HYPOMAGNESEMIA

Serum Mg <1.7 mg/dL — causes refractory hypokalemia and hypocalcemia, cardiac arrhythmias, and neuromuscular irritability; frequently overlooked

SYMPTOMS / ASSOCIATED SX

  • Often asymptomatic; symptoms overlap with hypokalemia and hypocalcemia (both co-occur with Mg deficiency)

  • Neuromuscular: tremor, fasciculations, muscle cramps, tetany, Chvostek/Trousseau signs (from accompanying hypoCa)

  • Cardiac: palpitations, QTc prolongation, ventricular arrhythmias (TdP), increased digoxin toxicity sensitivity

  • Refractory hypokalemia or hypocalcemia not responding to replacement → suspect underlying hypoMg

DENIES

  • Chronic PPI use >1 year (TRPM6 inhibition → hypoMg)

  • Diarrhea/malabsorption (GI loss)

  • Cisplatin, aminoglycoside, amphotericin use (renal wasting)

  • Alcohol use (poor intake + GI losses)

SOCIAL HISTORY

  • Alcohol use (direct GI losses, poor intake, malnutrition)

  • Chemotherapy regimen (cisplatin — renal Mg wasting that can be permanent)

MAIN ETIOLOGY

  • GI losses: diarrhea (most common), malabsorption, short bowel, NGT, vomiting, alcoholism

  • Renal wasting: loop/thiazide diuretics, aminoglycosides, cisplatin, amphotericin B, PPIs (chronic), tacrolimus/cyclosporine, cetuximab

  • Transcellular shift: refeeding syndrome, insulin administration, hungry bone syndrome

  • Gitelman syndrome: hypoMg + hypoK + metabolic alkalosis + hypocalciuria (distinguish from Bartter)

MOST COMMON DDX

  • Hypokalemia (check Mg whenever K is low — co-depletion common)

  • Hypocalcemia (Mg required for PTH secretion and action; severe hypoMg → functional hypoparathyroidism)

  • Alcohol withdrawal (low Mg + CNS hyperexcitability)

  • PPI-induced hypoMg (chronic PPI >1 year; check Mg annually on PPIs)

  • Cisplatin/aminoglycoside nephrotoxicity (permanent renal tubular Mg wasting)

  • Gitelman syndrome (hypoMg + hypoK + metabolic alkalosis + hypocalciuria)

DATA

  • Serum Mg (normal 1.7–2.4 mg/dL)

  • BMP (K, Ca, Na); ionized calcium; PTH if hypocalcemia present

  • Urine Mg/Cr ratio: >0.2 mmol/mmol = renal wasting; <0.2 = GI/inadequate intake

  • ECG (QTc prolongation, TdP); urine calcium (low in Gitelman)

HOME MEDS

  • PPIs — consider step-down or H2 blocker; supplement Mg orally; check Mg annually if continued

  • Loop diuretics — add amiloride (K- and Mg-sparing) or Mg supplement

  • Aminoglycosides — switch if possible; supplement Mg if continued

  • Digoxin — target Mg >2.0 to reduce toxicity risk

PLAN

  • Mild (Mg 1.2–1.7, asymptomatic):

    • Magnesium glycinate or citrate PO (better tolerated than oxide)

    • Magnesium oxide 400–800 mg PO daily (poorly absorbed; GI side effects)

  • Moderate (Mg 1.0–1.2) or symptomatic:

    • MgSO4 2 g IV over 2–4h; may repeat ×1–2 as needed; up to 4–8 g/day total

  • Severe (Mg <1.0) or arrhythmia/seizure/TdP:

    • MgSO4 2 g IV over 5–15 min (arrhythmia) or slow push (seizure); repeat 1–2 g IV over 1h PRN

    • TdP: MgSO4 2 g IV bolus over 15 min → infusion 3–20 mg/min; defibrillate if unstable

    • Pre-eclampsia/eclampsia: MgSO4 4–6 g IV loading then 1–2 g/h (target serum Mg 4–7 mg/dL)

  • Replete Mg BEFORE K — K will not normalize until Mg is repleted; Mg BEFORE Ca in hypocalcemia

  • Monitor toxicity during IV infusion: check knee jerk reflex q1h; areflexia = first sign → stop infusion; antidote: calcium gluconate 1 g IV

  • Amiloride 5–10 mg PO daily as maintenance if ongoing diuretic-related losses

  • DISCHARGE:

    • Oral Mg glycinate if ongoing losses; PPI review — consider H2 blocker or dose reduction

    • BMP in 3–5 days; nephrology or GI if refractory or malabsorption

RED FLAGS

  • TdP + hypoMg → MgSO4 2 g IV immediately; correct K >4.0 simultaneously

  • Mg <0.5 mg/dL → tetany, seizures; emergent IV correction; ICU monitoring

  • Mg toxicity: loss of DTRs → respiratory depression → cardiac arrest; STOP infusion; calcium gluconate 1 g IV

  • Refractory hypokalemia → ALWAYS check Mg; K will not normalize until Mg repleted

  • Hypomagnesemia + alcohol withdrawal → worsens seizure risk; aggressive replacement mandatory

SENIOR IM RESIDENT PEARLS

  • Mg is the "forgotten electrolyte" — 99% intracellular; normal serum Mg does not exclude significant total body depletion in alcoholics or critically ill

  • Mg required for PTH secretion AND PTH receptor signaling — severe hypoMg causes functional hypoparathyroidism; Ca will not correct until Mg is repleted

  • PPIs inhibit TRPM6 channels in gut/kidney — resolves with PPI discontinuation (Hoorn et al., Ann Int Med)

  • Cisplatin/aminoglycosides: irreversible tubular Mg wasting persisting months after drug stopped; may need indefinite oral supplementation

  • Common mistake: not checking Mg in refractory hypokalemia — hypoMg is almost always the cause

  • MgSO4 is first-line for TdP (Class I, AHA) — effective even with normal serum Mg

  • Common mistake: over-repleting Mg in CKD — reduced renal excretion; monitor reflexes frequently