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).

The effects of daily administration of 250-2,000 mg furosemide (F) were studied in patients on hemodialysis who still had residual renal function. In a short study, 10 patients (endogenous creatinine clearance 0.6-5.3 ml/min/1.73 m²) used 1,000 mg F twice daily during 7 days, and in a long-term study 13 patients (endogenous creatinine clearance 0.7-6.8 ml/min/1.73 m²) were treated during 1 year with 250-1,000 mg F orally each day. In the short study, we observed an increase in the 24-hour volume excretion with a median of 109% (p < 0.005). Urinary sodium excretion increased 210%, chloride 346% and potassium 65% when compared with the control period. In the long-term study, a marked initial rise in diuresis and electrolyte excretion was found. However, during a 1-year follow-up, a gradual decrease in response with time was found caused by progression of renal disease. There were no signs of ototoxicity. Side effects were bollous dermatosis on the limbs after exposure to sunlight during the summer (3 patients). We conclude that high-dose F is effective in patients on hemodialysis with residual urinary production. However, in the long term, the diuretic effects diminish because of progression of the underlying renal disease.

Introduction & Aims Small studies have found that black patient with autoimmune hepatitis (AIH) patients present with more aggressive disease. We aimed to characterize the presentation and outcome in black and white patients with AIH. Methods We performed a retrospective study, collecting information from databases of patients with

Continuous infusion of F under careful monitoring of the patient is a safe, controllable and efficient treatment in patients with severe congestive heart failure and diuretic resistance.

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BACKGROUND & AIMS:Biochemical remission, important treatment goal in autoimmune hepatitis (AIH), has been associated with better long-term survival. The aim of this study was to determine the independent prognostic value of aminotransferases and immunoglobulin G (IgG) during treatment on long-term transplant-free survival in AIH. METHODS:In a multicenter cohort alanine aminotransferase, aspartate aminotransferase (AST), and IgG were collected at diagnosis and 6, 12, 24, and 36 months after start of therapy and related to long-term outcome using Kaplan-Meier survival and Cox regression analysis with landmark analysis at these time points, excluding patients with follow-up ending before each landmark. RESULTS:A total of 301 AIH patients with a median follow-up of 99 (range Q3, 7-438) months were included. During follow-up, 15 patients required liver transplantation and 33 patients died. Higher AST at 12 months was associated with worse survival (hazard ratio [HR], 1.86; P < .001), while IgG was not associated with survival (HR, 1.30; P ¼ .53). In multivariate analysis AST at 12 months (HR, 2.13; P < .001) was predictive for survival independent of age, AST at diagnosis and cirrhosis. Multivariate analysis for AST yielded similar results at 6 months (HR, 2.61; P ¼ .001), 24