Lorazepam for Seizure

[EpiShock]

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How do you guys escalate dose of lorazepam for status.

When they let me run things I usually do 2mg -> 2mg -> 4mg -> 4mg -> 2nd/3rd line therapies.

Is there an optimal way to do this, to balance risk of respiratory depression, maybe just starting with a weight based dose?

 

[EpiShock]

Also, after you have given fosphenytoin/phenytoin and Propofol what do you guys use as a 4th line if they're still in status?

B6, Keppra, Valproate, Phenobarb, General Anesthesia? In what sequence?

Any advantage to a trial of phenobarb before just intubation/propofol. I figured people like to propofol because phenobarb is so long acting. Also, from what i've seen phenobarb seems to cause more hypotension than propofol. Any thoughts?

 

[cbrons]

what do you guys use as a 4th line if they're still in status?

B6, Keppra, Valproate, Phenobarb? In what sequence?

What is B6 going to do?

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[EpiShock]

What is B6 going to do?

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Its just a consideration for a tox seizure, ie the hydrazines

 

[Zebra Hunter]

Never seen respiratory depression with someone getting ativan for status. I give 4 up front, then another 4 in 5 minutes, and I'll keppra load w/ that second dose of ativan. If that doesn't work after another 5 minutes, I give fosphenytoin, intubate, start on prop, look at her old medical records, give whatever she is supposed to be on if it has not already been given, call neurology and let them figure it out from there.

The only reason keppra is not a current first line med for status is because it is a relatively new drug.

 

[EpiShock]

Never seen respiratory depression with someone getting ativan for status. I give 4 up front, then another 4 in 5 minutes, and I'll keppra load w/ that second dose of ativan. If that doesn't work after another 5 minutes, I give fosphenytoin, intubate, start on prop, look at her old medical records, give whatever she is supposed to be on if it has not already been given, call neurology and let them figure it out from there.

The only reason keppra is not a current first line med for status is because it is a relatively new drug.

What do you do after that? I had a case recently where the patient got a total of 12mg of ativan, then fosphenytoin, then propofol, thenb keppra, and was still seizing

 

[PTPoeny]

Phenobarb load, benzo drip, then if still seizing pentobarb drip. Some of my attendings argue the benzo drip is unlikely to work if you saw no response at all to the initial lorazepam.

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[Zebra Hunter]

well, I haven't seen that, but I suppose since they are already intubated I'd continue escalating doses of ativan and start a benzo drip, blood pressure permitting. These individuals can generally tolerate huge dosages of benzos.

 

[Apollyon]

Benzos, fos/phenytoin, phenobarb coma. It ain't brain surgery (although some of these pts WILL need neurosurg at some time).

 

[Psai]

Phenobarb load, benzo drip, then if still seizing pentobarb drip. Some of my attendings argue the benzo drip is unlikely to work if you saw no response at all to the initial lorazepam.

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Benzos work but there's tachyphylaxis and you have to keep going up on the dose

 

[deleted547339]

What do you do after that? I had a case recently where the patient got a total of 12mg of ativan, then fosphenytoin, then propofol, thenb keppra, and was still seizing

By that point, it shouldn't be your problem. You're an ER doc, not an epileptologist. If you've given a healthy dose of benzo, Dilantin and/or keppra, intubated and put on a proposal +/- versed drip you have already done your part and the patient needs to already be in an ICU. If you're in a place with a lot of ICU boarding, your neurologist should be helping drive the ship. If you're in a sending hospital, you probably don't have a stat EEG to know they are still seizing, so it's a moot point.

 

[gro2001]

You should look at what your institutional protocol is, as this varies slightly from place to place, and its always best to do what has been agreed on an inter departmental level. If there isn't one, its probably a good idea to bring that up as a thing to do at the next inter departmental meeting. You want these questions answered and agreed upon in the light of day, not in the middle of treating status or while being second guessed by consultants in the morning.

In terms of escalating benzos, it depends on whether I am treating seizure or status.

Seizure: 2 mg, followed by another 2 mg.
Status: 4 mg (upfront if they come in as meeting the definition of presumed status, or split as above if it started as simple seizure that just didn't stop), followed by another 4 mg.

8 mg of lorazepam is my (and my institutional protocol's) threshold for considering benzos to have failed. Then we progress to second line, which is by preference fosphenytoin. If that fails, I got to RSI with propofol. At that point they need EEG and a neurointensivist.

 

[Rendar5]

Ultrasound on belly for a fetus, check sodium, and consider INH overdose as those 3 causes of seizure don't respond typically to anti seizure mess. Then have neuro come in. Honestly never met someone who didn't stop seizing after keppra, Dilantin, and propofol.

 

[EpiShock]

Never seen respiratory depression with someone getting ativan for status. I give 4 up front, then another 4 in 5 minutes, and I'll keppra load w/ that second dose of ativan. If that doesn't work after another 5 minutes, I give fosphenytoin, intubate, start on prop, look at her old medical records, give whatever she is supposed to be on if it has not already been given, call neurology and let them figure it out from there.

The only reason keppra is not a current first line med for status is because it is a relatively new drug.

True not so much respiratory depression, but people stop protecting their airway and at the very least if they have underlying sleep apnea it will manifest itself.

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[WilcoWorld]

Ultrasound on belly for a fetus, check sodium, and consider INH overdose as those 3 causes of seizure don't respond typically to anti seizure mess. Then have neuro come in. Honestly never met someone who didn't stop seizing after keppra, Dilantin, and propofol.

What a great, succinct approach. My only comment is that I'd add hypoglycemia to your list.

 

[goodoldalky]

What do you do after that? I had a case recently where the patient got a total of 12mg of ativan, then fosphenytoin, then propofol, thenb keppra, and was still seizing

Phenobarbital

 

[RustedFox]

What do you do after that? I had a case recently where the patient got a total of 12mg of ativan, then fosphenytoin, then propofol, thenb keppra, and was still seizing

The patient was still displaying tonic-clonic seizure activity after you induced general anesthesia?

Sounds astronomically unlikely. Are you sure?

Etomidate. Succinylcholine. Fosphentyoin. Propofol drip. Ship.

 

[UKEMdoc]

I'm always nervous about lorazepam - I've seen too many respiratory arrests. I give 1mg alliquots up to a max of 8mg and once I'm on the second syringe we're mixing the phenytoin.

IIRC Etomidate lowers the seizure threshold, why not use thiopentone?

 

[deleted547339]

I'm always nervous about lorazepam - I've seen too many respiratory arrests. I give 1mg alliquots up to a max of 8mg and once I'm on the second syringe we're mixing the phenytoin.

IIRC Etomidate lowers the seizure threshold, why not use thiopentone?

Thiopentone??? Really?

A patient in extemis is not the patient to get fancy with. Propfol would probably be a better choice than etomidate for induction.

If I were to ask one of my nurses to get a barbiturate when I'm about to RSI someone, well, it would make for an interesting conversation.

 

[link2swim06]

Accucheck is a good idea too. Nothing like tubing a pt you find out later had a bs of 12...

 

[TooMuchResearch]

I'm always nervous about lorazepam - I've seen too many respiratory arrests. I give 1mg alliquots up to a max of 8mg and once I'm on the second syringe we're mixing the phenytoin.

IIRC Etomidate lowers the seizure threshold, why not use thiopentone?

Not an RSI agent in the US.

Ketamine, propofol, or midazolam.

 

[deleted547339]

Not an RSI agent in the US.

Ketamine, propofol, or midazolam.

To be fair, versed isn't really a true RSI med based on its onset of action. Or at the very least it isn't a good RSI med.

 

[TooMuchResearch]

To be fair, versed isn't really a true RSI med based on its onset of action. Or at the very least it isn't a good RSI med.

True, good point.

 

[southerndoc]

Accucheck is a good idea too. Nothing like tubing a pt you find out later had a bs of 12...

Been there, done that, felt like an idiot. EMS told me their glucose was "normal." Um, yea right.

 

[The White Coat Investor]

Never seen respiratory depression with someone getting ativan for status. I give 4 up front, then another 4 in 5 minutes, and I'll keppra load w/ that second dose of ativan. If that doesn't work after another 5 minutes, I give fosphenytoin, intubate, start on prop, look at her old medical records, give whatever she is supposed to be on if it has not already been given, call neurology and let them figure it out from there.

The only reason keppra is not a current first line med for status is because it is a relatively new drug.

Same. I keep giving the ativan but start adding on the others- Keppra, Fosphenytoin etc.

 

[The White Coat Investor]

Not an RSI agent in the US.

Ketamine, propofol, or midazolam.

If they're seizing use propofol for goodness sake. It's a great anti-epileptic.

 

[TooMuchResearch]

If they're seizing use propofol for goodness sake. It's a great anti-epileptic.

Yes, though apparently there is some data on lower mortality with midazolam as induction agent then straight to midazolam infusion. I haven't read the paper(s), though.

 

[The White Coat Investor]

Yes, though apparently there is some data on lower mortality with midazolam as induction agent then straight to midazolam infusion. I haven't read the paper(s), though.

I'd be interested in seeing that. That would certainly be a great reason to try it.

 

[WilcoWorld]

Yes, though apparently there is some data on lower mortality with midazolam as induction agent then straight to midazolam infusion. I haven't read the paper(s), though.

Must be specific to status epileptics, right? All the literature I've seen on post-intubation sedation suggest that we should NOT be using BZD's as they have longer ICU LOS, longer time on the vent, more delirium, etc...

 

[TooMuchResearch]

Must be specific to status epileptics, right? All the literature I've seen on post-intubation sedation suggest that we should NOT be using BZD's as they have longer ICU LOS, longer time on the vent, more delirium, etc...

Yes, it's only in status epilepticus.

It was discussed on an EM crit episode on status with some neuro crit care person sometime in the past 1-2 years.



Edit: it's emcrit episode 155. The link provided on the site (I didn't re-listen to the interview) was for this:

http://m.neurology.org/content/82/4/359.abstract

Which isn't exactly what I expected since it's high vs low dose midazolam infusion.

There was another link on the site about propofol and increased mortality, but I didn't read it.

Also something on there about ketamine for refractory status. Didn't read that one either.

 

[dotcb]

https://www.aesnet.org/about_aes/press_releases/guidelines2016

Lorazepam 4mg IV or 5mg midazolam IM while preparing fosphenytoin. Repeat benzo dose x1, begin infusing fosphenytoin while paging neurology. If patient still oxygenating and protecting airway, observe and attempt to give AED time to work. If no improvement at 20-30 min, intubate w/ rocuronium (could make argument for Sux), induction med optional if no mental status. Preferred sedation for status in my hospital network is midazolam drip (neurology consensus). Admit to ICU while EEG is being arranged.

 

[BoardingDoc]

https://www.aesnet.org/about_aes/press_releases/guidelines2016

Lorazepam 4mg IV or 5mg midazolam IM while preparing fosphenytoin.

Slight typo in your post. Looking at the chart you referenced, if you're giving 4mg of Lorazepam, the kid has to weigh at least 40 kg based on their dosing guidelines of 0.1mg/kg/dose, max dose 4mg. If that's the case, your alternative dose of midaz should be 10mg, not 5 (which makes sense seeing as the relative potency of IV ativan:midaz ~= 2:1)

 

[Druggernaut]

This would pretty much be my approach: http://emcrit.org/pulmcrit/rapid-sequence-termination-rst-of-status-epilepticus/

Keppra isn't approved for status, as much as the neurologists love it. All of our ED pharmacists prefer fosphenytoin, as well as a neurointensivist, so I'd stick to that until more data is available on Keppra.

A quick search on midazolam versus propofol doesn't seem to have much data one way or the other (https://www.ncbi.nlm.nih.gov/pubmed/11442156), but our neurologists prefer midazolam.

The biggest take away I had from a case seen by another resident last year is be aggressive and intubate before the neurologists get involved...

 

[Zebra Hunter]

This would pretty much be my approach: http://emcrit.org/pulmcrit/rapid-sequence-termination-rst-of-status-epilepticus/

Keppra isn't approved for status, as much as the neurologists love it. All of our ED pharmacists prefer fosphenytoin, as well as a neurointensivist, so I'd stick to that until more data is available on Keppra.

A quick search on midazolam versus propofol doesn't seem to have much data one way or the other (https://www.ncbi.nlm.nih.gov/pubmed/11442156), but our neurologists prefer midazolam.

The biggest take away I had from a case seen by another resident last year is be aggressive and intubate before the neurologists get involved...

Not "approved" by whom, exactly?

The Neuro Critical Care Society actually recommends considering keppra for refractory SE in the SE guidelines.

http://www.neurocriticalcare.org/Portals/61/Docs/Guidelines/SE Guidelines NCS 0412.pdf

 

[Druggernaut]

The Neuro Critical Care Society actually recommends considering keppra for refractory SE in the SE guidelines.

Sure. Refractory SE is "failure of adequately dosed initial benzodiazepine and one AED." "Isn't approved" is probably worded too strongly, but they do prefer fosphenytoin, phenobarbital, and Depakote over Keppra for first line AED therapy in Table 6 of the document you listed. It also brings up the rear for "urgent" and refractory treatment.

 

[Zebra Hunter]

Sure. Refractory SE is "failure of adequately dosed initial benzodiazepine and one AED." "Isn't approved" is probably worded too strongly, but they do prefer fosphenytoin, phenobarbital, and Depakote over Keppra for first line AED therapy in Table 6 of the document you listed. It also brings up the rear for "urgent" and refractory treatment.

True, but my neurointensivists like keppra because it seems to cause less hemodynamic instability and respiratory depression. Also, there was a randomized, open label pilot study back in 2012 comparing keppra to ativan that demonstrated similar rates of control of SE, mortality, and significantly reduced number of patients requiring intubation. I don't think it is necessary to give it, but it is a very reasonable option.

 

[gro2001]

I'm always nervous about lorazepam - I've seen too many respiratory arrests. I give 1mg alliquots up to a max of 8mg and once I'm on the second syringe we're mixing the phenytoin.

IIRC Etomidate lowers the seizure threshold, why not use thiopentone?

I am confused by your post.

You are concerned about causing respiratory depression with lorazepam, so you use it in very small doses while you are also getting the phenytoin ready...

If you are up to the 8 mg range (in 1 mg doses, too!), you are no longer treating simple seizure just by timeline alone... This patient is extremely likely to be intubated in the very near future anyway, because they are in status. Forget respiratory depression from benzos, how about lack of airway protection due to the status epilepticus itself?

 

[pulmoblast]

This would pretty much be my approach: http://emcrit.org/pulmcrit/rapid-sequence-termination-rst-of-status-epilepticus/

Keppra isn't approved for status, as much as the neurologists love it. All of our ED pharmacists prefer fosphenytoin, as well as a neurointensivist, so I'd stick to that until more data is available on Keppra.

A quick search on midazolam versus propofol doesn't seem to have much data one way or the other (https://www.ncbi.nlm.nih.gov/pubmed/11442156), but our neurologists prefer midazolam.

The biggest take away I had from a case seen by another resident last year is be aggressive and intubate before the neurologists get involved...

The latest status guidelines do include keppra...just at a higher dose 60mg/kg/min with a max of 4.5g. This is the go to drug at my ICU. No need to check levels , "broad spectrum" AED.


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