Cluster Buster Protocols for Seizure Care

What is a cluster seizure?

Cluster seizures are defined as 2 or more discrete seizures within a 24 hour period.1 Cluster seizures are different than status epilepticus (any one seizure lasting for an extended period of time, or 2 seizures in which poor recovery occurred between seizures). Cluster seizures pose a special concern for seizure patients because of they have been linked with poorer outcomes compared to dogs without a history of cluster seizures. 

The goal with cluster seizure management is to minimize the number and duration of seizures. A secondary goal is to reduce the need for hospital visit or stay thus reducing the financial burden to the client. 

When should I provide a cluster seizure plan to a client?

  • If a patient has a history of 2 or more times when they had cluster seizures

  • If the patient has a history of status epilepticus 

What drug choices, routes of administration and doses can I offer?

Levetiracetam

  1. Rectal administration – 40 mg/kg PR at the time of seizure, repeated once if needed within 24 hours. Results suggest an improvement in seizure management in the medium term using rectal levetiracetam AND standard anticonvulsant therapy in one stud

  2. Oral administration – start 20-30 mg/kg PO q8hr (NOT Extended release) levetiracetam after a pet experiences the first seizure and has recovered enough to eat and continue q8hr dosing for 2 days beyond the pet’s last seizure. The levetiracetam is then stopped, and standard anticonvulsant therapy is continued long-term. Clinical experience suggests this approach will reduce clinic visits, number of seizures during the cluster event. However, clinical side effects such as sedation or ataxia may be present during the dosing period. Note: This approach should NOT be used if levetiracetam is part of a patient’s standard oral therapy for long-term seizure control. Suddenly discontinuing an anticonvulsant medication can lead to breakthrough seizures or status epilepticus.

Benzodiazepine
Diazepam has been the main acute anticonvulsant treatment for veterinary patients.4–7

  1. Rectal -  Be sure to target the rectum, not colon, to avoid hepatic metabolism. Start 1-2 mg/kg per rectum.10  Compounded suppository formulations of diazepam have not demonstrated reliable serum diazepam concentrations in dogs therefore compounded suppositories are not currently recommended.9  

  2. Intranasal – preferred by some due to the ease of administration, and avoidance of the first pass effect of metabolism. Start with 0.5 mg/kg intranasal. 

Midazolam

  1. Intranasal – this is my preferred route and drug for at home benzodiazepine administration. Additionally, it was reported to be favorable compared to intravenous midazolam in 44 dogs. 11 Start with 0.2 mg/kg intranasal. 

  2. Intramuscular – this route is favored by some but is not my recommended route of administration for clients at home in emergency situations. In a clinical situation, intramuscular administration can be effective when intravenous access is limited. Starting dose of 0.2 mg/kg is recommended.

  3. Rectal – do not use midazolam rectally due to erratic and unpredictable plasma concentrations at standard doses.

 
Phenobarbital
Patients receiving daily phenobarbital administration can benefit from an increase, or pulse, of phenobarbital therapy during a cluster event.

  1. Oral increase – in my clinical practice we regularly recommend increasing a dog from q12h dosing to q8h dosing for 2 days beyond the last seizure. An example of this would be if a dog had a seizure Saturday morning. Upon recovery from the seizure an additional oral dose of phenobarbital (at the same oral dose administered) is recommended followed by q8hr dosing Sunday and Monday. Tuesday the dog would return to the standard twice daily dosing interval. This approach provides a slight increase of serum phenobarbital concentrations which may protect against further cluster seizures. Clinical adverse effects such as increased sedation, ataxia, polyuria, polydipsia, and polyphagia may become evident during the increased dosing period.

Summary
Providing options at home for cluster seizure care can reduce the need for hospitalization, or clinic visits. Additionally, any of the above treatments can be provided in hospital during seizure observation should that be needed. All the treatment choices discussed above are targeted for dogs and are rarely used in cats. Although the medications discussed have been evaluated for safety for use in cats, the specific protocols do not have clinical trial data, and minimal clinical experience.

Thanks for reading! Please let me know if you have any questions. I look forward to working with you soon!

References:
1.          Packer RMA, Shihab NK, Torres BBJ, Volk HA. Risk Factors for Cluster Seizures in Canine Idiopathic Epilepsy. Vol 105.; 2016: 136-138.
2.          Monteiro R, Adams V, Keys D, Platt SR. Canine idiopathic epilepsy: Prevalence, risk factors and outcome associated with cluster seizures and status epilepticus. J Small Anim Pract. 2012;53(September):526-530.
3.          Cagnotti G, Odore R, Bertone I, et al. Open-label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures. J Vet Intern Med. 2019;33(4):1714-1718.
4.          Eagleson JS, Platt SR, Elder Strong DL, et al. Bioavailability of a novel midazolam gel after intranasal administration in dogs. Am J Vet Res. 2012;73(4):539-545.
5.          Boothe DM. Anticonvulsant Therapy in Animals. Vet Clin NA Small Anim Pract. 1998;28(2):411-448.
6.          Patterson ENE. Status Epilepticus and Cluster Seizures. Vet Clin North Am Small Anim Pract. 2014;44(6):1103-1112.
7.          Charalambous M, Bhatti SFM, Van Ham L, et al. Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial. J Vet Intern Med. 2017;31(4):1149-1158.
8.          Podell M. The use of diazepam per rectum at home for the acute management of cluster seizures in dogs. J Vet Intern Med. 1995;9(2):68-74.
9.          Probst CW, Thomas WB, Moyers TD, Martin T, Cox S. Evaluation of plasma diazepam and nordiazepam concentrations following administration of diazepam intravenously or via suppository Per Rectum in Dogs. AJVR. 2013;74(4):611-615.
10.        Thomas WB. Idiopathic Epilepsy in Dogs and Cats. Vet Clin North Am Small Anim Pract. 2010;40(1):161-179.
11.        Charalambous M, Volk HA, Tipold A, et al. Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study. J Vet Intern Med. 2019.