Status epilepticus and cluster seizures are common neurological emergencies in both primary and specialty care. Status epilepticus is defined as a prolonged seizure lasting longer than five minutes, or two or more seizures without recovery of consciousness in between. Cluster seizures are defined as more than two self-limiting seizures over a 24-hour period. Early treatment is important to minimise the risk of severe systemic complications and irreversible brain damage. Thirty minutes is the duration of convulsive status epilepticus that will cause permanent complications and neuronal injury.
In this article, we will discuss the management of status epilepticus in dogs and cats with idiopathic epilepsy or structural epilepsy, in which epilepsy is caused by structural brain disease such as neoplasia or inflammatory brain disease.
First-line treatment
Rectal administration of diazepam has been the mainstay for emergency management of seizures in the home environment, or in situations where venous access has not yet been established. The recommended dosage for rectal or IV administration of diazepam is 0.5 to 1mg/kg. Patients on long-term phenobarbital therapy may require higher doses of diazepam (2mg/kg) due to activation of the liver’s hepatic cytochrome P450 enzyme system, resulting in increased metabolism of diazepam and its metabolites. Intramuscular absorption of diazepam is variable; therefore, this route of administration is not recommended. Administration of diazepam in cats has been associated with acute hepatic necrosis. However, this complication has only been reported when diazepam was administered orally; therefore, parenteral administration of diazepam in an emergency situation should not be withheld from cats.
In a recent study, intranasal midazolam administration in dogs with status epilepticus or cluster seizures appeared superior in efficacy to rectal diazepam for the control of status epilepticus in dogs (Charalambous et al., 2019). The recommended dosage for intranasal, intramuscular or intravenous midazolam in dogs and cats is 0.2mg/kg. Intranasal midazolam is administered by using an atomiser which is coupled to a syringe (Figure 1). If the volume is larger than 1ml, the midazolam can be divided over two nostrils.
Sedation and ataxia are the most common side effects reported after administration of benzodiazepines. If the seizure doesn’t stop, or the dog or cat has a second seizure, the administration of benzodiazepines can be repeated. The administration can be repeated up to three times within 24 hours. It is recommended to wait for two minutes in between bolus administration.
Intranasal midazolam administration in dogs with status epilepticus or cluster seizures appeared superior in efficacy to rectal diazepam for the control of status epilepticus in dogs
In cases of recurrent seizures after two benzodiazepine boluses, a third bolus immediately followed by a benzodiazepine IV constant-rate infusion (CRI) is recommended. Midazolam might be considered a more potent and safer benzodiazepine compared to diazepam. Diazepam poses some risks regarding its CRI administration as diazepam can be adsorbed to plastic leading to a loss of drug efficacy. Furthermore, diazepam is also light-sensitive. If diazepam is used, the administration set should be protected from light and changed every two hours. Care should also be taken when administering other medications into this line, as when combined with diazepam, many other medications will cause precipitates to form. The dosage for a CRI of diazepam ranges between 0.1 and 0.5mg/kg/hour. The dosage for a CRI of midazolam ranges between 0.05 and 0.3mg/kg/hour.
Second-line treatment
Levetiracetam and phenobarbital are initiated as second-line medications when the first-line treatment has failed to control the seizures. However, these medications can also be administered earlier, regardless of the response to first-line treatments, with the aim of maintaining adequate seizure control in the short and long term.
In dogs and cats that are prone to developing cluster seizures, levetiracetam pulse therapy can be considered to treat seizures and to attempt to prevent severe cluster seizures or status epilepticus from occurring. An initial oral or intravenous dose of 40 to 60mg/kg can be given after a seizure occurs, followed by 20mg/kg every eight hours until seizures do not occur for 48 hours.
Ataxia and sedation are commonly reported side effects. There is some evidence available that levetiracetam suspension can be administered and absorbed rectally (Cagnotti et al., 2018). Levetiracetam is not metabolised in the liver, so it is a suitable option for patients with liver disease. Excretion is purely renal, and therefore caution should be used in patients with deficient renal function.
If benzodiazepines are successful in controlling the status epilepticus or cluster seizures, phenobarbital should be considered as a long-term maintenance anticonvulsant
If benzodiazepines are successful in controlling the status epilepticus or cluster seizures, phenobarbital should be considered as a long-term maintenance anticonvulsant if the patient is not yet receiving any maintenance treatment. Phenobarbital can also be considered as the next therapeutic step if boluses of benzodiazepines are not successful in controlling the seizures.
Phenobarbital can be parenterally loaded to achieve a rapid steady-state concentration if necessary. Loading of phenobarbital is only carried out in patients who have not received the drug yet. The loading dose of phenobarbital is 12 to 24mg/kg IV. However, it is recommended that small boluses (2 to 4mg/kg) should be administered, repeated every 20 to 30 minutes to effect, but not exceeding 24mg/kg over 24 hours.
The parenteral version of phenobarbital can also be given intramuscularly. Side effects of phenobarbital include respiratory depression, hypotension and sedation. Close monitoring during the loading of phenobarbital is recommended. The medication should be switched to the regular twice-daily oral administration as soon as possible.
Third-line treatment
Third-line treatment refers to anaesthetic medications used for controlling seizure activity. Recommended agents are ketamine, (dex)medetomidine, barbiturates (thiopental or pentobarbital) and inhalant anaesthetics. As general anaesthetics, in particular barbiturates followed by propofol and inhalant anaesthetics, can be linked to safety issues and a higher rate of in-hospital complications, it is best to use the agents with a better safety profile ((dex)medetomidine or ketamine) first.
As general anaesthetics […] can be linked to safety issues and a higher rate of in-hospital complications, it is best to use the agents with a better safety profile ((dex)medetomidine or ketamine) first
Adverse effects of a dexmedetomidine CRI include decreased respiration, hypothermia, bradycardia and cardiac arrhythmias. Further, ketamine increases the blood pressure. Adverse effects from propofol include cardiovascular and respiratory depression, pain at the injection site and loss of gag reflex. Thus, if a CRI of propofol is used, adequate airway control and haemodynamic and possible ventilatory support should be available. Propofol is a phenol and can cause oxidative injury to the red blood cells of cats, resulting in Heinz body formation and haemolytic anaemia. Inhalant anaesthesia is considered a last resort in refractory status epilepticus. Maintaining a patient on an inhalant anaesthetic requires intensive monitoring and mechanical ventilation.
