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Biomedical subjects

Michael Allon

Publications and source records attributed to Michael Allon.

12 recordsLinked to original sources
PubMed2003

Prophylaxis against dialysis catheter-related bacteremia with a novel antimicrobial lock solution.

Catheter-related bacteremia, a frequent complication in patients who are undergoing hemodialysis, may be prevented by eradication of the catheter biofilm. Catheter lock solution (CLS) is an investigational preparation containing taurolidine, a biocompatible antimicrobial agent, and citrate, an anticoagulant agent. CLS was instilled into the catheter lumens after each dialysis session for 20 catheter-dependent hemodialysis patients. Catheter outcomes were compared with those observed in 30 concurrent control patients whose catheters were instilled with heparin. Bacteremia-free survival at 90 days was higher among patients who received CLS than among control patients who received heparin (94% vs. 47%; P<.001). Unassisted catheter patency (without tissue plasminogen activator instillation) was lower among patients who received CLS than among control patients (32% vs. 76%; P<.001). CLS dramatically reduces the frequency of catheter-related bacteremia among patients undergoing hemodialysis, although there is an increased requirement for thrombolytic interventions to maintain catheter patency.

Anti-Infective Agents↗
PubMed2003

Gender differences in outcomes of arteriovenous fistulas in hemodialysis patients.

BACKGROUND: The prevalence of arteriovenous (A-V) fistula use is lower among female than male hemodialysis patients. This difference may be due, in part, to smaller vessel diameter in women. However, even when routine preoperative vascular mapping is used to select vessels with suitable diameters, fistulas are still less likely to mature in women than in men. METHODS: To explore the reasons for this gender discrepancy, we evaluated the outcomes of 230 A-V fistulas placed at our institution after preoperative mapping. Vessel diameters, radiologic and surgical interventions, and fistula adequacy for dialysis were assessed. RESULTS: Fistula adequacy for dialysis was lower in women than men (31 vs. 51%, P = 0.001). The inferior outcome of fistulas in women was observed for both forearm fistulas (18 vs. 43%, P = 0.02) and upper arm fistulas (39 vs. 60%, P = 0.04). Differences in vessel diameter did not explain the lower patency rate of fistulas among women. Among fistulas not lost due to technical failure or early thrombosis, 31% underwent one or more interventions (salvage procedures) due to failure to mature. These interventions included angioplasty, ligation of tributaries, superficialization, and surgical revision of the anastomosis. A salvage procedure was more likely in women than in men (42 vs. 23%, P = 0.04). The likelihood of fistula maturation after an intervention was similar among women and men (50 vs. 37%, P = 0.40). Salvage procedures increased the proportion of adequate fistulas to a greater degree in women than in men (relative increases of 68 and 15%, respectively). CONCLUSIONS: These data suggest that fistulas are less likely to be useable for dialysis in women than in men, despite routine preoperative mapping and frequent interventions undertaken to salvage immature fistulas.

Adolescent↗
PubMed2003

Impact of dialysis dose and membrane on infection-related hospitalization and death: results of the HEMO Study.

Infection is the second most common cause of death among hemodialysis patients. A predefined secondary aim of the HEMO study was to determine if dialysis dose or flux reduced infection-related deaths or hospitalizations. The effects of dialysis dose, dialysis membrane, and other clinical parameters on infection-related deaths and first infection-related hospitalizations were analyzed using Cox regression analysis. Among the 1846 randomized patients (mean age, 58 yr; 56% female; 63% black; 45% with diabetes), there were 871 deaths, of which 201 (23%) were due to infection. There were 1698 infection-related hospitalizations, yielding a 35% annual rate. The likelihood of infection-related death did not differ between patients randomized to a high or standard dose (relative risk [RR], 0.99 [0.75 to 1.31]) or between patients randomized to high-flux or low-flux membranes (RR, 0.85 [0.64 to 1.13]). The relative risk of infection-related death was associated (P < 0.001 for each variable) with age (RR, 1.47 [1.29 to 1.68] per 10 yr); co-morbidity score (RR, 1.46 [1.21 to 1.76]), and serum albumin (RR, 0.19 [0.09 to 0.41] per g/dl). The first infection-related hospitalization was related to the vascular access in 21% of the cases, and non-access-related in 79%. Catheters were present in 32% of all study patients admitted with access-related infection, even though catheters represented only 7.6% of vascular accesses in the study. In conclusion, infection accounted for almost one fourth of deaths. Infection-related deaths were not reduced by higher dose or by high flux dialyzers. In this prospective study, most infection-related hospitalizations were not attributed to vascular access. However, the frequency of access-related, infection-related hospitalizations was disproportionately higher among patients with catheters compared with grafts or fistulas.

Catheterization↗
PubMed2003

Comparison of arteriovenous grafts in the thigh and upper extremities in hemodialysis patients.

Placement of a thigh graft is an option in hemodialysis patients who have exhausted all upper extremity sites for permanent vascular access. The outcome of thigh grafts has been reported only in retrospective studies. The outcomes of 409 grafts placed at a single institution during a 3.5-yr period were evaluated prospectively, including 63 thigh grafts (15% of the total). Information was recorded on surgical complications, dates of radiologic and surgical interventions, and date of graft failure. The technical failure rate was approximately twice as high for thigh grafts, as compared with upper extremity grafts (12.7 versus 5.8%; P = 0.046). Intervention-free survival was similar for thigh and upper extremity grafts (median, 3.9 versus 3.5 mo; P = 0.55). Thrombosis-free survival was also comparable for thigh and upper extremity grafts (median, 5.7 versus 5.5 mo; P = 0.94). Cumulative survival (time to permanent failure) was similar for thigh and upper extremity grafts (median, 14.8 versus 20.8 mo; P = 0.62). When technical failures were excluded, the median cumulative survival was 27.6 mo for thigh grafts and 22.5 mo for upper extremity grafts (P = 0.72). The frequency of angioplasty (0.28 versus 0.57 per year), thrombectomy (1.58 versus 0.94 per year), surgical revision (0.28 versus 0.18 per year), and total intervention rate (2.15 versus 1.70 per year) was similar between thigh and upper extremity grafts. Access loss as a result of infection tended to be higher for thigh grafts than for upper extremity grafts (11.1 versus 5.2%; P = 0.07). In conclusion, placement of thigh grafts should be considered a viable option among hemodialysis patients who have exhausted all options for a permanent vascular access in both upper extremities.

Aged↗
PubMed2002

Effect of dialysis dose and membrane flux in maintenance hemodialysis.

BACKGROUND: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. METHODS: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. RESULTS: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients. CONCLUSIONS: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.

Adult↗
PubMed2002

Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution.

BACKGROUND: Tunneled dialysis catheters are complicated by frequent systemic infections. Standard therapy of catheter-associated bacteremia involves both systemic antibiotics and catheter replacement. Recent data suggest that biofilms in the catheter lumen are responsible for the bacteremia, and that instillation of an antibiotic lock (highly concentrated antibiotic solution) into the catheter lumen after dialysis sessions can eradicate the biofilm. METHODS: We analyzed prospectively the efficacy of an antibiotic lock protocol, in conjunction with systemic antibiotics, for treatment of patients with dialysis catheter-associated bacteremia without catheter removal. Protocol success was defined as resolution of fever and negative surveillance cultures one week following completion of the protocol. Protocol failure was defined as persistence of fever or surveillance cultures positive for any pathogen. In addition, infection-free catheter survival was compared to that observed in institutional historical control patients treated with catheter replacement. RESULTS: Blood cultures were positive in 98 of 129 of episodes (76%) in which patients dialyzing with a catheter had fever or chills. Protocol success occurred in 40 of 79 infected patients (51%) treated with the antibiotic lock. Protocol failure occurred in 39 cases (49%): 7 had persistent fever, 15 had positive surveillance cultures (9 for Candida and 6 for bacteria), and 17 required catheter removal due to malfunction. Each of the pathogens in the surveillance cultures was different from the original pathogen in that patient. Eight of the 9 secondary Candida infections and all 6 secondary bacterial infections resolved after catheter exchange and specific antimicrobial treatment. Overall catheter survival with the antibiotic lock protocol was similar to that observed among patients managed with catheter replacement (median survival, 64 vs. 54 days, P = 0.24). CONCLUSIONS: Use of an antibiotic lock, in conjunction with systemic antibiotic therapy, can eradicate catheter-associated bacteremia while salvaging the catheter in about one half of cases. Moreover, this management approach offers clinical advantages over routine catheter exchange.

Aged↗
PubMed2002

Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis.

OBJECTIVE: The aim of this multicenter, randomized, open-label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis-stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis. METHODS: Forty-seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first. RESULTS: At each of the 3 time points evaluated, the terminal half-life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half-life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin. CONCLUSIONS: The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.

Adult↗
PubMed2002

Increasing arteriovenous fistulas in hemodialysis patients: problems and solutions.

National guidelines promote increasing the prevalence of fistula use among hemodialysis patients. The prevalence of fistulas among hemodialysis patients reflects both national, regional, and local practice differences as well as patient-specific demographic and clinical factors. Increasing fistula prevalence requires increasing fistula placement, improving maturation of new fistulas, and enhancing long-term patency of mature fistulas for dialysis. Whether a patient receives a fistula depends on several factors: timing of referral for dialysis and vascular access, type of fistula placed, patient demographics, preference of the nephrologist, surgeon, and dialysis nurses, and vascular anatomy of the patient. Whether the placed fistula is useable for dialysis depends on additional factors, including adequacy of vessels, surgeon's experience, patient demographics, nursing skills, minimal acceptable dialysis blood flow, and attempts to revise immature fistulas. Whether a mature fistula achieves long-term patency depends on the ability to prevent and correct thrombosis. An optimal outcome is likely when there is (1) a multidisciplinary team approach to vascular access; (2) consensus about the goals among all interested parties (nephrologists, surgeons, radiologists, dialysis nurses, and patients); (3) early referral for placement of vascular access; (4) restriction of vascular access procedures to surgeons with demonstrable interest and experience; (5) routine, preoperative mapping of the patient's arteries and veins; (6) close, ongoing communication among the involved parties; and (7) prospective tracking of outcomes with continuous quality assessment. Implementing these measures is likely to increase the prevalence of fistulas in any given dialysis unit. However, differences among dialysis units are likely to persist because of differences in gender, race, and co-morbidity mix of the patient population.

Arteriovenous Shunt, Surgical↗
PubMed2002

Hemodialysis arteriovenous fistula maturity: US evaluation.

PURPOSE: To compare various objective ultrasonographic (US) criteria for native arteriovenous fistula (AVF) maturation with subsequent fistula outcomes and clinical evaluation by experienced dialysis nurses. MATERIALS AND METHODS: US fistula evaluation results were analyzed retrospectively in 69 patients within 4 months after AVF placement; adequacy for dialysis was known in 54. Measurements included minimum venous diameter and blood flow rate. Experienced dialysis nurses examined 30 fistulas clinically. Predictors of fistula adequacy were analyzed with univariate and multivariate logistic regression. Mean fistula diameters and blood flow rates were compared by using analysis of variance or unpaired Student t tests. RESULTS: Fistula adequacy for dialysis doubled if the minimum venous diameter was 0.4 cm or greater (89% [24 of 27]) versus less than 0.4 cm (44% [12 of 27]; P <.001). Fistula adequacy for dialysis was nearly doubled if flow volume was 500 mL/min or greater (84% [26 of 31]) versus less than 500 mL/min (43% [nine of 21]; P =.002). Combining venous diameter and flow volume increased fistula adequacy predictive value: minimum venous diameter of 0.4 cm or greater and flow volume of 500 mL/min or greater (95% [19 of 20]) versus neither criterion met (33% [five of 15]; P =.002). Women were less likely to have an adequate fistula diameter of 0.4 cm or greater: 40% (12 of 30) of women versus 69% (27 of 39; P =.015) of men. No significant differences in blood flow or minimum venous diameter were found during 2-4 postoperative months. Experienced dialysis nurses' accuracy in predicting eventual fistula maturity was 80% (24 of 30). CONCLUSION: US measurements of AVF at 2-4 months in patients undergoing hemodialysis are highly predictive of fistula maturation and adequacy for dialysis.

Adult↗
PubMed1993

Glucose modulation of the disposal of an acute potassium load in patients with end-stage renal disease.

PURPOSE: Extrarenal potassium disposal plays an important role in the tolerance of an acute potassium load and is particularly critical in patients with renal failure. Insulin is known to stimulate this disposal by enhancing potassium uptake into the cells. Since dietary potassium is generally ingested in combination with carbohydrates, the predictable stimulation of endogenous insulin release may blunt the expected increase in plasma potassium. The goal of the current study was to evaluate the effect of oral glucose on the disposition of an acute oral potassium load in hemodialysis patients and in normal controls. PATIENTS AND METHODS: Eight hemodialysis patients and eight normal control subjects were studied after an overnight fast. Each subject received an oral load of potassium chloride elixir (0.25 mmol/kg). Plasma potassium was measured at baseline and at 30-minute intervals for 3 hours. On a separate study day, the subjects underwent the identical protocol, with the addition of 50 g of oral glucose to the potassium load to stimulate endogenous insulin release. The identical two experimental protocols were repeated in each subject during concomitant beta blockade with propranolol. RESULTS: The maximal increase in plasma potassium after the potassium load was significantly greater in the hemodialysis patients than in the controls (0.93 +/- 0.08 versus 0.52 +/- 0.04 mmol/L, p < 0.001). Concomitant oral glucose markedly blunted the maximal rise in potassium levels in both experimental groups (0.40 +/- 0.09 and 0.22 +/- 0.07 mmol/L, respectively, p < 0.005 versus potassium alone). With concomitant beta blockade, the maximal increase in plasma potassium after the potassium load was significantly greater in the hemodialysis patients than in the controls (1.11 +/- 0.12 versus 0.72 +/- 0.09 mmol/L, p = 0.02). Concomitant oral glucose again markedly blunted the maximal increase in potassium in both experimental groups (0.72 +/- 0.09 and 0.39 +/- 0.06 mmol/L, respectively, p < 0.01 versus potassium alone). The potassium load in the absence of glucose did not produce changes in plasma insulin concentration in either experimental group. The potassium load in combination with oral glucose load produced more sustained hyperinsulinemia in the dialysis patients than in the control subjects. CONCLUSIONS: Exogenous glucose, by stimulating endogenous secretion of insulin, enhances extrarenal disposal of a potassium load. This protective effect of exogenous glucose against hyperkalemia is independent of adrenergic stimulation. The beneficial effect of exogenous glucose defends against the development of severe hyperkalemia after dietary potassium ingestion, and is critically important in hemodialysis patients, due to their negligible renal potassium excretion.

Adult↗