September 13, 2012

IM Midazolam: Alternative to IV Medication for Seizure Termination

The seizure of Roger de Mortimer 1287-1330 in Nottingham Castle, 19th October 1330, from Illustrations of English and Scottish History Volume I. Image taken from this  [link]

IV Diazepam or Lorazepam are the first choice of medication for termination of seizure activity if it is not spontaneously aborted. Protocols varies when to start the medication. However, seizure that occurs for five minutes are unlikely to abort spontaneously and often treated as status epilepticus.

Complications of prolonged seizures include impaired ventilation and subsequent pulmonary aspiration, cardiac dysrhythmias, derangements of metabolic and autonomic function, and direct injury to the nervous system (Loweinstein DH 1998)
The randomized, controlled Prehospital Treatment of Status Epilepticus (PHTSE) trial compare the IV Diazepam, Lorazepam and placebo for seizure termination and both of the medication are effective in pre hospital care. However, both of them requires intravenous access to deliver the medication. Obtaining an IV access is difficult as all the muscle are contracting at this point. Setting an IV line in a convulsive patient also increase the risk of needle prick injury to the health care provider. Both Diazepam and lorazepam are poorly absorbed if given intramuscularly or across the mucous membrane. 

Another disadvantage of lorazepam is, the medication need to be stored inside the refrigerator.

In the prehospital setting, both IV medication shows good outcome in terminating the seizure activities. However, it is least feasible to be used due to the problem mentioned above. Furthermore, it is also not a friendly user involving the mass casualty.

In contrast to both of the medication, Midazolam is a highly lipophilic agent that is rapidly absorbed intramuscularly and subsequent rapid distribution in to the central nervous system. It is proven to be effective if given as a first line treatment or as a second line agent for refractory SE.

The Rapid Anticonvulsant Medications Prior to Arrival Trial (RAMPART) is a study used to compare IM midazolam and IV lorazepam in a prehospital basis. This study was published in The New England Journal of Medicine 2012 with a conclusion of: For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. The dosage used is 10 mg IM Midazolam in patient with estimated weight of more than 40kg and 5 mg if the estimated body weight is 13-40 kg.

 Usage of IM Midazolam in children is not something controversial. A prospective randomized study done by Chamberlain JM et al in 1997 shows that 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.

I think that we should consider this alternative in treating the prolong seizure. IM Midazolam can be safely replaced IV Diazepam or Lorazepam as a first line management for prolong seizure.


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

2. Robert Silbergleit et al, "Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus", The New England Journal of Medicine: 366;7, 2012

3. Shah I, Deshmukh CT, "Intramuscular midazolam vs intravenous diazepam for acute seizures.", Indian J Pediatr. 2005 Aug;72(8):667-70.

4. Towne AR, DeLorenzo RJ, "Use of intramuscular midazolam for status epilepticus.", J Emerg Med. 1999 Mar-Apr;17(2):323-8.

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