Metolazone is the thiazide-like drug usually used in patients refractory to loop agents alone, but it is likely that other thiazides at equipotent doses would be just as effective. Moreover, metolazone is available only in an oral preparation, whereas chlorothiazide can be given parenterally.
The combination of loop diuretics and thiazides can mobilize large amounts of fluid, even in patients who have not responded to single agents. Therefore, close hemodynamic monitoring is essential. Routine outpatient use is not recommended but may be possible with extreme caution and close follow-up. Furthermore, K+ wasting is extremely common and may require parenteral K+ administration with careful monitoring of fluid and electrolyte status. The first large-scale randomized controlled trial of combination loop and thiazide diuretic therapy in patients with heart failure is currently under way in the CLOROTIC (Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure) trial. Clinical experience suggests that in outpatients, adverse effects of thiazides as add-on therapy to loop diuretics can be mitigated by infrequent low-dose therapy. Add-on diuretic therapy with metolazone is started at 2.5 mg weekly and titrated up slowly as needed, with close monitoring of the patient’s blood pressure and serum potassium concentration.
POTASSIUM-SPARING DIURETICS & PROXIMAL TUBULE DIURETICS, LOOP AGENTS, OR THIAZIDES
Hypokalemia often develops in patients taking carbonic anhydrase inhibitors, loop diuretics, or thiazides. This can usually be managed by dietary NaCl restriction or by taking dietary KCl supplements. When hypokalemia cannot be managed in this way, the addition of a K+-sparing diuretic can significantly lower K+ excretion. Although this approach is generally safe, it should be avoided in patients with renal insufficiency and in those receiving angiotensin antagonists such as ACE inhibitors, in whom life-threatening hyperkalemia can develop in response to K+-sparing diuretics.
A summary of the effects of diuretics on urinary electrolyte excretion is shown in Table 15–2.
A common reason for diuretic use is for reduction of peripheral or pulmonary edema that has accumulated as a result of cardiac, renal, or vascular diseases that reduce blood flow to the kidney.
This reduction is sensed as insufficient effective arterial blood volume and leads to salt and water retention, which expands blood volume and eventually causes edema formation. Judicious use of diuretics can mobilize this interstitial edema without significant reductions in plasma volume. However, excessively rapid diuretic therapy may compromise the effective arterial blood volume and reduce the perfusion of vital organs. Therefore, the use of diuretics to mobilize edema requires careful monitoring of the patient’s hemodynamic status and an understanding of the pathophysiology of the underlying illness.
When cardiac output is reduced by heart failure, the resultant changes in blood pressure and blood flow to the kidney are sensed as hypovolemia and lead to renal retention of salt and water. This physiologic response initially increases intravascular volume and venous return to the heart and may partially restore the cardiac output toward normal (see Chapter 13).