Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs

Abstract

Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of N-methyl-D-aspartic (NMDA) receptors. Rodent models have shown the efficacy of ketamine (KET) in treating RSE, and its use has been reported in one canine case of RSE. Boluses of KET 5 mg/kg IV have become the preferred treatment for RSE in our hospital. A retrospective study was performed to evaluate and report our experience with KET IV bolus to treat prolonged and/or repeated seizure activity in cases of canine CS, SE, and RSE. A total of 15 dogs were retrieved, for 20 hospitalizations and 28 KET IV injections over 3 years. KET IV boluses were used 12 times for RSE (9 generalized seizures, 3 focal seizures) and KET terminated the episode of RSE 12/12 times (100%); however, seizures recurred 4/12 times (33%) within ≤6 h of KET IV bolus. When used for CS apart from episodes of RSE, KET IV bolus was associated with termination of the CS episode only 4/14 times (29%). Only 4/28 (14%) KET IV boluses were associated with adverse effects imputable only to the use of KET. One dog experienced a short, self-limited seizure activity during administration of KET IV, which was most likely related to a pre-mature use of KET IV (i.e., before GABAergic resistance and NMDA receptor overexpression had taken place). This study indicates that KET 5 mg/kg IV bolus may be successful for the treatment of RSE in dogs.

Constant rate infusion of diazepam or propofol for the management of canine cluster seizures or status epilepticus

“…Only one consistent retrospective study has been published on the utilization of ketamine in dogs affected by SE, refractory SE and CS. In those 15 cases reported, ketamine was administered at a dosage of 5 mg/kg IV boluses and resulted effective in 100% of cases of refractory SE, supporting the results obtained in experimental settings (36). In the present study, the treatment protocol did not include an NMDA receptor antagonist, therefore it is possible, but not confirmable, that some of the cases of poor outcome could be related to a reduction of efficacy of benzodiazepines in case of prolonged seizure activity, overexpression of NMDA receptors or both.…”

ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats

“…After the exclusion of duplicates, 87 (SE) and 28 (CS) studies remained and entered stage 2 screening. Of these, 38 clinical studies 2,3,37‐40,43‐74 (SE; dogs, n = 36; cats, n = 5) and 12 clinical studies 37,40,48,49,57,64,75‐80 (CS; dogs, n = 12; cats, n = 0) as well as 37 pharmacokinetic studies 49,57,65,81‐114 (dogs, n = 33; cats, n = 4) fulfilled stage 2 criteria and were selected for review. Some clinical studies included a mixed populations of dogs and cats.…”

“…The most commonly reported form of SE in animals is generalized (tonic-clonic) CSE. 4,[37][38][39][40][41] However, the diagnosis of CSE and, in particular, NCSE can be overlooked in veterinary patients mainly because of the broad lack of utilization of and expertise in ictal EEG. 42 There are only a few reports of the use of EEG for the diagnosis of NCSE.…”

“…However, the broad clinical semiology of CSE and NCSE reported in humans has not been observed or officially described in animals. The most commonly reported form of SE in animals is generalized (tonic‐clonic) CSE 4,37‐41 . However, the diagnosis of CSE and, in particular, NCSE can be overlooked in veterinary patients mainly because of the broad lack of utilization of and expertise in ictal EEG 42 .…”

Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus

“…39 Similarly, ketamine administration was followed by RSE termination in 100% of 12 dogs. 42 Ketamine rarely affected the EEG background, indicating the goal of ketamine administration is seizure improvement and not induction of a change in EEG background. However, this is discordant with a recent pediatric case series of 13 patients with 19 RSE episodes in which a ketamine bolus (3 mg/kg) was followed by a suppression-burst pattern in 10/14 RSE episodes that responded to ketamine.…”