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

- Rogue Medic

Does Room Air Reduce Mortality Among Term Neonates Requiring Respiratory Support at Birth?

     

The title of this meta-analysis suggests that it is important for us to have evidence in order to withhold treatments that are based on assumptions and anecdotes, rather than based on evidence. We should not even suggest this. Fortunately, the neonatal resuscitation guidelines have recommended not using the assumption-based and anecdote-based treatment since 2010.

 

Before 2000, resuscitation guidelines recommended 100% Fio2 for newborn respiratory support.6 However, hyperoxemia caused by high Fio2 results in the formation of free radicals, which can damage the lungs, brain, eyes, and other organs.7 Hypoxemia may also lead to harm. Literature in the early 2000s suggested no harm with room air resuscitation in term neonates, but also potentially an improvement in short-term mortality.8 In accordance with this literature, in 2010 and 2015 ILCOR recommended using room air for the initial resuscitation of term neonates.9, 10 [1]
 

The authors of this summary of the meta-analysis qualify this meta-analysis with a list of the weaknesses of the research. This is important for every analysis of research, but is it relevant, when there is no good reason to recommend the traditional intervention?  

According to these results with low evidence certainty, room air reduces short-term mortality compared with 100% Fio2 among term neonates requiring respiratory support at birth. Despite the low-quality evidence, these results are consistent across studies with low heterogeneity. The effect of intermediate Fio2 levels is not known and may benefit from further study. [1]
 

These are not reasons to reconsider, or oppose, the withholding of any treatments that are based on assumptions and anecdotes, rather than based on evidence.

The burden of proof is on those promoting any intervention. In the absence of valid evidence, we should limit ourselves to interventions that are supported by high quality evidence.

For epinephrine in cardiac arrest, there is no high quality evidence of benefit. The highest quality evidence is evidence of harm from epinephrine. The same is true for amiodarone, ventilation in cardiac arrest not due to a respiratory problem, furosemide in ADHF/CHF (Acute Decompensated Heart Failure/Congestive Heart Failure), and many other treatments we provide to patients, but definitely not for the benefit of patients.

We need to stop putting patients last in treatment decisions. The neonatal resuscitation guidelines are correct in their rejection of supplemental oxygen for neonatal resuscitation and the guidelines should not be changed.

Footnotes:

[1] Does Room Air Reduce Mortality Among Term Neonates Requiring Respiratory Support at Birth?

Brit Long, MD (EBEM Commentator), Michael D. April, MD, DPhil (EBEM Commentator) Department of Emergency Medicine, San Antonio Uniformed Services Health Education Consortium, Fort Sam Houston, TX

Annals of Emergency Medicine

October 2019, Volume 74, Issue 4, Pages 509–511

DOI:&nbps;https://doi.org/10.1016/j.annemergmed.2019.03.017

Free Full Text from Annals of Emergency Medicine. .

Happy Full Moon Friday the 13th


Technically, the full moon is not until 00:33 – 33 minutes after the end of Friday the 13th, so that may help the superstitious to feel better, since these superstition events are not actually coinciding – pitting twice as many Gods against the superstitious (a double whammy). Or the superstitious may feel worse, because they now have two days in a row of the Gods conspiring against them. The reality is that only their own beliefs conspire against them. it is all in the heads of the believers.

Even when someone does claim to come up with some evidence to support their beliefs, those conclusions are not supported by higher quality research.
 

In conclusion, Friday the 13th appears to be dangerous for some women. Since Friday falls on the 13th day of the month only twice a year on average, prospects for significant public health gains are limited. However, the risk of death for women who venture into traffic on this unlucky day is higher by 63%, and it should be possible to prevent one-third of the deaths occurring on this particular day. Even then, the absolute gain would remain marginal, since only one death per 5 million person-days could be prevented.[1]

 

The total number of deaths is small. Drawing that conclusion, based on a small sample size is a problem. In order to be able to come up with larger numbers, to minimize the effects of the small sample size, other researchers looked at the motor vehicle collisions, rather than just fatal motor vehicle collisions. The assumption that the cause of the fatalities was anxiety, produced by superstition among the drivers is projecting a lot onto the drivers – without any evidence to support this supposed cause.

It should not be a surprise that the results of a much larger sample size contradicts the assumptions based on the much smaller sample.
 

Conclusion:
We conclude that, in the Finnish traffic accident statistics for 1989–2002, females have not incurred more injury (or fatal) road traffic accidents on Fridays the 13th than expected, as a driver, bicyclist or pedestrian. We suggest that Näyhä’s contradicting result on fatalities is due to different sampling, non-optimal setting and chance in a fairly small data. However, this does not imply a nonexistent effect on accident risk as no exposure-to-risk data [18] are available. People who are anxious of “Black Friday” may stay home, or at least avoid driving a car. The only relevant data [4], suggesting a small decrease in highway traffic, is rather limited and should be confirmed with more extensive research.[2]

 

The law of small numbers is an attempt to expose the mistake of extrapolating from small numbers as if the small numbers are representative. Small numbers are misleading. Small numbers are often used to promote ideas that are not supported by adequate numbers – such as the claims that epinephrine improves cardiac arrest outcomes that matter, or that amiodarone improves cardiac arrest outcomes that matter.[3]

Footnotes:

[1] Traffic deaths and superstition on Friday the 13th.
Näyhä S.
Am J Psychiatry. 2002 Dec;159(12):2110-1.
PMID: 12450968

[2] Females do not have more injury road accidents on Friday the 13th.
Radun I, Summala H.
BMC Public Health. 2004 Nov 16;4:54.
PMID: 15546493

Free Full Text from PubMed Central.

[3] Chapter 10
The Law of Small Numbers

Thinking, Fast and Slow
Daniel Kahneman
2011
Wikipedia page

.

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    

.

Closed chest compressions reduce survival in an animal model of haemorrhage-induced traumatic cardiac arrest

   

This is an animal study, rather than a human study, but it has fewer disadvantages than the usual animal studies of medical cardiac arrest. Animals do not develop the comorbidities that humans do, but have artificially created heart attacks, rather than by the development of actual heart disease. In studying trauma, this is less of a problem, since trauma is artificially created. This study is much more representative of penetrating injuries with a low velocity objects, than blunt force trauma, or penetrating injury with a high velocity object.

Are we really killing trauma patients with our chest compressions?

Maybe. This is one small study (39 pigs), but it does raise questions about the ways we can minimize the harm we cause.

 

 
CCC were associated with increased mortality and compromised haemodynamics compared to intravenous fluid resuscitation. Whole blood resuscitation was better than saline.[1]

 
A soft tissue injury was created, with 3 shots to the right thigh using a captive bolt (Cash Special, Accles and Shelvoke, Sutton Coldfield, UK). Two minutes later animals underwent a controlled haemorrhage (30% blood volume) at an exponentially reducing rate as previously described12 until the mean arterial blood pressure (MAP) was 45 mmHg. Blood was collected into CPD (citrate phosphate dextrose) and stored at room temperature until required for later transfusion.[1]
 

Image source

 

This study, conducted in an animal model of haemorrhage-induced traumatic cardiac arrest, has demonstrated that chest compressions confer no benefit over fluid resuscitation alone, and blood should be the fluid therapy of choice.[1]

  That seems to be concluding too much, since this is just one study, but it does reinforce the results of other, similar studies. We should study the outcomes in humans, since there does appear to be equipoise. There never was a physiological justification for chest compressions in traumatic cardiac arrest which appears to be due to hemorrhage. Now there is more evidence that chest compressions produce more harm than benefit in traumatic cardiac arrest which appears to be due to hemorrhage.

 
One study using a baboon traumatic cardiac arrest model found that the improvements in haemodynamics seen with chest compressions for normovolaemic cardiac arrest were not reproduced in hypovolaemic arrest.14 The authors suggested that CCC should not delay correction of the underlying deficit causing TCA, but the study was undertaken in only three animals, perhaps limiting its clinical relevance. A more recent study using a canine model of pulseless electrical activity in TCA found no benefit of chest compressions over fluid therapy alone or fluid combined with chest compressions; in fact the chest compression only group had worse survival, base deficit and ejection fraction.15 The authors concluded that further research was required to determine whether CPR has a role for the patient in haemorrhagic shock.[1]

  Most important is that the outcome is ROSC (Return Of Spontaneous Circulation), not return to normal neurological function. Since these are pigs, even the appearance of normal neurological function may not mean anything in humans. Still, the treatment is not evidence-based, so there does not appear to be a good reason to prefer to continue using compressions for traumatic cardiac arrest which appears to be due to hemorrhage.

Here in America, we are unlikely to do the research, because we are more concerned with appearances than with improving outcomes for patients. Maybe somebody in Britain or Australia will have to demonstrate some responsibility, so we can stop using chest compressions to kill trauma patients.

  Footnotes:

  [1] Closed chest compressions reduce survival in an animal model of haemorrhage-induced traumatic cardiac arrest. Watts S, Smith JE, Gwyther R, Kirkman E. Resuscitation. 2019 May 9;140:37-42. doi: 10.1016/j.resuscitation.2019.04.048. [Epub ahead of print]

PMID: 31077754

Free Full Text from Resuscitation

  .

ILCOR wants the appearance of public comments with less than half the substance

 

The International Liaison Committee on Resuscitation (ILCOR) shows its priorities in the way it handles its problem with public comments.
 

Last week ILCOR posted the two new draft CoSTRs listed below for public comment. It became apparent that the commenting link was broken and those who visited the site could not comment. We apologize for the inconvenience. The commenting link is now fixed and we invite you to comment at ilcor.org/costr.

  • Advanced Airway Management During Adult Cardiac Arrest
  • Vasopressors in Adult Cardiac Arrest
  • As a reminder, the public comment period will close on 4 April 2019.[1]

     

    ILCOR made a mistake that prevented public comments from being submitted for most of the public comment period.

    ILCOR is so interested in your public comments that they have decided to send out an email to let people know that they have the same drop dead date for the comments as before, but this time they might actually be able to get the comments to work. Maybe.

    The lack of evidence of benefit of epinephrine (adrenaline in Commonwealth countries) has lasted over half a century, so what is the rush to get these new guidelines out?

    There is only one outcome that matters – survival without severe brain damage.
     


     

    ILCOR evaluates 23 outcomes.

    ILCOR considers 15 of these outcomes critical, but they are really just 5 outcomes, with some of them repeated over different rhythms. These are (in increasing order of importance to the only one that matters):

    1. For the critical outcome of survival to hospital discharge, 2. For the critical outcome of survival at 3 months, 3. For the critical outcome of favorable neurologic outcome at hospital discharge, 4. For the critical outcome of survival with unfavorable neurologic outcome at 3 months, 5. For the critical outcome of favorable neurologic outcome at 3 months,

    Many of them are repeated for each cardiac arrest rhythm or for each vasopressor, or vasopressor cocktail:

    1. Epinephrine plus vasopressin compared to epinephrine only – Any rhythm 2. Initial vasopressin compared to initial epinephrine – Any rhythm 3. Epinephrine compared to placebo – Non-shockable rhythms 4. Epinephrine compared to placebo – Shockable rhythms 5. Epinephrine compared to placebo – Any initial rhythm

    There is only one outcome that matters – survival without severe brain damage.

    There is only one study that was large enough to answer this:
     

    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 people at ILCOR really think that epinephrine is beneficial in cardiac arrest, they should encourage a much larger study.

    There were 4,000 patients in each group – 4,000 placebo and 4,000 epinephrine.

    Maybe with 8,000 patients in each group, the ever decreasing “trend toward better outcome” will reach significance. Maybe it will be shown to be just another insignificant appearance of a “trend” that is the result of having so few survivors to compare.

    There were only 161 survivors without severe brain damage out of 8,000 cardiac arrest patients – 74 placebo and 87 epinephrine.

    Those resuscitated before receiving epinephrine/placebo were excluded from the study, so this is not a case of EMS that only has a 2% resuscitation rate. The focus on epinephrine is a focus on the patients least likely to be resuscitated and a focus on counterproductive outcomes.

    Almost all of our good outcomes (without severe brain damage) will be without epinephrine, because these resuscitations happen before epinephrine can be give by even the most aggressive epi enthusiast.

    What we are doing is making excuses for memorizing ineffective interventions and requiring their application is a specific way, in order to determine the quality of care. We are promoting fantasy.

    We learned that distracting from the quality of chest compressions is the most deadly thing we can do in resuscitation.

    CPR = only chest compressions – the exception is when the arrest is believed to be due to a respiratory event, such as when the Smurf sign or a respiratory/choking history is present. Chest compressions provide all of the pulmonary resuscitation that a human needs for a non-respiratory event and the respiratory events are not easily missed.

    Why require a whole bunch of skills be applied for such a tiny portion of good outcomes among cardiac arrest patients?

    Why not give up on requiring these skills when the evidence makes it clear that there is no benefit?

    All we are doing is adding cognitive load to make us feel like we are doing something special.

    We could learn something that actually benefits patients, such as how to assess patients when giving high-dose NTG (NiTroGlycerin or GTN GlycerylTriNitrate in Commonwealth countries) for even hypotensive CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure), where we can make much more of a difference and prevent cardiac arrest, but we don’t.[3],[4],[5]
     


     

    Cognitive load is not just a problem for paramedics and nurses, or med/surg doctors, but also for emergency physicians:

    Cognitive Load and the Emergency Physician
    April 12, 2016
    James O’Shea
    emDocs
    Article

    Why are we distracting everyone from things that do improve the only outcome that matters, in order to promote things that do not improve any outcome that matters?

    Here is what I wrote –
     

    The primary source for the recommendation to keep things the same is a brand new study – PARAMEDIC2.

    This showed no statistically significant improvement in the only outcome that matter – survival without severe brain damage.

    A larger study might show that there is a real improvement – or it may put the epi hypothesis out of its misery.

    I will eventually have a cardiac arrest. If I am resuscitated, whom will ILCOR send to change my diaper, and attend to the other things I can no longer attend to?

    We need evidence of a significant benefit in order to justify distracting everyone from interventions that actually do improve survival without severe brain damage.

    .

     

    The commenting link is now fixed and we invite you to comment at ilcor.org/costr

    Maybe they will pay attention. Dr. Rory Spiegel of EM Nerd has a detailed comment that is also critical of ILCOR’s proposed “strong recommendation” of epinephrine.

    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.
     

    In a Bayesian analysis that used an assumption of no benefit from adrenaline, the posterior probability that the absolute rate of survival was at least 1 percentage point higher in the epinephrine group than in the placebo group was 37% (Fig. S3 in the Supplementary Appendix). The probability that the absolute survival rate was at least 2 percentage points higher was 0.2%. With respect to the rate of survival with a favorable neurologic outcome at hospital discharge, the probabilities that the rate was at least 1 or 2 percentage points higher with epinephrine were 1.9% and 0%, respectively (Fig. S4 in the Supplementary Appendix).

     

    The probability of a good outcome (no severe brain damage) is not improved with epinephrine.

    If we want to improve outcomes, we need to look elsewhere, because there is nothing to be gained with epi.

    [3] Intravenous nitrates in the prehospital management of acute pulmonary edema.
    Bertini G, Giglioli C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, Gensini G.
    Ann Emerg Med. 1997 Oct;30(4):493-9.
    PMID: 9326864 [PubMed – indexed for MEDLINE]

    [4] Unreasonable Fear of Hypotension and High-Dose NTG – Part I
    Thu, 29 Aug 2013
    Rogue Medic
    Article

    [5] Unreasonable Fear of Hypotension and High-Dose NTG – Part II
    Wed, 04 Sep 2013
    Rogue Medic
    Article

    .

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

     

    I showed the problems with amiodarone for both live patients and dead patients in Part I. The higher the quality of the evidence, the less the evidence supports the use of amiodarone on humans.

    Amiodarone is all sales pitch and no medical benefit, but Dr. Kudenchuk keeps trying to spin the results like an acupuncturist, when the evidence clearly does not support Dr. Kudenchuk’s claims.[1]
     

    What else should be de-emphasized?

    Obviously, adrenaline (epinephrine in non-Commonwealth countries) for cardiac arrest. As the quality of the epinephrine research has improved, the claims of supposed benefits have disappeared.[2], [3]

    Now, the goalposts have shifted, again, and the claims are that some other dosing is safe and effective, even though the evidence to support these claims does not exist. This is alternative medicine. This is dishonest. This is experimenting on patients without any kind of ethical approval, or collection of data, or anything else that would accompany a true experiment. We are learning that we are very good at lying to ourselves, but we knew that.

    Eventually, we may be claiming that we have not studied what happens when we stand on one leg while giving epinephrine.

    How can we possibly stop using adrenaline if we have not proven that it doesn’t work when standing on one leg? How can we refuse to provide this one legged hope to patients?

    We are sorry for what we did to your _______, but we consider justifying doing something harmful, based on low quality evidence and even lower quality excuses, to be more important than the outcomes of our patients. If we don’t throw in the kitchen sink, how can we claim that we did everything we could for to your _______?
     


    Click on the image to make it larger.
    I modified the original to add the outcomes reported by PARAMEDIC2. Severe neurological impairment is the wording from the conclusion, but that would not fit. If you think that harm is not an accurate synonym for impairment, you may be dangerous to patients.
    Source of original – R.E.B.E.L. EM – Beyond ACLS: Cognitively Offloading During a Cardiac Arrest
     

    If the next revision of ACLS/ILCOR (Advanced Cardiac Life Support/International Liaison Committee on Resuscitation) does not state that epinephrine/adrenaline should be limited to use in high quality research, it will be encouraging abuse of patients.

    This is alternative medicine. This is not medicine.

    The difference is that real medicine relies on valid evidence that it works, while alternative medicine relies on marketing strategies and misinformation.

    Do you want to be treated by someone who can tell the difference between these approaches?

    Medicine requires doing what is best for the patient.

    Alternative medicine requires doing what makes the guru look best, so that the guru can keep making sales.

    The doctors promoting this unethical approach do not appear to be ashamed of what they are doing, but they keep making excuses. We need to make it clear that their excuses are not ethical.

    To all of the doctors claiming that a drip works. Demonstrate that you are ethical and competent. Show that what you are doing improves outcomes that matter to patients, in a high quality study, or stop.

    If doctors won’t do that, maybe we should add DNA (Do Not Amio) and DNE (Do Not Epi) to our list of advance directives, for those who do not think that resuscitation to a come, where sepsis and aspiration pneumonia are what we aspire to.

    Footnotes:

    [1] 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.

     

    Here are some comments from Dr. Kudenchuk, which contradict the conclusion of Dr. Kudenchuk’s study:
     

    This trial shows that amiodarone and lidocaine offer hope for bringing patients back to life and into the hospital after cardiac arrest,” said principal study author Peter Kudenchuk, M.D.

     

    This trial shows that amiodarone and lidocaine offer no hope for outcomes that matter to patients.
     

    Importantly, there was a significant improvement in survival to hospital discharge with either drug when the cardiac arrest was bystander-witnessed.”

     

    There is no truth to Dr. Kudenchuk’s claim. This is what the authors of the study actually wrote:
     

    We observed an interaction of treatment with the witnessed status of out-of-hospital cardiac arrest, which is often taken as a surrogate for early recognition of cardiac arrest, a short interval between the patient’s collapse from cardiac arrest and the initiation of treatment, and a greater likelihood of therapeutic responsiveness. 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.

     

    The best that can be stated about these drugs is that if the researchers used a large enough study, they might be able to find a statistically significant result – or the researchers may demonstrate that this was just another example of a statistically insignificant run of luck, which means nothing and is just as likely to have gone the other way.

    A run of heads in a row, while flipping a coin is a reason to examine the coin for bias, but if no bias is found, it is expected to be just what is expected to happen in a large number of coin flips. A lack of understanding of coincidence leads to faulty conclusions.

    The difference in outcomes, that Dr. Kudenchuk claims is significant, not statistically significant.

    Does Dr. Kudenchuk not understand the way research works or does Dr. Kudenchuk have some unstated motive for distorting the results? It appears that the New England Journal of Medicine refused to publish the conclusion that Dr. Kudenchuk wanted, so Dr. Kudenchuk is using more gullible people to spread his misinformation.

    Go ahead and read the full paper, which is available from NEJM here.

    Also read Dr. Kudenchuk’s press release, which misrepresents the results of Dr. Kudenchuk’s study. You would think that Dr. Kudenchuk would know better.
     

    Antiarrhythmic drugs found beneficial when used by EMS treating cardiac arrest
    NHLBI NEWS|News Release
    April 4, 2016, 9:00 AM EDT
    Press Release
     

    I have nothing to hide. I want you to look all of the evidence.
     

    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

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

    Free Full Text PDF Download from semanticscholar.org
     

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

     

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

     

    The results do not show an improvement in the any outcome that matters to patients.
     

    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.

     

    [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 Jul 18. doi: 10.1056/NEJMoa1806842. [Epub ahead of print]
    PMID: 30021076

    Free Full Text from NEJM

    It appears that the full text of PARAMEDIC2 is no longer available for free from NEJM, but there is the option of registering for 3 free papers a month (Register for 3 FREE subscriber-only articles each month.) in a red pop-up banner at the bottom of the page.

    Once again, the results do not show an improvement in the any outcome that matters to patients.
     

    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.

     

    .