registered with the local trust's audit department and gained university ethical approval. It was anticipated that the data generated would be used to inform, question and improve practices. Patients who received renal replacement therapy (RRT) from May 2012 to January 2013 were retrospectively identified. Patients received continuous veno-venous haemofiltration for the duration of their treatment before September 2012 and continuous veno-venous haemodiafiltration after. A total of 78 patients were identified as receiving RRT; 41 of these patients had failed circuits. RESULTS: A total of 182 failed circuits were analysed. The median duration of failed circuits during continuous veno-venous haemofiltration was shorter (2·75 h, standard deviation (SD) = 13·82) when compared to continuous veno-venous haemodiafiltration (11 h, SD = 15·26, p < 0·001, 95% confidence interval (CI) 2·5-10). Circuit failure rate in continuous veno-venous haemofiltration was 56% compared to 43% in continuous veno-venous haemodiafiltration. After performing a Cox regression analysis, continuous veno-venous haemofiltration appeared to have a 1·87 times (CI 1·18-2·82, p > 0·007) more likely chance of failure. CONCLUSION: The use of continuous veno-venous haemodiafiltration has had an overall positive effect on the haemofiltration service by reducing the number of failed circuits and increasing circuit survival times, which may have improved the efficacy of the service. Continuous veno-venous haemodiafiltration may be a more appropriate modality of choice in non-septic patients requiring prolonged continuous RRT episodes.

Heparin-free continuous vena-venous hemofiltration as a veno-venous bypass in inferior vena cava reconstruction.

OBJECTIVE: This paper investigated the effects of continuous vena-venous hemofiltration on inferior vena cava reconstruction. METHOD: Totally, 11 patients were observed, vascular access in right internal jugular vein and femoral vein catheterization was established guided by ultrasound, and heparin-free continuous vena-venous hemofiltration was used to substitute for extracorporeal veno-venous bypass. Furthermore, blood pressure, central venous pressure, urine volume, blood platelet, serum albumin, renal function, serum cystatin C, CRP, TBil, AST, ALT, serum amylase, serum lipase, PLT, PT, APTT, Fig, D-mier, and adverse events were determined. RESULTS: All operations were completed successfully. Average time of continuous vena-venous hemofiltration was 2.96 ± 0.76 h. No hematoma and blood leakage was occurred when catheters were inserted, and no luminal stenosis and catheter-related infections were observed. Visceral congestion was observed when the inferior vena cava was clamped, but significantly improved immediately after the continuous vena-venous hemofiltration was begun. No hemofilter was changed due to clotting during continuous vena-venous hemofiltration therapy. Blood pressure, central venous pressure, and urine volume of the patients maintained stable. No significant change was observed in blood platelet, serum albumin, and serum creatinin. Serum cystatin and hsCRP increased after operation, but still in normal level. CONCLUSION: Heparin-free continuous vena-venous hemofiltration was an effective mode as veno-venous bypass in the treatment of inferior vena cava interruption and reconstruction.

Use of High-Flow Continuous Renal Replacement Therapy with Citrate Anticoagulation to Control Intracranial Pressure by Maintaining Hypernatremia in a Patient with Acute Brain Injury and Renal Failure.

Traumatic brain injury and intracranial hypertension often require treatment to optimize patient outcome. There are a variety of complex medical conditions that can preclude standard approaches to the treatment of intracranial hypertension. We describe a case where a novel approach using continuous dialysis with trisodium citrate was used to optimize the outcome of a young male with acute renal failure and acute respiratory distress syndrome in the setting of acute traumatic brain injury.

Treatment of severe hyponatremia in patients with kidney failure: role of continuous venovenous hemofiltration with low-sodium replacement fluid.

Patients with hypervolemic hyponatremia and kidney failure pose a special therapeutic challenge. Hemodialysis to correct volume overload, azotemia, and abnormal electrolyte levels will result in rapid correction of serum sodium concentration and place the patient at risk for osmotic demyelination syndrome. We present a patient with acute kidney injury and severe hypervolemic hypotonic hyponatremia (serum sodium<100 mEq/L) who was treated successfully with continuous venovenous hemofiltration. This teaching case illustrates the limitations of hemodialysis and demonstrates how to regulate the sodium correction rate by single-pool sodium kinetic modeling during continuous venovenous hemofiltration. Two methods to adjust the replacement fluid to achieve the desired sodium concentration are outlined.

Ceftriaxone pharmacokinetic properties during continuous veno-veno haemofiltration using an in vitro adult, paediatric and neonatal model.

During continuous venoveno haemofiltration (CVVH), extracorporeal drug clearance is dependant on blood flow, ultrafiltration rate, albumin binding, and the drug's molecular weight and volume of distribution. Drug doses are adjusted assuming reduced drug clearance by the renal system and CVVH. High volume haemofiltration, pre-dilution and different filter membranes can greatly alter drug clearance. Consequently, assessing the adequacy of cephalosporin dosing during CVVH is complex; under- or overdosing may occur. We studied the pharmacokinetic properties of ceftriaxone during CVVH in vitro. Renaflow filters were used to model 6, 20 and 50 kg patients. Each circuit and reservoir was prepared with a known volume of Hartmann's solution, human albumin solution 4.5% or blood. Pump speed and exchange rate were standardised for weight. Haemosol BO was used as the replacement fluid with 70% pre-dilution. Following paired sampling from the circuit and ultrafiltrate fluid, ceftriaxone was injected into the circuit. Paired samples were taken up to 720 minutes. Ceftraxione concentrations were determined using high performance liquid chromatography (HPLC). Maximum circuit concentrations (Cmax) at 2 minutes for albumin were 3.5, 2.65 and 4.85 mg/l, for blood were 4.5, 6.5 and 5.55 mg/l and for Hartmann's were 1.65, 2.95 and 3.65 mg/l for 6 kg, 20 kg and 50 kg models. The sieving coefficients (Sc) from blood (ratio of mean concentrations in the ultrafiltrate/circuits samples) were 0.31 and 0.51 with T1/2 (the half life) 62 and 20 minutes in the 6 kg and the 20 kg circuits, respectively. The data suggest in an in vitro model of ceftriaxone is rapidly cleared during CVVH. Albumin circuits had the lowest Sc and longest terminal T1/2, reflecting protein binding of the drug and suggest ceftriaxone clearance may be more rapid in hypoalbuminaemic patients. The Cmax was lower in the Hartmann circuits, possibly reflecting precipitation of the drug with calcium in this solution.

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.

Analysis of Leukocyte Recruitment in Continuous Veno-Venous Hemofiltration with Regional Citrate vs. Systemic Heparin Anticoagulation.

Acute kidney injury (AKI) is a frequent complication in critically ill patients. Supportive treatment of AKI patients is based on renal-replacement therapy, including continuous veno-venous hemofiltration (CVVH). To limit clotting events on extracorporeal surfaces, anticoagulants are administered, including systemic heparin and local citrate. The differential and comparative effects of these anticoagulants on leukocyte function in acute kidney injury patients are, so far, insufficiently understood. In this bio-add-on-study, AKI patients were randomized as part of a parallel-group trial to either systemic heparin or regional citrate anticoagulation. Patient samples were collected upon inclusion, prior to CVVH initiation at day 0, day 1, day 3 and day 5, following CVVH initiation, and one day after cessation of CVVH, then immediately analyzed. Flow cytometric assessment of surface-receptor molecules was conducted. Whole-blood-perfused human microfluidic chambers were used for the analysis of neutrophil rolling and adhesion. Acute kidney injury was associated with significant changes in the surface expression of CD182 and CD16 throughout CVVH treatment, independent of the anticoagulation regime. AKI furthermore abrogated selectin-induced slow leukocyte rolling and diminished chemokine-induced leukocyte arrest. Subgroup analyses of citrate vs. heparin treatment showed no significant differences between groups, independent of the duration of CVVH treatment. CD182 and CD16 expression remained low in both groups throughout CVVH therapy. These data confirm that AKI impairs selectin-mediated leukocyte slow rolling and chemokine-induced leukocyte arrest in vitro. Systemic heparin or local citrate anticoagulation have no differential effect on the leukocyte recruitment steps examined in this study.

"CATCH" Study: Correct Antibiotic Therapy in Continuous Hemofiltration in the Critically Ill in Continuous Renal Replacement Therapy: A Prospective Observational Study.

The proper posology of antibiotics in the critically ill in CRRT is difficult to assess. We therefore performed a prospective observational cohort study to make clear hints in this topic. Our results reveal a high Sieving Coefficient for all antibiotics, equal to or higher than those described in previous papers. CVVH clearance in relation to total body clearance was significant, (i.e., >than 25% for all classes). A strong correlation between the antibiotic concentrations obtained in plasma and ultrafiltrate was found both at the peak and in the valley, with the determination of two equations that allow a new method for calculating the amount of antibiotic lost in CVVH both for trough levels and peak. Based on the results of our study and considering the limitations we believe that we can extrapolate the following final considerations: (1) it is likely to carry out a loading dose for the main antibiotics (2) subsequent administrations must take into account the daily loss identified by the linear regression equation. This angular coefficient gives the idea that the average daily loss of given antibiotic is about 25%; this implies that on the basis of the linear regression equation that correlates ultrafiltered/plasma antibiotic concentration, the dosage should be increased by 25% every day, while still ensuring a daily plasma TDM of the drug.