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PubMed1995

Absorption of iron dextran from the peritoneal cavity of rats.

We investigated the absorption rate and acute toxicities of intraperitoneal iron dextran in rats. Eighteen Sprague-Dawley rats were divided into three groups (n = 6). The animals were given standard 1.5% Dianeal (group 1) or 1.5% Dianeal containing iron in a concentration of 2 mg/L (group 2) or 10 mg/L (group 3) as iron dextran. First, a predialysis blood sample was obtained, and 25 mL of the designated dialysis solution was instilled into the peritoneal cavity. After a 6-hour cycle the dialysate was drained, and a postdialysis blood sample and specimen of the peritoneum were obtained. The iron concentrations of the dialysis solution, the dialysate, and both serum samples were determined. Histological samples were processed by hematoxylin and eosin and Prussian blue stain. Results of the iron concentration (mg/L) of the dialysis solution, the dialysate, and the percent of the absorbed iron were as follows: group 1: 0.00, 0.20 +/- 0.15, N/A; group 2: 2.24, 0.66 +/- 2.8, 73.8 +/- 11.0; group 3: 9.84, 2.12 +/- 0.62, 80.8 +/- 5.7. The serum iron concentration did not change. No abnormal findings were found histologically. More than 70% of the iron dextran was absorbed from the peritoneal cavity of the rats during a 6-hour peritoneal dialysis exchange. Intraperitoneal iron dextran may be an alternative route of iron delivery.

Absorption↗
PubMed1995

The efficacy of iron dextran for the treatment of iron deficiency in hemodialysis patients.

We prospectively evaluated the efficacy of intravenous iron dextran for the replacement of iron stores in iron deficient hemodialysis patients. Twenty-eight patients with serum ferritin < 100 ng/ml were treated with 100 mg intravenous iron dextran for ten consecutive hemodialysis treatments. Therapy was considered successful if the serum ferritin remained > 100 ng/ml for 4 months after treatment. Mean hematocrit increased from 29.1 +/- 0.9% at baseline to 33.6 +/- 1.8% at ten weeks (p < 0.05). The mean erythropoietin dose decreased from 94.1 +/- 5.3 U/kg body weight per treatment at baseline to 82.6 +/- 4.4 U/kg body weight per treatment at 10 weeks (p < 0.05). The mean serum ferritin at baseline was 38.3 +/- 5.5 ng/ml, at 2 weeks 135.9 +/- 19.7 ng/ml, at 6 weeks 114.1 +/- 22.4 ng/ml, and 86.6 +/- 17.7 ng/ml at 10 weeks. The number of patients at the therapeutic target (serum ferritin > 100 ng/ml) was 13 of 28 at 2 weeks after therapy, 9 of 28 at 6 weeks, and 8 of 28 at 10 weeks. The initial serum ferritin was the variable most predictive of successful therapy. None of 15 patients with baseline serum ferritin less than 28 ng/ml had a serum ferritin > 100 ng/ml at 4 months, compared with 8 of 13 (61%) with initial ferritins > or = 28 ng/ml. Baseline hematocrit and transferrin saturation were not predictive of therapeutic success. In summary, this regimen for administration of intravenous iron dextran resulted in improved erythropoiesis, however, at study completion iron stores remained inadequate in the majority of patients. Baseline serum ferritin < 28 ng/ml was highly predictive of patients who failed to reach the therapeutic target.

Anemia↗
PubMedDate not supplied

Falsely decreased total serum calcium concentration associated with iron dextran injection.

We cared for a patient in whom iron dextran administration interfered with the determination of total serum calcium concentration. An unexpected elevation in serum phosphorus concentration also occurred after the iron dextran infusion. A MEDLINE search from 1966 to present was conducted, and the manufacturer of the iron dextran was contacted for information related to these findings. Several drugs and diseases were found that may decrease serum calcium and increase phosphorus concentrations. We found one anecdotal citation of iron dextran interfering with serum calcium concentrations, but no reports of interference with serum phosphorus concentrations. Doses of iron dextran in excess of 250 mg may cause a false decrease in total calcium concentration more than 4 hours after the infusion is completed. A false increase in serum phosphorus concentrations after the infusion requires further investigation.

Antiviral Agents↗
PubMed1977

Enhancement of survival in acute experimental fowl typhoid in chicks by the administration of iron dextran.

Chicks aged 15 days were infected orally with 10(6-4) living Salmonella gallinarum. Iron from iron dextran or ferric ammonium citrate (DFe and CFe respectively), in doses of 2-0 or 0-4 mg/kg given intramuscularly at the time of infection, had no effect on subsequent mortality compared with infected controls. Increasing the amount of CFe to the maximum (20 mg/kg) that was non-toxic intramuscularly was also ineffective but when the dose of DFe was increased to 20 or 50 mg/kg the survival rate rose sharply. If given at other times in relation to the time of infection, or more frequently, 50 mg/kg or more of DFe was less active. The increased survival rate among infected chicks given 50 mg/kg of DFe at the time of infection was accompanied by decreases in the severity of the morbid changes in the disease, and by reductions of between c 10- to 100-fold in the numbers of viable S gallinarum in the liver, spleen or blood at the height of the acute infection. DFe (50 mg/kg) given at the time of infection also eliminated the difference in the survival rate noted previously between infected chicks fed respectively with diets containing fish or meat meal as the sole source of supplementary protein.

Anemia↗
PubMed1996

Hematologic and erythropoietin responses to iron dextran in the hemodialysis environment.

OBJECTIVE: To investigate the hematologic and economic advantages of using iron dextran as the sole supplemental agent to safely increase and maintain hematocrit levels and iron availability while optimizing erythropoietin dosing in patients on chronic hemodialysis. DESIGN: Iron dextran 100 mg (2 ml) was administered i.v. slow push, undiluted three times per week, sometime during the last 30 minutes of each hemodialysis treatment, until a total required ml (determined by using the package insert's formula) was attained. Maintenance doses of either 25 or 50 mg per week (dependent upon body weight) were administered ongoing to compensate for dialytic and gastrointestinal blood losses. The analysis duration was 12 months. SAMPLE/SETTING: A prospective analysis was performed on 13 clinically stable hemodialysis outpatients in a rural community hospital-based dialysis facility (mean age 56.4 years ranging from 24-76; sample included 9 males, 4 females). METHODS: The means and medians were calculated for each variable: hematocrit, ferritin, transferrin saturation, and erythropoietin dose. A one-tailed paired student t test was performed on doses of erythropoietin at -1 and 6 months, -1 and 9 months, and -1 and 12 months. Cost per patient of iron dextran loading dose and maintenance, as well as cost savings from actual erythropoietin dose reductions, were calculated at 3, 9, and 12 months. Cost savings reflected the cost of iron dextran. RESULTS: After 6 months on the protocol, erythropoietin doses decreased an average of 3100 units per patient with an 8% increase in hematocrit and 66% and 78% increase in transferrin saturation and ferritin, respectively. Based on averages in actual reduced erythropoietin dosing, a savings of +5,070 per patient per year was realized. CONCLUSIONS: This analysis found the use of iron dextran in the hemodialysis setting to be an effective and economic means to maintain hematocrit values and iron availability while optimizing erythropoietin dosing.

Adult↗
PubMed1996

Efficacy of bolus intravenous iron dextran treatment in peritoneal dialysis patients receiving recombinant human erythropoietin.

The efficient use of recombinant human erythropoietin (rHuEPO) requires adequate body stores of iron. In peritoneal dialysis (PD) patients, iron replacement is most commonly administered orally. In this study, we prospectively followed 7 stable PD patients following bolus intravenous infusion of 1 g iron dextran in an outpatient setting. At 12 weeks, significant (p < 0.05) increments in mean hematocrit from 29.13% to 34.85%, transferrin saturation from 10.15% to 29.33%, serum iron from 27.38 to 67.00 micrograms/dL, and serum ferritin from 150.30 to 331.40 ng/mL were observed. Post-treatment, there was less requirement of rHuEPO, and at six months there was a 26% reduction in the mean weekly subcutaneous rHuEPO dose. At 12 weeks, serum albumin increased significantly from 3.50 to 3.76 g/dL (p < 0.05). There was no abnormality in any of the measured liver function tests. No patient developed an adverse or allergic reaction. We concluded that bolus intravenous infusion of iron dextran is an effective and well-tolerated method of repleting iron stores, and will allow a more efficient and economic use of rHuEPO in PD patients.

Adult↗
PubMed1977

Cellular distribution of orally and intramuscularly administered iron dextran in newborn piglets.

Histochemical studies were performed on tissues from piglets of different ages treated orally with iron dextran soon after birth. The mucosal cells in the distal region of the small intestine were heavily laden with stainable iron granules during the first three days after the iron administration. The absorptive epithelial cells are desquamated within seven to ten days after birth. Consequently, the number of iron granules gradually diminishes during the first seven days after treatment and no iron granules are demonstrated 12 days after the administration of iron. The iron dextran complex is pinocytosed in newborn piglets and then transported via the lymphatic system. Thus the sinusoidal lining cells of the body and mesenteric lymph nodes are already heavily laden with iron granules 24 hours after oral treatment. This iron store is released only slowing during the first weeks of life. Great amounts of iron granules are demonstrated in the liver and spleen macrophages during the first week after the administration of iron. Due to the rapid utilization of iron in growing piglets these iron stores diminish sharply during the weeks following birth. The distribution of stainable iron in the lymph nodes, liver and spleen seven days after intramuscular injection of iron dextran in newborn piglets was comparable to that for oral administration at that stage of the experiment.

Administration, Oral↗
PubMedDate not supplied

Chronic administration of iron dextran into the peritoneal cavity of rats.

OBJECTIVE: To determine the influence of chronic iron dextran administrations into the peritoneal cavity of rats on function and anatomy of the peritoneal membrane, as well as on erythropoiesis and serum iron. DESIGN: Prospective randomized animal study. SETTING: Animal laboratory. ANIMALS: 36 Sprague-Dawley rats. INTERVENTIONS: The rats were divided into three groups (n = 12). The animals were given standard 1.5% Dianeal (control group) or 1.5% Dianeal containing iron dextran in a concentration of 2 mg/L [low-dose group (LDG)] or 10 mg/L [high-dose group (HDG)]. MAIN OUTCOME MEASURES: On the 8th day, at 3 months, and at 6 months a 2-hour peritoneal equilibration test (PET) and blood tests including hematocrit, serum iron, and total iron-binding capacity (TIBC) were done. After the final PET at 6 months, the peritoneal membrane was evaluated by gross inspection and by light microscopy. RESULTS: Hematocrit and serum iron levels increased only in the HDG and LDG. Peritoneal transport of small solutes decreased significantly in the HDG compared to baseline. All cases of the HDG group revealed peritoneal adhesions and fibrosis around the peritoneal catheter as well as massive iron deposits on the peritoneum. Similar but less pronounced changes were found in the LDG. CONCLUSIONS: These findings suggest an efficient absorption of iron from the peritoneal cavity of rats, however, dialysate iron dextran concentrations of 2 mg/L or greater are toxic to the peritoneal membrane. Therefore, future studies should be performed to determine the minimal effective and nontoxic iron dextran concentrations for intraperitoneal administration.

Animals↗
PubMed1979

Endotoxin determination in viscous opaque solutions of iron dextran by Limulus amebocyte lysate.

LAL would not form a clot when mixed with a viscous, opaque parenteral preparation of iron dextran spiked with endotoxin. However, recoverable precipitate could be obtained by diluting the LAL iron dextran mixture with PBS and centrifuging. Although the pellet so formed was red colored the protein present could be quantitated by dissolving it in a Coomassie Blue stain solution. The very rapid change in color from reddish black to deep blue was measured quantitatively in a spectrophotometer and was sigmoidally related to the amount of endotoxin used to spike the iron dextran. This method is suggested to be generally useful to measure quantitatively endotoxin concentrations too low to form a clot with LAL but high enough to precipitate recoverable protein from LAL.

Animals↗
PubMed1998

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO).

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.

Aged↗
PubMedDate not supplied

The absence of toxicity in intraperitoneal iron dextran administration: a functional and histological analysis.

OBJECTIVE: To determine the influence of iron dextran intraperitoneal administration on the function and histology of the peritoneum in rats undergoing chronic peritoneal dialysis. DESIGN: Prospective, randomized experimental study. MATERIALS: Fifty-four Sprague-Dawley rats were divided into five groups: 3 study groups--high dose group (H), n = 12; intermediate dose (M), n = 12; and low dose group (L), n = 12--a dialysis control group (D), n = 12; and a tissue control (C), n = 7. INTERVENTIONS: The study groups were given Dianeal containing iron dextran in a concentration of 0.5, 0.25, and 0.125 mg/L (groups H, M, and L respectively). Group D was given standard Dianeal. Group C was never dialyzed. MAIN OUTCOME MEASURES: A 2-hour peritoneal equilibrium test (PET) was performed on the eighth day, at 3 months, and at 6 months. After the final PET, the animals were sacrificed and the peritoneal membrane was evaluated by gross inspection and light microscopy (silver, prussian blue, and trichrome staining). RESULTS: Peritoneal transport of small solutes followed the same pattern in all groups, increasing over time. The peritonitis index was similar in the groups. No iron deposits or morphologic differences were seen in the gross inspection of the peritoneal cavity. No peritoneal iron deposition was detected in the histological analysis with prussian blue staining. No differences were noted in the light microscopic analysis of the mesothelial cell layer (silver staining), nor did the morphometric analysis of the submesothelial space show any differences in thickness between the groups. CONCLUSION: These findings suggest the absence of toxic effects of iron dextran on the peritoneal cavity of rats in the concentrations studied. Further studies should be performed to evaluate the effectiveness of these dosages delivered intraperitoneally to maintain iron homeostasis.

Animals↗
PubMed1998

Maintaining iron balance with total-dose infusion of intravenous iron dextran.

Recombinant human erythropoietin (rHuEPO) is an important component of anemia management in patients with chronic renal failure, however, it can lead to functional iron deficiency (FID). Patients with FID are less likely to have an optimal response to rHuEPO (Cavill et al., 1997). Intravenous (i.v.) iron dextran is often required to replace iron losses, maintain adequate iron stores, and correct iron deficiency. The following article provides a rationale for the use of IV iron dextran and details one unit's protocol and experience with its use.

Anemia, Iron-Deficiency↗