By Sara Stream, MD
As resident physicians, we are taught to supplement serum potassium to a goal level of 4.0 mEq/L in all hospitalized patients. While the dangers of severe potassium abnormalities are well established, the benefit of routine potassium supplementation of normal serum levels in the general hospitalized population is unclear.
Potassium is predominantly an intracellular ion with 98% of total body potassium located in the intracellular space. The accepted reference range for serum potassium levels is 3.5 to 5.0 mEq/L. The kidneys are primarily responsible for potassium homeostasis with 90% of dietary potassium excreted in the urine.  Hypokalemia is frequently caused by excess urinary potassium excretion secondary to medications, especially loop and thiazide diuretics. It may also be caused by intracellular redistribution of potassium due to insulin or beta-adrenergic agonists. Gastrointestinal and non-diuretic renal losses are additional mechanisms of hypokalemia.
Hypokalemia is usually asymptomatic above levels of 3.0 mEq/L, and may be tolerated at or below this level in individuals with chronic hypokalemia. However, there is an increased risk of generalized weakness and constipation at levels between 2.5 and 3.0 mEq/L, particularly if this is an acute change. At levels below 2.5 mEq/L, muscle necrosis and rhabdomyolysis can occur, and levels less than 2.0 mEq/L can result in ascending paralysis and respiratory failure.  There is also an increased risk of potentially fatal cardiac arrhythmias as hypokalemia becomes more pronounced. A recent study highlighted the clinical significance of hypokalemia, showing that patients with potassium levels of less than 2.9 mEq/L on admission had significantly increased 7-day and 8 to 30-day in-hospital mortality, compared to those with reference levels of 3.4 to 3.8 mEq/L. 
While it is apparent that hypokalemia poses serious clinical complications, there is limited evidence for routine potassium repletion in the normal range within the general hospitalized population. Although individual institutions establish protocols specifying pre-determined potassium levels for all inpatients, there is a lack of published recommendations regarding goals for supplementation.  A recent study of more than 35,000 patients in Dublin sought to answer this question by analyzing the association between admission potassium level of inpatients and 30-day in-hospital mortality. They found that hypokalemia and hyperkalemia on admission were associated with an increased risk of in-hospital mortality, with the lowest rates of mortality in those with potassium ranging from 3.0 to 4.3 mEq/L. They also found that those with potassium levels in the upper range of normal (4.7-5.2 mEq/L) had increased mortality rates compared to the lower range of normal (4.3-4.7 mEq/L), leading to a recommendation against routine supplementation of potassium levels within the normal range.  However, it is important to note that these are measures of correlation between potassium levels and mortality, rather than causation. In addition, this study was not stratified based on cardiac and renal comorbidities, which may have resulted in significant confounding bias.
Given that there are minimal data to answer this clinical question, it is difficult to draw conclusions about the utility of routine potassium supplementation. However, the lack of published guidelines and an understanding of the levels at which potassium abnormalities manifest with clinical complications suggest that there may be minimal benefit of this common clinical practice. In addition, it is important to note that potassium supplementation is not a benign intervention, with iatrogenic hyperkalemia posing significant risks. For example, a recent study analyzed 451 hospitalized patients with hyperkalemia present upon or developed during admission and found that hyperkalemia associated with potassium supplementation had an increased independent risk of in-hospital mortality (OR 5.46, p<0.01). 
In contrast to the lack of evidence for routine potassium supplementation, there is abundant evidence for potassium repletion in those with underlying cardiac comorbidities. With respect to those with congestive heart failure (CHF), it has been shown that these patients are particularly sensitive to hypokalemia with increased risks of arrhythmia, syncope, cardiac arrest, and death.  A recent propensity-matched study of patients with chronic mild-moderate CHF showed that potassium levels less than 4.0 mEq/L were associated with increased all-cause mortality compared to potassium levels between 4.0 and 5.5 mEq/L, with each unit increase of serum potassium associated with a 22% reduction in risk of mortality (HR 0.78, p=0.003). These authors therefore recommend potassium-sparing diuretics and/or potassium supplementation to maintain levels greater than 4.0 mEq/L in those patients who require diuretics, and to avoid diuretics altogether in euvolemic patients with asymptomatic CHF due to the risk of hypokalemia.  In addition, a recent study of patients over 65 years old with CHF found that all-cause mortality was increased in patients with potassium of 3.5-4.0 mEq/L compared to those with potassium of 4.0-4.9 mEq/L (p=0.049), though there was no difference in hospitalizations among the groups. These findings resulted in a recommendation that elderly patients with CHF maintain a potassium level of 4.0-4.9 mEq/L, within and outside the hospital.  It has also been generally recommended to maintain a potassium level of 4.5 to 5.5 mEq/L in those with heart failure regardless of age, given the increased risk of sudden cardiac death and arrhythmias due to hypokalemia.  Potassium levels should therefore be monitored closely and supplemented appropriately in those with CHF, particularly in the setting of potential electrolyte abnormalities caused by chronic diuretic and ACE-inhibitor use within this patient population.
The role of potassium repletion has also been well studied in those with myocardial infarctions (MI). A recent study found that in-hospital mortality is increased in acute MI patients with post-admission potassium levels of less than 3.5 mEq/L and in those with levels greater than 4.5 mEq/L. Rates of ventricular arrhythmias and cardiac arrest were increased at levels less than 3.0 mEq/L and greater than 5.0 mEq/L, leading to a recommendation to maintain potassium levels between 3.5 and 4.5 mEq/L in patients with acute MIs.  It has also been recommended that potassium levels be maintained between 4.5 and 5.5 mEq/L during an acute MI, as hypokalemia has been associated with ventricular fibrillation.  Further studies suggest that long-term potassium levels greater than 4.5 mEq/L in those with prior MIs may be associated with increased mortality, with one study showing that patients with a first-time MI and a potassium level greater than or equal to 5.0 had increased 1, 3, 5, and 10 year mortality risks compared to reference groups.  Another study recommends maintaining long-term potassium levels between 3.5 and 4.0 in patients with MIs, as it was shown that there is an increased 3 year mortality risk following MI with potassium levels less than 3.5 mEq/L and greater than 4.5 mEq/L. 
While there is some disagreement about the ideal level at which potassium should be maintained in patients with cardiac comorbidities, it is evident that low normal and significantly elevated potassium levels are associated with increased complications and mortality. Therefore, potassium levels should be monitored closely in hospitalized patients with cardiac conditions and intervened upon in order to maintain ideal range potassium levels: generally between 4.0 to 5.5 mEq/L in those with CHF and between 3.5 and 4.5 mEq/L in those with MIs. In contrast, it is unclear if close monitoring and supplementation of normal potassium levels is beneficial in the general hospitalized population, raising questions about the utility of this common practice.
Dr. Sara Stream is an internal medicine resident at NYU Langone Health
Peer reviewed by David Goldfarb, MD, Clinical Chief, Nephrology, NYU Langone Health
Images courtesy of Wikimedia Commons
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