Continuous veno-venous hemofiltration using a phosphate-containing replacement fluid in the setting of regional citrate anticoagulation

Purpose: The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid. Methods: In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3- 30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion. Results: In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients. Conclusions: Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophospha-temia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs. © 2013 Wichtig Editore

Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation

Aims: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. Methods: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. Results: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. Conclusions: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid–base status and phosphate supplementation needs

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid--base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5--3 mmol/l) and a higher than usual target circuit-Ca2+ (<=0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca2+ in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 +/- 36.5 vs 53 +/- 32.6 hours). Protocol A required additional bicarbonate supplementation (6 +/- 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid--base balance without additional interventions: pH 7.43 (7.40--7.46), Bicarbonate 25.3 (23.8--26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 +/- 2.4 g/day) and in only 30% of group B patients (0.5 +/- 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97--1.45 mmol/l, IQR)

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Letter to the editor: a case of atheroembolic renal disease confirmed by skin biopsy and successfully treated with low-dose prednisone

On October 2015, an 81-year-old White man with clinical history of chronic kidney disease (CKD) stage 3b (sCr 1.6 mg/dL; eGFRMDRD 44 mL/min/1.73m2), type 2 diabetes mellitus, hypertension, dyslipidemia, and smoking habit was hospitalized for ST-elevation myocardial infarction. He underwent primary percutaneous coronary intervention (PCI) with transradial approach and placement of two drug-eluting stents (DES). Three days later, he had nonoliguric contrast-induced acute kidney injury with peak sCr 2.4 mg/dL, his kidney function was almost completely restored within 5 days (sCr 1.9 mg/dL). However, because of severe atherosclerotic disease, the first interventional procedure remained incomplete, and a second PCI was performed 7 days later by transfemoral approach with the placement of an additional DES. At the time of hospital discharge, sCr was comparable to basal values (1.6 mg/dL)

Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators

Due to its endogenously high oxygen consumption, the central nervous system (CNS) is vulnerable to oxidative stress conditions. Notably, the activity of several CNS-targeting compounds, such as antidepressant and hypnotic drugs, or endogenous mediators, such as melatonin, is indeed linked to their ability of mitigating oxidative stress. In this work, we report the synthesis of two organoselenium compounds of which the structure was inspired by CNS-targeting psychotropic drugs (zolpidem and fluoxetine) and an endogenous mediator (melatonin). The molecules were designed with the aim of combining the ROS-scavenging properties, which were already assessed for the parent compounds, with a secondary antioxidant action, a glutathione peroxidase (GPx) mimic role empowered by the presence of selenium. The compounds were obtained through a facile three-step synthesis and were predicted by computational tools to passively permeate through the blood–brain barrier and to efficiently bind to the GABA A receptor, the macromolecular target of zolpidem. Of note, the designed synthetic pathway enables the production of several other derivatives through minor modifications of the scheme, paving the way for structure–activity relationship studies

Radical Scavenging Potential of Ginkgolides and Bilobalide: Insight from Molecular Modeling

The reactive oxygen species (ROS) scavenging capacities of ginkgolides and bilobalide, which are the peculiar constituents of the extract of Ginkgo biloba, are investigated in silico (level of theory: (SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)). Unlike other popular antioxidant natural substances, the carbon backbones of these compounds are entirely aliphatic and exclusively single C–C bonds are present. The selectivity for alkoxyl radicals via hydrogen-atom transfer (HAT) is assessed; importantly, the scavenging of peroxyl radicals is also possible from a peculiar site, here labeled C10 both for ginkgolides and bilobalide. The energetics are described in detail, and the analysis discloses that the studied compounds are powerful scavengers, with thermodynamic and kinetic properties similar to those of Trolox and melatonin, and that, in addition, they display selectivity for peroxyl radicals. These are all chemical-reactivity features contributing to the therapeutic action of the extract of G. biloba

Regional citrate anticoagulation in CVVH: A new protocol combining citrate solution with a phosphate-containing replacement fluid

Regional citrate anticoagulation (RCA) is a valid anticoagulation method in continuous renal replacement therapies (CRRT) and different combination of citrate and CRRT solutions can affect acid-base balance. Regardless of the anticoagulation protocol, hypophosphatemia occurs frequently in CRRT. In this case report, we evaluated safety and effects on acid-base balance of a new RCA- continuous veno-venous hemofiltration (CVVH) protocol using an 18mmol/L citrate solution combined with a phosphate-containing replacement fluid. In our center, RCA-CVVH is routinely performed with a 12mmol/L citrate solution and a postdilution replacement fluid with bicarbonate (protocol A). In case of persistent acidosis, not related to citrate accumulation, bicarbonate infusion is scheduled. In order to optimize buffers balance, a new protocol has been designed using recently introduced solutions: 18mmol/L citrate solution, phosphate-containing postdilution replacement fluid with bicarbonate (protocol B). In a cardiac surgery patient with acute kidney injury, acid-base status and electrolytes have been evaluated comparing protocol A (five circuits, 301hours) vs. protocol B (two circuits, 97hours): pH7.39 +/- 0.03 vs. 7.44 +/- 0.03 (P<0.0001), bicarbonate 22.3 +/- 1.8 vs. 22.6 +/- 1.4mmol/L (NS), Base excess 2.8 +/- 2.1 vs. 1.6 +/- 1.2 (P=0.007), phosphate 0.85 +/- 0.2 vs. 1.3 +/- 0.5mmol/L (P=0.027). Protocol A required bicarbonate and sodium phosphate infusion (8.9 +/- 2.8mmol/h and 5g/day, respectively) while protocol B allowed to stop both supplementations. In comparison to protocol A, protocol B allowed to adequately control acid-base status without additional bicarbonate infusion and in absence of alkalosis, despite the use of a standard bicarbonate concentration replacement solution. Furthermore, the combination of a phosphate-containing replacement fluid appeared effective to prevent hypophosphatemia

Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution

Introduction: Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding and undergoing continuous renal replacement therapy (CRRT). The aim was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCAcontinuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. Methods: In high bleeding risk cardiac surgery patients, we adopted, as alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid. Statistical analysis: Student t-test or ANOVA with post-hoc tests; Wilcoxon or Kruskal-Wallis tests for nonparametric analysis; Kaplan-Meier survival analysis with Log Rank test. Results: 33 patients (age 70.8±9.5, SOFA score 13.9±2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8±35.4 h, median 41, 152 circuits) was significantly longer (p<0.0001) if compared with heparin (30.6±24.3 h, median 22, 73 circuits) or no anticoagulation (25.7±21.2 h, median 20, 77 circuits). Targets circuit and systemic Ca++ were easily maintained (0.37±0.09 and 1.18±0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8±5.9 mmol/h) in 27 patients. Probability of circuit running at 24, 48, 72 h was higher during RCA-CVVH (p<0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (p<0.0001). RCA was associated to a lower transfusion rate (p<0.02). Platelet count (p=0.012) and antithrombin III activity (p=0.004) increased throughout RCA-CVVH, reducing the need for supplementation. Conclusions: RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation