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

- Rogue Medic

Intramuscular Midazolam for Seizures – Part I

A study of IM (IntraMuscular) midazolam for EMS to treat seizures. The study looks at status epilepticus, but any seizure still present when EMS arrives should be treated. The terminology does not help. The only time I use the term status epilepticus is when teaching/writing about seizures; not when describing what I treated; not when thinking about what to do.
 

Many emergency medical services (EMS) systems, however, have begun to use intramuscular midazolam rather than an intravenous agent, largely because intramuscular administration is faster and is consistently achievable. 2 This practice has become increasingly common despite the lack of clinical-trial data regarding the efficacy and safety of intramuscular midazolam.[1]

 

Really?

In about an hour, using PubMed and Google, I found these. All of them examine the use of IM midazolam. Only one is not on humans.

1988

IM midazolam for status epilepticus in the emergency department.
Mayhue FE.
Ann Emerg Med. 1988 Jun;17(6):643-5.
PMID: 3377295 [PubMed – indexed for MEDLINE]
 

A 71-year-old man presented with a continuous generalized tonic-clonic seizure of 80 minutes duration. Multiple attempts to establish an IV line failed. Ten milligrams of midazolam hydrochloride was administered IM and was followed by prompt termination of seizure activity. This report discusses the pharmacokinetic and anticonvulsant properties of midazolam as an alternative to diazepam for the initial treatment of status epilepticus.

1991

A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy.
Bell DM, Richards G, Dhillon S, Oxley JR, Cromarty J, Sander JW, Patsalos PN.
Epilepsy Res. 1991 Nov-Dec;10(2-3):183-90.
PMID: 1817958 [PubMed – indexed for MEDLINE]
 

Since intravenous administration of AEDs including diazepam is not always feasible in status epilepticus there are obvious advantages in having an effective intramuscular formulation. Our data suggest that midazolam may be such a drug.

1992

Midazolam in treatment of epileptic seizures.
Lahat E, Aladjem M, Eshel G, Bistritzer T, Katz Y.
Pediatr Neurol. 1992 May-Jun;8(3):215-6.
PMID: 1622519 [PubMed – indexed for MEDLINE]
 

Midazolam (Versed), the first water-soluble benzodiazepine, has had widespread acceptance as a parenteral anxiolitic agent. Its antiepileptic properties were studied in adult patients with good results. Midazolam was administered intramuscularly to 48 children, ages 4 months to 14 years, with 69 epileptic episodes of various types. In all but 5 epileptic episodes, seizures stopped 1-10 min after injection. These results suggest that midazolam administered intramuscularly may be useful in a variety of epileptic seizures during childhood, specifically when attempts to introduce an intravenous line in convulsing children are unsuccessful.

1994

Intravenous versus intramuscular midazolam in treatment of chemically induced generalized seizures in swine.
Orebaugh SL, Bradford SM.
Am J Emerg Med. 1994 May;12(3):284-7.
PMID: 8179731 [PubMed – indexed for MEDLINE]
 

It is concluded that midazolam is effective in the control of tonic-clonic manifestations of generalized seizures when administered by the IV or the IM route

1997

Midazolam in treatment of various types of seizures in children.
Yakinci C, Müngen B, Sahin S, Karabiber H, Durmaz Y.
Brain Dev. 1997 Dec;19(8):571-2.
PMID: 9440805 [PubMed – indexed for MEDLINE]
 

No side effects were observed. These results suggest that i.m. administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (i.v.) line problem.

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]
 

CONCLUSIONS:
IM midazolam is an effective anticonvulsant for children with motor seizures. Compared to IV diazepam, IM midazolam results in more rapid cessation of seizures because of more rapid administration. The IM route of administration may be particularly useful in physicians’ offices, in the prehospital setting, and for children with difficult IV access.

1999

Use of intramuscular midazolam for status epilepticus.
Towne AR, DeLorenzo RJ.
J Emerg Med. 1999 Mar-Apr;17(2):323-8. Review.
PMID: 10195494 [PubMed – indexed for MEDLINE]
 

The pharmacodynamic effects of midazolam can be seen within seconds of its administration, and seizure arrest is usually attained within 5 to 10 min. Case reports and a recent randomized trial that demonstrate the successful use of i.m. midazolam in the termination of epileptic seizures are reviewed.

2002

Midazolam for the treatment of out-of-hospital pediatric seizures.
Vilke GM, Sharieff GQ, Marino A, Gerhart AE, Chan TC.
Prehosp Emerg Care. 2002 Apr-Jun;6(2):215-7.
PMID: 11962570 [PubMed – indexed for MEDLINE]
 

CONCLUSION:
Prehospital IV midazolam is an effective intervention for pediatric seizures, while IM midazolam was associated with a 20% failure rate, with both having minimal risk of respiratory compromise.

 

This was the only study of midazolam cited as a midazolam study by the authors.

Controlling seizures in the prehospital setting: diazepam or midazolam?
Rainbow J, Browne GJ, Lam LT.
J Paediatr Child Health. 2002 Dec;38(6):582-6.
PMID: 12410871 [PubMed – indexed for MEDLINE]
 

CONCLUSION:
Midazolam controls seizures as effectively as diazepam in the prehospital setting. Furthermore, midazolam potentially reduces respiratory depression and time to treatment.

2005

Status epilepticus: an evidence based guide.
Walker M.
BMJ. 2005 Sep 24;331(7518):673-7. Review. No abstract available.
PMID: 16179702 [PubMed – indexed for MEDLINE]
 

Free Full Text from PubMed Central.

Intramuscular midazolam vs intravenous diazepam for acute seizures.
Shah I, Deshmukh CT.
Indian J Pediatr. 2005 Aug;72(8):667-70.
PMID: 16131771 [PubMed – indexed for MEDLINE]
 

CONCLUSION:
i.m. midazolam is an effective agent for controlling acute convulsions in children especially in children with febrile convulsions. It has relatively no side effects as compared to Intravenous diazepam and can be used as a first line agent for treatment of acute convulsions in patients with difficult intravenous access.

2010

Human safety and pharmacokinetic study of intramuscular midazolam administered by autoinjector.
Reichard DW, Atkinson AJ, Hong SP, Burback BL, Corwin MJ, Johnson JD.
J Clin Pharmacol. 2010 Oct;50(10):1128-35. Epub 2010 May 13.
PMID: 20466872 [PubMed – indexed for MEDLINE]
 

Midazolam in an autoinjector was evaluated in an open-label dose escalation study involving 39 healthy participants. Safety and pharmacokinetic parameters were determined for doses ranging from 5 to 30 mg. No serious adverse events were noted during the study.

2011

RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics.
Silbergleit R, Lowenstein D, Durkalski V, Conwit R; Neurological Emergency Treatment Trials (NETT) Investigators.
Epilepsia. 2011 Oct;52 Suppl 8:45-7. doi: 10.1111/j.1528-1167.2011.03235.x.
PMID: 21967361 [PubMed – indexed for MEDLINE]

That is a preliminary release of information from the study that was just published in NEJM.
 

This practice has become increasingly common despite the lack of clinical-trial data regarding the efficacy and safety of intramuscular midazolam.[1]

 

I haven’t looked at the rest of the study, but I hope that more thought went into the study design than went into the search for other research.

Continued in Part II, 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
Robert Silbergleit, M.D., Valerie Durkalski, Ph.D., Daniel Lowenstein, M.D., Robin Conwit, M.D., Arthur Pancioli, M.D., Yuko Palesch, Ph.D., and William Barsan, M.D. for the NETT Investigators
N Engl J Med 2012; 366:591-600February 16, 2012
Preview from NEJM

Apparently, there is no PubMed abstract, yet.

Late entry 02/18/2012 22:27 – Correction, there is a PubMed abstract for this study –

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.

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Comments

  1. In both my primary AND my secondary EMS systems, Versed is the drug of choice for prolonged seizure activity (in fact, it’s the only benzo we carry). In both systems, IV is the preferred route and IM is indicated if no IV has been established or cannot be established. In my primary system, we are also permitted (and encouraged) to administer Versed IN in the case of prolonged or uncontrolled seizure activity. My secondary system does not permit Versed to be administered IN.

    IV is definitely the fastest in my anecdotal (read: personal) experience but I have found IM and IN administration to be effective in the cases where I did not have an IV, for whatever reason.

    I find it slightly amusing that there is a clinical trial being done on what I always assumed was a practice commonly accepted as effective. I find it even more assuming that this study you’re referencing plainly hasn’t checked to see if anyone else has already done a study. Of course, by amusing, I mean perplexing.

    • Not to imply that we should not trial things we assume to be effective. We SHOULD trial those things in order to PROVE or DISPROVE that they are effective. I was just under the impression that it had already been trialed.

      I am still perplexed at the study’s authors not researching the topic more thoroughly before deciding to conduct another study.

Trackbacks

  1. […] of IM Versed with IV Lorazepam for seizures.  Rogue Medic does a great five part write up of this, the first part of which can be found here.  The evidence is there, IM Versed works both for the patient, and is a safer route of […]

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

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

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

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

  6. […] 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 […]

  7. […] 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 […]

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

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