Notes supplied by Nadja Sigrist, DrMedVet, FVH(Small Animals), DACVECC.

Introduction

Status epilepticus is defined as generalised tonic-clonic seizure activity lasting longer than 5–10 minutes, focal seizures lasting longer than 20–30 minutes or multiple seizures without clinical or electroencephalographic normalisation between two seizures. Status epilepticus is a life-threatening condition that is diagnosed clinically and requires prompt management, including immediate seizure suppression, identification of a treatable underlying problem and supportive care followed by intensive care and monitoring.

Stabilisation of the Patient with Status Epilepticus

The medical interruption of seizure activity and prevention of subsequent damage are the main goals of stabilisation.

The emergency treatment follows the ABC. The patient should be supplemented with oxygen by mask or flow-by. An intravenous line should be placed whenever possible, as intravenous medication and fluids will be mandatory. Fluids are administered according to the patient's needs. If the patient is not in shock, isotonic crystalloid fluids are started at 10 ml/kg/hr unless fluid diuresis is contra-indicated. Blood should be taken for packed cell volume (PCV)/total solids, glucose, blood urea nitrogen (BUN) or creatinine, acid-base status (if available) and electrolytes including calcium.

Antiepileptic Therapy

Antiepileptic therapy is started as soon as possible and generally follows three steps:

1.  Diazepam. Diazepam is the first choice as it has a rapid onset of action within 5 minutes; however, duration of action is also short. Diazepam 0.5–1 mg/kg i.v. or rectally is given and may be repeated twice at intervals of 10 minutes. In the mean time, treatable causes such as hypoglycaemia or hypocalcaemia are identified and corrected.

2.  Phenobarbital/phenobarbitone. The antiepileptic medication of choice is phenobarbital. Phenobarbital is administered intravenously as a loading dose of 10–20 mg/kg. The onset of action of phenobarbital may take 20–30 minutes. Phenobarbital may be repeated up to a total initial dose of 25–30 mg/kg; however, sedation, respiratory depression and hypotension are common side effects of high doses of phenobarbital and may require intubation, ventilation and intensive care of the patient. It is important that all animals that continue to seizure after diazepam receive phenobarbital. After the loading dose, phenobarbital is continued at 5 mg/kg q12h.

3.  Other antiepileptic medications and/or anaesthesia. Depending on the (suspected) cause of seizure activity, other antiepileptic drugs may be tried or the patient is anaesthetised for 12–24 hours.

 Midazolam continuous rate infusion (CRI). Midazolam is, as diazepam, a GABA_A receptor agonist leading to hyperpolarisation of neurons, therefore inhibiting activation. In contrast to diazepam, which is light sensitive and may lead to thrombophlebitis if given as a CRI, midazolam is water-soluble and recommended for continuous administration of a benzodiazepine. The recommended CRI dose is 0.07–0.3 mg/kg/hr.

 Levetiracetam (Keppra®) is a newer anticonvulsive drug used commonly in human patients. Levetiracetam seems to be effective and safe in dogs and cats with idiopathic epilepsy not controllable with phenobarbital. However, there have been no pharmacokinetic studies for the establishment of the ideal treatment dose in animals with status epilepticus. The suggested dose is 20 mg/kg i.v./i.m.

 Anaesthesia using an anaesthetic with antiepileptic activity such as propofol and historically pentobarbital. Patients usually require 12–24 hours of anaesthesia, should be intubated and intensively monitored. This approach enables gastric lavage in cases of suspected intoxication.

 Pentobarbital is a barbiturate anaesthetic and GABA agonist with a fast onset of action (1 minute), but the anticonvulsant effect is less distinct than that of phenobarbital. Pentobarbital is titrated to effect (3–15 mg/kg i.v.) and repeated as required. Side effects are respiratory depression (especially in cats), a long recovery due to accumulation of the drug and excitement during recovery that may be difficult to differentiate from seizure activity.

 Propofol is a short-acting hypnotic and centrally acting GABA agonist with a potentially anticonvulsive effect. Propofol is titrated to effect and continued with boluses (1–4 mg/kg) or as a CRI (0.1–0.6 mg/kg/min). Propofol is biotransformed in the liver (glucuronide conjugation) to inactive metabolites and excreted by the kidneys and should be used carefully in cats. Side effects are respiratory depression, hypotension and seizure-like convulsions during recovery (usually shorter than with pentobarbital).

Ideally, inhibition of seizure activity is documented by electroencephalogram (EEG) analysis. This is especially important in animals under pentobarbital or propofol anaesthesia, as continued central seizure activity despite peripheral muscle relaxation is common.

Other treatment modalities that should be considered are gastric lavage and charcoal administrations in patients where intoxication cannot be ruled out, mannitol (0.5 g/kg i.v. over 20 minutes) in patients with signs of brain oedema (non-responsive dilated or pinpoint pupils) and steroids in patients with documented cerebral neoplasia. Steroids are contraindicated in all other patients with status epilepticus, as steroids may exacerbate hyperglycaemia and may actually increase mortality.

Patient Care

Patients under general anaesthesia should be intubated to decrease the risk of aspiration. Ventilation may not be required and oxygen can be supplemented via the endotracheal tube. End-tidal CO₂ or PCO₂ should be monitored in any case, as respiratory depression is a common side effect of the combination of phenobarbital with pentobarbital or propofol. The endotracheal tube should be suctioned and the cuff moved every 4–8 hours, and tube change should be planned every 12 hours. Sedated patients should be padded soft and dry, moved from one side to the other every 4 hours and require eye lubrication and mouth care every 2–4 hours. The head may be elevated slightly in order to decrease gastric reflux and risk of aspiration, especially after gastric lavage and/or charcoal application.

References

1.  Platt SR, McDonnell JJ. Status epilepticus: patient management and pharmacologic therapy. Compendium on Continuing Education for the Practicing Veterinarian 2000;22(8):722–729.