Page 419 - WSAVA2017
P. 419

S. Platt1
1College of Veterinary Medicine- University of Georgia, Small Animal Medicine and Surgery, ATHENS, USA
Simon R. Platt BVM&S MRCVS Dipl. ACVIM (Neurology) Dipl.ECVN
University of Georgia, Athens, GA.
The goals of anticonvulsant therapy in SE are to achieve cessation of clinical and electrical seizure activity and prevent its recurrence. Intravenous drug treatment for SE should be started without delay. This is necessary based upon the relationship between duration of SE and the extent of neurologic morbidity. This approach is also based upon experimental animal models that suggest that SE becomes progressively less responsive to treatment with diazepam.
Diazepam remains the first drug of choice for the treatment of SE in dogs and cats. With its relatively brief duration of action, diazepam is not a definitive therapy
for SE. It has been recommended to use 0.5 to 1.0 mg/ kg intravenously, up to a maximum dose of 20 mg, in dogs and cats. This dose can be repeated to effect
or twice within two hours. If the diazepam does not control the seizures, the use of phenobarbital should
be considered. 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 anti-epileptic drug. 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. Intravenous administration of diazepam may not be possible in some patients. It can be administered intramuscularly (IM), although absorption is not predictable. Rectal administration of diazepam may be considered initially at a dose of 0.5 to 2.0 mg/
kg body weight depending upon whether the animal was being treated with phenobarbitone before the onset of SE. It may be necessary to use the higher dose in dogs receiving long-term phenobarbitone therapy. In previously untreated dogs, a per rectum diazepam dose of 1 mg/kg results in a mean time to peak plasma concentration of approximately 14 minutes.
Midazolam is a recently developed water-soluble benzodiazepine which is biotransformed by hepatic microsomal oxidation followed by glucuronide conjugation. Midazolam has been shown to have a wide margin of safety and a broad therapeutic index. Unlike diazepam, with erratic and incomplete intramuscular absorption, midazolam is rapidly absorbed following
IM injection, with a high bioavailability, an early onset
of sedation, and early clinical effects. The peak plasma concentration in dogs after IM administration was seen within 15 minutes. The dose for cats and dogs is 0.066 - 0.3 mg/kg IM or IV.
Phenobarbital (PB) is a safe, inexpensive drug that may be administered orally, intravenously or intramuscularly. Phenobarbital increases the seizure threshold required for seizure discharge and acts to decrease the spread of the discharge to neighboring neurons The recommended loading dose is 12 to 24 mg/kg IV, if immediate therapeutic concentrations are desired but this can induce a profound stupor with concurrent suppression
of the cardiovascular and respiratory. Alternatively, the dose can initially be 2 mg/kg IV, repeating the dose every 20 - 30 minutes to effect and to a maximum total 24- hour dose of 24 mg/kg. The parenteral form can also be given IM, which is recommended if diazepam has already been administered. This will avoid the potentiation of profound respiratory and cardiovascular depression.
The depressant effects of PB on respiratory drive, level
of consciousness, and blood pressure may complicate management of the SE patient, especially when administered after benzodiazepine.
In human cases of refractory SE, the use of IV infusions of anesthetic doses of propofol, 2,6-diisopropylphenol, has become standard. This approach has recently been evaluated in veterinary patients. Propofol has barbiturate- and benzodiazepine-like effects on the (GABA)A receptor and can suppress CNS metabolic activity. Propofol can be administered by IV bolus (1-4 mg/kg) or by constant rate infusion (0.1-0.6 mg/kg/min titrated to effect or up to 6 mg/kg/hr). The advantages of this drug over the barbiturates are its rapid clearance, chiefly eliminated
by hepatic conjugation to inactive metabolites, and
less profound hypotensive effects. However, this drug should be used with caution, preferably in settings where definitive airway control and hemodynamic support
is possible, as hypoxemia secondary to apnoea is a primary side-effect as is myocardial depression.
An Urban Experience

   417   418   419   420   421