Milk-Alkali Syndrome (Calcium-Alkali Syndrome, MAS)

Who turns up with it - Postmenopausal women on over-the-counter calcium carbonate, CKD patients on calcium-based phosphate binders, patients on prolonged corticosteroids, pregnant patients using calcium carbonate for reflux, betel nut chewers, and heavy users of calcium-containing nicotine gum. Most are asymptomatic and it is found incidentally, so ask about antacids and supplements by name - patients do not volunteer them as medications.

Drugs that deepen it - Thiazides increase renal calcium reabsorption and add a contraction alkalosis; ACE inhibitors and NSAIDs cut renal calcium excretion; vitamin D increases gut absorption. Older patients are more vulnerable because bone buffers less of the calcium load.

Preop labs - Ionized calcium, a basic metabolic panel for creatinine, and a blood gas. This is a diagnosis of exclusion: PTH is low here, high in primary hyperparathyroidism, and PTH-related peptide is elevated in malignancy-associated hypercalcemia. See Hypercalcemia.

Read ionized, not total, calcium - Alkalosis increases calcium binding to albumin and lowers the ionized fraction, so total calcium misstates what the myocardium and nerve are actually seeing. The pH you set on the ventilator moves that number, and hyperventilating this patient drops ionized calcium further.

They are volume depleted - Hypercalcemia drives natriuresis and free water loss, so expect an exaggerated hypotensive response to induction and fill before you induce. Treatment is 0.9% saline at twice maintenance until the deficit is replaced and urine output reaches 200 to 300 mL/h.

Loop diuretics with caution - They can enhance renal calcium excretion but paradoxical hypercalcemia occurs through bone resorption. Hemodialysis is the treatment of choice when calcium must come down fast in a patient with heart failure or renal insufficiency.

ECG and neuromuscular effects - Prolonged PR, short QT, widened QRS, bradycardia. Severe hypercalcemia inhibits neuromuscular and myocardial depolarization, so muscle weakness and arrhythmias travel together. Levels above 14 mg/dL cause encephalopathy and above 15 mg/dL is a medical emergency - that is a case to delay, not to premedicate.

Renal handling of drugs - AKI is one leg of the triad, so check creatinine and dose renally cleared drugs to measured function. Skip perioperative NSAIDs; they reduce renal calcium excretion and add nephrotoxicity to a kidney that is already injured.

How it presents - Altered mental status, headache, vertigo, dizziness, malaise; nausea, vomiting, anorexia, constipation; polyuria, polydipsia, nephrolithiasis, palpitations. Chronic cases add pruritus, tremor, and psychosis. A confused patient on calcium supplements with a high calcium and a high bicarbonate is this until proven otherwise.

It resolves when the ingestion stops - Left untreated it progresses to acute renal failure and metastatic calcification, but stopping the calcium and alkali plus saline repletion is the definitive fix. Elective surgery waits for calcium, volume, and creatinine to come back.

Pregnancy - Severe cases are reported. Increased gut calcium absorption, higher calcitriol, and parathyroid-related peptide combine with the routine use of calcium carbonate for reflux, so an obstetric patient with hypercalcemia and alkalosis warrants a supplement history.

Milk-alkali syndrome is a triad of hypercalcemia, metabolic alkalosis, and acute kidney injury from co-ingesting large amounts of calcium and absorbable alkali. It was a disease of the Sippy regimen for peptic ulcer, nearly vanished once H2 blockers arrived, and came back with over-the-counter calcium carbonate for osteoporosis and dyspepsia - it now accounts for more than 10% of hypercalcemia and is the third most common cause in hospitalized patients, behind hyperparathyroidism and malignancy.

Hypercalcemia constricts the renal vasculature and drops GFR, inhibits the Na-K-2Cl channel in the medullary thick ascending limb causing natriuresis, and blocks V2 receptors so water is not reabsorbed. The resulting hypovolemia increases bicarbonate reabsorption, and the alkalosis in turn increases distal tubular calcium reabsorption - a self-feeding loop of hypercalcemia, alkalosis, and kidney injury.