Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Intramuscular Midazolam for Seizures – Part II


ResearchBlogging.org
Also posted over at Paramedicine 101 (now at EMS Blogs) and at Research Blogging. Go check out the excellent material at these sites.

While there have been studies comparing IM (IntraMuscular) midazolam (Versed) with IV (IntraVenous) anti-epileptic medications, this is a large study that compares IM midazolam with the best IV anti-epileptic medication in a double-blind, randomized, noninferiority trial.
 

All adults and those children with an estimated body weight of more than 40 kg received either 10 mg of intramuscular midazolam followed by intravenous placebo or intramuscular placebo followed by 4 mg of intravenous lorazepam.[1]

For the study, there were two different doses for the auto-injector (similar to an EpiPen auto-injector). The doses were not small.

Midazolam for seizures is an off-label use both when given IM and when given IV.[2]

The lorazepam IV doses in the study are according to the FDA label –
 

For the treatment of status epilepticus, the usual recommended dose of Lorazepam Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. If seizures cease, no additional Lorazepam Injection is required. If seizures continue or recur after a 10- to 15- minute observation period, an additional 4 mg intravenous dose may be slowly administered.[3]

 

Unfortunately, my protocols only permit 1/4 or 1/2 the dose of lorazepam for seizures, which may be repeated every 5 minutes up to a maximum of one full dose recommended as the initial dose by the FDA.[4] There is no adult IM use of midazolam.

There is often a concern about carefully adjusting pediatric doses. How did they handle that in this study?
 

In children with an estimated weight of 13 to 40 kg, the active treatment was 5 mg of intramuscular midazolam or 2 mg of intravenous lorazepam.[1]

But such high doses will lead to deadly outcomes

Except that this excuse to give low doses is not supported by the authors of this study.
 

The relationships among benzodiazepine dose, respiratory depression, and subsequent need for endotracheal intubation are poorly characterized, but higher doses of benzodiazepines may actually reduce the number of airway interventions. Our data are consistent with the finding that endotracheal intubation is more commonly a sequela of continued seizures than it is an adverse effect of sedation from benzodiazepines.11 [1]

 

That is a very interesting comment. The authors believe that intubations are increased by not controlling the seizure, rather than by giving large doses of a benzodiazepine. Unfortunately. I did not see anything to support that statement in the paper they cited as footnote 11.[5] This is explained in Part III.

See also Part I, Part III, Part IV, Part V, Part VI, and Images from Gathering of Eagles Presentation on RAMPART.

Footnotes:

[1] Intramuscular versus intravenous therapy for prehospital status epilepticus.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators.
N Engl J Med. 2012 Feb 16;366(7):591-600.
PMID: 22335736 [PubMed – in process]

Free Full Text from N Engl J Med.

[2] MIDAZOLAM HYDROCHLORIDE injection, solution
[Hospira, Inc.]

DailyMed
NLM
FDA label

I checked all of the injectable formulations of midazolam. They are the same. None include recommended dosing for seizures, but all include warnings about midazolam possibly causing seizures.

[3] Lorazepam (lorazepam) Injection, Solution
[Baxter Healthcare Corporation]

DailyMed
NLM
FDA label

[4] Seizure
Pennsylvania Statewide Advanced Life Support Protocols
7007 – ALS – Adult/Peds
Page 100/128
Free Full Text PDF of All ALS Protocols

Titrate until seizure stops.

or

Split the dose in half. Repeat the dose in 5 minutes.

There is no option for adult IM dosing.

[5] A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children.
Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y.
Pediatr Emerg Care. 1997 Apr;13(2):92-4.
PMID: 9127414 [PubMed – indexed for MEDLINE]

Silbergleit, R., Durkalski, V., Lowenstein, D., Conwit, R., Pancioli, A., Palesch, Y., & Barsan, W. (2012). Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus New England Journal of Medicine, 366 (7), 591-600 DOI: 10.1056/NEJMoa1107494

Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, & Waisman Y (1997). A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatric emergency care, 13 (2), 92-4 PMID: 9127414

.

Comments

  1. what many EMS personnel forget is that NOT every drug you have with you is quality controlled. For instance, read the many FDA investigative reports and warnings to DRUG manufacturers about their fraudulent and fake drugs that they push on public. So you may go through all this fancy training and school and then get out there thinking you’re helping people only to discover you’re carrying drugs that are adulterated or do NOT have the real amount of medication in them that they should have since they were shipped from India and compromised somewhere in between distributors. EMS personnel need to be aware of this growing threat to public health. It’s all about the bottom line. MONEY. ALWAYS check on line if the drug manufacturer (Hospira, for example) has any recent FDA warning letters about their drugs, especially IV drugs, being ADULTERATED. If you’ve ever wondered why some patients don’t respond to the same drugs, it’s because you have NO idea how corrupt this drug manufacturering buisness is. The RAW materials bought to make rescue meds, etc…sometimes come from China, etc…where there is ZERO quality controls. VERY SCARY.

    • Tom,

      That is something that rarely happens.

      Fortunately, these medications are much better regulated than the placebo medicines sold by the quacks pushing alternative medicine.

      .

    • Tom,

      It is ironic that you made this comment, since the email notification was right next to the following one from the FDA.

      Just another drug sold using fraudulent advertising by an alternative medicine manufacturer right here in the USA.

      For Immediate Release: June 6, 2012
      Media Inquiries: Pat El-Hinnaway, 301-796-4763, patricia.el-hinnawy@fda.hhs.gov
      Consumer Inquiries: 888-INFO-FDA

      U.S. Marshals seized misbranded drugs in Maine
      Portland company promoted their products for disease diagnosis, treatment

      On May 31, 2012, at the request of the U.S. Food and Drug Administration, U.S. Marshals seized drug products from Global Biotechnologies, Inc., of Portland, Maine, pursuant to a warrant issued by the U.S. District Court for the District of Maine.

      According to the complaint, the company has made claims on its website, in promotional materials, and on the products’ labels that its products can diagnose, cure, mitigate, treat or prevent human diseases. The company’s products, including Glucanol, Healthy Trac, Immunol, and Lactopril, meet the FDA definition of drugs because Global Biotechnologies promoted them to treat diseases. However, the company failed to provide adequate directions for use for its drug products, causing those products to be misbranded drugs in violation of the Federal Food, Drug and Cosmetic Act.

      “The public relies on the FDA to keep companies from claiming that their products improve medical conditions or diseases,” said Armando Zamora, acting director, office of enforcement, in the Office of Regulatory Affairs. “Using these products in the mistaken belief that they will cure a disease – especially when they cannot do so – represents a danger to the public’s health.”

      How much more dangerous is that?

      Taking a medication that has no possibility of benefit and less oversight of its manufacturing processes is bad medicine.

      Stay away from the fraud of alternative medicine.

      .

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  1. […] in Part II, Part III, Part IV, Part V, Part VI, and Images from Gathering of Eagles Presentation on […]

  2. […] have written about this in Intramuscular Midazolam for Seizures – Part I, Part II, Part III, Part IV, Part V, Part VI, Misrepresenting Current Topics in EMS Research from EMS Expo […]

  3. […] have written about this in Intramuscular Midazolam for Seizures – Part I, Part II, Part III, Part IV, Part V, Part VI, Misrepresenting Current Topics in EMS Research from EMS Expo […]

  4. […] also Part I, Part II, Part IV, Part V, Part VI, and Images from Gathering of Eagles Presentation on […]

  5. […] also Part I, Part II, Part III, Part V, Part VI, and Images from Gathering of Eagles Presentation on […]

  6. […] also Part I, Part II, Part III, Part IV, Part VI, and Images from Gathering of Eagles Presentation on […]

  7. […] also Part I, Part II, Part III, Part IV, Part V, and Images from Gathering of Eagles Presentation on […]

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