Anticonvulsants for Emergency Treatment of Seizures in Dogs and Cats

Clonazepam can be administered as a pulse treatment, orally, in dogs with cluster seizures, assuming the patient has recovered after the first seizure and is able to swallow medications.

Clonazepam is more potent than diazepam. Tolerance to this type of benzodiazepine takes longer to develop.

Lower doses might be necessary for dogs known to be susceptible to the sedative effect of benzodiazepines.

Adverse effects of clonazepam are similar to those of other benzodiazepines; they include sedation, lethargy, and ataxia. Some animals experience paradoxical excitation (excessive excitement, anxiety, or aggression).

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Pulse dosing of clorazepate in dogs has the potential to stop cluster seizures.

Adverse effects of clorazepate are similar to those of other benzodiazepines; they include sedation, lethargy, and ataxia. 

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Because diazepam has a rapid onset of action, it is usually the drug of choice to control status epilepticus and stop seizures in small and large animals. Diazepam has also been used for behavior disorders and as a muscle relaxant. In addition, it has been used as an appetite stimulant in cats. 

In large animal species, diazepam is routinely administered as well for emergency seizure treatment. It has been administered in foals as a CRI to control perinatal seizures.

Diazepam works as an anticonvulsant by hyperpolarizing neurons and suppressing neuronal activity via interaction with the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), mainly by modulating the GABA A receptor subunit. The result is increased activation of GABA-activated chloride channels, which leads to membrane hyperpolarization.

Because it is highly lipophilic, diazepam rapidly penetrates the CNS after IV injection, making this drug suitable in emergency situations to treat status epilepticus.

Per rectum is another convenient route of administration when the patient is in status epilepticus and there is no IV access. Rectal administration of diazepam (using the solution for injection) is routinely recommended as an at-home emergency treatment for some dogs with a history of cluster seizures; owners can give it up to 3 times in a 24-hour period.

Intranasal administration of diazepam has also been reported as viable; however, the bioavailability of the drug via this route is only approximately 40% in dogs (1). Clients must be counseled not to predraw dosages of diazepam into plastic syringes, because substantial drug loss resulting from adsorption to plastic (as well as exposure to light) is likely.

If diazepam is administered as an IV bolus, the dose can be repeated up to 3 times at intervals of 5–10 minutes. If seizures occur after the second or third bolus, however, a CRI of diazepam may be more effective (especially if titrated on the basis of seizure control and extent of sedation), and a maintenance anticonvulsant such as IV phenobarbital should be started as a preventative.

When diazepam is administered as a CRI, it should be mixed with saline solution (0.9% NaCl). It should never be administered with lactated Ringer's solution, because calcium in the solution can cause diazepam to precipitate.

Diazepam adsorbs (as much as 25–50% loss) to many plastics (eg, syringes, PVC bags, administration sets), so it should not be stored for long intervals (> 4 hours) in plastic-containing devices. When diazepam is administered as a CRI, the initial pass-through in the IV set is thought to saturate the surface of the tubing such that there is no further adsorption. Because diazepam is inactivated by light, the tubing should also be covered.

IM administration is not recommended, because of pain from the injection and unpredictable absorption.

Sedation is the most common adverse effect of diazepam. In dogs and cats, ataxia, increased appetite, paradoxical excitation, and agitation have also been reported. Just as with other benzodiazepines, the effects of diazepam can be reversed with flumazenil if adverse effects are too severe or in cases of overdose. Diazepam can cause phlebitis when administered intravenously. It can also cause increased intraocular pressure and should not be administered to patients with glaucoma.

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Midazolam has a mechanism of action similar to that of diazepam.

Because it is water-soluble, midazolam can be administered in aqueous vehicles and intramuscularly, in contrast to other drugs in this class; however, absorption after IM administration is variable. Like diazepam, midazolam can also be administered intranasally. 

The pharmacokinetics of midazolam have been studied in dogs. The drug's half-life is short in dogs (1–2 hours), with a high clearance (10–27 mL/kg/minute). Like other benzodiazepines, midazolam undergoes hepatic metabolism by cytochrome P450 enzymes.

Midazolam should not be administered per rectum, because absorption is poor via this route. However, midazolam has been shown to be superior to diazepam when administered intranasally to treat status epilepticus. It has also been shown to be a viable option and similar to diazepam when administered as a CRI to control status epilepticus or cluster seizures in dogs.

Adverse effects of midazolam are similar to those of other benzodiazepines; they include sedation, ataxia, and lethargy. Midazolam can also cause severe cardiovascular depression when administered intravenously. Paradoxical excitation has also been reported. In horses, midazolam can cause swaying, ataxia, agitation, and weakness shortly after IV administration. 

Just as with other benzodiazepines, midazolam can be reversed with flumazenil if the adverse effects are too severe. Like diazepam, midazolam can cause increased intraocular pressure and should not be administered to patients with glaucoma. 

Midazolam has been used in other species, such as pigs and sheep, mainly as a preanesthetic agent. Its use for seizure control has not been studied in these species but has been reported anecdotally.

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Despite growing interest in the use of cannabidiol (CBD) to treat seizures in humans and animals, only limited studies suggested a beneficial effect in epileptic dogs (2, 3), and no study has been conducted to assess the efficacy for seizure control in other species.

Ketamine, a dissociative anesthetic agent (see Tranquilizers, Sedatives, and Analgesics), has been anecdotally administered to manage refractory status epilepticus in some dogs. Larger-scale studies are needed to evaluate its efficacy to control status epilepticus in veterinary medicine. Because there are so few studies on its efficacy, ketamine should be administered with caution and only as a last resort.

Levetiracetam is available as an injectable solution and can be administered in emergency situations.

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

The drug's efficacy was shown to be superior to placebo in controlling seizures in dogs with status epilepticus or cluster seizures.

No data have been published on the use of levetiracetam to stop status epilepticus in other species.

Because it has minimal adverse effects and does not undergo hepatic metabolism, levetiracetam is a suitable option for treatment of status epilepticus in dogs with known or suspected liver disease.

In most dogs, rectal administration has allowed adequate therapeutic concentrations to be reached within 30 minutes. In a clinical trial in dogs with cluster seizures or status epilepticus, intrarectal levetiracetam appeared superior to IV phenobarbital combined with intrarectal or IV diazepam (4); however, the study was not conducted in a blinded fashion. High-dose oral administration of levetiracetam has been used by dog owners unable to seek emergency veterinary care.

Sedation and ataxia are reported adverse effects of levetiracetam in dogs. 

Because phenobarbital has a high bioavailability and is rapidly absorbed, it can be administered in cases of cluster seizures, reactive seizures, or status epilepticus to prevent further seizure activity.

For patients naive to the drug, a loading dose is recommended to try to achieve a higher serum concentration faster. This loading dose should either be administered slowly (via a syringe pump) or divided into 2 or 3 boluses to enable monitoring of the patient for severe respiratory depression.

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Some higher loading doses of phenobarbital have been reported; however, the risk of cardiorespiratory depression increases with higher doses. Severe respiratory depression requiring mechanical ventilation can occur with higher doses.

If injectable phenobarbital is effective in preventing or controlling seizures, an oral maintenance dosage can be initiated, with the plan to decrease or stop injectable anticonvulsant infusions within the following 24 hours (as long as the patient remains seizure-free).

Caution is necessary when administering both benzodiazepines and phenobarbital, because potentiation of their effects increases the risk of respiratory and cardiovascular collapse. 

Propofol is widely used as a short-acting anesthetic. Propofol can be administered to control status epilepticus in animals when all other anticonvulsants have failed, and it can be administered to effect to stop seizure activity.

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Propofol could have anticonvulsant activity because it is GABA-mimetic, thus stabilizing GABA-inhibitory neurotransmitter sites.

After IV administration, propofol rapidly crosses the blood-brain barrier and usually has an onset of action of < 1 minute. However, the duration of action after a single bolus is only approximately 2–5 minutes.

When propofol is administered as a single dose in dogs and cats, approximately 25% of the calculated dose is administered every 30 seconds until the desired effect is reached. If seizures recur after one or two injections, propofol can be administered as a CRI if definitive airway control and hemodynamic support are available, and the patient can be closely monitored.

During or after IV injection of propofol, seizure-like signs of excitement, paddling, nystagmus, muscle twitching, and opisthotonos can occur. These should not be mistaken as seizures.

Sodium pentobarbital is no longer recommended as an anticonvulsant; it could be considered, however, if all other options have failed or if alternative drugs are unavailable. Supplies of pure injectable pentobarbital not intended for euthanasia are in short supply.

For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.

Pentobarbital is a respiratory depressant, so if it is administered, respiratory assistance, via intubation and mechanical ventilation, will likely be required. Recovery is often associated with excitement, which can be mistaken for seizure activity.