How should cisplatin be dosed and hydrated (including magnesium sulfate, potassium chloride, and mannitol) in a patient with normal renal and cardiac function, and what alternative should be used if mannitol is contraindicated?

Cisplatin Administration Protocol

For patients with normal renal and cardiac function receiving cisplatin, administer adequate intravenous hydration (typically 1-2 liters normal saline pre- and post-cisplatin), supplement with magnesium sulfate 1-2 grams and potassium chloride 10-20 mEq in the cisplatin bag, and add mannitol 12.5-25 grams for forced diuresis when using doses ≥60-100 mg/m²; if mannitol is contraindicated, furosemide 20-40 mg IV can serve as an alternative diuretic. 1, 2, 3

Pre-Hydration Phase

Fluid Administration

• Administer 1-2 liters of 0.9% normal saline intravenously over 2-4 hours before cisplatin infusion 1, 2, 3
• Target urine output ≥100 mL/hour (or 3 mL/kg/hour in children <10 kg) during pre-hydration 1
• Short-duration hydration protocols (4-6 hours total) are as effective as traditional 12-24 hour regimens and reduce patient burden 2, 3

Electrolyte Supplementation

• Add magnesium sulfate 1-2 grams (8-16 mEq) to pre-hydration fluids or the cisplatin bag 2, 3, 4
• Add potassium chloride 10-20 mEq to pre-hydration fluids or the cisplatin bag 4
• Magnesium supplementation has demonstrated nephroprotective effects in multiple studies and helps prevent cisplatin-induced hypomagnesemia 2, 3

Cisplatin Infusion

Standard Dosing Regimens

• Triweekly regimen: 100 mg/m² every 3 weeks (total cumulative dose 200 mg/m² over 2 cycles) 5
• Weekly regimen: 40 mg/m² weekly for 6 weeks (total cumulative dose 240 mg/m²) 5
• Both regimens show similar efficacy, though the weekly schedule may offer improved quality of life 5

Concurrent Hydration

• Infuse cisplatin in 250-500 mL normal saline over 1-2 hours 2
• Add magnesium sulfate 1 gram and potassium chloride 10 mEq directly to the cisplatin bag 4
• This approach maintains electrolyte levels and reduces subsequent replacement requirements 4

Forced Diuresis

Mannitol Administration (First-Line)

• Add mannitol 12.5-25 grams (0.25-0.5 g/kg) to hydration fluids for cisplatin doses ≥60-100 mg/m² 2, 6, 3
• Infuse mannitol over 20-30 minutes during or immediately after cisplatin 5
• Mannitol is particularly important for high-dose cisplatin (≥100 mg/m²) or patients with preexisting hypertension 2, 6
• Place a urinary catheter when using mannitol to monitor urine output accurately 5
• Administer through a filter and do not use solutions containing crystals 5

Alternative: Furosemide (When Mannitol Contraindicated)

• If mannitol is contraindicated (e.g., congestive heart failure, significant urinary obstruction), use furosemide 20-40 mg IV as an alternative diuretic 1, 3
• Furosemide provides forced diuresis without the osmotic load of mannitol 3
• Monitor for hypokalemia and hypomagnesemia more aggressively with loop diuretics 3

Post-Hydration Phase

Fluid Continuation

• Continue IV hydration with 1-2 liters normal saline over 2-4 hours after cisplatin completion 2, 3
• Maintain urine output ≥100 mL/hour during post-hydration 1
• Many patients require outpatient IV fluids for 5-7 days post-chemotherapy to prevent dehydration 1, 7

Monitoring Requirements

• Check renal function (creatinine, BUN) and electrolytes (sodium, potassium, magnesium) before each cycle 1
• For high-risk patients (cumulative dose >400 mg/m²), monitor renal function and electrolytes on day 1 of each subsequent cycle 1
• Monitor for hypomagnesemia, which occurs in approximately 33% of patients despite routine supplementation 4
• Time to first rescue magnesium supplementation averages 4 weeks after cisplatin initiation 4

Special Considerations and Contraindications

Relative Contraindications to Aggressive Hydration

• Congestive heart failure requires careful fluid balance; consider lower-volume protocols 1
• Significant urinary obstruction necessitates resolution before cisplatin administration 1
• In these cases, use the minimum effective hydration volume (1 liter pre- and post-) with close monitoring 2, 3

Dose-Specific Protocols

• Conventional doses (<100 mg/m²): Pre- and post-hydration alone (without mannitol) is sufficient in patients with normal renal function 6
• High doses (≥100 mg/m²): Pre- and post-hydration plus mannitol is mandatory to ensure adequate diuresis 6
• Oral hydration alone is insufficient for cisplatin ≥60 mg/m² in curative-intent treatment; IV hydration must be employed 1

Cumulative Dose Considerations

• A cumulative cisplatin dose threshold of 200 mg/m² is required for efficacy in most regimens 5
• If induction chemotherapy precedes concurrent chemoradiotherapy, the cumulative cisplatin dose during the concurrent phase can be reduced to 160 mg/m² based on patient tolerance 5
• Nephrotoxicity risk increases significantly with cumulative doses >400 mg/m² 1

Common Pitfalls and How to Avoid Them

Inadequate Electrolyte Replacement

• Despite routine magnesium and potassium supplementation, 33% of patients develop hypomagnesemia and 17% develop hypokalemia 4
• Hypomagnesemia exacerbates potassium wasting and must be corrected first before potassium replacement 1
• Check magnesium levels every 2-4 weeks and replace aggressively (magnesium sulfate 2-4 grams IV) when levels fall below 1.8 mg/dL 4

Insufficient Hydration Duration

• Short-duration protocols (4-6 hours total) are safe and effective, but completely omitting post-hydration increases nephrotoxicity risk 2, 3
• Ensure at least 2 hours of post-hydration after cisplatin completion 3
• Arrange outpatient IV hydration for 5-7 days if patients develop nausea, vomiting, or dehydration 1, 7

Mannitol Misuse

• Do not use mannitol in patients with heart failure or urinary obstruction 1
• Monitor for hyperosmolality when using mannitol 5
• Always place a urinary catheter to accurately measure urine output when using mannitol 5

Concomitant Nephrotoxic Medications

• Avoid NSAIDs, aminoglycosides, and other nephrotoxic drugs during cisplatin administration 1
• Temporarily discontinue potentially nephrotoxic medications in patients with GFR <60 mL/min/1.73 m² 1

Alternative Platinum Agents

If cisplatin is contraindicated due to renal dysfunction or intolerance, consider alternative platinum compounds 5:

• Carboplatin: AUC 5-6 every 3 weeks (less nephrotoxic but may be less effective) 5
• Oxaliplatin: 70 mg/m² weekly (different toxicity profile with less nephrotoxicity) 5
• Nedaplatin: 100 mg/m² every 3 weeks (primarily used in Asia) 5