We conclude that in patients with severe heart failure, high dose furosemide administered as a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.

BACKGROUND & AIMS: There have been few reproducible studies of mortality in patients with autoimmune hepatitis (AIH) and its variants. We calculated mortality in a large national cohort of patients with AIH, with vs without cirrhosis, in the Netherlands. METHODS: We collected data from 449 patients with established AIH (77% female), from 6 academic and 10 non-academic hospitals in the Netherlands. We identified 29 patients with AIH and primary biliary cholangitis and 35 patients with AIH and primary sclerosing cholangitis (AIH-PSC). Mortality and liver transplantation data were assessed from August 1, 2006 through July 31, 2016. Standardized mortality ratios (SMR) were calculated using age-, sex-, and calendar yearmatched mortality for the general Dutch population.

Furosemide delivery rate in the nephron has been reported to be one of the major determinants of diuretic response. In a randomized, crossover double-blind study in eight healthy volunteers, we tested this hypothesis by comparing continuous intravenous infusion of furosemide (infusion rate, 4 mg/hr) during 8 hours after administration of an intravenous loading dose of 8 mg (total dose, 40 mg) with an intravenous bolus injection of 40 mg furosemide. During the study days subjects were rehydrated with isovolumetric amounts of fluid. Mean total urinary volume (Vw), sodium (U,,), potassium, and chloride excretion after 8 and 24 hours were significantly greater after treatment with continuous furosemide infusion when compared with bolus injection, whereas total urinary furosemide excretion showed no differences ( V , , bolus versus V , infusion, 5270 versus 6770 mV8 hours; UNa bolus versus UNa infusion, 314 versus 430 mmoV8 hours; bothp < 0.001). These findings strongly support the concept of the furosemide delivery rate into the nephron as a determinant of diuretic efficiency. (CLIN PHARMACOL THER 1992;s 1:440-4).