IM midazolam

Melclin

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Is anyone NOT using IM midaz? If so, why?

http://www.ncbi.nlm.nih.gov/pubmed/22335736

BACKGROUND: Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.

METHODS: This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.

RESULTS: At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.

CONCLUSIONS: For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.).
 

DrankTheKoolaid

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If i dont have a realiable first line, just go IN instead.
 
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Melclin

Melclin

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Why IN? Is it a safety thing? Or is there some lit on IN vs IM midaz?
 

DrankTheKoolaid

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No, not a safety thing. I use it when I have actively seizing patients and I see no rapid IV access. 0.5 mg/kg max of 10 split between the 2 nostrils. I personally have had rapid predictable results VS seizure activity, though I have heard mixed results from other medics when used as a anxiolitic when given IN.
 

Aidey

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I swear someone posted a study showing IN and IM were equally effective for terminating seizures. I'm on my phone, so I don't know if I will be able to find it. I personally like IN because it is safer for me and the pt. No risk of sticking a needle somewhere it doesn't belong or having a needle become dislodged from the pt. I've also found it takes less force/effort to stabilize a head vs an arm. I dislike forcing a seizure pt prone in order to give it in the glute.
 

DrankTheKoolaid

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Yeah lots of studies on Pub Med about it
 
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Melclin

Melclin

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If anyone comes across one, do post it. I was ganna say that I thought the IN route had been shown a poor second compared to IM but I'm pretty sure that was naloxone.

I like the idea of IN.

Mostly for safety reasons in the agitated pt. I'd like to explore it more.
 

DrankTheKoolaid

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Medic2409

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Quick chime in and warning.

IM Midazolam was highly effective in stopping a pedi. seizure that I ran on some time ago.

The warning is to be careful, as Midazolam at any dose is very likely to knock out the respiratory drive.

Long story short, a flight crew and a medical director did not know this.
 
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Melclin

Melclin

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Cheers corky.

What doses are you chaps using for IN, and how often? How quickly do you find it onsets?

The warning is to be careful, as Midazolam at any dose is very likely to knock out the respiratory drive.


Midaz is pretty famous for its variable affects.

Last time I gave it, I gave 20mg IM and my pt had a pleasant snooze. Not for long though. He needed another 10mgs after 30 mins on the dot to get back to dreaming about killing me. Another time, I saw 1mg render a bloke almost a tube needing.

What do you mean when you say a flight crew and a medical director didn't know that a benzo could depress a person's respiratory drive?
 
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Medic2409

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Cheers corky.

What doses are you chaps using for IN, and how often? How quickly do you find it onsets?




Midaz is pretty famous for its variable affects.

Last time I gave it, I gave 20mg IM and my pt had a pleasant snooze. Not for long though. He needed another 10mgs after 30 mins on the dot to get back to dreaming about killing me. Another time, I saw 1mg render a bloke almost a tube needing.

What do you mean when you say a flight crew and a medical director didn't know that a benzo could depress a person's respiratory drive?


In a nutshell, and short version, here is the story. I gave a seizing pediatric patient 1.1 mg Versed. (approx. 25 lb. pt, protocol called for 0.1 mg/kg) The seizing stopped, and so did his breathing. I already had air on the way, as this was a long way out. An OPA and a BVM kept the airway patent and the pt. SPO2 @ 99-100% just fine. The pt. had a return of gag reflex, followed by a return of spontaneous respirations, followed by a return of purposeful movement, all within about 15 minutes after the medication was given. The flight crew opted to RSI the kid, and the kid ended up on a vent for the next 8 hours. Per the medical director, obviously I must have overdosed the child causing the respiratory drive to drop and requiring the child to be on a vent.
 

Handsome Robb

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We give in IN.

I've always been told that midazolam IM isn't preferred since it is oil-based rather than water-based like diazepam but the only reference I have for that is my drug cards from class.

FWIW I've always been able to snipe IVs in seizing patients unless they are really thrashing about, then we don't even try and go straight to IN.

edit: crap I got it backwards. Midaz is water-based and works IM whilst diaz is oil-based and IM is not preferred :wacko: Please disregard my nonsense
 
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Aidey

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You've still got it mixed up. Diazepam and midazolam are water based. Lorazepam is oil based. That is why it can't be used with a MAD; it won't aerosolize properly.

Edit - I may be mixed up also. I am 100% sure that versed is water based and ativan is oil based, but I'm not sure about valium.
 
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Handsome Robb

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You've still got it mixed up. Diazepam and midazolam are water based. Lorazepam is oil based. That is why it can't be used with a MAD; it won't aerosolize properly.

Edit - I may be mixed up also. I am 100% sure that versed is water based and ativan is oil based, but I'm not sure about valium.

I'm pretty sure valium is oil-based but I've definitely been wrong in the past, if you can believe it :ph34r: :rofl:

Also it's a crappy reference but I did bust out my med list for school and it says valium is oil based but take that reference with a grain of salt.
 

Smash

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Midazolam is water based, and as far as I am aware it is the only commonly available benzo that is (never used lorazepam so I have no idea about it) Diazepam is very much not water based which is why it has poor effect given IM (tends to form sterile abcess rather than being absorbed)

Midazolam is great. You just need large doses for agitated patients who have acute benzopenia. I only wish we carried a second line age for seizures. Not that it's needed often but when it is needed it is really needed.
 

systemet

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The diazepam I've used is nasty, sort of yellow, obviously lipophilic stuff. I agree with everyone that it shouldn't be given IM.

I think the RAMPART study is great. It shows that I get roughly equivalent anti-seizure activity with IM midazolam versus the standard of care (IV lorazepam).

I think when I return to working as a paramedic, it will make me more willing to give IM midazolam, instead of fishing for an IV in borderline patients. My perception prior to this study was that IM benzodiazepines took longer to take effect, and were less likely to stop the seizure. I was more likely to delay giving benzo's IM and attempt an IV, even if conditions were marginal, previously.

It would be nice to see if an IN device is comparable --- this might avoid some of the theoretical risks with IM medication administration. But the major finding is pretty solid; IM midazolam is as effective as IV lorazepam. So we know that a tool many of us have been using for a long time us actually as good as the standard of care --- and we know that we can go IM without it being a poor second choice option.
 

systemet

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There's a bit of a discussion about benzodiazepine pharmacology here under "sedatives and analgesics":

http://emedicine.medscape.com/article/809993-overview#aw2aab6b3

Main points (in case anyone has trouble with access):

* Midazolam is water soluble (hydrophilic) at low pH (<4.0) -- injectable preparations are usually ~ pH 3.0. When it enters the more alkaline pH of the bloodstream, it becomes lipophilic, enabling it to cross the BBB rapidly. [When you think about it, this is pretty important for CNS drugs]. It undergoes hepatic metabolism, so might have prolonged effects in someone with HCV / cirrhosis, etc.

* Lorazepam is relatively slow-acting versus diazepam / midazolam, due to a lower lipophilicity (also becomes more lipophilic at higher pH). But it undergoes conjugation, and doesn't produce active metabolites.

* Diazepam produces lots of active metabolites, some with half-lives of several days. It's highly dependent on hepatic function.

* Midazolam has a much shorter duration of action (~ 30 mins), versus diazepam (2-4 hrs) and lorazepam (1-4 hrs).


Maybe it's not surprising, when you think about it, that IM midazolam works quicker versus IV lorazepam. It makes you wonder if a fairer test might be IV midazolam versus IM midazolam? [Although I think I remember seeing a paper on this some years ago]. Having just learned / refreshed a bit of knowledge about benzodiazepine pharmacology, I can see why some of the physicians would get irritated with us when we brought in an ecstasy overdose with 20mg + of IV diazepam on board.
 

Aidey

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I don't remember valium being as difficult to draw up as ativan, but it has been a while since I've used it.
 

Pavehawk

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The United States Pharmacopoeia lists diazepam as soluble 1 in 16 ethyl alcohol, 1 in 2 of chloroform, 1 in 39 ether, and practically insoluble in water.
 
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