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

- Rogue Medic

Intramuscular Midazolam for Seizures – Part VI


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.

How aggressive should we be in treating seizure patients based on this large double-blind, randomized, noninferiority trial comparing IM (IntraMuscular) midazolam (Versed) with IV (IntraVenous) lorazepam (Ativan)?

Which seizure patients should be treated with benzodiazepines?

Most patients stop seizing without any treatment and benzodiazepines can cause respiratory depression, so we need to be careful.

 

You can’t be too careful!

 

Right?
 

status epilepticus . . . occurs in approximately 6% of visits to the emergency department for seizures. . . . Although the term “prolonged” was previously used to refer to seizures lasting 30 minutes or longer, this interval has been shortened to 5 to 10 minutes in recent studies. This change occurred for several reasons. First, almost all convulsive seizures in adults cease in less than 5 minutes without treatment; seizures lasting longer than this are more likely to be self-sustained and to require intervention.3,4 [1]

 

We used to be much more careful. We would wait half an hour before treating seizures out of a fear of making things worse. That fear caused us to make things worse by being too careful.

5 minutes seems to be the dividing line between seizures that will stop on their own and seizures that require treatment.
 

Second, the longer seizures persist, the harder they are to terminate pharmacologically.5 [1]

 

Being too careful resulted in higher doses of medication being given, because the dose that could have worked earlier in the seizure is no longer effective. The larger dose is also not effective. A different medication may also need to be added, even though it may not be effective, because we waited too long by being too careful!.

Delaying by more than 5 minutes increases the likelihood of not being able to stop the seizure with any medication. This is far worse than the potential side effects of giving a benzodiazepine to a patient who would otherwise have his seizure resolve spontaneously.
 

Third, outcome tends to correlate with seizure duration even after one controls for other factors. Mortality among patients who present in status epilepticus is 15 to 22%; among those who survive, functional ability will decline in 25% of cases.6 [1]

 

Benzodiazepine side effects should be easily managed, even by people with just advanced first aid training – protect the airway and make sure the patient is breathing. In the absence of adequate breathing, getting the patient to talk is most effective. If getting the patient to talk is unsuccessful, painful stimulus is indicated. If painful stimulus is unsuccessful, rescue breathing is indicated.
 

The effects of midazolam on the CNS are dependent on the dose administered, the route of administration, and the presence or absence of other medications. Onset time of sedative effects after IM administration in adults is 15 minutes, with peak sedation occurring 30 to 60 minutes following injection.[2]

 

Midazolam given IM is not metabolized as quickly as when given IV, but midazolam should still be metabolized more quickly than IV lorazepam (Ativan). Unfortunately, the label does not include information about the time to return to being alert following IM midazolam, so I can only make this apples and oranges comparison. When I have given midazolam IV, I have had to give more midazolam before arriving at the hospital (after I had given a total dose that was successful) or more sedation has had to be given the hospital (after I had given a total dose that was successful). I have never seen IV lorazepam metabolized that quickly. So midazolam is metabolized much more quickly IV, than lorazepam is metabolized IV. Unfortunately, I could not find more appropriate information to compare the metabolism of IM midazolam and IV lorazepam.
 

The intended effects of the recommended adult dose of ATIVAN Injection usually last 6 to 8 hours.[3]


Image credit.
 

This study does show that the patients receiving IM midazolam did not end up hospitalized as often, which may be due to more rapid metabolism of IM midazolam.
 

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).[4]

What is needed is a good study comparing buccal midazolam, IN (IntraNasal) midazolam, and IM midazolam to find out which works best. Perhaps a rectal diazepam group could be included to put another nail in that coffin, but rectal diazepam has the one thing going for it that no amount of evidence seems to be able to overcome – tradition. We need to stop killing our patients with tradition.
 

Multiple studies have shown that nasal or buccal midazolam stops seizures faster than rectal or intravenous diazepam13 and is absorbed faster than intramuscular midazolam.13 – 15 [1]

 

Buccal or IN midazolam stops seizures faster than IV or rectal diazepam, but is only absorbed faster than IM midazolam?

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

Footnotes:

Correction 01/15/2014 15:00 – I had the wrong paper listed as the source of the material in Footnote [1]. I listed the RAMPART study, but the source is the editorial that was published in the same issue. The correct source is below with the paper I originally cited below it. There is nothing wrong with the paper crossed out – only with my use of it as the source of the material I included above.
 

[1] Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus.
Hirsch LJ.
N Engl J Med. 2012 Feb 16;366(7):659-60. doi: 10.1056/NEJMe1114206. No abstract available.
PMID: 22335744 [PubMed – indexed for MEDLINE]

Free Full Text PDF Download from the RAMPART Group.
 

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
FDA Label

[3] ATIVAN (lorazepam) injection, solution
[Baxter Healthcare Corporation]

DailyMed
FDA Label

[4] 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]

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

Hirsch LJ (2012). Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus. The New England journal of medicine, 366 (7), 659-60 PMID: 22335744

Hirsch LJ (2012). Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus. The New England journal of medicine, 366 (7), 659-60 PMID: 22335744

.

A Killer Diagnosis?


Expletive deleted Horror Shows! is firetender’s response to my Thanksgiving Day post Happy Excited Delirium.

Again, firetender is claiming that the officer is making a diagnosis. He is demonstrating this by using non-medical definitions of diagnosis and assessment. Is this any different from the creationists who pretend that a scientific theory is the same as an opinion.

We should not expect a fundamentalist to understand science. Likewise, we should not use a non-medical definition for medical terms.

At 23:48., the room is silent, the cop is on the phone and making the diagnosis.
(Let me say that again: Making a diagnosis!)

That is not a diagnosis. Here is what I wrote –

At 4:15 (of the linked video) the officer to tell the ambulance, I believe we have an excited delirium case.
This is excellent communication and the right assessment.

This is not a diagnosis.


Image credit.

So, technically, no, that was not an assessment. The Officer specifically used medical terminology to describe a medical condition

What if the police officer says –

I believe we have a diabetic emergency.

I believe we have a GSW (Gun Shot Wound).

I believe we have a cardiac arrest and I am initiating compressions and attaching the AED (Automated External Defibrillator.

Are these diagnoses? They all use medical terminology, but that does not make them diagnoses. Imagine if he had used the word that every EMT learns to use, rather than sweaty – diaphoresis? Would that be a diagnosis?

Once that call was made, a course of treatment was embarked on based on the protocols surrounding the intervention in such medical conditions; restraint and sedation.

If the police mention diabetic emergency on the radio, am I required to initiate treatment under the hypoglycemia portion of an altered mental status protocol?

If the police mention GSW on the radio, am I required to initiate treatment for a GSW under a trauma protocol?

If the police mention cardiac arrest on the radio, am I required to initiate treatment under a cardiac arrest protocol?

What if none of these assessments are accurate?

What if the diabetic patient is not really diabetic, or has a different cause of altered mental status, or does not even have altered mental status?

Once that call was made, a course of treatment was embarked on based on the protocols surrounding the intervention in such medical conditions; dextrose.

What if the GSW patient has not been shot, or the wound is minor, or something else?

Once that call was made, a course of treatment was embarked on based on the protocols surrounding the intervention in such medical conditions; 2 large bore IVs, non-rebreather mask/intubation, rapid transport to a trauma center.

What if the cardiac arrest patient never had a cardiac arrest?

Once that call was made, a course of treatment was embarked on based on the protocols surrounding the intervention in such medical conditions; CPR, intubation, epinephrine, defibrillation, therapeutic hypothermia, et cetera.

In other words, NO. The police do not determine EMS treatment.

Does EMS call the police for treatment orders?

No.

If the mention of excited delirium syndrome by a police officer caused some requirement for sedation, where was the sedation?

It is impossible at present to know how many patients receive a therapeutic intervention that stops the terminal progression of this syndrome.

One reason for that is, as the first article described, the diagnosis is most often applied to a dead person after the fact of forcible restraint by LEOs.

No, but feel free to try to come up with some evidence of this.

I don’t know how more clear this White Paper can get; The diagnosis of Excited Delirium is NOT derived from Evidence-Based Medicine. In that respect, I’d imagine Rogue would have to agree with me; DO NOT ACCEPT ExDS AS A VALID DIAGNOSIS!

The authors of the paper make it clear that they are basing this on the best available evidence. Writing in ALL CAPS does not change that.

There is no current gold standard test for the diagnosis of ExDS.
… combination of delirium, psychomotor agitation, and physiologic excitation differentiates ExDS from other processes that induce delirium only.
…Similarly, subjects who are agitated or violent but who do not also demonstrate features of delirium simply do not meet the definition of ExDS.

What is a syndrome?

Syndrome: A set of signs and symptoms that tend to occur together and which reflect the presence of a particular disease or an increased chance of developing a particular disease.

What was the title of the white paper?

White Paper Report on Excited Delirium Syndrome.

Do you assume that the definition of syndrome is something that is irrelevant, or do you just not know that it is relevant, or do you just not know what a syndrome is?

Basically, they’re saying that there doesn’t appear to be a “cause and effect” between use of restraint or chemical/electrical controls and death. But, really, how can they say that when the only cases of death through so-called ExDS are precisely on the heels of the application of force?

When people are killed by the application of force, there are usually some signs of the cause of death. Cause and effect. Excited delirium syndrome is different. There is no injury that explains the death. Fighting with police is not necessary, but extreme physical exertion does appear to be necessary.

If you figure out how to sedate people without the exertion, that would be great.

Getting excited delirium syndrome patients to voluntarily stay in a calm comfortable room is great – right up until the patient decides to leave and go play in traffic, and kick little old ladies over and over, and throw children around, and whatever else?

Until there is a safe, dependable, fast acting remote tranquilizer available, force is going to be a part of the solution.

Sedative or dissociative agents such as benzodiazepines, major tranquilizers, and ketamine are suggested but there is no evidence yet to prove that these will result in a lower morbidity or mortality.

There does not appear to be any research to demonstrate clearly that sedation saves lives, but we do know that continuing extreme exertion by these patients frequently results in death. What is frequently? That is difficult to answer. They do estimate that the dramatic decrease in estimates of the death rate is due to psychiatric medication.

What would be the treatment for a patient in an ICU with similar extremes of metabolism?

Sedation?

White Paper Report on Excited Delirium Syndrome
ACEP Excited Delirium Task Force
Vilke GM, Debard ML, Chan TC, Ho JD, Dawes DM, Hall C, Curtis MD, Costello MW, Mash DC, Coffman SR, McMullen MJ, Metzger JC, Roberts JR, Sztajnkrcer MD, Henderson SO, Adler J, Czarnecki F, Heck J, Bozeman WP.
September 10, 2009
Free Full Text PDF

Updated to add link to the White Paper being discussed on 7/23/2018. This should have been included originally.

Correction to Why doesn’t CPR work for trauma

In looking at the diagram I made of tension pneumothorax for Why doesn’t CPR work for trauma, I realized that there is no easy way to fix the errors I made. I made a lot.

As Jon Levine explains in the comments –

Nice commentary on the futility of CPR in trauma (hypovolemic) but to be more accurate you should show the tension pnuewmothorax causes blockage/kinking of the preload not afterload to be be more accurate and repersentaive of the poor cardiac output ” Nothing into the pump nothing out.”

So, I had a lot of corrections to make.


Click on the images to make them larger and easier to read.

There is a difference between the thickness, and strength, of the walls of the blood vessels. The aorta is a thick muscular walled artery. The pulmonary veins are thinner walled and weaker. When pressure is applied, the pulmonary veins will kink first.

When the veins kink, the heart will still be beating. The heart will empty, but will not be able to fill up again. After two, or three, beats there should be essentially no blood left in the heart. Even empty, the heart continues to beat.

This condition is the same as with a patient who bled out, except that all of the blood may still be in the body – except the lack of blood is limited to the heart and the blood vessels from the obstruction to the heart and coming from the heart. The patient is just as dead with no blood in the heart as when there is no blood anywhere in the body.

CPR (CardioPulmonary Circulation) can correct the problem of a heart that is not bleeding, but if there is no blood to circulate or if there is an obstruction to circulation, CPR will not be effective.

Resuscitation of the exsanguinated patient is much more difficult (refilling the body with blood before the damage becomes irreversible) than correcting an obstruction. Tension pneumothorax can be corrected by releasing the pressure. The pressure is in the pleural space, so a hole to drain that pressure out of the body is the solution. That hole can be a needle, if it is long enough to reach the pleural space and does not itself become obstructed, a knife, or a chest tube (after using a knife).

The obstruction of cardiac tamponade can be similarly released, but it is not as easy to remove the pressure of the blood in the pericardial space as it is to release the pressure of the air in the pleural space.

I hope this clarifies tension pneumothorax.

.

Why doesn’t CPR work for trauma

In Potentially Reversible Causes of Cardiac Arrest and the Futility of CPR for Trauma Arrest, I did not really explain, Why doesn’t CPR (CardioPulmonary Circulation) work for trauma?

So I asked myself How might someone, who is bad at drawing, demonstrate this? With bad drawings. Feast your eyes on these.

The heart is more complicated than a ball of blood, but for the purposes of explanation, a ball of blood is as complicated as the heart needs to be. In these diagrams, the ball of blood is the left ventricle.

Yes, the blood from the pulmonary veins is red, so that is in red. The time when the mitral valve is closed and the aortic valve is open, is what matters for compressions. Compressing a pulseless heart should create this condition.

As long as there is blood in the heart, it should flow in one direction during compressions.

By squeezing the bag of blood heart, an effective compression should produce some sort of circulation.

When there is no blood to squeeze out of the heart, there is no circulation.

An additional problem with CPR on the exsanguinated patient (patient who bled out) is that the heart is probably still beating. The purpose of CPR is to provide a poor substitute for real heart beats. If the heart is still beating, the poor substitute is not going to do a better job of moving the blood that is not there.

When the patient is pulseless due to blood loss –

The heart is probably still beating.

The heart rate is probably a lot faster than 100 – the poor substitute rate of chest compressions.

The problem is not a lack of cardiac activity.

What about tension pneumothorax?

The problem with tension pneumothorax is that the mediastinum is shifted to one side, or compressed, to the point that the major blood vessels are badly kinked. As with a straw that is kinked, nothing flows through a badly kinked blood vessel.

Compressing harder, or faster, or both, will not make any difference. The only way to improve cardiac output is not by compressions, but by decompression. This is why the patients in need of needle decompression will be losing their vital signs.

As with bleeding out, this pulseless patient’s heart should still be beating more effectively than anything any chest compression could produce. The heart just can’t push the blood through the kinked blood vessels – and neither can chest compressions. No circulation = no pulse, even though the heart is beating well.

What about cardiac tamponade?

A cardiac tamponade is similar to a tension pneumothorax. In stead of air leaking into the pleural space and preventing the expansion of the lung, there is blood leaking into the pericardial space and preventing the expansion of the heart. The heart and the lungs need to expand and contract to work. The pleural space and the pericardial space are not supposed to contain air or blood.

After each heartbeat, the heart needs to expand to allow blood back in for the next heartbeat.

If the heart cannot expand, it cannot effectively contract.

If the heart cannot expand, due to already being compressed by a huge hematoma in its lining, then compressing that heart will not improve the cardiac output. Again, the heart is beating, just not well enough because it cannot expand. Adding compressions will not improve anything.

Late entry – 14:30 on 11/17/2011 –
As Jon Levine explains in the comments –

Nice commentary on the futility of CPR in trauma (hypovolemic) but to be more accurate you should show the tension pnuewmothorax causes blockage/kinking of the preload not afterload to be be more accurate and repersentaive of the poor cardiac output ” Nothing into the pump nothing out.”

This is true. The blockage on the input (the more flexible/less rigid blood vessels) is more accurate than blockage on the output. This is something to help understand what is going on with a tension pneumothorax.

In the comments, Windy City Medic also provides an great explanation of the way that man made pumps fail in the same way that the heart fails. Link to comment

Anoxia is one exception to this, but it is easy to determine if there is any reason to use CPR. If appropriately done compressions do produce a pulse, then the potentially reversible cause of cardiac arrest is not exsanguination or obstruction.

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Corrections of Misleading Charts


Also posted over at Paramedicine 101, which is now at EMS Blogs. Go check out the excellent material there.

Back in September, I wrote Furosemide and Drug Shortages 2. I was just looking at the charts I made and realized that they were not at all helpful at explaining the information.

When I look at my own charts and have trouble figuring out what I was trying to explain, then I have completely failed.

I have edited the charts to do a better job of presenting the information I was trying to make clear.


Click on charts to make them larger.

When looking at the problems with the use of furosemide (Lasix), one import point to remember is that the authors only looked at the primary diagnosis. This is an important shortcoming of the study.

How many of the patients had a secondary diagnosis of CHF?

We don’t know.

It should be noted that seven patients without an ED diagnosis of CHF received ED furosemide and 43 patients received ED nitro with only eight of those having a primary diagnosis of ACS. This data put the accuracy of the primary ED final diagnosis as a reference standard into question,[1]

Another problem is that the authors seem to think that nitro is only for ACS (Acute Coronary Syndromes – essentially heart attacks). NTG (NiTroGlycerine) is the most effective medication for hypertensive CHF.

Only 43 out of 60 patients with a primary diagnosis of CHF received NTG – this needs to be studied.

Were these 17 patients not treated with NTG because they were hypotensive?

In the ED, it is much safer to give normotensive CHF patients NTG, because of IV (IntraVenous) NTG. EMS is usually limited to SL (SubLingual) NTG.

SL NTG is not what is best for patients, unless we feel that it is important to treat patients with NTG before starting an IV.

If we have IV access, we should be giving NTG the safer and more titratable way – IV NTG. (This sentence added 11:50 02/07/11)

This chart was just to show how little difference it would make to add in the patients who did not have a diagnosis.

This chart compares the deaths between the patients treated with furosemide by EMS and receiving a primary diagnosis of CHF and those not receiving a primary diagnosis of CHF.

Due to the shortcomings of this study, it should be replicated with the secondary diagnoses included. This is essential.

Footnotes:

[1] Correlation of paramedic administration of furosemide with emergency physician diagnosis of congestive heart failure
Thomas Dobson, Jan Jensen, Saleema Karim, and Andrew Travers.
Journal of Emergency Primary Health Care
Vol.7, Issue 3, 2009
Free Full Text . . . . . . . Free Full Text PDF

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