What is the recommended protocol for preventing renal failure after Hyperthermic Intraperitoneal Chemotherapy (HIPEC) using magnesium sulfate, mannitol, furosemide, and sodium thiosulfate?

Prevention of Renal Failure After HIPEC: Protocol for Magnesium, Mannitol, Furosemide, and Sodium Thiosulfate Use

Sodium thiosulfate should be administered as the primary nephroprotective agent for all patients undergoing HIPEC with cisplatin, as it completely prevents renal impairment compared to other approaches. 1, 2

Comprehensive Nephroprotective Protocol for HIPEC

Pre-HIPEC Preparation

• Sodium thiosulfate administration:

  • Initial dose: 9 mg/m² prior to HIPEC procedure 1
  • Follow-up dose: 12 mg/m² at the end of the HIPEC procedure 1
  • Note: Recent evidence shows sodium thiosulfate alone is sufficient without the need for preoperative hyperhydration 3

• Magnesium management:

  • Monitor serum magnesium levels before HIPEC
  • Use dialysis solutions containing magnesium during HIPEC to prevent hypomagnesemia 4
  • Target magnesium range: 0.1-0.15 mmol/kg/day (approximately 4-12 mmol/day for average adult) 4

During HIPEC

• Fluid management:

  • Maintain adequate hydration with 25-35 mL/kg/day of fluid 4
  • Monitor for signs of fluid overload or dehydration
  • Target urine output of at least 0.8-1 L per day 4

• Electrolyte monitoring:

  • Regular monitoring of serum sodium, potassium, chloride, and bicarbonate 4
  • Target serum potassium in the 4.0-5.0 mmol/L range 4

Post-HIPEC Management

• Mannitol and furosemide combination:

  • Mannitol alone increases glomerular filtration rate (GFR) but also increases renal oxygen consumption, which can worsen the oxygen supply/demand relationship 5
  • Add furosemide to mannitol to normalize renal oxygenation 5
  • Caution: High doses of mannitol (>189 g/day or cumulative doses >626 g) can paradoxically cause acute renal failure 6
  • Do not use furosemide unless hypervolemia, hyperkalemia, and/or renal acidosis are present 4

• Diuretic management:

  • If diuretics are needed, use loop diuretics (furosemide, bumetanide, torsemide) rather than thiazides 4
  • Starting dose of furosemide: 20-40 mg/day (maximum 160 mg/day) 4
  • If using spironolactone: 50-100 mg/day (maximum 400 mg/day) 4
  • Avoid monotherapy with loop diuretics; combine with aldosterone antagonists when needed 4

Monitoring Protocol

1. Daily monitoring:

   • Serum creatinine and GFR
   • Electrolytes (sodium, potassium, magnesium, phosphate, calcium)
   • Acid-base status (serum chloride and bicarbonate) 4
   • Daily weights and fluid balance

2. Weight management:

   • Limit weight loss to 0.5 kg/day in patients without edema 4
   • Monitor for signs of dehydration or fluid overload

3. Response assessment:

   • Monitor urine output (target >0.8-1 L/day) 4
   • Assess for signs of renal impairment (defined as serum creatinine >1.6 times baseline) 1

Important Considerations and Pitfalls

• Sodium thiosulfate efficacy: Studies show 0% renal impairment with sodium thiosulfate versus 31.4% without it, making it the most critical component of the protocol 1

• Avoid nephrotoxic combinations: Do not combine multiple nephrotoxic agents with cisplatin during HIPEC

• Mannitol cautions: Despite its traditional use for renal protection, mannitol can paradoxically cause acute renal failure at high doses by inducing renal vasoconstriction 6

• Electrolyte management: Hypomagnesemia is common during continuous renal replacement therapy and requires careful monitoring and replacement 4

• Monitoring osmolal gap: When using mannitol, monitor the osmolal gap rather than serum osmolality alone to prevent mannitol-induced renal failure 6

• Discontinue protocol: Stop diuretics in cases of hepatic encephalopathy, hyponatremia below 120 mmol/L, acute kidney injury, or lack of response to low-salt diet 4

This protocol prioritizes the use of sodium thiosulfate as the primary nephroprotective agent for HIPEC with cisplatin, supplemented with careful fluid, electrolyte, and diuretic management to optimize renal outcomes and prevent acute kidney injury.