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Abstract-There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP Ͼ140 mm Hg or diastolic BP Ͼ90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (nϭ59) or a placebo (nϭ58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was Ϫ5.4 mm Hg (95% CI Ϫ10.0; Ϫ0. R esistant hypertension is a common clinical problem faced by both primary care clinicians and specialists worldwide. It is defined as blood pressure (BP) that remains above goal despite the concurrent use of 3 antihypertensive agents of different classes prescribed at optimal dosages; one of the 3 agents used should be a diuretic. 1 The exact prevalence of resistant hypertension is not known, but it is estimated from large clinical trials to affect at least 10% to 15% of all hypertensive patients. 2,3 If no secondary cause of hypertension is found, the use of multidrug treatment regimens including 3, 4, or more antihypertensive drugs is usually necessary to lower BP and thus prevent future cardiovascular events. 4 Spironolactone is a mineralocorticoid receptor antagonist that was shown to lower BP effectively in both general hypertensive patients and patients with primary aldosteronism. 5-7 A number of small, uncontrolled trials showed the positive effect of small doses of spironolactone in lowering BP in patients with resistant arterial hypertension. 8 -11 In the nonrandomized post hoc analysis of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, the addition of spironolactone to a triple-drug treatment led, during an average of 1.3 years of follow-up, to a significant decrease of systolic BP of 21.9 mm Hg and diastolic BP of 9.5 mm Hg. 12 However, evidence from randomized trials was lacking, and it was necessary to provide definite proof for the efficacy of spironolactone as an add-on treatment in resistant hypertension. 12,13 Therefore, we designed a prospective randomized trial to evaluate the effect of adding spironolactone in patients with resistant arterial hypertension. We decided to administer a low dose of spironolactone (25 mg/day) in the trial, since the effect of this dose seemed to be substantial

Aims.To assess the influence of continuous venovenous hemofiltration (CVVH) at a filtration rate of 45 mL/kg/h on vancomycin pharmacokinetics in critically ill septic patients with acute kidney injury (AKI). Methods. Seventeen adult septic patients with acute kidney injury treated with CVVH and vancomycin were included. All patients received first dose of 1.0 g intravenously followed by 1.0 g/12 h if not adjusted. In sixteen patients vancomycin was introduced on the day of the start of CRRT therapy. Blood samples and ultrafiltrates were obtained before and 0.5, 1, 6 and 12 h after vancomycin administration. Results. On the first day, the median total vancomycin clearance (Cl tot ) was 0.89 mL/min/kg (range 0.31 -2.16). CRRT clearance accounted for around 50-60% of the total clearance of vancomycin found in a population with normal renal function (0.97 mL/min/kg). Vancomycin serum concentrations after the first dose were below the required target of 10 mg/L as early as 6 h in 10 patients, AUC 0-24 /MIC ≥ 400 ratio was achieved in 10 patients on the first day. Conclusions. CVVH at a filtration rate of 45 mL/kg/h leads to high and rapid extracorporeal removal of vancomycin in critically ill patients. Due to the rapid change in patient clinical status it was impossible to predict a fixed dosage regimen. We recommend blood sampling as early as 6 h after first vancomycin dose with maintenance dose based on vancomycin serum level monitoring.

Doppler-based LABP provides better results than the guideline-recommended HABP in diabetic patients, nevertheless even this method is not perfect. Increasing the cut-off value to 1.0 in these patients does not bring a substantial improvement of the test performance. Patients with high ABI should be automatically considered PAD-positive and referred for further investigation using imaging techniques.

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