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

- Rogue Medic

Images from Gathering of Eagles Presentation on RAMPART

Some images from the Gathering of Eagles presentation on RAMPART[1] can help to give an idea of what was done to blind EMS to the treatment being given, while minimizing any delay in care that might result from being part of a study. Thank you to Happy Medic for clarifying some of the information not spelled out in the paper.

 

First is the study kit that was used.

For subjects who met the eligibility criteria, the paramedics began the study procedure by opening an instrumented box containing a study drug kit. Each kit contained two color-coded, shrink-wrapped study-drug bundles, one for each dose tier; each bundle consisted of one intramuscular autoinjector (Investigational Midazolam Autoinjector [Meridian Medical Technologies]) and one prefilled intravenous syringe (Carpuject System [Hospira]).[2]

A voice recorder was activated by opening the study box. Paramedics were instructed to record oral statements when intramuscular treatment was administered, when intravenous access was obtained, when the intravenous study drug was administered, when any rescue treatments were given, and when convulsions were observed to stop. Each statement was time-stamped by the study box’s internal clock. Paramedics also stated whether the subject was convulsing on arrival at the emergency department.[1]

This is the autoinjector.

To assess the weight of the patient for the study, they used a simplified length-based resuscitation tape to measure children to determine whether they were large enough to participate in the trial (at least 13 kg – 28.6 pounds) and whether they would receive the adult dose (over 40 kg – 88 pounds). The low dose was 2 mg lorazepam (Ativan) IV (IntraVenous) or 5 mg midazolam (Versed) IM (Intramuscular). The standard adult dose was 4 mg lorazerpam IV or 10 mg of midazolam IM.

It took me a while to figure out what this was. I initially thought that it was just a label from the side of the study drugs, but when I read it, I realized that this is an image of a full-sized length-based resuscitation tape, just shrunk to fit on the page. That would be about 5 feet long. This is conveniently marked with sections stating DO NOT ENROLL at one end and USE 10 MG DOSE at the other end.

For those who think that randomized placebo controlled studies would interfere with patient care, or delay patient care, this demonstrates that it is pretty easy to get around obstacles and even deliver care faster than outside of the study.

This appears to be an excellent way of designing a randomized double-blind controlled trial.

I tried to get some sort of confirmation of the numbers on the IM midazolam group in this last image, but Dr. Jason McMullan does not have them and only the IV lorazepam numbers are in the original paper. I sent a couple of emails to Dr. Robert Silbergleit (the contact person for the paper), but I have not received any response.

The percentage of patients who had their seizures stop prior to starting an IV in the IV lorazepam matches the placebo group from the lorazepam vs. diazepam vs. placebo study.[3]

The IV lorazepam group had 21% of the patients not receive IV medication because the seizure stopped without medication.

The placebo group had 21.1% of the seizures stop without any active medication.

The IM midazolam group had 39% of the patients not receive IV medication (just saline since their package included the active midazolam auto-injector) because the seizure stopped before the IV could be started.

The seizures stopped at almost twice the rate that seizures have stopped with placebo treatment. These are just the seizures that stopped before an IV could be started.

This study is an excellent example of a prehospital randomized double-blind controlled study that would serve as a great model for a placebo controlled trial of epinephrine.

I 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 – RAMPART,
and Images from Gathering of Eagles Presentation on RAMPART.

Footnotes:

[1] Epileptic Fix: Hot-Off-the-Press Results from the RAMPART Trial
Jason T. McMullan, MD (Cincinnati)
Gathering of Eagles
Friday, February 24, 2012
Presentation

[2] 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

Free Full Text from N Engl J Med.

[3] A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.
Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O’Neil N, Neuhaus JM, Segal MR, Lowenstein DH.
N Engl J Med. 2001 Aug 30;345(9):631-7. Erratum in: N Engl J Med 2001 Dec 20;345(25):1860.
PMID: 11547716

Free Full Text from N Engl J Med. with link to PDF Download

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Gathering of Eagles 2012 Preview

Fossil Medic posted the schedule for tomorrow’s Gathering of Eagles conference.

I wish I could be there, but it is not in my budget.

What are the most interesting topics?

The Results Are In: The Outcomes of Recent Outcome Studies!

A block of 10 minute summaries of these recent outcomes studies. Unfortunately, I do not think that 10 minutes is appropriate coverage for these, because they have some important, but subtle points that probably cannot be adequately covered in 10 minutes.

9:00am-9:10am Epileptic Fix: Hot-Off-the-Press Results from the RAMPART Trial
Jason T. McMullan, MD (Cincinnati)

I have already written a few posts about this.[1]

My 30 second coverage –

This is a well done study that confirms what we should already have been doing. IM (IntraMuscular) midazolam (Versed) works significantly faster and significantly more often than IV (IntraVenous) benzodiazepines (lorazepam [Ativan] in this case).

There was no good reason to avoid using IM midazolam as the initial treatment before this study.

There is much less reason to avoid using IM midazolam as the initial treatment after this study.

9:15am-9:25am To ITD or Not To ITD: Reconciling the ROC and ResQ Trial Results
R. J. Frascone, MD (St. Paul)

Dr. Keith Wesley should have a lot to say about this.

I wonder about the wisdom of stopping any trial early because of the appearance no difference in outcomes.

In what way is that a good idea?

A study is supposed to generate the information we need to make decisions about future treatment. If there is no apparent difference, almost no reason to stop the trial early. Most of the money is already spent. There is no increased protection to patients. The people who think the intervention was a good idea will not be satisfied that it has been convincingly shown to be useless. Subgroup analyses that might lead to hypotheses for future studies may not be possible with smaller numbers.

Stopping this early was just a bad idea. Like a kid who does not see immediate results and decides he won’t play any more.

9:30am-9:40am CIRCular Arguments: Was It Win, Lose or Draw in the CIRC
Auto-Pulse Trial ?
David E. Persse, MD (Houston)

CIRC (Circulation Improving Resuscitation Care) will probably continue to produce more excuses than benefits.

The problem is the poor quality of human CPR.

The answer is not to get a machine to perform the CPR.

The answer is to improve our understanding of CPR. We do not think about what we are doing when we are compressing the chest. All other parts of CPR are a waste, so our misunderstanding encourages us to ventilate and transport.

Ventilation has not been demonstrated to improve outcomes.

Transportation has not been demonstrated to improve outcomes.

CPR machines have not been demonstrated to improve outcomes.

We have just been making excuses for bad education, bad oversight, and bad outcomes. The AutoPulse does not improve any of these.

9:45am-9:55am A Very Cool Way to Save Lives: Intra-Arrest Therapeutic Hypothermia
John P. Freese, MD (New York)

An interesting idea.

Is this a way to decrease the damage done by epinephrine?

Is this something that does improve outcomes?

10:10 am-10:30am The Eagles Wing It: Lightning Rounds # 1
with above speakers and several others…
U.S. Metropolitan Municipalities EMS &
Federal Agency Medical Directors

This should be very interesting. Fortunately, it is 20 minutes, rather than just 10 minutes.

And a topic I write about a lot –

2:40pm-3:00pm Do You Have the Backbone for this Debate?
Is Spinal Immobilization Really Good for You?
Neal J. Richmond, MD (Louisville) vs.
Jonathan Jui, MD, MPH (Portland)

The question is easy to answer.

 

We have no evidence to support the current use of spinal immobilization.

 

None.


Image credit from Voodoo Medicine Man.

We have evidence of pain, increased neck and back pain, decubiti, and airway compromise.

There is evidence of significantly increased disability with spinal immobilization.

We all want to decrease the rate of disability among people with unstable spinal fractures. There is no reason to assume that the current method of spinal immobilization does what its advocates claim it does – protect patients from worsening injury. There is evidence that it does exactly the opposite.

Out-of-hospital spinal immobilization: its effect on neurologic injury.
Hauswald M, Ong G, Tandberg D, Omar Z.
Acad Emerg Med. 1998 Mar;5(3):214-9.
PMID: 9523928 [PubMed – indexed for MEDLINE]

There is a lot more we should know about spinal immobilization, but this is the best available evidence.

Any advocate of spinal immobilization MUST come up with better evidence to justify continuing this demonstrably harmful practice.

Anything else is unethical.

Footnotes:

[1] Intramuscular Midazolam for Seizures
Rogue Medic

Part I

Part II

Part III

Part IV

Part V

Part VI

Images from Gathering of Eagles Presentation on RAMPART

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