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

- Rogue Medic

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 from semanticscholar.org
 

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.

 

Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 3.

.

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 from semanticscholar.org
 

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

Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 8.

.

When is a double dose of defibrillation a good idea?

 
In the comments to Double simultaneous defibrillators for refractory ventricular fibrillation, NCMedic and Ambulance Driver write that they have already begun using variations on double defibrillation.
 

That     is     excellent.

 


 

The changes in when to implement the change, as well as the vector to use, are reasons we need to have people publishing results on what is being done. Please, work with your medical directors and/or others to publish some results.

We have had epinephrine (Adrenaline in Commonwealth countries) in ACLS (Advanced Cardiac Life Support) guidelines, and our protocols, for decades, but we still do not know the best dose or even which patients benefit.

NCMedic writes –
 

Has been in our protocols for sometime now, we are finding it more beneficial sooner than later for obvious reasons, next protocol revision will most likely have it on the 4th shock with the 2nd set of pads placed A/P to cover from a different vector.

 

Epinephrine seems to be harmful when given later, or is epinephrine less beneficial later, or is epinephrine always harmful, just much more harmful later, or something else.[1]

The problem is that we do not know when, or for whom, epinephrine is indicated.

Epinephrine is probably indicated in some patients, but which patients, at what dose, and at what time? If epinephrine should be repeated all of the same questions apply to all further doses. Dr. Scott Weingart points out how little we know about the use of epinephrine, because his approach makes more sense than what ACLS recommends and the evidence is equally lacking.[2]

There are many things in the presentation to discuss, such as Dr. Weingart’s misunderstanding of what nihilism means, but that is for another time.
 

There does not appear to be any harm from double defibrillation. As we use more current more often, we should expect to learn of harms, as we do with almost every intervention. However, as NCMedic states, we may be doing harm by waiting too long to deliver the double dose.

Should it be a double dose?

What about 1 ½ times the maximum?

300 j bi-phasic or 540j mono-phasic or maybe some combination of bi-phasic and mono-phasic, and if a combination, what combination, with drugs or without, which drugs if with drugs, . . . ?

What about 3 times the maximum?

600 joules bi-phasic or 1,080 joules mono-phasic or . . . ?

Should the higher-dose defibrillation be after the fifth shock with a return to VF/pulseless VT (Ventricular Fibrillation/pulseless Ventricular Tachycardia)? After the fourth shock? After the third shock? After the second shock? After the first shock?

Is waiting longer to increase joules making it more likely that epinephrine will be given? Is epinephrine more harmful than a double shock, less harmful than a double shock, or roughly the same?

The amount we do not know is huge.

We should learn what we are doing to our patients and not arrogantly choose to remain ignorant, as we have chosen with epinephrine. That is changing, but some still defend the arrogance of ignorance at the expense of our patients.[3]

Footnotes:

[1] Does Faster Epinephrine Administration Produce Better Outcomes from PEA-Asystole?
Sun, 25 May 2014
Rogue Medic
Article

[2] Podcast 125 – The New Intra-Arrest from SMACCgold
EMCrit
Dr. Scott Weingart
Web page with video and show notes.

[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 from semanticscholar.org
 

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.

 

Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 3.

.

We all rely on evidence. The important difference is __________.

 
There are many people who will tell us that we should not demand evidence as the basis for our decisions, but what is the basis for their decisions?

Evidence, not logic.

We all rely on evidence. The important difference is the quality of the evidence we rely on.

We should not listen to those who are devoted to low standards that can support any bias at all.
 

Yes, you may have dozens of impressive anecdotes, but an anecdote is just the retelling of events with most of the variables ignored. The reader is encouraged to come to the conclusion that is being promoted. Anecdotes should be viewed as advertising – promotion of a product that hides reality.

When we see advertising for a big, juicy burger, we are being presented with evidence. When we go to buy that big, juicy burger, we are being presented with reality. The advertising used evidence to get us to buy their product. The actual sale was when we were presented with the evidence that we are easily fooled and manipulated by those who make money off of our low standards for evidence.
 

Medicine/EMS is just as susceptible to advertising biased promotion of a favored treatment.

Is it logical to choose a treatment (which can harm and/or help) based on weak evidence?

If we are going to risk harming our patients, why are so many of us in favor of such low standards?

Why are we so arrogant that we assume that unintended consequences do not affect our patients?

Maybe our treatments really can’t be tested.
 


 
Image credit.

Or we claim that a treatment is too important to study

For example, epinephrine (Adrenaline) in cardiac arrest.
 

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.[1]

 

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.[1]

 

Or spinal immobilization.
 

Perhaps it has not been demonstrated safe but it has never been demonstrated unsafe either. Better stay with the known than go to the unknown. If you want to develop a research project, please go ahead and do it. But without proof that they are bad, we cannot just assume that they are bad.

 

That could be the clap for Tinkerbell speech.[2] It could be Dr. Oz justifying his fraud,[3] but it isn’t. This defense of recklessness is from a surgeon who controls trauma policy in EMS.

This was a serious response to my criticism of the lack of evidence of benefit of spinal immobilization. He has studied the effect of oxygen on trauma patients, so he does not apply this Dark Ages thinking to everything.

We pretend that we are not harming patients, rather than find out how much harm we are doing. Everything we do is harmful, but when the benefits outweigh the harms, only then it is appropriate to use the harmful treatment.

We choose to pretend that we are not causing harm.

We can’t even be honest with ourselves.

Footnotes:

[1] 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 from semanticscholar.org

[2] Tinkerbell effect
Wikipedia
Article
 

The Tinkerbell effect is an American English expression describing things that are thought to exist only because people believe in them. The effect is named for Tinker Bell, the fairy in the play Peter Pan who is revived from near death by the belief of the audience.

[3] Dr. Oz Shows How He Lies with Bad Research
Tue, 17 Jun 2014
Rogue Medic
Article

Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 1.

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Why Do We Have So Little Respect For Our Patients?


 

Informed consent should require that we provide our patients with honest information about the treatment we are pushing.

Even implied consent assumes that an informed patient would make the decision to take the treatment if the patient had the capacity to make an informed decision and had honest information about the treatment.

What medical treatment do we use during cardiac arrest?

We use chest compressions and defibrillation.

Nothing else qualifies as medicine.
 

[youtube]HhGuXCuDb1U[/youtube]
 

Ventilations, epinephrine, norepinephrine, vasopressin, amiodarone, lidocaine, and procainamide, are witchcraft.

There is no evidence that ventilations, epinephrine, norepinephrine, vasopressin, amiodarone, lidocaine, or procainamide improve survival from cardiac arrest.

None.
 

 
Why don’t we limit treatments to what actually works, rather than what makes us feel like we are helping?

We are only exposing our patients to adverse effects for no benefit to the patient.

Nature has demonstrated a strong bias in favor of reality.

Our bias in favor of superstition is unnatural and unhealthy.
 

All treatments should be limited to high-quality controlled trials until there is valid evidence of improved outcomes with the treatment.

Surrogate endpoints do not count.

If we wish to develop an understanding of what we are doing, we need to study what we use.

If a treatment does not work under controlled conditions, why believe that it works in uncontrolled conditions?

Research gives the best opportunity to see the difference in outcome that is due to the just the treatment being studied.

If we think the treatment works, we should be insisting on showing off.

We are all talk.

We run away when challenged.

If we accept excuses for not finding out what we are doing, we end up with epinephrine for cardiac arrest – 50+ years of use, but we still do not know if it is beneficial, if it is beneficial in some patient populations and harmful in other patient populations, or if the effect is neutral.

There is no outcomes research that has shown improved outcomes, but epinephrine is the standard of care and research has been discouraged because it would be unethical to deprive patients of this witchcraft.

Any treatment that is used outside of controlled trials, without evidence of improved outcomes, is witchcraft. Why can’t we be honest about that?

I was a baby, when we started using epinephrine for cardiac arrest. I am a cantankerous old coot, now. There has been only one placebo controlled trial of epinephrine for cardiac arrest,[1] but that was crippled by political pressure because it would be unethical to deprive patients of the eye of newt.

Someday, medicine will grow up and start treating patients with something that actually works.

Footnotes:

[1] 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 from semanticscholar.org
 

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.

Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 1.

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Should Basic EMTs Give Naloxone (Narcan)?

 
Should basic EMTs be giving naloxone (Narcan) when paramedics do not really understand the drug?

If a patient wakes up after naloxone, does that mean the patient had a drug overdose?

No – but most paramedics do not understand that.[1]

As of January 1, 2014, there will be even more people giving Narcan with little understanding of what they are doing.
 


Peter Thomson.
 

La Crosse firefighters soon could start carrying a life-saving drug for heroin users. The department is applying to be one of the state’s first groups of emergency medical technicians to administer Narcan, the antidote to an opiate overdose.[2]

 

Does naloxone save lives or just make it less work for first responders?

If the basic EMTs are not good at basic ventilation, will they be any better at drug administration?

Are drugs the cure for ventilation problems?
 

The department has witnessed a 53 percent jump in the number of potential drug overdoses since 2009, Chief Gregg Cleveland said.

In 2012, firefighters responded to 98 potential overdoses and 86 so far this year.[1]

 

A 53% increase?

98 last year.

86 so far this year (as of October).

10 months in, so an average of 8.6 per month = 103.2 for the whole year.

Going from 98 to 103 is not a 53% increase.

It isn’t even a 5.3% increase, but only 5.1%
 

Only 5% – not 53%.
 

Bad math.

Correction (13:00 12/28/2013) – the math is not based on the numbers in the article and I did not read the article correctly. The bad math is mine, not Chief Gregg Cleveland’s. Thank you to Christopher Jennison, Jordan L, and Parastocles for pointing out my error.

I apologize to Chief Gregg Cleveland for misrepresenting his statement as bad math, when it was my mistake.
 

Bad decisions.

What kind of time would be saved by having the fire department give naloxone?

What kind of bad outcomes would be prevented?

What kind of better outcomes would be expected?

What is the added cost of implementing this program?

What other programs would be deprived of this money?

Those are just some of the questions that should be asked.

The main question is –

If your fire department is doing such a bad job of managing BLS skills (BVM, positioning, painful stimulus, . . . ), why should we allow you to harm patients with ALS skills?

If your department is not harming patients, then where is the need?

Naloxone does not appear to be the answer to either problem.

Will naloxone cure the math problems of these drug pushing managers?

Footnotes:

[1] Acute heroin overdose.
Sporer KA.
Ann Intern Med. 1999 Apr 6;130(7):584-90. Review.
PMID: 10189329 [PubMed – indexed for MEDLINE]
 

Six of the 25 complete responders to naloxone (24%) ultimately were proven to have had false-positive responses, as they were not ultimately given a diagnosis of opiate overdose. In four of these patients, the acute episode of AMS was related to a seizure, whereas in two, it was due to head trauma; in none of these cases did the ultimate diagnosis include opiates or any other class of drug overdose (which might have responded directly to naloxone). Thus, what was apparently misinterpreted as a response to naloxone in these cases appears in retrospect to have been due to the natural lightening that occurs with time during the postictal period or after head trauma.

[2] Firefighters could be getting medication to save drug users
October 31, 2013 12:00 am
By Anne Jungen
ajungen@lacrossetribune.com
LaCrosse Tribune
Article

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An EMS Giant is lost – Well-known educator Mike Smith dies at age 61

 


 

The EMS community lost one of its contemporaries early this morning. Mike Smith, chair of the Tacoma Community College EMS program and a well-known EMS speaker, died of an apparent heart attack.[1]

 

In EMS, we seem to die of things that as if they should be easily prevented. MVCs (Motor Vehicle Collisions) while not wearing a seat belt and heart attacks.

Why do I start writing about the death of Mike Smith by mentioning this? Because I think that is one thing he would want us to learn from his death at the ripe young age of 61.

We deal with death much more frequently than most other people, and yet we seem to be trying to get there faster than most other people.

Too many of us drink too much – and I do mean alcohol. Many of us drive while drunk and are able to get a free pass from the police, because we are the good guys. You didn’t kill anyone this time, so try harder next time. This is preventable.

Too many of us drive recklessly, even without the assistance of alcohol. The most common cause of LODD (Line Of Duty Death) is either heart attack or MVC, but how many of us regularly wear seat belts?

Mike Smith appears to have died of a heart attack.

What might Mike Smith use as lessons from this?

I barely knew him. I knew him well enough to say, Hi to him at EMS conferences.

I think that he would focus on preventing the pain that is inevitable from his death.
 

According to sources, Mike was transported by EMS from his home to a local hospital where he succumbed to a myocardial infarction.[1]

 

He might point out how painful this must have been for EMS, since he probably taught everyone who showed up.

He was a big guy, so maybe he had students press down on his chest in class to see that two inches is not going to do much on a big guy. But he would have been alive for that lesson.

How does EMS deal with the bad outcome, even if there was no way for EMS to change the outcome? This might be a class best taught by Shakespeare.
 

He is survived by his wife Sylvia and two grown children, as well as a new granddaughter.[1]

 

He might point out how much the patient would prefer to be around to see his children prosper and his grandchild grow up. How many things would he have told them, if he knew that he had so little time left?

Maybe the biggest lesson would be about taking better care of ourselves. We take care of other people, but we often do not take care of ourselves.
 

He was blunt and not afraid to share his thoughts and opinions with anyone. He was idealistic and filled with a zest for EMS and patient care. He loved people, and could be the best friend in the world or a formidable opponent if he thought you were unjust. Having grown up in Chicago, he would not back down from a fight when he was right.[2]

 

Are my comments too blunt?

Unlike his friend Jim Page, his death may not have been a tragedy of a lack of a defibrillator, but a tragedy of a big heart that did not beat long enough.

I have been trying to get rid of my EMS weight. I have lost about 20 pounds in the last five months, but I would like to lose another 30. Last night at work, I was the smallest person in the room at work, and I am not small.

I want to see my family grow old and become more successful. I want to make it beyond 61, 71, or even 81 – and with my brain still working. Exercise helps prevent stroke, too.[3]

It is painful for me to run, so I use a machine, then I walk for a while. I keep increasing the time. Eventually, I hope to be able to run, but even if I cannot, I can get good heart exercise from walking briskly. A few hours at about 140 beats per minute is over 75% of my calculated maximum heart rate and more than is recommended by the CDC (Centers for Disease Control and Prevention). This is prevention, the part that alternative medicine propagandists pretend that real doctors do not recommend.
 

10 minutes at a time is fine
We know 150 minutes each week sounds like a lot of time, but you don’t have to do it all at once. Not only is it best to spread your activity out during the week, but you can break it up into smaller chunks of time during the day. As long as you’re doing your activity at a moderate or vigorous effort for at least 10 minutes at a time.

Give it a try
Try going for a 10-minute brisk walk, 3 times a day, 5 days a week. This will give you a total of 150 minutes of moderate-intensity activity.[4]

 

It isn’t about me, or even Mike – it is about you and your family – even especially if you consider your family to be EMS – the people who would have to deal with treating you.

What is more important to you than your family, whoever your family may be?

 

Image replaced 17:10. Thank you to 9-ECHO-1. I had the wrong Mike Smith. I am not good at facial recognition and did not notice the differences. My apologies to everyone I upset with my error.

Footnotes:

[1] An EMS Giant is lost – Well-known educator Mike Smith dies at age 61
Art Hsieh
EMS1.com
Article

[2] Passing of an EMS Icon – Mike Smith, who died unexpectedly at age 61, was a well-known EMS educator and writer
A.J. Heightman, MPA, EMT-P
Letter by John Sinclair, Fire Chief, Emergency Manager, Kittitas Valley Fire Rescue, Ellensburg, WA
Monday, October 14, 2013
JEMS.com
Article

[3] Association of physical activity level and stroke outcomes in men and women: a meta-analysis.
Diep L, Kwagyan J, Kurantsin-Mills J, Weir R, Jayam-Trouth A.
J Womens Health (Larchmt). 2010 Oct;19(10):1815-22. doi: 10.1089/jwh.2009.1708. Review.
PMID: 20929415 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.
 

Although it is unclear how PA plays a protective role against stroke, results of this study suggest long-term benefits. Future research to examine the impact of PA on the pathophysiological mechanism of stroke will be desirable. Some studies37–41 have suggested that impact of PA on reducing the risk of stroke mortality could be explained by deceleration of the atherosclerotic process, amelioration of endothelial dysfunction, structural modification of the arteries, enhancement of myocardial electric stability, or attenuation of hypercoagulability.

 

[4] How much physical activity do adults need?
CDC (Centers for Disease Control and Prevention)
Physical Activity for Everyone
CDC page of recommendations.

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Do Paralytics Improve Outcomes Following Resuscitation?

ResearchBlogging.org
 

This study will get some people excited because of an impressive p value for an odds ratio of improved cardiac arrest outcomes – 7.23 (1.56–33.38) p = 0.01.

NMBs (NeuroMuscular Blockers/Blockade) are paralytic drugs that are used to prevent movement by the patient. Does this study truly show that immediate use of NMBs improves neurologically intact survival from cardiac arrest?
 

Side effects of therapeutic hypothermia include an increased risk for arrhythmia, infection or bleeding, and shivering.6 [1]

 

NMBs could cause worse outcomes from therapeutic hypothermia use following ROSC (Return Of Spontaneous Circulation).
 

the American Heart Association (AHA) has recommended minimizing the use of NMB in post-CA patients or avoiding it altogether.11 [1]

 

Is this enough to get the AHA to change their minds?
 

We included patients who were 18 years of age or older who had suffered OHCA with sustained ROSC (defined as the presence of palpable pulses for >20 min) and who were comatose (not following commands) upon presentation to the NPARC hospital.[1]

 

That is an unusual definition of comatose. It would be interesting to know how many patients had a GCS (Glasgow Coma Score) of at least 8, but were not following commands. Many people are taught that a low GCS means that we should intubate. The mnemonic Less than 8 – intubate, is taught as if it is a substitute for a thorough assessment.

Maybe not following commands is the right metric to use for administration of NMBs, but we might want to describe this level of consciousness with a term other than coma. There is a lot of connotation associated with coma that might complicate decisions about treatment. If we use NMBs for patients with ROSC and a motor score of less than 6, will some people start to use a motor score of less than 6 for intubation with NMBs? RSI (Rapid Sequence Induction/Intubation) is the use of NMBs to facilitate intubation. A better question is How many of us will do this?, rather than Will any of us will do this?
 

Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients - Fig 1
 

Impressive.

So why am I suggesting caution?
 

Compared to those who did not receive sustained NMB, patients with 24-h NMB had shorter intervals from collapse-to-ROSC (13 min [IQR: 9–25] versus 22 min [IQR: 13–30]; p = 0.04) and higher baseline blood pH values (pH = 7.30 [IQR: 7.26–7.36] versus 7.22 [IQR: 7.12–7.31]; p = 0.04). There was a lower incidence of chronic obstructive pulmonary disease in patients with NMB compared to patients without NMB (0% versus 22%; p = 0.02).[1]

 

Time to ROSC demonstrates one of the problems with small numbers. The IQRs (InterQuartile Ranges) do not show that much difference, but the median times to ROSC are much farther apart. 22 minutes is in the middle of the 13-30 minute IQR for control patients, but 13 minutes is much quicker than the middle of the IQR for NMB patients.

Why does this matter?

The control patients appear to be evenly distributed around 22 minutes from collapse to ROSC, but the NMB patients had an uneven distribution that masks a tendency toward much quicker ROSC.
 

It is also odd that the group with the smaller numbers has a narrower IQR. Is this because of some uncontrolled variable in choosing which patients received early, sustained NMB treatment?
 

This is a post hoc analysis of data collected for a study with a different hypothesis, so the best that can be stated is that immediate NMB use (continued for 24 hours) is a promising treatment for further study.

Another big problem with this study is that it is so small. 18 patients received NMBs. The authors started the paper by mentioning that there are 400,000 cardiac arrests in the US each year. We need to demonstrate benefit on much more than 18 patients, regardless of p value, if we are going to start using this treatment outside of controlled trials.
 

There were 77 (69%) patients documented to have received NMB at any point within the first 24 h following ROSC. A portion of these patients (18/111, 16%) patients had NMB initiated immediately and sustained for a minimum duration of 24 h following return of circulation.[1]

 

This is not really a study comparing NMB use with absence of NMBs. This is a study comparing immediate NMB use that was continued for at least 24 hours against control group patients – most of whom received NMBs, but did not meet the full criteria for inclusion in the study group.

How different were the treatments? We do not know.

59 out of the 111 patients in the No NMB group received NMBs.

53% of the No NMB group did receive NMBs, just not for at least 24 hours and/or not immediately following ROSC. Correction – 15:20 7/08/2013.

59 out of 93 patients in the No NMB group received NMBs.

63% of the No NMB group did receive NMBs, just not for at least 24 hours and/or not immediately following ROSC.
 

The following is the main limitation pointed out by the authors.
 

An important limitation of this observational study is the uncertainty about why NMB was used in certain patients. It is possible that patients with more intact reflexes, shivering or spontaneous movement were more likely to receive NMB than patients with less vigorous neurological examinations. Thus, the possibility remains that patients without sustained NMB were less responsive (i.e., worse neurological status) and therefore did not clinically require continued therapy therefore creating selection bias. Finally, whether heavy sedation in the post-CA period would confer similar results is possible but has yet to be explored.[1]

 

Is a good physiologic explanation is leading them to minimize the weaknesses of this study? I don’t know, but they are not recommending anything other than more study, which is a reasonable conclusion for this study.

Unfortunately, the abstract presents a different conclusion – a conclusion that assumes too much.

I would discuss the physiology that is the basis for this study, but with no clear evidence of benefit and a lot of evidence that the data are misleading, there is no reason to spin tales about any possible mechanism(s).

The hypothesis is still essentially untested.

Footnotes:

[1] Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients.
Salciccioli JD, Cocchi MN, Rittenberger JC, Peberdy MA, Ornato JP, Abella BS, Gaieski DF, Clore J, Gautam S, Giberson T, Callaway CW, Donnino MW.
Resuscitation. 2013 Jun 21. doi:pii: S0300-9572(13)00331-6. 10.1016/j.resuscitation.2013.06.008. [Epub ahead of print]
PMID:23796602[PubMed – as supplied by publisher]
 

The National Post-Arrest Research Consortium (NPARC) is a clinical research network conducting research in post-cardiac arrest care. The network consists of four urban tertiary care teaching hospitals and was established to evaluate treatment strategies for individuals who are successfully resuscitated after out-of-hospital cardiac arrest. The current investigation is a post hoc analysis of a prospectively conducted NPARC trial evaluating mitochondrial injury in post-cardiac arrest patients (NIH 3UL1RR031990-02S1).

Salciccioli JD, Cocchi MN, Rittenberger JC, Peberdy MA, Ornato JP, Abella BS, Gaieski DF, Clore J, Gautam S, Giberson T, Callaway CW, & Donnino MW (2013). Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients. Resuscitation PMID: 23796602

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