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

- Rogue Medic

Natural Alternatives to the EpiPen, Because We Believe in Parachutes

Wed, 23 Dec 2015 13:45:23 -0500 by
 

The evidence for epinephrine (Adrenaline in Commonwealth countries) in anaphylaxis is not the highest quality available, but that does not mean that the use of epinephrine to treat anaphylaxis is not EBM (Evidence Based Medicine).
 

Evidence Pyramid

Evidence Pyramid


Image credit.
 

The patients are not randomized to placebo vs. epinephrine treatments, but EBM is not limited to placebo studies[1] – unless you believe that the Parachute Study is valid evidence, rather than just satire.[2]

It is entirely appropriate to use logical fallacy for satire, since humor is not expected to be based on valid evidence. It is definitely not appropriate to use logical fallacy as scientific evidence. Logic is essential to science, while logical fallacy and the avoidance of rational analysis are essential to deception.

What does the Parachute study have to do with Natural Alternatives to Epipen?[3] The evidence supporting epinephrine is even weaker than the evidence supporting parachutes, since one of the advantages of parachutes is that their use can be adequately studied without using human subjects. Therefore we actually have excellent evidence that parachutes will deploy as expected (with the obvious error bars that apply to valid science), will slow the descent (again, with the obvious error bars that apply to valid science), et cetera.
 

Even the most dimwitted purveyor of “natural” cures should know that and stay away from “natural” treatments for anaphylaxis, while the smarter snake oil salesmen also know that you can’t afford to mess around with a medical condition that can cause such rapid deterioration from seemingly perfectly health to dead. It’s not good for business.[4]

 

Ignoring the pathetic absence of evidence for alternative medicine, what is the evidence that epinephrine does improve outcomes?

There is an excellent discussion of the evidence in an article available for free at PubMed Central.
 

International guidelines concur that epinephrine (adrenaline) is the medication of first choice in anaphylaxis because it is the only medication that reduces hospitalization and death.[5]

 

There is no reduction of hospitalization and death with Benadryl (diphenhydramine), with any of the steroids, or with any alternative medicine. Go read the full paper.

Also, go read the analysis of the problems in the article advocating the use of Natural Alternatives to Epipen at Respectful Insolence.

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Footnotes:

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[1] Evidence based medicine: what it is and what it isn’t.
Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS.
BMJ. 1996 Jan 13;312(7023):71-2.
PMID: 8555924 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.
 

Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.

 

Maybe the opponents of Evidence Based Medicine do not understand that using judgment to apply the best evidence to the patient is essential to EBM.

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[2] Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials.
Smith GC, Pell JP.
BMJ. 2003 Dec 20;327(7429):1459-61. Review.
PMID: 14684649 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

The authors searched the literature for parachute research, but eliminated all studies without control groups, which suggests that EBM has some sort of requirement that all research include a control group. That is one of the logical fallacies employed by the authors for humorous intent.
 

We excluded studies that had no control group.

 

Those who cite the parachute study as valid evidence do not seem to understand this sleight of hand. EBM does not exclude studies that have no control group. EBM even includes expert opinion.

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[3] Natural Alternatives to Epipen
Gazette Review
Dec 18, 2015
Adam Trent
Cached article

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[4] Worst idea ever: “Natural” alternatives to the Epipen
Respectful Insolence
Posted by Orac
December 22, 2015
Article

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[5] 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.
Simons FE, Ebisawa M, Sanchez-Borges M, Thong BY, Worm M, Tanno LK, Lockey RF, El-Gamal YM, Brown SG, Park HS, Sheikh A.
World Allergy Organ J. 2015 Oct 28;8(1):32. doi: 10.1186/s40413-015-0080-1. eCollection 2015.
PMID: 26525001

Free Full Text from PubMed Central.

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Filed Under: 'Alternative' Medicine, EBM, Epinephrine, Evidence, Heresy

Should ACLS Recommend the Unknown Based on Weak Evidence?

Thu, 29 Jan 2015 17:05:03 -0500 by

 
The AHA (American Heart Association) and ILCOR (International Liaison Committee on Resuscitation) will be meeting tomorrow to finalize the recommendations for the 2015 ACLS (Advanced Cardiac Life Support) guidelines. Here is the comment I submitted on the proposed recommendation for epinephrine (Adrenaline in Commonwealth countries) in cardiac arrest.

I have not received any information about where to submit SEERS comments, so I am sending this to you. Please forward it to whomever is supposed to receive comments.

Vasopressors for cardiac arrest (1. Epi v Placebo)
 

Consensus on Science:
For all four long term (critical) and short term (important) outcomes, we found one underpowered trial that provided low quality evidence comparing SDE to placebo (Jacobs, 2001, 1138).[1]

 

As a trial that is stated to be underpowered (through no fault of Dr. Jacobs),[2] is there any valid reason the Jacobs study should be considered to be superior to observational studies?
 

Among 534 subjects, there was uncertain benefit or harm of SDE over placebo for the critical outcomes of survival to discharge [RR 2.12, 95% CI 0.75-6.02, p=0.16] and good neurological outcome defined as CPC of 1-2 [RR 1.73, 95% CI 0.59-5.11, p=0.32].[1]

 

We do not have good evidence to tell us if this is harmful or beneficial and we do not have any way of determining which patients will be harmed or helped by administration of epinephrine.


 

However, patients who received SDE had higher rates of the two important outcomes of survival to admission [RR 1.95, 95% CI, 1.34-2.84, p=0.0004] and ROSC in the prehospital setting [RR 2.80, 95% CI 1.78-4.41, p<0.00001] compared to those who received placebo.[1]

 

Are these surrogate endpoints important?

How do we know?

If these surrogate endpoints are important, why is there no valid evidence to support this claim?

We have a history of being misled by surrogate endpoints. We used to bleed patients and that produced a number of clear benefits in surrogate endpoints.
 

Physicians observed of old, and continued to observe for many centuries, the following facts concerning blood-letting.

1. It gave relief to pain. . . . .

2. It diminished swelling. . . . .

3. It diminished local redness or congestion. . . . .

4. For a short time after bleeding, either local or general, abnormal heat was sensibly diminished.

5. After bleeding, spasms ceased, . . . .

6. If the blood could be made to run, patients were roused up suddenly from the apparent death of coma. (This was puzzling to those who regarded spasm and paralysis as opposite states; but it showed the catholic applicability of the remedy.)

7. Natural (wrongly termed ” accidental”) hacmorrhages were observed sometimes to end disease. . . . .

8. . . . venesection would cause hamorrhages to cease.[3]

 

We don’t do that any more, because medicine is not supposed to just create a superficial improvement.

We should not be making any recommendation to treat based on such weak evidence.
 

The evidence for the routine use of adrenaline is perceived to be at equipoise within the international community of resuscitation scientists requiring re-evaluation19 as suggested by this comprehensive systematic review and meta-analysis. There is a need for well-designed, placebo-controlled, and adequately powered RCTs to evaluate the efficacy of adrenaline and to determine its optimal dosing.11,16,54 The question as to the efficacy of adrenaline for OHCA remains unanswered.[4]

 

Since the question as to the efficacy of adrenaline for OHCA remains unanswered, we should avoid substituting a bad answer for We don’t know.

Maybe we should bring back the indeterminate class for these unanswerable questions.
 

Treatment Recommendation
Given the observed benefit in short term outcomes, we suggest Standard Dose Epinephrine be administered to patients in cardiac arrest.(weak recommendation, low quality)[1]

 

The benefit is considered important, but that is just an expert opinion, which is the lowest level of evidence.

A weak recommendation to give a treatment of unknown benefit and unknown harm, based on evidence that is admitted to be of low quality, should not set the standard of care. Even if the guidelines are explicitly stated to not be standards of care, they are adopted as standards of care by the emergency medicine community and by the EMS community.

We don’t know enough to make a recommendation about epinephrine, or most other treatments, in cardiac arrest.

We do not need to keep making the same recommendation just because we have made it before. We can leave it up to the treating physician or to the medical director writing the protocols for EMS.
 
 

See also – Proposed 2015 ACLS Epinephrine Recommendation – Vasopressors for cardiac arrest (1. Epi v Placebo)

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Footnotes:

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[1] Vasopressors for cardiac arrest (1. Epi v Placebo)
ILCOR Scientific Evidence Evaluation and Review System
Questions Open for Public Comment
Closing Date – February 28, 2015
Question page

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[2] 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.

 

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[3] Blood-Letting
Br Med J.
1871 March 18; 1(533): 283–291.
PMCID: PMC2260507

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[4] Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials.
Lin S, Callaway CW, Shah PS, Wagner JD, Beyene J, Ziegler CP, Morrison LJ.
Resuscitation. 2014 Jun;85(6):732-40. doi: 10.1016/j.resuscitation.2014.03.008. Epub 2014 Mar 15.
PMID: 24642404 [PubMed – in process]

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Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 2.

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Filed Under: ACLS, Correction, Critical Judgment, Epinephrine, Heresy, Pharmacology

Proposed 2015 ACLS Epinephrine Recommendation – Vasopressors for cardiac arrest (1. Epi v Placebo)

Tue, 27 Jan 2015 21:45:10 -0500 by

 
What do the AHA (American Heart Association) and ILCOR (International Liaison Committee on Resuscitation) plan to make their recommendation on use of epinephrine (Adrenaline in Commonwealth countries) in cardiac arrest (ACLS – Advanced Cardiac Life Support)?
 

Full Question:
Among adults who are in cardiac arrest in any setting (P), does does use of epinephrine (I), compared with placebo or not using epinephrine (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?

The information provided is currently in DRAFT format and is NOT a FINAL version[1]

 

Unless you are familiar with the way AHA/ILCOR ask questions, this may not seem to be a helpful way of addressing the question. Here is the format being used –

PICO:

Population/Patient/Problem

Intervention

Comparison/Control

Outcome
 

The Patients are adults who are in cardiac arrest in any setting.

The Intervention is use of epinephrine.

The Comparison is placebo or not using epinephrine.

The Outcome is a bit complicated – Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC. ROSC is Return Of Spontaneous Circulation.

Everything is reasonable – until they get to the outcome. Does anyone still think that it is really an improvement to get pulses back, be transported to the hospital, never wake up, and die in the ED (Emergency Department) or ICU (Intensive Care Unit)? What if the coma lasts for 30 days, 60 days, 180 days AND/OR 1 year. If you think that is an improvement, you may not have considered the cost. How much is it worth to give a family false hope? $10,000? Who pays for this deception?

Should we also try putting the patient in a helicopter to see if the magic rotor blades make the family feel that everything possible was done to deceive them?

These are considered to be important, because we do not seem to know what is important.

Why are ROSC and survival to admission considered important?

Where is the evidence that these measurements lead to better outcomes?
 

 

Studies that look at these outcomes show that real world patients treated with epinephrine are more likely to die in the hospital – and those who do not die in the hospital are more likely to have severe neurological impairment.
 

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.

The evidence evaluation focused on the Jacobs study,[8] which is randomized and placebo controlled, but only reaches the level of fair according to the analysis of all of the evidence. The reason is that politicians and the media combined to sabotage the study. Most of the ambulance services dropped out of the Jacobs study because of this interference. This is not the fault of Dr. Ian G. Jacobs, who deserves credit for setting up the first randomized placebo controlled study of this important topic.
 

For all four long term (critical) and short term (important) outcomes, we found one underpowered trial that provided low quality evidence comparing SDE to placebo (Jacobs, 2001, 1138).[1]

 

We need to bring back the Indeterminate class of recommendation for ACLS, because that is the best that we can come up with for epinephrine, unless we ignore the evidence or we just don’t understand the evidence.
 

Table 3.
Applying Classification of Recommendations and Level of Evidence

. . .

Class Indeterminate.
• Research just getting started
• Continuing area of research
• No recommendations until further research (eg, cannot recommend for or against)[11]

 

Does the proposed ACLS recommendation on epinephrine makes sense?

Consider that we do not know which patients benefit from epinephrine. The treatment for every cause of cardiac arrest includes epinephrine as the first drug, even if the cause of cardiac arrest is known to be an overdose of epinephrine.

Is epinephrine better than nothing for some patients in cardiac arrest? Yes.

Is epinephrine worse than nothing for some patients in cardiac arrest? Yes.

We do not know which patients we are harming with epinephrine and we don’t seem to want to stop harming those patients.

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Footnotes:

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[1] Vasopressors for cardiac arrest (1. Epi v Placebo)
ILCOR Scientific Evidence Evaluation and Review System
Questions Open for Public Comment
Closing Date – February 28, 2015
Question page

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[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.

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[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]

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[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]

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[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

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[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

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[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]

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[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.

 

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[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.

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[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.

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[11] Table 3. Applying Classification of Recommendations and Level of Evidence
2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 1: Introduction
Table 3

I have modified this table solely for the purpose of clarity of presentation, by modifying color and font. None of the words have been changed.

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

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Filed Under: ACLS, Cardiac Arrest, Correction, Epinephrine, Evidence, Pharmacology

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

Thu, 04 Sep 2014 21:15:28 -0400 by
 
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.

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Footnotes:

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[1] Does a Placebo vs. Adrenaline Study Deprive Patients of Necessary Care According to the Resuscitation Guidelines?
Wed, 27 Aug 2014
Rogue Medic
Article
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[2] UK To Experiment on Cardiac Arrest Patients Without Their Consent
8/27/2014 @ 3:55PM
Paul Hsieh – Contributor
Forbes
Article

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Filed Under: Epinephrine, Ethics, Heresy, Research

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

Wed, 27 Aug 2014 13:45:06 -0400 by

 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

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Footnotes:

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

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[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.

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[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.

 

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

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Filed Under: 2010 AHA Guidelines, Correction, Epinephrine, Evidence, Heresy

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

Thu, 21 Aug 2014 16:00:53 -0400 by

 

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

.

Filed Under: 'Alternative' Medicine, ACLS, EBM, Epinephrine, Evidence, Heresy, Unicorn Medicine

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

Wed, 13 Aug 2014 23:35:19 -0400 by
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.

.

Filed Under: ACLS, Correction, Epinephrine, Ethics, Evidence, Heresy, Research Blogging

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

Sun, 03 Aug 2014 17:00:01 -0400 by
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 – 1 – 2 – 3
 

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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Filed Under: ACLS, Assessment, CPR, Critical Judgment, Epinephrine, Heresy, Research Blogging, Toxicology
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