Research | Rogue Medic

If you have a BVM (Bag Valve Mask resuscitator), you should not need naloxone. The problem is inadequate respiration, not inadequate naloxonation.

- Rogue Medic

Studying complementary and alternative therapies

Mon, 07 May 2012 00:25:46 +0000 By Rogue Medic Leave a Comment

Dr. Paul Offit has an audio interview available at the link from the QR code to the right ->

Are we getting a benefit from the money being spent on NCCAM (the National Center for Complementary and Alternative Medicine)?

Although studies funded by NCCAM have failed to prove that complementary or alternative therapies are anything more than placebos, some proponents — pointing to studies of vaccine safety—argue that negative studies of biologically implausible hypotheses are worthwhile.^[1]

The ~~drugs~~ supplements don’t work.

Does the same value of rigorously conducted negative studies hold for studies of complementary and alternative therapies? Have negative studies changed behavior? The answer is probably best found in NCCAM-funded studies of dietary supplements and megavitamins. Several studies have shown that garlic does not lower low-density lipoprotein cholesterol, St John’s wort does not treat depression, ginkgo does not improve memory, chondroitin sulfate and glucosamine do not treat arthritis, saw palmetto does not treat prostatic hypertrophy, milk thistle does not treat hepatitis, and echinacea and megavitamins do not treat colds.⁶ ^[1]

Where are the studies that show any benefit?

Is it just a matter of repeating studies enough times that the improbable, and implausible, show a slight benefit, but only due to the normally expected statistical variation. Trying the same thing over and over until the equivalent of a streak of heads (or tails) comes up. What are the odds of __ heads in a row?

Significant

Mouseover text: ‘So, uh, we did the green study again and got no link. It was probably a–’ ‘RESEARCH CONFLICTED ON GREEN JELLY BEAN/ACNE LINK; MORE STUDY RECOMMENDED!’

Roll the dice enough times/flip the coin enough times/repeat the study enough times and there may be at least one study that produces misleading results.

Maybe they are just not doing the research the right way.

“The better the quality of the research, the less benefit [supplements] showed,” says Marion Nestle, professor of nutrition, food studies, and public health at New York University.^[2]

At least there is no evidence of harm.

The first red flags started emerging nearly 20 years ago. Researchers thought from early work that extra beta-carotene could help prevent lung cancer, but two randomized trials published in 1994 and 1996 showed an increased rate of lung cancer among smokers who took beta-carotene supplements.^[2]

These are not the only studies showing harm.^[2]

But the problem is Big Pharma – the evil drug companies.

In 2010, the vitamin and supplement industry grossed $28 billion, up 4.4% from the year before.⁸ “The thing to do with [these studies] is just ride them out,” said Joseph Fortunato, chief executive of GNC Corp. “We see no impact on our business.”⁷ ^[1]

Maybe we should discourage the use of dangerous supplements.

Because negative studies do not appear to change behavior and because studies performed without a sound biological basis have little to no chance of success, it would make sense for NCCAM to either refrain from funding studies of therapies that border on mysticism such as distance healing, purgings, and prayer; redefine its mission to include a better understanding of the physiology of the placebo response; or shift its resources to other NIH institutes. ^[1]

There are so many claims about the benefits of placebos and the mystical effects of placebos that we should find out if there is any truth to these claims.

Similar claims were made about supplements. These claims continue to be made, even though there is no evidence.

Listen to Dr. Offit explain this in an interview at this page from JAMA.

Footnotes:

^[1] Studying complementary and alternative therapies.
Offit PA.
JAMA. 2012 May 2;307(17):1803-4. No abstract available.
PMID: 22550193 [PubMed - indexed for MEDLINE]

^[2] Is This the End of Popping Vitamins?
By Shirley S. Wang
October 25, 2011
Article

^[3] Flipping Our Coin
March 30th, 2007
Article

Filed Under: Heresy, Research, Unicorn Medicine

Trauma Criteria – preventative medicine – Part II

Mon, 30 Apr 2012 10:15:57 +0000 By Rogue Medic 1 Comment

Continuing from Part I of an episode of the First Few Moments podcast where Kyle David Bates, Steve Murphy, Patrick Lickiss, and I discuss Patrick’s article about trauma triage criteria – Are Prehospital Trauma Triage Criteria Effective?

Table 3 only reinforces the uselessness of using just MOI (Mechanism Of Injury) to identify critical trauma patients.

This may actually demonstrate where we should focus our attention in trauma triage –

Click on the image to make it larger.^[1]

This table documents part of the continuing attempt to find some sort of magic bullet of trauma assessment.

What is the goal?

A combination of high sensitivity and high specificity.

High sensitivity means that we do not miss patients who die, or are disabled, due to transport to a hospital that is not a trauma center

High specificity means that we are close to the STEMI (ST segment Elevation Myocardial Infarction) triage rate of over 95% accurate identification, rather than the current trauma triage rate of around 5% accurate identification.

If the local hospital does not see any trauma patients, the doctors and nurses may forget how to treat the occasional trauma patient who stubbed his toe and is taking clopidogrel (Plavix – the once you start bleeding, you don’t stop bleeding until it is out of your system a week later drug). The patient drove to the hospital, thus depriving EMS of the opportunity to set up a landing zone, because we can always find some relevant mechanism – and if we can’t the QA/QI/CYA department will on review of the chart.

What can we do to improve our specificity, without missing more legitimate critical trauma patients?

Table 3 does give us a bit of a hint.

Rather than use individual ~~excuses~~ criteria we can combine them.

This is a very scary concept that could get out of control very quickly, because this involves more complex thought than see the mechanism, call the helicopter.

What would we call this magic?

If we added a lot more to it, including judgment, we could call it an assessment.

A true assessment is much more than just combining a few measurements. A true assessment also requires that the receiving facility does not violate HIPAA by refusing to provide information about the continuing treatment of the patient at their facility.

If we do not track the results of what we do, we are only engaging in witchcraft.

Footnotes:

^[1] Differentiation of confirmed major trauma patients and potential major trauma patients using pre-hospital trauma triage criteria.
Cox S, Smith K, Currell A, Harriss L, Barger B, Cameron P.
Injury. 2011 Sep;42(9):889-95. Epub 2010 Apr 28.
PMID: 20430387 [PubMed - indexed for MEDLINE]

Guidelines for field triage of injured patients. Recommendations of the National Expert Panel on Field Triage.
Sasser SM, Hunt RC, Sullivent EE, Wald MM, Mitchko J, Jurkovich GJ, Henry MC, Salomone JP, Wang SC, Galli RL, Cooper A, Brown LH, Sattin RW; National Expert Panel on Field Triage, Centers for Disease Control and Prevention (CDC).
MMWR Recomm Rep. 2009 Jan 23;58(RR-1):1-35. Erratum in: MMWR Recomm Rep. 2009 Feb 27;58(7):172.
PMID: 19165138 [PubMed - indexed for MEDLINE]

Free Full Text from MMWR with link to PDF Download

Filed Under: Assessment, First Few Moments, Heresy, Research

What should an epinephrine in cardiac arrest study look like?

Tue, 10 Apr 2012 08:00:34 +0000 By Rogue Medic 4 Comments

Since the Hagihara^[1] study was published, there is a lot more support for a study of epinephrine. One of the problems with studying epinephrine is the religious devotion that some have to maintaining the status quo.

How do we prevent paramedics from violating the study protocol?

I have been told of paramedics testing the study drug to see if it produces the cocaine-type of numbness to the tongue, since epinephrine produces effects similar to cocaine without the euphoria. If the study drug is not epinephrine, the syringe is broken, or replaced, or . . . .

How much epinephrine is needed on an ALS (Advanced Life Support) ambulance?

We generally carry a bunch of 1:10,000 epinephrine (1 mg in 10 ml) for cardiac arrest. Maybe 5 – 10 with a multi-dose 30 ml vial of 1:1,000 (1 mg in 1 ml) epinephrine for those prolonged arrests, so that 1 mg at a time can be drawn up and given to the patient.

We also carry some ampules of 1:1,000 epinephrine for IM (IntraMuscular), SC (SubCutaneous), or IV (IntraVenous) administration for anaphylaxis or asthma.

We can easily replace the 1:10,000 epinephrine and the multi-dose vial with just one study drug packet. After each code, a new packet would be placed in the ambulance’s drug bag/box. This would discourage the tendency to switch kits if the study drug is not epinephrine – not that there is any good reason for the medic to know what is being given.

For anaphylaxis/asthma, participating ambulances would be assigned only autoinjectors. This would decrease the availability of epinephrine available to violate protocol.

Supervisors would only carry study kits and autoinjectors.

Is it still possible to intentionally violate protocol? Yes, but anyone thinking that far ahead should be smart enough to realize that they are only harming patients by possibly requiring that the study be repeated. The maturity of the medics should be the best protection against protocol violation, but true believers can be immune to maturity.

What would the study kits include?

The RAMPART^[2], ^[3] study gives an excellent example of how to

Patients are not entered into the study unless they have reached the point in the algorithm where epinephrine would be given. When the kit is opened, the recording beginsand the first syringe of the study drug is given.

Monitors capable of recording the quality of CPR would also be used. The ROC (Resuscitation Outcomes Consortium) should already be using these, so it would not be an added expense.

What about patients who remain in a shockable rhythm after the syringes of study drug are all used? Transport them to the hospital. Let the hospital do whatever they want with these rare patients.

What if there is a problem with the study kit? Then the patient should not be receiving any medication and should be unblinded participants in the group not receiving epinephrine.

What about amiodarone/lidocaine? There is no good reason to give these derivative magic treatments until there is evidence that they work. This is to try to find out if the ~~primary magic treatment~~ epinephrine works, not to support the whole Chain of Magic.

Maybe the last part of that chain should not be there.

EMCrit Wee – Abandon Epinephrine?

Fri, 06 Apr 2012 08:00:11 +0000 By Rogue Medic 1 Comment

Dr. Weingart has a ~~mini~~ wee podcast about the recent epinephrine research and whether EMS should be using epinephrine. Maybe the EMCrit logo is too big for a wee podcast.

One of the EMCrit listeners, the medical director for a major EMS agency, wanted to know what Dr. Weingart thinks about removing epinephrine from their cardiac arrest protocols.

EMCrit Wee – Abandon Epinephrine?

While Dr. Weingart thinks that the evidence will show that epinephrine is beneficial in cardiac arrest . . .

Well, you’ll have to listen to the podcast, all five and a half minutes of it, to find out the rest of his thoughts on this topic.

He recommends reading what Dr. Radecki (EM Literature of Note) wrote about epinephrine here.

I think that there may be only isolated indications for epinephrine. I do not think that we will ever know what those legitimate indications are until after we do a large enough well designed randomized controlled trial to separate out any benefit in survival.

ROSC (Return Of Spontaneous Circulation) is not a valid endpoint after 50 years of routine use, but the only evidence we have in humans is ROSC. We would not settle for such flimsy evidence in treating cancer (unless using alternative medicine), so why is it acceptable in cardiac arrest?

While we have not yet reached double digits on studies showing harm from epinephrine, there still is not a single study showing improved survival with epinephrine in cardiac arrest.

Millions of cardiac arrest patients treated with epinephrine, but we still cannot find any valid evidence of improved survival.

Vladimir and Estragon would have stopped waiting long ago.

Expert recommendations must come with an expiration date.

No exceptions.

If the expert recommendation is not followed by appropriate research, then the expert recommendation should not be treated better than the patients.

I completely agree with Dr. Weingart’s recommended approach. We should also study nitrates in cardiac arrest.

Go listen to all 5 and a half minutes of the podcast.

Filed Under: ACLS, EMCrit, Epinephrine, Pharmacology, Research

A Critic Reads My Mind, But Does He Read What I Write

Thu, 29 Mar 2012 08:00:58 +0000 By Rogue Medic 6 Comments

In response to What Will Be the Next Standard Of Care We Eliminate is this attempt at reason from SARmission –

@Roguemedic. After reading a number of your blogs I have come to the following conclusion. Your purpose in writing is not to make, those reading, better medics. Rather it is to create controversy, and try to make statements that you are not qualified to make.

You are entitled to your opinion, but you have not provided any evidence to support your opinion. You appear to be just trying to create controversy.

I present people with both my opinion and the evidence on which I base that opinion.

You have based your whole position on this epi debate on an OPINION paper.

How do you know what I have based my conclusions on? Please provide some evidence of your psychic ability.

I have been writing about epinephrine since long before the editorial by Dr. Callaway. I was also teaching about the problems with epinephrine before the AAEM Position statement and AAEM Working Group Report, but I was not writing a blog at that time.

Perhaps you are referring to the AAEM Position Paper, which includes a review of the literature and analysis by Amal Mattu, MD FAAEM, Carey Chisholm, MD FAAEM, and Jerome R. Hoffman, MA MD FAAEM.

I have written about epinephrine a lot –

2008

Epinephrine in Cardiac Arrest
Sun, 06 Apr 2008

Dead VT vs Not Quite Dead, Yet VT.
Tue, 08 Apr 2008

More on Epinephrine in Cardiac Arrest.
Sat, 19 Apr 2008

Narrative Fallacy I
Fri, 24 Oct 2008

2009

EMS Mythology Starter Kit
Tue, 10 Feb 2009

EMS Garage, CPR, Continuous Compressions, and Resuscitation – Jamie Davis comment
Tue, 21 Apr 2009

Why Can’t Medics Resuscitate? II
Tue, 14 Jul 2009

Narrative Fallacy II
Wed, 15 Jul 2009

C A S T and Narrative Fallacy comment from Shaggy
Wed, 22 Jul 2009

The Blame Game
Tue, 27 Oct 2009

Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Thu, 24 Dec 2009

2010

EMS EdUCast – Journal Club 2: Episode 43
Thu, 28 Jan 2010

Correction on Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Sun, 07 Mar 2010

How to Study Epinephrine in Cardiac Arrest
Fri, 30 Apr 2010

Current Drug Shortages
Fri, 30 Jul 2010

More on Drug Calculations
Mon, 02 Aug 2010

A Letter To Mom
Tue, 14 Sep 2010

Most Survive with Mystery Treatment for Cardiac Arrest – Comments from Christopher
Tue, 14 Sep 2010

More Drug Shortage Paranoia – Epinephrine
Wed, 06 Oct 2010

Ethics, Research, and IRBs – Part II
Tue, 26 Oct 2010

Ethics, Research, and IRBs – Part III
Fri, 29 Oct 2010

A Mistaken Bolus of Epinephrine Given to a Living Patient
Tue, 07 Dec 2010

2011

Changes to Pennsylvania Protocols – Post-Resuscitation Care – Part I
Wed, 20 Apr 2011

Rhythm Interpretation and Inattentional Blindness
Tue, 19 Jul 2011

Bogus Ethics and Epinephrine in Cardiac Arrest
Sat, 30 Jul 2011

A Couple of Comments on Bogus Ethics and Epinephrine in Cardiac Arrest – Part I
Sun, 31 Jul 2011

A Couple of Comments on Bogus Ethics and Epinephrine in Cardiac Arrest – Part II
Wed, 03 Aug 2011

A Couple of Comments on Bogus Ethics and Epinephrine in Cardiac Arrest – Part III
Mon, 08 Aug 2011

Cardiac Arrest Management is an EMT-Basic Skill
Wed, 07 Dec 2011

Does Epinephrine Improve Survival from Cardiac Arrest
Mon, 12 Dec 2011

Cardiac Arrest Management is an EMT-Basic Skill – The BLS Evidence – Comment from Windy City Medic
Sat, 17 Dec 2011

Where is the Evidence for Epinephrine in the 2010 ACLS Guidelines
Mon, 19 Dec 2011

The Danger of ROSC – Return Of Spontaneous Circulation
Tue, 20 Dec 2011

Why Does Epinephrine Cause Brain Damage During Resuscitation
Mon, 26 Dec 2011

2012

When Does Post-Resuscitation Care Begin
Wed, 18 Jan 2012

Why We Deceive Ourselves With Explanations
Sat, 04 Feb 2012

Killing Patients Just to Get a Temporary Pulse With Epinephrine
Wed, 21 Mar 2012

Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part I
Thu, 22 Mar 2012

Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part II
Fri, 23 Mar 2012

PROVE Epinephrine is Harmful
Mon, 26 Mar 2012

What Will Be the Next Standard Of Care We Eliminate
Wed, 28 Mar 2012

The Importance of Having ROSC
Sun, 01 Apr 2012

Before you start beating your drum, wait for the FACTS.

Facts?

The evidence that we are not waiting for before we give dangerous drugs to patients?

We should have been waiting for evidence that epinephrine works, or demanding that somebody find out with a large, randomized placebo controlled trial.

We have based treatment with epinephrine on only superficial facts.

Here is the research, look closely:

There isn’t anything there – just a black hole full of nothing.

Consider these statements by the AHA (American Heart Association) – the people who write the guidelines that guide cardiac arrest treatment in the US – about the research on epinephrine –

Deemphasis on Devices and Advanced Cardiovascular Life Support Drugs During Cardiac Arrest
At the time of the 2010 International Consensus Conference there were still insufficient data to demonstrate that any drugs or mechanical CPR devices improve long-term outcome after cardiac arrest.⁴⁵ Clearly further studies, adequately powered to detect clinically important outcome differences with these interventions, are needed.^[1]

The AHA calling for research a couple of years ago.

Why?

Lack of evidence of benefit from epinephrine.

To date no placebo-controlled trials have shown that administration of any vasopressor agent at any stage during management of VF, pulseless VT, PEA, or asystole increases the rate of neurologically intact survival to hospital discharge. There is evidence, however, that the use of vasopressor agents is associated with an increased rate of ROSC.^[2]

We have evidence of improved ROSC. I have never denied that.

I do not think that we should be harming patients just for ROSC.

There is no evidence that increasing ROSC with epinephrine improves any important outcome.

There are no RCTs that adequately compare epinephrine with placebo in treatment of and outcomes related to out-of-hospital cardiac arrest. A retrospective study²⁶⁷ compared epinephrine to no epinephrine for sustained VF and PEA/asystole and found improved ROSC with epinephrine but no difference in survival between the treatment groups. A meta-analysis and other studies have found improved ROSC, but none have demonstrated a survival benefit of high-dose epinephrine versus standard-dose epinephrine in cardiac arrest.^{135,268,–,272} ^[2]

No facts to justify routinely using epinephrine.

The causes of cardiac arrest are numerous; by far the most common in adults is ischemic cardiovascular disease.^4-6 The arrest is usually associated with the lethal arrhythmia of ventricular fibrillation triggered by an acutely ischemic or infarcted myocardium or by a primary electrical disturbance.^[3]

Are we supposed to be giving epinephrine to patients having heart attacks?

We are routinely giving epinephrine to patients who are likely to be having heart attacks.

There is very little high-level evidence for resuscitation therapies, and many traditional treatment recommendations such as the use of epinephrine/adrenaline, are based on animal studies and reluctance to change an existing treatment recommendation until it is proven ineffective or less effective than a novel therapy.^[4]

We don’t seem to need facts to use a treatment on a patient.

We do not seem to believe in the ethics of first, do no harm.

We seem to wait until there is so much evidence of harm that we cannot ignore the evidence any longer.

Then we get rid of the dangerous treatment.

Epinephrine is ordinarily administered with extreme caution to patients who have heart disease.^[5]

There is nothing cautious about the routine administration of 1 mg epinephrine every 3 to 5 minutes to everybody who is still dead when we reach that part of the algorithm.

Before you say it, I know that reading a blog is a choice. I choose to stop reading yours. Thank you for you time.

That suggests that this is not exactly your first time making controversial comments on a blog.

Is making controversial comments constructive when you do it, but destructive when others do it?

I present people with both my opinion and the evidence on which I base that opinion.

Footnotes:

^[1] Deemphasis on Devices and Advanced Cardiovascular Life Support Drugs During Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 1: Executive Summary
John M. Field, Co-Chair*; Mary Fran Hazinski, Co-Chair*; Michael R. Sayre; Leon Chameides; Stephen M. Schexnayder; Robin Hemphill; Ricardo A. Samson; John Kattwinkel; Robert A. Berg; Farhan Bhanji; Diana M. Cave; Edward C. Jauch; Peter J. Kudenchuk; Robert W. Neumar; Mary Ann Peberdy; Jeffrey M. Perlman; Elizabeth Sinz; Andrew H. Travers; Marc D. Berg; John E. Billi; Brian Eigel; Robert W. Hickey; Monica E. Kleinman; Mark S. Link; Laurie J. Morrison; Robert E. O’Connor; Michael Shuster; Clifton W. Callaway; Brett Cucchiara; Jeffrey D. Ferguson; Thomas D. Rea; Terry L. Vanden Hoek
New Developments in Resuscitation Science Since 2005
Free Full Text from Circulation with link to PDF Download

^[2] Vasopressors
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text from Circulation with link to PDF Download

^[3] Cardiac resuscitation.
Eisenberg MS, Mengert TJ.
N Engl J Med. 2001 Apr 26;344(17):1304-13. Review. No abstract available.
PMID: 11320390 [PubMed - indexed for MEDLINE]

Free Full Text with link to Free Full Text PDF Download

^[4] Controversial Topics from the 2005 International Consensus Conference on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
Nolan JP, Hazinski MF, Steen PA, Becker LB.
Resuscitation. 2005 Nov-Dec;67(2-3):175-9. No abstract available.
PMID: 16324986 [PubMed - indexed for MEDLINE]

Free Full Text from Circulation

^[5] EPIPEN (epinephrine) injection
EPIPEN JR (epinephrine) injection
[DEY]
DailyMed
FDA Label

Filed Under: ACLS, Epinephrine, Heresy, Mythology, Pharmacology, Research

What Will Be the Next Standard Of Care We Eliminate

Wed, 28 Mar 2012 08:00:46 +0000 By Rogue Medic 17 Comments

We have too many harmful Standards Of Care. Which will be the next to go?

Will it be Spinal Immobilization using a long spine board, straps, head blocks, and a cervical collar?

Will it be epinephrine in cardiac arrest?

Will it be amiodarone or lidocaine in cardiac arrest?

Will it be ventilations by EMS in cardiac arrest?

Will it be the idea that any treatment can become the Standard Of Care without any evidence of improvement in patient outcomes?

None of these have any evidence that they improve outcomes.

We have put ourselves in a difficult situation, where people claim that it would be unethical to find out if these treatments work. If medicine is about providing the best care to patients, then how can we use fashion to determine what is required patient care, even when all of the research shows that the Standard Of Care is harmful?

From the very beginning of the use of amiodarone in cardiac arrest, the idea of making amiodarone a Standard Of Care was rejected by emergency physicians.

AAEM Position Statement: Use of Amiodarone in Refractory Pulseless VT/VF
“It is the position of the American Academy of Emergency Medicine that the use of amiodarone in refractory pulseless ventricular tachycardia or ventricular fibrillation (VT/VF) should not be considered the current ‘standard of care’ for this condition. The Academy does not condemn non-research use of amiodarone given the absence of any proven beneficial alternatives, however, there is currently no reason to conclude that its use is mandatory or represents a ‘standard of care.’ Until ongoing or future research clarifies this issue, emergency physicians should use their own discretion regarding antiarrhythmic therapy in patients with cardiac arrest.”^[1]

Has anything changed?

Where is the survival research that was supposed to convince us that amiodarone did not just result in more people dying in the hospital?

They state this about High-Dose Epinephrine (HDE) –

Although it was assumed by some that a medication that is associated with improved ROSC and survival to hospital admission would also be associated with improved survival to hospital discharge and neurologic recovery, this was never the case with HDE. Subsequent studies confirmed that HDE in adult victims of cardiac arrest is not associated with an improvement in patient survival to hospital discharge or neurologic recovery (14-20). As a result, the use of high dosages of epinephrine is no longer recommended in the most recent Guidelines (5). =[1]

Does the AAEM consider the ACLS Guidelines to set the Standards Of Care?

Conclusion: This Working Group finds that the use of amiodarone in refractory pulseless VT/VF should not be considered “standard of care” for this condition. Indeed, it could be argued that amiodarone should only be used in cardiac arrest (if at all) in the context of further study protocols. Nevertheless, the Working Group believes it would be inappropriate to condemn non-research use of amiodarone, given the absence of any proven beneficial alternatives. On the other hand, there is certainly no reason to conclude that its use is mandatory, or represents a “standard of care.” Ongoing and future studies may clarify this issue, but until such time, emergency physicians should use their own discretion regarding antiarrhythmic therapy in patients with cardiac arrest.=[1]

Apparently not.

How long did it take to even start a study looking at survival from cardiac arrest with groups randomized to amiodarone, and placebo (with lidocaine thrown in as a crowd favorite in some areas)?

Why are we going to have results from this study?

Drug: amiodarone

300 mg will be given IV/IO push for reoccurrence of ventricular fibrillation or pulseless ventricular tachycardia after 1 or more shocks. A second dose of 150 mg will be given if VF/pulseless VT reoccurs after initial dose and a subsequent shock. The initial dose for patients estimated to be less than 100 pounds will be 150 mg, followed by a second dose of 150 mg if the VF/pulseless VT persists.
Other Name: PM 101, Nexterone^[2]

It is interesting that there is no mention of epinephrine. Based on the attitude of the investigators toward epinephrine, I don’t think they will be omitting that drug, but there is no mention of epinephrine, or any other pressor, in the study description.

Detailed Description:
The primary objective of the trial is to determine if survival to hospital discharge is improved with early therapeutic administration of a new Captisol-Enabled formulation of IV amiodarone (PM101) compared to placebo.

The corresponding null hypothesis is that survival to hospital discharge is identically distributed when out-of-hospital VF/VT arrest is treated with PM101 or placebo.

The secondary objectives of the trial are to determine if survival to hospital discharge is improved with early therapeutic administration of:

Lidocaine compared to placebo

PM101 compared to lidocaine The corresponding null hypotheses are that survival to hospital admission is identically distributed when out-of-hospital VF/VT arrest is treated with lidocaine as compared with placebo, and with PM101 as compared with lidocaine.^[2]

This study is expected to last 3 years and enroll 3,000 patients in three arms in an attempt to refute what people have been saying since the 1990s – Amiodarone just changes the location of death.

September 2015 is the estimated completion date, so this is unlikely to affect the next revision of ACLS (Advanced Cardiac Life Support) Guidelines.

Footnotes:

^[1] Position Statement on the Use of Amiodarone in Refractory Pulseless VT/VF
The AAEM Amiodarone for Refractory VT/VF Working Group is comprised of Amal Mattu, MD FAAEM, Carey Chisholm, MD FAAEM, and Jerome R. Hoffman, MA MD FAAEM.
American Academy of Emergency Medicine
Position Statements
May 5, 2001
Position Statement

^[2] Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia (ALPS)
ClinicalTrials.Gov
Last Updated on September 21, 2011
ClinicalTrials.gov Identifier: NCT01401647
Trial data

Filed Under: ACLS, Heresy, Pharmacology, Research

Images from Gathering of Eagles Presentation on RAMPART

Tue, 27 Mar 2012 08:00:51 +0000 By Rogue Medic 3 Comments

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.

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 [PubMed - in process]

^[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 [PubMed - indexed for MEDLINE]

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

Filed Under: Heresy, Midazolam, Pharmacology, Research, Sedation

Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part II

Fri, 23 Mar 2012 08:00:35 +0000 By Rogue Medic 3 Comments

Dr. Ken Grauer wrote a couple of extended comments in response to Killing Patients Just to Get a Temporary Pulse With Epinephrine.

Dr. Grauer has provided some commentary on this on his web site – KG-EKG Press.

ISSUE #10: Should We Still Use Epinephrine for Cardiac Arrest?

So, how bad was epinephrine in this study?

Dr. Grauer writes –

I am not a statistician – and I admit to not understanding much of the technical jargon in the methodological portions of this manuscript – BUT – the cited “propensity score” data for Epi administration to my reading seems highly contrived – and I have trouble accepting this concept as being valid in this nonrandomized observational study …

I am not a statistician, either. However, the epinephrine group had a bunch of large advantages in this study.

Click on images to make them larger.

In spite of those large advantages, the only advantage to the no epinephrine group was in response times being 7:18 vs. 7:54, the unadjusted results showed that patients did better without epinephrine.

What did the 2010 ACLS Guidelines recommend about epinephrine before this study was completed?

It is reasonable to consider administering a 1 mg dose of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest (Class IIb, LOE A).^[2]

It is only reasonable to consider giving epinephrine.

Not – It is mandatory to consider epinephrine.

Not – It is reasonable to give epinephrine.

Definitely Not – It is mandatory to give epinephrine.

Certainly Not – It is unethical to withhold epinephrine.

Absolutely Not – Giving epinephrine will improve outcomes.

ACLS does not state any of that.

Deemphasis on Devices and Advanced Cardiovascular Life Support Drugs During Cardiac Arrest
At the time of the 2010 International Consensus Conference there were still insufficient data to demonstrate that any drugs or mechanical CPR devices improve long-term outcome after cardiac arrest.⁴⁵ Clearly further studies, adequately powered to detect clinically important outcome differences with these interventions, are needed.^[3]

Clearly further studies, . . . , are needed.

It looks as if the AHA (American Heart Association) is ready to give up on epinephrine in cardiac arrest unless someone provides evidence of actual benefit to real patients.

50 years of traditional use of epinephrine, unimpeded by a lack of evidence.

Thus, properly evaluating this traditional therapy now seems necessary and timely and should consist of a rigorously conducted and adequately powered clinical trial comparing epinephrine with placebo during cardiac arrest. Such a trial has previously seemed unethical, and investigators who have attempted to perform this comparison have received unwarranted criticism in their communities.^17,19 While awaiting results of such a definitive trial, physicians and other practitioners involved in cardiac resuscitation must consider carefully whether continued use of epinephrine is justified.^[4]

You will notice that the list of authors for the 2010 ACLS Guidelines includes the same Dr. Callaway who wrote this editorial. This should be a hint of what we can expect from the next change in the guidelines. Dr. Callaway is not the only doctor involved in writing the guidelines, but the ACLS Committee as a whole has been moving away from medications and has been emphasizing high-quality chest compressions.

Unless there is a miracle and a new study shows some benefit from epinephrine in cardiac arrest, I expect epinephrine to be removed from the next revision of the ACLS Guideline.

The 2015 ACLS Guidelines –

Epinephrine is only recommended for asthma and anaphylaxis.

Why?

Those are the only medical emergencies that have evidence of benefit from epinephrine.

No more voodoo.

Footnotes:

Free Full Text in PDF format

^[2] Epinephrine
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Robert W. Neumar, Chair; Charles W. Otto; Mark S. Link; Steven L. Kronick; Michael Shuster; Clifton W. Callaway; Peter J. Kudenchuk; Joseph P. Ornato; Bryan McNally; Scott M. Silvers; Rod S. Passman; Roger D. White; Erik P. Hess; Wanchun Tang; Daniel Davis; Elizabeth Sinz; Laurie J. Morrison
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Vasopressors
Free Full Text from Circulation with link to PDF Download

^[3] Deemphasis on Devices and Advanced Cardiovascular Life Support Drugs During Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 1: Executive Summary
John M. Field, Co-Chair*; Mary Fran Hazinski, Co-Chair*; Michael R. Sayre; Leon Chameides; Stephen M. Schexnayder; Robin Hemphill; Ricardo A. Samson; John Kattwinkel; Robert A. Berg; Farhan Bhanji; Diana M. Cave; Edward C. Jauch; Peter J. Kudenchuk; Robert W. Neumar; Mary Ann Peberdy; Jeffrey M. Perlman; Elizabeth Sinz; Andrew H. Travers; Marc D. Berg; John E. Billi; Brian Eigel; Robert W. Hickey; Monica E. Kleinman; Mark S. Link; Laurie J. Morrison; Robert E. O’Connor; Michael Shuster; Clifton W. Callaway; Brett Cucchiara; Jeffrey D. Ferguson; Thomas D. Rea; Terry L. Vanden Hoek
New Developments in Resuscitation Science Since 2005
Free Full Text from Circulation with link to PDF Download

^[4] Questioning the Use of Epinephrine to Treat Cardiac Arrest
Clifton W. Callaway
JAMA. 2012;307(11):1198-1200.
doi:10.1001/jama.2012.313

And the accompanying interview in mp3 format on JAMA’s site –

Questioning the Use of Epinephrine to Treat Cardiac Arrest
Clifton W. Callaway
JAMA: March 21, 2012; Vol 307, No. 11,
Author Interview
podcast in mp3 format (06:29, 3.7 MB)

Hagihara, A., Hasegawa, M., Abe, T., Nagata, T., Wakata, Y., & Miyazaki, S. (2012). Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest JAMA: The Journal of the American Medical Association, 307 (11), 1161-1168 DOI: 10.1001/jama.2012.294

Callaway, C. (2012). Questioning the Use of Epinephrine to Treat Cardiac Arrest JAMA: The Journal of the American Medical Association, 307 (11), 1198-1200 DOI: 10.1001/jama.2012.313
.

Filed Under: 2010 AHA Guidelines, Epinephrine, Heresy, Pharmacology, Research