Diazepam and cluster seizures

STXmedic

STXmedic

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So I had a call recently with an elderly female patient who was presenting with her second grand mal seizure on our arrival, per FD. I started a line and gave her an initial 5mg diazepam*, which appeared to terminate the seizure. While we were getting ready to put her on the stretcher (postictal), she began seizing again. By the time we got her on the stretcher and I had the second dose ready to administer, the seizure terminated. Since this was her third seizure, even after 5mg diazepam, I assumed that I could reasonably expect another seizure to return. I decided to give the second dose of 5mg as a prophylactic measure. The patient was then transported without further seizure activity.

Well, neither my supervisor nor clinical coordinator liked this one bit. The initial gripe was that we don't administer "prophylactic" diazepam. Okay, cool. Then it went to "what were you thinking, diazepam would have no effect" and treating it like it was a medication error. Their argument being diazepam can only terminate a current seizure, and not prevent one from starting.

I have a pretty good understanding of the physiology of seizures. I also have a pretty good understanding of the mechanism of diazepam. Understanding both of these, it seems logical that diazepam would be effective in preventing the recurrence of a cluster seizure as was encountered. If the potentiation of the GABAergic receptor site kept the cells in a hyper-polarized state, then it would reasonably prevent the immediate return of a seizure in the same way it would terminate one.

However, I'll be the first to admit that I have much to learn. I did a quick Google and PubMed search that came up empty on the efficacy of prophylactic diazepam in recurrent seizures. It did have significant data on its use in preventing recurrence of febrile seizures in children, but not quite what I was looking for.

So does anybody have any more insight in this? Anybody know of any studies that examine this? Or am I totally off on my rationale?


*Yes, the patient was showing signs of hypoxia with a good pleth and irregular respirations on capnography
 
I started to reply a few times and did some searches but came up as empty handed as you did. I found a ton of publications regarding it's use as prophylaxis in dogs....

The explanation as increasing inhibition versus excitation seems like it would make sense based on the mechanism of generalized seizures.

My unscientific thought is that you are correct - your specific protocol being a different issue.
 
Any benzodiazepine can prevent seizures via the mechanism you cited, though there are better drugs for long term prevention (diazepam is FDA approved for adjunctive use in the treatment of epilepsy). One of the common indications is the patient experiencing alcohol withdrawal. The benzo will decrease agitation and prophylax against seizures.

Personally, I would have held off; though the onset of action is pretty quick, it takes longer for it to reach it peak affect as it has to cross the blood brain barrier (15-30min per Nursing Spectrum Drug Handbook 2009).
 
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Thanks. Good to know I'm not crazy :p Can honestly say I didn't think about the difference of onset to peak effect.
 
We use Valium for alcohol withdrawal stepping it down over seven days after a quick loading regimen. It was better than Ativan because the effect was longer. It was way better than the former meds (Librium, Phenobarbital) because of fewer side effects like respiratory arrest.

I'm thinking you didn't have a protocol for Valium JIC (just in case) and since it is a singed-out type medication it makes them antsy.
 
Was she hypoxic before the seizure or just during the postictal stage? Hypoxia is the leading cause of non-epileptic seizures. If you think about how you react to ischemic injury on a cellular level, where the NA-K-ATP shut down, potassium leaking out, NACL getting trapped inside causing the tissue to swell and depolarize, it would make a pretty good explanation.

To put it perspective, and change it to the heart, why do you see PVC'S during cardiac ischemia? Why do you see st depression early on? (Think of the injured cardiac cells losing tons of positive charges when the pump shuts down, which makes the effected area more negative)

What drug do you use to control multifocal PVC's if theyre greater than 6 per minute? That same class is great in seizures, and would be any anticonvulsant with quinidine-like effects. These are also hung In a drip after a loading dose. I don't think that valium is hung as a drip for maintenence for serial episodes, or given in successive doses after the seizure is terminated. In the ED I think they go with lorazepam, which lasts roughly 12 hours.

But the concept you're thinking of is spot on, though GABA is secondary In the case of hypoxia. You may just be getting Monday morning quarterbacked.
 
I'm suprised your protocols allow use of the drug in such way. Again we use Midazolam and can only give it with generalised seizure activity or focal seizure activity with GCS = < 12, no prophylaxis.
 
Our protocols permit 5mg with a repeat of 5mg for presenting seizure activity, same as yours I imagine.

We also have standing order 10mg versed IM/IN or ativan 2mg/2mg IV/IN/IM. (agencies carry one or the other in the region)

I don't see why it wouldn't prevent another seizure? You are increasing the effects of GABA one way or another and it is going to last for some time with Valium? Im certainly nowhere near as informed as many on this forum but i'm not seeing the issue.

She didn't have another seizure, who is to say it didn't work?
 
@Doczilla: I completely understand what you are saying. In this patient, however, I had no reason to suspect this was the cause. According to the husband, she had a diagnosis of epilepsy (even though prior to this call, she'd only had two seizures ever...). The husband told us that she was up and about, baking cookies when it started. Had not been feeling ill or complaining of anything. Could she have just been toughing it out? I guess it's possible. Regardless, hypoxia was corrected, and I can only imagine how mad they'd have been if I tried to give her lido :rofl:

Yeah, in the hospital I'm sure they use different medications, such as lorazepam or phenytoin, for the management of these patients. There are without a doubt much better alternatives. Just usin' what I got :p

@negro: Our protocols don't expressly say that we have this as an option. However, out protocols do provide us with a fair amount of "wiggle room". They allow for, and our med director supports, some deviation depending on the patient and in the patients best interest. My sup and coordinator just weren't tickled pink by this deviation ;) Haven't heard anything from my medical director, and really don't expect to. I'll see him in a week and bring it up there.

@Ny: Ours permits up to 20mg diazepam IV/IM/IO in 5-10 increments, or up to 10 midazolam IV/IN/IM/IO. I tend to prefer diazepam or seizures for its longer duration. Midaz I like better for sedation.

@Mycroft: I think you're spot on.
 
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Lack of JIC protocols

JIC* orders in protocols are rare because they will usually be used, whether it is really appropriate, either because practitioners are gunhappy, or afraid of missing something and getting in trouble.

To delete any observation period, our bosses verbally contradicted the standardized procedures and told us to start everyone on Valium who claimed to have drunk alcohol before arrest, then send them to a holding floor, which required them to be brought to our workstation twice a shift for vital signs. Quite a few had to be shaken awake....

It can also be argued they are used to inflate bills to third party payers.


*Just In Case, or "prophylactic"
 
@Doczilla: Just reread my last post. The tone kind of sounds defensive, which is not at all the case. Definitely appreciate the input! :D
 
PoeticInjustice said:
So I had a call recently with an elderly female patient who was presenting with her second grand mal seizure on our arrival, per FD. I started a line and gave her an initial 5mg diazepam*, which appeared to terminate the seizure. While we were getting ready to put her on the stretcher (postictal), she began seizing again. By the time we got her on the stretcher and I had the second dose ready to administer, the seizure terminated. Since this was her third seizure, even after 5mg diazepam, I assumed that I could reasonably expect another seizure to return. I decided to give the second dose of 5mg as a prophylactic measure. The patient was then transported without further seizure activity.

Well, neither my supervisor nor clinical coordinator liked this one bit. The initial gripe was that we don't administer "prophylactic" diazepam. Okay, cool. Then it went to "what were you thinking, diazepam would have no effect" and treating it like it was a medication error. Their argument being diazepam can only terminate a current seizure, and not prevent one from starting.

I have a pretty good understanding of the physiology of seizures. I also have a pretty good understanding of the mechanism of diazepam. Understanding both of these, it seems logical that diazepam would be effective in preventing the recurrence of a cluster seizure as was encountered. If the potentiation of the GABAergic receptor site kept the cells in a hyper-polarized state, then it would reasonably prevent the immediate return of a seizure in the same way it would terminate one.

However, I'll be the first to admit that I have much to learn. I did a quick Google and PubMed search that came up empty on the efficacy of prophylactic diazepam in recurrent seizures. It did have significant data on its use in preventing recurrence of febrile seizures in children, but not quite what I was looking for.

So does anybody have any more insight in this? Anybody know of any studies that examine this? Or am I totally off on my rationale?


*Yes, the patient was showing signs of hypoxia with a good pleth and irregular respirations on capnography
Click to expand...

I suggest you take up the issue with your medical director.

But I doubt you will find any satisfaction, it sounds more like a question of protocol and procedure than actual medical thought process.

By the definition of medication error, EMS providers make medication errors on a regular basis, simply by following protocol.

These errors are dismissed as "acceptable losses" as a matter of convention.
 
Doczilla said:
Yeah I wasnt suggesting lidocaine, I was pointing to the quinidines :P
Click to expand...

Lol yes, I know :P I was referring to the "use what I got" :D
 
Veneficus said:
I suggest you take up the issue with your medical director.

But I doubt you will find any satisfaction, it sounds more like a question of protocol and procedure than actual medical thought process.

By the definition of medication error, EMS providers make medication errors on a regular basis, simply by following protocol.

These errors are dismissed as "acceptable losses" as a matter of convention.
Click to expand...

I'm not too concerned about the protocol aspect. I'm not looking at any punishment from this at all. I think it's just more of a "don't tell me I'm wrong when you can't back it up" pride thing. Just wanting to make sure my thought process was right; and if it wasn't, then correct it. :)
 
My foreigner two cents on the issue... Our (UK) guidance states this:

"The earlier the drug is given the more likely the
patient is to respond, which is why the rectal route
is preferred in children, while the IV route is sought.

Diazepam should only be used if the patient has
been fitting for >5 minutes (and is still fitting), or if
fits recur in rapid succession without time for full
recovery in between. There is no value in giving
this drug “preventatively” if the fit has ceased. In
any clearly sick or ill child, there must be no
delay at the scene while administering the drug,
and if it is essential to give diazepam, this should
be done en route to hospital."

http://www2.warwick.ac.uk/fac/med/r...e/guidelines/diazepam_final_19apr10sb-jdf.pdf

Its of little value as it isn't backed up with literature or evidence, but it is mentioned. Btw your reasoning makes perfect sense to me. Diazepam works on the underlying cause by binding to the GABAa receptor- It surely has a preventative effect, blocking calcium channels and preventing a seizure initiating in the first place.
 
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Veneficus said:
I suggest you take up the issue with your medical director.

But I doubt you will find any satisfaction, it sounds more like a question of protocol and procedure than actual medical thought process.

By the definition of medication error, EMS providers make medication errors on a regular basis, simply by following protocol.

These errors are dismissed as "acceptable losses" as a matter of convention.
Click to expand...

Off topic, but i'm starting to feel like you look similar to this in person

Yoda_SWSB.jpg
 
The anti-seizure duration of activity of diazepam is short (~20 minutes) as compared to the duration of the sedation. It's easy for the cumulative effects of repeated doses of valium, phenobarbital, and other sedating anti-seizure medications to become a problem of its own. And having given one dose of valium too many (the second dose to a patient with undiagnosed liver disease) to a patient who immediately became apneic - which responded quickly to flumazenil thank goodness - there's something to be said for avoiding prophylactic valium for seizures as a rule. Was it best in this case with a patient having her second cluster seizure in a very short time? Not sure...
 
Here's a good bit of loosely related trivia: why does the Harriet lane handbook (bible for peds) discourage RSI for status epilepticus in children ?
 
I did searches of the full text of both the 16th and 18th editions and couldn't find where they outright discourage it. In the 16th edition it mentions that general anesthesia in the ICU may be necessary. In the 18th edition that part was modified to exclude paralytics.
 
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