In a patient on chronic levetiracetam (Keppra) undergoing surgery, should the drug be continued perioperatively, how should it be administered if the patient is nil per os, are dose adjustments needed for impaired renal function, and what are the relevant anesthetic and neuromuscular blocker interactions?

Perioperative Management of Levetiracetam (Keppra) in Surgical Patients

Continue levetiracetam throughout the perioperative period without interruption, as discontinuation risks breakthrough seizures and there are no significant anesthetic interactions that would necessitate stopping the medication. 1, 2

Continuation Strategy

• Never discontinue levetiracetam perioperatively in patients on chronic therapy, as maintaining therapeutic levels prevents breakthrough seizures during the physiologic stress of surgery 1, 2
• Levetiracetam has minimal drug interactions with anesthetic agents and does not induce cytochrome P450 enzymes, making it safe to continue throughout the perioperative period 3, 2
• The latest generation antiepileptic drugs like levetiracetam are better tolerated and induce fewer drug interactions compared to older agents like phenytoin or carbamazepine 2

Administration When NPO (Nil Per Os)

Switch to intravenous levetiracetam at the same total daily dose when the patient cannot take oral medications. 4

IV Dosing Protocol:

• Administer the patient's usual oral dose intravenously, divided into the same dosing schedule (typically every 12 hours) 5, 4
• Rapid IV push administration of undiluted levetiracetam is safe and well-tolerated for doses up to 4500 mg, allowing immediate drug delivery without dilution delays 4
• IV levetiracetam demonstrates rapid and complete absorption with high bioavailability, making dose conversion from oral to IV 1:1 3
• Local injection site reactions (redness, burning) occur rarely but are the only documented adverse events with rapid IV push administration 4

Renal Dose Adjustments

Reduce levetiracetam dosing in patients with impaired renal function, as the drug is primarily eliminated renally. 5, 3

Specific Dosing by Renal Function:

• Normal renal function (CrCl >80 mL/min): Standard dosing of 500-1500 mg every 12 hours 3
• Moderate renal impairment (CrCl 30-80 mL/min): Reduce dose by 25-50% 3
• Severe renal impairment (CrCl <30 mL/min): Reduce dose by 50-75% 3
• Patients on continuous venovenous hemofiltration (CVVH): Consider initial dosing of 1000 mg every 12 hours with therapeutic drug monitoring, as CVVH significantly removes levetiracetam due to its low molecular weight, hydrophilicity, and minimal protein binding 5
• The volume of distribution (0.65 L/kg) and clearance in CVVH patients are similar to healthy patients, but elimination half-life extends to 8.7-10.1 hours 5

Anesthetic Drug Interactions

Avoid alfentanil, remifentanil, and sevoflurane in patients on levetiracetam when reasonable alternatives exist, though these contraindications are relative. 2

Safe Anesthetic Choices:

• Most anesthetic agents are compatible with levetiracetam due to its lack of enzyme induction and minimal pharmacokinetic interactions 3, 2
• Levetiracetam does not interact with other drugs through cytochrome P450 pathways, unlike older antiepileptic drugs 3
• The primary mechanism of levetiracetam clearance is renal (hydrolysis of the acetamide group), not hepatic metabolism, eliminating most drug-drug interaction concerns 3

Neuromuscular Blocker Considerations

No specific neuromuscular blocker adjustments are required for patients on levetiracetam. 6

• Reverse neuromuscular blockade using standard nerve stimulator guidance to restore motor capacity before emergence 6
• Ensure complete return of airway reflexes and adequate tidal volumes before extubation 6
• Levetiracetam does not alter neuromuscular blocker pharmacokinetics or pharmacodynamics 3

Hemodynamic Management in Renal Dysfunction

Maintain mean arterial pressure between 60-70 mmHg (or >70 mmHg if hypertensive) to preserve renal perfusion pressure in patients with chronic kidney disease. 6, 7

• Implement goal-directed fluid therapy with stroke volume monitoring during procedures with hemodynamic instability risk (hemorrhagic, major, or emergency surgery) 6, 7
• Avoid nephrotoxic agents perioperatively, as diabetes and chronic kidney disease are independent risk factors for perioperative acute renal failure 6

Critical Pitfalls to Avoid

• Do not stop levetiracetam abruptly perioperatively, as this creates unnecessary seizure risk in a patient population already at elevated risk from surgical stress 1, 2
• Do not use intramuscular administration of any medications in surgical patients due to unpredictable pharmacokinetics 6
• Do not fail to adjust doses for renal dysfunction, as levetiracetam accumulation can occur with standard dosing in patients with reduced creatinine clearance 5, 3
• Do not assume levetiracetam is being used for prophylaxis in your patient—if they are on chronic levetiracetam, they have either had seizures or have a structural brain lesion requiring secondary prevention, making continuation mandatory 1