General Information and Epidemiology

• Though cutoffs vary, hyperkalemia is generally considered to be an elevated potassium level above 5.5 mEq/L
• Symptoms are usually not present until the potassium is above 7.0 mEq/L or if the level rapidly rises due to an acute insult
• There is no consensus definition for what is considered acute vs chronic hyperkalemia
• Hyperkalemia is present in about 2-3% of the population but can be present in up to half of patients with CKD

Pathophysiology

• Hyperkalemia influences resting membrane potential which can lead to increased excitability of cells 
• Only 2% of total body potassium is extracellular, and this level is tightly regulated
• The resting membrane potential is -90 mV. This potential becomes lower (LESS negative i.e negative 90 to negative 80) when there is more K outside cells, which means less of a signal is needed to fire an action potential, leading to increased excitability and possibly arrhythmias, especially if the changes to the potential are acute
• Chronic changes in extracellular potassium leads to compensatory mechanisms to reduce excitability
• K is exchanged for Na in the distal nephron - if RAAS is on (i.e due to hypovolemia, CHF, cirrhosis), less Na makes it to this portion, and K is not excreted in exchange for the Na, potentially leading to hyperkalemia
• Acidosis causes hyperkalemia by messing with Na/H antiporter efficacy which leads to decreased intracellular Na, which impacts the efficacy of the Na/K-ATPase, and leads to increased extracellular K, leading to hyperkalemia
• Insulin stimulates and BB inhibits the Na/K-ATPase pump leading to K+ staying outside the cell
• Hyperkalemia from acute insults is usually short-lived unless there is a chronic, ongoing process such as hypoaldosteronism, renal disease, or certain medication use

Etiology and Risk Factors

• The most common cause of hyperkalemia is decreased renal function or missed dialysis sessions in those with ESRD
• Common outpatient medicines that can cause hyperkalemia include ACE/ARBs, MRAs, NSAIDs, TMP-SMX all of which exert their effects by lowering the release of aldosterone; beta-blockers, digoxin, calcineurin inhibitors, and succinlycholine exert their effect by redistributing potassium
• Under normal conditions, human kidneys should be able to excrete up to 400 mmol of potassium each day - the risk of hyperkalemia is thus only really possible in those with renal disease
• Some of the most common sources of dietary K+ are potatoes, cereals (bran products, granola), meat, and dairy (milk, yogurt). Other potassium-rich foods include avocados, bananas, leafy green vegetables (except for kale), root vegetables (beets, carrots), and tomatoes
• Type IV RTA leads to reduced ability to reabsorb sodium in the distal tubule, thus less K excretion
• Hypoaldosteronism leads to hyperkalemia due to a lack of mineralocorticoids

Clinical Presentation and Diagnosis

• Patients with severely elevated or acutely elevated potassium levels are more likely to have symptoms; patients with chronic elevations will often be asymptomatic and may be diagnosed incidentally on lab work
• VBG/ABG potassium levels may not perfectly correlate with BMP but should be within 0.5 mmol/L
• In vivo hemolysis is a genuine cause of hyperkalemia, whereas hemolysis in vitro as part of the blood drawing process will lead to pseudohyperkalemia - most labs will report this as “hemolyzed” rather than report an inaccurate level
• The EKG does not always correlate with the actual K level - it depends in part on the chronicity of the elevation; as such, EKG is not a sensitive test for hyperkalemia but can alert you to the risk of an adverse cardiac event
• Classic EKG progression - peaked T waves → increased P interval, flattening of P wave → wide QRS and BBB → sine wave → PEA/asystole/VF
• Note that these changes do not necessarily happen in this order
• Atria are more susceptible to K which is why we tend to see p-wave flattening earlier than changes in QRS
• Hypo/Hyperkalemia is one of the H’s in the H’s and T’s for causes of PEA arrest; at very high levels hyperkalemia can lead to asystole - never a bad idea to give calcium gluconate if there is a suspicion
• The weakness associated with hyperkalemia often starts in the legs and then progresses to the arms (ascending paralysis)
• If a patient is in DKA, they may be hyperkalemic since insulin is not present to push potassium into cells, but TOTAL body K will be low, so you need to replete when less than 5.2 and hold insulin if less than 3.3

Treatment

• Calcium gluconate should reverse EKG changes in 5 minutes, if not, push again
• Calcium chloride has a higher risk of tissue necrosis at the IV site and should be given centrally
• Calcium salts have no actual effect on potassium levels, and don’t last more than 30-60 minutes - you must always give other treatments beyond calcium
• Temporizing and redistributing K can drive the K down ~0.5-1.5 in the short term
• Patients receiving insulin to temporize should not receive concomitant D50 if the glucose level is >250 - hyperglycemia can lead to worse extracellular potassium levels (like in DKA pathology); if you do administer dextrose, the insulin may outlast it, so watch for the development of hypoglycemia
• Giving insulin leads to potassium entering cells, commonly in the liver and skeletal muscle; this happens with normal physiology so that some can be released later on when patients are fasting to maintain balance, like with glucose
• Inhaled SABA (albuterol) should not be used as a monotherapy and is less likely to work in patients taking beta blockers or with CKD
• In normal conditions, 90% of potassium is eliminated renally, and 10% in stool
• Elimination via furosemide or Lokelma requires urine or stool output. If the patient cannot do either, the only other way to eliminate potassium is via dialysis
• Elimination is not required in all patients - especially if the acute insult has been addressed
• Cation-exchange resins like kayexalate and lokelma work by releasing sodium ions which are in turn exchanged with potassium in the gut
• Resins commonly lead to constipation and should be given with laxatives
• Sodium polystyrene sulfonate (also known as Kayexalate) has been shown to have rare but serious adverse effects, specifically gut necrosis
• Bicarbonate should only be used in patients with severe acidosis 

• Clinical Management of Hyperkalemia (Mayo Clin Proc, 2021)
• An Integrated View of Potassium Homeostasis (NEJM, 2015)
• Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age (JAMA, 2019) - Kayexalate is associated with serious GI adverse events over 30 days (0.2% of people who take vs. 0.1% who don’t) - NNH is 1000; intestinal ischemia is the most common‍
• Sodium zirconium cyclosilicate in hyperkalemia(NEJM 2015) - reduces K over placebo

• Clinical Problem Solvers - Hyperkalemia Schema
• Core EM - Hyperkalemia (good EKG change images)
• Life in the Fastlane - EKG Features of Hyperkalemia‍
• Strong Medicine - Hyperkalemia