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

- Rogue Medic

Safety and Effectiveness of Field Nitroglycerin in Patients with Suspected ST Elevation Myocardial Infarction

 

Is prehospital use of NTG (NiTroGlycerin; GTN GlycerylTriNitrate in Commonwealth countries) safe for treating prehospital suspected STEMI (ST segment Elevation Myocardial Infarction) patients?

The evidence is limited, but does not suggest that prehospital NTG produces enough harm to discourage use in suspected STEMI. These researchers looked at the emergency department assessments of patients following prehospital NTG for suspected STEMI.  

Despite the theoretical risk, the limited retrospective studies of NTG in the prehospital setting for multiple indications suggest that the medication is safe.(10-13) However, with regard to NTG use for STEMI, the AHA International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care concluded that there was not enough evidence to determine the benefit or harm of out-of-hospital use of NTG.(14) Given the high false positive rates for STEMI identified in the field, an additional concern is that many patients treated with NTG for presumed STEMI will ultimately have an alternate etiology for their pain.(15, 16) Therefore, it is not clear that the benefits outweigh the risks of administering NTG to all patients with suspected STEMI in the field.[1]
 

This paper helps to show the safety of prehospital NTG for suspected STEMI, providing evidence that blood pressure changes were similar in suspected STEMI patients with an SBP (Systolic Blood Pressure) of 100, or higher, regardless of whether they were treated with NTG. The study is a retrospective chart review, so we do not know why some of the patients were not treated with NTG.

One reason mentioned, but not discussed, is that only 22% (96 of 440) suspected STEMI patients not treated with NTG are documented to have had pain, but there is no information on the type of pain or other cardiac symptoms of the patients. Were the paramedics avoiding treating atypical chest pain, such as pressure, heaviness, gastric discomfort, difficulty breathing, et cetera? We do not know. Was only chest pain being documented, rather than shoulder, or arm, or jaw, pain? We do not know. Did the pain resolve prior to EMS arrival? We do not know. Were the paramedics correctly recognizing when the machine interpretation of the ECGs (ElectroCardioGrams) were wrong? We do not know.

The median Initial Pain Score is documented as 8, with an IQR (Inter-Quartile Range) of 5-9 for those treated with NTG. For those not treated with NTG the Initial Pain Score is documented as 0, with an IQR of 0-0. We do not know the Initial Pain Score of those who did have pain, but were not treated with NTG. All of these patients were in an IQR that was not documented in the paper. The good news is that the suspected STEMI patients not treated with NTG act as a control group, although possibly with important differences that are not discussed in the paper.

Click on the image of the LA County protocol to make it larger.[2]

What about the 17% of suspected STEMI patients with SPB <100 mmHg who were treated with NTG?

Was medical command (California has certified MICNs [Mobile Intensive Care Nurses] providing medical command on the radio, with physicians available, as well) contacted for authorization to deviate from the protocol? If so, that is something that should be documented in the charts, which were reviewed for this paper. That information is not included in this paper. Those patients are much more interesting to me.

I do not object to using NTG to treat suspected STEMI with an SBP below 100 mmHg, but the authors seem to think that EMS should not even consider it. Do the outcomes of those patients support the approach of the authors? We do not know.

I suspect that the fears of bottoming out the blood pressure are very exaggerated, but it would be nice to have some evidence either way.

An important secondary end point was the differences between those with inferior/right ventricular STEMI, but treated with NTG.  

By vasodilating all blood vessels, and the venous system in particular, it causes a drop in blood pressure and preload. Thus, there is concern for precipitating hypotension in ACS involving the right ventricle.(1-3) Contraindications to the use of NTG, as outlined by the American Heart Association (AHA) Guidelines on the treatment of ACS, include right ventricular infarction.(4) This raises concern for use in inferior ST-segment elevation myocardial infarction (STEMI) in the prehospital setting, since many inferior STEMI result from proximal right coronary artery (RCA) occlusion and 50% involve the right ventricle.(3) Traditional 12-lead ECG is focused mainly on the left side of the heart and typically EMS protocols do not include acquisition of right-sided ECG leads. Further, in many systems, Basic Life Support (BLS) protocols allow for administration of NTG without differentiating the location of STEMI. There is also risk of other adverse events including bradycardia and cardiac arrest.(5-9)[1]
 

I have aggressively promoted the use of NTG for even hypotensive CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure). Many physicians are not comfortable with that, even though the available evidence shows that aggressive IV NTG doubled the survival rate for these hypotensive patients. More research is needed on the use of NTG, especially in hypotensive patients.  

Further, we did not find an increased risk of hypotension among patients with proximal or mid RCA occlusions confirmed on coronary angiography. There are several possible reasons for our findings. First, while right ventricular involvement in inferior STEMI is common, hemodynamic instability is actually rare due to the right ventricle’s more favorable oxygen supply-demand ratio compared to the left heart and more extensive collateral flow.(3, 22) In addition, left heart occlusions may also involve the right ventricle and result in a preload dependent condition.(23-25) While limited by sample size, our results suggests that specifically avoiding NTG use in inferior STEMI, which is common in EMS systems, may be misguided. One quarter of the local EMS agencies in the state of California, for example, currently prohibit the use of NTG in inferior STEMI.(26) This analysis would benefit from additional study with a larger sample size and specific information about the infarct territory. Further studies are needed to determine which patients, in particular, are at increased risk for hypotension when treated with NTG.[1]
 

Perhaps NTG is also safe for treating patients with inferior ischemia and even right ventricular ischemia.

Footnotes:

[1] Safety and Effectiveness of Field Nitroglycerin in Patients with Suspected ST Elevation Myocardial Infarction.

Bosson N, Isakson B, Morgan JA, Kaji AH, Uner A, Hurley K, Henry TD, Niemann JT.

Prehosp Emerg Care. 2018 Dec 17:1-9. doi: 10.1080/10903127.2018.1558318. [Epub ahead of print]

PMID: 30556765

[2] Treatment Protocol: Chest Pain */ Acute MI

Reference No. 1244

LA County Paramedic Protocols

Los Angeles County Department of Health Services – Emergency Medical Services

Protocol

.

Association of ventilation with outcomes from out-of-hospital cardiac arrest

 

Does this study compare chest compressions with pauses for ventilation (regular CPR [CardioPulmonary Resuscitation]) against continuous chest compressions with no ventilations (compression-only CPR)?

Absolutely not.

This only compares compressions with pauses for good ventialtions against compressions with pauses for bad ventilations.

Will this be used to justify including ventilations in CPR, in spite of the absence of any valid evidence that ventilations improve outcomes?

Yes. It already has in the editorial about the study, published in the same issue.[1]

The authors of the paper were clear about the actual comparison in the discussion.
 

Why did so few patients in our study receive ventilation during CPR? Ventilation with a BVM device is a difficult skill to perform properly and must be practiced to maintain proficiency.22 The person performing ventilation must extend the neck, or place an oral airway, and/or perform a jaw thrust maneuver in order to maintain an open airway, a tight mask seal on the face must be maintained to prevent air from leaking around the mask, and the rescuer must then simultaneously squeeze the manual ventilator over 1 to 1.5 s. Our study showed no significant difference in the number of pauses between Group 1 and Group 2 patients (11 vs. 12 pauses). However, Group 2 patients received significantly more ventilations than Group 1 patients (8 vs. 3 ventilations). The study suggests that the rescuers in both Groups attempted ventilation about the same number of times per patient, but these attempts frequently did not result in lung inflation in Group 1 patients.[2]

 

In other words, this is a study of 30 compressions with a pause for 2 adequate ventilations to 30 compressions with a pause for 2 inadequate ventilations. This is important to know, but it has nothing to do with compression-only resuscitation.
 


 

Were the ventilations in the bad ventilation group going into the stomach? There are not a lot of possibilities, but not much of the ventilations were not going into the lungs or the ventilations were very shallow.

The authors do not mention if there is any difference in the rate of vomiting, aspiration, or other side effects expected from bad ventilation, between the groups.

The authors appear to be measuring the quality of ventilation, which is has never been shown to improve outcomes over compression-only resuscitation.

There is research showing that ventilations do not improve outcomes:
 

Cardiocerebral resuscitation improves survival of patients with out-of-hospital cardiac arrest.
Kellum MJ, Kennedy KW, Ewy GA.
Am J Med. 2006 Apr;119(4):335-40.
PMID: 16564776 [PubMed – indexed for MEDLINE]

Cardiocerebral resuscitation improves neurologically intact survival of patients with out-of-hospital cardiac arrest.
Kellum MJ, Kennedy KW, Barney R, Keilhauer FA, Bellino M, Zuercher M, Ewy GA.
Ann Emerg Med. 2008 Sep;52(3):244-52. Epub 2008 Mar 28.
PMID: 18374452 [PubMed – indexed for MEDLINE]

Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest.
Bobrow BJ, Clark LL, Ewy GA, Chikani V, Sanders AB, Berg RA, Richman PB, Kern KB.
JAMA. 2008 Mar 12;299(10):1158-65.
PMID: 18334691 [PubMed – indexed for MEDLINE]

Free Full Text at JAMA

Passive oxygen insufflation is superior to bag-valve-mask ventilation for witnessed ventricular fibrillation out-of-hospital cardiac arrest.
Bobrow BJ, Ewy GA, Clark L, Chikani V, Berg RA, Sanders AB, Vadeboncoeur TF, Hilwig RW, Kern KB.
Ann Emerg Med. 2009 Nov;54(5):656-662.e1. Epub 2009 Aug 6.
PMID: 19660833 [PubMed – indexed for MEDLINE]

And more.

 

 

Footnotes:

[1] Ventilation during cardiopulmonary resuscitation-Only mostly dead!
Mosesso VN Jr.
Resuscitation. 2019 Aug;141:200-201. doi: 10.1016/j.resuscitation.2019.06.274. Epub 2019 Jun 22. No abstract available.
PMID: 31238035

 

[2] Association of ventilation with outcomes from out-of-hospital cardiac arrest.
Chang MP, Lu Y, Leroux B, Aramendi Ecenarro E, Owens P, Wang HE, Idris AH.
Resuscitation. 2019 Aug;141:174-181. doi: 10.1016/j.resuscitation.2019.05.006. Epub 2019 May 18.
PMID: 31112744

.

How Effective Is Epinephrine for Improving Survival Among Patients in Cardiac Arrest?

   

There have been two studies comparing epinephrine with placebo to treat out of hospital cardiac arrest. The Jacobs study was stopped early, because of interference by those who do not want to know if their medicine actually works.[1] The purpose of research is to determine, as objectively as possible, if a treatment is better than placebo nothing.  

Click on the image to make it larger.  

Even the small sample size shows a impressive p values of <0.001 for both ROSC (Return Of Spontaneous Circulation) and being admitted to the hospital. Unfortunately, that does not lead to outcomes that are better than placebo.

The Perkins study (PARAMEDIC2) did not find a significant difference between adrenaline (epinephrine in non-Commonwealth countries) and placebo.[2] The Jacobs study also did not find a difference, but the numbers were small, due to the interference by the less than knowledgeable. Following the Jacobs study, some intervention proponents have suggested that the problem is not a lack of evidence of benefit, but need to look at the evidence from the right perspective. The inadequate evidence is not “inadequate”, but really just misunderstood. All we need to do is use a method of analysis that compensates for the tiny sample size. A Bayesian approach will produce the positive outcome that is not justified by so few patients.[3]

What happens when the numbers are combined, so that the sample size is large enough to eliminate the need for statistical chicanery to come up with something positive?

The outcomes do not improve.  

Neither standard dose adrenaline, high-dose adrenaline,vasopressin nor a combination of adrenaline and vasopressin improved survival with a favourable neurological outcome.[4]
 

If the Bayesian approach were appropriate, then the much larger sample size would have provided more than enough patients to confirm the optimism of the epinephrine advocates. The result is still not statistically significant. Maybe a much, much larger study will show a statistically significant, but tiny, improvement in outcomes with epinephrine, but don’t hold your breath for that. It took half a century to produce the first study, then seven more years for the second. With the cost of research and the problems coordinating such a large study, it is more likely that the guidelines will continue to recommend spending a lot of time and money giving a drug that diverts attention from the interventions that do improve outcomes.

There is still no evidence that adrenaline provides better outcomes than placebo in human cardiac arrest patients.

  –  

Footnotes:

  –  

[1] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Resuscitation. 2011 Sep;82(9):1138-43. doi: 10.1016/j.resuscitation.2011.06.029. Epub 2011 Jul 2. PMID: 21745533

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.

  –  

[2] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators. N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18. PMID: 30021076

Free Full Text from N Engl J Med.

  –  

[3] Regarding “Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial”. Youngquist ST, Niemann JT. Resuscitation. 2012 Apr;83(4):e105; author reply e107. doi: 10.1016/j.resuscitation.2011.09.035. Epub 2012 Jan 18. No abstract available. PMID: 22266068

Free Full Text from Resuscitation.

  –  

[4] Adrenaline and vasopressin for cardiac arrest. Finn J, Jacobs I, Williams TA, Gates S, Perkins GD. Cochrane Database Syst Rev. 2019 Jan 17;1:CD003179. doi: 10.1002/14651858.CD003179.pub2. PMID: 30653257    

.

ACLS Excuses for Causing Harm with Epinephrine

 

The next ACLS guidelines are available for review and comment, before they are finalized. The Consensus on Science with Treatment Recommendations (CoSTR) from the International Liaison Committee on Resuscitation (ILCOR) are available for two guidelines:

Vasopressors in Adult Cardiac Arrest

Advanced Airway Management During Adult Cardiac Arrest

We have been using these interventions for so long, that there should be great evidence to show that benefits and harms of both interventions, but there is no good evidence to support either intervention.

For epinephrine (adrenaline in Commonwealth countries), the most commonly used vasopressor and the only one rally being considered, there is no evidence of actual benefit – increased survival without severe brain damage.

Nothing else matters.

There is no valid evidence that increasing any surrogate endpoint improves survival without severe brain damage. The evidence cited by ILCOR shows that epinephrine increases the rate of severe brain damage.
 

Intervention: Vasopressor or a combination of vasopressors provided intravenously or intraosseously during cardiopulmonary resuscitation.[1]

 

Here are the outcomes that are supposed to indicate that the patient is better.
 

Outcomes: Short-term survival (return of spontaneous circulation (ROSC) and survival to hospital admission), mid-term survival (survival to hospital discharge, 28 days, 30 days, or 1 month), mid-term favorable neurological outcomes (Cerebral Performance Category score of 1-2 or modified Rankin Scale 0-3 at hospital discharge, 28 days, 30 days, or 1 month) and long-term favorable and poor (modified Rankin Score 4-5) neurological outcomes (after 1 month).[1]

 

Is ROSC an improvement?

We aren’t supposed to ask that question. These are faulty assumption that the guidelines are based on.

1. Doing something more is better than only doing things supported by valid evidence of improved survival without severe brain damage.

No.

How much harm is being caused in this rush to get a pulse back?

We are supposed to ignore our understanding of research, look at a statistically insignificant “trend”, and extrapolate that statistically insignificant “trend” to support the prejudice that our intervention has not been harmful.

That is not good science.

That is not good medicine.
 

Why aren’t there any studies large enough to show improved survival without severe brain damage for anything other than rapid defibrillation (when indicated VF/pulseless VT) and chest compressions?

The research has only produced excuses and surrogate endpoint. Surrogate endpoints are for hypothesis generation and sales pitches to the least knowledgeable, but not for treatment guidelines.

ILCOR has told us this before, but that was because the choice was between large doses of epinephrine and small doses of epinephrine, not between epinephrine and no epinephrine.

The choice is the same.

Is the more aggressive intervention helping?

The answer is the same. No. That is not the conclusion of the evidence.
 

CONCLUSIONS
In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.[2]

 

If the goal is a pulse with more severe brain damage, then epinephrine is the way to go.

If the goal is increased survival without severe brain damage, we have to keep looking.

We should limit the use of epinephrine to well controlled research until there is evidence of improvement in outcomes that matter.

If this evidence is never found, our patients will not have been harmed by epinephrine.

If this evidence is eventually found, it is something that should have been insisted on decades ago. We should not use wishful thinking and surrogate endpoints to justify interventions that harm patients.

We used to stop compressions to let the medic/nurse/doctor intubate, or start an IV (IntraVenous) line.

We knew that the tube was more important.

We knew that the drugs given through the IV line were more important.

The 2005 guidelines told us to continue compressions during intubation and during IV attempts and to improve the quality of the compressions.

That focus on high quality compressions is the only time we have improved outcomes that matter.
 

CONCLUSIONS: Compared with controls, patients with out-of-hospital cardiac arrest treated with a renewed emphasis on improved circulation during CPR had significantly higher neurologically intact hospital discharge rates.[3]

 

33 1/3% vs 60% increased survival without severe brain damage.
 

In 2004, we began a statewide program to advocate chest compression-only CPR for bystanders of witnessed primary OHCA. Over the next five years, we found that survival of patients with a shockable rhythm was 17.7% in those treated with standard bystander CPR (mouth-to-mouth ventilations plus chest compression) compared to 33.7% for those who received bystander chest-compression-only CPR.[4]

 

18% vs 34% increased survival only – not increased survival without severe brain damage.
 

In the analysis of MICR [Minimally Interrupted Cardiac Resuscitation] protocol compliance involving 2460 patients with cardiac arrest, survival was significantly better among patients who received MICR than those who did not (9.1% [60/661] vs 3.8% [69/1799]; OR, 2.7; 95% CI, 1.9-4.1), as well as patients with witnessed ventricular fibrillation (28.4% [40/141] vs 11.9% [46/387]; OR, 3.4; 95% CI, 2.0-5.8).[5]

 

9% vs 4% increased survival only – not increased survival without severe brain damage.
 

Neurologic outcomes were also better in the patients who received CCR (OR=6.64, 95% CI=1.31 to 32.8).[6]

 

6 2/3 more likely to have increased survival without severe brain damage. The range is 1 1/3 to almost 33 times, because of the small numbers, but unlike epinephrine, this is statistically significant and supported by other research.

We are still making excuses for using a drug that causes harm and does not appear to provide a benefit that is greater than the harm. If there is more benefit, it is too small to be measured, even in a study with over 9,000 patients. We do not know which patients benefit and which patients are harmed, so we do not know how to minimize the harm that we cause.

Our patients deserve better.

Footnotes:

[1] Vasopressors in Adult Cardiac Arrest
Time left for commenting: 11 days 15:49:49
ILCOR staff
Created: March 21, 2019 · Updated: March 21, 2019
Draft for public comment
Consensus on Science with Treatment Recommendations (CoSTR)
Vasopressors in Adult Cardiac Arrest page for comments until April 04, 2019 at 06:00 Eastern Time

[2] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18.
PMID: 30021076

Free Full Text from N Engl J Med.

[3] Implementing the 2005 American Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest.
Aufderheide TP, Yannopoulos D, Lick CJ, Myers B, Romig LA, Stothert JC, Barnard J, Vartanian L, Pilgrim AJ, Benditt DG.
Heart Rhythm. 2010 Oct;7(10):1357-62. doi: 10.1016/j.hrthm.2010.04.022. Epub 2010 Apr 24.
PMID: 20420938

Free Full Text from Heart Rhythm.

[4] The cardiocerebral resuscitation protocol for treatment of out-of-hospital primary cardiac arrest.
Ewy GA.
Scand J Trauma Resusc Emerg Med. 2012 Sep 15;20:65. doi: 10.1186/1757-7241-20-65. Review.
PMID: 22980487

Free Full Text from PubMed Central.

[5] Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest.
Bobrow BJ, Clark LL, Ewy GA, Chikani V, Sanders AB, Berg RA, Richman PB, Kern KB.
JAMA. 2008 Mar 12;299(10):1158-65. doi: 10.1001/jama.299.10.1158.
PMID: 18334691

Free Full Text from JAMA.

[6] 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. doi: 10.1111/j.1553-2712.2010.00689.x.
PMID: 20370759

Free Full Text from Acad Emerg Med.

.

What Treatments May Be De-Emphasized by EM/EMS in 2019? Part I

 

EM (Emergency Medicine) and EMS (Emergency Medical Services) have already started to eliminate/decrease use of a lot of our failed treatments, because people started to see through our excuses. Atropine for asystole stuck around for a long time, then just vanished.[1]. Calcium for cardiac arrest is also something that used to be standard of care, then we raised our standards.

We need to keep raising our standards, because our patients’ outcomes – their lives, their brains, their everything – depend on raising our standards.

We used to give antiarrhythmics to almost anyone with a cardiac complaint. Then there was CAST (The Cardiac Arrhythmia Suppression Trial[2]). While CAST did not study lidocaine, it did study longer term use of antiarrhythmics. Lidocaine is too dangerous for long term use, so the results of CAST may be much worse for lidocaine. We thought that the increased deaths among patients with frequent PVCs (Premature Ventricular Contractions) after having a heart attack was due to a problem with the conduction system. PVCs indicate a problem with conduction and antiarrhythmics cause the PVCs to go away.
 

Before receiving the antiarrhythmic (PVCs are circled in red).


 

After receiving the antiarrhythmic.


 

Problem solved.

Now the problem is, How do we get paid more? These drugs were the biggest selling drugs at the time. They making the drug companies a fortune. Whichever company made the drug that saved the most lives would make a lot more money then the others. Provide evidence that ______ saves more lives than all of the others.

The problem of the PVCs was solved, but the solution was killing many more patients than not giving drugs.

The result was not celebrated by the drug companies. The patients taking antiarrhythmics were dying at three times the rate of the patients taking placebos. A plausible physiological mechanism suggested the drugs would save lives, but that was based on an assumption that was not justified. This is the kind of reasoning that appeals to those who reject EBM (Evidence-Based Medicine). The evidence should convince these EBM opponents of the folly of relying on physiology and on a plausible explanation to justify not looking for the evidence that might expose their unreasonable assumptions. These otherwise reasonable people start making excuses for unreasonable assumptions, because they believe. They seem to need to convince others to join in and multiply their mistakes.[3]

The PVCs appear to have been just an indicator of an unhealthy heart.

Getting rid of the PVCs may have made the conduction in the heart less healthy.

Giving the drugs may have killed tens of thousands of patients.

Antiarrhythmic use decreased dramatically after the harm demonstrated in CAST, but some drug pushers are trying to get one of the worst antiarrhythmics (amiodarone, now in a new formula) to make a comeback, by creatively spinning research to claim results the research was never designed to evaluate.

Not having learned from the evidence, even though he has been the lead author on some of it, Dr. Peter Kudenchuk has been claiming that in EMS witnessed arrests, there was a significant improvement, even though his own published results contradict this claim. Here is what the results actually state:
 

Though prespecified, this subgroup analysis was performed in the context of an insignificant difference for the overall analysis, and the P value for heterogeneity in this subgroup analysis was not adjusted for the number of subgroup comparisons. Nonetheless, the suggestion that survival was improved by drug treatment in patients with witnessed out-of-hospital cardiac arrest, without evidence of harm in those with unwitnessed arrest, merits thoughtful consideration.[4]

 

Amiodarone has also been shown to be horrible for patients with ventricular tachycardia with a pulse. Amiodarone is so ineffective, that the rate of severe side effects is greater than the rate of improved outcomes. Amiodarone is more likely to make your patient’s medical condition much worse, but it is still considered to be the standard of care and amiodarone is still in EMS protocols.[5]

Maybe amiodarone can produce better results if it is used for execution by lethal injection.

I am expecting that there will be more failed treatments removed from our standards of care.

We need to raise our standards to improve outcomes, not lower our standards to make us look better than we are.

Continued in Part II. I will add Part III and others at some point and provide the links here.

Footnotes:

[1] Why Did We Remove Atropine From ACLS?
Rogue Medic

Part I
Sun, 13 Oct 2013

Part II
Wed, 16 Oct 2013

[2] Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.
Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al.
N Engl J Med. 1991 Mar 21;324(12):781-8.
PMID: 1900101 [PubMed – indexed for MEDLINE]

Free Full Text from NEJM.
 

CONCLUSIONS. There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

[3] Why US EMS will never get to sit at the adult table – The Appeal to Authority
Sun, 04 May 2014
Rogue Medic
Article

Since Mike cites the original parachute study, as if it is not satire, it is amusing to point out that there is a new Parachute Study! Read Dr. Radecki’s description of this satirical poke at those who do not understand research in the satire issue of the BMJ, which they put out every Christmas as sort of a British IgNobel.

Don’t Bother With the Parachute!
Emergency Medicine Literature of Note
Dr. Ryan Radecki
December 21, 2018
Article
 

Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial.
Yeh RW, Valsdottir LR, Yeh MW, Shen C, Kramer DB, Strom JB, Secemsky EA, Healy JL, Domeier RM, Kazi DS, Nallamothu BK; PARACHUTE Investigators.
BMJ. 2018 Dec 13;363:k5094. doi: 10.1136/bmj.k5094. Erratum in: BMJ. 2018 Dec 18;363:k5343.
PMID: 30545967

Free Full Text from BMJ.

[4] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.
Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators.
N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4.
PMID: 27043165

Free Full Text from NEJM.

CONCLUSIONS Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

 

Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’
Tue, 12 Apr 2016
Rogue Medic
Article
 

Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
Mon, 04 Apr 2016
Rogue Medic
Article

[5] The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia
Rogue Medic
Wed, 17 Aug 2016
Article
 

Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study.
Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J; PROCAMIO Study Investigators.
Eur Heart J. 2016 Jun 28. pii: ehw230. [Epub ahead of print]
PMID: 27354046

Free Full Text from European Heart Journal.
 

Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison.
Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, Ellinor PT.
Acad Emerg Med. 2010 Mar;17(3):297-306.
PMID: 20370763 [PubMed – indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.
 

Amiodarone is poorly effective for the acute termination of ventricular tachycardia.
Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, Ruskin JN.
Ann Emerg Med. 2006 Mar;47(3):217-24. Epub 2005 Nov 21.
PMID: 16492484 [PubMed – indexed for MEDLINE]
 

Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment?
Tomlinson DR, Cherian P, Betts TR, Bashir Y.
Emerg Med J. 2008 Jan;25(1):15-8.
PMID: 18156531 [PubMed – indexed for MEDLINE]
 

Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction.
Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, Ceremuzyński L.
Europace. 2000 Jul;2(3):207-15.
PMID: 11227590 [PubMed – indexed for MEDLINE]

Free Full Text PDF + HTML from Europace
 

Adenosine for wide-complex tachycardia – diagnostic?
Thu, 23 Aug 2012
Rogue Medic
Article
 

Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia.
Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, Fontaine G.
World J Cardiol. 2012 Oct 26;4(10):296-301. doi: 10.4330/wjc.v4.i10.296.
PMID: 23110246 [PubMed]

Free Full Text from PubMed Central.

.

The Grinch Who Stole Reality

 

And the Grinch, with his Grinch-feet ice cold in the snow, stood puzzling and puzzling, how could it be so?

It came without ribbons epi.

It came without tags amio.

It came without packages oxygen, boxes tubes or bags.

And he puzzled and puzzled ’till his puzzler was sore. Then the Grinch thought of something he hadn’t before.

Maybe Christmas living, he thought…doesn’t come from a store drug.

Maybe Christmas living, perhaps…means a little bit more!

 

With apologies to Dr. Seuss (Theodore Geisel) for the modification of his parable.

There are important differences between the minimal criteria for life and the criteria for a meaningful life. Many of us don’t like to think about that, because many of us don’t like thinking. Thinking can be hard. Making excuses for not thinking – priceless (at least, as long as you don’t think about it).

We have been focusing on the least honest way of reporting outcomes – a pulse – Oooh!, or maybe even 30 days of a pulse – Oood-Ahhh! After all, reality does not support continuing to do what we have been doing. If we admit that we have been causing harm, then we may have to take responsibility for our actions.

We do not want to take responsibility for our actions. We were only following orders.

Doctors, PAs (Physician Assistants), NPs (Nurse Practitioners), nurses, paramedics, EMTs, techs, . . . do not want to take responsibility for what we get paid for. Accountability is for people who think – not for us.

We have blamed science/evidence for requiring that we confront reality. As explained by Dr. Seuss, we want simple answers that do not require understanding. Give us algorithms to mindlessly follow. Give us mnemonics.

We have been giving epinephrine (adrenaline in Commonwealth countries) for over half a century with no evidence of safety or improvement in the outcome that matters most.

Why?

We haven’t wanted to know.

The first study to look at the effect of placebo vs. epinephrine on neurological survival was cut short – with only a tiny fraction of what would be needed to produce any kind of statistically useful information, except for some of the true believers, who made the same kinds of mistakes that have been made for other discarded treatments – treatments discarded due to failure to work, discarded due to harm, or discarded due to both.

Don’t study this. Just believe. Belief makes us feel good. Attack science for encouraging understanding.
 

This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.[1]

 

In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.[1]

 

What was the conclusion produced by the Jacobs study?
 

CONCLUSION: Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.[1]

 

As the homeopaths put their spin on studies that do not really support their claims, people who do not understand science put similar spin on the results of this. For example, if you take a Bayesian approach[2], but distort it to mean that you give extra weight to everything that supports your belief and take away credit from everything else, you can claim that this is an example of science proving that epinephrine works.

Another way of doing this is to claim that you don’t give the 1 mg dose of epinephrine, therefore the study does not apply to your patients. After all, you are just engaging in a poorly documented, unapproved study, which allows you to think of the survivors as examples of the drug working and make excuses for the rest. Of course, if you don’t give the 1 mg dose of epinephrine, is there any evidence that your treatment is safe or effective? No.

Rather than insisting that this method of dosing patients be studied, in order to determine if it really is safe or if it really is effective at anything other than getting a pulse in a brain-dead body, claim to be ahead of the science.

Why find out what is really best for the patients, when there are so many ways of declaring victory and running away?

In 2018, we had the results of the next study of placebo vs. adrenaline (epinephrine in non-Commonwealth countries, but only Commonwealth countries have bothered to do the research). The conclusion was the same as the conclusion for the only previous study.
 

CONCLUSIONS: In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.[3]

 

Has anyone else stated that the use of epinephrine should be limited to controlled trials?

Not that I know of.

Everyone else seems to be claiming that giving smaller boluses of epinephrine. or giving titrated infusions of epinephrine is different. Some claim that it is nihilism to refuse to believe in their slightly different treatment – at least until there is undeniable evidence of lack of benefit, or undeniable evidence of harm, or both.

Requiring evidence of benefit, before using a treatment on a patient is being reasonable.

Using inadequately studied treatments on people when they are at their most vulnerable is not good medicine.

A doctor’s oath to Apollo does not include a requirement to perpetuate dogma, but medicine is only slowly starting to focus on what is best for patients, rather than what is best for appearances.

Dr. Ryan Jacobsen addressed a similar dogma, when he got rid of the long spine board in the system where he was medical director. His description of the evidence applies to epinephrine (bolus, mini-bolus, infusion, patch, inhaler, down the tube, oral, whatever) –

Other than historical dogma and institutional EMS medical culture we can find no evidence-based reason to continue to use the Long Spine board epinephrine as it currently exists in practice today.[4]

I changed EMS to medical and the Long Spine board to epinephrine.

We have good evidence that if your loved one is a laboratory pig, rat, dog, . . . we can kill them and get them back neurologically intact with epinephrine – and with other treatments that have been discarded because they do not have the same effect on humans as on lab animals.

Let us treat your loved ones like the lab animals we think they are.

Don’t use EBM (Evidence-Based Medicine), because belief is more important than reality.

The world is a comedy to those that think; a tragedy to those that feel. – Horace Walpole.

Keep thinking. Keep demanding evidence. After the nonsense being preached by the believers is exposed, we can improve the outcomes for our patients, because medicine is about doing what is best for the patient, and not about protecting the dogma.

Footnotes:

[1] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
Resuscitation. 2011 Sep;82(9):1138-43. doi: 10.1016/j.resuscitation.2011.06.029. Epub 2011 Jul 2.
PMID: 21745533

Free Full Text PDF Download from semanticscholar.org

[2] Bayesian inference
Wikipedia
Article

[3] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18.
PMID: 30021076

[4] Johnson County EMS System Spinal Restriction Protocol 2014
Ryan C. Jacobsen MD, EMT-P, Johnson County EMS System Medical Director
Jacob Ruthsrom MD, Deputy EMS Medical Director
Theodore Barnett MD, Chair, Johnson County Medical Society EMS Physicians Committee
Johnson County EMS System Spinal Restriction Protocol 2014 in PDF format.

.

Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial

ResearchBlogging.org
 
Also to be posted on ResearchBlogging.org when they relaunch the site.

This is a nice study, which unfortunately ran into problems with enrollment and funding. There are some things that I think should have been done differently.

The doses of chilled IV (IntraVenous) fluid were not weight-based, while the fluid in the human body is weight-based. If midazolam (Versed) was given, the dose was just a single dose of 5 mg, or 2 doses of 5 mg each. The effects of midazolam are much less weight-based, than fluid, but the appropriate way to administer midazolam is to titrate to effect. Even if administering 10 mg of midazolam produces the desired effect in 80%, or 90%, of patients, that can still leave a significant portion inadequately sedated. The goal of TTM (Targeted Temperature Management) may be defeated by the movement of an even mildly agitated patient.

Would another drug, such as ketamine, be more appropriate? How much does use of midazolam affect the use of pressors to counter the vasodilatory effects of midazolam? Unlike other sedatives, ketamine does not seem to produce vasodilation and/or depress cardiac activity. The midazolam was only mentioned in the description of the study interventions and only described as being given to prevent shivering, so the dose may be adequate, but there is only the one mention in the entire paper.

The fluid administration was shown to be different with a p value of <0.0001. The difference is only 170 ml (5 3/4 oz), so it is a distinction described as significant by p value, but it does not appear to be a significant difference in any way that would affect patients. The SD (Standard Deviation - how much variability exists in about 2/3 of patients) is the same as the amount of fluid given to the control group and 2 3/4 times the amount of the difference. In other words, there was a lot of overlap in the volumes administered to the patients in the two groups. While the p value of <0.0001 suggests confidence in the results being due to change only one time in 10,000, that is misleading.  

Total fluid infused was not documented for 98 (35%) patients who received Prehospital Cooling and 121 (40%) control patients.[1]

 


 

The raw data on the volumes is not included, nor is the shape of the graph of distribution of the volumes, but it looks as if 20%, or 30%, of the control group may have received more fluid that the intervention group – and then there are the more than 35% of patients without documentation of fluid volumes.

Since the amount of difference is small, it does not seem to matter, but the intervention group was forcing the chilled fluid into the patients with pressure bags, so why so little difference between the groups?

How long does it take to administer 170 ml of chilled IV fluid by pressure infusion? Does it take longer than it takes to get from the ambulance to the hospital stretcher?

That is just a statistical oddity that is not going to affect outcomes.

The next may be the true the significant finding of the study.
 

Patients in the prehospital cooling group were more likely to (ever) receive TTM in hospital [190 (68%) vs 170 (56%); RR 1.21, p = 0.003] than patients in the control group.[1]

 


 

TTM (Targeted Temperature Management) is the new term for therapeutic hypothermia, which has been shown to be effective.

If not, why not?
 

Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.[2]

 

With no difference in the rhythms of the control group and the intervention group, why the difference in the rate of TTM in the hospital?

Will this be similar to the case of waveform capnography? EMS ended up pressuring many/some EDs to begin to use EtCO2 on all intubated patients. This was a change from the previous, much too common, ED practice of complaining about and pulling at the EtCO2 tubing, because it was an unknown item that was in the way.

EMS should not need to encourage the ED to provide better care, especially about treatments/assessments that originated as in-hospital treatments/assessments. It should be the reverse.

There is an excellent review of TTM research at Life In The Fast Lane.[3]

Footnotes:

[1] Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial.
Scales DC, Cheskes S, Verbeek PR, Pinto R, Austin D, Brooks SC, Dainty KN, Goncharenko K, Mamdani M, Thorpe KE, Morrison LJ; Strategies for Post-Arrest Care SPARC Network.
Resuscitation. 2017 Dec;121:187-194. doi: 10.1016/j.resuscitation.2017.10.002. Epub 2017 Oct 5.
PMID: 28988962

Free Full text Article from Resuscitation.

[2] Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.
Arrich J, Holzer M, Havel C, Müllner M, Herkner H.
Cochrane Database Syst Rev. 2016 Feb 15;2:CD004128. doi: 10.1002/14651858.CD004128.pub4. Review.
PMID: 26878327

[3] Targeted temperature management (TTM) after cardiac arrest
Life In The Fast Lane
Chris Nickson
Reviewed and revised Aug 1, 2017 @ 7:07 pm
Article

Scales DC, Cheskes S, Verbeek PR, Pinto R, Austin D, Brooks SC, Dainty KN, Goncharenko K, Mamdani M, Thorpe KE, Morrison LJ, & Strategies for Post-Arrest Care SPARC Network (2017). Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial Resuscitation, 121 (December), 187-194 : PMID: 28988962

Arrich J, Holzer M, Havel C, Müllner M, & Herkner H (2016). Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation Cochrane Database Syst Rev : PMID: 26878327

.

Is placebo better than aggressive medical treatment for patients NOT having a heart attack?

Also to be posted on ResearchBlogging.org when they relaunch the site.
 

Is cardiac catheterization placebo better than aggressive medical treatment for patients not having a heart attack?

No.
 

The answer is not really different from before. This should not be surprising for anyone who pays attention to EBM (Evidence-Based Medicine). We should all pay attention to EBM, because it is the best way to find out what works.

Many routine treatments are not beneficial to patients, but are considered to be standards of care. We continue to give these treatments out of unreasonable optimism, a fear of litigation, or fear of criticism for not following orders. The difference between the banality of evil and the banality of incompetence does not appear to be significant in any way that matters.

PCI (Percutaneous Coronary Intervention) treatment does not add any benefit – unless you are having a heart attack.

The placebo group received sham PCI in addition to optimized medical treatment. this did not provide any benefit over actual PCI in addition to optimized medical treatment. The patients in the placebo group received all of the same medications that the patients in the PCI group received.

Why is this news today?

A recent article in The Lancet is encouraging snake oil salesmen and snake oil saleswomen to claim that it shows the miracle healing power of placebos, but this is not true.

Apparently, Big Placebo (the multi-billion dollar alternative medicine industry) is trying to use this to promote their scams (homeopathy, acupuncture, Reiki, naturopathy, prayer, . . . ).

Big Placebo seems to think that this study shows that placebo is better than medical treatment. A placebo is an inactive intervention that is undetectable when compared with the active treatment. The placebo group received the same aggressive medications that the treatment group received.
 

All patients were pretreated with dual antiplatelet therapy. In both groups, the duration of dual antiplatelet therapy was the same and continued until the fial (unblinding) visit. Coronary angiography was done via a radial or femoral arterial approach with auditory isolation achieved by placing over-the-ear headphones playing music on the patient throughout the procedure.[1]

 

What is new about this?

A much larger study a decade ago showed that aggressive medical therapy was as good as PCI and aggressive medical therapy. The difference is the use of sham PCI to create a placebo group for comparison, rather than using a No PCI group for comparison.
 

CONCLUSIONS:
As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.
[2]

 

Compare that with the conclusion (interpretation) of the new paper.
 

INTERPRETATION:
In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.
[1]

 

The unfortunate outcome is that we will have fewer hospitals providing PCI, so patients with heart attacks (STEMI – ST segment Elevation Myocardial Infarctions) may have to wait longer for emergency PCI, which really does improve outcomes.
 

What other Standards Of Care are NOT supported by valid evidence?

Amiodarone is effective for cardiac arrest, whether unwitnessed, witnessed, or witnessed by EMS.

Kayexalate (Sodium Polystyrene) is a good treatment for hyperkalemia. Anything that causes diarrhea will lower your potassium level, but that does not make it a good treatment, unless you are in an austere environment (in other words – not in a real hospital).

Amiodarone is effective for VT (Ventricular Tachycardia).

Backboards are effective to protect against spinal injury while transporting patients.

Blood-letting is effective for anything except hemochromatosis (and some rare disorders).

More paramedics are better for the patient.

Prehospital intravenous lines save lives.

IV fluid saves lives in hemorrhagic shock.

Oxygen should be given to everyone having a heart attack.

The Golden Hour is important.

Driving fast saves lives. For only some rare conditions, it probably does – and that depends on traffic.

Flying people to the hospital saves lives. Again, for only some rare conditions, it probably does – and that depends on traffic and distance.

Tourniquets are dangerous. As with anything else, if used inappropriately, they are dangerous, but tourniquets save lives.

Prehospital intubation saves lives.

Ventilation in cardiac arrest improves outcomes (other than for respiratory causes of cardiac arrest, which are easy to identify).

Epinephrine improves outcomes in cardiac arrest. It does produce a pulse more often, but at what cost to the long-term survival of the patient and the patient’s brain? PARAMEDIC2 should help us to identify which patients benefit from epinephrine, since it is clear that many patients are harmed by epinephrine in cardiac arrest. If we limit treatment to patients reasonably expected to benefit from the treatment, we can improve long-term survival.

And there are many more.

Footnotes:

[1] Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.
Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS, Petraco R, Cook C, Ahmad Y, Howard J, Baker C, Sharp A, Gerber R, Talwar S, Assomull R, Mayet J, Wensel R, Collier D, Shun-Shin M, Thom SA, Davies JE, Francis DP; ORBITA investigators.
Lancet. 2017 Nov 1. pii: S0140-6736(17)32714-9. doi: 10.1016/S0140-6736(17)32714-9. [Epub ahead of print]
PMID: 29103656

[2] Optimal medical therapy with or without PCI for stable coronary disease.
Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group.
N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.
PMID: 17387127

Free Full Text from N Engl J Med.

.