A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.     

Limitation of thrombin generation, platelet activation, and inflammation by elimination of cardiotomy suction in patients undergoing coronary artery bypass grafting treated with heparin-bonded circuits

OBJECTIVE: Reports evaluating the efficacy of heparin-bonded circuits to blunt inflammation, platelet dysfunction, and thrombin generation in response to cardiopulmonary bypass have varied. We hypothesized that this variability may in part be related to the use of cardiotomy suction, which has been demonstrated to reintroduce procoagulant and proinflammatory factors into the systemic circulation during cardiopulmonary bypass. A prospective, randomized study was undertaken to evaluate the specific effects of cardiotomy suction. METHODS: Thirty-six patients undergoing first-time, nonemergency coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to one of three treatment groups: group I, non-heparin-bonded circuits with the use of cardiotomy suction (n = 12); group II, Duraflo II (BCR-3500; Jostra Bentley Corp, Irvine, Calif) heparin-bonded circuits with cardiotomy suction (n = 12); and group III, Duraflo II heparin-bonded circuits without cardiotomy suction (n = 12). Thrombin generation, neutrophil activation (polymorphonuclear elastase), platelet activation (beta-thromboglobulin), and neuronal injury (neuron-specific enolase) were analyzed by enzyme-linked immunosorbent assays after cardiopulmonary bypass and compared with prebypass levels. Results are presented as mean +/- SEM. RESULTS: Prebypass levels of all markers were similar among treatment groups. However, postbypass levels were significantly and consistently highest in group I relative to groups II and III. Thrombin generation levels were 5.0 +/- 0.9 nmol/L in group I, 3.0 +/- 0.6 nmol/L in group II, and 1.5 +/- 0.1 nmol/L in group III (P <.05 vs group II and P <.001 vs group I). Polymorphonuclear elastase levels were 307 +/- 64 microg/L in group I, 128 +/- 24 microg/L in group II (P <.05 vs group I), and 75 +/- 14 microg/L in group III (P <.001 vs group I). beta-Thromboglobulin levels were 2692 +/- 401 IU/mL in group I, 912 +/- 99 IU/mL in group II (P =.001 vs group I), and 646 +/- 133 IU/mL in group III (P =.001 vs group I). Neuron-specific enolase levels were 9.8 +/- 0.9 ng/mL in group I, 10.5 +/- 1.6 ng/mL in group II, and 4.2 +/- 0.5 ng/mL in group III (P =.001 vs groups I and II). CONCLUSIONS: Use of cardiotomy suction resulted in significant increases in thrombin, neutrophil, and platelet activation, as well as the release of neuron-specific enolase, after cardiopulmonary bypass. Limiting increases in these markers would be best accomplished by eliminating cardiotomy suction and routinely using heparin-bonded circuits whenever possible.     

Serum concentration of adhesion molecules in postoperative biliary atresia patients: relationship to disease activity and cirrhosis

BACKGROUND/PURPOSE: Biliary atresia (BA) is associated with progressive liver fibrosis, which may be mediated by immunologic abnormalities involving adhesion molecules. This study investigates the relationship between serum intercellular adhesion molecule-1 (sICAM-1), serum vascular cell adhesion molecule-1 (sVCAM-1), and the clinical and histologic severity of BA. METHODS: Serum ICAM-1 and VCAM-1 levels were measured by enzyme-linked immunosorbent assay in 35 patients with BA and 20 healthy controls. Standard liver function tests (LFTs), and frozen section liver biopsy specimens were used to determine liver status. On the basis of LFT results, the BA patients were classified into group I (n = 10; normal LFTs), group II (n = 15; elevated LFTs, anicteric), and group III (n = 10; elevated LFTs, icteric). Eight subjects in group II, and all subjects in group III had portal hypertension (PH). RESULTS: sICAM-1 levels were significantly elevated in group III (1760.0 +/- 717.5 ng/mL) compared with group II (555.1 +/- 199.4 ng/mL), group I (272.1 +/- 59.9 ng/mL) and controls (256.3 +/- 71.6 ng/mL). Although sVCAM-1 levels were significantly elevated in group III (1932.9 +/- 282.6 ng/mL) compared with group II (1054.3 +/- 297.0 ng/mL), group I (605.4 +/- 112.4 ng/mL), and controls (616.0 +/- 112.0 ng/mL; P <.001), there was no statistically significant difference between groups I, II, or controls. sVCAM-1 levels were elevated significantly in BA subjects in group II with PH (1253.0 +/- 245.1 ng/mL) compared with those who did not have PH (827.3 +/- 151.7 ng/mL; P <.01). PH did not affect sICAM-1 levels. There was strong expression of ICAM-1 and VCAM-1 in proliferating bile ductules, endothelial cells, and liver cells in group III compared with group II and controls. CONCLUSIONS: In BA, sICAM-1 and sVCAM-1 levels could be useful as markers of end-stage liver disease, with sVCAM-1 being more specific for PH. Induction of ICAM-1 and VCAM-1 may be an important factor in the development of cirrhosis.     

Comparison of intravenous ascorbic acid versus intravenous iron for functional iron deficiency in hemodialysis patients

The effect of intravenous ascorbic acid was compared with that of intravenous iron in the treatment of functional iron deficiency, as defined as serum ferritin levels over 300 ng/ml and serum iron levels below 50 microg/dl, in patients on chronic hemodialysis. Thirteen patients on chronic hemodialysis with functional iron deficiency received intravenous injections of ascorbic acid, 100 mg, three times a week, after hemodialysis. The therapy was continued until serum ferritin decreased to below 300 ng/ml (3 months at the maximum). The iron and control group were composed of patients who had serum iron levels below 50 microg/dl within 3 months after serum ferritin rose to over 300 ng/ml. Seven patients with the iron group received more than a total of 10 intravenous injections of saccharated ferric oxide (40 mg/dose) after hemodialysis, and seven patients with the control group received no iron preparation during the 3 months. In the ascorbic acid group, while hemoglobin did not change from 10.9 +/- 0.5 g/dl (mean +/- SE) during the three-month period, serum iron increased significantly from 37 +/- 4 microg/dl to 49 +/- 4 microg/dl after one month (p<0.01), and remained elevated until the end of the three-month period. Serum ferritin decreased significantly from 607 +/- 118 ng/ml to 354 +/- 30 ng/ml after 3 months (p<0.01). In the iron group, hemoglobin and serum iron increased significantly from the respective pre-treatment levels during the 2-month period, and serum ferritin rose significantly after 3 months. In the control group, hemoglobin, serum iron and ferritin levels decreased significantly from the respective pre-treatment levels during the 3 months. The recombinant erythropoietin dose remained stable for three months in the ascorbic acid, iron, and control groups, respectively. These results suggest that in hemodialysis patients with a functional iron deficiency, treatment with intravenous ascorbic acid can prevent iron overload due to treatment with intravenous iron, and provide a useful adjuvant means of maintaining hemoglobin and serum iron levels.     

Melatonin corrects reticuloendothelial blockade and iron status in haemodialysed patients

AIM: Treatment of anaemia in haemodialysed patients in the setting of inflammation usually displays high levels of serum ferritin (>800 ng/mL) and low transferrin saturation (TSAT) (<20%) despite i.v. iron supplementation, thus proving iron trapping in the reticuloendothelial system. Melatonin has been reported to reduce cytokine production and, in dialysis patients, to prevent oxidative stress resulting from iron and erythropoietin treatment. METHOD: In this study, we evaluated a group of 10 patients undergoing haemodialysis who displayed elevated serum ferritin (981 +/- 44.6 ng/mL) and TSAT <20% (15.6 +/- 3.8%) after having received 1.2 g of i.v. iron dextran over a period of 8 weeks. These patients received oral melatonin, 6 mg/day at night for 30 days. RESULTS: After this treatment, all of them markedly increased TSAT values, reaching 35.5 +/- 6.7% (P < 0.0001 vs basal values). In addition, ferritin values decreased to 754.4 +/- 263.7 ng/mL (P < 0.05), and serum iron dramatically increased in all of the patients under study (42.4 +/- 9.4 vs 109.7 +/- 24.3 microg/dL; P < 0.0001). Values for haematocrit (28.6 +/- 2.7 vs 31.9 +/- 3.57%; P < 0.05) and haemoglobin (9.19 +/- 0.97 vs 10.04 +/- 1.29 g/dL; P < 0.05) were also improved. Measurements were then repeated 2 weeks after melatonin withdrawal, showing an impressive decrease in TSAT (16.4 +/- 5.3%; P < 0.00001) and serum iron (48 +/- 14.7 microg/dL; P < 0.0001) values and an almost significant increase in ferritin values (954.4 +/- 86 ng/mL; P < 0.054). CONCLUSION: The present study demonstrates that melatonin may strongly correct the reticuloendothelial blockade seen in dialysis patients under an inflammatory status, thus allowing a better management of iron derangements and renal anaemia.     

The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney disease

BACKGROUND: Provision of adequate iron to support erythropoiesis in patients with chronic kidney disease (CKD) is time consuming and may present adherence problems for patients in the outpatient setting. We studied an accelerated regimen of high-dose intravenous iron sucrose therapy in a cohort of iron-deficient, anemic CKD patients. METHODS: Intravenous iron sucrose 500 mg was infused over three hours on two consecutive days in 107 CKD patients (glomerular filtration rate, 32.3 +/- 19.6 mL/min/1.73m2, baseline hemoglobin 10.2 +/- 1.7 g/dL). Iron indices (transferrin saturation, ferritin) were measured at baseline and at two and seven days after completion of the iron regimen. Blood pressures were monitored immediately prior to, and hourly throughout the iron sucrose infusions. RESULTS: Transferrin saturation and serum ferritin increased from 18.5 +/- 8.5% and 177 +/- 123.8 ng/mL at baseline to 40.2 +/- 22.3% and 811 +/- 294.1 ng/mL in 102 evaluated patients (P < 0.015). In 55 patients with additional measurements at 7 days post-dosing, the transferrin saturation and ferritin had fallen to 26.3 +/- 10.6% and 691 +/- 261.8 ng/mL (P < 0.015 compared to two days' post-dose). Blood pressure rose slightly, but not significantly, throughout the infusions, and altering the infusion rate was not necessary. Two patients had seven adverse events that were considered related to iron sucrose. CONCLUSION: An accelerated regimen of high-dose intravenous iron sucrose therapy in CKD patients is safe and effective in restoring iron stores, and may potentially save time and improve patient adherence.     

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.     

Comparison of the effects of on-pump versus off-pump coronary artery bypass surgery on serum prostate-specific antigen levels

AIM: To compare the effects of coronary artery bypass operation with or without extracorporeal circulation on serum total prostate-specific antigen levels. METHODS: Seventy-six men with a mean age of 57.04+/-9.27 years (range 44-77 years), who underwent coronary artery bypass surgery were enrolled to the study. In 50 patients (Group I), coronary revascularization was performed using extracorporeal circulation, and in 26 patients (Group II) coronary bypass grafting was performed on the beating heart without using extracorporeal circulation. All the patients had serum total prostate-specific antigen levels measured preoperatively and twice postoperatively in the first and fifth postoperative days. Differences in mean total prostate-specific antigen levels between the two groups in the postoperative period were analysed. RESULTS: The mean preoperative total prostate-specific antigen levels in Group I and Group II were 1.28+/-1.13 ng/mL and 1.11+/-0.93 ng/mL, respectively, and there was no significant difference in the preoperative total prostate-specific antigen values between the two groups (P=0.519). In Group I, postoperative means were 4.96+/-6.29 ng/mL and 5.86+/-9.09 ng/mL in the first and fifth days, respectively (P=0.0001, P=0.0001). Total prostate-specific antigen means in the same postoperative period for Group II were 2.13+/-2.72 ng/mL and 2.00+/-2.20 ng/mL, respectively (P=0.014, P=0.024). The comparison of total postoperative prostate-specific antigen levels between the groups showed significantly higher elevation in Group I (postoperative day 1: P=0.013; day 5: P=0.05). CONCLUSIONS: Coronary revascularization can cause a statistically significant rise in serum total prostate-specific antigen levels. This rise is more marked in patients undergoing conventional coronary revascularization.     

The influence of hepatitis C and iron replacement therapy on plasma pentosidine levels in haemodialysis patients.

BACKGROUND: Chronic liver disease and intravenous (i.v.) iron therapy can enhance oxidative stress. The aim of this study was to assess the influence of hepatitis C virus (HCV) and i.v. iron administration on oxidative stress in chronic haemodialysis (HD) patients. METHODS: A total of 115 HD patients (47% males, age 47 +/- 13 years) were placed in two groups according to the presence (HCV(+)) or absence (HCV(-)) of serum antibodies against HCV. Plasma pentosidine, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and alanine aminotransferase (ALT) levels were measured. The patients were also analysed according to the tertiles of serum levels of ferritin: group 1 (ferritin <380 ng/ml), group 2 (ferritin 380-750 ng/ml) and group 3 (ferritin >750 ng/ml). The cumulative iron dose was recorded during 6 months prior to the study. RESULTS: HCV(+) patients had significantly higher levels of plasma pentosidine and ALT than HCV(-) patients. Age, gender, serum albumin, IL-6 and hsCRP did not differ according to HCV serology. The levels of pentosidine were related to the ferritin levels and were significantly higher in group 3 compared with group 1. Moreover, the cumulative dose of iron was significantly higher in group 3 than in group 1. Plasma pentosidine showed a positive correlation with age, HCV and ferritin. In a stepwise backward multiple regression model, age and HCV were independent predictors of pentosidine levels. CONCLUSION: HCV in HD patients is associated with increased pentosidine levels, possibly reflecting increased oxidative stress. The association between pentosidine and ferritin levels may suggest an impact of i.v. iron therapy.     

Effect of repeated intravenous iron administration in haemodialysis patients on serum 8-hydroxy-2'-deoxyguanosine levels.

BACKGROUND: Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients. METHODS: Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks. RESULTS: At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner. CONCLUSIONS: Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.     

Zinc levels after iron supplementation in patients with chronic kidney disease.

OBJECTIVE: The goal of this study was to evaluate the effects of iron supplementation on zinc distribution in nondialyzed chronic kidney disease (CKD) patients. DESIGN: Prospective nonrandomized observational study. SETTING: Outpatients of the Nephrology Division at Federal University of S?o Paulo. PATIENTS: Zinc and iron status of 38 nondialyzed patients (63% male; creatinine clearance, 34.5+/-13.3 mL/min/1.73 m2) was evaluated before and after 3 intramuscular injections of 100 mg iron each. MAIN OUTCOME MEASURES: The following parameters were analyzed: erythrocytes and plasma zinc, zinc protoporphyrin (ZPP), plasma ferritin, transferrin saturation (TFS), and total iron. The patients' diets were analyzed by the Association of Official Analytical Chemists method for macronutrients, and neutron activation analysis was used for iron and zinc concentration determinations. RESULTS: Ferritin and TFS increased from 86.3+/-67.5 ng/mL to 105.4+/-63.7 ng/mL and from 19.5+/-7.4% to 23.2+/-6.7% (P <.05), respectively, after iron supplementation. Absolute iron deficiency (ferritin <100 microg/L and TFS <20%) was present in 41% of the patients and decreased to 15.7% after iron treatment. In comparison with baseline values (76.4+/-16.7 microg/dL), there were no significant changes in plasma zinc levels, but after supplementation the number of patients with low plasma zinc levels decreased from 46.1% to 23.7% (P =.08). At baseline, erythrocyte zinc was 49.0+/-7.6 microg Zn/gHb, and 76.3% of the patients had high erythrocyte zinc concentration. After iron treatment, erythrocyte zinc decreased to 45.5+/-7.3 microg Zn/gHb (P =.001). No significant change was observed in ZPP concentration. The analysis of the diet showed energy and protein intakes of 26.2+/-7.1 kcal/kg/day and 0.89+/-0.2 g/kg/day, respectively, and a low intake of both iron and zinc. CONCLUSIONS: This study suggests that iron deficiency may contribute to the inadequate distribution of zinc in patients with CKD and that iron supplementation may decrease the abnormal elevated erythrocyte zinc levels of these patients.     

Intraoperative amiodarone as prophylaxis against atrial fibrillation after coronary operations

BACKGROUND: New onset of atrial fibrillation is a frequent complication after coronary artery bypass grafting and is a major cause of postoperative morbidity. Preoperative oral treatment with amiodarone hydrochloride has been shown to be efficacious as prophylaxis. The present study investigated whether intraoperative use of intravenous amiodarone has a preventive effect on the incidence of atrial fibrillation after coronary revascularization. METHODS: In a prospective study, 150 consecutive patients (mean age, 63 +/- 8 years; 132 men and 18 women) undergoing coronary artery bypass grafting were randomly assigned to one of three groups. Two groups received different doses of intravenous amiodarone (group I, 300-mg bolus and 20 mg x kg(-1) x day(-1) for 3 days; group II, 150-mg bolus and 10 mg x kg(-1) x day(-1) for 3 days) after aortic cross-clamping and one group, placebo (group III). Continuous electrocardiographic online monitoring was performed for 10 days. Arrhythmias were analyzed with respect to type, frequency, duration, and clinical relevance. RESULTS: New onset of atrial fibrillation occurred in 24% of patients in group I, 28% in group II, and 34% in group III (p = not significant). Atrial fibrillation with a rapid ventricular response (>120 beats per minute) was significantly more frequent in the control group (group I, 14%; group II, 24%; group III, 32%; p < 0.05, group I versus group III) and appeared significantly earlier (group I, day 4.3 +/- 2.5; group II, day 4.8 +/- 2.9; group III, day 2.6 +/- 1.3; p < 0.05, group III versus groups I and II). Temporary atrial pacing because of bradycardia (<60 beats per minute) was necessary significantly more often in group I (group I, 48%; group II, 40%; group III, 28%; p < 0.05, group I versus group III). Early mortality rate (group I, 4%; group II, 2%; group III, 4%), rate of perioperative complications (group I, 14%; group II, 20%; group III, 14%), and duration of hospital stay (group I, 14.0 days; group II, 14.4 days; group III, 14.7 days) were not different between groups. CONCLUSIONS: Intraoperative prophylactic use of amiodarone does not prevent new onset of atrial fibrillation in patients undergoing coronary artery bypass grafting and had no effect on outcome. Therefore, intraoperative prophylactic treatment with amiodarone at the tested doses does not appear to be justified.     

Post-haemodilution anaemia in paediatric cardiac surgery: benefit of intravenous iron therapy

OBJECTIVE: Anaemia is the main complication following haemodilution in paediatric cardiac surgery. Iron oral therapy is ineffective to improve anaemia. The aim of this study is to assess the effect of a single dose of intravenous iron saccharate Venofer. STUDY DESIGN: Open, randomized. PATIENTS AND METHODS: 93 patients were randomized in two groups. The first one is the control group without iron supplementation and the second one received a 5 mg/kg injection of Venofer administered at day 1. Three biological factors were studied on day 1 and day 5 following surgery: haemoglobin, ferrritin and reticulocyte rate. Student test was used for statistical analysis of results. RESULTS: Age, weight, haemoglobin, ferritine and reticulocyte on day 1 were similar in both group (no significant difference). On day 5 ferritin was higher in the treated group 215+/-87 vs 101+/-55 mug/l in the non treated group (P<0.001). Reticulocyte rate was also higher in the treated group 3.25+/-1.16 vs 2.65+/-0.97% (P<0.005) in the untreated group. CONCLUSION: Postoperative systemic inflammation is probably the factor which impaired the effect of oral iron therapy. Parenteral iron may act by treating a functional iron deficiency and/or by increasing endogenous erythropoietin synthesis. Faster reversibility of anaemia following iron injection improves quality of the postoperative recovery.     

Effect of naloxone infusion on analgesia and respiratory depression after epidural fentanyl

The efficacy of two dosage regimens of intravenous naloxone were compared to avoid nonrespiratory side effects and respiratory depression and yet to preserve analgesia (maximum tolerance to periostial pressure over the tibia) after administration of 200 micrograms epidural fentanyl. Three groups of eight patients were studied: group 1 patients received a loading dose of 0.4 mg IV naloxone followed by naloxone infusion at a rate of 10 micrograms.kg-1.hr-1. Group II patients received a loading dose of 0.2 micrograms naloxone followed by a naloxone infusion at a rate of 5 micrograms.kg-1.hr-1. Group III patients received a saline infusion at a rate of 20 ml/hr. Epidural fentanyl significantly increased tolerance to periostial pain in all three groups (respectively, +38 +/- 20%, +36 +/- 16%, and +35 +/- 14%) (mean +/- SD; P less than 0.05). The naloxone infusion significantly reduced this effect in groups I and II, respectively, -40 +/- 20% and -37 +/- 28% below prenaloxone levels) (P less than 0.05). Nonrespiratory side effects were also reversed in groups I and II. In group III, neither periostial analgesia nor nonrespiratory side effects were affected. The baseline slopes of VE/PETCO2 were 2.34 +/- 1.01, 2.14 +/- 0.66, and 2.68 +/- 1.14 L.min-1.mm Hg-1, respectively, in groups I, II, and III. Epidural fentanyl significantly decreased the slope below baseline levels in each group: -21 +/- 16%, -22 +/- 17%, and -19 +/- 32%, respectively, in groups I, II and III.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of parenteral iron administration for HCV-positive hemodialysis patients

BACKGROUND: It is well recognized that parenteral iron administration is recommended for hemodialysis (HD) patients treated with rHuEPO. On the other hand, hepatic iron concentration increases in chronic hepatitis C, and iron reduction improves serum transaminase levels in these patients. METHODS: We compared the rHuEPO doses with hematological parameters in HCV-positive (n = 7) and HCV-negative (n = 32) HD patients when parenteral low-dose iron was administered for one year (target ferritin level: 200-300 ng/ml, target hematocrit level: 30-33%). RESULTS: None of the parameters was significantly different between the groups at the start of the study. One year later, levels of hematocrit and serum ferritin significantly increased compared with those at the start in each group (HCV-positive group: 28.0 +/- 2.7-->31.3 +/- 1.5%, p < 0.01, 119.3 +/- 171.9-->303.3 +/- 77.7 ng/ml, p < 0.05, respectively, HCV-negative group: 26.8 +/- 2.2-->30.0 +/- 3.5%, p < 0.01, 69.8 +/- 100.5-->278.4 +/- 66.4 ng/ml, p < 0.01, respectively). Serum transaminase levels were not significantly different between the start and end points in the HCV-positive group, but 2 patients showed an increase in these levels. In the HCV-negative group, the rHuEPO dose at the end point was significantly reduced compared with that at the start (4,875 +/- 2,089-->4,031 +/- 2,203 IU/W, p < 0.05). In the HCV-positive group, however, it was difficult to reduce the rHuEPO dose in order to maintain the target hematocrit level (4,071 +/- 1,134-->3,857 +/- 1,464 IU/W, NS). CONCLUSION: We suggested that rHuEPO should be used together with parenteral iron administration, even in HCV-positive HD patients, because it is safe at low doses under careful observation.     

Red cell lipid peroxidation and antioxidant system in haemodialysed patients: Influence of recombinant human erythropoietin (r-HuEPO) treatment

In order to determine the role of correcting anaemia with r-HuEPO on susceptibility of red cell to lipid peroxidation, 15 patients on maintenance haemodialysis treated with r-HuEPO for at least one year (group I), 15 patients on maintenance haemodialysis without r-HuEPO (group II) and 30 persons as a control group (group III) were included in the study. We measured erythrocyte superoxide dismutase (e-SOD), erythrocyte catalase (e-CAT) activities, plasma malonyldialdehyde (p-MDA) and serum vitamin E levels in all patients. The healthy controls (group III) had significantly lower levels of p-MDA in comparison to those measured in haemodialysed patients (groups I–II) (p<0.0001). e-SOD activity in group III was significantly higher than in groups I and II, respectively (p<0.0001 and p<0.00001), and e-SOD activity was significantly lower in group II than in group I (p<0.0001). e-CAT activity in group III was higher than in groups I and II, respectively (p<0.0001 and p<0.00001) and it was significantly lower in group II than in group I (p<0.0001). Vitamin E concentration in group III was lower than in group I and group II, respectively (p<0.0001 and p<0.0001). But there is no difference between groups I and II. This study suggests that r-HuEPO therapy improves anaemia by decreasing lipid peroxidation and increasing antioxidant activity.     

Predictive value of troponin T levels for ischemic heart disease and mortality in patients on hemodialysis

BACKGROUND: Serum cardiac troponin T (cTnT) levels are elevated in a high percentage of hemodialysis (HD) patients and as a result, they have been considered low specificity for ischemic heart disease (IHD). Recently, several authors have indicated the value of cTnT as a marker of IHD and left ventricular hypertrophy (LVH), as well as a mortality predictor. We try to establish the value of cTnT as an IHD marker and a mortality predictor in our patients on HD. SUBJECTS AND METHODS: Fifty-eight HD patients were prospectively studied from October 2000 to April 2002. Clinical and laboratory evaluations, including cTnT, C-reactive protein (CRP) and N terminal fragment of brain natriuretic peptide (pro-BNP) levels, were performed at the beginning of the study and at 6 and 18 months. HD patients with two or more cTnT measurements were classified in four groups: group I with all levels <0.04 ng/mL; group II with all levels between 0.04 and 0.1 ng/mL; group III with all levels >/=0.1 ng/mL; and group IV including those patients in whom cTnT levels increased during follow-up, switching from one group to another (from <0.04 to 0.04-0.1 or from 0.4-0.1 to >0.1 ng/mL). RESULTS: Mean and median cTnT levels were 0.07 +/- 0.09 and 0.04 ng/mL, respectively. Of clinically stable dialysis patients 15.5% had cTnT levels >0.1 ng/mL. In the stepwise multiple regression analysis, the subset of variables best explaining cTnT levels were pro-BNP levels, history of IHD and residual diuresis volume (r2=0.45). The analysis of variance (ANOVA linear regression analysis for repeated measures) showed an increase in cTnT and pro-BNP levels (significantly from 18 months). cTnT and CPR levels were the only variables predicting mortality (Cox's proportional hazards model). When patients were analyzed according to cTnT groups during the follow-up, no patient in group I (n=23) and only one patient in group II (n=11) experienced IHD; three patients in group III (n=12) had been diagnosed with IHD at the start of the study, and five patients in group IV (n=16) developed de novo IHD. CONCLUSIONS: Of patients on HD 15.5% had cTnT levels >0.1 ng/mL. The main variables associated with cTnT levels were IHD, pro-BNP levels and residual diuresis. cTnT and pro-BNP levels tended to increase with time on dialysis. cTnT together with CRP levels were the best mortality predictors in our HD patients. The stability over time of cTnT levels within normal ranges (<0.1 ng/mL) suggests a very low risk of subsequent IHD development, while a progressive and sustained increase in cTnT levels suggests a high risk of IHD development.     

Elevated cardiac troponin T in hemodialysis patients receiving more intravenous iron sucrose

Elevated cardiac troponin T (cTnT) has been associated with shorter survival in hemodialysis patients. Moreover, intravenous (IV) iron treatment has been held responsible for oxidative stress and accelerated atherosclerosis in these patients. In the present study, we investigated the relationship between cTnT concentration, IV iron treatment, and parameters of iron status. In addition, parameters of oxidative stress, inflammation, and atherosclerosis were evaluated. Predialysis blood samples of 78 chronic hemodialysis patients were analyzed for cTnT, malondialdehyde, creatine kinase (CK), and CK-isoenzyme MB (CK-MB). In addition, the mean value of predialysis serum samples collected during the last year, were considered for homocysteine, ferritin, iron, iron binding capacity, blood cell counts, blood urea nitrogen, creatinine, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), calcium, phosphate, iPTH, cholesterol, and triglyceride. The quantity of IV iron sucrose administered during the last two years was counted from the patients' files. Echocardiography, all events related to ischemic heart disease, and urine volume were also recorded. Elevated cTnT levels (> or =0.10 ng/mL) were found in 18 patients (23.1%). The amount of iron administered was 2264+/-1871 mg with a range 0-7000 mg. Patients with elevated cTnT levels received more IV iron than those with normal cTnT (3692+/-1771 vs. 1761+/-1595 mg, p<0.001). The serum ferritin level was higher in patients with elevated cTnT (median levels; 477 vs. 288 ng/mL; P<0.05). Patients with elevated cTnT were longer on dialysis compared to those with normal levels (median times; 35.5 vs. 15 months, P<0.01) and regression analysis identified the amount of administered iron as an independent factor for elevated cTnT (P<0.01). Intravenous iron treatment and high ferritin concentration are related to high cTnT level, which has previously been incriminated as a survival marker in hemodialysis patients.     

Timing of steroid treatment is important for cerebral protection during cardiopulmonary bypass and circulatory arrest: minimal protection of pump prime methylprednisolone.

OBJECTIVES: The contact of cardiopulmonary bypass surface and patient's blood activates systemic inflammatory response which aggravates ischemia-reperfusion injury. This study evaluates the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on cerebral protection using different steroid administration protocols. METHODS: Eighteen (n=6/group) 4 week-old piglets were divided in three groups. Methylprednisolone (30 mg/kg) was administered intravenously 4 h prior to CPB in Group I, or added in pump prime in group II. Group III received no steroid. All animals were cooled to 15 degrees C followed by 100 min of DHCA, then rewarmed over 40 min and sacrificed 6 h after CPB. Post-operative weight gain, bioelectrical impedance, colloid oncotic pressure (COP) and interleukin-6 (IL-6) were evaluated. Determination of cerebral trypan blue and immunohistochemical assays of transforming growth factor (TGF)-beta1 and caspase-3 activities were performed. RESULTS: Post-operative % weight gain (13.0+/-3.8 (I) versus 26.4+/-9.9 (II) versus 22.6+/-6.4 (III), P=0.02); % bioimpedance reduction (14.5+/-8.0 (I) versus 38.3+/-13.3 (II) versus 30.5+/-8.0 (III), P=0.003); mean COP (mmHg) (14.9+/-1.8 (I) versus 10.9+/-2.0 (II) versus 6.5+/-1.8 (III), P=0.0001) and systemic IL-6 levels (pg/ml) (208.2+/-353.0 (I) versus 1562.1+/-1111.4 (II) versus 1712.3+/-533.2 (III), P=0.01) were significantly different between the groups. Spectrophotometric analysis of cerebral trypan blue (ng/g dry weight) was significantly different between the groups (0.0053+/-0.0010 (I) versus 0.0096+/-0.0026 (II) versus 0.0090+/-0.0019 (III), P=0.004). TGF-beta1 scores were 3.3+/-0.8 (I) versus 1.5+/-0.8 (II) versus 1.5+/-0.5 (III), P<0.05, groups I versus II and I versus III. Remarkable perivascular caspase-3 activity was observed in groups II and III. CONCLUSION: Different timing of steroid administration results in different inflammatory mediator response. Steroid in CPB prime is not significantly better than no steroid treatment, while systemic steroid pre-treatment significantly decreases systemic manifestation of inflammatory response and brain damage.     

Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring.

BACKGROUND: Interest has recently been expressed in tacrolimus and mycophenolate mofetil (MMF), two potent immunosuppressants, for a variety of transplant indications. The efficacy of this combination was assessed as primary therapy following cardiac transplantation. METHODS: Forty-five patients were enrolled; 15 into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was administered for 2-3 days to all patients prior to conversion to oral therapy; target blood concentrations were 10-15 ng/mL. Treatment also consisted of steroids and MMF. During Phase I, a fixed 2 g/day dose of MMF was given whilst doses were adjusted according to mycophenolic acid (MPA) plasma levels during Phase II (target range 2.5-4.5 microg/mL). Mean follow-up was 696 +/- 62 days and 436 +/- 88 days for Phases I and II, respectively. RESULTS: Phase I: Patient survival was 100%. Rejection was diagnosed in 66.7% of patients (mean number of episodes per patient 1.33 +/- 1.18). Retrospective analyses indicated that whereas mean MPA plasma levels >3.0 microg/mL were not associated with rejection, no correlation was found with tacrolimus blood concentrations. Phase II: A survival rate of 96.7% was evident, one patient having died from aspergillosis. Diagnoses of rejection were made in 10.0% of patients (0.10 +/- 0.31 episodes per patient) and confounding factors were present in all 3 cases. MPA trough levels were 1.0 +/- 0.3 microg/mL at this time. Resolution was apparent following pulse steroid therapy. Steroids were successfully withdrawn from all patients who completed 6 months' treatment. CONCLUSIONS: Combination therapy with tacrolimus and MMF is associated with suppression of acute myocardial rejection; however, this is dependent upon routine therapeutic drug monitoring.