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Sildenafil citrate for penile hemodynamic determination: an alternative to intracavernosal agents in Doppler ultrasound evaluation of erectile dysfunction.

OBJECTIVES: To suggest a new noninvasive method for penile Doppler ultrasound (PDU) evaluation of erectile dysfunction using oral sildenafil citrate as an erection induction agent. METHODS: A total of 20 patients admitted with the complaint of erectile dysfunction were evaluated by the short form of the International Index of Erectile Function. A total score of less than 25 was accepted as erectile dysfunction and PDU was performed. The initial penile study consisted of PDU examination under visual sexual stimulation (VSS), and the peak systolic velocity, end-diastolic velocity, and resistance index were recorded. Measurements of all the parameters were repeated on the same patients after intracavernosal papaverine, intracavernosal prostaglandin E(1) (PGE(1)), and oral sildenafil citrate administration, plus VSS. All patients had these four tests in the same order at weekly intervals. Sildenafil citrate was given orally 45 minutes before Doppler investigation, and patients had VSS during the waiting period. The patients were asked about their satisfaction and comfort after each test. Statistical analysis was performed using the Wilcoxon and Mann-Whitney U tests. RESULTS: The measurements with papaverine, PGE(1), and sildenafil citrate were significantly different from those after only VSS (P <0.008); however, the papaverine, PGE(1), and sildenafil citrate results were not different from each other according to the peak systolic velocity, end-diastolic velocity, and resistance index measurements (P >0.008). Patients commented that although PGE(1) was the strongest erectogenic agent, sildenafil citrate was the most convenient. CONCLUSIONS: Since the results of PDU with oral sildenafil citrate in association with VSS were not statistically different, we suggest a new noninvasive erection induction method for the purpose of PDU evaluation of erectile dysfunction.

Adult↗

Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys.

It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day.

Absorption↗

Citrate and renal calculi: new insights and future directions.

Citrate is pathogenetically important in stone formation, because it retards the crystallization of stone-forming calcium salts and because its level in urine is low in many patients with nephrolithiasis. Potassium citrate is useful therapeutically, because it can often restore normal urinary citrate. Hypocitraturia often results from dietary aberrations, including sodium excess, and exaggerated intake of animal proteins. Hypocitraturia is frequently accompanied by a low net gastrointestinal absorption of alkali. New drugs are under development as improvements or refinements of currently available potassium citrate. They are potassium citrate 10-mEq-tablet preparation, effervescent calcium citrate, and potassium-magnesium citrate.

Animals↗

Effect of ACTH and oxytocin treatment on lactoferrin and citrate in cows' milk.

Six dairy cows were treated before milkings with either oxytocin (Pitocin, 20 i.u.) or ACTH (Synacthen, 150 i.u.), principally to determine their effect on the ratio of citrate: lactoferrin concentrations in the milk. With ACTH treatment, after 3 d milk yield and citrate concentration decreased significantly, lactoferrin and bovine serum albumin (BSA) concentrations increased significantly. Somatic cell counts (SCC) increased temporarily in the milk of three of the cows which previously had greater than 100 000 cells/ml. Lactoferrin yield remained fairly constant but citrate yield was significantly reduced. The citrate: lactoferrin molar ratio decreased from 1373 to 606. With oxytocin treatment, after 4 d milk yield first increased and then significantly decreased, citrate concentration decreased significantly while there were no significant changes in lactoferrin or BSA concentration or in the yield of any other milk constituents. The citrate: lactoferrin molar ratio decreased from 1621 to 1301. There were no significant changes in SCC either during treatment or 4 d after treatment but there was a significant rise at 16 d after treatment. It was concluded that in lactating cows both hormones affected citrate and lactoferrin concentrations in the direction that would improve the antibacterial properties of milk, but that this was accompanied by adverse effects on milk secretion. The extent of the change was not sufficient to be likely to produce inhibition of coliform bacteria.

Adrenocorticotropic Hormone↗

Conformational stability of pig citrate synthase and some active-site mutants.

The conformational stabilities of native pig citrate synthase (PCS), a recombinant wild-type PCS, and six active-site mutant pig citrate synthases were studied in thermal denaturation experiments by circular dichroism and in urea denaturation experiments by using DTNB to measure the appearance of latent SH groups. His274 and Asp375 are conserved active-site residues in pig citrate synthase that bind to substrates and are implicated in the catalytic mechanism of the enzyme. By site-directed mutagenesis, His274 was replaced with Gly and Arg, while Asp375 was replaced with Gly, Asn, Glu, or Gln. These modifications were previously shown to result in 10(3)-10(4)-fold reductions in enzyme specific activities. The thermal unfolding of pig citrate synthase and the six mutants in the presence and absence of substrates showed large differences in the thermal stabilities of mutant proteins compared to the wild-type pig citrate synthase. The functions of His274 and Asp375 in ligand binding were measured by oxalacetate protection against urea denaturation. These data indicate that active-site mutations that decrease the specific activity of pig citrate synthase also cause an increase in the conformational stability of the protein. These results suggest that specific electrostatic interactions in the active site of citrate synthase are important in the catalytic mechanism in the chemical transformations as well as the conformational flexibility of the protein, both of which are important for the overall catalytic efficiency of the enzyme.

Animals↗

The quaternary structure of citrate synthase from Escherichia coli K12.

A combination of equilibrium ultracentrifugation and polyacrylamide gel electrophoresis techniques has been used to establish the quaternary structure of citrate synthase from acetate-grown Escherichia coli K12 3000. In polyacrylamide gels containing 0.1% sodium dodecyl sulfate (SDS), the pure enzyme showed one major band whose mobility was consistent with a molecular weight of 46,000 plus or minus 2000 g/mol, and a little material of 87,000 plus or minus 5000 g/mol. When first cross-linked with dimethyl suberimidate and then submitted to electrophoresis in SDS, citrate synthase showed six bands, in widely different amounts, whose apparent molecular weights were almost integral multiples of 47,000 g/mol. The dimer was the major product of the cross-linking procedure. In 6 M guanidine HCl at pH 7.0, citrate synthase behaved as a single component in high-speed sedimentation equilibrium experiments, with a weight average molecular weight of 43,400 plus or minus 300 g/mol. The molecular weight of native citrate synthase was investigated by high-speed sedimentation equilibrium ultracentrifugation under different conditions of pH and KCl concentration. In 0.02 M Tris-Cl at pH 7.0 and 7.8, the enzyme was a mixture of oligomers, with species ranging from monomer (47,000 g/mol) to greater than decamer being present. At pH 9.0, only dimer was seen (94,000 g/mol). Large aggregates were present at pH 10.0. The addition of small amounts of KCl, a potent activator of the enzyme, simplified the mixture of oligomers considerably at pH 7.8. A detailed analysis of the data with 0.05 M KCl indicated that dimer and hexamer were the only species present, with marked nonideality. Increasing the KCl concentration to 0.10 M converted all the enzyme to hexamer. The amino acid composition of E. coli citrate synthase was presented. Taken together with peptide mapping experiments of others (J. A. Wright and B. D. Sanwal (1971), J. Biol. Chem. 246 1689), it indicates that the subunits have all the same or very similar amino acid sequences. The dansylation method revealed only methionine at the N-termini of the citrate synthase polypeptide chains. Citrate synthase from E. coli thus resembles the enzyme from eukaryotes in that it consists of subunits weighing just under 50,000 g/mol, although these subunits are more highly aggregated in the bacterial enzyme under most conditions. This conclusion is in disagreement with that of Wright and Sanwal (1971, see above), who reported a subunit size of 62,000 g/mol.

Amino Acids↗

Citrate and the conversion of carbohydrate into fat. The regulation of fatty acid synthesis by rat liver extracts.

1. The rate of fatty acid synthesis by particle-free extracts prepared from rat liver is increased greatly if the enzyme system is first activated with citrate. 2. The extent of the activation depends on the citrate concentration and on the time of activation in an interdependent manner. 3. Citrate activation is strongly dependent on temperature. 4. Tricarballylate can replace citrate as an activator, but its presence in the assay inhibits fatty acid synthesis. 5. Mg(2+) ions can replace citrate in the activation but not in the complete reaction system. 6. ATP prevents the activating effect of citrate and Mg(2+) ions. 7. The rate of fatty acid synthesis is increased by palmitoyl-dl-carnitine. This type of activation, additional to that caused by citrate, is rapid and does not depend on prior incubation. 8. Inhibition of fatty acid synthesis by palmitoyl-CoA can be prevented by palmitoyl-dl-carnitine or by increasing the concentration of protein.

Adenosine Triphosphate↗

The effect of citrate, calcium, and magnesium ions on the potassium movement across the human platelet membrane.

The intracellular K+ concentration in platelets is reduced during storage in citrated plasma. As shown previously, pH has a marked influence on this reduction. The effect of citrate and Ca2+ and Mg2+ on the K+ permeability of the membrane and on the active K+ transport across the membrane was investigated. Platelets were incubated in dialyzed plasma at 37 degrees C, pH 5.5 to 7.9, with and without added Ca2+ and Mg2+ and citrate. After 60- to 120-minute incubation, a steady state was reached, and ouabain was added to inhibit the active K+ transport. In the pH interval 5.5 to 6.2 citrate, Ca2+ and Mg2+ had no influence on either the active K+ transport or the K+ permeability. Between pH 7.1 and 7.9, Ca2+ and Mg2+ decreased the permeability, whereas citrate increased it. At pH 7.9, citrate had a depressing effect on the active transport. These results indicate that a low citrate concentration and a pH below 7 are important for maintaining a high intracellular K+ of platelets during storage in plasma.

Blood Platelets↗

Simplified citrate anticoagulation for high-flux hemodialysis.

In a randomized crossover trial, we compared a simple citrate anticoagulation protocol for high-flux hemodialysis with standard anticoagulation by low-molecular-weight heparin (dalteparin). Primary end points were urea reduction rate (URR), Kt/V, and control of electrolyte and acid-base homeostasis. Secondary end points were bleeding time at vascular puncture sites and markers of activation of platelets, coagulation, and fibrinolysis. Solute removal during citrate dialysis was excellent (URR, 0.71 +/- 0.06; Kt/V, 1.55 +/- 0.3) and similar to results of conventional bicarbonate hemodialysis anticoagulation with dalteparin (URR, 0.72 +/- 0.04; Kt/V, 1.56 +/- 0.2). Electrolyte control was effective with both anticoagulation regimens, and total and ionized calcium, sodium, potassium, and phosphate concentrations at the end of dialysis did not differ. Alkalemia was less frequent after citrate than conventional dialysis (pH 7.5 in 25% versus 62% of patients; mean pH at end of dialysis, 7.46 +/- 0.06 versus 7.51 +/- 0.07; P < 0.01). Bleeding time at puncture sites was shorter by 30% after citrate compared with dalteparin anticoagulation (5.43 +/- 2.80 versus 7.86 +/- 2.93 minutes; P < 0.001). Activation of platelets, coagulation, and fibrinolysis was modest for both treatments and occurred mainly within the dialyzer during dalteparin treatment and in the vascular-access region during citrate anticoagulation. Citrate-related adverse events were not observed. We conclude that citrate anticoagulation for high-flux hemodialysis is feasible and safe using a simple infusion protocol.

Adult↗

Continuous venovenous hemofiltration with citrate-based replacement fluid: efficacy, safety, and impact on nutrition.

BACKGROUND: Citrate-based continuous venovenous hemofiltration (CVVH) replacement fluids provide effective and simple regional anticoagulation. However, concern over toxicity has limited citrate use, especially at the high filtration rates advocated for better outcomes. We used volumes of 72 L/d in patients at high risk for bleeding and investigated the treatment's efficacy, safety, and clinical results, especially with regard to nutrition supplementation. METHODS: A standard replacement solution (trisodium citrate, 13.3 mmol/L) was infused at up to 3 L/h in predilution CVVH, and ultrafiltration was increased further for net fluid removal. Calcium was repleted centrally. We retrospectively evaluated metabolic control, citrate toxicity, circuit patency, hemorrhagic complications, hemodynamics, vasopressor use, nutrition, renal recovery, and mortality. RESULTS: Seventy-six patients with 766 CVVH patient-days were analyzed. Mean replacement fluid rate was 31 mL/kg/h (35 mmol/h of citrate), with hemofiltration of 35 mL/kg/h (67 +/- 11 L/d). No significant bleeding, citrate toxicity, or hypocalcemia was observed, and 74% required additional alkali therapy. Dialyzer patency was 58% at 48 hours. Control of fluid, electrolytes, and azotemia was excellent (serum creatinine level, 1.7 mg/dL [150 micromol/L]; blood urea nitrogen, 42 mg/dL [15 mmol/L]). Fluid removal permitted protein (1.7 g/kg/d) and calorie (30 kcal/kg/d) nutrition in high fluid volumes. Vasopressor use and central pressures decreased significantly. Cumulative 28-day intensive care unit survival was 58%, and 41% of these patients had renal recovery in the intensive care unit. Thirty percent of the entire cohort survived the hospitalization, and 53% of these patients recovered renal function. CONCLUSION: CVVH with 3 L/h of citrate-based replacement fluid is a safe, efficient, and simple technique in patients at high risk for bleeding. It allows superb control of uremia and fluid balance and thereby permits aggressive nutritional support.

Acute Kidney Injury↗

Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells.

Prostate epithelial cells possess a uniquely limiting mitochondrial (m-) aconitase activity that minimizes their ability to oxidize citrate. These cells also possess uniquely high cellular and mitochondrial zinc levels. Correlations among zinc, citrate, and m-aconitase in prostate indicated that zinc might be an inhibitor of prostate m-aconitase activity and citrate oxidation. The present studies reveal that zinc at near physiological levels inhibited m-aconitase activity of mitochondrial sonicate preparations obtained from rat ventral prostate epithelial cells. Corresponding studies conducted with mitochondrial sonicates of rat kidney cells revealed that zinc also inhibited the kidney m-aconitase activity. However the inhibitory effect of zinc was more sensitive with the prostate m-aconitase activity. Zinc inhibition fit the competitive inhibitor model. The inhibitory effect of zinc occurred only with citrate as substrate and was specific for the citrate --> cis-aconitate reaction. Other cations (Ca2+, Mn2+, Cd2+) did not result in the inhibitory effects obtained with zinc. The presence of endogenous zinc inhibited the m-aconitase activity of the prostate mitochondrial preparations. Kidney preparations that contain lower endogenous zinc levels exhibited no endogenous inhibition of m-aconitase activity. Studies with pig prostate and seminal vesicle mitochondrial preparations also revealed that zinc was a competitive inhibitor against citrate of m-aconitase activity. The effects of zinc on purified beef heart m-aconitase verified the competitive inhibitor action of zinc. In contrast, zinc had no inhibitory effect on purified cytosolic aconitase. These studies reveal for the first time that zinc is a specific inhibitor of m-aconitase of mammalian cells. In prostate epithelial cells, in situ mitochondrial zinc levels inhibit m-aconitase activity, which provides a mechanism by which citrate oxidation is limited.

Aconitate Hydratase↗

Radicicol binds and inhibits mammalian ATP citrate lyase.

Six different biotinylated radicicol derivatives were synthesized as affinity probes for identification of cellular radicicol-binding proteins. Derivatives biotinylated at the C-17 (BR-1) and C-11 (BR-6) positions retained the activity of morphological reversion in v-src-transformed 3Y1 fibroblasts. Two radicicol-binding proteins, 120 and 90-kDa in size, were detected in HeLa cell extracts by employing BR-1 and BR-6, respectively. The 90-kDa protein bound to BR-6 was identified to be Hsp90 by immunoblotting. The 120-kDa protein bound to BR-1 was purified from rabbit reticulocyte lysate, and its internal amino acid sequence was identical to that of human and rat ATP citrate lyase. The identity of the 120-kDa protein as ATP citrate lyase was confirmed by immunoblotting. Interaction between BR-1 and ATP citrate lyase was blocked by radicicol but not by herbimycin A that interacts with Hsp90. These results suggest that radicicol binds the two proteins through different molecular portions of its structure. BR-1-bound ATP citrate lyase isolated from rabbit reticulocyte lysate showed no enzymatic activity. The activity of rat liver ATP citrate lyase was inhibited by radicicol and BR-1 but not by BR-6. Kinetic analysis demonstrated that radicicol was a non-competitive inhibitor of ATP citrate lyase with K(i) values for citrate and ATP of 13 and 7 microm, respectively.

ATP Citrate (pro-S)-Lyase↗

Mono ferrous acid citrate (FeC6O7H2O) as an iron fortificant.

1. Iron absorption from ferrous citrate (monoferrous acid citrate, FeC6H6O7H2O) was studied in normal healthy male and female volunteers using ferrous citrate labelled with radioactive Fe and whole-body counting. Ferrous citrate was either given alone or with a rice-based meal. 2. Fe absorption from ferrous citrate was satisfactory and was comparable to that from ferrous sulphate. 3. Fortification of crude cooking salt with ferrous citrate was not satisfactory due to colour development on storage. Ferrous citrate can, however, serve as an effective Fe fortificant with sugar or wheat flour.

Adult↗

Sensitizing effects of gallium citrate on hyperthermic cell killing in vitro.

The lethal effects of gallium citrate in combination with heat were studied using four cell lines, L5178Y, FM3A, P388 and HeLa. Cells were incubated with different concentrations (0.2 2 mM) of gallium citrate at 37 degrees C for 24 h and heated at a range of temperatures from 40-44 degrees C for various time periods up to 6 h in the absence of gallium citrate. Survival and cell viability were determined by clonogenic assay and the dye-exclusion test, respectively. All of the cell lines tested were insensitive to heat below 41 degrees C, but were very sensitive to heat above 43 degrees C. Gallium citrate was cytotoxic to these cell lines at different levels: P388 and HeLa were far more sensitive than L5178Y and FM3A. The killing effects of heat at 41 degrees C were greatly enhanced by gallium citrate in L5178Y and P388 cells. The Arrhenius analysis for the lethal effect of heat, determined by clonogenic assay, in L5178Y cells showed that the transition temperature was remarkably decreased for the gallium-treated cells from approximately 43 degrees C to 41 degrees C. The mechanism for this decrease in the transition temperature may be attributable to the additional effects of gallium citrate on energy metabolism. Preincubation with 0.05 mM gallium citrate at 37 degrees C for 7 days also enhanced heat sensitization at 41 degrees C in L5178Y. This preincubation condition may correspond to the condition for the continuous infusion of gallium that is clinically used for cancer treatment. In contrast, treatment with gallium did not greatly enhance the sensitivity of FM3A or HeLa cells to heat at 41 degrees C, but the effects of gallium were significant.

Adenosine Triphosphate↗

Differentiation of low-grade gastric MALT lymphoma and high-grade gastric MALT lymphoma: the clinical value of Ga-67 citrate scintigraphy--a pilot study.

Ga-67 citrate scintigraphy has been routinely and extensively used to evaluate non-Hodgkin's lymphoma (NHL) for more than 20 years. Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is by far the most common extranodal primary NHL. Gastric MALT lymphoma can be classified as low-grade (LG) or high-grade (HG). Low-grade gastric MALT lymphoma can be cured by eradication of Helicobacter pylori; but radiotherapy and/or chemotherapy and/or surgery are the major methods of treatment for the HG gastric MALT lymphoma. However, it is difficult to differentiate these two groups by clinical parameters and endoscopic findings. The purpose of this study was to determine whether Ga-67 citrate scintigraphy can distinguish the LG gastric MALT lymphoma from the HG gastric MALT lymphoma. Twenty-one patients (11 men and 10 women ranging in age from 38 to 83 years) with histologically confirmed gastric MALT lymphoma were enrolled. Twelve patients had LG and nine patients had HG. All 21 patients underwent Ga-67 citrate scintigraphy before treatment. The results of Ga-67 citrate scintigraphy were classified as positive or negative. In the LG group, nine patients had negative results and three patients had positive results. In the HG group of nine patients, all patients had positive results. Among the three patients who had positive results in the LG group, the uptake of gastric MALT lymphoma was lower than that of the liver. The Ga-67 citrate scintigraphy is of good clinical value for the differentiation of the LG gastric MALT lymphoma and the HG gastric MALT lymphoma. We think that the major value of Ga-67 citrate scintigraphy will be in following the patients with HG gastric MALT lymphoma after treatment to assess response of therapy and to detect possible recurrence and perhaps in determining transformation from the LG to HG gastric MALT lymphoma. However, further investigation is needed to understand the relationship between the uptake of Ga-67 citrate in gastric MALT lymphoma and transformation.

Adult↗

Effect of K-252a and abscisic acid on the efflux of citrate from soybean roots.

The Al-induced release of organic acid has been suggested as an important mechanism for Al resistance in plants. In this study, the effect of K-252a and abscisic acid (ABA) on the efflux of citrate was investigated in soybean (Glycine max L.) roots. Al initiated citrate efflux from the root apices 30 min after the addition of Al. The Al-triggered efflux of citrate was sensitive to metabolic inhibitors and anion channel inhibitors. Pretreatment or treatment with K-252a, an inhibitor of protein kinase, severely inhibited the Al-induced efflux of citrate accompanying an increase in Al accumulation and intensified Al-induced root growth inhibition. Al-treatment increased the endogenous level of abscisic acid (ABA) in soybean roots in a dose- and time-dependent manner, while K-252a failed to inhibit the Al-induced increase in endogenous ABA. Exogenous application of ABA increased the activity of citrate synthase (EC 4.1.3.7) by 26.2%, and decreased Al accumulation by 32.3%, respectively. ABA-induced increases in citrate efflux and root elongation were suppressed by K-252a, while ABA could not reverse the K-252a effects. Taken together, these results suggest that ABA is probably involved in the early response, after which K-252a-sensitive protein kinases play a key step in regulating the activity of an anion channel, through which citrate is released from the apical cells of soybean roots.

Abscisic Acid↗

Efficacy of oral citrate administration in primary hyperoxaluria.

Urinary citrate is a potent inhibitor of calcium oxalate (CaOx) crystallization, but oral citrate has rarely been used in patients with primary hyperoxaluria (PH). We studied the effect of sodium citrate administration (0.1-0.15 g/kg/day) on urinary citrate excretion and CaOx saturation in seven paediatric patients and the clinical response to long-term treatment (average 4 years) in five patients. Urinary citrate increased from 0.73 to 2.54 mmol/24 h/1.73 m2 and urinary saturation for CaOx (calculated by equil 2) decreased from 11.41 to 6.79 (for both, p < 0.02). Long-term administration of alkali citrate [0.15 g (0.5 mmol)/kg/day] resulted in stable or improved renal function in three and slow deterioration in two partially non-compliant patients. Alkali citrate is effective in patients with PH.

Administration, Oral↗

Trisodium citrate 4%--an alternative to heparin capping of haemodialysis catheters.

BACKGROUND: Central venous catheters (CVCs) continue to be used at a high rate for dialysis access and are frequently complicated by thrombus-related malfunction. Prophylactic locking with an anticoagulant, such as heparin, has become standard practice despite its associated risks. Trisodium citrate (citrate) 4% is an alternative catheter locking anticoagulant. METHODS: The objective was to prospectively study the clinical effectiveness, safety and cost of citrate 4% vs heparin locking by comparing rates of CVC exchanges, thrombolytic use (TPA) and access-associated hospitalizations during two study periods: heparin period (HP) (1 June 2003-15 February 2004) and Citrate Period (CP) 15 March-15 November 2004. Incident catheters evaluated did not overlap the two periods. RESULTS: There were 176 CVC in 121 patients (HP) and 177 CVC in 129 patients (CP). The event rates in incident CVC were: CVC exchange 2.98/1000 days (HP) vs 1.65/1000 days (CP) (P = 0.01); TPA use 5.49/1000 (HP) vs 3.3/1000 days (CP) (P = 0.002); hospitalizations 0.59/1000 days (HP) vs 0.28/1000 days (CP) (P = 0.49). There was a longer time from catheter insertion to requiring CVC exchange (P = 0.04) and TPA (P = 0.006) in the citrate compared with the heparin lock group. Citrate locking costs less than heparin locking but a formal economic analysis including indirect costs was not done. CONCLUSION: Citrate 4% has equivalent or better outcomes with regards to catheter exchange, TPA use and access-related hospitalizations compared with heparin locking. It is a safe and less expensive alternative. Randomized trials comparing these anticoagulants with a control group would definitively determine the optimal haemodialysis catheter locking solution.

Adult↗