HF diuretic resistance....the causes and management

Diuretic resistance is multifactorial.

• Patients with heart failure often have some degree of chronic kidney disease.  As previously discussed, loop diuretics reached the tubular lumen by active secretion.  In renal insufficiency, secretion of loop diuretics is reduced.  This is in part because of accumulated, endogenous organic anions, which compete with loop diuretics at the transporter site.  Increased doses of loop diuretics are thus required to overcome this competitive inhibition.  Additionally, renal blood flow may be decreased in states of renal impairment, further interfering with diuretic secretion. Peak urinary concentrations of loop diuretics are reduced and delayed, resulting in a diminished diuretic effect.
• Non-adherence to sodium restriction can obviate the benefits of loop diuretics.
• Non-steroidal anti-inflammatory drugs interfere with prostaglandin synthesis and can antagonize the response to loop diuretics.

Resistance management 

Considering the mechanisms of diuretic resistance discussed above, there are 4 strategies to manage diuretic resistance:

• Ensure adherence to sodium restriction and medical regimen.

• Escalate the dose of the loop diuretic.  Alternatively, some clinicians favor changing to a different loop diuretic.  For example, bumetanide has better oral bioavailability than furosemide (80% versus 40%, respectively).  Although bumetanide is more potent than furosemide by a factor of 40 based on weight, both drugs should be equally effective in equivalent dosing.
• Consider changing intravenous bolus injections to continuous infusion of a loop diuretic.  Continuous intravenous infusion has the advantage of maintaining an effective urinary drug concentration and avoiding periods of post-diuresis sodium retention.  An IV drip may be considered if patients with CHF are refractory to 250 mg of furosemide given orally or intravenously (e.g. continuous furosemide infusion of 10 to 20 mg/hr or bumetanide infusion of 0.5 mg/hr).
• Consider combination diuretic therapy.  At least 3 studies support the use of thiazide diuretics in addition to loop diuretics for patients resistant to high doses of loop diuretics.  Although there was survival benefit to spironolactone in the RALES study, this was not specifically tested in the context of diuretic resistance and CHF.