Sodium thiosulfate-based treatment in calcific uremic arteriolopathy: a consecutive case series.

BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare complication in end stage renal disease with high mortality. Numerous case reports and one case series of 3 patients report the benefit of sodium thiosulfate (STS) for treatment of CUA. The purpose of this evaluation was to examine the response to a STS-based treatment approach in patients with CUA with 1 year follow up. METHODS: A retrospective case series of 6 consecutive patients from Manitoba, Canada who met predefined diagnostic criteria for CUA and received STS between 2006 and 2008 were included. STS responders were defined as improvement in at least one of the following three parameters: pain severity, wound size and diagnostic imaging/radiography. Mortality, STS dose, duration, adverse events and cost were also collected. RESULTS: Four patients were classified as responders. The 2 responders who survived at 1 year of follow-up demonstrated an improvement in all 3 parameters examined including an improvement in their follow-up diagnostic imaging results within the first 4 - 6 weeks of STS treatment. At 1 year of follow-up, 3 patients died. CONCLUSION: Using an STS-based multifaceted treatment approach for CUA, 4 patients responded but 3 of 6 patients died within 1 year. Further larger prospective studies are needed to delineate STS responders from non-responders.

Desensitization protocols for vancomycin hypersensitivity.

OBJECTIVE: To discuss the pathophysiology of vancomycin-induced immediate hypersensitivity reactions, review the process of vancomycin desensitization, and provide specific directions for ordering and preparing rapid and slow desensitization protocols. DATA SOURCES: A MEDLINE search (1966-February 2001) of English-language literature pertaining to vancomycin desensitization and hypersensitivity reactions was performed. Tertiary sources were also used. DATA EXTRACTION: Published clinical studies and case reports. DATA SYNTHESIS: The pathophysiology of vancomycin-induced hypersensitivity reactions is discussed along with the procedure of vancomycin desensitization. Desensitization should be considered in Red Man syndrome (RMS) that does not respond to the usual treatment measures, and in vancomycin-induced anaphylaxis. Rapid desensitization is preferred as it is effective in the majority of patients and enables therapeutic dosing of vancomycin within 24 hours. In patients who fail rapid desensitization, a slow desensitization protocol may be tried. CONCLUSIONS: Vancomycin-induced immediate hypersensitivity reactions include RMS and anaphylaxis. Vancomycin desensitization should be considered for severe RMS reactions not responding to usual measures and in anaphylactic reactions to vancomycin, when substitution of another antbiotic is not feasible.

The pharmacokinetics of subcutaneous enoxaparin in end-stage renal disease.

STUDY OBJECTIVE: To evaluate the pharmacokinetics of enoxaparin in end-stage renal disease (ESRD), and determine if dosage reduction is necessary to maintain antifactor Xa activity concentrations within the therapeutic range. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: University-affiliated general clinical research center. PATIENTS: Eight nonthrombosed patients with ESRD requiring hemodialysis. INTERVENTION: All subjects received a single dose of enoxaparin sodium 1 mg/kg subcutaneously and had serial plasma antifactor Xa activity concentrations measured over 24 hours. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of enoxaparin were determined from plasma antifactor Xa activity concentrations, and various multiple-dose regimens were simulated. After administration of the drug, total body clearance was 14.6 ml/minute and there was a 2-fold prolongation in antifactor Xa activity half-life compared with values reported in healthy subjects. All other pharmacokinetic parameters were similar to those in healthy subjects and patients with chronic renal insufficiency. An accumulation ratio of 1.6 was estimated for a dosing interval of every 12 hours based on single-dose pharmacokinetics. When various therapeutic regimens were simulated to predict average steady-state antifactor Xa activity, standard enoxaparin dosages of 1 mg/kg subcutaneously every 12 hours and 1.5 mg/kg every 24 hours resulted in average steady-state concentrations within the therapeutic range. CONCLUSIONS: Based on antifactor Xa activity, ESRD has little effect on the pharmacokinetics of enoxaparin, and dosing adjustments are unnecessary.

Evaluation and management of drug-induced thrombocytopenia in the acutely ill patient.

The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug-induced thrombocytopenia. Such patients tend to have preexisting hemostatic defects that place them at additional risk of complications as a result of the drug-induced thrombocytopenia. The clinical challenge is to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis results. Drug-induced thrombocytopenic disorders can be classified into three mechanisms: bone marrow suppression, immune-mediated destruction, and platelet aggregation. Clinical characteristics, preliminary laboratory findings, and drug history specific to the mechanisms can assist clinicians in rapidly isolating the causative drug.

Amiloride for the prevention of amphotericin B-induced hypokalemia and hypomagnesemia.

OBJECTIVE: To review the published clinical data assessing the role of amiloride in the prevention of amphotericin B (AmB)induced electrolyte disorders. DATA SOURCES: A MEDLINE search (January 1966-April 1999) of English-language literature pertaining to AmB, amiloride, potassium, and magnesium was performed. Tertiary sources were also used. DATA EXTRACTION: In vivo and in vitro human and animal data and case reports were included due to the lack of published clinical trials. DATA SYNTHESIS: AmB administration can result in severe hypokalemia and hypomagnesemia requiring chronic supplementation. In one prospective, controlled study of hypokalemia with AmB administration, patients receiving concomitant amiloride had significantly greater potassium concentrations (p < 0.01) and required significantly less potassium supplementation (p < 0.001). Amiloride may also reduce the amount of magnesium supplementation required by sparing elimination through the kidneys. CONCLUSIONS: Amiloride may be considered for the prevention of AmB-induced hypokalemia and hypomagnesemia, especially in patients at high risk for complications resulting from these electrolyte disorders. Further studies are needed to assess concomitant use of other potassium-sparing diuretics and AmB.

Pharmacotherapy of dyslipidemia in postmenopausal women: weighing the evidence.

In the United States, coronary heart disease (CHD) is the leading cause of death in women. The incidence of CHD rises dramatically in women following menopause, which can be partially attributed to a more atherogenic lipoprotein profile. For years, observational and epidemiological data have suggested that estrogen and progesterone therapy reduced CHD end points. However, the first prospective trial that evaluated hormone replacement therapy (HRT) for secondary CHD prevention demonstrated no positive cardiovascular benefit of HRT compared with placebo. In interventional studies, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors significantly reduced CHD outcomes in postmenopausal women, and these agents have emerged as the drugs of choice for primary and secondary CHD prevention. The selective estrogen receptor modulators (SERMs) may have a role in CHD prevention, but long-term clinical trials evaluating end points are needed. An evidence-based approach is necessary when deciding the appropriate pharmacotherapy of dyslipidemia in postmenopausal women.