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Ketamine in status epilepticus
Status epilepticus is defined as 2 or more seizures without complete recovery of consciousness between seizures, or persistent seizure activity for more than 30 minutes constitute the definition of status epilepticus (SE) in human medicine. There are various `classic` therapeutics like diazepam or barbiturates. Ketamine might be a new option...

For practical purposes in small animals, any patient with witnessed persistent seizure activity, or who does not regain consciousness in five minutes or more after a seizure might be in SE. In some cases, it may be necessary to record an electroencephalogram (EEG) to determine whether a patient is in SE. Regardless of the etiology, SE is a life-threatening condition that requires immediate and aggressive treatment.

Death during or immediately after seizures is thought to be due to a centrally induced respiratory failure in animal models (Graham, Lantos, Greenfield`s Neuropathology, Vol. 1). Occasional fatal arrhythmias are also documented with SE.

It is critical to be aware of the systemic complications and the extensive brain damage induced by SE. Metabolic acidosis, hypoxia, hypercapnia, hypoglycemia, hyperpyrexia, electrolyte disturbances incontinence, myoglobinuria, renal failure, respiratory failure and arrhythmias might accompany seizure activity (J. Sirven et al.: Management of Status Epilepticus; American Family Physician, 2003, Vol. 68, No. 3). All of these changes can be exaggerated in SE.

The epileptic brain damage is due to a so-called consumptive hypoxia. It is documented in human patients that during ictus there is an actual cerebral hyperperfusion with hypermetabolism of the epileptogenic areas in the brain. In spite of the hyperperfusion, the increased oxygen and glucose demand (required by the increased metabolic rate) overcomes the increased cerebral blood flow, and eventually leads to consumptive hypoxia with subsequent neuronal cell loss. Certain areas such as the hippocampus, selected laminas of the neocortex and the Purkinje layer of the cerebellum are more affected than others.

In cases of SE, systemic stabilization and cessation of the seizure activity can lead to successful outcomes. Small animal clinicians have long used diazepam, propofol, sodium pentobarbital and inhalation anesthesia to help manage SE. It is noteworthy that 24-hour EEG monitoring of human patients (after presumed successful treatment of their clinical seizure activity) demonstrate periodic discharges of seizure activity in about half of the patients.

In a recent article (S. Serrano et al.: `Use of Ketamine for the Management of Refractory Status Epilepticus in a Dog`, J Vet Intern Med 2006:20:194-197) the authors achieved the cessation of seizures using bolus and constant-rate infusion (CRI) of ketamine in a dog with granulomatous meningoencephalomyelitis and SE that was refractory to IV diazepam and propofol.

According to the authors` explanation, ketamine antagonizes a certain ionotropic receptor subtype (the N-methyl-d-aspartic acid, NMDA). Activation of NMDA receptors during SE enhances the calcium influx and promotes subsequent cell death by a cascade of reactions (Graham, Lantos, Greenfield`s Neuropathology, Vol. 1).

The mitochondria become damaged by the heavy load of calcium, leading to superoxide generation that is toxic to the cell and the mitochondrial DNA. The nucleus and the cytoskeleton are also damaged by the calcium overload, and various toxic proteases (calpain), phospholipases become activated causing the formation of cytotoxic molecules.

Controversially, according to S. Serrano et al., excessive NMDA receptor antagonism can also be toxic, which could explain the ketamine neurotoxic effects on selected cortical neurons and Purkinje cells.

In conclusion, although there is not enough evidence for a clear recommendation regarding the use of ketamine in SE, NMDA receptor antagonism may deserve consideration in clinical research and selected clinical cases of refractory SE in veterinary medicine



Source: Dr. Beatrix Nanai, Dr. Ronald Lymann (2006): Status epilepticus: theoretical and clinical considerations. In: DVM Newsmagazine Jun 1, 2006
www.dvmnewsmagazine.com/dvm/


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SMALL ANIMAL PRACTICE

Reference intervals for blood parameters in Shetland Sheepdogsmembers
Several breeds have physiological peculiarities that induce variations in reference intervals (RIs) compared with the general canine population. Shetland sheepdogs (SSs) are reported to be more predisposed to different diseases (eg, hyperlipidemia, gallbladder mucocele, and hypothyroidism). Consequently, a breedâ€specific approach is more often required. Thus, the aim of this study was to determine whether the RIs of the general canine population could be applied to that of SSs, and to generate breedâ€specific RIs, where appropriate.

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