Intravenous Diuretic Therapy for the Management of Heart Failure and Volume Overload in a Multidisciplinary Outpatient Unit.

OBJECTIVES: This study sought to evaluate the effectiveness of intravenous (IV) diuretic treatment for volume management in heart failure (HF). BACKGROUND: Limited data exist regarding IV diuretics for the outpatient treatment of volume overload in HF patients. METHODS: We analyzed 60 consecutive patients with chronic HF and clinical evidence of worsening congestion who received a bolus and 3-h IV infusion of furosemide at an outpatient HF clinic. Diuretic dosing was derived from the maintenance oral loop diuretic dose with a standardized conversion algorithm. Outcomes included urine output during the visit, weight loss at 24 h, and hospitalization and mortality at 30 days. Safety outcomes included hypokalemia and worsening of renal function. Outcomes were analyzed across subgroups defined by maintenance diuretic dose and ejection fraction (EF). RESULTS: The median age of the cohort was 70 years (interquartile range [IQR]: 58 to 80 years), and the median daily loop diuretic dose was 240 mg (IQR: 80 to 800 mg) oral furosemide or equivalent. Twenty-six patients (43.3%) were women, and 36 (60%) had an EF ≤45%. For the entire cohort, the median urine output and 24-h weight loss were 1.1 l (IQR: 0.6 to 1.4 l) and 1.1 kg (IQR: 0.2 to 1.9 kg), respectively. Outcomes were similar across patients with varying maintenance diuretic doses (<40 mg, 40 to 160 mg, 160 to 300 mg, or >300 mg of furosemide or equivalent) and in patients with reduced or preserved EF. Transient worsening of renal function and hypokalemia occurred in 10 patients (8.9%) and 4 patients (3.5%). Although hospitalization was reported as imminent for 28 patients (52.8%), the observed rate of all-cause hospitalization was 31.7% at 30 days with no deaths. CONCLUSIONS: Short courses of IV diuretics for volume management in patients with HF were safe and associated with significant urine output and weight loss across a wide range of maintenance diuretic doses and EF. This strategy may provide an alternative to hospitalization for the management of selected HF patients.

Seeding conditions of the halophyte Atriplex patula for optimal growth on a salt impacted site.

Salt-impacted soils resulting from oilfield brine spills are increasingly becoming a significant problem in oil-producing areas of Canada such as Alberta and Saskatchewan. The native halophyte Atriplex patula is being considered a potential species for phytoremediation of brine-impacted sites in these hemiboreal climactic zones. The objective of this study was to investigate the optimal seeding conditions under field conditions (with no irrigation) of A. patula for phytoremediation of salt from a brine-impacted site. Atriplex patula was identified in preliminary greenhouse trials to have one of the highest salt accumulations in relation to plant yields. Different seeding methods of A. patula were assessed in an attempt to achieve reproducible growth of this species. While plant yields for A. patula were improved on compacted soil by approximately 30-50%, growth was uneven with regard to density and height. The uneven growth may be due to seed quality and low precipitation during the field season, while improvements in plant yield on compact soil might be due to a lack of competition with other species.

Intensity and focus of heart failure disease management after hospital discharge.

BACKGROUND: Although features of heart failure disease management programs are broadly outlined, little is known about which interventions are actually used in the outpatient setting or which patients are most likely to require interventions. METHODS AND RESULTS: Between September 2001 and June 2002, we enrolled 32 patients admitted to the Brigham and Women's Hospital Heart Failure Services, Boston, Mass, with decompensated heart failure. The intensity of care and outcomes of these patients were prospectively tracked for more than 90 days. During this time, there were 325 patient contacts (median 8.5 per patient), including 247 calls (median 7 per patient) and 78 clinic visits (median 2 per patient). Brigham and Women's Hospital clinicians adjusted diuretics a total of 109 times (median 2.5 times per patient). When frequency of diuretic adjustments was used to estimate the intensity of care, higher values of blood urea nitrogen at discharge predicted an increased intensity of care during the 90-day follow-up (relative risk [RR] 1.2, 95% confidence interval [CI] 1.0-1.3, P = .02). When frequency of clinic visits, telephone calls, and diuretic adjustments were used to estimate intensity of care, discharge creatinine (RR 1.03, 95% CI 0.99-1.06, P = .05), discharge blood urea nitrogen (RR 1.13, 95% CI 1.04-1.23, P = .004), and length of stay (RR 1.07, 95% CI 1.00-1.13, P = .04) were predictors of the composite end point. CONCLUSIONS: Even after undergoing optimization of medications during admission for acute heart failure, patients in a comprehensive disease management program required frequent interventions to maintain clinical stability. Renal dysfunction was the strongest predictor of increased interventions and worse outcome.

5-Lipoxygenase inhibition by N-hydroxycarbamates in dual-function compounds.

A series of N-hydroxycarbamates containing a histaminergic H(1) receptor antagonist pharmacophore was synthesized. In vitro assays determined the compounds had both histaminergic binding and 5-lipoxygenase inhibiting activities comparable to the corresponding N-hydroxyurea analog. Animal models demonstrated antihistaminergic and the 5-lipopxygenase inhibitory activity, with the N-hydroxyurea analog having a better overall profile.

Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity.

A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models.