Canine Seizure Treatment Protocol

Step 1 - Definitions & Indications to Treat

• 2+ seizures within 6 months
• Any episode of SE or cluster seizures
• Severe/prolonged postictal period
• Increasing seizure frequency, duration, or severity
• Structural brain lesion or history of brain injury

Step 2 - Emergency Treatment (Active Seizure / SE / Cluster Seizures)

First-Line: Benzodiazepines

• Can repeat benzodiazepine up to 3 doses total
• If seizures continue after 3 doses, escalate to second-line

Second-Line: Loading Dose of Maintenance ASM

Both can be given together if needed. If the dog is already on phenobarbital maintenance, levetiracetam loading is preferred as second-line.

Third-Line: Anesthetic/Refractory SE

Step 3 - Maintenance (Long-Term Antiseizure Medications)

First-Line Maintenance Drugs

1. Phenobarbital (Highest Recommendation)

• Dose: 2-5 mg/kg PO q12h (starting at 2-3 mg/kg)
• Adjust based on serum concentrations, seizure control, and adverse effects
• Target trough serum concentration: 15-35 mcg/mL
• Time to steady state: ~2-3 weeks
• Monitoring: Serum levels at 2-3 weeks after starting or dose change, then every 6 months; liver enzymes (ALT, ALP) and bile acids every 6-12 months
• Side effects: Polyuria/polydipsia/polyphagia (PU/PD/PP), sedation, hepatotoxicity (long-term), facial pruritus

2. Imepitoin (High Recommendation - Europe; not available in all countries)

• Dose: 10-30 mg/kg PO q12h (starting at 10 mg/kg)
• Partial benzodiazepine receptor agonist - lower abuse/tolerance risk
• First-line for newly diagnosed idiopathic epilepsy in dogs
• Fewer adverse effects than phenobarbital; no hepatotoxicity

Second-Line / Add-On Drugs

3. Potassium Bromide (KBr) (Moderate Recommendation)

• Dose (add-on): 15-20 mg/kg/day PO (divided to reduce GI upset)
• Dose (monotherapy): 40 mg/kg/day PO
• Sodium bromide: decrease dose by ~15% compared to KBr
• Target serum concentration: 1-2.5 mg/mL (with phenobarbital); 1-3 mg/mL (monotherapy)
• Time to steady state: ~3-4 months without loading
• Check levels at 8-12 weeks, then every 6-12 months
• Note: NOT for use in cats (causes irreversible pulmonary disease)

4. Levetiracetam (Low Recommendation for monotherapy; widely used as add-on)

• Immediate-release: 20-60 mg/kg PO q8h (starting at 20 mg/kg)
• Extended-release: 30 mg/kg PO q12h
• IV emergency dose: 30-60 mg/kg over 5-15 min
• Increase by 20 mg/kg increments if needed
• Minimal adverse effects - considered very safe
• Clearance increased when combined with phenobarbital or KBr - dose adjustments likely needed

5. Zonisamide (Low Recommendation; useful as add-on)

• Dose: 5-10 mg/kg PO q12h (dogs)
• Hepatic metabolism; potential hepatotoxicity - monitor liver enzymes
• Useful in dogs intolerant of phenobarbital

6. Gabapentin (Adjunct)

• Dose: 5-10 mg/kg PO q8-12h
• Primarily adjunctive; limited evidence as sole ASM

Pulse Therapy for Cluster Seizure Prevention

• Dose: 0.5-1 mg/kg PO q8h, started at onset of first seizure in a cluster, continued for 24-48h
• Reduces risk of additional seizures within the cluster period

Step 4 - Supportive Care (All Seizure Presentations)

• Secure IV access immediately
• Check blood glucose - treat hypoglycemia if present (dextrose 0.25-0.5 mL/kg of 50% dextrose IV diluted 1:4)
• Monitor body temperature - active cooling if >40.5°C (hyperthermia secondary to seizure activity)
• Monitor respiration and oxygen saturation
• Baseline labs: CBC, chemistry, electrolytes, urinalysis; check for metabolic/toxic causes
• Keep in visible monitored kennel for at least 24h after cluster seizures or SE
• Treat underlying cause if identified (e.g., hypoglycemia, toxin, hepatic encephalopathy)

Summary Flow Chart

ACTIVE SEIZURE
     |
     v
1st LINE: Benzodiazepine
  - IN Midazolam 0.2 mg/kg  (preferred out-of-hospital)
  - IV Diazepam 0.5 mg/kg   (preferred in-hospital)
  - Repeat up to 3x
     |
  No response
     v
2nd LINE: Load ASM
  - IV Phenobarbital 15-20 mg/kg (divided)
  - IV Levetiracetam 30-60 mg/kg (if already on pheno)
     |
  No response (Refractory SE)
     v
3rd LINE: Anesthesia
  - Ketamine CRI
  - Propofol CRI
  - Dexmedetomidine CRI
  - Pentobarbital (last resort)
     |
     v
MAINTENANCE ASM
  - Phenobarbital 2-5 mg/kg PO q12h (1st line)
  + KBr or Levetiracetam if needed

Key Monitoring Parameters

Important: Primidone is no longer recommended due to significantly higher hepatotoxicity risk compared to phenobarbital. All dosing should be individualized based on patient response, serum drug concentrations, and adverse effects. Consult a veterinary neurologist for refractory cases.