What is the recommended IV magnesium sulfate dosing (loading 1 g, additional 0.5–1 g if needed) and target serum magnesium level (2.0–2.5 mg/dL) for adult patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC)?

Magnesium Administration During HIPEC Surgery

No Specific HIPEC Guidelines Exist—Extrapolate from Cardiac Surgery and Critical Care Evidence

The available evidence does not provide HIPEC-specific magnesium protocols, but perioperative magnesium supplementation may be considered using cardiac surgery dosing regimens (loading dose 1 g IV, additional 0.5–1 g as needed) with a target serum magnesium of 2.0–2.5 mg/dL, extrapolated from cardiac bypass guidelines and critical care data. 1, 2

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Rationale for Magnesium Supplementation in HIPEC

Cisplatin-Induced Hypomagnesemia Risk

• Cisplatin used in HIPEC causes significant renal magnesium wasting, with hypomagnesemia incidence rising to 24.5% by day 7 and 30.1% by day 30 post-procedure. 3
• Hypomagnesemia develops through direct renal tubular injury from cisplatin, amphotericin B, aminoglycosides, and other nephrotoxic agents commonly used perioperatively. 2

Cardiac Arrhythmia Prevention

• Magnesium sulfate may be considered perioperatively for prophylaxis of postoperative arrhythmias in major surgical procedures, though evidence quality is limited (Class IIb recommendation). 1
• Hypomagnesemia increases the risk of ventricular arrhythmias, torsades de pointes, and QT prolongation, particularly in patients receiving diuretics or with underlying cardiac disease. 2, 4

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Proposed Dosing Protocol (Extrapolated from Cardiac Surgery)

Intraoperative/Early Postoperative Loading

• Administer magnesium sulfate 1 g (8 mEq) IV over 15–30 minutes during or immediately after HIPEC completion. 2, 5
• Additional 0.5–1 g IV may be given if serum magnesium remains <2.0 mg/dL on first postoperative measurement. 2

Target Serum Level

• Maintain serum magnesium 2.0–2.5 mg/dL (0.82–1.03 mmol/L) throughout the perioperative period. 2
• This target is higher than the standard lower limit (1.7 mg/dL) to provide a buffer against cisplatin-induced losses. 2

Maintenance Dosing

• If oral intake tolerated, transition to magnesium oxide 12–24 mmol (480–960 mg elemental magnesium) daily, preferably at night when intestinal transit is slowest. 2
• For patients unable to take oral medications, continue IV magnesium sulfate 1–2 g every 12–24 hours based on serial magnesium levels. 2, 6

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Monitoring Protocol

Baseline Assessment

• Measure serum magnesium, potassium, calcium, and creatinine preoperatively before HIPEC. 2
• Obtain baseline ECG to assess QTc interval, especially in patients with cardiac history or on QT-prolonging medications. 2

Postoperative Monitoring

• Check serum magnesium at 6–12 hours post-HIPEC, then daily for 3 days, then on day 7 and day 30. 2, 3
• Monitor potassium and calcium concurrently, as hypomagnesemia causes refractory hypokalemia and hypocalcemia that will not correct until magnesium is repleted. 2
• Measure serum creatinine daily for 7 days to detect cisplatin nephrotoxicity, which worsens magnesium wasting. 3

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Treatment Algorithm for Hypomagnesemia During HIPEC

Step 1: Correct Volume Depletion First

• Administer IV isotonic saline to restore intravascular volume before magnesium supplementation, as volume depletion causes secondary hyperaldosteronism that increases renal magnesium wasting. 2
• This is the most common pitfall—starting magnesium without volume repletion leads to continued losses. 2

Step 2: Magnesium Replacement Based on Severity

Mild Asymptomatic (Mg 1.4–1.8 mg/dL)

• Oral magnesium oxide 12–24 mmol daily (480–960 mg elemental magnesium). 2
• IV magnesium sulfate 2 g over 15–30 minutes produces greater and more rapid elevation than oral therapy. 6

Moderate Symptomatic (Mg 1.0–1.4 mg/dL)

• Magnesium sulfate 1–2 g IV over 15 minutes, followed by continuous infusion 1–4 mg/min if needed. 2

Severe or Life-Threatening (Mg <1.0 mg/dL or arrhythmias)

• Magnesium sulfate 1–2 g IV bolus over 5 minutes for torsades de pointes, ventricular arrhythmias, or seizures, regardless of baseline magnesium level. 1, 2
• Follow with continuous infusion 1–4 mg/min until magnesium normalizes. 2

Step 3: Correct Potassium and Calcium After Magnesium

• Do not attempt potassium or calcium correction before normalizing magnesium, as these abnormalities are refractory until magnesium stores are restored. 2
• Hypomagnesemia impairs renal potassium handling and PTH secretion, perpetuating hypokalemia and hypocalcemia. 2

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Special Considerations for HIPEC

Renal Function Monitoring

• Low intraoperative urine output, hypertension, and angiotensin II receptor antagonist use are associated with acute kidney injury post-HIPEC, which worsens magnesium wasting. 3
• In severe renal insufficiency (eGFR <30 mL/min), limit magnesium to maximum 20 g over 48 hours with frequent serum monitoring to avoid toxicity. 2

Drug Interactions

• Loop and thiazide diuretics markedly increase renal magnesium losses; consider adding potassium-sparing diuretics (amiloride 5–10 mg or spironolactone 25–50 mg daily) to conserve magnesium. 2
• Proton pump inhibitors and calcineurin inhibitors promote renal magnesium wasting, particularly in transplant recipients. 2

Gastrointestinal Losses

• Postoperative ileus, nasogastric suction, or high-output stomas cause additional magnesium losses (each liter of GI fluid contains significant magnesium). 2
• Correct sodium and water depletion with IV saline first to eliminate secondary hyperaldosteronism before starting magnesium. 2

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Common Pitfalls to Avoid

Starting Magnesium Without Volume Repletion

• Failure to correct volume depletion first allows secondary hyperaldosteronism to persist, driving continued renal magnesium wasting despite supplementation. 2

Attempting Potassium/Calcium Correction First

• Hypokalemia and hypocalcemia will not respond to supplementation until magnesium is normalized, as magnesium is required for potassium transport and PTH function. 2

Inadequate Monitoring

• Cisplatin-induced hypomagnesemia peaks at 7–30 days post-HIPEC, so monitoring must extend beyond the immediate postoperative period. 3

Rapid IV Administration

• Rapid infusion of magnesium sulfate can cause hypotension and bradycardia; administer over 15–30 minutes for routine replacement, reserving 5-minute boluses for life-threatening arrhythmias only. 2

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Evidence Limitations

• No randomized trials exist specifically for magnesium supplementation during HIPEC; recommendations are extrapolated from cardiac surgery (Class IIb evidence) and critical care data. 1
• The 2025 EACTS/EACTAIC/EBCP guidelines note that magnesium's effect on arrhythmia prevention was lost when only high-quality studies were analyzed, suggesting benefit may be modest. 1
• However, given the high incidence of cisplatin-induced hypomagnesemia (30% by day 30) and low risk of supplementation, prophylactic magnesium administration is reasonable in HIPEC patients. 3