After all the patients I’ve seen with ascites secondary to hepatic cirrhosis, I wondered why we tend to start them on 100 mg Aldactone (spironolactone) with a 40 mg Lasix (furosemide) adjuvant. What’s the rationale behind this ratio? What’s the added benefit of using two different kinds of diuretics to reduce the excessive fluid volume typically found in cirrhotics?
I searched PubMed and Harrison’s Principles of Internal Medicine, but no where did I see a reference to a clinical trial which established the 100:40 mg ratio. Further research from multiple sources led to the following conclusion.
Aldactone is a relatively weak potassium-sparing diuretic which works in the cortical collecting tubule by inhibiting aldosterone receptors (typically responsible for the reabsorption of sodium with concurrent excretion of potassium into the urine). Lasix is a significantly more potent diuretic which works in the ascending Loop of Henle by inhibiting the Na-K-2Cl channel which can lead to secondary hypomagnesemia and hypocalcemia.
Because of all the extravascular fluid in hepatic cirrhosis (ascites, third spacing, etc.), the body’s effective circulating volume decreases. The kidneys sense this as a decreased perfusion and ramp up the renin-angiotensin-aldosterone system (RAAS) leading to increased retention of sodium in the distal convoluted tubule (and retention of even more fluid). By antagonizing the aldosterone receptor, Aldactone is able to offset the RAAS activation but increases serum potassium. This is where the Lasix comes in. As a more powerful diuretic, it’s able to eliminate the excess potassium in addition to large volumes of filtrate in the nephron.
Another way to think about this is that, in a normal kidney, more distal delivery of sodium leads to a rapid reabsorption of that sodium while sacrificing potassium (thanks to unopposed aldosterone). Aldactone counteracts this by blocking aldosterone receptors. Its been cited by many different sources I’ve read that the 100 mg Aldactone : 40 mg Lasix ratio maintains normokalemia while diuresing patients with volume overload.
Pretty nifty. 🙂