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

- Rogue Medic

Why is progress so slow in resuscitation research?

ResearchBlogging.org
 

Why is progress so slow in resuscitation research? A lot of money and time went in to finding out which type of blood-letting ventilation works best – ignoring the absence of valid evidence that ventilation is better than no ventilation. Why not gamble with our patients?

In response to The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR,[1],[2] Kenny commented that –
 

there are many things in your blog that are not correct.[1]

 

I asked for specifics and received the following from Anonymous (maybe Kenny and maybe not) –
 

That the study design ASSUMES we don’t want to know if ventilation is useful or not.[1]

 

Ventilation study implied facepalm
 

Assumes is not many things, but the comments may be from different people and there may be so many things, that Kenny is still documenting all of the examples. Perhaps the following is more specific wording that will satisfy defenders of the study –

    The study design strongly suggests that

        in the attempted resuscitation of adult patients

            with cardiac causes of cardiac arrest

                which is almost all cardiac arrest patients

                    active ventilation does not need evidence,

                        but selecting the favorite flavor of ventilation

                            does need expensive high quality evidence

                                just in case someone ever produces valid evidence

                                    that these patients are not harmed by ventilations

                                        and that these patients receive some benefit from ventilations.
 

That is a lot to assume believe without appropriate evidence.

Based on the available evidence, what are the odds that ventilations are not harmful and are beneficial?
 

Does anyone have any good argument to give ventilations as much as a 50% chance?
 

What about a 40% chance that ventilations will survive a valid study?

How about a 30% chance?

20%?

Is there any justifiable reason to be so optimistic?

If there isn’t any justifiable reason to be optimistic, then we are only making assumptions when we take shortcuts to eliminate the essential research in order to study something that is traditional, rather than based on valid evidence.
 

Do the authors understand that there isn’t valid evidence of any benefit/lack of harm from active ventilations?

Do the authors care that there is not valid evidence of any benefit/lack of harm from active ventilations?

If I have overlooked a third possibility, somebody should let me know. If there is valid evidence, somebody should provide it.

Footnotes:

[1] The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR
Wed, 25 Nov 2015 10:15:20
by Rogue Medic
Article

[2] Trial of Continuous or Interrupted Chest Compressions during CPR.
Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP; ROC Investigators.
N Engl J Med. 2015 Nov 9. [Epub ahead of print]
PMID: 26550795

Free Full Text from NEJM.

Nichol, G., Leroux, B., Wang, H., Callaway, C., Sopko, G., Weisfeldt, M., Stiell, I., Morrison, L., Aufderheide, T., Cheskes, S., Christenson, J., Kudenchuk, P., Vaillancourt, C., Rea, T., Idris, A., Colella, R., Isaacs, M., Straight, R., Stephens, S., Richardson, J., Condle, J., Schmicker, R., Egan, D., May, S., & Ornato, J. (2015). Trial of Continuous or Interrupted Chest Compressions during CPR New England Journal of Medicine DOI: 10.1056/NEJMoa1509139

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The Fatal Flaw in Trial of Continuous or Interrupted Chest Compressions during CPR

ResearchBlogging.org
 

Trial of Continuous or Interrupted Chest Compressions during CPR — NEJM
 

In conclusion, among patients with out-of-hospital cardiac arrest in whom CPR was performed by EMS providers, a strategy of continuous chest compressions with positive-pressure ventilation did not result in significantly higher rates of survival or favorable neurologic status than the rates with a strategy of chest compressions interrupted for ventilation.[1]

 

This is not a study that has a valid control group to determine if there is any benefit from ventilation. There is no group that does not receive ventilations, so it is like a study of one type of blood-letting vs. another type of blood-letting with the researchers taking for granted that blood-letting does improve outcomes. That is not a problem if blood-letting actually improves outcomes.

Should we take it for granted that blood-letting improves outcomes and that the only hypothesis worth studying is which brand to choose?

Should we assume that ventilations are too sacred to ever be doubted?

Should we assume that there are better arguments for ventilations than for blood-letting? That is not true.
 

If we ignore this fatal flaw, the study is very well done. I really like the study design. It is an excellent example of how to study two different versions of an intervention after that intervention has been demonstrated to improve outcomes, but ventilations have never been demonstrated to improve outcomes in adult patients with cardiac causes of cardiac arrest.

Should we have assumed that blood-letting was too sacred to ever be doubted?
 

We do know that outcomes for seizure patients improve when EMS gives benzodiazepines, because some people cared enough to find out.[2]

Assuming that a treatment is too important to study is like building on a foundation in a swamp.
 


 

We still do not know if there is any benefit from including ventilations, because the study design assumes that we don’t want to know.

There is no good reason to believe that ventilations improve outcomes for adult patients with cardiac causes of cardiac arrest. This study has not done anything to change that.

Our patients deserve better. Why aren’t we finding out what improves outcomes?

Footnotes:

[1] Trial of Continuous or Interrupted Chest Compressions during CPR.
Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP; ROC Investigators.
N Engl J Med. 2015 Nov 9. [Epub ahead of print]
PMID: 26550795

Free Full Text from NEJM.

[2] A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.
Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O’Neil N, Neuhaus JM, Segal MR, Lowenstein DH.
N Engl J Med. 2001 Aug 30;345(9):631-7. Erratum in: N Engl J Med 2001 Dec 20;345(25):1860.
PMID: 11547716 [PubMed – indexed for MEDLINE]

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

Nichol, G., Leroux, B., Wang, H., Callaway, C., Sopko, G., Weisfeldt, M., Stiell, I., Morrison, L., Aufderheide, T., Cheskes, S., Christenson, J., Kudenchuk, P., Vaillancourt, C., Rea, T., Idris, A., Colella, R., Isaacs, M., Straight, R., Stephens, S., Richardson, J., Condle, J., Schmicker, R., Egan, D., May, S., & Ornato, J. (2015). Trial of Continuous or Interrupted Chest Compressions during CPR New England Journal of Medicine DOI: 10.1056/NEJMoa1509139

Alldredge BK,, Gelb AM,, Isaacs SM,, Corry MD,, Allen F,, Ulrich S,, Gottwald MD,, O’Neil N,, Neuhaus JM,, Segal MR,, & Lowenstein DH. (2001). A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus New England Journal of Medicine, 345 (25), 1860-1860 DOI: 10.1056/NEJM200112203452521

.

Our current ambulance system is based on little scientific evidence

 

Our current ambulance system is based on little scientific evidence.

This is one comment by Prachi Sanghavi that has some paramedics very upset.

The video of her short speech at Harvard was posted on EMS1.com[1] and the responses suggested that there is something horribly wrong in the statement, or in any of what followed. There isn’t.
 


 

The problem is with the attitude of those who think that they know everything.

The problem is with the people who oppose finding out if treatments work.

The problem is with people who oppose protecting our patients from harmful treatments.

Prachi Sanghavi discusses the difference between BLS (Basic Life Support) treatment and ALS (Advanced Life Support) treatment. BLS includes all of the prehospital treatment that have evidence of benefit. All of them. ALS includes all of the cool things that paramedics and doctors do before getting to the hospital based on a wish and a prayer, but not on any valid evidence.
 


 

This is a comparison of cardiac arrest outcomes between two similar counties looking at the lack of expected benefit with ALS. There are more variables than just ALS vs. BLS, but we do need to ask Why are these cardiac arrest outcomes so bad with ALS?

Prachi Sanghavi is incorrect about a few things. Paramedics generally use a manual defibrillator, not a semi-automatic defibrillator. Taking longer at a cardiac arrest scene is probably not a problem. Those patients transported without pulses can be expected to end up in the morgue. Moving the patient with ineffective compressions, rather than staying on scene to do compressions well, is not recommended, because it is not supported by evidence. Rushing the patient to the hospital is just rushing the patient to ALS in a building. Yes, there is more ALS available at the hospital, but nothing that has good evidence of improving outcomes. Therapeutic hypothermia, is part of post-resuscitation treatment, not resuscitation treatment. That may change.[2]

Prachi Sanghavi also looked at trauma, stroke, and heart attack. The results were the same. Patients had better outcomes with Basic Life Support.

Our response should be to ask questions.

Are we doing something wrong?

What evidence do we have that ALS treatment improves outcomes?

The problem is that we ignore evidence and make excuses for our willful ignorance.

We are slow to adopt ALS treatments that have good evidence of improving outcomes and much, much slower to get rid of treatments that have only the weakest evidence of benefit – expert opinion. Expert opinion is the basis for all treatments that are later demonstrated to be harmful, so expert opinion isn’t worth bragging about. Real experts understand and learn from the evidence.

Should we trust the people criticizing the message that Maybe more is not better, or should we examine what we have been doing to find out what works?

Why are we opposed to providing the best care we can?

Footnotes:

[1] Researcher: Is BLS better than ALS?
EMS1.com
November 13, 2015
Article

[1] Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial).
Stub D, Bernard S, Pellegrino V, Smith K, Walker T, Sheldrake J, Hockings L, Shaw J, Duffy SJ, Burrell A, Cameron P, Smit de V, Kaye DM.
Resuscitation. 2015 Jan;86:88-94. doi: 10.1016/j.resuscitation.2014.09.010. Epub 2014 Oct 2.
PMID: 25281189

Free Full Text from Resuscitation.

This is a tiny study that suggests a grouping of treatments that may work (or that may include a treatment, or two, that may lead to improved outcomes. The results are good, but it is just one tiny study that needs replication and each of the treatments should be studied individually.

.

How Bad is the Evidence for the New 2015 ACLS Guidelines?

ResearchBlogging.org
 
    The new ACLS guidelines are out. How bad is the evidence?

    The short answer – The Advanced Cardiac Life Support guidelines could be worse.

How does the American Heart Association determine that a recommendation is not beneficial?
 

Class III: No Benefit, is a moderate recommendation, generally reserved for therapies or tests that have been shown in high-level studies (generally LOE A or B) to provide no benefit when tested against a placebo or control.[1]

 

The tobacco enema has been used successfully as a treatment for cardiac arrest, so the evidence of lack of benefit is poor.[2] Clearly, the Advanced Cardiac Life Support guidelines cannot claim that the tobacco enema is Class III. Successfully? The treatment was used and a dead person was no longer dead. In other words, just as successfully as most of the ACLS treatments.
 

From Eisenberg, MS. Life in the balance: emergency medicine and the quest to reverse sudden death. 1997; Oxford University Press. [betterworldbooks][3]

 

This is one way to make excuses for justify doing something just because of ideology. In the absence of good evidence of benefit, we should not harm our patients to protect our ideology. We used to do this with blood-letting, which was defended even after there was clear evidence of harm. That is just the best known example, but this dishonesty continues and continues to be defended.

Why don’t we hold anyone accountable, when we have the evidence that our treatments are harmful? Because we all seem to go along to get along.

The 2015 ACLS guidelines are not all bad, but they clearly do not encourage withholding harmful treatments until we have obvious evidence of harm. Should we assume that a treatment works just because the explanation appeals to some experts as much as the explanation for blood-letting appealed to the experts when that was in vogue?

This is not medicine. This is a fashion show. Our patients are the ones harmed.
 

Footnotes:

[1] 2015 AHA Classes of Recommendation
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 2: Evidence Evaluation and Management of Conflicts of Interest
Development of the 2015 Guidelines Update
Circulation.
2015; 132: S368-S382
Free Full Text from Circulation.

[2] Tobacco smoke enemas
Ghislaine Lawrence
Volume 359, No. 9315, p1442,
20 April 2002
Lancet
Abstract with link to Full Text PDF download.

[3] Ever tried smoking?
by Chris Nickson
Life in the Fast Lane
Article

Morrison LJ, Gent LM, Lang E, Nunnally ME, Parker MJ, Callaway CW, Nadkarni VM, Fernandez AR, Billi JE, Egan JR, Griffin RE, Shuster M, & Hazinski MF (2015). Part 2: Evidence Evaluation and Management of Conflicts of Interest: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 132 (18 Suppl 2) PMID: 26472990
 

Lawrence, G. (2002). Tobacco smoke enemas The Lancet, 359 (9315) DOI: 10.1016/S0140-6736(02)08339-3

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Will the Upcoming Pennsylvania Paramedic Protocols Eliminate Our Use of Not-So-Therapeutic Hypothermia?

 
Will Pennsylvania continue its trend of rejecting treatments that do not work and medicine that is not medicine?

One place to get a clear indication is the Post-resuscitation Care protocol, which has encouraged testing the ice waters of therapeutic hypothermia as an optional treatment that requires medical command orders. Backing away from further use of cold IV fluid for no known benefit to patients should be easy to do without political backlash from those more interested in doing something than in protecting patients from treatment for the sake of treatment.
 

Possible Medical Command Orders:

A. In adult patient, cold (4º C) NSS bolus of 20-30 mL/kg, if available, may be ordered if patient not following commands after ROSC from nontraumatic cardiac arrest.[1]

 

But wait.

      I know that therapeutic hypothermia works.

That is misleading. There is plenty of evidence that cooling patients in the hospital improves outcomes, but for prehospital patients the use of cold IV fluids has only been shown to improve outcomes for asystole/PEA (Pulseless Electrical Activity) patients and only in one study.[2]

For the patients most likely to survive cardiac arrest, the initial rhythm is V Fib (Ventricular Fibrillation). For these patients we need to stop the ice water infusions. Prehospital cold IV fluids following resuscitation of V Fib patients has been studied to death – more deaths in the treatment groups than in the no treatment groups. There has been no evidence of any benefit from IV ice water.[3],[4],[5]
 


Image credit.
 

This method of administration would probably be better for V Fib patients than IV ice water, because the adverse effects of IV ice water appear to be due to fluid overload.

I do not mean that prehospital therapeutic hypothermia is always a bad idea for V Fib patients – only that we need to find a way that is less harmful than dumping ice water into these recently dead patients for no benefit.
 


Click on image to make it larger.[3]
 

First, do no harm.

If the treatment is not beneficial, there is no good reason to expose patients to the adverse effects of the treatment for no known benefit.

Will we stop making excuses for endangering our patients with treatments that do not work?

Science teaches us to learn from our mistakes, while human nature encourages us to make excuses and continue to make the mistakes. Will we make the mistake of continuing to dump cold ice water into these recently dead patients for no good reason?

Footnotes:

[1] Post-Resuscitation Care
Pennsylvania Statewide ALS Protocols 2013
pp. 34-36 – 3080 – ALS – Adult/Peds
Protocols in PDF Download format.

[2] Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest*.
Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W; Rapid Infusion of Cold Hartmanns Investigators.
Crit Care Med. 2012 Mar;40(3):747-53. doi: 10.1097/CCM.0b013e3182377038.
PMID: 22020244 [PubMed – indexed for MEDLINE]

[3] Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial.
Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W; Rapid Infusion of Cold Hartmanns (RICH) Investigators.
Circulation. 2010 Aug 17;122(7):737-42. doi: 10.1161/CIRCULATIONAHA.109.906859. Epub 2010 Aug 2.
PMID: 20679551 [PubMed – indexed for MEDLINE]

Free Full Text from Circulation.

[4] Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest: A Randomized Clinical Trial.
Kim F, Nichol G, Maynard C, Hallstrom A, Kudenchuk PJ, Rea T, Copass MK, Carlbom D, Deem S, Longstreth WT Jr, Olsufka M, Cobb LA.
JAMA. 2013 Nov 17. doi: 10.1001/jama.2013.282173. [Epub ahead of print]
PMID: 24240712 [PubMed – as supplied by publisher]

Free Full Text from JAMA.

[5] Targeted temperature management at 33°C versus 36°C after cardiac arrest.
Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators.
N Engl J Med. 2013 Dec 5;369(23):2197-206. doi: 10.1056/NEJMoa1310519. Epub 2013 Nov 17.
PMID:24237006[PubMed – indexed for MEDLINE]

Free Full Text from NEJM.

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Dextrose in Cardiac Arrest – More Kitchen Sink Medicine

 
Should we treat hypoglycemia in a dead person?

How do we determine hypoglycemia in a dead person?

Is there any evidence that giving dextrose, in any concentration, will help to resuscitate a dead person?

Should we treat patients based on the philosophy of Who knows? Maybe it could work? Bleach enemas are currently in fashion among the alternative to medicine crowd,[1] so we could use the same reasoning to give bleach enemas in cardiac arrest. Who knows? Maybe it could work.

Is Kitchen Sink Medicine significantly different from any other alternative to medicine?

The dead person is not breathing, so we have to provide ventilations.[2], [3], [4]

The dead person is dead, so we have to do something.

We do compressions and (when indicated) defibrillation, because those are the only treatments that have been demonstrated to work.

 


 
 

The foundation of successful ACLS is high-quality CPR, and, for VF/pulseless VT, attempted defibrillation within minutes of collapse. For victims of witnessed VF arrest, early CPR and rapid defibrillation can significantly increase the chance for survival to hospital discharge.128–133 In comparison, other ACLS therapies such as some medications and advanced airways, although associated with an increased rate of ROSC, have not been shown to increase the rate of survival to hospital discharge.31,33,134–138 [5]

 

Ventilations are only a part of high-quality CPR for children and people who have a respiratory cause of cardiac arrest.

But what about dextrose for hypoglycemic cardiac arrest?

We may already be raising the blood sugar with epinephrine.
 

Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues.[6]

 

We seem to have trouble understanding that dead people do not respond to treatments the same way that living people do.
 

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.[7]

 

Maybe we should find out what we are doing and not blindly throw kitchen sinks at dead people based on hunches.

Dr. Brooks Walsh gave a good review of the evidence in his article written three years ago.[8]
 

What about my original questions?

Should we treat hypoglycemia in a dead person?

There is no evidence that giving dextrose is safe or effective for any cardiac arrest patients.

How do we determine hypoglycemia in a dead person?

We guess or check a capillary blood sugar, which is not reliable.

Is there any evidence that giving dextrose, in any concentration, resuscitates a dead person?

No.
 

Go read Using Dextrose in Cardiac Arrest at Mill Hill Ave Command.
 

Footnotes:

[1] Bleaching away what ails you
Science-Based Medicine
David Gorski
May 28, 2012
Article

[2] Cardiocerebral Resuscitation: An Approach to Improving Survival of Patients With Primary Cardiac Arrest.
Ewy GA, Bobrow BJ.
J Intensive Care Med. 2014 Jul 30. pii: 0885066614544450. [Epub ahead of print]
PMID: 25077491 [PubMed – as supplied by publisher]

[3] Cardiocerebral resuscitation is associated with improved survival and neurologic outcome from out-of-hospital cardiac arrest in elders.
Mosier J, Itty A, Sanders A, Mohler J, Wendel C, Poulsen J, Shellenberger J, Clark L, Bobrow B.
Acad Emerg Med. 2010 Mar;17(3):269-75.
PMID: 20370759 [PubMed – indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.

[4] Cardiac Arrest Management is an EMT-Basic Skill – The Hands Only Evidence
Fri, 09 Dec 2011
Rogue Medic
Article

[5] Management of Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8.2: Management of Cardiac Arrest
Overview
Free Full Text from Circulation.

[6] Effect of epinephrine on glucose metabolism in humans: contribution of the liver.
Sherwin RS, Saccà L.
Am J Physiol. 1984 Aug;247(2 Pt 1):E157-65.
PMID: 6380304 [PubMed – indexed for MEDLINE]

[7] 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

[8] Using Dextrose in Cardiac Arrest
Wednesday, March 14, 2012
Mill Hill Ave Command
Dr. Brooks Walsh
Article

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Proposed 2015 ACLS Chest compression only CPR vs conventional CPR Recommendation


 
The AHA (American Heart Association) and ILCOR (International Liaison Committee On Resuscitation) 2015 resuscitation guidelines evidence reviews appear to be merely justifications for continuing to use treatments that do not improve survival with good neurological function, which is the only outcome that matters. What do the AHA and ILCOR intend to recommend for ventilation of patients who appear to be adults and pulseless due to non-respiratory conditions?
 

Full Question:
Among adults who are in cardiac arrest outside of a hospital (P), does provision of chest compressions (without ventilation) by untrained/trained laypersons (I), compared with chest compressions with ventilation (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, bystander CPR performance, CPR quality (O)?
[1]

 

Do we really want to increase the rate of survival of permanently comatose patients?
 


Image credit.
 

That is not a goal. That is only a first step if we can do something to change the outcome for this comatose patient. There is no reason to believe that ventilations during CPR will do anything to improve the neurological outcome of these patients. We want to improve the survival of neurologically intact patients, not fill nursing homes with comatose patients until sepsis finishes them off.
 

We suggest performing chest compressions alone for trained laypersons if they are incapable of delivering airway and breathing manoeuvres to cardiac arrest victims (weak recommendation, very low quality of evidence).[1]

 

The AHA and ILCOR want us to provide this intervention that is based on tradition and disproven pathophysiology, rather than based on any valid evidence, except if we are incapable of providing the intervention.

Ventilations do not improve outcomes. However, ventilations may be harmful, so we should avoid using them in all cases where ventilations are not supported by valid evidence. Ventilations are not supported by valid evidence for non-respiratory causes of adult cardiac arrest.
 

We suggest the addition of ventilations for trained laypersons who are capable of giving CPR with ventilations to cardiac arrest victims and willing to do so (weak recommendation, very low quality of evidence).[1]

 

Each study cited to support ventilations showed no significant difference between compression only and standard CPR according to the AHA/ILCOR evidence review. That is the way to imitate Rube Goldberg. That is not support for any kind of medical intervention.
 

This recommendation places a relatively high value in [1] harm avoidance (not performing CPR or performing ineffective chest compressions and ventilations) and [2] simplifying resuscitation logistics, than potential benefit of an intervention of routine ventilations and compressions.[1]

 

That statement misrepresents harm avoidance and simplification of resuscitation logistics, since it encourages the potentially harmful treatment that has no valid evidence that the intervention increases any benefit that matters. How does adding ventilations simplify resuscitation logistics?

There is no evidence that passive ventilation provides inadequate oxygenation during chest compressions.

There is no evidence that passive ventilation provides inadequate removal of carbon dioxide during chest compressions.

Where is the need for any positive pressure ventilation to decrease blood return to the heart and increase the likelihood of vomiting?

Why continue to recommend doing something harmful for no benefit to the patient?

Footnotes:

[1] Chest compression only CPR vs conventional CPR
ILCOR Scientific Evidence Evaluation and Review System
Questions Open for Public Comment
Closing Date – February 28, 2015
Question page

.

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


 
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.

Footnotes:

[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

[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] 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.

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

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