Protein-bound uraemic toxins (PBUTs) cause various deleterious effects in end-stage kidney disease patients, because their removal by conventional haemodialysis (HD) is severely limited by their low free fraction in plasma. Here we provide an experimental validation of the concept that the HD dialytic removal of PBUTs can be significantly increased by extracorporeal infusion of PBUT binding competitors. The binding properties of indoxyl sulfate (IS), indole-3-acetic acid (IAA) and hippuric acid (HIPA) and their binding competitors, ibuprofen (IBU), furosemide (FUR) and tryptophan (TRP) were studied in uraemic plasma. The effect of binding competitor infusion on fractional removal of PBUT was then quantified in an ex vivo single-pass HD model using uraemic human whole blood. The infusion of a combination of IBU and FUR increased the fractional removal of IS from 6.4 ± 0.1 to 18.3 ± 0.4%. IAA removal rose from 16.8 ± 0.3 to 34.5 ± 0.7%. TRP infusion increased the removal of IS and IAA to 10.5 ± 0.1% and 27.1 ± 0.3%, respectively. Moderate effects were observed on HIPA removal. Pre-dialyzer infusion of PBUT binding competitors into the blood stream can increase the HD removal of PBUTs. This approach can potentially be applied in current HD settings.
High-flux dialysis membranes used with bicarbonate dialysis fluid increase the risk of back diffusion of bacterial endotoxin into the blood during hemodialysis. Endotoxin transfer of various synthetic fiber membranes was tested with bacterial culture filtrates using an in vitro system testing both diffusive and convective conditions. Membranes were tested in a simulated dialysis mode with endotoxin challenge material (approximately 420 EU/mL) added to the dialysis fluid, with saline used to model both blood and dialysis fluid. Samples were taken of both blood and dialysis fluid, and analyzed using a kinetic turbidimetric Limulus amoebocyte lysate assay. Endotoxin was found in all of the blood circuit samples, except for the Fresenius Optiflux F200NR(e) and thick-wall membranes. All membranes tested removed approximately 95% of the endotoxin from solution, with the residual approximately 5% recirculating within the dialysis fluid compartment. Endotoxin distribution through the fiber membrane was examined using a fluorescent-labeled endotoxin conjugate. Fluorescence images indicate that adsorption occurs throughout the membrane wall, with the greatest concentration of endotoxin located at the inner lumen. Contact angle analysis was able to show that all membranes exhibit a more hydrophilic lumen and a more hydrophobic outer surface except for the polyethersulfone membranes, which were of equal hydrophobicity. Resulting data indicate that fiber geometry plays an important role in the ability of the membrane to inhibit endotoxin transfer, and that both adsorption and filtration are methods by which endotoxin is retained and removed from the dialysis fluid circuit.
Introduction: Palpation of a thoracic rib is a common method for reducing the risk of pneumothorax during electromyographic examination of the rhomboid major muscle, but its accuracy is unknown. Methods: Two physicians palpated healthy subjects to attempt to identify the center of a rib located beneath the rhomboid major muscle. The identified location was examined with ultrasonography to examine its accuracy and the subject's anatomical depths. Results: Forty-four subjects (88 ribs) were studied. Palpation demonstrated a 66.3% accuracy rate, with significantly more incorrect palpations seen with greater muscle thickness (P 5 0.004) and body mass index (P 5 0.037), but not adipose thickness, age, or skin thickness (P > 0.05). Discussion: Palpation of the ribs in an attempt to avoid inadvertent pneumothorax while examining the rhomboid major may be inaccurate, primarily in patients with large muscle bulk. We suggest a brief ultrasound evaluation before electromyography to gauge correct needle depth.
During hemodialysis bacterial lipopolysaccharide (LPS) in contaminated dialysate solution may translocate across the hollow fiber membrane (HFM) to a patient's blood, resulting in fever and possible systemic shock. This study investigates LPS transfer across, and adsorption within, native and modified Fresenius Optiflux® F200NRe polysulfone (PS)/polyvinyl pyrrolidone (PVP) HFMs. Modifications include varied PVP content, addition of a PS‐poly(ethylene glycol) copolymer (PS‐PEG), and bleach sterilization. Under clinically relevant flow conditions LPS from >400 EU mL−1 spiked dialysate is not detected (<0.1 EU mL−1) in the lumens of native fibers, but is detected to varying degrees (0.2–15 EU mL−1) in the lumens of the modified fibers. Fluorescently labeled LPS predominantly adsorbs near the lumen of all membranes except the PS‐PEG containing membrane, where LPS localizes on the outer wall. Thus, addition of PS‐PEG may entrap LPS in the HFM spongy matrix, away from the blood‐contacting fiber lumen. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41550.
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