How are Hypokalemia and Hyperkalemia treated?

Hypokalemia and Hyperkalemia: Clinical Management

Hypokalemia

Classification and Risk Assessment

Hypokalemia severity is classified as mild (3.0-3.5 mEq/L), moderate (2.5-2.9 mEq/L), or severe (≤2.5 mEq/L), with moderate hypokalemia requiring prompt correction due to increased risk of cardiac arrhythmias, especially in patients with heart disease or those on digitalis. 1

• Patients with potassium levels below 2.7 mEq/L are at higher risk for clinical problems, including ventricular tachycardia, torsades de pointes, and ventricular fibrillation 1
• ECG changes typically manifest as ST-segment depression, T wave flattening/broadening, and prominent U waves 1
• Very low serum potassium levels (≤2.5 mEq/L) can lead to muscle necrosis, paralysis, cardiac arrhythmias, and impaired respiration, which can be life-threatening 2
• Only 2% of total body potassium is extracellular, so small serum changes reflect massive total body deficits 1

Initial Assessment

Before initiating treatment, verify the potassium level with a repeat sample to rule out fictitious hypokalemia from hemolysis during phlebotomy, and immediately check magnesium levels (target >0.6 mmol/L), as hypomagnesemia is the most common reason for refractory hypokalemia and must be corrected before potassium levels will normalize. 1

• Obtain an ECG to assess for arrhythmias and conduction abnormalities 1
• Evaluate renal function (creatinine, eGFR) and glucose to identify contributing factors 1
• Review all medications, particularly diuretics (loop diuretics and thiazides are the most common cause), corticosteroids, beta-agonists, and insulin 1, 3
• Assess for gastrointestinal losses, inadequate dietary intake, or transcellular shifts 1

Treatment Algorithm

Severe Hypokalemia (≤2.5 mEq/L or with ECG changes/symptoms)

Severe hypokalemia requires immediate aggressive treatment with intravenous potassium supplementation in a monitored setting due to the high risk of life-threatening cardiac arrhythmias. 1

• Establish large-bore IV access for rapid potassium administration 1
• Administer IV potassium at rates not exceeding 10-20 mEq/hour through peripheral lines, or up to 40 mEq/hour through central lines with continuous cardiac monitoring 1
• Recheck serum potassium within 1-2 hours after IV potassium correction to ensure adequate response and avoid overcorrection 1
• Continue monitoring potassium levels every 2-4 hours during the acute treatment phase until stabilized 1
• Critical pitfall: Too-rapid IV potassium administration can cause cardiac arrhythmias and cardiac arrest; rates exceeding 20 mEq/hour should only be used in extreme circumstances with continuous cardiac monitoring 1

Moderate Hypokalemia (2.5-2.9 mEq/L)

For moderate hypokalemia, oral potassium chloride 20-60 mEq/day divided into 2-3 doses is the preferred treatment to maintain serum potassium in the 4.0-5.0 mEq/L range. 1

• Divide doses throughout the day to avoid rapid fluctuations in blood levels and improve gastrointestinal tolerance 1
• Recheck potassium and renal function within 3-7 days after starting supplementation 1
• Continue monitoring every 1-2 weeks until values stabilize, then at 3 months, and subsequently at 6-month intervals 1

Mild Hypokalemia (3.0-3.5 mEq/L)

For mild hypokalemia in stable patients, dietary advice to increase intake of potassium-rich foods (bananas, oranges, potatoes, tomatoes, legumes, yogurt) may be sufficient, with oral potassium chloride 20-40 mEq daily reserved for those who cannot achieve adequate dietary intake. 1

Special Clinical Scenarios

Diuretic-Induced Hypokalemia

For persistent diuretic-induced hypokalemia despite supplementation, adding potassium-sparing diuretics (spironolactone 25-100 mg daily, amiloride 5-10 mg daily, or triamterene 50-100 mg daily) is more effective than chronic oral potassium supplements, providing more stable levels without peaks and troughs. 1

• Check serum potassium and creatinine 5-7 days after initiating potassium-sparing diuretic, and continue monitoring every 5-7 days until potassium values stabilize 1
• Avoid potassium-sparing diuretics in patients with significant chronic kidney disease (GFR <45 mL/min) due to increased hyperkalemia risk 1
• Use caution when combining potassium-sparing diuretics with ACE inhibitors or ARBs due to increased hyperkalemia risk 1

Diabetic Ketoacidosis

In DKA, add 20-30 mEq potassium (2/3 KCl and 1/3 KPO4) to each liter of IV fluid once K+ falls below 5.5 mEq/L and adequate urine output is established. 1

• If K+ <3.3 mEq/L in DKA patients, delay insulin therapy until potassium is restored to prevent life-threatening arrhythmias 1
• Monitor potassium levels every 2-4 hours during active treatment 1

Patients on RAAS Inhibitors

In patients taking ACE inhibitors or ARBs alone or in combination with aldosterone antagonists, routine potassium supplementation may be unnecessary and potentially deleterious, as these medications reduce renal potassium losses. 1

• Reduce or discontinue potassium supplementation when initiating aldosterone receptor antagonists to avoid hyperkalemia 1
• Monitor potassium levels within 7-10 days after starting or increasing RAAS inhibitors 1

Critical Medications to Avoid in Hypokalemia

Digoxin orders should be questioned in patients with severe hypokalemia, as this medication can cause life-threatening cardiac arrhythmias when administered during severe hypokalemia. 1

• Most antiarrhythmic agents should be avoided as they can exert important cardiodepressant and proarrhythmic effects in the setting of hypokalemia; only amiodarone and dofetilide have been shown not to adversely affect survival 1
• Thiazide and loop diuretics can further deplete potassium levels and should be questioned until hypokalemia is corrected 1
• NSAIDs should be avoided as they can cause sodium retention, peripheral vasoconstriction, and attenuate treatment efficacy 1

Refractory Hypokalemia

When hypokalemia persists despite adequate supplementation, the most common reason is uncorrected hypomagnesemia, which causes dysfunction of potassium transport systems and increases renal potassium excretion. 1

• Use organic magnesium salts (aspartate, citrate, lactate) rather than oxide or hydroxide due to superior bioavailability 1
• Correct any sodium/water depletion first, as hypoaldosteronism from volume depletion paradoxically increases renal potassium losses 1
• Investigate constipation (can increase colonic potassium losses) and tissue destruction (catabolism, infection, surgery, chemotherapy) 1

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Hyperkalemia

Classification and Risk Assessment

Hyperkalemia is classified as mild (>5.0 to <5.5 mEq/L), moderate (5.5 to 6.0 mEq/L), or severe (>6.0 mEq/L), with patients having severe hyperkalemia (>6.0 mEq/L), ECG changes, or symptoms requiring immediate hospital admission due to high risk of cardiac arrhythmias and sudden death. 4, 5

• ECG changes progress in a characteristic pattern: peaked T waves → flattened or absent P waves → prolonged PR interval → widened QRS complex → deepened S waves 5
• Critical pitfall: Hyperkalemia is often asymptomatic, and the first indicator may be peaked T waves on ECG rather than clinical symptoms 5
• Neuromuscular symptoms include flaccid paralysis, paresthesias, depressed deep tendon reflexes, respiratory difficulties, and muscle weakness 5

Initial Assessment

Rule out pseudohyperkalemia by repeating the measurement with proper blood sampling technique, as hemolysis or tissue breakdown during phlebotomy can falsely elevate potassium levels. 4

• Obtain an ECG immediately to assess for cardiac effects 4
• Review medications that may contribute to hyperkalemia: RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists), potassium-sparing diuretics, NSAIDs, and potassium supplements 4
• Assess for underlying conditions: chronic kidney disease, diabetes mellitus, heart failure, adrenal insufficiency 4
• Evaluate for non-dietary causes: metabolic acidosis, tissue destruction, constipation, inadequate dialysis 4

Emergency Management of Severe Hyperkalemia (>6.5 mEq/L or ECG changes)

Immediate multi-pronged treatment is required for life-threatening hyperkalemia, including calcium for membrane stabilization, agents to shift potassium intracellularly, and measures to remove potassium from the body. 5

Step 1: Cardiac Membrane Stabilization (Onset: 1-3 minutes)

• Administer calcium gluconate 10% (15-30 mL IV over 2-5 minutes) or calcium chloride 10% (5-10 mL or 500-1000 mg IV over 2-5 minutes) to stabilize cardiac membranes 5
• This does not lower potassium levels but protects against arrhythmias 5
• If no ECG improvement within 5-10 minutes, repeat the dose 1
• Caution: Use calcium with extreme care in patients on digoxin due to risk of digitalis toxicity 6

Step 2: Shift Potassium Intracellularly (Onset: 30-60 minutes)

• Administer 25 g glucose (50 mL of D50) with 10 U regular insulin IV over 15-30 minutes 5
• Nebulized albuterol (10-20 mg) can be used as adjunctive therapy 5
• Sodium bicarbonate (50-100 mEq IV) if metabolic acidosis is present 6
• Recheck potassium levels within 1-2 hours after insulin/glucose or beta-agonist therapy, as these agents have a short duration of effect (2-4 hours) and rebound hyperkalemia can occur 1

Step 3: Remove Potassium from the Body

• Loop diuretics (furosemide 40-80 mg IV) if patient has adequate kidney function 5
• Newer potassium binders (patiromer or sodium zirconium cyclosilicate) are superior to sodium polystyrene sulfonate (SPS) due to limited efficacy data and serious gastrointestinal adverse effects associated with SPS 1
• Hemodialysis for refractory cases or severe renal impairment 5

Management of Chronic/Recurrent Hyperkalemia

For patients with chronic hyperkalemia (K+ >5.0 mEq/L) on RAAS inhibitors, initiate approved potassium-lowering agents (patiromer or sodium zirconium cyclosilicate) to maintain serum potassium 4.0-5.0 mEq/L while continuing cardioprotective and renoprotective RAAS inhibitor therapy. 7, 1

RAAS Inhibitor Management Algorithm

• K+ 4.5-5.0 mEq/L not on maximal RAASi therapy: Initiate or up-titrate RAASi therapy and closely monitor K+ levels 7, 1
• K+ >5.0-<6.5 mEq/L not on maximal RAASi therapy: Initiate an approved K+-lowering agent; if levels <5.0 mEq/L are detected, up-titrate RAASi 7
• K+ >5.0-<6.5 mEq/L on maximal RAASi therapy: Initiate K+-lowering agent and maintain treatment unless alternative treatable etiology is identified 7
• K+ >6.5 mEq/L: Discontinue or reduce RAASi immediately and initiate K+-lowering agent as soon as K+ levels >5.0 mEq/L 7, 1

Dietary Management

• Restrict potassium intake to <3 g/day (approximately 50-70 mmol/day) 4
• Avoid high-potassium foods: bananas, oranges, melons, potatoes, tomato products, salt substitutes containing potassium, legumes, lentils, chocolate, yogurt 4
• Avoid herbal supplements that raise K+: alfalfa, dandelion, horsetail, nettle 1

Monitoring Protocol

• Check serum potassium and renal function within 1 week of starting potassium binder therapy 1
• Monitor weekly during dose titration phase, at 1-2 weeks after achieving stable dose, at 3 months, and every 6 months thereafter 1
• When initiating K+-lowering therapy, monitor closely not only for efficacy but also to protect against hypokalemia, which may be even more dangerous than hyperkalemia 1

Management of Moderate Hyperkalemia (5.5-6.0 mEq/L)

For asymptomatic moderate hyperkalemia with normal ECG, implement dietary potassium restriction, review and adjust contributing medications, and consider loop diuretics if adequate kidney function is present. 4

• Recheck serum potassium within 24-48 hours to assess response to initial interventions 4
• Schedule additional follow-up potassium measurement within 1 week 4
• Do not prematurely discontinue beneficial RAAS inhibitors; dose reduction and addition of potassium binders is preferred to maintain cardioprotective and renoprotective benefits 4, 5

High-Risk Populations Requiring Close Monitoring

• Advanced chronic kidney disease (up to 73% risk of hyperkalemia) 5
• Chronic heart failure (up to 40% risk) 5
• Diabetes mellitus 4
• Elderly patients 5
• Patients on spironolactone or other RAAS inhibitors (combination RAAS therapy increases hyperkalemia risk to 5-10%) 4

Critical Pitfalls to Avoid

• Failing to rule out pseudohyperkalemia before initiating aggressive treatment 4
• Overlooking ECG changes in patients with hyperkalemia 4
• Delaying treatment of severe hyperkalemia while waiting for confirmation of repeat laboratory values when clinical suspicion is high 4
• Permanently discontinuing beneficial RAAS inhibitors after a single elevated potassium measurement, which offsets survival benefits 5
• Too rapid lowering of serum potassium in patients stabilized on digitalis can produce digitalis toxicity 6

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Clinical Vignettes

Vignette 1: Moderate Hypokalemia in a Patient on Furosemide

Clinical Presentation: A 68-year-old woman with heart failure presents with fatigue and muscle weakness. She takes furosemide 40 mg daily. Serum potassium is 2.9 mEq/L. ECG shows ST-segment depression and prominent U waves.

Management:

• This represents moderate hypokalemia requiring prompt correction 1
• Check magnesium level immediately (target >0.6 mmol/L) and correct if low 1
• Initiate oral potassium chloride 40 mEq daily divided into two doses 1
• Consider adding spironolactone 25 mg daily for more stable long-term potassium control 1
• Recheck potassium and renal function within 3-7 days 1
• Target potassium range: 4.0-5.0 mEq/L 1

Vignette 2: Severe Hyperkalemia with ECG Changes

Clinical Presentation: A 72-year-old man with stage 4 CKD on lisinopril and spironolactone presents with weakness. Serum potassium is 7.2 mEq/L. ECG shows peaked T waves and widened QRS complex.

Management:

• This is a medical emergency requiring immediate multi-pronged treatment 5
• Step 1: Administer calcium gluconate 10% (15-30 mL IV over 2-5 minutes) for cardiac membrane stabilization 5
• Step 2: Give 25 g glucose (50 mL D50) with 10 U regular insulin IV over 15-30 minutes to shift potassium intracellularly 5
• Step 3: Discontinue spironolactone and reduce lisinopril dose 7
• Step 4: Administer furosemide 40-80 mg IV if adequate kidney function 5
• Recheck potassium within 1-2 hours after insulin/glucose therapy 1
• Initiate patiromer or sodium zirconium cyclosilicate for chronic management once potassium <6.0 mEq/L 1
• Carefully reintroduce RAAS inhibitor at lower dose once potassium stabilizes 7

Vignette 3: Refractory Hypokalemia

Clinical Presentation: A 55-year-old woman with cirrhosis on furosemide 80 mg daily has persistent hypokalemia (K+ 3.0 mEq/L) despite oral potassium chloride 60 mEq daily.

Management:

• Check magnesium level immediately—this is the most common reason for refractory hypokalemia 1
• If magnesium is low, administer organic magnesium salts (aspartate, citrate, or lactate) 1
• Consider switching from oral potassium supplements to spironolactone 50-100 mg daily for more stable potassium levels 1
• Adjust furosemide:spironolactone ratio to 40:100 mg to maintain adequate serum potassium 1
• Monitor potassium and creatinine every 5-7 days until values stabilize 1
• Never supplement potassium without checking and correcting magnesium first—this is the most common reason for treatment failure 1