What short‑hydration regimen (fluid volume, magnesium/potassium supplementation, and diuretics) is recommended for an adult with normal renal function (creatinine clearance ≥60 mL/min) and normal cardiac function receiving cisplatin ≥60 mg/m² (curative intent) to prevent nephrotoxicity?

Cisplatin Hydration Protocol for Nephrotoxicity Prevention

Recommended Short-Hydration Regimen

For adults with normal renal and cardiac function receiving cisplatin ≥60 mg/m², use a short-duration hydration protocol consisting of 1000 mL isotonic saline before and after cisplatin (total 2000 mL), supplemented with 8-16 mEq magnesium sulfate and 10 mEq potassium chloride, with mannitol 12.5-25 g for forced diuresis. 1, 2

Pre-Hydration Phase

• Administer 1000 mL isotonic saline containing:
  • 8-16 mEq magnesium sulfate (typically 1 g) 3, 1, 2
  • 10 mEq potassium chloride 3
  • 12.5-25 g mannitol 1, 2, 4
• Infuse over 1-2 hours prior to cisplatin administration 1, 2
• Target urine output ≥100 mL/hour during pre-hydration 5

Cisplatin Administration

• Administer cisplatin in 500 mL isotonic saline 3

Post-Hydration Phase

• Administer 1000 mL isotonic saline containing:
  • 8-16 mEq magnesium sulfate 3, 1
  • 10 mEq potassium chloride 3
• Infuse over 1-2 hours after cisplatin 1, 2
• Continue to target urine output ≥100 mL/hour 5

Evidence Supporting Short-Hydration Protocols

The most recent systematic review (2024) found that all six studies investigating duration and volume of hydration demonstrated that short-hydration schemes resulted in less cisplatin-induced nephrotoxicity than longer hydration schemes 2. This is reinforced by the 2017 systematic review showing short-duration, low-volume outpatient hydration regimens are safe and feasible even for intermediate- to high-dose cisplatin 1.

A 2017 retrospective study specifically demonstrated that short hydration with potassium and magnesium supplementation resulted in only 22.7% prevalence of nephrotoxicity with no hypokalemia or hypomagnesemia at a median cumulative dose of 465 mg/m² 3.

Role of Magnesium Supplementation

Magnesium supplementation is strongly recommended as it provides nephroprotection beyond hydration alone. The 2024 systematic review found that seven out of nine studies evaluating electrolytes demonstrated that magnesium supplementation reduced the risk of nephrotoxicity 2. The 2017 systematic review similarly concluded that magnesium supplementation (8-16 mEq) may limit cisplatin-induced nephrotoxicity 1.

A 2012 study showed that hydration with magnesium and mannitol without furosemide was an independent protective factor against nephrotoxicity (HR 0.232,95% CI: 0.055-0.986, P=0.039) 4.

Role of Forced Diuresis with Mannitol

Mannitol should be included in the hydration protocol for patients receiving ≥60 mg/m² cisplatin. The 2024 systematic review found that four out of seven studies investigating diuretics found a protective effect of adding mannitol to the hydration scheme 2. The 2017 systematic review concluded that mannitol forced diuresis may be appropriate in select patients receiving cisplatin 1.

The 2012 study demonstrated that mannitol with magnesium (without furosemide) significantly increased creatinine clearance (P=0.0004) and decreased serum creatinine (P=0.0148) after one course of chemotherapy 4.

Avoid Furosemide

Do not use furosemide routinely in cisplatin hydration protocols. The evidence shows that mannitol with magnesium without furosemide provides superior nephroprotection 4. Furosemide may exacerbate electrolyte wasting and does not improve outcomes compared to mannitol 1, 2.

Monitoring Requirements

• Baseline assessment: Serum creatinine, BUN, electrolytes (sodium, potassium, magnesium) 5, 6
• During treatment: Monitor urine output to maintain ≥100 mL/hour 5
• Post-treatment: Check renal function and electrolytes on day 1 of each subsequent cycle 3
• High-risk patients: Consider more frequent monitoring if cumulative doses exceed 400 mg/m² 7

Extended Outpatient Hydration Considerations

The NCCN guidelines note that patients often require IV fluids for 5-7 days in the outpatient setting post-chemotherapy to prevent or treat dehydration 7, 5. However, the short-hydration protocol described above (total 2-3 hours) is sufficient for most patients with normal renal function receiving curative-intent therapy 1, 2.

Critical Contraindications and Precautions

• Relative contraindications to aggressive hydration: Congestive heart failure and significant urinary obstruction 5
• Avoid concomitant nephrotoxic medications (NSAIDs, aminoglycosides) during cisplatin administration 7, 5
• Hypomagnesemia exacerbates potassium wasting and must be aggressively corrected 5

Common Pitfalls to Avoid

• Do not use prolonged hydration protocols (8-12 hours pre/post) as they increase toxicity without improving nephroprotection 1, 2
• Do not omit magnesium supplementation—it is a critical nephroprotectant with strong evidence 1, 2, 4
• Do not substitute furosemide for mannitol—mannitol provides superior outcomes 2, 4
• Do not use oral hydration alone for patients receiving ≥60 mg/m² cisplatin in curative-intent settings 7