Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a comparison between 2 citrate modalities and unfractionated heparin.

PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated continuous hemodiafiltration (CVVHDF) modalities and a heparin modality. MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium-containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium citrate with calcium-free low-bicarbonate buffered fluids (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher blood flow used in this modality and the calcium-containing dialysate. CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate and citrate. The amount substantially differs between modalities despite a similar CVVHDF dose and is unacceptably high when using ACD with calcium-containing lactate-buffered solutions and a higher blood flow. When calculating nutritional needs, we should account for the energy delivered by CVVHDF.

A validated bowel-preparation tolerability questionnaire and assessment of three commonly used bowel-cleansing agents.

BACKGROUND AND STUDY AIMS: Bowel-cleansing studies are frequently underpowered, poorly designed, and with subjective assessments. Consensus on tolerability of the bowel-cleansing agents is thus lacking. This study developed and validated a bowel-preparation tolerability questionnaire and used it to assess the tolerability of three bowel-cleansing agents, sodium phosphate (NaP), polyethylene glycol (PEG), and sodium picosulphate (Pico), in a prospective randomized single-blinded trial of ambulatory patients. PATIENTS AND METHODS: The bowel-preparation tolerability questionnaire was validated in 125 consecutive patients and then bowel-preparation agent tolerability was assessed in 634 patients in a prospective randomized single-blinded trial. RESULTS: The questionnaire's internal consistency was satisfactory with good to excellent "test-retest" reliability for aggregate tolerability and visual analogue scores. Validity assessment confirmed it as reliable and accurate. Of 634 patients, 97.8 % took >75 % of the allocated preparation and 98.9 % completed the questionnaire. Overall, Pico was better tolerated than PEG (p < 0.001) and NaP (p < 0.001). NaP was better tolerated than PEG (p < 0.001). Regardless of the bowel-preparation agent used, males tolerated them better than females (p = 0.009) as did patients having their procedure in the AM. Older patients, however, tolerated all preparations better than younger patients (p = 0.006). CONCLUSIONS: This study used the first validated bowel-preparation tolerability questionnaire and identified that age, sex, and procedure time all impacted tolerability. Overall, Pico was best tolerated, but PEG's tolerability in patients ≥60 years was equal to that of Pico and NaP, suggesting that PEG can be recommended for older patients to avoid the electrolyte disturbances associated with the osmotic preparations.

Trisodium citrate: an alternative to unfractionated heparin for hemodialysis catheter dwells.

The use of tunneled hemodialysis catheters, or permcaths, either for temporary dialysis access before arteriovenous fistula or arteriovenous graft maturation or for long-term dialysis access, is associated with increased risk of catheter clotting and infection. Catheter locking solutions are routinely used to maintain patency in these catheters between dialysis sessions. Unfractionated heparin has traditionally been used for this purpose; however, trisodium citrate (also known as sodium citrate or citrate) has recently been shown to be an efficacious alternative to heparin as a locking solution. Citrate exerts both its anticoagulant and antimicrobial properties by chelating calcium to disrupt the normal coagulation pathway and by interfering with the formation of biofilm and the bacterial cell wall. Citrate is at least equivalent to heparin as an anticoagulant and antimicrobial agent for catheter locking, and in some clinical studies citrate was shown to be superior. Two different concentrations of sodium citrate were previously available; however, concerns of safety led to the removal of citrate 46.7% from the United States and Canadian markets in 2000, leaving only citrate 4% available for use as a catheter locking solution. The systemic hypocalcemic effects that were reported with citrate 46.7% have not been observed with citrate 4% in clinical trials, and the risk of systemic anticoagulation and bleeding was shown to be lower than that with unfractionated heparin. In addition, most comparative cost data indicate that citrate is a more cost-effective alternative than heparin; however, costs can vary by institution. Despite inconclusive evidence of clinical superiority, citrate 4% appears to provide a safe and at least equivocal alternative to heparin as a catheter locking agent.

The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience.

BACKGROUND: Regional anticoagulation with trisodium citrate is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients at a high risk of bleeding. In a prospective, observational study we compared an established regional citrate anticoagulation protocol [Mehta R et al: Kidney Int 1990;38:976-981] versus a standard heparin anticoagulation protocol focusing on acid-base and electrolyte derangements as well as on cost effectiveness. METHODS AND RESULTS: 209 patients were included in the study. In 37 patients, citrate was used as the sole anticoagulant, 87 patients received low-dose heparin plus citrate, and 85 patients received only heparin as anticoagulant. A customized dialysate solution was used for citrate-anticoagulated CRRT (no buffer, no calcium, reduced sodium concentration). Filter life was significantly higher during citrate anticoagulation compared to heparin anticoagulation (80.2 +/- 60 vs. 30.2 +/- 32 h; p < 0.001). No difference was found between citrate and citrate-heparin anticoagulation (p = 0.310). Metabolic alkalosis was observed in more than 50% of patients on citrate anticoagulation. Alkalosis developed within the first 72 h after initiating treatment and could be reversed in almost all cases by increasing the dialysate flow rate. Hypercalcemia was observed in 13 patients on citrate anticoagulation. Patients with impaired liver function were particularly at risk. Systemic hypocalcemia, hypernatremia, and anion gap acidosis were not observed. Citrate anticoagulation was well tolerated hemodynamically. A longer filter life during citrate anticoagulation translated into a significant cost reduction compared to standard heparin anticoagulation (p < 0.01). CONCLUSION: Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.

Final report on the safety assessment of acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, and acetyl trioctyl citrate.

Acetyl Triethyl Citrate, Acetyl Tributyl Citrate, Acetyl Trihexyl Citrate, and Acetyl Trioctyl Citrate all function as plasticizers in cosmetics. Additionally, the Trihexyl and Trioctyl forms are described as skin-conditioning agents-emollients, although there are currently no reported uses of Acetyl Trihexyl Citrate or Acetyl Trioctyl Citrate. Acetyl Triethyl Citrate and Acetyl Tributyl Citrate are used in nail products at concentrations up to 7%. Recognizing that there are no reported uses of Acetyl Trihexyl or Trioctyl Citrate, if they were to be used in the future, their concentration of use is expected to be no higher than that reported for Acetyl Triethyl and Tributyl Citrate. These ingredients were sufficiently similar in structure that safety test data on one were considered applicable to all. Approximately 99% of orally administered Acetyl Tributyl Citrate is excreted-intermediate metabolites include acetyl citrate, monobutyl citrate, acetyl monobutyl citrate, dibutyl citrate, and acetyl dibutyl citrate. In acute, short-term, subchronic, and chronic feeding studies, these ingredients were relatively nontoxic. Differences from controls were either not statistically significant or not related to any organ toxicity. Ocular exposures produced moderate reactions that cleared by 48 hours after instillation. Dermal application was not toxic in rabbits. In a guinea pig maximization test, Acetyl Triethyl Citrate was a sensitizer whereas Acetyl Tributyl Citrate was not. Limited clinical testing of Acetyl Triethyl Citrate and Acetyl Tributyl Citrate was negative for both skin irritation and sensitization. These clinical data were considered more relevant than the guinea pig maximization data, suggesting to the Cosmetic Ingredient Review Expert Panel that none of these ingredients would be a sensitizer. Physiologic effects noted with intravenous delivery of Acetyl Triethyl Citrate or Acetyl Tributyl Citrate include dose-related decreases in blood pressure and intestinal muscular spasms. These ingredients were not genotoxic in bacterial or mammalian test systems. No significant differences in tumor induction (lymphomas) were noted in rats fed Acetyl Tributyl Citrate for 2 year. Acetyl Tributyl Citrate was not a developmental or reproductive toxicant in studies in mice and rats. Based on all the available data, these ingredients were considered safe as used in cosmetics.