Torasemide in advanced renal failure.

In patients with advanced renal failure, high doses of loop diuretics are required to promote negative sodium and water balance and to treat hypertension. Torasemide is a new loop diuretic that has a high bioavailability of 90% and a plasma half-life of 3-5 hours, which remains unchanged in chronic renal failure. Even in patients with advanced renal failure, intravenous and oral high-dose torasemide proves effective in increasing fluid and sodium excretion in a dose-dependent manner. A number of studies in renal failure patients provide evidence that, on a weight-by-weight basis, the ratio of diuretic potency between torasemide and furosemide is 1:2.5 after oral dosing and 1:1 after intravenous administration. The lack of a substantial calciuretic effect of torasemide in chronic renal disease needs further confirmation. Two controlled multicenter clinical trials comparing high oral doses of furosemide and torasemide in patients with end-stage renal disease requiring maintenance hemodialysis demonstrated a substantial increase in urinary volume and electrolyte excretions in patients receiving 100 or 200 mg oral torasemide once daily. A dose of 200 mg oral torasemide appears equally natriuretic to oral furosemide 500 mg, whereas the antihypertensive effect of torasemide is more pronounced. Neither torasemide nor furosemide in the above doses has a negative influence on the neurological status of hemodialysis patients.

Torasemide for diuretic treatment of advanced chronic renal failure.

In a double-blind randomized clinical trial the efficacy and safety of oral high-dose torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea, T) therapy was compared with that of furosemide (F) in 10 patients with advanced chronic renal failure. The efficacy on edema, fluid and electrolyte balance including the influence on renin-angiotensin-aldosterone system and cochlear function was evaluated. Patients were randomly allocated to either 500 mg F/d (group 1) or 200 mg T/d (group 2). After 14 days of treatment doses were doubled in each group for further 14 days. With respect to the 2.5 times lower dose of T the clinical effect of both drugs on edema, fluid and sodium excretion was equipotent. Significant differences were noted on calciuresis. Serum calcium levels were reduced with F, while T had no influence on calcium balance. A significant increase in plasma renin activity (PRA) was observed after F, whereas T had no raising effect on PRA. No significant alteration of plasma aldosterone concentration occurred with T or F. No adverse effects were noted in both groups. Serial audiometries showed no significant impairment of cochlear function with both drugs. In conclusion, these results indicate that high-dose T is efficient and safe in the treatment of advanced chronic renal failure. The lack of a calciuric effect with T can be regarded as an advantage in patients with hypocalcemia in chronic renal failure.

Empiric antibiotic treatment of infections in myelosuppressed cancer patients. Preliminary results.

A prospective, randomized study was performed to compare the efficacy and safety of mezlocillin plus sisomicin (Regimen A) and cefamandole plus tobramycin (Regimen B). Sixty-one episodes of documented infections were treated in 49 adult myelosuppressed cancer patients. About two-thirds of the patients treated with either regimen responded to this antibacterial therapy. The patients failing to respond to the initial therapy were treated with additional antibiotics, either with the empiric Regimen C (cefotaxime plus amikacin plus azlocillin) or with antibiotics selected on the basis of bacteriological results (Regimen D). With these schedules, the over-all response rate was increased to about 90%. The data suggest that febrile granulocytopenic cancer patients may profit from this empiric and sequential antibiotic treatment.