What is the recommended protocol for using magnesium, mannitol, and furosemide to prevent renal failure after Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

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

Preoperative hydration with isotonic saline and careful intraoperative fluid management are the cornerstones of preventing renal failure after HIPEC, while mannitol should be used cautiously and furosemide should not be given solely for renal protection. 1

Pre-HIPEC Protocol

Hydration Strategy

• Begin hydration with 0.9% normal saline at 1-1.5 ml/kg/hour at least 1 hour before the procedure 2
• Administer pre-procedure hydration of 3 ml/kg over 1 hour before HIPEC 2
• Continue hydration at 1 ml/kg/hour for 6 hours post-procedure 2
• Discontinue potentially nephrotoxic medications (NSAIDs, aminoglycosides) before the procedure 2

Electrolyte Management

• Monitor baseline electrolytes, especially magnesium levels
• For patients with magnesium deficiency:
  • Mild (1.2-1.7 mg/dL): Oral magnesium oxide/citrate 400-800 mg/day divided doses 2
  • Moderate (0.8-1.2 mg/dL): Oral magnesium 800-1600 mg/day divided doses 2
  • Severe (<0.8 mg/dL): IV magnesium sulfate 1-2 g over 1 hour, followed by 0.5-1 g every 6 hours 2

Intraoperative Protocol

Fluid Management

• Maintain adequate intravascular volume guided by hemodynamic parameters
• Target mean arterial pressure of at least 65 mmHg 2
• Avoid excessive fluid administration that can contribute to complications 2
• Consider balanced crystalloid solutions to avoid hyperchloremic acidosis 2

Mannitol Use

• Mannitol should be used cautiously and not given solely for the purpose of renal protection 1
• If used, administer mannitol 0.25 g/kg every 12 hours for no more than 2 postoperative days 3
• Note: The Class III recommendation from guidelines explicitly states that mannitol should not be given solely for renal protection in descending aortic repairs, which can be extrapolated to HIPEC procedures 1

Post-HIPEC Protocol

Diuretic Management

• Furosemide should not be given solely for the purpose of renal protection 1
• Only use furosemide if there are signs of fluid overload or congestion 1
• If needed for volume management, initial IV furosemide dose should be 20-40 mg in patients without prior diuretic use 1
• For patients with previous diuretic use, higher doses may be required 1

Monitoring Protocol

• Monitor urine output hourly, targeting >0.5 mL/kg/hour 1
• Check electrolytes, creatinine, and BUN every 6-12 hours for the first 48 hours
• Follow the FACTT-lite protocol for fluid management 1:
  • If CVP >8 mmHg and urine output <0.5 mL/kg/h: Administer furosemide and reassess in 1 hour
  • If CVP 4-8 mmHg and urine output <0.5 mL/kg/h: Give fluid bolus and reassess in 1 hour
  • If CVP <4 mmHg: Give fluid bolus and reassess in 1 hour

Special Considerations

Combined Therapy Approach

• The combination of mannitol and furosemide has not shown superior results compared to proper hydration alone 3
• A study by Bragadottir et al. showed that mannitol alone increased GFR but also increased renal oxygen consumption, potentially worsening the renal oxygen supply/demand relationship 4
• When furosemide was combined with mannitol, it normalized renal oxygenation while maintaining elevated GFR 4

Pitfalls and Caveats

• Avoid excessive mannitol use as it can lead to osmotic nephrosis and worsen renal function
• Excessive furosemide can cause volume depletion and electrolyte disturbances, particularly hypokalemia and hypomagnesemia
• Continuous monitoring of electrolytes is essential when using diuretics
• Discontinue nephrotoxic medications before HIPEC to reduce the risk of renal injury
• Minimize contrast volume if imaging studies are required perioperatively

Algorithm for Renal Protection in HIPEC

1. Preoperative Phase:

   • Optimize hydration with 0.9% saline
   • Correct electrolyte imbalances, especially magnesium
   • Discontinue nephrotoxic medications

2. Intraoperative Phase:

   • Maintain adequate MAP (≥65 mmHg)
   • Ensure euvolemia with careful fluid management
   • Avoid hypotension and hypovolemia

3. Postoperative Phase:

   • Monitor urine output hourly
   • Check electrolytes and renal function regularly
   • Use diuretics only if clinically indicated for volume management, not for renal protection
   • Maintain adequate hydration for 48-72 hours post-procedure

The evidence strongly suggests that proper perioperative hydration is the cornerstone of preserving adequate renal function following HIPEC, while the administration of mannitol or furosemide solely for renal protection is not supported by current guidelines 1, 3.