# Diazepam and cluster seizures



## STXmedic (Jun 13, 2012)

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


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## Cawolf86 (Jun 13, 2012)

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.


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## medicsb (Jun 13, 2012)

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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## STXmedic (Jun 14, 2012)

Thanks. Good to know I'm not crazy  Can honestly say I didn't think about the difference of onset to peak effect.


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## mycrofft (Jun 14, 2012)

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.


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## Doczilla (Jun 14, 2012)

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.


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## the_negro_puppy (Jun 14, 2012)

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.


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## NYMedic828 (Jun 14, 2012)

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?


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## STXmedic (Jun 14, 2012)

@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 

@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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## mycrofft (Jun 14, 2012)

*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"


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## STXmedic (Jun 14, 2012)

@Doczilla: Just reread my last post. The tone kind of sounds defensive, which is not at all the case. Definitely appreciate the input!


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## Doczilla (Jun 14, 2012)

Yeah I wasnt suggesting lidocaine, I was pointing to the quinidines


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## Veneficus (Jun 14, 2012)

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 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.


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## STXmedic (Jun 14, 2012)

Doczilla said:


> Yeah I wasnt suggesting lidocaine, I was pointing to the quinidines



Lol yes, I know  I was referring to the "use what I got"


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## STXmedic (Jun 14, 2012)

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.
> 
> ...



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.


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## ShockableAsystole (Jun 14, 2012)

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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## NYMedic828 (Jun 14, 2012)

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.
> 
> ...



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


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## Murphy (Jun 14, 2012)

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...


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## Doczilla (Jun 14, 2012)

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 ?


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## Aidey (Jun 14, 2012)

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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## Veneficus (Jun 14, 2012)

Doczilla said:


> 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 ?



If I am not mistaken, Nelson Textbook of Pediatrics is the bible for peds?


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## Dwindlin (Jun 14, 2012)

Veneficus said:


> If I am not mistaken, Nelson Textbook of Pediatrics is the bible for peds?



For text books maybe, but no one carries one around in their coat pocket like they do Harriet Lane.


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## Veneficus (Jun 14, 2012)

Dwindlin said:


> For text books maybe, but no one carries one around in their coat pocket like they do Harriet Lane.



Gave up on those books, they make the coat too heavy and lopsided. 

(though I was rather fond of the oxford guides a while back)


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## medicsb (Jun 14, 2012)

Murphy said:


> The anti-seizure duration of activity of diazepam is short (~20 minutes) as compared to the duration of the sedation.



Would you happen to have a source for the anti-SZ duration of action vs. sedation?  Basic & Clinical Pharmacology, 12e (Katzung, et al.) doesn't mention there being a difference.  Pretty much all I can find on the preference of non-benzos is the side-effect profile and development of tolerance.


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## mycrofft (Jun 15, 2012)

Speaking from experience, once you have an effective blood level established, Valium's effective life to prevent irritability/excitement (and hence delirium tremens and seizures) from ETO detox is much longer than 20 min.The protocol was a three-dose loader (10 mg po Q 2 hrs times three), then three ays at 10 mg po TID, three at BID, three at 5 mg BID, then qd of 5 mg for two days. Later they dropped the last step and it was just as good.
Ativan...rollercoastering vital signs and some tremors.


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## Doczilla (Jun 15, 2012)

Hmm, I gotta dig it up. There's a comment that says " avoid paralytics". I can understand why RSI isn't definitive for status epilepticus, but I can't get a clear answer on why its frowned upon.


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## Melclin (Jun 15, 2012)

Doczilla said:


> Hmm, I gotta dig it up. There's a comment that says " avoid paralytics". I can understand why RSI isn't definitive for status epilepticus, but I can't get a clear answer on why its frowned upon.



Is it an issue of lasting paralysis obscuring further seizure activity perhaps?


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## Smash (Jun 15, 2012)

Long term neuromuscular blockade would obviously be problematic in that you could obviously not monitor seizure activity, so would have no idea if therapy is effective or not (pre-hospital of course, with no EEG capability)

However in terms of straight RSI, I can't see any issue with a short term NMB.  It is not an uncommon thing to intubate a status epilepticus patient so airway, ventilation and oxygenation cease to be an issue whilst giving large doses of first and/or second line anticonvulsants. 

For the OP, did the patient ever regain consciousness between seizures?


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## Smash (Jun 15, 2012)

Obviously I need to not post when I am hungry and tired.  Obviously.


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## STXmedic (Jun 15, 2012)

Smash: No, the patient never regained consciousness. The best response we ever got was appropriate withdrawal from pain.


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## mycrofft (Jun 15, 2012)

Status epileptics or this close analogue are sometime unrecoverable. The seizure is not only a problem itself but a symptom, in tho case most likely of a fatal insult like a CVA or neoplastic body or ???.

I'm curious also about paralyzing people undergoing seizures then taking  over their respirator functions. On the surface it sounds reasonable. Frag em, gag em, bag em and start a benzo drip.


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## Doczilla (Jun 15, 2012)

I hope you don't have that patented, because I'm going to use that expression  

I'm thinking that maybe they don't want providers to "forget" that the parylized child is still seizing neurologically. I'm guessing that the harriet lane handbook assumes EEG capability, but maybe not. 

I've RSI's seizing kids before, but the seizures were always secondary to head trauma, or in the case of last year, a little girl caught frag to her c-cpine, and the RSI was to prevent further movement.


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## Aidey (Jun 15, 2012)

Doczilla said:


> Hmm, I gotta dig it up. There's a comment that says " avoid paralytics". I can understand why RSI isn't definitive for status epilepticus, but I can't get a clear answer on why its frowned upon.



Yup, it is in the acute seizure management table in chapter 3 I think, 18th edition. It isn't in the 16th edition.


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## RocketMedic (Jun 15, 2012)

I'd reckon it's a multi-part thing.

1. RSI in children (even moreso than adults) is a situation where you need the tube, because most supralingual airways won't fit, the airway is smaller, and we don't really have a good alternate for ETI except for BLS airway management.

2. Accidental overdoses leading to respiratory arrest may be more common in children? -medication error. 2a- medication reactions stemming from sedation/continued sedation, as the peak affect would occur later with benzodiazepenes than is workable in RSI.

2b. Paradoxical reactions? 

3. The aforementioned masking characteristics of benzodiazepenes may make it more difficult to assess therapies and/or the root cause of the seizure, particularly with trauma patients (did the seizure cause trauma, or is trauma the result of the seizure?)

4. Amidate may worsen seizure conditions.
EDIT- I found a research paper that trialed amidate in 105 patients under 10- none seized or experienced a myoclonic reaction. 

I'm not sure why, to be honest. RSIing a kid seems like something to do to protect the airway in the context of refractory seizures.


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## Murphy (Jun 15, 2012)

About the ~20 minute efficacy of valium for seizures - I can't say that I've seen it in a drug reference manual, but I have heard it repeatedly in neurology classes and texts and in other reference books on seizure treatment.  I don't have accesses to manuals right now... the best that I can do with a web search is:

Oops, I wasn't allowed to post the links without a higher post count.  I found an article on professionals dot epilepsy dot com about diazepam that mentions it, and I had a link to a training article by the Foundation for Education and Research for Neurological Emergencies.

I know there are better references on line, but I keep finding research papers about longer acting or newer benzos instead... several reference the short seizure control timeframe for valium but none of those gave an actual duration.  I'm giving up on the web search.

Neither of the links are medical texts, but both reference the duration of valium.  The reason is because it is highly lipid soluble and rapidly redistributes.  Hope this helps.


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## mycrofft (Jun 16, 2012)

Murph, send one of us the links as a message and we can post them


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