Can beta blockers or Hydrochlorothiazide (HCTZ) cause hyperkalemia?

From the Guidelines

Beta blockers can potentially cause hyperkalemia, while hydrochlorothiazide (HCTZ) typically causes hypokalemia rather than hyperkalemia. According to the most recent evidence from 1, hyperkalemia is a potentially life-threatening electrolyte abnormality that can be increased in patients with chronic kidney disease (CKD), diabetes, and heart failure (HF) and in individuals receiving renin-angiotensin-aldosterone system inhibitors (RAASis). Beta blockers, especially non-selective ones like propranolol, can lead to mild hyperkalemia by decreasing potassium excretion and shifting potassium from intracellular to extracellular spaces, as noted in 1. This effect is generally modest but may become clinically significant in patients with kidney dysfunction or those taking other medications that raise potassium levels.

Key Points to Consider

• HCTZ, on the other hand, is a thiazide diuretic that increases potassium excretion in the urine, typically resulting in hypokalemia (low potassium) 1.
• For patients on beta blockers who develop hyperkalemia, monitoring potassium levels is important, especially when starting therapy or adjusting doses.
• Risk factors for developing hyperkalemia while on beta blockers include renal impairment, diabetes, advanced age, and concurrent use of medications like ACE inhibitors, ARBs, or potassium-sparing diuretics.
• In some cases, the potassium-lowering effect of HCTZ may actually be beneficial when used in combination with beta blockers to counterbalance potential hyperkalemic effects.

Clinical Implications

The management of hyperkalemia involves a comprehensive approach, including the identification and treatment of underlying causes, as well as the use of medications that can help lower potassium levels. Given the potential for beta blockers to contribute to hyperkalemia, clinicians should be vigilant in monitoring patients, especially those with risk factors for hyperkalemia. The use of HCTZ in combination with beta blockers may offer a therapeutic strategy to mitigate the risk of hyperkalemia, but this should be carefully considered on a case-by-case basis, taking into account the individual patient's clinical profile and the potential benefits and risks of such a combination.

From the Research

Hyperkalemia Causes

• Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L 2
• Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice 2
• A wide range of drugs can cause hyperkalemia by a variety of mechanisms, including:
  • Promoting transcellular potassium shift
  • Impairing renal potassium excretion
  • Increasing potassium supply
• Medications that alter transmembrane potassium movement include beta-blockers 2, 3

Beta Blockers and Hyperkalemia

• Beta-blockers may increase the risk of hyperkalemia, particularly when used in combination with other medications such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists 3, 4, 5
• The risk of hyperkalemia associated with beta-blockers is higher in patients with chronic kidney disease, older age, male sex, heart failure, and peripheral vascular disease 3

Hydrochlorothiazide (HCTZ) and Hyperkalemia

• HCTZ is not typically associated with an increased risk of hyperkalemia, but rather with hypokalemia (low potassium levels) 6
• However, the use of HCTZ in combination with other medications, such as potassium-sparing diuretics, may increase the risk of hyperkalemia 4

Clinical Implications

• Hyperkalemia can be asymptomatic, but it may also be dramatic and life-threatening, posing diagnostic and management problems 2
• The therapy of hyperkalemia can involve both acute and semiacute management phases, including measures to block the adverse membrane effects of hyperkalemia and efforts to shift potassium intracellularly 5
• Prevention is the cornerstone of hyperkalemia management, and requires careful attention to identifying exogenous sources of potassium and pinpointing the maximum tolerable dose of medications that may increase the risk of hyperkalemia 5