Potassium supplements to reduce arrhythmias in the ICU: Review

TIGHT K trial tests potassium targets immediately post-CABG

“I can’t prove it was the reason, but we kept everyone’s K over 4 and Mag over 2 and we didn’t have a single code this month.” – my senior resident on an internal medicine rotation, circa 2005

As many as one-fifth of hospitalized patients develop hypokalemia, commonly defined as serum potassium less than 3.5 mEq/L.

Hypokalemia has been associated with the development of arrhythmias including premature ventricular complexes, atrial fibrillation, atrial flutter, supraventricular tachycardia, torsade de pointes, ventricular tachycardia, and ventricular fibrillation. 

Although the precise arrhythmogenic mechanisms are poorly understood, hypokalemia increases resting membrane potential in myocardial tissue, increases the duration of the action potential and the refractory period, and decreases conductivity. Low intracellular potassium levels (suggested by serum hypokalemia) can increase spontaneous depolarization and ectopy. Reentrant arrhythmias are considered especially provokable by hypokalemia.

In the hospital, hypokalemic patients also have an increased incidence of ventricular fibrillation compared to those with normal potassium levels. Hypokalemia is associated with higher in-hospital mortality rates—up to 10-fold in one widely cited series—and this is commonly attributed to its pro-arrhythmic tendencies.

Such studies are potentially confounded, though, in that:

• Patients with hard-to-treat hypokalemia are at increased risk for death independent of their potassium levels;

• Patients with heart failure are both more likely to develop arrhythmias and to be taking loop diuretics that cause hypokalemia (without their arrhythmias being caused by the hypokalemia);

• Higher mortality observed with uncorrected hypokalemia may be due to a decreased quality of care generally in the patients who died.

Because of the potentially life-threatening risks of hypokalemia-induced arrhythmias, potassium supplementation became increasingly protocolized in ICUs throughout the 2000s and 2010s. Protocols commonly default to supplementing potassium to a target of at least 3.6 mmol/L, or to greater than 4.0 mmol/L. (One millimole equals one milliequivalent; mmol = mEq.)

Malignant arrhythmias like ventricular fibrillation occur too uncommonly to be easily studied in short-term prospective trials. Atrial fibrillation, on the other hand, is common in critically ill patients and is strongly believed to be provoked or exacerbated by hypokalemia.

A randomized trial tested the effects of two potassium supplementation targets in patients undergoing coronary artery bypass grafting (CABG), about 30% of whom typically develop atrial fibrillation in the first 5 postoperative days.

TIGHT K Trial

Between 2020 and 2023, at 23 cardiac surgical centers in the United Kingdom and Germany, 1,690 patients without a history of atrial fibrillation undergoing CABG (without additional procedures such as valve replacements) were randomized to either receive potassium supplementation as needed to a K⁺ target of ≥4.5 mEq per liter or ≥3.6 mEq/L.

Also excluded were patients with a history of high-degree atrioventricular block, history of anti-arrhythmic medication, or end-stage renal disease. Although about 10% had left ventricular ejection fractions ≤45%, only ~2% of patients had a diagnosis of congestive heart failure.

There was no difference in the incidence of new-onset atrial fibrillation in 5 days after surgery (26.2% in the ≥4.5 mEq/L group and 27.8% in the ≥3.6 mEq/L group, 95% confidence interval −2.6% to 5.9%). There were no differences in the incidence of other arrhythmias, mortality, or length of stay.