What is the recommended dose of cefepime for patients with impaired renal function after cardiac arrest?

Cefepime Dosing in Patients with Impaired Renal Function After Cardiac Arrest

Cefepime dosing must be significantly reduced in patients with impaired renal function after cardiac arrest, with specific adjustments based on creatinine clearance to prevent neurotoxicity while maintaining antimicrobial efficacy. 1

Renal Dysfunction After Cardiac Arrest

Acute kidney injury (AKI) is common following cardiac arrest:

• 37% of pediatric post-cardiac arrest patients develop AKI
• 11.5% develop severe AKI
• 6.4% require renal replacement therapy (RRT) within 48 hours of return of spontaneous circulation 2

Risk factors for severe AKI after cardiac arrest include:

• Abnormal baseline creatinine
• Higher number of epinephrine doses during arrest
• Worse post-cardiac arrest acidosis
• In-hospital arrest location 2

Cefepime Dosing Based on Renal Function

Standard FDA-Approved Dosing Adjustments

Creatinine Clearance (mL/min)	Standard Dose Adjustment
>60	500 mg q12h - 2 g q8h (normal dosing)
30-60	2 g q24h (for 2 g q12h regimen)
11-29	1 g q24h (for 2 g q12h regimen)
<11	500 mg q24h (for 2 g q12h regimen)
Hemodialysis	1 g on day 1, then 500 mg q24h
CAPD	2 g q48h (for 2 g q12h regimen)

1

Risk of Cefepime-Induced Neurotoxicity

Cefepime has significant potential for neurotoxicity, particularly in patients with renal dysfunction:

• Cefepime has high pro-convulsive activity (relative activity of 160) compared to other beta-lactams 3
• Neurotoxicity can manifest as seizures, encephalopathy, myoclonus, confusion, and status epilepticus 3
• 10% of critically ill adults with renal dysfunction receiving higher-dose cefepime develop neurotoxicity 4
• Risk increases significantly with severe renal dysfunction (CrCl <11 mL/min) 4

Plasma Concentration Thresholds for Neurotoxicity

• Trough concentrations >22 mg/L or steady-state concentrations >35 mg/L are associated with neurotoxicity in 50% of patients 3
• When free drug concentration exceeds 8 times the MIC of target bacteria, neurotoxicity risk increases 3

Monitoring Recommendations

For patients with impaired renal function after cardiac arrest:

1. Calculate creatinine clearance using Cockcroft-Gault equation:

   • Males: CrCl (mL/min) = Weight (kg) × (140 – age) / (72 × serum creatinine [mg/dL])
   • Females: CrCl (mL/min) = 0.85 × male value 1

2. Monitor for signs of neurotoxicity:

   • Altered mental status (most common, 92% of cases) 4
   • Confusion
   • Myoclonus
   • Seizures 3, 5

3. Consider therapeutic drug monitoring when available, especially in:

   • Patients with fluctuating renal function
   • Patients with CrCl <30 mL/min 6

Special Considerations

Patients with Severe Renal Impairment

• Even with appropriate dose adjustments, 10% of patients with renal dysfunction may develop cefepime-induced neurotoxicity 6, 4
• Consider alternative antibiotics in patients with severe renal impairment (CrCl <11 mL/min) if possible
• If cefepime is necessary, use 500 mg q24h and monitor closely for neurotoxicity 1

Patients on Renal Replacement Therapy

• For patients on continuous renal replacement therapy (CRRT):

  • Consider higher dosing than traditional recommendations
  • A regimen of 2 g loading dose followed by 1.5-1.75 g every 8 hours may be needed for adequate coverage of gram-negative infections 7

• For patients on intermittent hemodialysis:

  • 1 g on day 1, then 500 mg every 24 hours
  • Administer after hemodialysis on dialysis days 1

Common Pitfalls and Caveats

1. Inadequate dose adjustment: Failure to adjust cefepime dose based on renal function is a common error that can lead to neurotoxicity.

2. Missing neurotoxicity symptoms: Symptoms of cefepime-induced neurotoxicity may be mistakenly attributed to post-cardiac arrest encephalopathy or other causes.

3. Inadequate coverage for resistant organisms: Using excessively reduced doses may lead to treatment failure for pathogens with MICs ≥8 mg/L 6.

4. Failure to reassess: Renal function may improve or worsen after cardiac arrest, requiring dose adjustments throughout the treatment course.

5. Drug interactions: Nephrotoxic medications should be used with caution in post-cardiac arrest patients with renal dysfunction 2.

By carefully adjusting cefepime dosing based on renal function and monitoring for signs of neurotoxicity, clinicians can optimize antimicrobial therapy while minimizing adverse effects in patients with impaired renal function after cardiac arrest.