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Antiepileptic Drugs Used to Stop Ongoing Seizure Activity

By Linda Shell, DVM, DACVIM-Neurology, Professor, Small Animal Internal Medicine, Ross University School of Veterinary Medicine

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In status epilepticus, treatment is essential to prevent death from hyperthermia, acidosis, hypoperfusion, and hypoxia. Because diazepam has a rapid onset of action that prevents the spread of the seizure, it is usually the drug of choice to control status epilepticus and stop seizures in small and large animals.

Foals and Horses

Diazepam in horses has a long elimination half-life (7–22 hr). In foals, the dosage is 0.05–0.4 mg/kg, slowly IV (or about 5–20 mg/dose); higher doses can be fatal to neonates. For seizures in adult horses, diazepam can be given at 25–50 mg/horse, IV. To prevent further seizures after initial diazepam injection, IV phenobarbital may be started as a follow up at 12–20 mg/kg, IV over 20 min, and then maintained at a dosage of 6.65–9 mg/kg over 20 min, bid or tid. If sedation occurs, the dose should be reduced. Alternatively, treatment of seizures in foals can be initiated with phenytoin at 5–10 mg/kg, IV or PO, with subsequent treatments of 1–5 mg/kg, IV, IM, or PO, every 2–4 hr for 12 hr and later maintained with oral phenytoin at 2.83–16.43 mg/kg, tid, although erratic plasma concentrations may limit usefulness. The dose may need to be reduced if sedation occurs.

Other ways to control ongoing seizure activity include sodium pentobarbital (2–4 mg/kg, IV to effect), a mixture of 12% chloral hydrate and 6% magnesium sulfate at a rate not exceeding 30 mL/min to avoid excessive depression, or a mixture of 44–88 mg/kg of 5% guaifenesin and 2.2–6.6 mg/kg thiamyal, given IV to effect. Horses with seizures induced by toxins or adverse drug effect (eg, xylazine) can be treated with diazepam (0.1–0.15 mg/kg, IV). If cerebral edema is suspected, see Principles of Therapy of Neurologic Disease.

Ruminants

Diazepam has been used at 0.5–1.5 mg/kg, IM or IV. In sheep and goats, pentobarbital at 20–30 mg/kg can be used IV to effect to induce anesthesia. The duration of effect is 5–30 min.

Dogs and Cats

A variety of drugs can be used to stop seizures in dogs and cats.

Benzodiazepines:

Diazepam is the most common benzodiazepine used in dogs and cats to reduce motor activity and permit placement of an IV catheter. When used as an IV bolus (0.5–2 mg/kg), the dose may be repeated up to three times at intervals of 5–10 min. However if seizures occur after the second or third bolus, a constant-rate infusion (CRI) of diazepam at 0.5–2 mg/kg/hr may be more effective (especially if titrated based on seizure control and sedation level), and IV phenobarbital should be started as a preventive (see Barbiturates). When diazepam is used as a CRI, it should be mixed with 5% dextrose or 0.9% saline. It should not be mixed with lactated Ringer’s solution, because the calcium may cause precipitation of the diazepam. Because plastic will absorb diazepam, it should not be left in plastic syringes or IV sets for prolonged intervals. When diazepam is administered as a CRI, it is thought that the initial pass-through in the IV set saturates the surface of the tubing such that there is no further absorption. If IV access is not possible in dogs, diazepam can be administered rectally at 0.5–2 mg/kg (2 mg/kg if the dog is receiving phenobarbital) or intranasally at 0.5 mg/kg. Rectal diazepam has been recommended as an at-home emergency treatment for some dogs that have clusters of seizures; it can be administered up to three times in a 24-hr period by owners.

Other benzodiazepines that can be used in dogs to stop seizure activity are clonazepam (0.05–0.2 mg/kg, IV; the IV form of the drug may not be available in the USA), lorazepam (0.2 mg/kg, every 4–6 hr), and midazolam (0.2 mg/kg, IV or IM; CRI dose 0.05–0.5 mg/kg/hr).

Barbiturates:

Phenobarbital is often used in status epilepticus cases to prevent further seizure activity. For animals not already on maintenance phenobarbital, a loading dose of 15 mg/kg, slow IV or IM, can be used. Alternatively, 3–6 mg/kg, IV or IM, can be administered every 15–30 min to attain the desired serum concentration; serum level increases by ~5 mcg/mL for every 3 mg/kg dose of phenobarbital. It is usually not necessary to exceed a total dose of 20 mg/kg. If injectable phenobarbital is effective in preventing or controlling seizures, an oral maintenance dose may be initiated, with the plan to decrease or stop injectable anticonvulsant infusions within the following 24 hr. Caution is necessary when administering both diazepam and phenobarbital, because a potentiation of their effects increases the risk of respiratory and cardiovascular collapse.

Propofol is a short-acting IV hypnotic anesthetic agent that may have anticonvulsant activity because it is GABA-mimetic, stabilizing GABA-inhibitory neurotransmitter sites. After IV administration, propofol rapidly crosses the blood-brain barrier and usually has an onset of action of <1 min. However, the duration of action after a single bolus is only ~2–5 min. When used as a single dose (2.5–4 mg/kg, IV) in dogs and cats, ~25% of the calculated dose is administered every 30 sec until the desired effect is reached. If seizures recur after 1–2 injections, a propofol CRI (0.05–0.2 up to 0.4 mg/kg/min) can be used if definitive airway control and hemodynamic support are available and if the animal can be closely monitored. During IV injection, seizure-like signs of excitement, paddling, nystagmus, muscle twitching, and opisthotonos may sometimes be seen.

Sodium pentobarbital is generally reserved for treatment of uncontrollable status epilepticus in dogs and cats, especially when diazepam and phenobarbital have failed (see Table: Drugs Used for Treatment of Status Epilepticus). In these species, it is administered at 2–15 mg/kg to effect for anesthesia. Pentobarbital is a respiratory depressant, so respiratory assistance must be readily available. The drug is irritating if administered perivascularly or subcutaneously. As the animal recovers from the drug’s effects, excitement may occur, which can be mistaken for seizure activity.

Inhalation Anesthesia:

In some cases, inhalation anesthesia is necessary to control or stop seizure activity. This requires constant monitoring and mechanical ventilation.

Alternative Methods to Stop a Seizure:

Phenytoin at 2–5 mg/kg has been used as a slow IV infusion in dogs to stop a seizure. Ocular compression (application of digital pressure to one or both eyes) may be beneficial via stimulation of the vagus nerve. An implantable pacemaker device that delivers repetitive stimulation to the left cervical vagus nerve has been investigated in dogs and may be of benefit in some epileptic animals. Acupuncture points KID 1 and/or GV 26 might also be of benefit.