Status and Cluster Seizures
Disclaimer: These questions were generated at a CE lecture of AVMA. There may be context provided in the lecture that is not addressed in the answer to these questions. Paper links have been provided where possible/applicable. I linked to the publisher’s site to avoid any copyright issues. Some papers may be behind paywalls, though I try to use mostly open-access journals. Finally, many of these comments are opinions or thoughts based on experience in my situation; your patient’s situation may not apply to all comments. I try to link sources to questions about doses. It is recommended that you consider rechecking all doses prior.
What resources do you like to use for owners with pets who have seizures, especially cluster seizures
a. There are many support sites on different platforms. I will mention one I am involved in: Pet Parent Educators. This new group aims to support pets with chronic conditions (including epilepsy, tumors, diabetes, Cushing’s, etc). We are in the process of setting it up as a 501c3 Charitable Organization so that we can offer free (or low-cost) support to Pet Parents and veterinarians. Many social media pages do have poor or misinformation on them, so I am hesitant to encourage their use, but in some cases, they can be great support networks.
Do you have to have a special applicator for IN midazolam, or can you just shoot it in with a regular syringe?
a. The atomizer I use (link here) has been very helpful because it turns the medication into a fine mist to help coat the nasal mucosa. That being said, I have also used boradella tips in a pickle and without tips if the situation calls for it. That being said, what is nice about the atomizer linked above is that it has that soft padding around the tip that does 2 things. First, it protects the nose, second, it creates a seal around the nose to prevent loss.
b. I want to address when I use/script out intranasal midazolam. I think it is MOST effective for animals that have prolonged seizure activity or cluster seizures that don’t break. In these situations, the goal is to stop the active seizure activity or prevent another cluter seizure in a very short time frame. This is where I find it the most effective. For situations where the patient has short seizure activity but clusters after a good recovery, a pulse therapy approach may be more beneficial.
Do you have to use the mister (atomizer) to give intranasal midazolam?
a. The benefit of it is that it coats the nasal mucosa. When administering without it you increase the chance of the majority of the dose just sliding down the back of the nose and getting swallowed.
What is your clorazepate protocol/dose?
a. I like to use clorazepate (oral benzodiazepine) around 0.5 to 1 mg/kg qh8 in dogs. (Thomas, W.B.: Seizures and narcolepsy. A Practical Guide to Canine and Feline Neurology). I have not used it in cats, given the same concern as oral diazepam. I typically start on the lower end (especially for animals on multiple other seizure medications). I may even begin BID if I am worried about sedation, then get it to q8h (half-life is only 4-6 hours). Then I titrate up on the dose if they are handling it okay from a sedation standpoint. I have them use it q8h for three days. This is by far my favorite “cluster buster”! I figure if I haven’t controlled the clusters within three days, I probably need to consider something else, and, like diazepam, dogs will get used to this when used long-term.
Can you post the ketamine bolus and CRI papers?
a. Yes! Here you are:
Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs -> Click Here
Use of Ketamine for the Management of Refractory Status Epilepticus in a Dog -> Bolous and CRI -> Click Here
Investigation of the effect and availability of ketamine on electroencephalography in cats with temporal lobe epilepsy -> Click Here
Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy? -> Click Here
ACVIM Consensus on Status and Clusters: -> Click Here
How do you manage a puppy who has seizures at 8 weeks? How often to change dose and monitor?
a. I would say the first thing I do is that I am a little more aggressive with my initial workup. I may consider infectious disease serology or use bile acids in my initial workup. I also talk about discussing referrals with owners (when doing vet-to-vet consultations) a little heavily in terms of the higher possibility of something congential or infectious occurring, but it does not guarantee it and have certainly have had some idiopathic epileptics (I.E.) come in this early on.
b.For the puppy regarding treating it for presumptive or known idiopathic epilepsy. I will have them come every 1 to 2 weeks for a “Free Weight Check”, then the nurses will give me the weight. From there, I aim to keep it at the same mg/kg or as close as I can based on pill size. Depending on the medication, it varies how much I may allow for going over. For example, if I’m shooting for 30mg/kg but 2 pill sizes push me to 25 or 35mg/kg, I’m going to go for the 35. I may not be willing when it comes to phenobarbital. For phenobarbital, I do check all bloodwork/levels 2 weeks after starting to get a sense of where we are at. Then I try to keep my mg/kg as close to there as possible, then repeat serum levels in about 4-6 weeks or if I lose seizure control. The young puppies absolutely make things harder because they change so frequently!
Do you use a higher mg/kg dose for Keppra ER?
a. I do. However, I generally use a higher dose of Keppra. Notably, this may be a bias of being a part of cases where I’m not the first person prescribing usually. I start at 30mg/kg and then round up for the XR (to fit the tabs). There is some debate, but even with a current review out of VECCS (click here) there still isn’t a consensus on dosing recommendations for XR.
So, do we know if hypertonic saline can be helpful in these cases (of status)?
a. Yes, mannitol and hypertonic saline have the same efficacy, and there is no proof that one is better. Hypertonic may help with hypovolemia more.
What are your tips for seizure management at home (e.g., cameras to monitor for seizure activity)? (owner resources answered in first question)
a. I have had good luck with cameras in the home based on where the pet spends most of their day. One paper also suggested that this helped ease owners' nerves in their findings. Some groups sell various seizure-monitoring wearables. My biggest issue with wearables is that they don’t always catch seizure activity (or are too sensitive). Often, these are worn on the collar, one area that doesn’t move as much during a seizure. There are many companies, however, working and looking at these devices. Sometimes, less is more. Many owners don’t have great compliance with apps and such for keeping track of seizures. A paper or calendar attached above the food back with an attached pen is just as good sometimes.
What is your thoughts on splitting Keppra XR to make IR for cluster seizure to aid in control?
a. I do it all the time and have no issue with it, but we need to recognize that the data is limited on Keppra. There are a couple of ways to go about this. Splitting it and dosing q8h is one of those ways. Another way I have pulsed Keppra (depending on client factors) is to go to TID dosing on the XR. The other is prescribing regular-release tablets for use following a seizure. Note that no data supports one method over another at this time. Even in a very good and very recent review on Keppra, they recognized there was limited data on this topic. (VECCS Article)
Are there anesthetic med protocols you steer away from for seizure patients (e.g. I have been told Ace lowers seizure threshold)? When you have a patient on seizure meds, do you reccomend anesthesia (annual dental cleanings)?
I don’t avoid anesthesia in anesthetic patients per se, but I do think we have to give it the credit and awareness it is due. A few recommendations I have (or have heard from anesthesiologists) include: Give morning seizure medications as normal, even if NPO. That way, they are in the system. You may need to take into account that they have these medications in their system, and it may alter their needed MAC, prolong recovery, or even make them more sedate in the premedication phase. I have seen opioids and propofol as some of the most recommended medications, as these tend not to hit the system so much. I use a lot of torb and dexmedetomidine in my MRI protocols, but of course, each patient gets their protocol after assessment. Some people talk about using midazolam as a premed, but it will only be in the system for a short time, so unless it is a super short procedure, I am not sure how useful it is for seizures. It doesn’t hurt to have a dose ready to go in case, especially around recovery (usually a smaller dose) as they are going through changes in brain activity. I think if you had to pick one thing, it would be not to skip doses. This is another reason why having at least one IV anti-seizure med is useful in case of prolonged recovery or inability to get orals in. Sometimes in vet med, we are a little too cavalier, I think, compared to humans, but our studies are limited, and I’m not sure I fully subscribe to the idea that “they are under anesthesia,” and that stops seizures. . . I get it, but they do have to wake up at some point. Again, I don’t worry to much – many of us put seizure dogs under anesthesia a lot for MRIs.
There is a lot of debate about acepromazine, but a few papers have come out suggesting it may not be what we were taught in school. That said, I know of at least one neurologist who had a bad experience with it and their pet, so each pet should be considered an individual. (Acepromazine Paper 1, Acepromazine Paper 2 = paywalled)
What about stress-induced seizures? Do you give meds each time?
So, the best situation is to avoid stress-based events. That being said, that is not always real life. There are two approaches to go with. You can use anti-anxiety medications (see conversation above). Also, especially in cats, the use of gabapentin for behavior has become popular (it is not a great seizure medication). Or consider pulse therapy for known episodes. There are no studies, but perhaps gabapentin in cats and diazepam/clorazepate in dogs would be worth considering. If you are referring to giving meds after a seizure event due to stress, I would say it depends on the pattern. If it is always a one-and-then-done, I wouldn’t. If it leads to clusters, I absolutely would.
Can you clarify the pulse keppra protocol?
a. Happy to clarify! If pulsing use 20-30 mg/kg (based on tablet size) PO q8hr (NOT Extended release) levetiracetam after a pet experiences a seizure and continue q8hr dosing for 2 days beyond the pet’s last seizure. This isn’t a great protocol if they are already on keppra however.
If you have a hospitalized patient who’s on Keppra ER but doesn’t carry that, should you give the regular form at the same dose every 8 hours? Or split the total dose?
a. Honestly, I have the owner go to the pharmacy or bring theirs. If that isn’t an option I would go to a regular formulation at the same dose q8h hours. We have no studies that show how or if the doses are computable, but there is discussion that XR may have lower doses, so one would assume the regular may bump us up a little.
For status, what steroid dose do you use (if giving)?
I use an anti-inflammatory dose, typically a pred equivalent of 1mg/kg/day.
If you give a dose of IN midazolam initially, can you switch to diazepam IV, or do you have to continue with IV midazolam?
a. You can. I am not aware of any studies that suggest you can’t. Always be cautious of total doses, but I have had to switch before because I ran out of midazolam. Be aware of the possible sedation using them together.
For a patient who has been put on anticonvulsant therapy years ago and has not had a seizure in years is it reasonable to wean them from the medication?
a. absolutely! I usually say around a year is when we can have that chat, but I am willing to discuss it with owners once we hit the 6 month mark, though a year is better.
You talked about intranasal midazolam, can you give diazepam intranasally? If so, what dose do you use? If not, what dose of midazolam do you use intranasal?
a. You can use both intranasal! Here are some papers on it! I prefer midazolam (some support for it being a tich better) and I dose it at 0.3mg/kg noting I anticipate some spillage by owner when giving with the hopes that about 0.2mg/kg get in. Note that the literature has a much wider range.
First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines. (Click here)
Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial (Click Here)
Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study (Click Here)
Comparison of plasma benzodiazepine concentrations following intranasal and intravenous administration of diazepam to dogs (Click Here)
Disclaimer: These questions were generated at a CE lecture of AVMA. There may be context provided in the lecture not addressed in the answer to these questions. Paper links have been provided where possible/applicable. I linked to the publisher’s site to avoid any copyright issues. Some papers may be behind paywalls, though I try to use mostly open-access journals. Finally, many of these comments are opinions or thoughts based on experience in my situation; your patient’s situation may not apply to all comments. I try to link sources to questions about doses. It is recommended that you consider rechecking all doses prior.