What is the recommended management and dosing of antiepileptic medications, such as levetiracetam (Keppra) and lamotrigine, for patients experiencing seizures during hemodialysis due to impaired renal function?

Management of Seizures During Hemodialysis

Immediate Seizure Management: Critical Safety Warning

For acute seizure management in dialysis patients, limit IV lorazepam to 1-2 mg initially with a maximum cumulative daily dose of <1 mg/kg due to propylene glycol toxicity risk, or preferentially use midazolam as an alternative benzodiazepine. 1

Propylene Glycol Toxicity - A Commonly Overlooked Danger

• IV lorazepam contains propylene glycol as a diluent, which accumulates in renal failure and causes metabolic acidosis and acute kidney injury at doses as low as 1 mg/kg/day 1
• This toxicity is easily missed because metabolic acidosis and kidney injury are already common in dialysis patients, making it appear as worsening uremia 1
• Screen for propylene glycol accumulation using serum osmol gap >10-12 mOsm/L 1
• Reduce lorazepam doses by 50% based on increased half-life and volume of distribution in dialysis patients 1
• Consider midazolam for prolonged or frequent seizure management to avoid propylene glycol exposure 1

---

Chronic Antiepileptic Drug Management in Hemodialysis

Levetiracetam (First-Line Choice)

Levetiracetam requires dose adjustment in hemodialysis patients with supplemental dosing after each dialysis session, as approximately 50% of the drug is removed during a standard 4-hour hemodialysis procedure. 2, 3

Dosing Algorithm for Levetiracetam in Hemodialysis:

• Initial dosing: 500-1000 mg after dialysis on dialysis days 2, 3
• Maintenance: 500-1000 mg daily (given after dialysis on dialysis days) 3, 4
• Supplemental post-dialysis dose: Give 250-500 mg (50% of maintenance dose) after each 4-hour hemodialysis session 2, 3
• Maximum dose: Up to 1500 mg twice daily may be needed, adjusted for dialysis schedule 2

Evidence Supporting Twice-Daily Dosing Strategy:

• A 2017 prospective study demonstrated that twice-daily (BID) levetiracetam dosing achieves significantly higher and more stable plasma levels compared to once-daily dosing in hemodialysis patients 4
• BID dosing achieved 81.4% recovery to predialysis levels after supplementation versus only 65.7% with daily dosing (p=0.045) 4
• Mean predialysis levels were 43.1 µg/mL with BID versus 21.1 µg/mL with daily dosing (p<0.05) 4
• Consider BID dosing (e.g., 500 mg BID with 250 mg post-dialysis supplement) rather than once-daily to maintain therapeutic levels 4

Clinical Pitfall:

• Hemodialysis can reduce levetiracetam levels to subtherapeutic ranges, potentially triggering breakthrough seizures during or immediately after dialysis 5
• A 2017 case report documented generalized tonic-clonic seizures occurring during hemodialysis due to inadequate levetiracetam supplementation 5
• Always administer the supplemental dose immediately after dialysis, not before the next scheduled dose 3, 5

---

Lamotrigine (Alternative Option)

Lamotrigine is less affected by renal dysfunction and hemodialysis compared to levetiracetam, making it a reasonable alternative, though specific dosing data in dialysis patients are limited. 6

• Lamotrigine undergoes hepatic metabolism and is less renally cleared 6
• Standard dosing can generally be used, but monitor for accumulation due to potential hypoalbuminemia in dialysis patients 6
• No routine supplemental dosing after hemodialysis is required 6

---

Understanding Seizure Etiology in Dialysis Patients

Common Causes (3-5% incidence):

• Dialysis disequilibrium syndrome: Rapid osmotic shifts during dialysis causing cerebral edema 1
• Electrolyte disturbances: Hyponatremia, hypocalcemia, hypomagnesemia 6
• Uremic encephalopathy: Accumulation of uremic toxins 6
• Intracranial hemorrhage: Increased risk due to anticoagulation during dialysis 6
• Medication-related: Immunosuppressant toxicity in transplant recipients, drug accumulation 6

---

Drugs to Avoid or Use with Extreme Caution

• Gabapentin, vigabatrin, topiramate: Extensively renally cleared and accumulate significantly in renal failure, requiring substantial dose reductions 6
• Phenytoin: Accumulates in renal failure; hypoalbuminemia increases free fraction, necessitating monitoring of free (not total) levels 6
• Valproate: Potentially hepatotoxic and should be avoided in patients with concurrent hepatic dysfunction 6

---

Monitoring Recommendations

• Check levetiracetam levels pre-dialysis and post-supplementation to ensure therapeutic range (12-46 µg/mL) 4
• Monitor for breakthrough seizures, particularly during or immediately after hemodialysis sessions 5
• Assess serum osmol gap if using IV lorazepam to screen for propylene glycol toxicity 1
• Monitor electrolytes (sodium, calcium, magnesium) before and after dialysis 6