Furosemide is good for filling the patient’s bladder, but the patient probably did not call for help filling his/her bladder.

- Rogue Medic

The Media are Just As Bad at Ethics As They are at Science

 
There is another article about the adrenaline (epinephrine in non-Commonwealth countries) vs. placebo in cardiac arrest trial that is about to start in England.[1] Media sites no longer seem to want to spend money to get valid information on science or ethics. Forbes provides another example of the writer completely missing the obvious.
 

It’s one thing to treat an incapacitated emergency patient without consent, when you’re administering a standard therapy already proven to be beneficial.[2]

 

Nobody is being deprived of anything that has been adequately tested on humans. Why assume that the untested and unknown standard treatment is beneficial?

The active drug (adrenaline) is an unknown. There is no good evidence that adrenaline improves outcomes.

If you disagree, provide some evidence that shows that adrenaline is better than placebo at anything that matters.

Adrenaline is an unknown because it has never been adequately studied. The only study that has tried to compare it to placebo was limited by politicians and the media – the people who know the least about how science works.

This is like being told that you will be put in a room with either a killer or a mannequin. Which one do you want. Except that we do not know if adrenaline is a killer. We do not have enough information. The only way to find out is to study it.

The research so far is negative. Is that because the adrenaline is given too late? Is that because too much adrenaline is given? Is that because we give it to everyone still dead after a few minutes?

We do not know.

We treat adrenaline like snake oil – Able to cure all kinds of cardiac arrest. Step right up and get your magic elixir. Cures baldness, too!
 


Image credit.
 

When the sales pitch is that the drug fixes everything, we should be very suspicious.

Cardiac arrest due to blood loss?   Give adrenaline.

Cardiac arrest due to slow heart rate?   Give adrenaline.

Cardiac arrest due to fast heart rate?   Give adrenaline.

Cardiac arrest due to irritated heart?   Give adrenaline.

Cardiac arrest due to not enough stimulus to the heart?   Give adrenaline.

Cardiac arrest due to drug over-dose?   Give adrenaline.

Cardiac arrest due to drug under-dose?   Give adrenaline.

Cardiac arrest due to diabetes problem?   Give adrenaline.

Cardiac arrest due to infectious disease?   Give adrenaline.

Cardiac arrest due to lightning strike?   Give adrenaline.

Cardiac arrest due to drowning?   Give adrenaline.

Cardiac arrest due to asthma?   Give adrenaline.

Cardiac arrest due to stroke?   Give adrenaline.

Cardiac arrest due to cancer?   Give adrenaline.

Cardiac arrest due to adrenaline overdose?   Give adrenaline.

We do not discriminate. We just give adrenaline. All of the other drugs have failed to produce a benefit, but we still believe in adrenaline without good evidence. We have been using adrenaline for over half a century on unsuspecting people and we still have no evidence that it works.
 

However, the more important issue is what you as a patient think. Should scientists be able to enroll you in a life-or-death medical experiment without your consent?[2]

 

Adrenaline has worked in laboratory animals, but every drug that is tested in humans is supposed to have worked in animals. Why doesn’t adrenaline work in humans? If it does work, where is the evidence?

The standard of care is an experiment that is not controlled and not even acknowledged. The guidelines clearly state that we do not know what works and that we should only consider adrenaline, but that we do not have any good evidence that adrenaline improves outcomes for anyone.

The ethical failure is that we have failed to find out if what we are giving is harmful.
 

We have only improved outcomes when we have ignored the drugs and paid attention to chest compressions and defibrillation.
 

We are lying to patients when we tell them that we know what works in cardiac arrest.

How much worse than placebo is adrenaline? We don’t know. Failing to find out is what is unethical.

Footnotes:

[1] Does a Placebo vs. Adrenaline Study Deprive Patients of Necessary Care According to the Resuscitation Guidelines?
Wed, 27 Aug 2014
Rogue Medic
Article

[2] UK To Experiment on Cardiac Arrest Patients Without Their Consent
8/27/2014 @ 3:55PM
Paul Hsieh – Contributor
Forbes
Article

.

Does a Placebo vs. Adrenaline Study Deprive Patients of Necessary Care According to the Resuscitation Guidelines?


 Some in the media have been critical of the upcoming British study of adrenaline (epinephrine) vs. placebo for cardiac arrest.[1] They assume that the guidelines require that we give adrenaline, but that is not true.

The guidelines only state that adrenaline may be considered.

If you are a dog, pig, or rat in a laboratory and you have had an artificially induced cardiac arrest, then adrenaline will help resuscitate you. If you are a human who has a cardiac arrest for any one of a variety of reasons, then there is not a good reason to give this rat resuscitation drug, which has not been adequately studied in humans.

There probably are some human patients who do benefit from adrenaline in cardiac arrest, but we have no idea which patients those are and there probably are humans who are harmed by adrenaline. The most common cause of cardiac arrest is heart attack, but you were having a heart attack while still alive, is there a worse drug we could give you than adrenaline? Does adrenaline suddenly become sugar and spice and everything nice, just because we cannot feel a pulse? Maybe, but should we assume that?

What if you have lost so much blood that your heart is not able to produce a pulse, even though your heart is beating as hard as it can? Adrenaline is indicated according to the same guidelines. Why? Unreasonable optimism.

Which patients benefit from adrenaline? We don’t know.

Which patients are harmed by adrenaline? We don’t know.

How do we find out? Research, such as the upcoming study of adrenaline (epinephrine).

What do the guidelines say about conducting this research?
 

Given the observed benefit in short-term outcomes, the use of epinephrine or vasopressin may be considered in adult cardiac arrest.

Knowledge Gaps

Placebo-controlled trials to evaluate the use of any vasopressor in adult and pediatric cardiac arrest are needed.[2]

 

Vasopressors are adrenaline, vasopressin, norepinephrine, and phenylephrine. We need evidence to find out if any of them work.

When the 2010 guidelines were written there was an inescapable need for placebo studies.

Has anything changed?

No.

There was a placebo study in 2012 that was aborted by pressure from media and politicians before any useful results could be obtained.[3]
 

There is evidence that adrenaline improves the return of a pulse, but that appears to just produce comatose patients who die in the hospital without waking up, so the initial improvement appears to be very misleading.

We could try real medicine, where we find out what the right treatment is and give the right treatment to the right patient, but that seems to be asking too much for some people.
 

The Media are Just As Bad at Ethics As They are at Science

Footnotes:

[1] The Controversy of Admitting ‘We Do Not Know What Works’
Wed, 13 Aug 2014
Rogue Medic
Article

[2] Part 8: Advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.
Morrison LJ, Deakin CD, Morley PT, Callaway CW, Kerber RE, Kronick SL, Lavonas EJ, Link MS, Neumar RW, Otto CW, Parr M, Shuster M, Sunde K, Peberdy MA, Tang W, Hoek TL, Böttiger BW, Drajer S, Lim SH, Nolan JP; Advanced Life Support Chapter Collaborators.
Circulation. 2010 Oct 19;122(16 Suppl 2):S345-421. doi: 10.1161/CIRCULATIONAHA.110.971051. No abstract available.
PMID: 20956256 [PubMed – indexed for MEDLINE]

Free Full Text from Circulation.

[3] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
Resuscitation. 2011 Sep;82(9):1138-43. Epub 2011 Jul 2.
PMID: 21745533 [PubMed – in process]

Free Full Text PDF Download of In Press Uncorrected Proof from xa.yming.com
 

This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.

 

In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.

 

.

Opponents of EBM Now Have More Evidence to Justify Their Rejection of Evidence


 

Those scientists clearly can’t get it right. They are constantly changing the guidelines to correct their mistakes. Why don’t they just do it right the first time.

Finally, somebody is recognizing that a treatment should only be eliminated when there is clear evidence that it harms patients – and only when we have run out of excuses to ignore the irrefutable evidence.
 

The 2015 American Heart Organization (AHO) Cardiovascular Care Guidelines will introduce three new levels of evidence in addition to the current existing levels of evidence
In addition to the current levels of evidence classes the AHO’s 2015 guidelines will include Class IVa (Anecdotal Evidence), Class V (Provider Opinion) and Class XI (Treatments Not Proven to Not Work)
[1]

 

When I was in paramedic school we were told the rules. Intubation is the most important treatment, because the airway is the most important part of patient care, because Airway begins with A, Breathing begins with B, and Circulation begins with C. A comes before B and B comes before C.

Do you think that is a coincidence? No. There’s a reason for that. We are supposed to treat the airway first – no matter what. A paramedic can only have one thought in his head at a time, so it has to be the one best thought. Airway always comes first. Did you ever try to live without an airway? Well, did you? It just doesn’t happen. The Gold Standard of Airway is intubation, so we have to intubate people or they will be dropping like flies. You don’t hear about people surviving in places where medics don’t intubate. Dead! All of ‘em. Dead! It’s a fact.

This is serious business people. Every second counts, but there are a lot of seconds, so we don’t count seconds. We count minutes. So every minute counts, but only with an Airway. Without an Airway, you are dead, but you are only dead after we race your cadaver to the hospital and a doctor pronounces you dead and mutters something under his breath about us being straight out of the Dark Ages. We do respect the classics. We have to honor our roots. We can’t be eliminating traditional treatments just because they seem to harm patients.
 

AHO includes the following in the new guidelines, section IVa (Anecdotal Evidence): “Many people have seem something work or they know of someone who has seen something work, or perhaps have heard of someone who knows someone that has seem something work. If a treatment has been said to work in the past then it stands to reason that it will work again. The AHA now accepts anecdotal evidence as equivalent to and just as valid as a Class I intervention provided that the evidence is no more than 4 degrees of separation from the person.”[1]

 

They shouldn’t have left out treatments based on animal research. We have to include everything. It doesn’t matter that people do not do as well with these treatments as animals do. Don’t you love dogs and cats, or are you some kind of monster? If a treatment can bring a dog back to life then that is good enough for grandpa. If cancer can be cured in animals, but we don’t give the treatments to people we are killing people. It is a Big Pharma conspiracy to find cures and then hide them from everyone, because that is why these scientists do all of this research – so they can have the cures for themselves and watch us die. If it works in animals, there is no reason to not use it in people.

All of this research is just too expensive.

We need to just use what we know works.
 

Go read the full article.

Footnotes:

[1] Heart Organization Endorses New Level of Evidence Guildlines
Call The Cops
Posted by: RJ Beam
8/20/2014
Article

.

The Controversy of Admitting ‘We Do Not Know What Works’

ResearchBlogging.org

 

There are several news articles today criticizing a study because the patients might be deprived of a drug that has not been adequately studied in humans. This criticism is coming from journalists – the people who publicized the fraudulent vaccines research by Andrew Wakefield, who was trying to sell his competing vaccine and was being paid to produce negative research by lawyers suing the vaccine companies.[1]

The real controversy is that this untested drug became the standard of care with no evidence that it improves outcomes that matter.

Is it controversial to give a placebo, rather than a drug not yet adequately tested in humans?

No.

We are not informing patients that there is no evidence that the standard treatment is effective. We are not obtaining consent to give the unproven drug – epinephrine (Adrenaline in Commonwealth countries). How are the ethics different when we substitute a placebo for a mystery medicine?

What is less ethical than continuing the tradition of giving an inadequately studied drug to people who cannot consent to treatment?

Are we depriving patients of effective medicine or are we depriving them of witchcraft?

If you think that epinephrine is effective medicine at improving survival to discharge, provide the evidence and stop this study. The reason the study is being done is that evidence of benefit does not exist.
 

Click on image to make it larger.[2] The studies are in the footnotes.[3],[4],[5],[6],[7],[8],[9],[10]
 

Is Adrenaline beneficial in cardiac arrest?

Probably, but only for some patients and we do not know which patients benefit.

Is Adrenaline harmful in cardiac arrest?

Probably, but only for some patients and we do not know which patients are harmed.

What is the right dose of Adrenaline in cardiac arrest?

Pick a number – any number. We do not know the right dose.
 

 

Even the patients who only received the minimum dose – 1 mg – had worse outcomes.[11]

Wrong timing? Wrong dose? Wrong drug?

We do not know.
 

We have used this untested treatment for half a century and not bothered to find out if it works. A recent study shows that epinephrine produces worse outcomes when given by EMS later,[12] but that does not mean that the outcomes are good when epinephrine is given early. The study had no placebo group, so like a study comparing different doses of cyanide, just because one dose is not as bad as another dose, the results do not suggest that cyanide is beneficial.
 


 

This is comparing three different treatments HDE (High-Dose Epinephrine), SDE (Standard-Dose Epinephrine), and NE (NorEpinephrine). The lines for the HDE and NE are so close to each other, that you may not be able to see the gold line.[13] Other studies produce similar results.[3],[14],[15],[16],[17] Only one study showed better ROSC with standard dose epinephrine.[18]
 

Epinephrine does produce more ROSC (Return Of Spontaneous Circulation – at least a temporary pulse) than placebo, but high dose epinephrine produces even more ROSC than standard dose epinephrine, so why do we give the standard dose that only produces middling ROSC?

Is ROSC the goal? No.

For the guidelines (ACLS and ILCOR), ROSC is the basis for giving standard dose epinephrine, but it would make more sense to give high dose epinephrine if the goal is ROSC. More ROSC, but no more survivors leaving the hospital. If all we want is put the patient in a coma long enough to run up a big hospital bill, then the drugs are great.

If we want people to leave the hospital alive, then We Do Not Know What Works.
 

The guidelines are based on wishful thinking and rationalization. They are not based on improved survival. A lot of research is cited (hundreds of papers), but the research does not show improved survival with any drug(s).

Will the guidelines be revised to remove epinephrine? Maybe.
 

The exciting development is that these data create equipoise about the current standard of resuscitation care. The best available observational evidence indicates that epinephrine may be harmful to patients during cardiac arrest, and there are plausible biological reasons to support this observation. However, observational studies cannot establish causal relationships in the way that randomized trials can.[19]

 

Some cocktails have produced better results than epinephrine in tiny studies. It is too probably too early to tell if these are just statistical aberrations. I will write about them later.

Continued in Does a Placebo vs. Adrenaline Study Deprive Patients of Necessary Care According to the Resuscitation Guidelines?

Footnotes:

[1] “Piltdown medicine” and Andrew Wakefield’s MMR vaccine fraud
Science-Based Medicine
Posted by David Gorski
January 6, 2011
Article
 

In a mere decade and a half, several decades of progress in controlling this scourge had been unravelled like a thread hanging off a cheap dress, all thanks to Andrew Wakefield and scandal mongers in the British press.

[2] Vasopressors in cardiac arrest: a systematic review.
Larabee TM, Liu KY, Campbell JA, Little CM.
Resuscitation. 2012 Aug;83(8):932-9. Epub 2012 Mar 15.
PMID: 22425731 [PubMed – in process]
 

CONCLUSION: There are few studies that compare vasopressors to placebo in resuscitation from cardiac arrest. Epinephrine is associated with improvement in short term survival outcomes as compared to placebo, but no long-term survival benefit has been demonstrated. Vasopressin is equivalent for use as an initial vasopressor when compared to epinephrine during resuscitation from cardiac arrest. There is a short-term, but no long-term, survival benefit when using high dose vs. standard dose epinephrine during resuscitation from cardiac arrest. There are no alternative vasopressors that provide a long-term survival benefit when compared to epinephrine. There is limited data on the use of vasopressors in the pediatric population.

[3] High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest.
Woodhouse SP, Cox S, Boyd P, Case C, Weber M.
Resuscitation. 1995 Dec;30(3):243-9.
PMID: 8867714 [PubMed – indexed for MEDLINE]

[4] Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference?
Herlitz J, Ekström L, Wennerblom B, Axelsson A, Bång A, Holmberg S.
Resuscitation. 1995 Jun;29(3):195-201.
PMID: 7667549 [PubMed – indexed for MEDLINE]

[5] Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest.
Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, Ong VY, Lim SH, Yap S, Tham LP, Ng KS, Venkataraman A; Cardiac Arrest and Resuscitation Epidemiology Study Group.
Ann Emerg Med. 2007 Dec;50(6):635-42. Epub 2007 May 23.
PMID: 17509730 [PubMed – indexed for MEDLINE]

Free Full Text Download in PDF format from prdupl02.ynet.co.il

[6] Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L.
JAMA. 2009 Nov 25;302(20):2222-9.
PMID: 19934423 [PubMed – indexed for MEDLINE]

Free Full Text from JAMA

[7] Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial.
Olasveengen TM, Wik L, Sunde K, Steen PA.
Resuscitation. 2011 Nov 22. [Epub ahead of print]
PMID: 22115931 [PubMed – as supplied by publisher]

[8] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
Resuscitation. 2011 Sep;82(9):1138-43. Epub 2011 Jul 2.
PMID: 21745533 [PubMed – in process]

Free Full Text PDF Download of In Press Uncorrected Proof from xa.yming.com
 

This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.

 

In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.

 

[9] Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.
Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S.
JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
PMID: 22436956 [PubMed – indexed for MEDLINE]

Free Full Text from JAMA.

[10] Impact of early intravenous epinephrine administration on outcomes following out-of-hospital cardiac arrest.
Hayashi Y, Iwami T, Kitamura T, Nishiuchi T, Kajino K, Sakai T, Nishiyama C, Nitta M, Hiraide A, Kai T.
Circ J. 2012;76(7):1639-45. Epub 2012 Apr 5.
PMID: 22481099 [PubMed – indexed for MEDLINE]

Free Full Text from Circulation Japan.

[11] Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium.
Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P; Resuscitation Outcomes Consortium Investigators.
Resuscitation. 2012 Nov;83(11):1324-30. doi: 10.1016/j.resuscitation.2012.07.008. Epub 2012 Jul 31.
PMID: 22858552 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

[12] Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C; American Heart Association’s Get With The Guidelines-Resuscitation Investigators.
BMJ. 2014 May 20;348:g3028. doi: 10.1136/bmj.g3028.
PMID: 24846323 [PubMed – in process]

Free Full Text from BMJ.

[13] A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest.
Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J.
JAMA. 1992 Nov 18;268(19):2667-72.
PMID: 1433686 [PubMed – indexed for MEDLINE]

[14] A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group.
Brown CG, Martin DR, Pepe PE, Stueven H, Cummins RO, Gonzalez E, Jastremski M.
N Engl J Med. 1992 Oct 8;327(15):1051-5.
PMID: 1522841 [PubMed – indexed for MEDLINE]

Free Full Text from NEJM.

[15] Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital.
Choux C, Gueugniaud PY, Barbieux A, Pham E, Lae C, Dubien PY, Petit P.
Resuscitation. 1995 Feb;29(1):3-9.
PMID: 7784720 [PubMed – indexed for MEDLINE]

[16] A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group.
Gueugniaud PY, Mols P, Goldstein P, Pham E, Dubien PY, Deweerdt C, Vergnion M, Petit P, Carli P.
N Engl J Med. 1998 Nov 26;339(22):1595-601.
PMID: 9828247 [PubMed – indexed for MEDLINE]

Free Full Text from NEJM.

[17] High dose versus standard dose epinephrine in cardiac arrest – a meta-analysis.
Vandycke C, Martens P.
Resuscitation. 2000 Aug 1;45(3):161-6.
PMID: 10959014 [PubMed – indexed for MEDLINE]

[18] High-dose epinephrine in adult cardiac arrest.
Stiell IG, Hebert PC, Weitzman BN, Wells GA, Raman S, Stark RM, Higginson LA, Ahuja J, Dickinson GE.
N Engl J Med. 1992 Oct 8;327(15):1045-50.
PMID: 1522840 [PubMed – indexed for MEDLINE]

Free Full Text from NEJM.

[19] Questioning the use of epinephrine to treat cardiac arrest.
Callaway CW.
JAMA. 2012 Mar 21;307(11):1198-200. doi: 10.1001/jama.2012.313. No abstract available.
PMID: 22436961 [PubMed – indexed for MEDLINE]

Link to a free 6 1/2 minute recording of an interview with Dr. Callaway about this paper.

On the right side of the page, to the right of the First Page Preview, is a section with the title Multimedia Related by Topic. Below that is Author Interview. Below that is some information about the edition, . . . , and below that is an embedded recording of the interview. Press on the arrow to play. That has the recording of the interview with Dr. Callaway.

The interview with Dr. Callaway is definitely worth listening to.

Larabee TM, Liu KY, Campbell JA, & Little CM (2012). Vasopressors in cardiac arrest: a systematic review. Resuscitation, 83 (8), 932-9 PMID: 22425731

Woodhouse SP, Cox S, Boyd P, Case C, & Weber M (1995). High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest. Resuscitation, 30 (3), 243-9 PMID: 8867714

Herlitz J, Ekström L, Wennerblom B, Axelsson A, Bång A, & Holmberg S (1995). Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference? Resuscitation, 29 (3), 195-201 PMID: 7667549

Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, Ong VY, Lim SH, Yap S, Tham LP, Ng KS, Venkataraman A, & Cardiac Arrest and Resuscitation Epidemiology Study Group (2007). Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Annals of emergency medicine, 50 (6), 635-42 PMID: 17509730

Olasveengen, T., Sunde, K., Brunborg, C., Thowsen, J., Steen, P., & Wik, L. (2009). Intravenous Drug Administration During Out-of-Hospital Cardiac Arrest: A Randomized Trial JAMA: The Journal of the American Medical Association, 302 (20), 2222-2229 DOI: 10.1001/jama.2009.1729

Olasveengen TM, Wik L, Sunde K, & Steen PA (2011). Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial. Resuscitation PMID: 22115931

Jacobs IG, Finn JC, Jelinek GA, Oxer HF, & Thompson PL (2011). Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation, 82 (9), 1138-43 PMID: 21745533

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), 1161-8 PMID: 22436956

Hayashi Y, Iwami T, Kitamura T, Nishiuchi T, Kajino K, Sakai T, Nishiyama C, Nitta M, Hiraide A, & Kai T (2012). Impact of early intravenous epinephrine administration on outcomes following out-of-hospital cardiac arrest. Circulation journal : official journal of the Japanese Circulation Society, 76 (7), 1639-45 PMID: 22481099

Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P, & the Resuscitation Outcomes Consortium Investigators (2012). Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium. Resuscitation PMID: 22858552

Donnino, M., Salciccioli, J., Howell, M., Cocchi, M., Giberson, B., Berg, K., Gautam, S., Callaway, C., & , . (2014). Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry BMJ, 348 (may20 2) DOI: 10.1136/bmj.g3028

Callaham M, Madsen CD, Barton CW, Saunders CE, & Pointer J (1992). A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. JAMA : the journal of the American Medical Association, 268 (19), 2667-72 PMID: 1433686

Brown CG, Martin DR, Pepe PE, Stueven H, Cummins RO, Gonzalez E, & Jastremski M (1992). A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. The New England journal of medicine, 327 (15), 1051-5 PMID: 1522841

Choux C, Gueugniaud PY, Barbieux A, Pham E, Lae C, Dubien PY, & Petit P (1995). Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital. Resuscitation, 29 (1), 3-9 PMID: 7784720

Gueugniaud PY, Mols P, Goldstein P, Pham E, Dubien PY, Deweerdt C, Vergnion M, Petit P, & Carli P (1998). A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group. The New England journal of medicine, 339 (22), 1595-601 PMID: 9828247

Vandycke C, & Martens P (2000). High dose versus standard dose epinephrine in cardiac arrest – a meta-analysis. Resuscitation, 45 (3), 161-6 PMID: 10959014

Stiell IG, Hebert PC, Weitzman BN, Wells GA, Raman S, Stark RM, Higginson LA, Ahuja J, & Dickinson GE (1992). High-dose epinephrine in adult cardiac arrest. The New England journal of medicine, 327 (15), 1045-50 PMID: 1522840

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

.

Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest

ResearchBlogging.org
 

This study is interesting for several reasons.

In a system that claims excellence, the most consistent way to identify the study group is by documentation of a protocol violation – but it is not intended as a study of protocol violations.

This may hint at some benefit from epinephrine (Adrenaline in Commonwealth countries), but that would require some study and we just don’t study epinephrine. We only make excuses for not studying epinephrine.

The atropine results suggest that the epinephrine data may be just due to small numbers, or that we may want to consider atropine for drug overdose cardiac arrest patients, or . . . .

The Sodium Bicarbonate (bicarb – NaHCO3) results suggest a flaw in EMS education (probably testing, too). If the patient is acidotic, this is one type of cardiac arrest where hyperventilation may be beneficial. Bicarb is the part of the drug that doesn’t do much, especially if the patient is dead. The sodium is what works, such as when the patient has taken too much of a sodium channel blocker, such as a tricyclic antidepressant or a class I antiarrhythmic. Acidosis is treated by hyperventilation. Use capnography.

Most important – antidotes probably don’t work as expected during cardiac arrest. Not even naloxone (Narcan).
 

Despite clear differences in the etiology of suspected OD [OverDose] and non-OD OHCA [Out of Hospital Cardiac Arrest], the International Liaison Committee on Resuscitation guidelines published in 2010 do not specify different treatments for suspected OD-OHCA patients during resuscitation,and state that there is no evidence promoting the intra-arrest administration of the opioid antagonist naloxone.8 [1]

 

What did they find in the study?

They may have located the highest concentration of heroin overdose in the country. 93% of OD-OHCA patients were treated with naloxone.
 

We relied on either naloxone administration or clear description of circumstantial evidence in the PCR [Patient Care Recod] to identify a suspected OD. Clear descriptions are also rare, and most (93%) of the cases were identified by naloxone administration. Naloxone during cardiac arrest is not part of any regional protocol, and all of these administrations are deviations from recommended practice. There may be other cases in which paramedics suspected OD, but did not deviate from protocol to administer naloxone. Therefore, it is impossible to be certain whether the actual number of OD cases is larger or smaller than the reported number. However, the use of naloxone as a proxy indicator of suspected OD has been supported in the literature.11 [1]

 

The EMS approach to naloxone still appears to be –
 


Image credits – 123
 

These results seem to show better response to the prehospital drugs in the OD-OHCA patients, but that ignores the ROSC (Return Of Spontaneous Circulation) rates.
 


Click on images to make them larger.
 

Why would OD-OHCA patients do better than non-OD-OHCA patients if they get a pulse back?

The average non-OD-OHCA patient is 20+ years older. These older patients may not be as capable of recovery nor as capable of tolerating the toxicity of the drugs they were treated with.

The change after ROSC is dramatic. Is that the important point of this study?

Are they doing anything special for OD patients in the hospital, or is it just a matter of That which does not kill me by anoxic brain damage, may allow me to recover twice as often as a typical cardiac arrest patient.
 

Do drugs (antidotes, antiarrhythmics, . . . ) work the same way in dead people as in living people?
 

Pharmacologic insults are just so massive and normal metabolism and physiology so deranged that no mere mortal can make a meaningful intervention. The seriously poisoned who maintain vital signs in the ED have the best, albeit never guaranteed, chance of rescue from a modicum of antidotes and intensive supportive care.[2]

 

We should understand that normal metabolism is irrelevant to cardiac arrest.

We should understand that we do not need to ventilate adult cardiac arrest patients, when the cause is cardiac. An absence of ventilation would not be appropriate in a living adult, but dead metabolism is not normal. If something as basic as oxygen changes, when the patient is dead, how much less do we understand the behavior of other drugs in dead patients?

Footnotes:

[1] Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest.
Koller AC, Salcido DD, Callaway CW, Menegazzi JJ.
Resuscitation. 2014 Jun 26. pii: S0300-9572(14)00581-4. doi: 10.1016/j.resuscitation.2014.05.036. [Epub ahead of print]
PMID: 24973558 [PubMed – as supplied by publisher]

[2] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Emergency Medicine News:
October 2011 – Volume 33 – Issue 10 – pp 16-18
doi: 10.1097/01.EEM.0000406945.05619.ca
InFocus
Roberts, James R. MD
Article

Roberts, J. (2011). InFocus: Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions Emergency Medicine News, 33 (10), 16-18 DOI: 10.1097/01.EEM.0000406945.05619.ca

Koller, A., Salcido, D., Callaway, C., & Menegazzi, J. (2014). Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest Resuscitation DOI: 10.1016/j.resuscitation.2014.05.036

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NYFD EMS Loses $172 Million Suit

 

What does a $172 million loss mean?

1. Something very bad happened.

2. The jury probably thought that the defense sucked.

3. The amount paid will probably be much lower.

4. We continue to face the opposite of intermittent reinforcement – intermittent negative reinforcement – and we continue to respond unwisely.[1]

5. This will be the excuse for a lot of bad management decisions.

What happened?
 

Image credit.
 

 

A girl who suffered brain damage while waiting for an ambulance won a $172 million judgment against New York City on Wednesday when a Bronx jury determined that Fire Department paramedics could be held liable for giving her mother bad advice.[2]

 

Bad advice?

Wait for the paramedics during a cardiac arrest, rather than transport to the hospital. The medics took 20 minutes to arrive. The child has brain damage.

Was the advice bad?

This took place in 1998, when transport was considered to be important by a lot of people, because the hospital can do so much more of the things that improve outcomes than EMS can, except that the only two treatments that we know improve outcomes are continuous chest compressions and defibrillation. We knew that back then. The main thing we have learned since then is that interruptions of compressions, such as for transport, worsen outcomes.
 

Tiffany’s mother, Samantha Applewhite, called 911, and the city sent two Fire Department medics in a basic ambulance, without the advanced life support equipment she needed, the documents said. One medic began cardiopulmonary resuscitation while the other called for an ambulance with the proper equipment. The city paramedics also failed to bring oxygen or a defibrillator, evidence at trial showed.[2]

 

ALS (Advanced Life Support) equipment has never been shown to improve outcomes, unless the BLS (Basic Life Support) ambulances did not carry defibrillators (AEDs – Automated External Defibrillators). This states that they did not bring their defibrillator, which suggests that they carried and AED, but left it in the ambulance with the oxygen.

Should they have brought the AED to the scene? What did dispatch tell them was going on? NYFD EMS (New York Fire Department EMS) probably had a policy describing what equipment is required for certain calls. Cardiac arrest should require an AED (and oxygen and especially suction [because everyone seems to forget suction]), but was this dispatched as a cardiac arrest? The article does not tell us.

Suppose they do transport. One person is doing compressions, while the other is driving, or did they have more personnel on scene? We do not know.

Was the rhythm shockable? We don’t know. If they had brought the AED, it should have recorded the rhythm and would be able to answer that question, but according to the article, they did not.
 

Ms. Applewhite begged the city paramedics to take her daughter to Montefiore Hospital, a few minutes away, but they advised her to wait for the private ambulance with advanced life support equipment to arrive, the evidence showed.[1]

 

Does it really matter how far away the hospital is?

No.

What about immunity from liability?
 

A trial court at first dismissed the lawsuit, ruling the Applewhites had failed to prove the city had assumed a special affirmative duty to take care of the girl by responding to the call.

But the appellate division disagreed, saying the mother “justifiably relied” on the emergency responders, “who had taken control of the emergency situation and who elected to await” the private ambulance.[2]

 

Maybe we should be a lot better at sharing information and decisions with patients.

Maybe our protocols should be a lot better at encouraging us to share information and decisions with patients.

Did the crew do a bad job? Did they coerce decisions from the mother?

I don’t know.

A bad outcome is not proof of bad patient care.

How much do law suits improve our care?

Do law suits lead to improved patient care?

Do law suits lead to worse patient care?

Maybe a bit of both. Maybe a lot more harm than benefit? The evidence on law suits is that they are unpredictable

Footnotes:

[1] Intermittent reinforcement
Wikipedia
Article

[2] Jury Awards $172 Million in Verdict Against New York City
By James C. McKinley Jr.
May 29, 2014
NY Times
Article

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Does Faster Epinephrine Administration Produce Better Outcomes from PEA-Asystole?

ResearchBlogging.org
 

If we are going to give epinephrine (Adrenaline in Commonwealth countries) to patients with rhythms that are not shockable (PEA [Pulseless Electrical Activity] or Asystole), it appears that patients receiving epinephrine earlier have better outcomes than patients who receive epinephrine later in the hospital in the less acute care settings.

Does this mean that patients who receive epinephrine have better outcomes than patients who do not receive epinephrine?

We remain willfully ignorant of the answer to that question.
 

Apart from cardiopulmonary resuscitation, no intervention has been shown to be efficacious in patients with non-shockable cardiac arrest.[1]

 

Would a placebo group have had better outcomes than the patients who received epinephrine the earliest? We have no way of knowing, because we discourage asking about what we take for granted.

 

We excluded patients with cardiac arrest in the emergency department, intensive care unit, or surgical or other specialty care or procedure areas,[1]

 


 

This does show an impressive association between giving epinephrine earlier and improved outcomes.

Does this mean that we should avoid giving epinephrine (a drug not yet adequately tested in humans) after a certain amount of time?

Does this mean that we should prioritize giving epinephrine (a drug not yet adequately tested in humans) before a certain amount of time?

Until we find out how harmful/beneficial epinephrine is compared to placebo, we do not know if we are helping with epinephrine, harming with epinephrine, or which patients we might be helping and which patients we might be harming. We have a half a century of I don’t know and I don’t care.
 

Despite a strong physiologic rationale and anecdotal reports of efficacy, there are no well controlled trials of epinephrine to assess endpoints such as improved survival and neurologically intact survival. A randomized trial failed to show efficacy for advanced cardiac life support drugs, and extrapolation to the potential lack of efficacy of epinephrine has been suggested; the dose, timing, and even use of epinephrine remains controversial.15-16 [1]

 

But some of the anecdotes are really good anecdotes!

Anecdote-based treatment is just ignorance-based treatment. We assume that we know what we are doing, but we are only imitating Skinner’s pigeons in our reaction to stimuli.
 


Download YouTube Video | YouTube to MP3: Vixy | Replay Media Catcher
 

We have fancier uniforms than the pigeons, but we are just as unaware of the source of our stimuli.
 

The data was prospectively obtained using specifically defined variables, but the study was a retrospective analysis of that data.
 

Because data were used primarily as the local site for quality improvement, sites were granted a waiver of informed consent under the common rule.[1]

 

Because of the way the data are entered, any errors are likely to be at time of entry and may not be capable of being detected at the time of analysis for research. The numbers are very large – 25,095 patients – so that should correct for idiosyncratic errors, but what about cultural errors?

 

In the sensitivity analyses with adjustment for delays in initiation of cardiopulmonary resuscitation, time to epinephrine administration remained independently associated with survival to hospital discharge after multivariable adjustments.[1]

 

In the context of our findings, future investigations should consider timing of epinephrine administration in design and interpretation.[1]

 

We should also consider that epinephrine, if it is beneficial, is probably only beneficial to some patients. We need to try to identify those patients. Our current method of give epinephrine to everybody and let the emergency department sort them out is not reasonable.

This study ran from 2000 to 2009, so the improvements due to the focus on chest compressions might only affect a tiny portion of patients.[2]

Does epinephrine administration – at any time – produce better outcomes from PEA-asystole?

We still have no idea.

Footnotes:

[1] Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C; American Heart Association’s Get With The Guidelines-Resuscitation Investigators.
BMJ. 2014 May 20;348:g3028. doi: 10.1136/bmj.g3028.
PMID: 24846323 [PubMed – in process]

Free Full Text from BMJ.

[2] Delayed prehospital implementation of the 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care.
Bigham BL, Koprowicz K, Aufderheide TP, Davis DP, Donn S, Powell J, Suffoletto B, Nafziger S, Stouffer J, Idris A, Morrison LJ; ROC Investigators.
Prehosp Emerg Care. 2010 Jul-Sep;14(3):355-60.
PMID: 20388032 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

On December 13, 2005, the AHA published “Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care”

ROC EMS agencies required an average of 416 days to implement the 2005 AHA guidelines for OHCA. Small EMS agencies, BLS-only agencies, and nontransport agencies took longer than large agencies, agencies providing ALS care, and transport agencies, respectively, to implement the guidelines.

How relevant is that to implementation in the less acute care settings studied in these hospitalized patients?

Bigham BL, Koprowicz K, Aufderheide TP, Davis DP, Donn S, Powell J, Suffoletto B, Nafziger S, Stouffer J, Idris A, Morrison LJ, & ROC Investigators (2010). Delayed prehospital implementation of the 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors, 14 (3), 355-60 PMID: 20388032

Donnino, M., Salciccioli, J., Howell, M., Cocchi, M., Giberson, B., Berg, K., Gautam, S., Callaway, C., & , . (2014). Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry BMJ, 348 (may20 2) DOI: 10.1136/bmj.g3028

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The Silver Lining of Epi – Organ Donation – Part 2

 

Continuing from Part 1. In writing about why we should not get rid of epinephrine, Scott makes the following statement –
 

Patients who receive epinephrine in cardiac arrests have worse outcomes.[1]

 

Go read the full paragraph. I am not taking that out of context.

Scott suggests that this is acceptable, because some of these patients will be brain dead and some of those brain dead patients will end up being organ donors.

While it is true that some of those resuscitated from cardiac arrest following administration of epinephrine will end up being organ donors, should that affect our attempts to resuscitate the patient? Currently, the AHA (American Heart Association) does not encourage using treatments that may produce worse outcomes just for the purposes of increasing the number of organ donors.[2]
 

Even hearts can be transplanted from cardiac arrest patients can produce good outcomes.[3]
 


 

So far, so good.
 

Maybe it is time to look at them from a different angle. We need to look at dealing with a cardiac arrest in stages. Stage one, of course, is to work as hard as we can to achieve ROSC. ROSC is an absolute: there is a pulse, or there is not a pulse.[1]

 

How much harm do we do in order to get more ROSC (Return Of Spontaneous Circulation)?

ROSC is binary, but there are many ways to obtain ROSC.

The way we obtain ROSC seems to affect the survival of the patient and the brain function in those who do survive.
 

This is comparing three different treatments HDE (High-Dose Epinephrine), SDE (Standard-Dose Epinephrine), and NE (NorEpinephrine). The lines for the HDE and NE are so close to each other, that you may not be able to see the gold line.[4]
 

Compare that chart of HDE, SDE, and NE with this chart comparing Epinephrine and No Epinephrine.[5]
 


 

More ROSC, but fewer survivors.[6]

More organs, because of fewer survivors of cardiac arrest?

Is this our goal?

We could take the extreme utilitarian approach of Your organs can benefit far more people – if they are not in you.

Scott wouldn’t advocate for that with any other patient, so why head that way with cardiac arrest?
 

Patients who receive epinephrine in cardiac arrests have worse outcomes.[1]

 

Is epinephrine the cause of the harm? We do not know and we are perversely not trying to find out.

If giving epinephrine decreases survival from cardiac arrest, then giving epinephrine increases the pool of available organs at the expense of our original cardiac arrest patients. That is not the goal.

Organ donation is important. Harming patients, in order to obtain more organs, is not the goal of organ donation.

Footnotes:

[1] The Silver Lining of Epi
February 3, 2014
EMS in the New Decade
Scott
Article

[2] Organ Donation After Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 9: Post–Cardiac Arrest Care
Free Full Text from AHA.

[3] Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation.
Ali AA, Lim E, Thanikachalam M, Sudarshan C, White P, Parameshwar J, Dhital K, Large SR.
Eur J Cardiothorac Surg. 2007 May;31(5):929-33. Epub 2007 Mar 26.
PMID: 17387020 [PubMed – indexed for MEDLINE]

Free Full Text from Eur J Cardiothorac Surg.

[4] A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest.
Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J.
JAMA. 1992 Nov 18;268(19):2667-72.
PMID: 1433686 [PubMed – indexed for MEDLINE]

[5] Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.
Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S.
JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
PMID: 22436956 [PubMed – indexed for MEDLINE]

Free Full Text from JAMA.

[6] Are We Killing People With ROSC?
Wed, 05 Jun 2013
Rogue Medic
Article

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