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February 16, 2012

Study: Injection offers faster help for seizure patients

Results probably will change how seizures are treated by paramedics

By Erin Allday
The San Francisco Chronicle 

SAN FRANCISCO —  Injecting patients in the thigh with a drug-loaded syringe is a safe and effective way to stop a seizure in an emergency, according to results of a national study released Wednesday, a finding that could pave the way toward making such syringes as widely available as EpiPens used to treat severe allergic reactions.

The two-year study, published in the New England Journal of Medicine, concluded that a single stab from an auto-injector was more effective in stopping a prolonged seizure than the traditional method of inserting an intravenous line and delivering the drug directly into the bloodstream.

The results probably will change how such seizures, which can be life-threatening if they're not stopped right away, are treated by paramedics. But they could have more long-term repercussions if doctors start giving the auto-injectors to epileptic patients, some of whom have several severe seizures a year, to use at home, much as people with severe allergies carry epinephrine syringes with them.

"I don't think we're ready to hand these out at epilepsy clinics for people to take home right now," said Dr. J. Claude Hemphill, chief of neurology at San Francisco General Hospital, who led the San Francisco arm of the study. "But that may be a follow-up some folks want to do."

The U.S. Department of Defense also has taken special interest in the study, because auto-injectors would be much more convenient than IV drug treatment in a large-scale bioterrorism attack involving seizure-inducing nerve gas.

"The advantage is you can give it the auto-injection faster," said Dr. Walter Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke. "If you have 100 people simultaneously seizing, no way can you do all those IVs. But you could just run around and inject everybody for their seizures."

Seizures are caused by a disruption in the brain's electrical system, and in most cases they resolve themselves after a minute or so. Roughly 2 percent of Americans have epilepsy, a condition marked by chronic seizures.

Some seizures, known as status epilepticus or prolonged seizures, can last several minutes or longer, and they may require drugs to stop them. More than 50,000 people in the United States die from prolonged seizures every year, either from brain damage due to the seizure itself or from accidents related to passing out mid-attack.

The study, which was funded primarily by the National Institutes of Health, involved 79 hospitals nationwide, including several in the Bay Area. More than 4,000 paramedics were trained to participate in the study and 893 patients were treated.

A drug and a placebo
Every patient was given both the auto-injector shot, usually to the thigh, and an intravenous injection. But in half the cases the auto-injector was filled with a placebo, and in the other half the IV drug was a placebo. Neither patients nor paramedics knew which treatment was the placebo in any given case.

Researchers found that 73 percent of patients who were given the auto-injector drug had stopped seizing by the time they reached the emergency room; 63 percent of patients who got the IV drug were seizure-free.

Patients who were given the auto-injector drug were less likely than the IV group to be admitted to the hospital after their seizure.

"This auto-injection should be the new standard of care," said Dr. James Quinn, a professor of surgery and emergency medicine at Stanford who led the study there. "It's great when you can do a study and it's probably going to change how we do things."

Although two different drugs were used in the trial - midazolam for the auto-injector and lorazepam for the intravenous injection - researchers don't believe that the drugs made a difference in how effective the treatments were. Rather, they said, the auto-injectors are simply easier to use.

It's much simpler to give a single shot than to try to start an intravenous line on a patient who is actively convulsing, doctors and paramedics said. In the study, 42 patients did not receive the intravenous treatment because the paramedic couldn't start the IV, whereas only five patients didn't receive the auto-injector shot because the syringe malfunctioned.

"It takes time to set up an IV. You have to find a vein that's going to be good, you have to isolate the arm and hold it still, you have to clean the arm, you have to insert the needle," said Judy Klofstad, a paramedic with the San Francisco Fire Department who participated in the study. "If you're really good, it can take 2 1/2 minutes."

Paramedics took on average just 20 seconds to use the auto-injector, according to the study. "You just hold their thigh down, target it, and it can go right through their clothing, through jeans even," Klofstad said.

Doctors said that because the auto-injection drug causes heavy sedation and can lead to respiratory problems and low blood pressure, more research is needed before the syringes are handed out to patients.

But Tiffany Manning, who has epilepsy and suffers a prolonged seizure every two or three months, said she's excited about someday being able to carry around an auto-injector. Her doctor at the UCSF epilepsy clinic has prescribed an oral drug that her parents can give her when she has a seizure, but it can be time-consuming and difficult to measure out the proper dosage and make sure she swallows it, she said.

"And when I wake up I have a funny taste in my mouth," said Manning, 30. "My doctor doesn't prescribe it very often. You can overdose someone on it. ... I'd rather just have a shot in the leg."

Copyright 2012 San Francisco Chronicle

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Comments
The comments below are member-generated and do not necessarily reflect the opinions of EMS1.com or its staff.
Arron Martinez Arron Martinez Thursday, February 16, 2012 11:07:05 AM You can find the study here: http://www.nejm.org/doi/full/10.1056/NEJMoa1107494. 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; 366:591-600.
Sue Geyster Sue Geyster Thursday, February 16, 2012 11:10:04 AM Sounds amazing and such an asset to everyone in the healthcare field. Please continue the research on the adverse effects.
Rogue Medic Rogue Medic Sat Feb 18 10:11:03 PST 2012 Sue Geyster, "The frequencies of endotracheal intubation, recurrent seizures, and other predefined safety outcomes were similar in the two study groups (Table 2)." "the proportion of subjects admitted was significantly lower (and the proportion discharged from the emergency department was significantly higher) in the intramuscular group than in the intravenous group (P=0.01)." This is a very large study that shows that IM midazolam has fewer side effects than IV lorazepam. .
Steve Price Lpn Steve Price Lpn Thursday, February 16, 2012 11:12:32 AM Is there a difference between the 2 drugs they should do a study with an auto injector of Valium And use the other drugs in the Iv See if there is a difference between the 2
Roc-Anthony Smith Roc-Anthony Smith Thu Feb 16 14:12:33 PST 2012 Valium is contraindicated in IM use...
Para Medic Para Medic Fri Feb 17 04:19:59 PST 2012 say what?????
Rogue Medic Rogue Medic Sat Feb 18 09:46:59 PST 2012 Roc-Anthony Smith, Diazepam (Valium) is not contraindicated IM. It just is not commonly used that way. EMS has just had a fascination with rectal administration. "Dosage should be individualized for maximum beneficial effect. The usual recommended dose in older children and adults ranges from 2 mg to 20 mg IM or IV, depending on the indication and its severity." "In the convulsing patient, the IV route is by far preferred. This injection should be administered slowly. However, if IV administration is impossible, the IM route may be used." From the FDA label, available at DailyMed. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=9112 .
Chris Kaiser Chris Kaiser Thursday, February 16, 2012 11:14:13 AM Interesting study. I would like to see the comparison done showing how IM Versed (midazolam) does over going the Intranasal (MAD device) route. In a similar study, Intranasal versed was shown to be more effective than IV Valium at stopping seizure activity in pediatric patients when viewed on an EEG.
Paul T Salos Paul T Salos Thursday, February 16, 2012 11:45:53 AM Rectal valium is more quickly absorbed, and is very effective in stopping sz activity quickly.
Jr First Jr First Fri Feb 17 05:04:00 PST 2012 it might be quicker than IM injection but do you know how many lawsuits would arise from paramedics putting there finger up someones butt in the back of an ambulance.....seriously!? think about. Glad i work for a service that has IM protocol even though we don't have the injectors
Kyle Kindness Kyle Kindness Fri Feb 17 07:10:17 PST 2012 Rectal valium is severely difficult to administer to a seizing patient
John Morrison John Morrison Fri Feb 17 08:00:03 PST 2012 Jr First Rectal Valium is very common. There would be zero lawsuits from it because it's an acceptable and safe route.
John Morrison John Morrison Fri Feb 17 08:00:24 PST 2012 Kyle Kindness I would argue, based on my opinion, that it's less difficult than giving IM Versed. For the simple reason of when giving an IM drug you're approaching an out of control patient with a needle. Rectally there is no needle.
Rogue Medic Rogue Medic Sat Feb 18 10:00:08 PST 2012 Paul T. Salos, Please provide some evidence that rectal diazepam works more quickly than IM midazolam. IV medication is more quickly absorbed. Should we only give IV medication? What good reason is there for EMS to be giving rectal medications? .
Rogue Medic Rogue Medic Mon Feb 20 17:49:43 PST 2012 Jr First, Rectal diazepam is NOT quicker than IM midazolam. .
Rogue Medic Rogue Medic Mon Feb 20 17:51:46 PST 2012 John Morrison, There were no reported problems using IM midazolam. Why do you assume that there would be easier to pull down the patient's pants, lubricate a catheter, inject the drug in the rectum, and keep the medication from leaking out of the rectum? .
Johnny Torres Johnny Torres Thursday, February 16, 2012 12:15:15 PM I thought about this method over 10 years ago, glad to finally see it happening...
Ashley Fox Ashley Fox Thursday, February 16, 2012 2:30:58 PM I love my Epi-Pen. I know that seizure patients will love to have an auto-injector too. :)
Casey Edwards Casey Edwards Thursday, February 16, 2012 7:08:53 PM I'm with Chris...we have the MAD and I'm curious to compare.
Matthias Schaper Matthias Schaper Thursday, February 16, 2012 9:34:48 PM We used the nasal application with the MAD (with versed) too. It works really well and it is safe. Matt
Michael Krtek Michael Krtek Friday, February 17, 2012 12:06:57 AM Drug and dosage? I don't see it listed...
Rogue Medic Rogue Medic Mon Feb 20 17:55:33 PST 2012 Michael Krtek, "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. 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.
Michael Krtek Michael Krtek Mon Feb 20 21:26:17 PST 2012 Rogue Medic _ Thank you for your answer. About how long before you get an effect from IM injection? I guess this is mostly for status or prophylaxes for re-occurrence?
Rogue Medic Rogue Medic Mon Feb 20 23:10:18 PST 2012 Michael Krtek, Yes, this is for status or re-occurrence. "Subjects were enrolled if they were having convulsive seizures at the time of treatment by paramedics and were reported by reliable witnesses to have been continuously convulsing for longer than 5 minutes or if they were having convulsive seizures at the time of treatment after having intermittent seizures without regaining consciousness for longer than 5 minutes." - "The median time to administration of active treatment was significantly shorter by the intramuscular route than by the intravenous route (1.2 vs. 4.8 minutes), but the onset of action (i.e., termination of convulsions) occurred sooner after intravenous administration than after intramuscular administration (1.6 vs. 3.3 minutes)." If an IV is already in place, it is better to give the IV medication (midazolam should also be quicker IV). Without an IV, the time to start an IV plus the time to stop the seizure takes much longer than the time for IM administration plus the time to stop the seizure. IO (IntrOsseous) access was permitted for the IV group, but they do not provide any information on how many patients had IO access or how long it took to place the IOs in the patients during the seizures. The total mean time to termination of seizure - 6.4 minutes with IV lorazepam. vs. 4.5 minutes with IM midazolam. 2 minutes (1.9) may not be a lot for most things, but during a seizure, it may be important. More important than the mean time is the success rate - 63.4% with IV lorazepam. vs. 73.4% with IM midazolam. An extra 10% failure rate with IV lorazepam is a very important difference. .
Nathan Stanaway Nathan Stanaway Friday, February 17, 2012 4:33:24 AM I was able to enroll two or three people in this study. Its interesting to finally see the results!
Paul T Salos Paul T Salos Friday, February 17, 2012 5:51:02 AM Rectal valium is in our protocols. And has proven effective and no problems have arisen as a result thereof. Our medical director is spot on with us and he is awesome. He used to be a paramedic with FDNY.
Rogue Medic Rogue Medic Mon Feb 20 17:36:52 PST 2012 Paul T. Salos, These are just the first 5 papers I looked at comparing rectal diazepam with other treatments. Rectal diazepam is SLOWER. Rectal diazepam is LESS EFFECTIVE. Perhaps your medical director should review the research on rectal diazepam, because there is no good reason to continue to use it. Rectal diazepam has only been demonstrated to be superior to is placebo - in other words, it does work, but not as well as any of the other treatments available. - Intranasal midazolam vs rectal diazepam in acute childhood seizures. Bhattacharyya M, Kalra V, Gulati S. Pediatr Neurol. 2006 May;34(5):355-9. PMID: 16647994 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/16647994 - Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Scott RC, Besag FM, Neville BG. Lancet. 1999 Feb 20;353(9153):623-6. PMID: 10030327 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/10030327 - Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Holsti M, Dudley N, Schunk J, Adelgais K, Greenberg R, Olsen C, Healy A, Firth S, Filloux F. Arch Pediatr Adolesc Med. 2010 Aug;164(8):747-53. PMID: 20679166 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/20679166 - Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. Fisgin T, Gurer Y, Tezic T, Senbil N, Zorlu P, Okuyaz C, Akgun D. J Child Neurol. 2002 Feb;17(2):123-6. PMID: 11952072 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/11952072 - Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, Martland T, Berry K, Collier J, Smith S, Choonara I. Lancet. 2005 Jul 16-22;366(9481):205-10. PMID: 16023510 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/16023510 .
Dustin Krtek Dustin Krtek Friday, February 17, 2012 7:02:48 AM How do you inject some one having a seizure without them beating you half to death?
Zachary Prejean Zachary Prejean Friday, February 17, 2012 8:09:48 AM I was wondering the same thing. Which drug and dose are they talking about here. Plus thats gonna be another drug abusers dream.. Great idea, but i agree that it needs more research
Rogue Medic Rogue Medic Mon Feb 20 17:46:59 PST 2012 Zachary Prejean, Worrying more about the potential for drug abuse than about the care of patients is a very bad idea. How do you know so much about drug abuse and what drug abusers dream about? Why do you have so little concern for seizure patients? How is this " gonna be another drug abusers dream.. "? There has been a lot of research on this. Maybe you should read some of the research before you comment. How would you know what needs research? I listed a dozen earlier studies of IM midazolam in the link below. http://roguemedic.com/2012/02/intramuscular-midazolam-for-siezures-part-i/ .
Zachary Prejean Zachary Prejean Mon Feb 20 18:12:58 PST 2012 Without even taking the time to read your link, i know about drug abuse because i have a family member that has had problems his entire life. Thanks for the asshole response though...where in any way, shape, or form did i say i had little concern for seizure patients. Again..thanks for the asshole assumption. And I have an opinion just as well as to what needs research as you. Who are you to call me out on that? :)
Rogue Medic Rogue Medic Mon Feb 20 18:16:41 PST 2012 Zachary Prejean, So you know a drug abuser and you think that is an excuse to discourage use of this safe, effective, and well studied treatment for seizures. Apparently, you do not know a thing about the studies and you wish to keep it that way. .
Zachary Prejean Zachary Prejean Mon Feb 20 18:34:39 PST 2012 Guess your just butthard for this drug. Because obviously it does need more research since its not being used in this form currently. so do not call me out with you posts that have nothing to do with my initial comment. I never discouraged the use of it at all. So guess you just keep having fun bein an internet troll.
Zachary Prejean Zachary Prejean Mon Feb 20 18:37:35 PST 2012 In fact, i said "great idea". So where did you get that im downing the use of such a great, powerful drug?
Rogue Medic Rogue Medic Mon Feb 20 19:22:14 PST 2012 Zachary Prejean, "Great idea, but . . ." That is not support. That is a backhanded compliment. Not only is IM midazolam well studied, but it is commonly used as an IM treatment for seizures. You would have to read a bit about the subject to know that. Why do you keep making false statements about the lack of research on IM midazolam? I provided a link to a dozen studies, but you are too smart to look. Here is just one. From 1992. Were you working in EMS then? Were you born yet? The study shows that this IM midazolam nothing new or unsupported by research. 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] http://www.ncbi.nlm.nih.gov/pubmed/1622519 Just because the use of a drug is off-label does not mean that it is not appropriate. A lot of the medications used in EMS are used off-label. .
Rogue Medic Rogue Medic Saturday, February 18, 2012 9:38:54 AM "'This auto-injection should be the new standard of care,' said Dr. James Quinn, a professor of surgery and emergency medicine at Stanford who led the study there. 'It's great when you can do a study and it's probably going to change how we do things.'". No. IM midazolam should be the standard of care, not the expensive "fool-proof" device. From the study - "Similarly, an autoinjector was used in this study to optimize the speed and efficiency of intramuscular delivery, but it is not possible to determine the importance of using this tool for intramuscular injections, as compared with conventional intramuscular injections." Why does Dr. Quinn claim so much more knowledge of results than the study is capable of providing. This study reinforces the results of the many previous studies of IM midazolam..
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