Combination diuretic therapy in severe congestive heart failure.

Severe congestive heart failure (CHF) is often characterised by fluid retention. A (chronic) state of overhydration has a negative influence on both the quality of life and prognosis of these patients. Therefore, the use of diuretics remains a cornerstone in the treatment of heart failure. However, diuretic resistance, a failure to correct the hydration state adequately with the use of conventional dosages of loop diuretics, is a frequently occurring complication in the treatment of advanced stages of CHF. Several intra- and extrarenal mechanisms may be involved in the development of diuretic resistance. An important pathophysiological mechanism leading to diuretic resistance seen after chronic use of loop diuretics is the functional adaptation of the distal tubule. Studies in animals demonstrate that the sodium reabsorption capacity of this nephron segment increases significantly when the sodium delivery to this segment is augmented, as is the case during administration of loop diuretics. The use of combinations of diuretics acting on different segments of the nephron appears to be an effective option in the treatment of diuretic resistance. Several combinations have been used; however, the combination of a loop diuretic and a thiazide drug acting on the distal tubule appears to be the most effective. However, since the use of this combination may lead to serious adverse effects such as hypokalaemia, metabolic alkalosis and dehydration, careful monitoring of the patient of combination diuretic therapy is necessary.