The influence of posture on the response to loop diuretics in patients with chronic cardiac failure is reduced by angiotensin converting enzyme inhibition

Abstract

The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.

CHF: Circulatory Homeostasis Gone Awry

“…34,35 PRA and plasma aldosterone become elevated with upright posture and ambulation. Urinary sodium excretion is greater in the supine position than with 4 or 6 hours of upright posture combined with activities of daily living.…”

“…23 Nephrosis. 34 Loop Diuretic Pharmacokinetics/Pharmacodynamics in Patients With Sodium Retention. 47 Diuretic and saluretic responses to intravenous furosemide are greater with 6 hours of bedrest than with a comparable period of physical activity.…”

Fluid Management In Patients With Chronic Heart Failure

“…67 During times of severe fluid retention, simple interventions, such as continuous bed rest, might enhance diuresis and significantly reduce body weight compared with bed rest during night only; 68 also diurnal postural changes might influence the diuretic action, which is enhanced by supine position compared to the erect. 69 Although fluid restriction is an intervention mentioned by current guidelines for patients with HF, a recent meta-analysis including five studies suggests this therapy has no benefit compared with liberal fluid intake on mortality, admission or thirst in patients with HF. 70 The role of sodium restriction is not clear, although part of the traditional management of HF and recommended in guidelines (albeit with an acknowledged low grade of evidence to support the recommendations).…”

Drug Absorption in the Management of Congestive Heart Failure: Loop Diuretics

“…For example, the bioavailability of torsemide does not differ between CHF and normal patients. 50,51 Interestingly, the posturally related reduction in loop diuretic effect fades when an ACE inhibitor like enalapril is coadministered with intravenous furosemide. Torsemide is extremely well absorbed after oral administration, with peak plasma concentrations in normal volunteers within 1 hour of its administration and an absolute bioavailability of approximately 80% in normal volunteers.…”

“…40 Torsemide. 51 This interaction between posture, ACE inhibition, and loop diuretic effect has not been explored with oral loop diuretic therapy. 41,42 In CHF patients the bioavailability of torsemide is the same as that observed in normal volunteers with values approximating 90%.…”