What are the recommended dosing and administration methods for pharmacologic correction of electrolyte abnormalities such as hyponatremia, hypernatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, hypermagnesemia, and hypophosphatemia?

Pharmacologic Correction of Electrolyte Imbalances: Dosing and Administration

Hypokalemia

Severity Classification and Treatment Approach

For mild hypokalemia (3.0-3.5 mEq/L), oral potassium chloride 20-60 mEq/day divided into 2-3 doses is the preferred treatment, targeting serum levels of 4.0-5.0 mEq/L. 1

• Moderate hypokalemia (2.5-2.9 mEq/L) requires prompt correction with oral potassium chloride 40-60 mEq/day, as this level increases cardiac arrhythmia risk, especially in patients with heart disease or on digitalis 1
• Severe hypokalemia (≤2.5 mEq/L) mandates IV replacement with continuous cardiac monitoring due to life-threatening arrhythmia risk 1, 2

Intravenous Potassium Replacement

The maximum peripheral infusion rate is ≤10 mEq/hour, using a concentration of ≤40 mEq/L to minimize cardiac complications. 1

• Add 20-30 mEq potassium per liter of IV fluid, preferably 2/3 KCl and 1/3 KPO4 to address concurrent phosphate depletion 3, 1
• Central line access allows higher concentrations and faster rates (up to 20 mEq/hour) but only in extreme circumstances with continuous cardiac monitoring 1
• Recheck potassium within 1-2 hours after IV administration to prevent overcorrection 1

Critical Pre-Treatment Requirements

Always check and correct magnesium levels first—hypomagnesemia is the most common reason for refractory hypokalemia and must reach >0.6 mmol/L before potassium will normalize. 1

• Verify adequate urine output (≥0.5 mL/kg/hour) before initiating potassium replacement 3, 1
• In diabetic ketoacidosis, delay insulin therapy if K+ <3.3 mEq/L until potassium is restored 1
• Add 20-40 mEq/L potassium to IV fluids once K+ falls below 5.5 mEq/L in DKA with adequate urine output 3, 1

Monitoring Protocol

• Check potassium and renal function within 2-3 days and again at 7 days after starting supplementation 1
• Continue monitoring every 1-2 weeks until stable, then at 3 months, then every 6 months 1
• More frequent monitoring required for renal impairment (eGFR <45 mL/min), heart failure, or concurrent RAAS inhibitors 1

Special Considerations

• Potassium-sparing diuretics (spironolactone 25-100 mg daily, amiloride 5-10 mg daily, or triamterene 50-100 mg daily) are superior to chronic oral supplements for diuretic-induced hypokalemia 1
• Patients on ACE inhibitors/ARBs alone or with aldosterone antagonists frequently do not require routine potassium supplementation, which may be deleterious 1
• Avoid potassium-sparing diuretics when GFR <45 mL/min or baseline K+ >5.0 mEq/L 1

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Hyperkalemia

Emergency Management

For severe hyperkalemia (>6.5 mEq/L) or ECG changes, immediately administer IV calcium gluconate 10%: 15-30 mL over 2-5 minutes to stabilize cardiac membranes, followed by insulin 10 units IV with 25 grams dextrose (D50W 50 mL) to shift potassium intracellularly. 1

• Calcium onset is 1-3 minutes; repeat dose if no ECG improvement within 5-10 minutes 1
• Insulin/glucose lowers K+ by 0.5-1.2 mEq/L within 30-60 minutes 1
• Add albuterol 10-20 mg nebulized over 10 minutes to augment effect (lowers K+ by 0.5-1.0 mEq/L) 1, 2

Potassium Removal Strategies

• Infuse isotonic saline (0.9% NaCl) with IV furosemide to enhance renal excretion 2
• Initiate newer potassium binders: patiromer (Veltassa) or sodium zirconium cyclosilicate (ZS-9) for sustained management 1, 4
• Avoid sodium polystyrene sulfonate (Kayexalate) due to severe GI adverse effects including bowel necrosis 1
• Hemodialysis for refractory cases or when K+ >6.5 mEq/L with renal failure 2

Monitoring Requirements

• Continuous cardiac monitoring for K+ >6.5 mEq/L or any ECG changes 1
• Recheck potassium within 1-2 hours after insulin/glucose, then every 2-4 hours during acute phase 1
• Rule out pseudohyperkalemia from hemolysis or inadequate phlebotomy technique before aggressive treatment 5, 6

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Hyponatremia

Initial Assessment and Fluid Management

For hypovolemic hyponatremia, infuse isotonic saline (0.9% NaCl) at 10-20 mL/kg/hour for the first hour, not exceeding 50 mL/kg over the first 4 hours. 3

• Assess volume status clinically: hypovolemic patients require isotonic saline; euvolemic patients (SIADH) require fluid restriction 2
• Measure serum electrolytes, glucose, serum and urine osmolarity, and urine sodium for diagnostic workup 2

Correction Rate Limits

The increase in sodium concentration must not exceed 10 mmol/L within the first 24 hours and 18 mmol/L within the first 48 hours to prevent central pontine myelinolysis. 2

• Rapid correction causes osmotic demyelination syndrome with permanent neurologic injury 7
• Monitor sodium levels every 2-4 hours during active correction 2

Severe Symptomatic Hyponatremia

• Symptoms include cerebral seizures, somnolence, coma, and altered mental status 2, 7
• Consider hypertonic saline (3% NaCl) for severe symptomatic cases with seizures or coma, but maintain strict correction rate limits 2

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Hypernatremia

Fluid Replacement Strategy

Administer isotonic saline (0.9% NaCl) initially at 10-20 mL/kg/hour for severely dehydrated patients, then transition to hypotonic fluids once hemodynamically stable. 3

• Gradual reduction in osmolality at ≤3 mOsm/kg H2O/hour prevents cerebral edema 3
• Monitor mental status closely to detect iatrogenic complications from fluid overload 3
• Symptoms include circulatory failure, muscular weakness, disorientation, convulsions, and coma 8

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Hypocalcemia

Acute Symptomatic Treatment

For tetanic spasms or severe symptoms, administer IV calcium gluconate 10%: 15-30 mL over 2-5 minutes. 1

• Hypocalcemia causes tetanic spasms, seizures, and cardiac arrhythmias 8, 7
• Correct concurrent hypomagnesemia and alkalosis before calcium administration 7
• Monitor for secondary hypocalcemia from hyperphosphatemia in renal failure 5

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Hypercalcemia

Emergency Management

• Infuse physiological saline solution to enhance renal calcium excretion 8
• Administer calcitonin or mithramycin for severe cases 8
• Symptoms include lassitude, tachycardia, nausea, vomiting, renal dysfunction, and neurologic symptoms 8

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Hypomagnesemia

Oral vs. Intravenous Replacement

For stable patients, use oral magnesium supplementation 200-400 mg elemental magnesium daily divided into 2-3 doses, preferring organic salts (aspartate, citrate, lactate) over oxide or hydroxide for superior bioavailability. 1

• Target magnesium level >0.6 mmol/L (>1.5 mg/dL) 1
• For severe symptomatic hypomagnesemia with cardiac manifestations, administer 1-2 g MgSO4 IV push for life-threatening arrhythmias including torsades de pointes 1
• For severe refractory asthma, give 2 g magnesium sulfate IV over 20 minutes 1

Safety Considerations

• Too-rapid magnesium administration causes hypotension, bradycardia, and cardiac arrhythmias 1
• Avoid magnesium supplements when creatinine clearance <20 mg/dL due to hypermagnesemia risk 1
• Continuous cardiac monitoring required during IV infusion in cardiac patients 1

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Hypophosphatemia

Replacement Dosing

• For serum phosphorus 1.8 mg/dL to lower end of normal: 0.16-0.31 mmol/kg phosphorus (0.23-0.46 mEq/kg potassium) 1
• For serum phosphorus 1.0-1.7 mg/dL: 0.32-0.43 mmol/kg phosphorus (0.47-0.63 mEq/kg potassium) 1
• For serum phosphorus <1.0 mg/dL: 0.44-0.64 mmol/kg phosphorus (0.64-0.94 mEq/kg potassium), maximum single dose 45 mmol phosphorus (66 mEq potassium) 1

Critical Pre-Administration Checks

• Verify serum potassium <4.0 mEq/L before giving IV potassium phosphate 1
• Check and normalize calcium first 1
• Hypophosphatemia develops in 60-80% of ICU patients on intensive kidney replacement therapy when standard phosphate-free solutions are used 4

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Special Populations

Diabetic Ketoacidosis (DKA)

Add 20-40 mEq/L potassium (2/3 KCl and 1/3 KPO4) to each liter of IV fluid once K+ falls below 5.5 mEq/L with adequate urine output established. 3, 1

• Typical total body potassium deficits are 3-5 mEq/kg body weight despite initially normal or elevated serum levels 3, 1
• Delay insulin therapy if K+ <3.3 mEq/L until potassium restored to prevent life-threatening arrhythmias 1
• Monitor potassium every 2-4 hours during active treatment 3

Acute Kidney Injury (AKI)

Use concentrated "renal" enteral or parenteral formulas with lower electrolyte content in patients with hyperkalemia and hyperphosphatemia. 4

• Measure serum urea, creatinine, sodium, potassium, bicarbonate, phosphorus, calcium, and magnesium at least every 48 hours, or more frequently if clinically indicated 4
• Use dialysis solutions containing potassium 4 mEq/L during continuous kidney replacement therapy to prevent hypokalemia 1, 4
• Hyperkalemia and hyperphosphatemia typically improve when kidney replacement therapy is initiated 4

Chronic Kidney Disease (CKD) Stage 4

Implement dietary potassium restriction and newer potassium binders (patiromer or sodium zirconium cyclosilicate) to maintain serum potassium 4.0-5.0 mEq/L while continuing RAAS inhibitor therapy. 1

• Start potassium supplementation at 10 mEq daily initially if needed, with monitoring within 48-72 hours 1
• Check potassium and renal function within 1 week of starting potassium binder therapy 1
• Avoid potassium-sparing diuretics when GFR <45 mL/min 1

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Critical Safety Protocols

Medication Handling

Remove concentrated potassium chloride vials from patient care areas and replace with premixed potassium-containing solutions to reduce dosing errors. 1

• Institute mandatory double-check policy for all potassium infusion preparation and administration 1
• Use distinct, standardized labeling and packaging 1
• Never administer potassium as IV push or bolus—this is ill-advised and potentially fatal 3, 1

High-Risk Medication Interactions

• Avoid NSAIDs entirely during potassium replacement, especially with RAAS inhibitors, as they cause acute renal failure and severe hyperkalemia 1
• Do not combine potassium supplements with potassium-sparing diuretics without specialist consultation 1
• Avoid routine triple combination of ACE inhibitor + ARB + aldosterone antagonist due to extreme hyperkalemia risk 1

Common Pitfalls to Avoid

• Never supplement potassium without checking and correcting magnesium first—this is the single most common reason for treatment failure 1
• Do not administer digoxin before correcting hypokalemia, as this significantly increases life-threatening arrhythmia risk 1
• Avoid aggressive potassium repletion during high-dose insulin therapy, as moderate hypokalemia (2.5-2.8 mEq/L) may be acceptable 1
• Do not use potassium citrate or other non-chloride salts for supplementation, as they worsen metabolic alkalosis 1