Critical Care Medicine-Neurologic Disorders>>>>>Heart Failure
Question 3#

A 79-year-old male with acutely decompensated systolic heart failure is admitted from the emergency department with respiratory failure and acute anuric renal failure. The patient is bradycardic and hypotensive. At home, the patient has been taking atenolol, digoxin, hydrochlorothiazide, and lisinopril. A milrinone infusion is started for inotropic support. The patient’s renal function did not improve over the following days ultimately requiring renal continuous venovenous hemofiltration (CVVH).

Which of the statements regarding the medical therapy is CORRECT?

a. Milrinone metabolism is highly dependent on hepatic function
b. Milrinone’s terminal elimination halflife is approximately 2 hours in patients with normal renal function
c. Milrinone can safely be used in patients requiring CVVH
d. CVVH clears digoxin from the patient’s plasma
e. Atenolol metabolism is independent of renal function

Correct Answer is B

Comment:

Correct Answer: B

While up to 15% of milrinone undergoes hepatic metabolism (glucuronidation), the vast majority of milrinone is excreted unchanged via the kidneys. Milrinone’s terminal elimination half-life is approximately 2 hours in patients with normal renal function. There appears to exist a linear relationship between creatinine clearance and the renal clearance of milrinone. The terminal elimination half-life of milrinone in subjects receiving CVVH is longer compared with that in subjects with normal renal function (up to 20 hours have been reported). Digoxin metabolism is dependent on renal function. Dialysis does not eliminate digoxin from the patient’s plasma. Digoxin-specific Fab-antibody fragments are the antidote for digoxin overdose. Hypokalemia as oppose to hyperkalemia increases digoxin toxicity because of increased binding of digoxin to the Na/KATPase (digoxin competes with potassium for the binding at the Na/KATPase), thus the combination of dialysis and digoxin confers the risk of inducing digoxin toxicity. Likewise, atenolol metabolism is dependent on renal function while other beta-blockers, such as metoprolol and carvedilol, are not.

References:

  1. Thiemann DR. Digitalis and hemodialysis is a bad combination. J Am Soc Nephrol. 2010;21:1418-1420.
  2. Taniguchi T, Shibata K, Saito S, et al. Pharmacokinetics of milrinone in patients with congestive heart failure during continuous venovenous hemofiltration. Intensive Care Med. 2000;26:1089-1093.
  3. Hartmann B, Czock D, Keller F. Drug therapy in patients with chronic renal failure. Dtsch Arztebl Int. 2010;107:647-655; quiz 655-646.