Electrolytes

Evaluation 

• Determine Severity 
  • Mild – Total Ca <12 or iCa 5.6-8.0 
  • Moderate – Total Ca 12-13.9 or iCa 8-10 
  • Severe – Total Ca >14 or iCa >10 
• History and Physical 
  • Symptom presentation is quite variable and nonspecific 
  • Obtain malignancy history, review meds/supplements, FHx for hypercalcemia/PHPT 
  • Exam is typically normal in mild-moderate cases 
  • Lymphadenopathy and bony tenderness can be indicative of secondary cause 
• Workup 
• Review prior BMP, LFTs if available to determine chronicity 
• If serum albumin or acid/base status abnormal, obtain iCa if clinical uncertainty to confirm prior to treating 
• Once HyperCa confirmed, obtain same-day PTH 
• PTH elevated or normal: confirm Primary Hyperparathyroidism, consider Urine Ca testing for FHH 
• PTH suppressed: Consider stepwise testing based on clinical suspicion for Vit D toxicity, granulomatous disease, hematologic malignancy with Vit D metabolites (25-OH Vit D, 1,25-OH Vit D), suspected malignancy-based testing (CBC, SPEP/UPEP/FLC, PTHrP, imaging) 
• Cortisol, IGF-1 and metanephrines if rarer cause suspected when Vit D and cancer screening WNL (pheochromocytoma, acromegaly)

Acute Management Options

Chronic Management by Etiology

Evaluation 

• Confirm hypocalcemia with corrected Ca for albumin and iCa if acidosis/alkalosis or clinical uncertainty 
• Review medications, obtain serum Mg, Phos, LFTs, Cr, PTH, 25-OH Vit D 
• Further management depending on PTH status as below (AAFP has a good algorithmic chart)

PTH-Deficient Hypocalcemia (Low or Inappropriately Normal PTH)

PTH-Elevated Hypocalcemia (PTH Resistance or Secondary Causes)

Acute Management of Severe/Symptomatic Hypocalcemia 

• See VUMC Electrolyte Replacement Guidelines for dosing and route of administration per VUMC-specific practice.
• For general management considerations, see below

Transfusion-Associated Calcium Considerations 

• Standard transfusions (1-2 units over hours) do not require calcium supplementation as citrate is rapidly metabolized.
• Hepatic dysfunction and renal failure (especially CRRT with citrate anticoagulation) impair citrate metabolism—check ionized calcium after every 2-4 units, with a total-to-ionized calcium ratio >2.4 suggesting citrate accumulation.
• Rapid transfusion (>1 unit/hour) may overwhelm metabolic clearance, warranting ionized calcium monitoring after 2-4 units. 
• Patients with baseline hypocalcemia, hypoparathyroidism, or critical illness with shock/acidosis have reduced buffering capacity and warrant lower thresholds for monitoring and supplementation. 
• Chronically transfusion-dependent patients (MDS, thalassemia) rarely develop calcium issues; the primary concern is iron overload (~250 mg/unit) with hemosiderosis risk after 75-100 lifetime units.

Etiologies 

(by volume status)

• Hypovolemic hypernatremia results from renal losses (osmotic diuresis, diuretics) or extrarenal losses (diarrhea, burns, sweating). 
• Euvolemic hypernatremia occurs with central DI (post-pituitary surgery, TBI, tumors), nephrogenic DI (lithium, hypercalcemia, hypokalemia), or insensible losses. 
• Hypervolemic hypernatremia is typically iatrogenic (hypertonic saline, NaHCO₃) or from mineralocorticoid excess.

Diagnostic Evaluation 

• Assess volume status and check UOsm 
  • A Uosm >800 mOsm/kg indicates appropriate renal response suggesting extrarenal losses (GI, insensible) or inadequate intake. 
  • A Uosm <300 mOsm/kg suggests diabetes insipidus; a desmopressin trial differentiates central DI (Uosm increases >50%) from nephrogenic DI (no response). 
  • Copeptin testing offers 96.5% diagnostic accuracy for differentiating DI subtypes.

Management

Evaluation 

• Once Na <135 confirmed on BMP, assess for severe symptomatic (confusion, ataxia, seizure, obtundation) versus mild or asymptomatic (headache, lethargy, lightheadedness) 
• If mild or asymptomatic, next determine Serum Osm 
• Isotonic (SOsm 280-285) 
  • Assess for pseudohyponatremia causes (hyperproteinuria, hyperlipidemia) 
    • Hypotonic (SOsm <280) 
      • Hypovolemic 
        • UNa <20: Extrarenal losses (GI, third-spacing) 
        • UNa >20: Renal losses (or diuretics) 
      • Euvolemic (UNa usually >20) 
        • UOsm >100: SIADH, Hypothyroidism, adrenal insufficiency, stress, drug use 
        • UOsm <100: Primary polydipsia or low solute intake (beer potomania) 
        • Variable UOsm: reset osmostat 
      • Hypervolemic 
        • UNa <20: CHF, cirrhosis, nephrosis, hypoalbuminema 
        • UNa >20: renal failure 
  • Hypertonic (SOsm >285) 
    • Assess for recent mannitol, sorbitol, radiocontrast media use

Acute Management

Other Pearls

• Thiazide, SSRIs/SNRIs/TCAs, Antiepileptics, Antipsychotics, Opioids, Antineoplastic agents, Desmopressin, and PPIs are the most common medication-related etiologies of hyponatremia with varying mechanisms 
• SIADH is a diagnosis of exclusion requiring: clinical euvolemia, serum osmolality <280 mOsm/kg, urine osmolality >100 mOsm/kg, urine sodium >30 mEq/L, normal thyroid/adrenal/kidney function, and no recent diuretic use. 
• Major risk factors for Osmotic Demyelination Syndrome include severe hyponatremia (≤105 mEq/L), alcohol use disorder, advanced liver disease/transplantation, malnutrition, and concurrent hypokalemia (potassium repletion accelerates sodium correction). 
• Limit correction to ≤8 mEq/L/24 hours in high-risk patients; otherwise ≤10-12 mEq/L/24 hours.

Initial Assessment (K >5.0) 

• Check for pseudohyperkalemia (hemolysis, traumatic draw, thrombocytosis, leukocytosis) 
• Obtain ECG 
• Check EKG for hyperkalemic changes (sensitivity for EKG findings in hyper K is poor) 
  • K+ 5.5-6.5: peaked T waves, prolonged PR interval 
  • K+ 6.5-8: prolonged QRS, loss of P wave, ST elevation, ectopic beats 
  • K+ >8: sine wave pattern, asystole, PEA, VF 
  • Assess for warning signs: severe hyperkalemia (K+ >6.5), muscle weakness or paralysis, rapid K rise, or high-risk conditions (CKD, HF, MI)

Emergent Management 

(Warning signs present + ECG changes) 

• Cardiac Membrane Stabilization 
  • Calcium gluconate 10%: 1-2 g (10-20 mL) IV over 2-3 min 
  • Repeat in 5 min if ECG changes persist 
• Shift K+ Intracellularly 
  • Regular insulin 5-10 units IV + dextrose 50% 50 mL (if glucose 250 mg/dL) 
  • +/- Albuterol 10-20 mg nebulized over 10 min 
  • Monitor glucose q1h × 4-6 hours 
• Remove K+ from Body 
  • Sodium bicarbonate 50 mEq IV (if metabolic acidosis present) 
  • Loop diuretic (if volume overloaded) 
  • Potassium binders: Patiromer or sodium zirconium cyclosilicate (preferred over sodium polystyrene sulfonate)
  • Dialysis (for ESRD, severe renal impairment, or ongoing K+ release)

Non-Emergent Management 

(No warning signs or ECG changes) 

• Acutely Management 
  • Discontinue K+ supplements and K+-sparing diuretics 
  • Stop NSAIDs and other contributing medications 
  • Consider loop diuretic if volume overloaded 
  • Potassium binders if K+ remains elevated 
• Chronically 
  • Dietary counseling (reduce non-plant K+ sources) 
  • Medication review and adjustment 
  • Optimize diuretic therapy 
  • Correct metabolic acidosis if present 
  • Consider newer K+ binders (patiromer, sodium zirconium cyclosilicate; rather than older sodium polystyrene sulfonate) 
  • RAASi should generally be continued if K⁺ is 5.0-5.5 mEq/L; dose reduction (not below 50% of target) is preferred over discontinuation

Initial Assessment (K+ <3.5 mEq/L) 

• Confirm hypokalemia with repeat testing if needed 
• Obtain ECG 
• Assess for severe signs and symptoms (arrhythmia, paralysis, respiratory failure, or severe weakness) 
• Common offending medications: All diuretics, amphotericin B, aminoglycosides, cisplatin, highdose penicillins, and corticosteroids. 
  • Beta-agonists (albuterol, terbutaline) cause temporary shifts

Emergent Management (Severe signs/symptoms OR K+ ≤2.5 mEq/L) 

• Place patient on telemetry if not already on 
• Administer potassium chloride 5-10 mEq IV over 15-30 minutes 
  • Repeat until hemodynamically stable with resolution of ECG changes and K+ >3 mEq/L 
  • Use glucose-free fluids with added KCl if needing IV resuscitation (glucose stimulates insulin release and worsens intracellular shift) 
• Further IV treatment: 20-40 mEq in isotonic fluids infused up to 10 mEq/hour 
  • Rates up to 20 mEq/hour require cardiac monitoring and central access to avoid pain or venous sclerosis

Non-emergent Treatment (K+ >2.5 mEq/L, no severe symptoms, functioning GI tract) 

• Oral potassium chloride is preferred (lower risk of rebound hyperkalemia) 
  • KCl is most effective formulation: 10-40 mEq two to four times daily 
  • Potassium bicarbonate preferred for patients with metabolic acidosis 
  • Potassium phosphate appropriate for refeeding syndrome 
  • See VUMC Electrolyte Replacement Protocol for dosing and route of administration

Chronic Management 

• Identify and address underlying etiology 
• For diuretic-induced hypokalemia: discontinue if possible, adhere to low-salt diet, or add potassium-sparing diuretic, ACE inhibitor, ARB, or beta blocker 
• Dietary potassium alone is inadequate (most food potassium is coupled with phosphate, not chloride). 
• Oral KCl supplementation 50-75 mEq/day increases serum K+ by approximately 0.14 mEq/L 
  • Effect enhanced with ACE inhibitor or ARB use

Renal-Related Causes

• Decreased GFR → CKD/ESRD/AKI 
• Increased Tubular Resorption → Hypoparathyroidism, pseudohypoparathyroidism, acromegaly, bisphosphonate therapy, tumoral calcinosis

Non-Renal Related Causes

• Cell lysis → Tumor lysis syndrome, rhabdomyolysis, hemolysis, bowel infarction, malignant hyperthermia 
• Increased Exogenous Load → Phosphate-containing enemas/laxatives (Fleet enema), IV phosphate overdose, excessive oral phosphate intake 
• Transcellular shifts → Any acidotic state 
• Increased GI Resorption → Vitamin D toxicity, granulomatous diseases (sarcoidosis) 
• Spurious → Pseudohyperphosphatemia (paraprotein interference with assay—consider in monoclonal gammopathy)

Clinical Manifestations

• Acute → nausea, vomiting, diarrhea, lethargy, and seizures. 
• Secondary hypocalcemia → tetany, muscle cramps, cardiac arrhythmias, and hypotension 
• Chronic → vascular calcification, secondary hyperparathyroidism, and increased cardiovascular mortality

Diagnosis

• Check PTH level 
  • Low PTH suggests hypoparathyroidism or pseudohypoparathyroidism 
  • High PTH with normal calcium suggests acromegaly or tumoral calcinosis 
• When HyperPhos occurs with normal or near-normal renal function and PTH result does not explain the findings:
  • When PTH is low: 25-OH vitamin D and 1,25-dihydroxyvitamin D to evaluate for vitamin D toxicity or granulomatous disease 
• If vitamin D levels are normal, DDx includes hypoparathyroidism (surgical, autoimmune, genetic) 
  • When PTH is normal elevated (with normal Ca): FGF23 testing to differentiate acromegaly vs tumoral calcinosis

Management 

• Mild/asymptomatic (3.0-5.0 mg/dL): Dietary phosphate restriction; oral phosphate binders if chronic and refractory to dietary modification, Limit processed foods with phosphate additives 
• Moderate (5.0-6.5 mg/dL): IV saline with diuresis + oral phosphate binders, Aggressive hydration increases renal phosphate excretion 
• Severe (>6.5 mg/dL) without complications (typically seen in ESRD): Hemodialysis + binders, Continuous methods preferred (time-dependent phosphate removal); prevents rebound 
• Severe (>6.5 mg/dL) with AKI/ESRD and/or symptomatic hypocalcemia, Hemodialysis or CRRT, Definitive therapy when conservative measures fail

Phosphate Binder Review

• Calcium acetate, 667 mg (169 mg elemental Ca) with meals; start 1-2 tabs TID 
  • Inexpensive, effective; risk of hypercalcemia, vascular calcification; limit 1 g elemental Ca/day 
• Sevelamer (carbonate/HCl), 800-1600 mg TID with meals 
  • No calcium load; may reduce mortality vs calcium binders; GI side effects; expensive 
• Lanthanum carbonate, 500-1000 mg TID with meals (chewable) 
  • No calcium load; biliary excretion; nausea/constipation common 
• Sucroferric oxyhydroxide, 500 mg TID with meals (chewable) 
  • Iron-based; lower pill burden; minimal systemic iron absorption 
• Ferric citrate, 210 mg ferric iron TID with meals 
  • Iron-based; may improve iron stores/anemia; GI side effects 
• Aluminum hydroxide, 300-600 mg TID with meals 
  • Highly effective; limit to 1-2 days due to aluminum toxicity

Other Pearls

• KDIGO guidelines suggest lowering elevated phosphate toward the normal range and restricting calcium-based binders to limit elemental calcium intake to <800-1000 mg/day. 
• Don’t be afraid to consult nephrology, endocrinology 
• Keep non-renal etiologies on differential if unclear or no significant renal dysfunction 
• In tumor lysis syndrome, hyperphosphatemia may be the best predictor of AKI and CRRT is preferred over iHD to prevent rebound

Overview and Clinical Manifestations

• Mild (1.8-2.5 mg/dL), moderate (1.0-1.7 mg/dL), or severe (<1.0 mg/dL) 
• Acute severe hypophosphatemia → rhabdomyolysis, respiratory failure, hemolysis, cardiac dysfunction, and neurologic symptoms 
• Chronic hypophosphatemia causes osteomalacia (adults) or rickets (children), bone pain, proximal muscle weakness, waddling gait, and insufficiency fractures

Etiologies by Inpatient Encounter Frequency

• Most Common (Intracellular Shift—Acute) 
• Sepsis, Respiratory alkalosis, Refeeding syndrome; occurs within 2-5 days of nutritional repletion, Insulin/IV dextrose administration treatment, TPN initiation, Post-surgical/hungry bone syndrome (after parathyroidectomy or thyroidectomy) 
  • Common (Decreased Intake/Absorption) 
• Chronic alcoholism, Malnutrition/prolonged NPO status, Phosphate-binding antacids 
  • Moderately Common (Medication-Induced) 
• IV iron infusions, Diuretics (acetazolamide, thiazides), Chemotherapy (cisplatin, ifosfamide), Antiretrovirals (tenofovir) 
  • Less Common (Renal Losses—Chronic) 
• Primary hyperparathyroidism, Post-kidney transplant, Vitamin D deficiency (secondary hyperparathyroidism) 
  • Rare (Genetic/FGF23-Mediated) 
• X-linked hypophosphatemia, Tumor-induced osteomalacia, Other hereditary hypophosphatemias

Management

• See VUMC Electrolyte Replacement Guidelines for dosing and route of administration 
  • Generally, IV replacement is indicated for severe (<1 mg/dL) or symptomatic hypophosphatemia; oral replacement is preferred for mild-moderate asymptomatic cases 
  • Type of replacement formula should be dictated in-part by serum K and Na levels to avoid iatrogenic over/undercorrection of those levels 
• Lab monitoring is recommended in high-risk settings: refeeding syndrome, DKA, alcoholic ketoacidosis, COPD/asthma exacerbations, post-kidney transplant, and after IV iron infusions, typically checked thrice weekly 
• Always check and correct concurrent HypoMg and HypoK 
• In FGF23-mediated diseases, burosumab (anti-FGF23) is now approved for X-linked hypophosphatemia 
• In Hypophosphatemic rickets/osteomalacia with Hypercalciuria, oral phosphate alone is used (active vitamin D contraindicated)

Clinical Manifestations

• Often presents with nonspecific symptoms (lethargy, muscle cramps, weakness) 
• Severe hypomagnesemia (<1.2 mg/dL) causes neuromuscular irritability (carpopedal spasm, tremors, seizures), cardiac arrhythmias (atrial fibrillation, torsades de pointes, prolonged QT), and metabolic derangements 
• Usually associated with concurrent hypocalcemia, hypokalemia, and metabolic alkalosis

Etiologies

• Decreased PO intake, GI/Renal losses, Transcellular shifts (Refeeding, insulin, hungry bone syndrome), Endocrine/Metabolic (T2DM, hyperaldosteronism, hyperthyroidism) 
• Common offending medications: PPIs, diuretics, Calcineurin inhibitors, cisplatin, EGFR antagonists (cetuximab, erlotinib), aminoglycosides, amphotericin B, pentamidine, and foscarnet

Management

• See VUMC Electrolyte Replacement Guidelines for dosing and route of administration 
• Generally IV preferred over PO due to better absorption and diarrhea limiting PO dosing.

Overview 

• Generally occurs only with renal insufficiency combined with excessive magnesium intake/replacement 
• Elderly patients with bowel disorders (ulcer disease, gastritis, colitis, bowel obstruction) may develop even without severe renal impairment due to enhanced GI absorption

Clinical Manifestations 

• 4-6 mg/dL: nausea, flushing, hypotension, and diminished reflexes 
• 6-10 mg/dL: loss of deep tendon reflexes (patellar reflex loss is an early warning sign), lethargy, and ileus 
• 10-12 mg/dL: flaccid paralysis, respiratory depression, and ECG changes (prolonged PR, QRS, QT)
• Above 12 mg/dL: complete heart block, respiratory arrest, and cardiac arrest

Management 

• Simply discontinuing exogenous magnesium is sufficient in patients with adequate renal function 
• For symptomatic patients, IV calcium gluconate (1-2 g over 5-10 min) is first-line to temporize neuromuscular/cardiac effects 
• Loop diuretics with saline can enhance renal excretion if GFR is adequate 
• Hemodialysis is indicated for severe cases (Mg >9 mg/dL), refractory symptoms, or ESRD