STATUS

EPILEPTICUS

Status epilepticus (SE), can be defined as:

continuous seizure activity lasting longer than 30 minutes or

the occurrence of two or more seizures without full recovery of consciousness
during the interictal period

 

The first definition can be impractical, as emergency treatment measures should be taken well before the 30-minute time-line (and many texts define SE as seizure activity lasting more than 5 minutes). Almost any type of seizure may become prolonged or repetitive and thereby constitute a potentially greater threat to the patient than a single ictus. A more practical definition of SE is that of a continuous series of two or more discrete seizures lasting at least 5 minutes between which there is incomplete recovery of consciousness.

 

Although SE is primarily a central nervous system abnormality it results in significant systemic pathophysiological changes. In the early stages of SE there is increased autonomic discharge causing tachycardia, hypertension, and hyperglycaemia. These changes help to compensate for the increased metabolic demands of the brain. However, after about 30 minutes decompensation and hypotension, hypoglycaemia, hyperthermia, and hypoxia develop. Reduced cerebral blood flow results in ischaemia and neuronal death.

 

Skeletal muscle activity and impaired ventilation may lead to lactic acidosis, hyperkalaemia, hypoxia, hypercarbia and hyperthermia. Severe muscle activity during seizure activity can result in muscle damage. Myoglobinuria may cause renal dysfunction (particularly when accompanied by systemic hypotension).

 

SE can affect any epileptic and is associated with a variety of underlying diseases. The prevalence of SE in veterinary medicine has not been evaluated, however the prevalence of dogs with either SE or cluster seizures has been estimated to be 0.44% of the total hospital admissions.

 

Immediate treatment is necessary because SE can cause permanent neurological sequelae or even death. The profound haemodynamic and metabolic abnormalities occurring during seizures may cause significant morbidity. Early, aggressive treatment of prolonged seizures can result in their termination with smaller doses of medication and less overall risk to the patient.

 

In a recent study of dogs with idiopathic epilepsy 2.5% of dogs presented with SE and 41% with cluster seizures. However, sudden onset of severe generalised seizures should raise the suspicion of significant underlying pathology. Diseases commonly associated with SE are tumours, central nervous system infections, trauma, metabolic disorders such as electrolyte disturbances, and cerebrovascular events (stroke).

Initial management of status epilepticus

On initial presentation of a patient in SE, it is prudent to examine the skull and spine for any evidence of recent trauma. This should be done by gentle palpation of the animal, paying particular attention to the head and spine, assessing for crepitation, pain, and asymmetry. Stabilise the patient by securing an airway and providing intravenous access. Blood samples can be collected at this point for future analysis and anticonvulsants should be administered (within 5 minutes of presentation).

 

Benzodiazepines are the anticonvulsants of choice for first line management of SE. Diazepam can be given IV (0.5-1.0 mg/kg), intranasally or per rectum (1-2 mg/kg). This dose can be repeated 5-10 minutes later. This is followed by an IV bolus of phenobarbital (5-10 mg/kg), although this takes 10-15 minutes to have an effect the anticonvulsant effects will be prolonged. The combined effects of diazepam and phenobarbital may produce pronounced cardiac and respiratory depression.

 

Probably the most common and most dangerous error made in the management of SE is to treat repeated seizures with repeated doses of IV diazepam without administering an adequate loading dose of a longer-acting anticonvulsant. In this situation, the patient will continue to have seizures, toxic concentrations of diazepam or diazepam metabolites will accumulate, and serious morbidity may result from diazepam over-dosage.

Continuous patient monitoring is important assessing the following:

• Clinical and neurological status

• Blood pressure

• Blood gases if available

• A cerebral mass, such as a tumour

 

Standard laboratory blood tests should be performed including evaluations for glucose, sodium and calcium level abnormalities, renal and hepatic dysfunction, and serum acetylcholinesterase levels. Liver enzyme concentrations might be increased shortly after seizure activity because of the effects of hypoxia and hypotension. If hypoglycaemia is a potential cause of SE, or if blood glucose determination is unavailable, give 500 mg/kg of 50% dextrose (preferably diluted to 25%) IV over 15 minutes. If the patient has been receiving phenobarbital or other anticonvulsants prior to the development of SE, serum levels of these drugs should be obtained. If encephalitis is suspected, a cerebrospinal fluid analysis should be considered as soon as seizure stabilisation is achieved – CSF may be abnormal in more 1 in 3 dogs with sudden onset SE or cluster seizures. Patients with new-onset seizures should be considered for brain imaging procedures such as computed tomographic (CT) scanning or a magnetic resonance imaging (MRI). Concurrently, a medical history should be obtained from the owners or retrieved from available medical records.

Treatment of the refractory status epilepticus patient

Status epilepticus (SE) that does not respond to a benzodiazepine or phenobarbital is considered refractory and requires more aggressive treatment. Potential reasons for resistant seizure activity include:

 

inadequate doses of anticonvulsant

an uncorrected metabolic abnormality

a cerebral mass, such as a tumour

 

Short-acting anaesthetic drugs eg propofol infusion (0.1-0.6 mg/kg/min) are the most commonly used agents for treating resistant SE, as they have a rapid onset of action, short half-lives, and reduce cerebral metabolic rates. These drugs should be used only in an intensive care setting because of the need for continuous blood pressure monitoring and ideally, central venous pressure monitoring. General anaesthesia prevents tonic-clonic movements and allows manual control of respiration.

Barbiturates

Thiopentone and pentobarbitone have potential, though unproven, cerebral protective effects in the management of SE. In adequate doses these drugs will almost always control the physical manifestations of seizures, but severe hypotension limits their safety. Pentobarbitone should be given to effect not as a specific dose (3-15 mg/kg body weight IV) as there is tremendous individual variation in response. Thiopentone has been associated with a higher degree of cardiac toxicity than pentobarbitone.

 

If “barbiturate coma” is induced patients will require an extended period of mechanical ventilation. In general, the side effects of barbiturate coma include depression of myocardial metabolism, vasodilation with a decreased venous return, and decreased cardiac perfusion. These effects can be minimised by the use of saline infusion and small doses of dopamine.

Inhalational Anaesthesia

Inhalational anaesthetics have been recommended as a last resort in cases of resistant SE. The equipment and personnel necessary to administer inhalational anaesthesia may not be readily available. Isoflurane may be efficacious in the treatment of resistant SE, however; enflurane may actually increase seizure activity.

Outcome

An unbiased mortality rate of dogs with SE is unknown, because many animals are euthanased prior to aggressive diagnosis and treatment. The overall mortality rate among human adults with SE varies in the literature from 3 to 22%! This is difficult to interpret given the variety of underlying problems that can cause SE, which may be an explanation as to why the mortality rate associated solely with SE has not been evaluated in veterinary patients. Approximately 25% of 156 dogs with SE or cluster seizures, died or were euthanased in one study. A significant negative association was identified between the outcome and the diagnosis of granulomatous meningoencephalitis (GME) and the outcome and loss of control of the seizure activity at 6 hours after admission.

 

As more evidence accumulates about SE and cluster seizures, we can become more comfortable advising the owners about their concerns. Until all the information is at hand, aggressive early treatment and diagnosis with realistic expectations remain pivotal.

References:

Bunch SE, Castlemann WL, Hornbuckle WE et al (1982) Hepatic cirrhosis associated with long-term anticonvulsant drug therapy in dogs. JAVMA 18, 357-362. - PubMed -

 

Gaskill CL, Burton SA, Gelens HCJ et al (2000) Changes in thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year. J Vet Pharmacol Ther 23, 243-249. - PubMed -

 

Heynold Y, Faissler D, Steffen F et al (1997) Clinical, epidemiological and treatment results of idiopathic epilepsy in 54 Labrador Retrievers: a long-term study. JSAP 38, 7-14. - PubMed -

 

Jull P, Risio LD, Horton C, Volk HA (2011) Effect of prolonged status epilepticus as a result of intoxication on epileptogenesis in a UK canine population. Vet Rec. 169(14):361. Epub 2011 Aug 18. - PubMed -

 

Kathmann I, Jaggy A, Busato A et al (1999) Clinical and genetic investigations of idiopathic epilepsy in the Bernese Mountain Dog. JSAP 40, 319-325. - PubMed -

 

Leppik IE, Patterson E, Hardy B, Cloyd JC (2009) Canine status epilepticus: Proof of principle studies. Epilepsia. 50 Suppl 12:14-5. - PubMed -

 

Lowenstein DH, Alldredge BK (1998) Status epilepticus. New Engl.J.Med 338, 970-976. - PubMed -

 

Platt SR, Haag M (2002) Canine status epilepticus: a retrospective study of 50 cases. JSAP 43, 151-153. - PubMed -

 

Saito M, Munana, KR, Sharp N et al (2001) Risk factors for development of status epilepticus in dogs with idiopathic epilepsy and effects of status epilepticus on outcome and survival time. JAVMA 219, 618-623. - PubMed -

 

Zimmermann R, Hülsmeyer VI, Sauter-Louis C, Fischer A (2009) Status epilepticus and epileptic seizures in dogs. JVIM 23(5):970-6. - PubMed -

 

 

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