What studies are available demonstrating use of amiloride in metabolic alkalosis for volume‐overloaded patients? What are dosing suggestions/trends?

What studies are available demonstrating use of amiloride in metabolic alkalosis for volume‐overloaded patients? What are dosing suggestions/trends?

Comment by InpharmD Researcher

Studies demonstrating the use of amiloride for metabolic alkalosis in volume-overloaded patients are limited, but one investigation in post-cardiac surgery patients found that 10 mg of amiloride daily reduced the need for potassium supplementation and appeared to lessen the alkalosis. The consensus from limited resources is that amiloride is a rational treatment for this condition in edematous states like heart failure, as it addresses the underlying aldosterone-driven alkalosis. Dosing suggestions are sparse, but a small, studied dose of 10 mg daily can be considered a starting point.

Background

According to the Internet Book of Critical Care (IBCC), amiloride is not commonly used for metabolic alkalosis, but may be helpful for volume-overloaded patients requiring ongoing diuresis to achieve euvolemia. These benefits may include limiting potassium losses, treatment of metabolic alkalosis, and mild promotion of oral diuretic efficacy. However, dosing or clinical evidence was not provided. [1]

According to StatPearls, the treatment for chloride-resistant metabolic alkalosis involves treating the underlying condition, often related to the renin-angiotensin-aldosterone system. Inhibiting the effect of aldosterone on the nephron using potassium-sparing diuretics such as amiloride is a key part of this strategy. Furthermore, in edematous states like congestive heart failure (CHF), diuresis using potassium-sparing diuretics is considered essential. [2]

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What studies are available demonstrating use of amiloride in metabolic alkalosis for volume‐overloaded patients? What are dosing suggestions/trends?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Table 1 for your response.

Effect of amiloride on metabolic alkalosis and hypokalaemia after cardiopulmonary bypass surgery
Design	Randomized controlled trial N= 26
Objective	To investigate the effects of the potassium-retaining diuretic, amiloride, on the potassium balance and on the alkalosis which occurs in patients after open-heart surgery
Study Groups	Control group (n= 14) Amiloride group (n= 12)
Inclusion Criteria	Patients who underwent valve replacement operations between January 1, 1973, and July 31, 1973, except those with isolated aortic valve replacements not taking diuretics pre-operation
Exclusion Criteria	Isolated aortic valve replacements not taking diuretics pre-operation
Methods	Patients were divided into two groups, one receiving 10 mg amiloride daily from the third postoperative day onward. Urine and blood samples were collected on the 3rd, 4th, 7th, and 14th postoperative days. Sodium, potassium, and pH were measured in both blood and urine. Potassium supplements were given if plasma potassium fell below 3.9 mEq/l.
Duration	January 1, 1973, to July 31, 1973
Outcome Measures	Primary: Plasma potassium levels, urinary potassium excretion
Baseline Characteristics		Control group (n= 14)	Amiloride group (n= 12)
	Mean age, years	41.43	49.67
	Mean frusemide dose, mg	276.6	231.25
Results		Control group (n= 14)	Amiloride group (n= 12)	p-value
	Outcomes were primarily presented as a graph
	Plasma potassium on day 4	Lower	Higher	<0.05
	Plasma potassium on day 7	Lower	Higher	<0.05
	Urinary potassium on day 4	Higher	Lower	<0.02
	Urinary potassium on day 7	Higher	Lower	<0.01
	Urinary potassium on day 14	Higher	Lower	<0.005
Adverse Events	No side effects were observed in patients receiving amiloride
Study Author Conclusions	Amiloride is a potentially useful drug after cardiac surgery, decreasing metabolic alkalosis and reducing the need for potassium supplementation while maintaining plasma potassium levels within normal limits.
Critique	The study was limited by its small sample size and short duration, along with being an older study study from 1973, which may not capture long-term effects. The lack of a parenteral form of amiloride limits its immediate postoperative use. The study's findings may not be generalizable to all cardiac surgery patients due to the specific inclusion criteria.

References:

Hocking MA, Bain WH. Effect of amiloride on metabolic alkalosis and hypokalaemia after cardiopulmonary bypass surgery. Br Heart J. 1974;36(6):597-602. doi:10.1136/hrt.36.6.597